Note: Descriptions are shown in the official language in which they were submitted.
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ISOMETRIC SYSTEM, METHOD AND APPARATUS FOR ISOMETRIC
EXERCISE
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Patent Application Serial
No.
13/753,854 entitled "Isometric System, Method and Apparatus for Isometric
Exercise," and filed on January 30, 2013, claiming priority to and the benefit
of
the filing date of U.S. Patent Application Serial No. 61/723,981, having the
same
title and filed on November 8, 2012; and this application claims priority to
U.S.
Patent Application Serial No. 13/753,889 entitled "Isometric System, Method
and
Apparatus for Isometric Exercise," and filed on January 30, 2013, claiming
priority to and the benefit of the filing date of U.S. Patent Application
Serial No.
61/723,998, having the same title and filed on November 8, 2012; and this
application claims priority to U.S. Patent Application Serial No. 13/753,950
entitled "Isometric System, Method and Apparatus for Isometric Exercise," and
filed on January 30, 2013, claiming priority to and the benefit of the filing
date of
U.S. Patent Application Serial No. 61/724,008, having the same title and filed
on
November 8, 2012. The disclosures of all the above identified applications are
incorporated by reference herein in their entireties.
[0002] FIELD OF THE INVENTION
[0003] Various aspects of the present invention are generally directed to
isometric exercise and a system, method, and apparatus for isometric exercise,
and more specifically to the use of the system, method, and apparatus for
isometric exercise to treat various conditions.
BACKGROUND OF THE INVENTION
[0004] This section is intended to introduce the reader to various aspects of
art that may be related to various aspects of the present invention, which are
described and/or claimed below. This discussion is believed to be helpful in
providing the reader with background information to facilitate a better
understanding of various aspects of the present invention. Accordingly, it
should
be understood that these statements are to be read in this light, and not as
admissions of prior art.
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[0005] The use of isometric exercise, as opposed to rhythmic exercise, in the
general field of athletic strength development, as well as a therapy for
strength
recovery, has been the subject of somewhat controversial discourse over the
past decades. In general, isometric exercise has been considered to promote
coronary risk factors (among other deleterious effects) [See generally: Vecht
R
J, Graham G W S, Sever P S. "Plasma Noradrenaline Concentrations During
Isometric Exercise." Brit Heart J. 1978;40:1216-20; and Chrysant S G.
"Hemodynamic Effects of Isometric Exercise in Normotensive Hypertensive
Subjects": Hypertension. Anglology 1978:29(5):379-85].
[0006] Because isometric exercise was thought to promote coronary risk
factors, it was generally not considered useful in treating conditions such as
hypertension and other conditions that may include a condition of the
circulatory
system, such as erectile dysfunction, type II diabetes, obesity, etc. Indeed,
in
many of these cases, isometric exercise was thought of as being
contraindicated.
[0007] Hypertension (also known as high blood pressure) is a chronic
medical
condition in which the blood pressure in the arteries is elevated, thereby
causing
the heart to work harder than normal to circulate blood through the body.
Hypertension is associated with an increased risk of a wide range of disease
and
disorder, including stroke, organ failure, and cardiopathy. Risk factors for
hypertension include obesity, genetic factors, smoking, diet, and inactivity.
[0008] Erectile dysfunction (ED) is a sexual dysfunction characterized by
the
inability to develop or maintain an erection of the penis. Stimulation of
penile
shaft by the nervous system leads to the relaxation of smooth muscles of
corpora cavernosa (the main erectile tissue of penis) and the inflow of blood
to
that tissue, which results in penile erection. Impotence may develop due to a
lack of adequate penile blood supply, and so there may be various circulatory
causes of ED. For example, restriction of blood flow can arise from impaired
endothelial function due to the usual causes associated with coronary artery
disease. Diabetes may be another cause of ED.
[0009] Diabetes mellitus type 2 ("type 2 diabetes," also known as non-
insulin-
dependent diabetes mellitus or adult-onset diabetes) is a metabolic disorder
that
is characterized by high blood glucose, insulin resistance, and relative
insulin
deficiency. Obesity is thought to be one primary cause of type 2 diabetes in
people who are genetically predisposed to the disease.
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[0010] Obesity is a medical condition in which excess body fat has
accumulated to the extent that it may have an adverse effect on health,
leading
to reduced life expectancy and/or increased health problems. Body mass index
(BMI), a measurement which compares weight and height, presently defines
people as overweight (pre-obese) if their BM1 is between 25 and 30 kg/m2, and
obese when it is greater than 30 kg/m2. Obesity increases the likelihood of
various diseases, such as heart disease and type 2 diabetes. Obesity is most
commonly caused by a combination of excessive food energy intake, lack of
physical activity, and genetic susceptibility.
[0011] Hypertension, hypercholesterolemia, atherosclerosis and
cardiovascular disease are interrelated in their causes, treatment and effect
on
the body (and, as can be seen from the discussion above, ED, diabetes, and
obesity may also have interrelated causes ¨ or be the cause of one another, as
well as with hypertension). The class of drugs known as HMG-CoA reductase
inhibitors or statins is widely prescribed for treatment of
hypercholesterolemia
and associated cardiovascular disease, including the debilitating effects of
progressive atherosclerosis. Various statins that have been clinically
utilized
include atovastatin, cerivastatin, fluvastatin, ovastatin simvastatin among
others.
The statin drugs were initially prescribed to relieve hypercholesterolemia,
and to
reduce the blood concentrations of low-density lipoprotein (LDL) and
triglycerides. It has become apparent that the statin drugs apparently have
additional therapeutic benefits that are independent and or interrelated with
the
effects of reduction in blood cholesterol concentration. The effect of statin
drugs
thus includes a reduction in vascular inflammation, and a protection of the
heart
against ischemic disorders. [For more information on the pleiotropic effects
of
the statin drugs see generally: Davignon J., Beneficial cardiovascular
pleiotropic
effects of statins, Circulation, 109 (23 Suppl 1):11139-43 (2004); Elrod J W,
Lefer
D J The effects of statins on endothelium, inflammation and cardioprotection,
Drug News Perspect, 18(4):229-36 (2005, May); Assanasen C, et al.,
Cholesterol binding, efflux, and a PDZ-interacting domain of scavenger
receptor-
BI mediate HDL-initiated signaling, J Clin Invest., 115(4):969-77 (2005
April)]
[0012] Although the exact mechanism of statin drug action for
cardioprotection is not fully known, it is widely believed that statin drugs
stimulate
nitric oxide synthase activity in vascular endothelium, and presumably in
other
tissues. Disorders of the vascular endothelium related to nitric oxide
metabolism
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are believed to play a crucial role in the pathogenesis of atherosclerosis in
hypercholesterolemia. Thus, certain cardioprotective effects of statin drugs
can
be mimicked in part by other physiological stimuli that induce nitric oxide
synthase and increase nitric oxide availability. Moreover, nitric oxide
metabolism
is interconnected with the metabolism and regulation of LDL, cholesterol and
triglycerides, and with the progress of atherosclerosis. As one example of
this
interrelationship, changes in nitric oxide levels have been inversely
correlated
with changes in LDL-cholesterol concentrations.
100131 Nitric oxide (NO) has been identified as a signaling molecule in
mammalian and other systems. NO, is a labile, endogenously produced gas that
is enzymatically synthesized, can rapidly diffuse, and quickly disappear. NO
is
known to be a potent regulator of blood pressure due to its activity as a
vasodilator, but has a diverse action on a wide variety of organ systems.
Endothelial nitric oxide synthase (eNOS) is induced to synthesize NO by blood
vessel wall shear stress. Upon the activation of eNOS and induction of NO
synthesis, NO is released by endothelial cells. Based on the position of
endothelial cells lining the inner surface of blood vessels, NO can be
released
into the blood stream, where it can act both locally and systemically. NO
induces
vasoclilation by a reduction in the contraction of smooth muscle cells lining
blood
vessels. NO acts as a negative feedback for mean arterial pressure, since as
arterial pressure increases, wall shear stress increases, inducing eNOS and
increasing the NO concentration. As NO concentration increases, smooth
muscle contraction is decreased, blood vessel lumen diameter increases,
arteriole resistance decreases and arterial pressure decreases. The modulating
action of wall shear stress on eNOS activity and NO production serves to
maintain wall shear stress at a constant level. A diagram highlighting some of
the
interactions between NO, local metabolites, wail shear stress and smooth
muscle contraction is shown in FIG. 20.
100141 Prolonged elevation of wall shear stress, in addition to activation
of
eNOS, leads to the transcriptional activation of the eNOS gene in endothelial
cells. After several hours, eNOS enzyme levels increase due to the induced
transcription of the eNOS gene. Increased levels of eNOS enzyme in endothelial
cells increases those cells ability to release NO following induction of eNOS
activity. It is thus expected that those cells which have experienced
prolonged
elevation of wall shear stress will have an increased ability to synthesize
NO,
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and the same levels of wall shear stress will result in a greater synthesis of
NO.
One effect of increased eNOS levels is a reduction in the amount of wall shear
stress that is required to induce biologically significant NO levels. Blood
vessels
that have been entrained by prolonged elevation of wall shear stress will
release
more NO relative to shear stress, and the vasodilation effect of NO will be
increased, Higher relative NO concentration leads to reduced smooth muscle
contraction, increased blood vessel lumen diameter and decreased arteriole
resistance. Assuming that the cardiac output of the heart does not change, the
net effect of a lower "set point" for responding to wall shear stress is a
reduction
in total peripheral resistance in blood vessels and a reduction in mean
arterial
pressure.
[0015] Similar to the effects of the statin drugs, an improvement in
endothelial
function is interconnected with LDL and cholesterol blood levels and NO
bioavailability. LDL and cholesterol have been shown to prevent the down-
regulation of eNOS. In turn, down-regulation of eNOS is apparently mediated by
the stimulation of levels of caveolin-1 by LDL. Caveolin-1 is an important
inhibitor
of eNOS catalytic activity. Modulation of NO is expected to affect the
interrelated
blood lipid concentrations of VHDL, HDL, LDL, and cholesterol. To the extent
that the pleiotropic activity of the cholesterol lowering statin drugs is
modulated
by NO levels, stimulation of NO bioavailability is expected to affect blood
lipid
composition. For additional background on the interrelationship between LDL
and NO, see generally: Martinez-Gonzalez, J., et al., Arterioscler. Thromb.
Vasc.
Biol. 21: 804-809 (2001).
[0016] As described above, it has been known for some time that exercise
can provide relief from hypertension in certain individuals. As the modulation
of
nitric oxide levels is part of a feedback system that responds in part to the
stretching and extensibility of blood vessels of the body, it is hypothesized
that
exercise in general plays a role in stimulating cycles of NO release, and
effectively providing some of the benefits of statin drugs, including
improvement
in endothelial function, increased nitric oxide bioavailability, anti-oxidant
effects,
anti-inflammatory protection, and stabilization of atherosclerotic plaques.
Notwithstanding the effects of the modulation of NO bioavailability, exercise
is
known to modulate blood cholesterol and blood lipid composition.
[0017] However, as also stated above, previous conventional wisdom would
suggest that isometric exercise would be ineffective in treating such
conditions
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(as opposed to rhythmic or dynamic exercise), due to the belief that isometric
exercise promotes coronary risk factors (among other deleterious effects). And
so, rhythmic or dynamic exercise is primarily used as a therapy for various
conditions (rather than isometric exercise).
SUMMARY OF THE INVENTION
[0018] Certain exemplary aspects of the invention are set forth below. It
should be understood that these aspects are presented merely to provide the
reader with a brief summary of certain forms the invention might take and that
these aspects are not intended to limit the scope of the invention. Indeed,
the
invention may encompass a variety of aspects that may not be explicitly set
forth
below.
[0019] One aspect of the present invention includes a system and method of
using isometric exercise to treat various conditions, including erectile
dysfunction, type 2 diabetes, and obesity. In general, the system includes
applying a force to an isometric exercising mechanism via an elected
exercisable
muscle group of the musculature of a user. The mechanism is responsive to the
force applied, and the application of force increases shear stress on a blood
vessel wall of the user. This induces the synthesis of endothelial nitric
oxide
synthase, which results in synthesis of NO in the user, thereby increasing the
amount of bioavailable NO in the user. In certain embodiments, through the
selection of the particular muscle group used, or through the particular
exercise
protocol, or any combination, a therapy for a particular condition (e.g., ED,
obesity, or diabetes) may be provided.
[0020] Another aspect of the present invention provides an apparatus for
carrying out a controlled isometric regimen by a user. In one exemplary
embodiment, the apparatus may include a handgrip-based dynamometer. Being
microprocessor driven, the instrument is programmed to carry out established
diagnostic as well as newly developed grip-based isometric regimens. When
employed for carrying out a diagnostic maximum grip test, the diagnostician
selects configuration parameters and the instrument provides both visual and
audible prompts and cues throughout the procedure. Maximum grip forces for
each of the sequence of trials of this procedure are selected typically by the
diagnostician and when so selected are recorded in instrument memory along
with calendar data, and processor computed values for average grip force,
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standard deviation of the force values throughout a sequence of tests and
corresponding coefficients of variation. At the termination of the diagnostic
procedure, memory recorded test data are displayable to the diagnostician and
may be downloaded through a communications port to a computer facility.
[0021] When used for a therapeutic purpose, use of the apparatus begins
with a determination of the maximal isometric force which can be exerted by a
patient with any given muscle (e.g., skeletal muscle or group of muscles) of
such
patient. The determined maximal isometric force is recorded. The patient,
then,
is periodically permitted to intermittently engage in isometric contraction of
the
given muscle at a fractional level of the maximal force determined for a given
contraction duration followed by a given resting duration. A perceptible
indicia
correlative to the isometric force exerted by the given muscle is displayed to
the
patient so that the patient can sustain the given fractional level of maximal
force.
[0022] As described above, it has been known for some time that exercise
can provide relief from hypertension in certain individuals. As the modulation
of
nitric oxide levels is part of a feedback system that responds in part to the
stretching and extensibility of blood vessels of the body, it is hypothesized
that
exercise in general plays a role in stimulating cycles of NO release, and
effectively providing some of the benefits of statin drugs, including
improvement
in endothelial function, increased nitric oxide bioavailability, anti-oxidant
effects,
anti-inflammatory protection, and stabilization of atherosclerotic plaques.
Notwithstanding the effects of the modulation of NO bioavailability, exercise
is
known to modulate blood cholesterol and blood lipid composition.
[0023] However, as also stated above, previous conventional wisdom would
suggest that isometric exercise would be ineffective in treating such
conditions
(as opposed to rhythmic or dynamic exercise), due to the belief that isometric
exercise promotes coronary risk factors.
[0024] In addition to
the coronary risk factors believed to be promoted by
isometric exercise, early subjects or trainees undergoing isometric exercise
stressed the involved musculature to their full or maximum capability
(Kiveloff, et
al., "Brief Maximal Isometric Exercise in Hypertension", J. Am. Geriatr. Soc.,
9:1006-1012, 1971) or at some submaximal force as long as it could be
sustained, in either case only terminating with the onset of unendurable
fatigue.
Such approaches often have incurred somewhat deleterious results as
evidenced by the injuries sustained in consequence of improper weightlifting
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procedures. Weightlifting procedures or endeavors exhibit a significant
isometric
factor. See generally: Lind A R. "Cardiovascular Responses to Static
Exercise"(lsometrics, Anyone?) Circulation 1970:41(2):173-176; and Mitchell J
H, Wildenthal K. "Static (Isometric) Exercise and the Heart: Physiological and
Clinical Considerations". Ann Rev Med 1974;25:369-81.
[0025] However, as such attitudes persisted, some investigators commenced
to observe contradictions to these generally accepted beliefs. See for,
example,
the following publications: Buck, et at., "Isometric Occupational Exercise and
the
Incidence of Hypertension", J. Occup. Med., 27:370-372, 1985; Choquette. et
al., "Blood Pressure Reduction in 'Borderline' Hypertensives Following
Physical
Training" Can. Med. Assoc. J. 1108:699-703, 1973; Clark, et al., "The Duration
of Sustained Contractions of the Human Forearm of Different Muscle
Temperatures", J. Physiol., 143:454-473, 1958; Gliders, et at., "Endurance
Training and Blood Pressure in Normotensive and Hypertensive Adults", Med.
Sci. Sports Exerc. 21:629-636, 1989; Hagberg, et at., "Effect of Weight
Training
on Blood Pressure and Hemodynamics in Hypertensive Adolescents", J. Pediatr.
1104:147-151, 1984; Harris, et al., "Physiological Response to Circuit Weight
Training in Borderline Hypertensive Subjects", Med. Sci. Sports Exerc., 19:246-
252, 1987; Hurley, et al., "Resistive Training Can Induce Coronary Risk
Factors
Without Altering Vo2 max or Percent Body Fat" Med. Sci. Sports Exerc.
20:150-154, 1988; Hypertension Detection and Follow-up Program Cooperative
Group, "The Effect of Treatment on Mortality in 'Mild' Hypertension", N. Engl.
J.
Med., 307:976-980, 1982; Kiveloff, et al., "Brief Maximal Isometric Exercise
in
Hypertension", J. Am. Geriatr. Soc., 9:1006-1012, 1971; Merideth et al.,
"Exercise Training Lowers Resting Renal but not Cardiac Sympathetic Activity n
Humans", Hypertension, 18:575-582, 1991; Seals and Hagberg, "The Effect of
Exercise Training on Human Hypertension: A Review", Med. Sci. Sports Exerc.
16:207-215, 1984; and Hanson P. Nagle F. "Isometric Exercise: Cardiovascular
Responses in Normal and Cardiac Populations." Cardiology Clinics 1987; 5(2):
157-70. Such speculation on the part of these early observers was confirmed by
Wiley, and was taken further by Wiley in the 1990s as a possible treatment for
hypertension, as described in U.S. Pat. No. 5,398,696 entitled "Isometric
Exercise Method for Lowering Resting Blood Pressure and Grip Dynamometer
Useful Therefore", issued Mar. 21, 1995 and as described in the following
publication: Wiley, et al., "Isometric Exercise Training Lowers Resting Blood
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Pressure, Med. Sci. Sports Exerc. 29:749-754, 1992 incorporated by reference
herein in its entirety.
[0026] With the approach of protocol developed by Wiley, the isometric
regimen is closely controlled both in terms of exerted force and in the timing
of
trials or exertions. The system and method described by Wiley are known to be
useful for treating hypertension. Hypertension is associated with an increased
risk of a wide range of disease and disorder, including stroke, organ failure,
and
particularly cardiopathy. The exact causes of hypertension are rarely known
with
certainty, but risk factors for hypertension include obesity, genetic factors,
smoking, diet and inactivity. As Wiley has shown, not all forms of exercise
provide equivalent therapeutic benefit to the cardiovascular system and for
the
treatment of hypercholesterolemia, with a protocol for brief maximal isometric
exercise providing a clear benefit.
[0027] In about 1998, the above-noted Wiley protocols as described in
connection with Merideth et al., "Exercise Training Lowers Resting Renal but
not
Cardiac Sympathetic Activity n Humans", Hypertension, 18:575-582, 1991, were
incorporated in a compact, lightweight isometric device. This device was a
hand-
held dynamometer. The diagnosis of patient hand-arm strength using isometric-
based testing has been employed by physiologists, physical therapists and
medical personnel for over three decades. These procedures function to
evaluate hand-arm trauma or dysfunction and involve the patient use of a
handgrip-based dynamometer. The dynamometer is grasped by the patient and
squeezed to a maximum capability under the verbal instruction of an attending
therapist or diagnostician. The hand dynamometer most widely used for these
evaluations incorporates a grip serving to apply force through closed circuit
hydraulics to a force readout provided by an analog meter facing outwardly so
as
to be practitioner readable. Adjustment of the size of the grip of the
dynamometer is provided by inward or outward positioning of a forwardly
disposed grip component. The dynamometers currently are marketed under the
trade designation: "Jamar Hydraulic Hand Dynamometer" by Sammons Preston
of Bolingbrook, Ili. An extended history of use of these dynamometers has
resulted in what may be deemed a "standardization" of testing protocols. For
instance, three of the above-noted grip length adjustments are employed in a
standardized approach and verbal instructions on the part of the testing
attendant, as well as the treatment of force data read from the analog meter
are
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now matters of accepted protocol. In the latter regard, multiple maximum
strength values are recorded whereupon average strengths, standard deviations
and coefficients of variation are computed by the practitioner. In one test,
the
instrument is alternately passed between the patient's right and left hands to
derive a maximum strength output reading each 1.5 seconds or 2.5 seconds.
Reading and hand recording strength values for such protocols has remained
problematic. The protocols, for example, have been the subject of
recommendations by the American Society of Hand Therapist (ASHT) and have
been discussed in a variety of publications including the following:
Mathiowetz
V., Federman S., Wiemer D. "Grip and Pinch Strength: Norms for 6 to 19 Year
Olds." The American Journal of Occupational Therapy 40:705-11, 1986;
Mathiowetz V., Donohoe L., ReneIls C. "Effect of Elbow Position on Grip and
Key
Pinch Strength." The Journal of Hand Surgery 10A;694-7, 1985; Mathiowetz V.,
Dove M., Kashman N., Rogers S., VoHand G., Weber K. "Grip and Pinch
Strength: Normative Data for Adults." Arch Phys Med Rehabilitation 66:69-72,
1985; and Mathiowetz V., Vo'land G., Kashman N., "Reliability and Validity of
Grip and Pinch Strength Evaluations." The Journal of Hand Surgery 9A:22-6,
1984.
[0028] Described in
detail in U.S. Pat. No. 5,904,639 entitled "Apparatus,
System, and Method for Carrying Out Protocol-Based Isometric Exercise
Regimens" by Smyser, et al., the hand-held dynamometer has a hand grip which
incorporates a load cell assembly. Extending from the hand grip is a liquid
crystal
display and two user actuated control switches or switch buttons. The display
is
mounted in sloping fashion with respect to the grip such that the user can
observe important visual cues or prompts while carrying out a controlled
exercise
regimen specifically structured in terms of force values and timing in
accordance
with the Wiley protocols. This device is therapeutic as opposed to diagnostic
in
nature and is microprocessor driven with archival memory. External
communication with the battery powered instrument is made available through a
communications port such that the device may be configured by programming
and, additional data, such as blood pressure values and the like may be
inserted
into its memory from an external device. Visual and audible cueing not only
guides the user through a multi-step protocol but also aids the user in
maintaining pre-computed target level grip compression levels.
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[0029] This described apparatus, incorporating the protocol of Wiley,
provided
a system for treating hypertension. However, while Wiley has previously shown
the possible benefits of isometric exercise in the treatment of hypertension,
there
still is lacking a similar treatment for afflictions such as ED, diabetes, and
obesity.
[0030] To that end, there is widespread discourse on the relative benefits
of
particular forms of exercise, and there is an ongoing need for patients
suffering
from hypertension, hypercholesteremia, atherosclerosis, and other
cardiovascular and cardiopulmonary diseases, as well as ED, diabetes, and
obesity to be provided a therapeutic treatment, and to obtain the maximum
benefit from the exercise utilized. Patients who are suffering from severe
cardiovascular disease may be unable to engage in intense exercise, and many
patients may be unable to engage in other forms of exercise due to limitations
in
time or facility availability. The invention disclosed herein provides for a
device,
system and method of exercise that can be optimized to provide an improved
benefit to the patient in stimulating endothelial function, overall blood
vessel
health, and cardiovascular benefit while at the same time limiting the
dangerous
side effects of intensive exercise. Thus, aspects of the present invention
provide
for the treatment of hypertension via isometric exercise. Aspects of the
present
invention also provide for treatment of ED, diabetes, and obesity via
isometric
exercise (which was heretofore nonexistent).
[0031] Of course, it will be beneficial to incorporate improved diagnostic
features for hand-arm evaluation techniques with therapist or practitioner
designed therapeutic protocols specifically tailored to the condition of a
given
patient and which provide a control over such therapies clearly establishing
such
therapies as beneficial to strength development and recovery. One particular
diagnostic and therapeutic feature that would be beneficial to incorporate is
protocol that modulates wall shear stress of blood vessels so as to increase
the
bioavailability of nitric oxide and foster a reduction in total peripheral
resistance
in blood vessels and a reduction in mean arterial pressure, along with the
other
physiologic benefits associated with stimulation of NO signaling pathways,
including reduction in LDL and cholesterol concentrations and an increase in
arterial flexibility. Such a device could also be used with protocols designed
to
treat other conditions, such as ED, obesity, and diabetes.
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[0032] For each of the diagnostic procedures, the widthwise extent of the
instrument grip may be both varied in standard 1/2 inch increments from a
minimum width. The grip is further configured such that the visually
perceptible
readout of the instrument may be viewed only by the diagnostician where
deemed appropriate.
[0033] An important aspect of the therapeutic method associated with the
instrument of the invention resides in the limiting of user performance to
carry out
the regimen of trials. In this regard, the instrument is programmed to perform
only within predetermined and mandated test limits. Each therapeutic regimen
is
based upon an initial evaluation of the maximum gripping force capability of
the
user. Under that limitation, target load factors, hold on target load
intervals,
intervening rest intervals and trial repetition numbers may be elected only
from
pre-established and mandated memory retained ranges. The program also
nominates rest intervals and hold on target intervals in correspondence with
user
elected target force factors. Thus, valuable strength recovery and development
may be achieved but only within safe limits.
[0034] During each of the above therapeutic regimens, an audible warning
is
elicited whenever the user grip force value exceeds a computed upper limit.
During each timed interval wherein the user is prompted to grip at a target
force
value computed with respect to the pre-tested maximum grip force, a dynamic
bar graph and center point display is provided as a visual cue related to
desired
grip performance. Additionally, a rapid succession of score values are
computed
and the average thereof recorded at the end of each trial of a given regimen.
These scores permit a therapist to access the quality of the performance of
the
user. In general, trial data is recorded in conjunction with calendar data
and, as
before, may be downloaded to a computer facility from an instrument contained
communications port.
[0035] An additional aspect of the invention is to influence biological
parameters of the user by selecting target loads that stimulate particular
biological pathways. In one target force mode, the invention allows
stimulation of
nitric oxide bioavailability, which directly influences resting blood pressure
and
overall cardiovascular health. In other instances, the target force mode can
be
directed to maximize the exercise benefit for modulating blood lipid
composition,
including reducing low density lipoprotein (LDL) and cholesterol in the blood.
The system, method, and apparatus described herein also provide for treatment
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of various other conditions, such as erectile dysfunction, obesity, and type
II
diabetes.
BRIEF DESCRIPTION OF THE DRAWINGS
[0036] The accompanying drawings, which are incorporated in and constitute
a part of this specification, illustrate embodiments of the invention and,
together
with the general description of the invention given above and the detailed
description of the embodiments given below, serve to explain the principles of
the present invention.
[0037] FIG. 1 is a perspective view of apparatus according to the
invention
showing its orientation with respect to a users hand wherein its display is
viewable by such user;
[0038] FIG. 2 is a perspective view of the apparatus of FIG. 1 showing the
orientation of the apparatus with respect to the users hand wherein the
display
thereof is not visually accessible to the user;
[0039] FIG. 3 is an exploded perspective view of the apparatus of FIG. 1;
[0040] FIG. 4 is a side sectional view of the apparatus of FIG. 1;
[0041] FIG. 5 is a side view of the apparatus of FIG. 1 showing a minimum
grip width configuration;
[0042] FIG. 6 is a side view of the apparatus of FIG. 1 showing an
orientation
for user viewing of its display and a grip widthwise extent 112 inch greater
than
the grip orientation of FIG. 5;
[0043] FIG. 7 is a side view of the instrument of FIG. 1 showing an
orientation
for user viewing of its display and illustrating a grip widthwise extent of
maximum
value;
[0044] FIG. 8 is a side view of the instrument of FIG. 1 showing an
orientation
for diagnostic viewing and a grip widthwise extent corresponding with that of
FIG.
6;
[0045] FIG. 9 is a side view of instrument of FIG. 1 showing a display
orientation for viewing of a display by a diagnostician and having a grip
widthwise extent corresponding with that of FIG. 7;
[0046] FIG. 10 is a block diagrammatic drawing of the circuit employed
with
the apparatus of FIG. 1;
[0047] FIG. 11 is a flow chart describing the start up components of the
program of the instrument of FIG. 1 as well as a configuration routine;
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[0048] FIGS. 12A and 12B combine as labeled thereon to provide a flow chart
of a maximum grip test diagnostic procedure;
[0049] FIG. 13 is a flow chart illustrating a rapid exchange diagnostic
procedure;
[0050] FIGS. 14A-14C combine as labeled thereon to illustrate a flow chart
describing a therapeutic fixed exercise regimen carried out by the instrument
of
FIG. 1;
[0051] FIG. 15 is a flow chart demonstrating the technique by which a
score
value is developed by the apparatus of the invention;
[0052] FIGS. 16A-16E are a sequence of displays provided by the instrument
of the invention showing a publication of score, a dynamic bar graph with
center
pointer and a time remaining cue;
[0053] FIGS. 17A-17C combine as labeled thereon to illustrate a flow chart
of
a step therapeutic exercise which may be carried out with the instrument of
the
invention;
[0054] FIG. 18 is a flow chart showing an intentional power off sequence;
and
[0055] FIG. 19 is a flow chart describing the applicability of the use of
isometric exercise in conjunction with safe muscle strengthening and therapy
protocols for a broad range of muscle groups.
[0056] FIG. 20 is a flow chart describing the interrelationship between
mean
arterial pressure, tissue pressure, perfusion pressure, heart rate, wall shear
stress and nitric oxide levels.
DETAILED DESCRIPTION OF THE INVENTION
[0057] One or more specific embodiments of the present invention will be
described below. In an effort to provide a concise description of these
embodiments, all features of an actual implementation may not be described in
the specification. It should be appreciated that in the development of any
such
actual implementation, as in any engineering or design project, numerous
implementation-specific decisions must be made to achieve the developers'
specific goals, such as compliance with system-related and business-related
constraints, which may vary from one implementation to another. Moreover, it
should be appreciated that such a development effort might be complex and time
consuming, but would nevertheless be a routine undertaking of design,
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fabrication, and manufacture for those of ordinary skill having the benefit of
this
disclosure.
[0058] One aspect of the present invention includes a system and method of
using isometric exercise to treat various conditions, including erectile
dysfunction, type 2 diabetes, and obesity. In general, the system includes
applying a force to an isometric exercising mechanism via an elected
exercisable
muscle group of the musculature of a user. The mechanism is responsive to the
force applied, and the application of force increases shear stress on a blood
vessel wall of the user. This induces the immediate release of increased
amounts of NO, and the increased synthesis of endothelial nitric oxide
synthase,
which results in longer term increased synthesis of NO in the user, thereby
increasing the amount of bioavailable NO in the user. In certain embodiments,
through the selection of the particular muscle group used, or through the
particular exercise protocol, or any combination, a therapy for a particular
condition (e.g., ED, obesity, or diabetes) may be provided.
[0059] Another aspect of the present invention provides an apparatus for
carrying out a controlled isometric regimen by a user. In one exemplary
embodiment, the apparatus may include a handgrip-based dynamometer. Being
microprocessor driven, the instrument is programmed to carry out established
diagnostic as well as newly developed grip-based isometric regimens. When
employed for carrying out a diagnostic maximum grip test, the diagnostician
selects configuration parameters and the instrument provides both visual and
audible prompts and cues throughout the procedure. Maximum grip forces for
each of the sequence of trials of this procedure are selected typically by the
diagnostician and when so selected are recorded in instrument memory along
with calendar data, and processor computed values for average grip force,
standard deviation of the force values throughout a sequence of tests and
corresponding coefficients of variation. At the termination of the diagnostic
procedure, memory recorded test data are displayable to the diagnostician and
may be downloaded through a communications port to a computer facility.
[0060] The isometric exercise apparatus under which the methodology of the
invention may be carried out is lightweight, portable, battery powered and
sufficiently rugged to withstand the compressive pressures which it
necessarily
endures during use. The instrument is programmable such that it may be
utilized
by a therapeutic practitioner for diagnostic purposes employing established
grip
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test modalities. Strength measurements carried out during these modes are
compiled in memory and the practitioner is afforded calculated values for
average grip force, standard deviation and coefficient of variation with
respect to
grip force trials. Furthermore, individual strength measurements compiled in
these averages, whether taken rapidly or slowly, are stored in memory and may
be reviewed by the therapist.
[0061] Additionally, the instrument is employable as a therapeutic device.
First a protocol is nominated by prescribing nominal parameters of the effort.
Each isometric regimen is controlled initially by requiring that a maximum
grip
strength be established for each individual patient or user. Then, the
practitioner
may elect parameters of grip force and timing under mandated memory
contained parameter limits. Accordingly, the user will be unable to carry out
strength enhancement therapies which would otherwise constitute an excessive
grip force regimen. For carrying out the noted diagnostic procedures as well
as
therapy activities, the grip widthwise extent is variable from 1.875 inches to
2.875
inches, such variation being adjustable in 1/2 inch increments. This is in
keeping
with standardized diagnostic practices. Further with respect to diagnostic
procedures, the display or readout of the instrument can be adjusted with
respect
to the grip structuring such that only the practitioner or therapist may
observe the
data which is being developed during a diagnostic protocol.
[0062] Looking to FIG. 1, the instrument or apparatus is represented
generally at 10 as having a housing identified generally at 12. Housing 12 is
formed of acrylonitrile butadiene styrene (ABS) and, thus, is resistant to
impact
phenomena and the like. FIG. 1 shows that the housing 12 includes a hand
grasping portion 14 and an integrally formed interacting portion 16.
Interacting
portion 16 supports a readout assembly 18 which is configured as an elongate
liquid crystal display (LCD). Additionally located at the interacting portion
are two
finger actuable switches represented generally at 20. Of these switches,
switch
22 is designated as a "menu" switch, while switch 24 is designated as a
"select"
switch. Note that the readout assembly 18 is angularly oriented with respect
to
the grip axis 26 of the apparatus 10. With this configuration, the user may
observe prompts and cues appearing at the readout 18 as represented by the
symbolic user eye station 28 and line of sight represented symbolically at
arrow
30. In this regard, note that the hand 32 of the user is grasping the hand
grasping portion 14. For the arrangement shown, the hand grasping portion 14
is
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represented as exhibiting its largest widthwise extent, i.e., 27/8 inches. To
gain
this larger widthwise extent, auxiliary grip components 34 and 36 are employed
in conjunction with the hand grasping portion 14. These auxiliary grip
components will be seen to be removable as well as universally positionable so
as to provide the noted widthwise adjustments in 1/2 inch increments.
[0063] Referring to FIG. 2, the instrument 10 is shown as it is employed
for
diagnostic activities. For this purpose, the auxiliary grip components 34 and
36
as seen in FIG. 1 have been reversed in their orientation at hand grasping
portion 14. Note, additionally, that the symbolic eye station at 38 is now
that of
the diagnostician with a line of sight as represented symbolically at arrow 40
addressing the readout 18 (not shown). Note that the line of sight 40 is
directed
toward the auxiliary grip component 36 and the data readout for diagnostic
purposes is not visually available to the user whose hand is represented at
32.
Seen additionally in FIG. 2 is a serial communications port 40 and a battery
compartment access cover 42. The serial port offers, for diagnostic purposes,
the instantaneous transfer of real-time data to remote monitoring and data
archiving equipment.
[0064] Looking to FIG. 3, an exploded perspective view of the apparatus 10
is
provided. In the figure, the grasping portion 14 is seen to be comprised of
two
mirror image sides 52 and 54. Integrally molded with the sides 52 and 54 are
the
two housing components of the interactive portion 16 as shown respectively at
56 and 58. Plastic inserts or plugs are shown at 60 and 62 which are
insertable
within respective screw cavities 64 and 66. Extending from grasping portion
side
54 is an integrally molded screw receiving post 68. In similar fashion, screw
receiving post 70 is integrally formed with and extends from component 58.
Additionally, a screw receiving post 72 extends from component 58. Post 72
receives a screw inserted through a battery cavity 74 inwardly disposed from
cover 42. Post 72 additionally functions to contribute to the support of a
printed
circuit board 76 by virtue of its insertion through an aperture 78 formed
therein.
Note that the printed circuit carrying board 76 also supports communications
port
40. In this regard, the port 40 extends into a rectangular opening 80 formed
within interactive portion 58 of housing 12. Further extending inwardly from
component 52 are two force plate support plates 53 and 55
[0065] Disposed centrally within the cavity defined by gripping portion
sides
52 and 54 is a steel thrust plate 82 having a thickness and rigidity elected
to
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withstand compressive gripping forces which may range, for example, up to
about 205 pounds. Plate 82 is configured with two holes 81 and 83 which are
used to restrain the plate from disengaging from the assembly when fitted over
respective posts 53 and 55. Elongate side 84 of thrust plate 82 is configured
for
insertion within an elongate groove 86 of a base grip component 88. Grip
component 88 is formed of a rigid plastic and includes an outwardly disposed
base grasping surface 90 upwardly located in adjacency with the grasping
surface 90 is one component of a base connector assembly represented
generally at 92 and which is seen to be integrally molded with the grip
component 88 and incorporates a slot or opening 94 in conjunction with a tab
receiving trough 96. A tab component (not shown) of the base connector
assembly feature of the base grip component 88 will be seen to extend from the
end thereof opposite connector assembly component 92.
[0066] Two oppositely disposed edge extensions 98 and 100 of the trust plate
82 are configured for operative association with a load cell assembly
represented
generally at 102. Load cell assembly 102 includes an elongate steel base 104
incorporating two slots for receiving extensions 98 and 100, one such slot
being
revealed at 106. Connection between the base 104 and thrust plate 82 is
provided by pins (not shown) which extend through mated bores 108 and 110
and 112 and 114. The load cell assembly 102 further includes an elongate outer
force component 116. Two field plate-form load cells 118 and 120 are mounted
from load cell mount structures shown, respectively at 122 and 124 formed
within
base 104. Such mounting is in cantilever fashion, the load cell 118 being
attached to mount 122 by a screw and mounting plate assembly 126. Similarly,
load cell 120 is attached in cantilever fashion to mount structure 124 by a
screw
and mounting plate assembly 128. Outer force component 116 is seen to have a
centrally disposed rectangular post portion 120 which is attached by a
connector
plate assembly to the mutually inwardly extending ends of the load cells 118
and
120. the attachment plate assembly for this union is seen in general at 132.
Assembly 132 is seen to be formed of two plate components 132a and 132b
coupled, in turn, to load cells 120 and 118. Screws are used to effect the
attachment.
[0067] The base grip component positioned oppositely of base grip
component 88 is shown at 134. In similar fashion as component 88, the base
grip component 134 is configured with a base connector assembly having one
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component at 136 which incorporates a slot and trough (not shown) in similar
fashion as described at 92 in connection with component 88, a tab protrusion
of
generally cylindrical configuration shown at 138 is disposed oppositely from
connector assembly component 136. The rigid plastic base component 134 is
attached to elongate outer force component 116 of the load cell assembly 102.
This attachment is provided by the insertion and crimping of two posts 134a
and
134b (FIG. 4) within respective holes 117 and 119 formed within force
component 116. a slot in component 1134 is provided to positively locate it
onto
the outer profile of component 116. In general, posts 134a and 134b (FIG. 4)
are
inserted through holes 117 and 119 and then melted with a hot iron to
mechanically secure the two pieces 134 and 116 together as one sub-assembly.
With the arrangement shown, gripping compressive force is asserted from the
base component 188 through the thrust plate 82 into the load cell assembly
102.
This force is counteracted by gripping force asserted from base gripping
component 134.
[0068] Auxiliary grip component 34 is shown in the figure in spaced adjacency
with respect to the base grip component 134. Auxiliary component 34 is
configured with an outwardly disposed auxiliary grasping surface of generally
half cylindrical cross section with a grasping surface profile curved
concavely
outwardly, for example, at region 140. This curvature is provided for
enhancing
grip contact with the palm of the user hand and for applying force centrally
to the
load cell assembly. Component 34 is formed with an auxiliary connector
assembly which includes a flexible engaging tab 150 configured for insertion
within the connector component 136 of base grip component 134. Connection at
the opposite end is provided by a curved slot (not shown) which receives the
tab
protrusion 138 of base grip component 134. The connector assemblies are
universal such that each of the auxiliary grip components may be mounted upon
either of the base grip components 88 or 134. In this regard, not that a
similar
flexible engaging tab 152 is positioned upwardly upon auxiliary grip component
36. Similarly, the component 36 is configured having a curved slot 154 at its
opposite end which receives tabs, for example, as at 138. The mounting of
either
auxiliary grip component 36 or 34 will increase the widthwise extent of the
grip by
one half inch. Accordingly, with both auxiliary grip components installed, the
widthwise extent of the grip is increased to 27/8 inches.
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[0069] Interacting region 16 also includes a top cover 156. Formed, as the
other components, of ABS plastic, the cover 156 includes a rectangular bezel
opening 158 within which the LCD 18 is positioned. Integrally formed with top
cover 156 is a downwardly depending switch cover 160 through which two
rectangular openings 162 and 164 are provided. The switching function 20 is
mounted upon a separate circuit board 166 which is seen to carry two push
actuated switches as earlier described at 22 and 24 and identified by the same
numeration in the instant figure. Located over the switches 22 and 24 is a
flexible
polymeric cover 168 formed of a flexible polymeric material such as
Santoprene,
a thermoplastic elastomer marketed by General Polymers of Charlotte, N.C.
Circuit board 166 is supported between two slots formed in the interior of
side
components 56 and 58, one of these slots is seen at 170. The LCD 18 is
mounted upon a circuit board 172 supported in turn, from interactive
components
56 and 58. A bus-type wiring harness electrically associates the switching
function 20, LCS 18, load cell assembly 102, the battery within compartment 74
and the circuitry carried by circuit board 76.
[0070] A sectional view of the instrument 10 is provided at FIG. 4. In the
figure, base grip component 88 is shown in conjunction with base connector
assembly component 92. In that regard, the slot 94 again is revealed as well
as
the tab receiving trough 96. At the opposite end, the base connector assembly
includes an outwardly extending arcuate tab 174. Auxiliary gripping component
= 36 is shown coupled to the base grip 88. Note that the auxiliary
component 36
has a grasping surface 176, the profile of which is undulatory to provide a
finger
grasping configuration. This undulatory profile further functions to provide a
finger grasping configuration which centers the gripping force on handle 88.
The
lower portion of the base grip component 88 is seen to be formed having an
outwardly extending arcuate tab 174 which slideably nests within the
corresponding arcuate slot 154 in auxiliary grip 36. The connector assembly
for
base grip component 134 is identical. In this regard, the component 134
includes
an arcuate outwardly extending tab 138 and a slotted receiver 136 structured
identically as that described at 92. Auxiliary grip component 34 is connected
to
base grip component 134 by sliding a protruding tab or tongue 138 into arcuate
slot 178. Additionally, the flexible engaging tab 150 is shown extending
through a
slot in connector component 136.
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[0071] FIGS. 5-7 illustrate variations of grip widthwise extent available
for
utilization of instrument 10 in conjunction with therapeutic protocols. In
general,
for such therapeutic protocols, the readout assembly 18 is arranged to face
the
eye station of the user. In FIG. 5, no auxiliary grip components are mounted
upon either base grip component 88 or base grip component 134. Accordingly
the widthwise extent of the grip is 17/8 inch. Looking to FIG. 6, the palm
engaging auxiliary grip component 34 is shown mounted over base grip
component 134. The increases the widthwise extent of the grip for therapeutic
applications to 23/8 inches. FIG. 7 illustrates the utilization of both
auxiliary grip
components 34 and 36 to provide a grip widthwise extent of 27/8 inches. As
before, the auxiliary grip components are arranged such that the user may
observe readout 18.
[0072] FIGS. 8 and 9 illustrate grip arrangements particularly suited for
diagnostic purposes wherein the diagnostician has exclusive access visual to
the
readout assembly 18. In FIG. 8, base grip component 134 is combined with
auxiliary grip component 34 to provide a widthwise grip extent of 23/8 inches.
Removal of the auxiliary grip component 34 returns the grip widthwise extent
to
17/8 inches.
[0073] In FIG. 9, both auxiliary grip components 34 and 36 are employed to
provide a maximum widthwise grip extent of 27/8 inches. It may be observed in
FIGS. 8 and 9 that the positioning of the auxiliary grips is reversed in the
sense
of the grip configuration shown in FIGS. 5-7.
[0074] Turning to FIG. 10, a block diagrammatic representation of the
controller components of instrument 10 is revealed. In general, the instrument
10
is microprocessor driven, for example, employing a type 8051 microprocessor as
represented at block 180. The controller is powered by a standard 9 volt
battery.
That voltage then is regulated to 5 volts for use by the circuit components. A
power supply to the strain gauge implemented load cells 118 and 120 is dropped
by a resistor such that the maximum current applied is limited to 50
milliamps.
Such power supply is represented in the figure at block 182 which, in turn, is
seen to be associated with microprocessor 180 via line 184 and with switch 24
via lines 186 and 188. Note that switches 22 and 24 respectively are labeled
"menu" and "select". Switch 24 serves the additional function of an on switch
or
enablement switch. Power also is seen to be supplied to the communications
connector 40 as represented at line 190. Communications connector 40, in turn,
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is seen coupled to a communications driver 192 as represented at line 194.
Driver 192 associated with the microprocessor 180 as represented at line 196.
The microprocessor 180 also provides control over an annunciator or buzzer as
represented at block 198 and line 200. Similarly, control to the liquid
crystal
display (LCD) 18 from microprocessor 180 is represented at line 202. A real-
time
clock is provided with the controller circuit as represented at block 204.
Time and
date data from that clock are used in conjunction with the monitoring and
memory features of the instrument 10 such that important data, including date
and time of a given trial regimen can be retained in memory and downloaded via
the communications port 40 when called for. The association of the real-time
clock function 204 and microprocessor 180 is represented at line 206. Archival
memory as well as temporary memory are provided with the controller. Archival
memory may be provided, for example, as an electrically erasable programmable
read only memory (EE PROM), an 8 kilobyte device which requires no power to
sustain its memory retention, i.e., it is non-volatile. The archival memory is
represented at block 208 and its association with the microprocessor 180 is
represented at line 210.
[0075] Load cells 118 and 120 are represented with that numeration in FIG.
10. These load cells are each configured as a four resistance balance bridge-
type load cell. The outputs of load cells 118 and 120 are directed to the
amplification function as represented by respective lines 212 and 214
extending
to amplifier block 216. The output of amplifier 216 is represented at line 218
extending to an analog-to-digital converter function represented at block 220.
Correspondingly, output of the converter function 220 is directed to the
microprocessor 180 as represented at line 222. Microprocessor 180 converts the
signal to a force value in pounds or kilograms which is displayed in the LCD
18.
The menu switch 22 is shown associated with microprocessor 180 via line 224,
while the select switch 24 is associated with that processing function as
represented at line 188.
[0076] Each of the instruments 10 is calibrated using nineteen
combinations
of six standard weights. A best fit is determined and the instrument is called
upon
to have a root mean square error (RMS) of 0.1 pounds or less to pass
calibration
requirements. Once the calibration constants has been determined, the system
is loaded with two redundant copies of the calibration constants. The zero
point
of the load cell is monitored at all times during the use of the instrument
10. If a
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drift is found, then a warning is shown at the LCD display 18. If any lead
wire to
the load cell becomes disconnected, then the built-in monitoring detects this
occurrence, shows an error message, and disables further use of instrument 10
until the power is reset. These features insure that the force reading shown
is
accurate and true. Absolute values of the outputs of load cells 118 and 120
are
summed to provide a force output signal. In general, the load measurement
accuracy of instrument 10 is better than 0.1 pound or 0.1% of applied force
whichever is greater.
(00771 In the discourse to follow, the sequences of the program protocol
carried out by instrument 10 are represented in flow chart fashion. In
general,
these flow charts commence with a configuration sequence if desired and then
look to two diagnostic protocols followed by two therapeutic protocols.
[0078] Turning to FIG. 11, the procedure seen to commence as represented
at block 230 with the selection of the grip widthwise extent. In general, that
grip
width is elected to accommodate variations in user hand sizes. The program
then continues as represented at line 232 and block 234 wherein, where
appropriate, one or two auxiliary grip components as at 34 and 36 are
installed in
an orientation providing for user viewing of display 18 as illustrated in
connection
with FIG. 1, or in an arrangement for therapeutic practitioner viewing to the
exclusion of the user as described in connection with FIG. 2. The program then
continues as represented at line 236 and block 238 providing for the
enablement
of instrument 10 by actuation of select switch 24. Upon such actuation, as
represented at line 240 and block 242 a start-up message is provided at
display
assembly 18 for an interval of two seconds. Then, as represented at line 244
and
block 246 a prompt is displayed at readout 18 identifying a default
configuration
wherein pounds as opposed to kilograms are elected; an audible tone is
enabled, and for a diagnostic test referred to as "rapid exchange" wherein
instrument 10 is passed from one hand of the user to the other and then back
for
a number of exchanges, the user providing a grip force trial at each exchange.
The rapid exchange default values are ten exchanges with 1.5 seconds available
for user gripping or squeezing. Following the publication of the screen as
represented at block 246, should the user not actuate either the switches 22
or
24, then as represented at line 248 and block 250 the instrument 10 will turn
off
or power down at the end of a five minute interval. This feature is always
active,
i.e., turning off five minutes after a last switch actuation.
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[0079] With the publication of the screen as represented at block 246, then as
represented at line 252 and block 254 the practitioner or user is called upon
to
determine whether to enter a configuration sequence or to progress to a
diagnostic grip test. To enter the latter diagnostic grip test sequence, as
represented at line 256 and block 258 by pressing switch 24 display 18 will
prompt the user to press the select switch 24 to commence a diagnostic grip
test
sequence. Where the select switch 24 is actuated, then the program enters the
diagnostic grip test sequence as represented at line 260 and node A.
[0080] Where a determination on the part of the practitioner or user is made
to enter a configuration sequence, then as represented at line 262 and block
264
the configuration sequence is entered by actuating switch 22. As represented
at
line 266 and block 268 the initial configuration looks to units. Recall from
block
246 that the instrument 10 defaults to a units evaluated in pounds. As
represented at line 270 and block 272 by actuating select switch 24 the units
parameter can be converted to kilograms instead of pounds. The program then
continues upon depressing or actuating menu switch 22 as represented at either
lines 274 or 276 leading to block 278. As represented at block 278, the user
then
is given the opportunity to delete the audible tone. In this regard, by
actuating
select switch 24, as represented at line 280 and block 282, the tone is
deleted,
display 18 showing the term "tone" in connection with the letter N.
[0081] The configuration sequence then continues as represented at either
lines 283 or 284 with the actuation of menu switch 22. This actuation of
switch 22
provides for the establishing of a rapid exchange diagnostic test cycle time
change. As set forth at block 286 the default cycle time is 1.5 seconds.
However,
by actuation of select switch 24, as represented at line 288 and block 290 the
operator may change the cycle time to 2.5 seconds. The program then continues
by actuating the menu switch 22 as represented at either of lines 292 or 294.
These lines lead to the configuration alteration represented at block 296.
Recall
from block 246 that the default number of exchanges for the rapid exchange
diagnostic procedure is 10.
[0082] However, as represented at line 298 and block 300 the operator may
change the number of exchanges from 10 to 20 by actuation of select switch 24.
The program then returns to line 244 by actuation of the menu switch 22 as
represented at lines 302 and 304. As described in connection with block 258,
line
260 and node A, the operator may elect to proceed with a diagnostic grip test.
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[0083] Referring to FIG. 12A, node A reappears in conjunction with line
306
extending to the query posed at block 308 wherein a determination is made as
to
whether or not to enter a diagnostic grip test mode. Where the operator
determines that the diagnostic grip test mode should be entered, then as
represented at line 310 and block 312, the grip test mode is entered by
actuating
select switch 24. The operator is then prompted at display 18 to actuate
select
switch 24 to enter a max test mode. Accordingly, with the actuation of switch
24,
as represented at line 314 and block 316 the maximum diagnostic grip test mode
is entered. On the other hand, as represented at line 318 and node B by
actuating the menu switch 22, the practitioner may cause instrument 10 to
enter
a rapid exchange sequence.
[0084] Returning to block 316, the maximum strength grip test can be
carried
out with 10 maximum squeezing force trials. At the conclusion of a given
number
of such trials, the practitioner actuates select switch 24, whereupon
computations are carried out. Accordingly, as represented at line 320 and
block
322 the user is prompted with the message "squeeze hard!!!" at the readout 18.
The program will elect the highest force applied during such squeezing
activity,
whereupon the user releases the grip force as represented at line 324 and
block
326. Then instrument 10 will publish the maximum force applied by the user as
represented at line 328 and block 330, a first maximum grip evaluation being
shown as an example as 64.4 pounds. Block 330 also indicates that the user is
prompted to either actuate the select switch 24 to accept the published
maximum
squeeze evaluation as set forth at block 330 or to squeeze the grip 14 again.
Such squeezing again will provide a substitute maximum grip force evaluation.
Then, as represented at line 332 and block 334 the query is posed as to
whether
the select switch 24 has been actuated. In the event that it has not, then the
program loops as represented at line 336 extending to line 320, whereupon a
maximum grip effort again is undertaken. Where the operator elects the
maximum first trial grip force evaluation, then as represented at line 338 and
block 340, the program will compute an average of force values, standard
deviation and coefficient variation, albeit it for one trial at this junction
in the
procedure.
[0085] The program then continues as represented at line 342 and block 344
to display computed values which, as noted above, for the first trial are
irrelevant.
However, as the number of trials increases, those computed values gain
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significance. Next, as represented at line 346 and block 348 the program
commences to carry out a next maximum grip test by providing a prompt at
readout 18 which advises the user to "squeeze hard!!!" and indicates that this
is
a second trial as represented by the terms: "MAX 2". Following a squeezing of
the grip region 14, as represented at line 350 and block 352 the user releases
the grip force and, as represented at line 354 and block 356 the maximum force
asserted by the user is published, for example, showing 60 pounds for a "MAX
2"
trial. This prompt further advises the user to actuate select switch 24 to
elect the
published grip force value or to squeeze again to carry out a next trial. The
program then continues as represented at line 360 and block 362 to determine
whether or not select switch 24 had been actuated. In the event that it had
not
been actuated then the program loops as represented at lines 364 and 346
whereupon the user again may carry out the second maximum grip trial. Where
switch 24 has been actuated, then as represented at line 366 and block 368,
the
program carries out a computation of the average of the maximum forces
asserted and computes standard deviation and coefficient of variation which
are
submitted to memory. The program then continues as represented at line 370
and block 372 whereupon the values computed in connection with block 368 are
published at display 18. The above maximum grip test trials may be reiterated
for
trials. Accordingly, as represented at line 374 and block 376 the maximum
test trials are reiterated for a total of N tests (10 maximum) and the
computed
values of average force, standard deviation and coefficient of variation are
both
submitted to memory and published at display 18. As represented at line 378
and block 380 the user may restart this max test sequence following the Nth
trial
by actuating select switch 24, whereupon the program returns as represented at
line 382 to 310 (FIG. 12A). Returning to block 380, by actuating menu switch
22,
as represented at line 384 and block 386, a subsequent actuation of select
switch 24 will return the program to a previous menu. As represented at line
388
and block 390 by again actuating menu switch 22, as represented at line 392
the
program reverts to node B as described in conjunction with FIG. 12A. By again
actuating select switch 24, as represented at line 394 the program returns to
entry into the maximum grip diagnostic test, line 394 extending to line 314
seen
in FIG. 12A. This circular logic is made available at a variety of locations
within
the program.
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[0086] Returning to FIG. 12A, where the query posed at block 308 results
in a
negative determination that the maximum grip test diagnostic mode is not to be
entered, then, by actuation of menu switch 22, as represented at line 396 and
block 398 a determination is made as to whether to exit a diagnostic mode and
enter a therapy based mode. Where a therapy mode is not elected, then as
represented at line 400 and block 402 a previous menu may be elected by
actuating the select switch 24 as represented at line 404 and node D. By
actuating menu switch 22, then as represented at line 406, the program loops
to
line 306 and the query posed at block 308. Where a therapy mode is elected by
the user, then as represented at line 408, the program diverts to a therapy
mode
of performance as represented at line 408 and node E.
[0087] Looking back to the query posed at block 334, where the menu switch
22 is actuated as opposed to electing a maximum grip value, then as
represented at line 410 and block 412 the program will reconfigure for
restarting
the grip test mode. Once at this point in the program as represented at block
412, by again actuating select switch 24, the program reverts as represented
at
line 414 to line 320 to carry out another maximum grip trial. On the other
hand,
where menu switch 22 is actuated, as represented at line 416 and block 418 an
indication will be given to the operator that to elect previous menu, select
switch
24 is to be actuated. As represented at line 419, the program then reverts to
node C. Node C again appears in FIG. 12A in conjunction with line 420
extending to line 310. Where menu switch 22 is again actuated, the program
reverts to block 412 as represented at line 422.
[0088] Looking again to FIG. 12B and the query posed at block 362, where
the second maximum grip test is not selected by menu switch 22 is actuated,
then as represented at line 424 and block 426 the program enters a mode for
restarting the maximum grip test. By again actuating menu switch 22, as
represented at line 428 and block 430 the user is prompted to enter the
previous
menu position in the program by actuating the select switch 24. Accordingly,
by
actuating switch 24 as represented at line 432, the program reverts to node C.
Returning to block 426, where the select switch 24 is actuated, then the
program
loops as represented at line 434, to line 346 to again undertake the second of
the maximum grip tests. By actuating menu switch 22 from the program location
of block 430, as represented at line 436 the program reverts to its position
at
block 426.
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[0089] The diagnostic performance mode of the instrument 10 also provides
for the carrying out of a rapid exchange (RE) test. With the rapid exchange
test,
the user may grip instrument 10 in the manner shown in FIG. 2 such that the
therapist or practitioner may observe readout 18 to the exclusion of the user
or
patient. With the rapid exchange, a maximum grip force is exerted by the user
or
patient in exchanging between the right and left hands under a controlled
exchange timed cycle which will have been elected, for example, in connection
with the configuration mode described in connection with FIG. 11. It may be
recalled that the number of exchanges may also be elected by the diagnostician
as 10 or 20 efforts or trials. The rapid exchange mode of performance is
elected
as represented at block 312 and line 318 extending to node B described in
connection with FIG. 12A. Node B reappears in FIG. 13 in association with line
440 and block 442. Referring to that figure, block 442 is seen to provide for
a
prompt to the practitioner to actuate select switch 24 to enter the rapid
exchange
mode. Upon actuating switch 24, as represented at line 444 and block 446 a
prompt is provided at readout assembly 18 advising the user to squeeze the
grip
14 with the right hand to start the rapid exchange sequence. As represented at
line 448 and block 450 the program awaits the presence of a right hand
squeezing force. Until that squeezing force is asserted, the program dwells as
represented at loop 452 extending to line 444. Where a squeezing force is
detected, then as represented at line 454 and block 456 the program
commences to time out the succession of periods or time-hacks allocated for
this
cycle of the rapid exchange diagnostic procedure. That time interval may have
been elected in the configuration mode as described in conjunction with blocks
286 and 290 (FIG. 11). For example, the cycle time, Tr has a default value of
1.5
seconds or the last value selected.
100901 As represented at line 458 and block 460 the user will have squeezed
the grip region 14 and the maximum hand force value evolved will be submitted
to memory. Then as represented at line 462 and block 464 a determination is
made as to whether the menu switch 22 has been actuated. In the event that it
has not, as represented at line 466 and block 468 the program determines
whether the Nth, i.e., 10th or 20th trial has been completed. In the event
that it has
not, then as represented at line 470 and block 472 the rapid exchange test has
not been completed and an audible tone cue (time hack) is provided indicating
that the instrument should be switched to the opposite hand. A short dwell
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occurs as represented at line 474 and block 476 wherein the instrument
determines whether or not a squeeze force has been asserted. In the event that
it has not, then the program loops as represented at line 478. Where the user
has imparted a squeezing force to the instrument, the program continues or
loops as represented at line 480 extending to line 458 leading to a next trial
in an
alternate hand.
[0091] Returning to block 464 where menu switch 22 is actuated in the
course
of carrying out rapid exchange trials, an affirmative determination will be
made
with respect to the query posed at that block. Accordingly, as represented at
line
482 and block 484 the user is prompted to restart the rapid exchange test by
actuating select switch 24. Where select switch 24 is actuated, then as
represented at line 486 the program reverts to line 444 and block 446. On the
other hand, where menu switch 22 is actuated, then as represented at line 488
and block 490 the user is prompted to revert to the previous menu by actuating
select switch 24. Where select switch 24 is so actuated, then the program
reverts
to node C as represented at line 492. Note, additionally, that if menu switch
22 is
actuated in conjunction with the prompt provided at block 442, then as
represented at line 494 the program reverts to line 488. Returning to block
490,
where menu switch 22 is actuated then as represented at line 496 and block 498
the program computes and displays the overall average of the maximum trial
values, standard deviation and coefficient of variation for the N trials. That
data is
submitted to memory. Should menu switch 22 be actuated at this juncture, then
as represented at lines 500 and 482, the program returns to block 484. Where
the select switch 24 is actuated, however, as represented at line 502 and
block
504 the maximum force value for trial N and the average SE and CD for all
trials
is displayed. On the other hand, where the menu switch 22 is actuated, then as
represented at lines 506 and 482, the program reverts to block 484.
[0092] Where the select switch 24 is actuated repetitively, then as
represented at line 508 and block 510 the succession of trials 1 through N is
displayed. Additionally, the unchanging average for all those trials is
displayed
for convenience. Further, a query is posed as to whether the Nth trial has
been
displayed. Where it has not, then the display program loops as represented at
line 512 extending to line 502. On the other hand, where the Nth trial has
been
displayed, then as represented at line 514, the program loops to line 502 to
repeat the succession of displays.
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[0093] It may be
recalled that in conjunction with block 398 in FIG. 12A, a
therapy mode may be entered by actuation of select switch 24 as discussed in
connection with line 408 and node E. Node E reappears in FIG. 14A in
conjunction with line 520 and block 522. Block 522 indicates that the readout
18
will publish information that a grip therapy is available by actuation of
select
switch 24. It may be recalled that the parameters of time and force are
somewhat
pre-established under the regimen of the instant program. In this regard, it
is
important that the isometric grip exercise be constrained within predefined
force
and time interval of holding and resting limits. These parameters are
nominated
in the program and while some variations are permitted, those variations are
retained within physiologically determined limit values. Of importance to the
grip
therapy at hand, it may be observed that it is predicated upon the patient or
users actual and unique the maximum gripping force which initially is
evaluated
and then treated by a preordained but still electable target valuation. In
general,
the prompt and cues provided at display 18 are made available to the patient
or
user by a handle configuration as described in conjunction with FIG. 1.
Looking
to FIG. 14A, block 522 provides for a display at readout 18 indicating that a
grip
therapy mode is available by actuation of select switch 24. As represented at
line
524 and block 526 a determination is made as to whether a fixed mode of
therapy or a stepped mode of therapy is to be elected. A fixed therapy is
elected
by actuation of select switch 24 as represented at line 527 extending to block
528. Block 528 indicates that the fixed exercise configuration mode has
entered.
With such entry, as represented at line 530 and block 532 readout 18 prompts
that the user will be given opportunities to adjust the target load factor,
the
number of repetitions of trials of the grip therapy, the duration of the
holding of
the grip force at a target value and the interval for a intergripping rest.
However,
as an initial component of the procedure, the maximum grip force value for a
given patient is determined. Accordingly, upon actuating switch 24 as
represented at line 534 and block 536 the user is prompted to squeeze the grip
with maximum force by publishing the terms: "squeeze hard!!!". Then, as
represented at line 538 and block 540, the squeeze generated load or force
value is outputted to the microprocessor 180 (FIG. 10). The maximum valuation
of this initial force evaluation then is displayed at readout 18 as
represented at
line 542 and block 544. In the latter block, it may be observed that a sample
force valuation of 90.3 pounds is published at readout 18. The user can elect
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valuation as the maximum force value to be used in the program by actuating
select switch 24 as represented at line 546 and block 548. However, a prompt
at
readout 18 also provides that the user may retry this maximum grip force
evaluation as represented at loop line 550 extending to line 538. Where the
user
or therapist determines that an appropriate grip force has been derived, then
as
represented at line 552 and block 554 the elected maximum force value is
submitted to memory and the program continues as represented at line 556 and
block 558. employing the elected maximum squeeze force, the program
computes a target grip force using a default factor of 50%. Additionally, the
program establishes a trial repetition number at a default number of 4; a hold
on
target force interval of 45 seconds; and a default rest interval of 120
seconds. As
represented at line 560 and block 562 the computed target level then is
displayed at readout 18 along with the value of the elected maximum grip force
and the default target factor of 50%. The terms "Target 451b" blink as a
prompt
that the factor can be altered within an established range. The user or
practitioner then is given the opportunity to adjust the target factor
percentage in
10% increments from 10% to 100% as represented at line 564 and block 566 by
actuating the menu switch 22. Next, as represented at line 568 and block 570
the
program computes at a new target value based upon the elected factor, an
arbitrary designation "AA" being shown. A lower enabling grip force threshold
also is derived. Should the user elect a target factor other than the 50%
value by
adjustment in connection with block 566, the program will automatically
nominate
hold on target intervals and rest intervals for each available 10% selection
from
within the range from 10% to 100% which the user may have elected. This,
again, is for the purpose of protecting the user from excessive effort
intervals and
inadequate rest intervals. However, still within the mandated overall ranges,
the
user or therapist can change those values for the hold on target effort and
rest
effort. The nominated hold or "Effort" and rest intervals contained in the
program
are summarized in Table 1 below.
TABLE
10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Max Max Max Max Max Max Max Max Max Max
120 120 90 60 45 15 12 10 5 3
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sec. sec. sec. sec. sec. sec. sec. sec. sec. sec.
Effort Effort Effort Effort Effort Effort Effort Effort Effort Effort
60 120 120 120 120 120 120 60 60 60
sec sec sec sec sec sec sec sec sec sec
Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest
[0094] Following the target load computation, as represented at line 572
and
block 573 the program displays the newly computed target force value at
readout
18 along with the default values for number of repetitions (which defaults at
4),
and the nominated hold on target interval and the rest interval (Table 1). As
a
prompt, the readout "4 REP" blinks to indicate that adjustment is available to
the
user. The program then continues as represented at line 574 which reappears in
FIG. 14B extending to block 576 which provides for adjusting the number of
repetitions between the values 1 and 10 by actuating menu switch 22. Note that
the maximum number of repetitions made available to the user is 10. The
program then continues by actuating switch 24 as represented at line 578 and
block 580 indicating that the computed target force level (AA) and the newly
elected repetition number herein represented as "B" is provided at the display
along with the nominated values for hold on target interval (CCC) and rest
interval (DDD). In this display, the terms: "CCC HOLD" blink to prompt the
user
to make any desired adjustments within the mandated limits of from 5 seconds
to
120 seconds. Accordingly, as represented at line 582 and block 584 the user or
practitioner may adjust the hold on target interval by actuating menu switch
22.
When the desired hold on target interval has been displayed at readout 18, the
select switch 24 is actuated and the program progresses as represented at line
586 and block 588 to provide a display at readout 18 which indicates the
computed target force level AA; the elected repetition number (B) and the
elected hold on target interval (CCC). The display also will blink the terms
"DDD
REST" to prompt the user to adjust the rest interval to a desired value within
the
mandated interval range of 10 seconds to 120 seconds. Accordingly, as
represented at line 590 and block 592 the user or practitioner can adjust (by
decade components) the extent of the rest interval by actuating menu switch 22
until a desired interval value is displayed. Once the desired interval is so
displayed, an actuation of select switch 24 will enter it into memory. Next,
as
represented at line 594 and block 596 the program displays the now elected
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values including the target force (AAlb); repetitions (B REP); the hold on
target
interval (CCC); and the rest interval (DDD). The program then provides a
prompt
to the user to start the therapy by actuating the select switch 24 as
represented
at line 598 and block 600. Upon such actuation of switch 24, as represented at
line 602 and block 604 the program prompts the user at readout 18 to apply a
gripping force at the target level along with the further prompt "squeeze".
Next,
as represented at line 606 and block 608 the program determines whether the
grip force applied by the user is within 10% of the computed target force
value
(AA). This is the lower threshold determination as described in conjunction
with
block 570. In the event that the applied gripping force is not within 10% of
the
computed target value, the program loops as represented at line 610 extending
to block 604 providing for a continuation of the prompt to hold on target.
Where
the applied grip force is within 10% of the computed target force value, then
as
represented at line 612 and block 614 the program commences to time out the
hold on target interval previously elected or nominated (CCC) as discussed in
connection with block 584. While this hold on target force interval is
underway,
as represented at line 616 and block 618 a dynamic comparison value
computation is carried out over a sequence of short time components within the
hold time out interval. That comparison value is utilized in driving a bar
graph
form of display functioning to cue the user as to a proper grip force level.
During
this hold interval, as represented at line 620 and block 622 the program also
compares the applied grip force with a force upper limit which is computed as
125% of the target force. In the event that the applied grip force is above
that
upper limit, then as represented at line 624 and block 626 an audible cue is
sounded to warn the user that excessive force is being applied which is
outside
the proper protocol for the therapy. The program then continues as represented
at lines 628 and 630 whereupon as set forth at block 632 a score as a
percentage of target value is computed for a sequence of time increments. This
score may be utilized by the user and the therapist for purposes of evaluating
the
quality of the exercise regimen carried out by the user.
100951 Turning momentarily to FIG. 15, a routine is depicted functioning to
carry out the computation and display of the noted score values. This routine
is
entered into as represented at node 634 identifying it as a display of the
score
value. The routine commences as represented at line 636 and block 638
indicating that the currently applied grip force or load value is read as the
user
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attempts to match the target force value. Then, as represented at line 640 and
642, the score is determined by dividing that read force by the pre-computed
target force and multiplying the result by 100 to provide the score as a
percent.
This score is developed for sequential increments of time, preferably each
increment representing 1% of the hold on target interval (CCC). As represented
at line 644 and block 646, the score is converted into three display
characters.
Then, as represented at line 648 and block 650, three characters representing
the score are sent to readout 18 for display. The score may be above or below
100%, 100% representing an on target grip force.
[0096] Returning to FIG. 14B, the program continues as represented at line
652 which reappears in FIG. 14C extending to block 654. Block 654 indicates
that a display is provided at readout 18 which cues the user as to essentially
instantaneous score value, the time remaining for holding on target and
further
cues the user as to the level of grip force being applied with respect to
target
through the utilization of a center pointer visual cue representing the target
load
value and an effort dynamic bar graph visual cue having a top position present
as a bar graph top line. That top line will be aligned with the center pointer
when
the load value at output represents a force equal to the target load value.
The top
line will move away from the center pointer when the load value output or grip
force exerted by the user represents a force which deviates from the target
load
value.
[0097] Looking momentarily to FIGS. 16A-16E, a representation of the
display
so provided for differing grip force activity is set forth. In FIG. 16A, the
dynamic
bar graph extends to the right of the center pointer indicating a grip force
which is
too low. This lower grip force also is indicated by the lower score value of
62%.
The display also includes an indication of the time remaining for the hold on
target interval, for example, 100 seconds. FIG. 16B also indicates through the
dynamic bar graph that the asserted grip force is still too low but improved
over
that shown in FIG. 16A as indicated by the shorter extent of the dynamic bar
graph to the right of the center pointer and a higher score value of 75%. FIG.
16C shows a cue wherein the user grip force is at the target force, the top
line of
the bar graph being aligned with the center pointer and a score of 100% being
displayed. Additionally, as before, the time remaining for the hold on target
interval is displayed. FIG. 16D shows that an excessive grip force is being
applied by the user, the dynamic bar graph extending to the left of the center
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pointer. This excessive force also is indicated by a score value of 125%. Time
remaining in seconds within the hold on target interval also is displayed.
Finally,
FIG. 16E shows a still more excessive application of grip force on the part of
the
user, the dynamic bar graph top line extending well to the left of the center
pointer and a score of 137% being represented. As before, time remaining in
the
"on target interval" is also displayed.
100981 Returning to FIG. 14C the program is seen to continue as
represented
at line 656 and block 658 wherein a query is made as to whether the hold on
target interval has timed out. In the event that it has not, then the program
dwells
as represented by loop line 660 extending to node I which reappears in FIG.
148
with line 662 extending to line 620. In the event of an affirmative
determination
with respect to the query posed at block 658, then as represented at line 662
and
block 664 an audible cue is generated at the annunciator 198 (FIG. 10). With
the
generation of this audible cue, then as represented at line 666 and block 668
the
rest interval commences to be timed out. It may be recalled that the rest
interval
was elected in conjunction with block 592 (FIG. 14B). during this rest
interval, as
represented at line 670 and block 672 the program will provide a display at
readout 18 which indicates the number of trials or efforts remaining in
conjunction with the elected repetition value. At the termination of the first
trial,
that value will be B-1. The display also provides the average value of score
and
the interval of time remaining in the rest interval. Next, as represented at
line 674
and block 576 a query is made as to whether the rest interval has timed out.
In
the event that it has not, then the program dwells as represented at loop line
678. Where the query posed at block 676 results in an affirmative
determination,
then as represented at line 680 and block 682 an audible cue is generated and
the program continues as represented at line 684 and block 686 providing for a
reiteration of the trial sequence. As represented at line 688 and block 690 a
query is made as to whether the elected number of repetitions of the trial (B)
has
been accomplished. In the event that that elected number of repetitions has
not
been completed, then the program dwells as represented at line 692. In the
event of an affirmative determination with respect to the query posed at block
690, then as represented at line 694 and block 696 a final or average score is
computed and submitted to archival memory in conjunction with calendar and
force data. In the latter regard, each of the average grip force values
asserted by
the user for each trial are recorded. Next, as represented at line 698 and
block
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700 the program determines or selects an appropriate message of congratulation
or warning base upon the computed final score. The program then continues as
represented at lines 702 and block 704 to publish the selected message at
readout 18 and continues as represented at line 706 to node G.
[0099] Node G reappears in conjunction with line 708 (FIG. 14A) and block
526. Where the user or therapist has determined to cause instrument 10 to
enter
into a stepped therapy mode, menu switch 22 is actuated as represented at line
710 and the program displays a prompt to the user as represented at block 712
indicating that the step therapy mode may be entered by actuating select
switch
24 as represented at line 714 and node F.
1001001 Referring to FIG. 17A, node F reappears in conjunction with line 716
and block 718 providing for the entry of instrument 10 into a stepped exercise
configuration mode. In this therapeutic mode the maximum grip strength unique
to the user or patient is determined, whereupon the therapeutic gripping
regime
is one wherein the target load level as well as hold on target intervals and
rest
intervals vary in accordance the sequence of steps or gripping trials. The
program opens as represented at line 720 and block 722 with a display at
readout 18 prompting that the user is to be called upon to establish a maximum
grip force level and carry out a setting of the number of steps and
repetitions of
the therapy. The user then actuates the select switch 24 and, as represented
at
line 724 and block 726 the program displays a prompt at readout 18 indicating
that the user should carry out a maximum grip force exercise, the prompt
including the terms; "squeeze hard!!!". Then, as represented at line 728 and
block 730 the user will have applied maximum squeezing force to the grip and
that will have generated a load value output. While this load value output is
being
generated, as represented at line 732 and block 734 the program displays a cue
at readout 18 which publishes the value of the maximum gripping force. Should
the practitioner or user wish to attempt to improve that value, he or she is
prompted to actuate select switch 24 and elect the value published or to
squeeze
the grip again. Where the user elects the value published, then as represented
at
line 736 and block 738 a determination is made as to whether the select switch
24 has been actuated. In the event that it has not, then the system dwells as
represented at loop line 740 extending line 728. Where the select switch 24
has
been actuated, then as represented at line 742 and block 744 the maximum
gripping force value which was selected is submitted to memory and, as
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represented at line 746 and block 748 the system provides a 1 step default
value
and a repetition of the step exercise is defaulted to a value of four. The
program
then continues as represented at line 750 wherein the system provides a prompt
at readout 18 which displays the value of a selected maximum gripping force
and
further prompts the user that a default of 1 step is present and a default of
four
repetitions is present. The term "1 step" is intermittent or blinks as a part
of this
prompt to the user to elect the number of steps desired. This display is
represented at block 752. Then, as represented at lines 754 and block 756 the
user or practitioner is permitted to adjust the number of steps within a range
of 1
to 5 steps. As discussed above, this range is mandated within the system and
the adjustment in the number of steps may be carried out by actuating menu
switch 22.
[001011 The number of steps elected adjusts the percentage of maximum grip
force factor in accordance with a preordained schedule. That schedule is
provided in Table 2 below. For example, if only one step is elected, that
target
grip factor will be 20%. On the other hand if five steps are elected, the
first trial
will be at 100% of maximum grip force. The second step will be at 80% of
maximum grip force and so forth. On the other hand, if four steps are elected,
the
initial trial will be in conjunction with an 80% maximum grip force factor;
the
second step will be at 60% and so forth as set forth in Table 2. For each of
these
percentages as set forth in Table 2, the corresponding hold on target or
effort
interval and rest intervals will follow the values given above in Table 1.
TABLE 2
No. of Steps Elected
1 2 3 4 5
1 StStep as % Max 20% 40% 60% 80% 100%
2nd Step as % Max 20% 40% 60% 80%
3rd Step as % Max 20% 40% 60%
4th Step as % Max 20% 40%
5th Step as % Max 20%
1001021 The step value is elected by actuation of select switch 24 and the
program continues as represented at line 758 and block 760. Block 760
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replicates a display at readout 18 which prompts the user by indicating that
the
maximum elected gripping force selected was 90 pounds and that A steps were
selected and a further prompt is provided showing blinking or intermittent
display
of 114 REPS". Then, as represented at line 762 and block 764 the operator may
adjust the number of repetitions of the program to a value within a
preordained
number of 1 through 10 by actuating menu switch 22. The elected number of
repetitions then is selected by actuation of switch 24 and, as represented at
line
766 and block 768 the system displays the now selected parameters of a
maximum grip force, for example, 90 pounds, an election of A steps in the
regimen and an election of "B" repetitions. Next, as represented at line 770
and
block 772 the stepped exercise therapy is entered. Upon entry into this
stepped
exercise trial mode, target values are computed based upon the number of steps
elected and the hold on target and rest intervals will be acquired, such data
with
respect to target factors being set forth in Table 2 and the latter hold on
target
and rest intervals being set forth in Table 1. This function is represented in
block
776. Line 778 reappears in FIG. 178 extending to block 780 which prompts the
user with a display indicating that to start the step therapy the select
switch 24
should be actuated. The operator may return the system to a previous menu at
this juncture by actuating menu switch 22. In this regard, as represented at
line
782 and block 784 by actuating switch 22, the program will again display that
initially elected maximum 90 pound grip force along with the prompt to squeeze
again or press select as represented at line 785 and node K. This returns the
program to block 752 (FIG. 17A) where node K reappears at line 750. While
again actuating switch 22, as represented at line 786 and block 788 a
restarting
of the step therapy test prompt is provided advising the user to actuate
switch
24. Again where switch 22 is actuated, then as represented at line 790 and
block
792 the user is provided a prompt display at readout 18 advising that the
previous menu may be elected by actuating select switch 24. Where that switch
is actuated, then as represented at line 794 and node H the program returns to
block 712 as earlier described in connection with FIG. 14A. In this regard,
node
H reappears in that figure in conjunction with line 796 extending to block
712.
Where menu switch 22 is actuated the program loops as represented at line 795
extending to line 782.
[00103] Returning to block 780, where switch 24 has been actuated, then as
represented at line 798 and block 800 the user is prompted to hold the grip
force
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at the computed target level for 100%. Additionally, the prompt term "SQUEEZE"
is provided within the readout 18. Next, as represented at line 802 and block
804
a determination is made as to whether the grip force exerted by the user is
within
10% of the computed target value. Where it is not, then the system dwells as
represented at loop line 806 and the display represented at block 800
continues.
Where the asserted grip force is within 10% of the target load, then as
represented at line 808 and block 810 the mandated hold on target interval
timeout set forth in Table 1 commences and, as represented at line 812 and
block 814 a dynamic comparison value is derived for dynamic bar graph cueing.
Next, as represented at line 814 and block 816 a computation then is made as
to
whether the instantaneous grip force is at or above 125% of the target value.
Where that is the case, then as represented at line 820 and block 822 an
audible
warning cue is sounded. The program then continues as represented at lines
824 and 826 when the excessive force has been lessened. Line 826 is directed
to block 828 which provides for carrying out a computation of a score value as
a
percentage of target for a sequence of time increments. Computation of this
score has been discussed in connection with FIG. 15. The program then
continues as represented at line 830.
[00104] Line 830 reappears in FIG. 17C extending to block 832 which provides
a display at readout 18 with essentially instantaneous score values, the noted
dynamic bar graph and hold time remaining for the initial step at hand. The
dynamic bar graph has been described in conjunction with FIGS. 16A-16E. Next,
as represented at line 834 and block 836 a query is posed as to whether the
hold
time interval has expired. Where it has not, then the system dwells as
represented at loop line 838 extending to node J. Node J reappears in FIG. 17B
in conjunction with the line 840 extending to line 816. However, where the
hold
on target interval has expired, then as represented at line 842 and block 844
an
audible cue is generated and, as represented at line 846 and block 848 a Table
1 mandated rest interval is commenced. The program then continues as
represented at line 850 and block 852 wherein the system cues the user that (A
x B)-1 efforts remain out of the previously selected (A x B) efforts and
further
advises of the time remaining for the rest interval and the current score
value.
With this display, the system queries as to whether the rest interval has
expired
as represented at line 854 and block 856. Where the rest time remains at hand,
then the system dwells as represented at loop line 858 extending the line 850.
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However, where the rest interval has expired, then as represented at line 860
and block 862 an audible cue is generated.
1001051 Following the generation of this audible cue, as represented at line
870
and block 872 the program reiterates the trial sequence following the mandates
of Tables 1 and 2 and the elected parameters. As represented at line 874 and
block 876, a query then is made as to whether the repetitions and associated
efforts are complete. This value is the product of the elected number of steps
A
multiplied by the elected number of repetitions, B. Where that number of
reiterations has not occurred, then the program continues as represented by
look
line 878 extending to line 870. Where the number of repetitions is completed,
then as represented at line 880 and block 882 a final score is computed and
submitted to memory with calendar and force data. Next, as represented at line
884 and block 886 the program selects a message to the user which will be
based upon the final score. For example, the user may be advised to consult a
therapist or the program directions in the event of the low score and is
congratulated in the event of a good score. As represented at line 888 and
block
890 those messages are selected. Where the user actuates select switch 24, the
program continues as represented at line 892 and node H.
[00106] Turning again to FIG. 14A, node H reappears in conjunction with line
796 leading to the block 712 displaying a prompt that, to cause the program to
enter the stepped therapy mode, the select switch 24 should be actuated.
However, where menu switch 22 is actuated, then as represented at line 896 and
block 898 the program displays a prompt that to enter the previous menu, the
select switch 24 should be actuated. Where that select switch is so actuated,
then as represented at line 900, the program reverts to node E which reappears
in the instant figure in conjunction with line 520 extending to block 522. On
the
other hand, where the user actuates menu switch 22, then as represented at
line
902 the program reverts to node G. Node G is shown in the instant figure in
conjunction with line 708 extending to block 526.
[00107] The user has the option of powering down instrument 10 by pressing
select switch 24 for an interval of at least 2 seconds. This power off
sequence is
represented in the flow chart of FIG. 18. The sequence opens with node 910 and
line 912 extending to block 914. Block 914 indicates that select switch 24 is
being actuated and held in an actuated state. During this actuated state, as
represented at line 916 and block 918 a determination is made as to whether
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2 second interval has elapsed. If it has not, then as represented at line 920
and
block 922 a query is posed as to whether the select switch 24 has been
released
before the termination of 2 seconds. If it has not, the system dwells as
represented at loop line 924 extending to line 916. Where the query at block
918
results in an affirmative determination, then as represented at line 926 and
block
928 the instrument 10 is powered down. Where the determination at block 922
indicates that the switch 24 has been released prior to the elapsing of 2
seconds,
then as represented at line 930 and block 932 the program reverts to the
previous or last display which was published at readout 18.
100108] The protocol based isometric exercise approach of the invention has
applicability to a broad range of muscle groups of the user. By employing the
protocol which, inter alia, involves the evaluation of maximum muscle group
strength as a precondition to then applying a factor related protocol, one of
those
factors may apply to the measured maximum strength value. The remaining
factors which involve, for example, variations of target loads, hold times,
rest
intervals and exercise regimen planning in terms of calendar days achieves a
safe and effective utilization of isometric activities. The exercisable
anatomical
features to be strengthened are generally identifiable as muscle groups of the
human anatomy which may include but are not limited: jaw muscles, neck
muscles, shoulder muscles, upper arm muscles, lower arm muscles, hand
muscles, finger muscles, diaphragm muscles, abdominal muscles, lower back
muscles, upper leg muscles, lower leg muscles, ankle muscles, foot muscles,
and toe muscles.
1001091 Looking to FIG. 19, a flow diagram is presented which outlines the
methodology achieving this safe utilization of isometric exercises. In the
figure,
block 950 reveals that the user or therapist may establish a goal of strength
for
the muscle group involved. This may be achieved by measuring the maximum
strength of an unimpaired contralateral muscle group. For example, a left arm
or
upper leg muscle group may be tested to determine a strength goal for a right
arm or right upper leg muscle. Where no unimpaired contralateral muscle group
is available to set this goal strength, a medical professional will establish
an
appropriate goal strength. The method continues as represented at line 952 of
block 954 providing for the measurement of maximum strength of the specific
anatomical feature to be treated. As represented at line 956 and block 958,
the
methodology identifies a protocol matrix of factors. In this regard, a
strengthening
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protocol is derived which is based upon timed efforts which are equal to a
percentage of the measured maximum strength as derived in connection with
block 954. The matrix of factors further include hold times at a factor or
factors of
the measured maximum strength, the repetition of these efforts for a given
trial or
exercise session and the duration of rest periods where repetitions are
involved.
Such protocol further will indicate the intervals of repetitions of the
exercise
sessions themselves during a stated period of time in hours, days, weeks,
months and the like. This matrix of factors may be contained, for example, in
computer memory. Looking to line 960 and block 962, the procedure next
nominates values to the factors provided in conjunction with block 958. In
this
regard, the strengthening protocol which is developed utilizes nominated
factors
from the matrix of these exercise factors. In effect, the nominated factors
may be
identified as "effort" applied by the specific anatomical feature and the
effort time
period during which the effort is to be applied such that there is a
relationship
among the percentage of the measured maximum strength of time wherein the
higher the percentage, the shorter the effort time and the number of
repetitions of
these efforts during an exercise session, the rest period time between
cessation
of one effort and the beginning of the next succeeding effort such that there
is a
relationship between the percentage of the measured maximum strength and the
rest time wherein the higher the percentage the longer the rest time and the
number of exercise sessions in a given time period (hours, days, weeks,
months). As represented at line 964 and block 966, the procedure initiates and
monitors the exercise protocol with nominated factors. In this regard, the
procedure monitors and guides the exercise effort to be applied and while
being
applied, provides visual and/or audible cues to encourage compliance to the
elected protocol using symbols as the visual cues and words which clearly
guide
the effort to be applied. While that effort is being applied, using audible
cues and
words which assist to properly perform the effort, rest periods and
repetitions for
each exercise session. Looking to line 968 of block 970, the method provides
for
annunciating an alarm when an exercise effort level is exceeded. In this
regard,
an audible alarm is produced if the exercise effort exceeds a predetermined or
factor determined level beyond which it is considered that the exercise effort
could be damaging to the human physiology or the specific anatomical feature
at
hand. As represented at line 972 and block 974 the method provides compliance
scores in real-time and in summation during the course of an exercise effort
and
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subsequent thereto. As described herein, the program calculates a compliance
score during each exercise effort in percent of that effort required in the
strengthening protocol and provides this compliance score in real-time as the
effort is being accomplished on the specific anatomical feature. An averaging
of
this compliance score over each exercise effort time period is devised to
depict
the degree to which the exercise effort applied has been accomplished. By
accumulating the compliance scores during each rest period and then presenting
a final compliance score issued in the form of both a number as a percent
accomplished and in an instruction set an indication is derived as to how well
the
exercise protocol was performed or how to improve future compliance. Next, as
represented at line 976 at block 978 the exercise data is archived for review
and
potential transfer to a remote interactive entity. This step in the procedure
accumulates real-time and summary data for each effort or trial and the
specific
protocol being utilized. It may be noted that these protocols are selected
each
time the exercisable anatomical feature is elected to be strengthened such
that
the elected protocol, the effort being applied and the compliance being
calculated during and at the conclusion of each effort may be reviewed
remotely
as it is being accomplished using suitable data communication assistance and
at
the conclusion of each effort. The archive data is time-stamped and uniquely
identified for retrieval.
[001101 Through use of the invention, cardiac function and a variety of
physiologic effects are produced, including effects on the endothelium and the
release of biological active signaling molecules, including nitric oxide.
[00111] The following studies demonstrate the measureable biochemical and
biophysical effect of utilization of the system, method, and apparatus of the
invention.
[00112] Use of Isometric Exercise to Treat Hypertension
[00113] Among many other factors, both hypertension and arterial
distensibility
are independent risk factors for cardiovascular disease. The research of Wiley
et
al. (1992) and Taylor et al. (2003) demonstrated that isometric training is
effective for reducing resting blood pressure (RBP). NO is a potent
vasodilator,
and crucial component of the regulation of vascular tension (See FIG. 20),
thus,
isometric exercise is expected to affect NO production and bioavailability.
[00114] As NO is a rapidly diffusible gas, release of NO in the blood vessels
of
the arms or other muscle groups, in response to isometric training, is
expected to
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have both a local and systemic effect on vasoclilation, arterial
distensibility and
resting blood pressure. Thus an increase of arterial distensibility in
response to
isometric exercise may contribute to reduction in RBP and increased NO
bioavailability. A wide variety of muscle groups such as from exercisable
regions
of the musculature of the user including jaw muscles, neck muscles, shoulder
muscles, upper arm muscles, lower arm muscles, hand muscles, finger muscles,
diaphragm muscles, abdominal muscles, lower back muscles, upper leg
muscles, lower leg muscles, ankle muscles, foot muscles, and toe muscles may
provide a therapeutic benefit by utilization of the isometric exercise
protocols of
the invention.
1001151 To demonstrate the systemic effect of practicing the system and
method of the invention, the impact of isometric arm and leg exercise on RBP
and central and peripheral arterial distensibility was tested in patients
being
medicated for hypertension. Resting blood pressure was measured by brachial
oscillometry, and arterial distensibility, as measured by Doppler ultrasound
and
applanation tonometry in the carotid, brachial and femoral arteries. Study
participants were directed to perform isometric handgrip (IHG) exercise
(n=10),
or isometric leg press (ILP) exercise (n=6) according to the method of the
invention three times per week for eight weeks. Exercise intensity was
maintained at 30% of maximal voluntary contraction.
[00116] Following eight weeks of HG exercise, systolic blood pressure
decreased significantly (from 140.2 mmHg+/-3.82 to 132.3 mmHg+/-3.97), while
no decrease was observed after isometric leg press exercise. Diastolic blood
pressure did not change after either IHG or ILP exercise. Measurement of
carotid
arterial distensibility showed a significant improvement following IHG
exercise
(from 0.1105 mmHg-/-1×10-2 0.0093 to 0.1669 mmHg+/-
1×10-2 0.0221), while no such changes occurred in the ILP exercise
group. Peripheral arterial distensibility did not change following either IHG
or ILP
exercise. These studies demonstrate that the isometric handgrip exercise
according to the invention improves resting systolic blood pressure and
carotid
arterial distensibility. As arterial tension is under the direct control of
the NO/LDL-
cholesterol signaling system, the system and method of the invention allows
modulation of NO and indirectly of the LDL-cholesterol components.
[00117] As described previously, hypertension is associated with endothelial
dysfunction, reduced NO bioavailability, and the development of coronary
artery
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disease among other effects on the body of the patient. The isometric hand
grip
exercise protocol of the invention further reduces blood pressure even in
patients
already medicated for hypertension. In order to demonstrate the mechanisms of
IHG affect on hypertension, endothelial function was studied in patients
practicing the system and method of the invention. Study participants (n=8,
62+/-
3.5 years) performed 4 sets of 2-minute isometric contractions at 30% of their
maximal voluntary contraction. Ulnar reactivity was assessed in alternate
hands,
3x/week for 8 weeks. Resting blood pressure was measured using automated
brachial oscillometry. Vascular reactivity was measured in both arms using
ultrasound imaging to determine brachial artery flow-mediated dilation (FMD).
Following utilization of the IHG protocol of the invention, systolic blood
pressure
decreased (137 mm Hg+/-5.3 to 121.7 mm Hg=/-4.8 mmHg, p=0.03). Relative
FMD increased (1.6%+/-0.3 to 4.5%+/-0.5 and normalized to average shear rate,
0.007%+/-0.001 to 0.02+/-0.004%/s-1). Reactive hyperemic flow decreased
(peak, 344.3+1-36.5 to 258.2+/-27.2 ml/min and average, 301.6+1-33.1 to
239.0+/-28.4 ml/min). Average resting blood vessel diameter and resting flow
rates remained unchanged.
[00118] As systemic shear stress is known to induce the activity of NO as a
vasodilator, the 1HG training apparently causes the release of NO, as shown by
an increase in flow mediated arterial dilation. The IHG exercise protocol
produced a reduced reactive hyperemic flow, accompanied by improvements in
normalized FMD, and a heightened vasoreactive sensitivity to the reactive
hyperemic stimulus. The IHG protocol by providing an improved cardiovascular
function, demonstrates a modification of the wall shear stress setpoint for
the
activation of eNOS to produce biologically active levels of NO.
[00119] The statin class of drugs used in the treatment of
hypercholesterolemia surprisingly has a pleiotropic effect on a variety of
other
systems of the body, including on the bioavailability of NO. Thus, by down-
modulating cholesterol biosynthesis, statin drugs affect systems that are
controlled by NO dependent signaling systems. The method and apparatus of
the invention, surprisingly, by stimulating changes in the structure of the
vasculature, and by creating increased wall shear stress in the blood vessels
experiencing the effects of the inventive protocol, also induces broad effects
on
signaling systems including those that regulate the bioavailability of NO and
serum cholesterol and LDL-cholesterol levels.
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[00120] The above-described studies demonstrate use of the system and
apparatus described herein to dilate blood vessels (e.g., arteries,
arterioles) by
causing the increased secretion of NO by inducing shear stress on blood vessel
walls, resulting in positive effects on reducing hypertension. Thus, the
system
and apparatus described herein is also beneficial in treating other
afflictions
which may have their cause rooted in problems with the circulatory system (or
which may be treated via improvement to the circulatory system of an affected
individual). As described below, such afflictions may include ED, type 2
diabetes, and obesity.
[00121] Use of Isometric Exercise to Treat Erectile Dysfunction in Males
[00122] As described above, the system and method of the present invention
may be used to dilate blood vessels by causing the increased secretion of NO
by
inducing shear stress on blood vessel walls. As ED is known to often have a
circulatory component to its cause, and as the NO pathway plays an important
role in the process of penile erection, the system and apparatus described
herein
is also beneficial in treating ED.
[00123] Mechanism of Penile Erection
[00124] As is known, penile erection may be achieved via two different
mechanisms. The first is the reflex erection, which is achieved by a direct
touching of the penile shaft. The second is the psychogenic erection, which is
achieved by erotic or emotional stimuli. In general, stimulation of the penile
shaft
by the nervous system leads to the secretion of nitric oxide (NO), which
causes
the relaxation of smooth muscles of corpora cavemosa (the main erectile tissue
of penis). If viewed in cross section, the penis consists of three tube-like
projections of spongy tissue, the corpus spongiosum, located ventrally and the
paired corpi cavernosi located dorsally. In each of the latter is the deep
artery of
the penis which carries blood over the length of the penis into the open
channels
that make up the corpus cavernosum. The blood carried out of the corpi
cavernosi empties into the dorsal vein of the penis which then returns the
blood
to the body. The level of rigidity of the penis is due to the relationship
between
arterial inflow and venous outflow in the penis. This means that the larger
the
diameter of the arteries, the more blood enters the corpus cavernosum and
enlarges the penis.
[00125] In the process of penile erection, NO is released with sexual
stimulation from nerve endings and endothelial cells in the corpus cavernosum
of
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the penis. NO activates soluble guanylate cyclase, enhancing production of
guanosine 3',5'-cyclic monophosphate (cGMP), by converting guanosine
triphosphate (GTP) into cGMP. cGMP causes the smooth muscle to relax, which
causes an inflow of blood, which then leads to an erection. cGMP is then
hydrolyzed back to the inactive GMP by phosphodiesterase type 5 (PDE5).
[00126] Impotence may develop due to lack of adequate penile blood supply.
For example, restriction of blood flow can arise from impaired endothelial
function. This may be due to causes associated with coronary artery disease.
Other conditions, such as diabetes and/or obesity may contribute to ED.
[00127] Medications to Treat ED
[00128] As is known to those of ordinary skill in the art, various medications
may be taken to treat ED. The most common of these medications are
phosphodiesterase type 5 inhibitors (PDE-5 inhibitors). The PDE-5 inhibitors
sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are
prescription drugs
which are taken orally. They work by blocking the action of PDE5, which causes
cGMP to degrade (cGMP being necessary to a successful erection, as described
above, by causing smooth muscle to relax, thereby causing inflow of blood to
the
penis; if cGMP is degraded, there is less smooth muscle relaxation, less
inflow of
blood, and no or weak erection).
[00129] The levels of cGMP are therefore controlled by the activation of
cyclic
nucleotide cyclase and the breakdown by PDE5. It is the latter that sildenafil
acts upon. Men who suffer from erectile dysfunction often produce too little
amounts of NO. This means that the small amount of cGMP they produce is
broken down at the same rate and therefore doesn't have the time to accumulate
and cause a prolonged vasodilation effect. Sildenafil works by inhibiting the
enzyme PDE-5 by occupying its active site. This means that cGMP is not
hydrolyzed as fast and this allows the smooth muscle to relax.
[00130] Use of Isometric Exercise with individuals Suffering from ED
[00131] In view of the discussion above, it is clear that the NO pathway has
an
important role in achieving and maintaining an erection. It is also clear
that,
currently, expensive medications are the main treatment prescribed to those
suffering from ED. However, with the principles of the method, system, and
apparatus of the present invention, one may treat ED, and achieve and maintain
erection, without the use of such medications, but rather through the use of
isometric exercise.
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[00132] Thus, like the method of the present invention for lowering the
resting
systolic and diastolic blood pressures of patients (described above), another
aspect of the present invention includes a method for treating ED via
isometric
exercise (to stimulate increase of NO, and thus arterial dilation). In one
embodiment, this method may begin by determining the maximal isometric force
which can be exerted by a patient with any given muscle (e.g., skeletal muscle
or
group of muscles). The determined maximal isometric force is recorded, and the
patient is periodically permitted to intermittently engage in isometric
contraction
of the given muscle at a fractional level of the maximal force determined for
a
given contraction duration followed by a given resting duration. When using a
apparatus, (such as one described above), a perceptible indicia correlative to
the
isometric force exerted by the given muscle may be displayed to the patient so
that the patient can sustain the given fractional level of maximal force.
[00133] A representative procedure for a patient to follow includes the
patient
exerting a force with a selected muscle or muscle group to about 50%±5% of
the previously determined maximal isometric force (of that muscle or muscle
group) and holding that 50% force for 45 seconds; resting for one minute; and
then repeating multiple times. The particular muscle or muscle group may be
selected based upon the treatment desired. For example, the method may
include exerting a squeezing force with either hand equal to about 50%±5%
of
the previously determined maximal isometric force and holding that 50% force
for
45 seconds; resting for one minute; exerting a force with the other hand equal
to
50% of the maximum for 45 seconds; resting one minute; exerting a force of 50%
of maximum for 45 seconds again with the first hand; resting one minute; and
exerting a force of 50% for 45 seconds again with the second hand. This
completes the isometric exercise for that day. The same procedure may be
followed by the patient multiple days (e.g., at least five days per week). It
will be
recognized by those of ordinary skill in the art that the use of "hand" for
the
muscle group is exemplary. It will also be recognized by those of ordinary
skill
in the art that the protocol may be adapted based on the patient, the muscle
group, the affliction, or other factors.
[00134] Thus, the isometric component of exercise alone can be used to
stimulate NO production to increase arterial diameter and treat ED (via
subsequent increased blood flow into the penis), by following a simple, yet
effective, regimen that includes exerting fractional isometric force by any
given
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muscle (for present purposes, "muscle" includes any skeletal muscle or group
of
muscles) for a given duration followed by a given duration of resting. This
sequence is repeated several times (say, from about 3 to 6 times) and the
entire
regimen is repeated several times per week (say, from about 3 to 7 times per
week). Since the regimen takes only several minutes per day to complete, it is
believed that patients will be better able to stay with the program and, thus,
receive long term benefits in treating ED. Moreover, since the patient exerts
only
a fraction of the maximal force of the given muscle, the patient's blood
pressure
during the exercise protocol does not rise to unacceptably high values whereat
the patient's health would be at risk.
[00135] Another aspect of the therapeutic method associated with the
instrument of the invention resides in the limiting of user performance to
carry out
the regimen of trials. In this regard, the instrument is programmed to perform
only within predetermined and mandated test limits. Each therapeutic regimen
is
based upon an initial evaluation of the maximum gripping force capability of
the
user. Under that limitation, target load factors, hold on target load
intervals,
intervening rest intervals and trial repetition numbers may be elected only
from
pre-established and mandated memory retained ranges. The program also
nominates rest intervals and hold on target intervals in correspondence with
user
elected target force factors. Thus, valuable strength recovery and development
may be achieved but only within safe limits.
[00136] Additionally, the instrument is employable as a therapeutic device.
First a protocol is nominated by prescribing nominal parameters of the effort.
Each isometric regimen is controlled initially by requiring that a maximum
grip
strength be established for each individual patient or user. Then, the
practitioner
may elect parameters of grip force and timing under mandated memory
contained parameter limits. Accordingly, the user will be unable to carry out
strength enhancement therapies which would otherwise constitute an excessive
grip force regimen. For carrying out the noted diagnostic procedures as well
as
therapy activities, the grip widthwise extent is variable from 1 7/8 inches to
2 7/8
inches, such variation being adjustable in 1/2 inch increments. This is in
keeping
with standardized diagnostic practices. Further with respect to diagnostic
procedures, the display or readout of the instrument can be adjusted with
respect
to the grip structuring such that only the practitioner or therapist may
observe the
data which is being developed during a diagnostic protocol.
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[00137] More particular description of examples of protocols are shown in FIG.
19, (described in greater detail above), which presents a flow diagram that
outlines the methodology achieving this safe utilization of isometric
exercises.
[00138] Use of Isometric Exercise to Enhance Sexual Stimulation in Females
1001391 Apart from the use of isometric exercise to treat sexual dysfunction
(e.g., erectile dysfunction) in males, another aspect of the present invention
also
contemplates use of isometric exercise to enhance sexual function in females,
particularly by enhancing clitoral sensitivity.
[00140] To that end, as described above, it is known that sildenafil (and
other
medications; PDE5 inhibitors) are effective treatments for male ED. Recent
studies, however, have also shown that sildenafil can improve uterine
circulation
and clitoral artery blood flow, and that this occurs due to the same NO
pathway
as in penile erection.
[00141] For example, Alatas E, Yagcl AB., The effect of sildenafil citrate on
uterine and clitoral arterial blood flow in postmenopausal women, MedGenMed.
2004 Oct 13;6(4):51, incorporated by reference herein in its entirety,
determined
the effect of sildenafil on uterine circulation and clitoral artery blood flow
in
postmenopausal women using color Doppler sonography. After sildenafil
administration, the mean resistance and pulsatility indexes of uterine artery
were
significantly lower (0.73 0.08 vs 0.80 0.07, P < .001 and 1.66 0.50 vs
2.08
0.52, P < .001, respectively) in comparison to baseline values, and the mean
peak systolic velocity of clitoral artery was significantly higher (17.9 8.6
cm/sec
vs 12.9 5.8 cm/sec, P < .001). Sildenafil did not cause any significant
change
in the mean resistance and pulsatility indexes of the clitoral artery (P =
.683 and
P = .714, respectively). Thus, it was determined that sildenafil improves the
clitoral and uterine blood flow in healthy postmenopausal women without any
erotic stimulus. As a result, the NO pathway may be a candidate target for
drug
therapy for female sexual dysfunction.
[00142] Further studies have revealed that the neurovascular mechanism of
this clitoral stimulation is NO-dependent. In one such study [Ferrante, S. G.,
et
al., The neuro vascular mechanism of clitoral erection: nitric oxide and cGMP-
stimulated activation of BKCa channels, The FASEB Journal. 2004;18:1382-
1391, incorporated by reference herein in its entirety], the investigators
hypothesized that rat clitorises relax by a similar mechanism as seen in
penile
erection (i.e., via the NO pathway). Rat clitorises express components of the
CA 02893192 2015-05-07
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proposed pathway: neuronal and endothelial NO synthases, soluble guanylyl
cyclase (sGC), type 5 phosphodiesterase (PDE-5), and BKCa channels. The
NO donor diethylamine NONOate (DEANO), the PKG activator 8-pCPT-cGMP,
and the PDE-5 inhibitor sildenafil, cause dose-dependent clitoral relaxation
that
is inhibited by antagonists of PKG (Rp-8-Br-cGMPS) or BKCa channels
(iberiotoxin). Electrical field stimulation induces tetrodotoxin-sensitive NO
release and relaxation that is inhibited by the Na+ channel blocker
tetrodotoxin
or sGC inhibitor 1H-(1,2,4)oxadiozolo(4,3-a)quinoxalin-1-one. Human BKCa
channels, transferred to Chinese hamster ovary cells via an adenoviral vector,
and endogenous rat clitoral smooth muscle K+ current are activated by this
PKG-dependent mechanism. Laser confocal microscopy reveals protein
expression of BKCa channels on clitoral smooth muscle cells; these cells
exhibit
BKCa channel activity that is activated by both DEANO and sildenafil. Thus,
the
investigators concluded that neurovascular derived NO causes clitoral
relaxation
via a PKG-dependent activation of BKCa channels.
[00143] Further, as described previously, various PDE-5 inhibitors have been
developed for human use (including sildenafil, vardenafil, and tadalafil) and
they
inhibit PDE-5 in cultured clitoral corpus cavernosal smooth muscle cells,
relax
the corpus cavernosum of the rabbit clitoris, and increase blood flow to the
genitalia of the female dog. Thus, the present inventors conclude that use of
such treatments for female mammals would be indicated across species, and
thus would include humans (i.e., medications such as sildenafil would be
useful
for female sexual dysfunction in humans).
[00144] Berman JR, et al., Effect of sildenafil on subjective and physiologic
parameters of the female sexual response in women with sexual arousal
disorder, J Sex Marital Ther. 2001 Oct-Dec;27(5):411-20, incorporated by
reference herein in its entirety, supports this conclusion. Berman notes that
sexual dysfunction is a complaint of 30-50% of American women and, aside from
hormone replacement therapy, there currently are no FDA-approved medical
treatments for female sexual complaints. The goal of the Berman study was to
determine safety and efficacy of sildenafil for use in women with sexual
arousal
disorder (SAD). Following administration of sildenafil, poststimulation
physiologic measurements improved significantly compared to baseline.
Baseline subjective sexual function complaints, including low arousal, low
desire,
low sexual satisfaction, difficulty achieving orgasm, decreased vaginal
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lubrication, and dyspareunia [painful intercourse] also improved significantly
following 6 weeks home use of sildenafil. Thus, Berman concluded that
sildenafil
significantly improves both subjective and physiologic parameters of the
female
sexual response. A follow-up study by Berman, [Berman JR, et al., Safety and
efficacy of sildenafil citrate for the treatment of female sexual arousal
disorder: a
double-blind, placebo controlled study, J Urol. 2003 Dec;170(6 Pt 1):2333-8,
incorporated by reference herein in its entirety], also supported these
conclusions.
[00145] For males, sildenafil may overcome the lack of penile erection, which
disallowed intercourse. In females, this suggests that sildenafil may allow or
enhance engorgement of the clitoris, which may enhance the pleasure of
intercourse.
[00146] However, as with the drawbacks to drug therapies for male ED, similar
issues exist with treatments for female sexual dysfunction, and so an aspect
of
the present invention provides a method, system, and apparatus for isometric
exercise to improve clitoral artery blood flow for treatment of female sexual
dysfunction, thereby obviating the need for drug-based treatment (such as with
sildenafil or other drug compositions). Due to the studies showing potential
use
of sildenafil in females, the present invention also contemplates use of
isometric
exercise to allow or enhance engorgement of the clitoris, which may enhance
the
pleasure of intercourse. And so an aspect of the present invention provides a
method, system, and apparatus for isometric exercise to improve clitoral
artery
blood flow for treatment of female sexual dysfunction.
[00147] Thus, like the method of the present invention for lowering the
resting
systolic and diastolic blood pressures of patients (described above), another
aspect of the present invention includes a method for treating female sexual
dysfunction via isometric exercise (to stimulate increase of NO, and thus
arterial
dilation). This method may begin with a determination of the maximal isometric
force which can be exerted by a patient with any given muscle (e.g., skeletal
muscle or group of muscles) of such patient. The determined maximal isometric
force is recorded. The patient, then, is periodically permitted to
intermittently
engage in isometric contraction of the given muscle at a fractional level of
the
maximal force determined for a given contraction duration followed by a given
resting duration. A perceptible indicia correlative to the isometric force
exerted by
52
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the given muscle is displayed to the patient so that the patient can sustain
the
given fractional level of maximal force.
[00148] A representative procedure for a patient to follow includes the
patient
exerting a force with a selected muscle or muscle group to about 50%±5% of
the previously determined maximal isometric force (of that muscle or muscle
group) and holding that 50% force for 45 seconds; resting for one minute; and
then repeating multiple times. The particular muscle or muscle group may be
selected based upon the treatment desired. For example, the method may
include exerting a squeezing force with either hand equal to about 50%±5%
of
the previously determined maximal isometric force and holding that 50% force
for
45 seconds; resting for one minute; exerting a force with the other hand equal
to
50% of the maximum for 45 seconds; resting one minute; exerting a force of 50%
of maximum for 45 seconds again with the first hand; resting one minute; and
exerting a force of 50% for 45 seconds again with the second hand. This
completes the isometric exercise for that day. The same procedure may be
followed by the patient multiple days (e.g., at least five days per week). It
will be
recognized by those of ordinary skill in the art that the use of "hand" for
the
muscle group is exemplary.
1001491 Thus, the isometric component of exercise alone can be used to
stimulate NO production to increase arterial diameter and treat female sexual
dysfunction, by following a simple, yet effective, regimen that includes
exerting
fractional isometric force by any given muscle (for present purposes, "muscle"
includes any skeletal muscle or group of muscles) for a given duration
followed
by a given duration of resting. This sequence is repeated several times (say,
from about 3 to 6 times) and the entire regimen is repeated several times per
week (say, from about 3 to 7 times per week). Since the regimen takes only
several minutes per day to complete, it is believed that patients will be
better
able to stay with the program and, thus, receive long term benefits in
treating
female sexual dysfunction. Moreover, since the patient exerts only a fraction
of
the maximal force of the given muscle, the patient's blood pressure during the
exercise protocol does not rise to unacceptably high values whereat the
patient's
health would be at risk.
[00150] An important aspect of the therapeutic method associated with the
instrument of the invention resides in the limiting of user performance to
carry out
the regimen of trials. In this regard, the instrument is programmed to perform
53
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only within predetermined and mandated test limits. Each therapeutic regimen
is
based upon an initial evaluation of the maximum gripping force capability of
the
user. Under that limitation, target load factors, hold on target load
intervals,
intervening rest intervals and trial repetition numbers may be elected only
from
pre-established and mandated memory retained ranges. The program also
nominates rest intervals and hold on target intervals in correspondence with
user
elected target force factors. Thus, valuable strength recovery and development
may be achieved but only within safe limits.
[00151] Additionally, the instrument is employable as a therapeutic device.
First a protocol is nominated by prescribing nominal parameters of the effort.
Each isometric regimen is controlled initially by requiring that a maximum
grip
strength be established for each individual patient or user. Then, the
practitioner
may elect parameters of grip force and timing under mandated memory
contained parameter limits. Accordingly, the user will be unable to carry out
strength enhancement therapies which would otherwise constitute an excessive
grip force regimen. For carrying out the noted diagnostic procedures as well
as
therapy activities, the grip widthwise extent is variable from 1 7/8 inches to
2 7/8
inches, such variation being adjustable in 1/2 inch increments. This is in
keeping
with standardized diagnostic practices. Further with respect to diagnostic
procedures, the display or readout of the instrument can be adjusted with
respect
to the grip structuring such that only the practitioner or therapist may
observe the
data which is being developed during a diagnostic protocol.
[00152] More particular description of examples of protocols are shown in FIG.
19, (described in greater detail above), which presents a flow diagram that
outlines the methodology achieving this safe utilization of isometric
exercises.
[00153] Use of Isometric Exercise to Treat Obesity
[00154] As described above, obesity is a medical condition in which excess
body fat has accumulated to the extent that it may have an adverse effect on
health, leading to reduced life expectancy and/or increased health problems.
Obesity increases the likelihood of various diseases, such as heart disease
and
type 2 diabetes. And obesity is most commonly caused by a combination of
excessive food energy intake, lack of physical activity, and genetic
susceptibility.
[00155] Persons who are obese have increased, and often tremendous,
amounts of fat stored in their bodies. The primary cells that make up these
fat
stores are white adipocytes (which make up the white adipose tissue). Apart
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from white adipose tissue, brown adipose tissue (BAT), or brown fat, is
another
type of fat. BAT is especially abundant in newborns and in hibernating
mammals. Its primary function is to generate body heat in animals or newborns
that do not shiver. In contrast to white adipocytes (fat cells), which contain
a
single lipid droplet, brown adipocytes contain numerous smaller droplets and a
much higher number of mitochondria (these are involved in the metabolism of
fat
molecules, which release energy and heat, and get rid of the fat). Brown fat
also
contains more capillaries than white fat, since it has a greater need for
oxygen
than most tissues.
[00156] Recent studies using Positron Emission Tomography scanning of adult
humans have shown that brown fat is present in adults in the upper chest and
neck, though not to the extent it is present as a percentage of fat in
newborns.
These remaining deposits become more metabolically active with cold exposure,
and less metabolically active if an adrenergic beta blocker is given before
the
scan. This could suggest a new method of weight loss, since brown fat takes
calories from normal fat and burns it.
[00157] And indeed, more recently, it has been determined that by activating
brown fat, one can burn white fat. For example, Cederberg A, et al., FOXC2 is
a
winged helix gene that counteracts obesity, hypertnglyceridemia, and diet-
induced insulin resistance, Cell. 2001 Sep 7;106(5):563-73 (incorporated by
reference herein in its entirety), identified the human winged helixtforkhead
transcription factor gene FOXC2 as a key regulator of adipocyte metabolism.
Increased FOXC2 expression, in adipocytes, has a pleiotropic effect on gene
expression, which leads to a lean and insulin sensitive phenotype. FOXC2
affects adipocyte metabolism by increasing the sensitivity of the beta-
adrenergic-
cAMP-protein kinase A (PKA) signaling pathway through alteration of adipocyte
PKA holoenzyme composition.
[00158] Further, Bostrorn, P., et al., A PGCI-a-dependent myokine that drives
brown-fat-like development of white fat and thermogenesis, Nature, Volume 481,
pp. 463-468, January 26,2012, incorporated by reference herein in its
entirety,
demonstrated mechanisms by which exercise can improve metabolic status in
obesity and type 2 diabetes.
[00159] As noted by Bostrom et al., exercise increases whole body energy
expenditure beyond the calories used in the actual work performed. Because
transgenic mice expressing PGC1-a selectively in muscle showed a remarkable
CA 02893192 2015-05-07
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resistance to age-related obesity and diabetes, Bostrom et al. sought factors
secreted from muscle under the control of this co-activator that might
increase
whole body energy expenditure, and ultimately described a new polypeptide
hormone, irisin (a cleaved and secreted portion of FNDC5), which is regulated
by
PGC1-a, secreted from muscle into blood, and activates thermogenic function in
adipose tissues. lrisin has powerful effects on the browning of certain white
adipose tissues, both in culture and in vivo. Nanomolar levels of this protein
increase UCP1 in cultures of primary white fat cells by 50 fold or more,
resulting
in increased respiration. Further, viral delivery of irisin that causes only a
moderate increase (-3 fold) in circulating levels stimulates a 10-20 fold
increase
in UCP1, increased energy expenditure and an improvement in the glucose
tolerance of mice fed a high fat diet. As this is in the range of increases
seen with
exercise in mouse and man, it is likely that irisin is responsible for at
least some
of the beneficial effects of exercise on the browning of adipose tissues and
increases in energy expenditure.
[00160] Further, irisin is highly conserved in all mammalian species that have
been sequenced. Mouse and human irisin are 100% identical, compared to 85%
identity for insulin, 90% identity for glucagon, and 83% identity for leptin.
This
implies a highly conserved function that is likely to be mediated by a cell
surface
receptor.
[00161] On the basis of the gene structure of FNDC5, BostrOm et al.
considered that FNDC5 might be a secreted protein. They observed that the
signal peptide is removed, and the mature protein is further proteolytically
cleaved and glycosylated, to release the 112-amino-acid polypeptide irisin.
The
cleavage and secretion of irisin is similar to the release/shedding of other
transmembrane polypeptide hormones and hormone-like molecules such as
epidermal growth factor (EGF) and transforming growth factor-a (TGF-a).
[00162] Thus, irisin would seem to have therapeutic potential. Exogenously
administered irisin induces the browning of subcutaneous fat and
thermogenesis,
and it presumably could be prepared and delivered as an injectable
polypeptide.
Increased formation of brown or beige/brite fat has been shown to have anti-
obesity, antidiabetic effects in multiple murine models, and adult humans have
significant deposits of UCP1-positive brown fat. Data presented by Bostrom et
al.
show that even relatively short treatments of obese mice with irisin improves
glucose homeostasis and causes a small weight loss. Whether longer treatments
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with irisin and/or higher doses would cause more weight loss remains to be
determined. The worldwide, explosive increase in obesity and diabetes renders
attractive the therapeutic potential of irisin in these and related disorders.
[00163] However, a treatment for obesity that includes injections of irisin
presents drawbacks (e.g., medical supervision for injection ¨ which involves
time
and travel; cost; etc.). Thus, like the method of the present invention for
lowering
the resting systolic and diastolic blood pressures of patients (described
above),
another aspect of the present invention includes a method for treating obesity
via
isometric exercise (to stimulate production and secretion of irisin). This
method
may begin with a determination of the maximal isometric force which can be
exerted by a patient with any given muscle (e.g., skeletal muscle or group of
muscles) of such patient. The determined maximal isometric force is recorded.
The patient, then, is periodically permitted to intermittently engage in
isometric
contraction of the given muscle at a fractional level of the maximal force
determined for a given contraction duration followed by a given resting
duration.
A perceptible indicia correlative to the isometric force exerted by the given
muscle is displayed to the patient so that the patient can sustain the given
fractional level of maximal force.
[00164] A representative procedure for a patient to follow includes the
patient
exerting a force with a selected muscle or muscle group to about 50%±5% of
the previously determined maximal isometric force (of that muscle or muscle
group) and holding that 50% force for 45 seconds; resting for one minute; and
then repeating multiple times. The particular muscle or muscle group may be
selected based upon the treatment desired. For example, the method may
include exerting a squeezing force with either hand equal to about 50%±5%
of
the previously determined maximal isometric force and holding that 50% force
for
45 seconds; resting for one minute; exerting a force with the other hand equal
to
50% of the maximum for 45 seconds; resting one minute; exerting a force of 50%
of maximum for 45 seconds again with the first hand; resting one minute; and
exerting a force of 50% for 45 seconds again with the second hand. This
completes the isometric exercise for that day. The same procedure may be
followed by the patient multiple days (e.g., at least five days per week). It
will be
recognized by those of ordinary skill in the art that the use of "hand" for
the
muscle group is exemplary.
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[00165] Thus, the isometric component of exercise alone can be used to
stimulate production and secretion of irisin, to promote the browning of white
fat,
and treat obesity by following a simple, yet effective, regimen that includes
exerting fractional isometric force by any given muscle (for present purposes,
"muscle" includes any skeletal muscle or group of muscles) for a given
duration
followed by a given duration of resting. This sequence is repeated several
times
(say, from about 3 to 6 times) and the entire regimen is repeated several
times
per week (say, from about 3 to 7 times per week). Since the regimen takes only
several minutes per day to complete, it is believed that patients will be
better
able to stay with the program and, thus, receive long term benefits in
treating
obesity. Moreover, since the patient exerts only a fraction of the maximal
force of
the given muscle, the patient's blood pressure during the exercise protocol
does
not rise to unacceptably high values whereat the patient's health would be at
risk.
[00166] An important aspect of the therapeutic method associated with the
instrument of the invention resides in the limiting of user performance to
carry out
the regimen of trials. In this regard, the instrument is programmed to perform
only within predetermined and mandated test limits. Each therapeutic regimen
is
based upon an initial evaluation of the maximum gripping force capability of
the
user. Under that limitation, target load factors, hold on target load
intervals,
intervening rest intervals and trial repetition numbers may be elected only
from
pre-established and mandated memory retained ranges. The program also
nominates rest intervals and hold on target intervals in correspondence with
user
elected target force factors. Thus, valuable strength recovery and development
may be achieved but only within safe limits.
[00167] Additionally, the instrument is employable as a therapeutic device.
First a protocol is nominated by prescribing nominal parameters of the effort.
Each isometric regimen is controlled initially by requiring that a maximum
grip
strength be established for each individual patient or user. Then, the
practitioner
may elect parameters of grip force and timing under mandated memory
contained parameter limits. Accordingly, the user will be unable to carry out
strength enhancement therapies which would otherwise constitute an excessive
grip force regimen. For carrying out the noted diagnostic procedures as well
as
therapy activities, the grip widthwise extent is variable from 1 7/8 inches to
2 7/8
inches, such variation being adjustable in 1/2 inch increments. This is in
keeping
58
CA 02893192 2015-05-07
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with standardized diagnostic practices. Further with respect to diagnostic
procedures, the display or readout of the instrument can be adjusted with
respect
to the grip structuring such that only the practitioner or therapist may
observe the
data which is being developed during a diagnostic protocol.
[00168] More particular description of examples of protocols are shown in FIG.
19, (described in greater detail above), which presents a flow diagram that
outlines the methodology achieving this safe utilization of isometric
exercises.
[00169] Use of Isometric Exercise to Treat Diabetes
[00170] As described above, type 2 diabetes is a metabolic disorder that is
characterized by high blood glucose in the context of insulin resistance and
relative insulin deficiency. Obesity is thought to be the primary cause of
type 2
diabetes in people who are genetically predisposed to the disease. It is well
known that there is an intimate link between type 2 diabetes and obesity.
Above
is disclosed the use of isometric exercise to combat obesity in individuals.
As
reduction of obesity is known to improve the diabetic condition by improving
insulin sensitivity, another aspect of the present invention therefore
contemplates
the use of isometric exercise as therapy for type 2 diabetes.
[00171] In fact, recent studies have demonstrated an increase in the metabolic
breakdown of glucose (and other carbohydrates) following isometric contraction
of muscle, thereby reducing blood sugar levels. For example, in Katz A, Lee
AD,
G-1,6-P2 in human skeletal muscle after isometric contraction, Am J Physiol.
1988 Aug;255(2 Pt 1):C145-8 (incorporated by reference herein in its
entirety),
the content of glucose 1,6-bisphosphate (G-1,6-P2), an in vitro activator of
phosphofructokinase (a rate-limiting enzyme for glycolysis), and the
glycolytic
rate in skeletal muscle during isometric contraction were determined. In the
study, subjects contracted the knee extensor muscles at two-thirds maximal
voluntary force to fatigue, and biopsies from the quadriceps femoris muscle
were
obtained before and immediately after contraction. G-1,6-P2 increased in all
subjects from a mean of 101 +/- 15 (SE) mumol/kg dry wt at rest to 128 +/- 24
at
fatigue (P less than 0.05). Muscle glucose did not change significantly,
whereas
hexosemonophosphates were significantly increased after contraction. The
glycogenolytic and glycolytic rate averaged 70.0 +/- 13.8 and 47.3 +/- 6.7
mmol.kg dry wt mm-I, respectively, and the glycolytic rate was positively
correlated with the accumulation rates of fructose 6-phosphate (F-6-P) (r =
0.95,
P less than 0.01) and G-6-P (r = 0.96, P less than 0.01). Phosphocreatine and
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ATP decreased by 87 and 17%, respectively, whereas ADP increased by 31%
after contraction. These data demonstrate that intense, short-term isometric
contraction results in an elevation of the muscle content of G-1,6-P2.
[00172] In another study, it was shown that diabetics respond the same as
non-diabetics to stressors from isometric contractions (see, Kelleher C,
Ferriss
JB, Ross H, O'Sullivan DJ, The pressor response to exercise and stress in
uncomplicated insulin-dependent diabetes, J Hum Hypertens. 1987 Jun;1(1):59-
64, incorporated by reference herein in its entirety).
[00173] In that study, Kelleher et al. investigated whether or not an
increased
pressor response to exercise (i.e., the rise in blood pressure during
isometric
contractions) or stress is a feature of the diabetic state per se or a feature
of its
complications. Twelve insulin-dependent diabetic patients without clinical
evidence of complications and with normal albumin excretion rates (less than
20
mg/min) were studied with 12 control subjects. Each underwent a study protocol
of isometric handgrip exercise at 30% of maximum capacity for four minutes, a
cold pressor test with immersion of one hand in ice-cold water for two
minutes,
and bicycle ergometry at a resistance of 105 watts per minute for six minutes.
Both groups showed a similar and significant rise in systolic blood pressure
and
pulse rate in response to each stimulus. Diastolic pressure also rose
significantly
in response to handgrip exercise and to cold pressor stimulation. Mean plasma
noradrenaline concentration rose in response to each stimulus but the changes
reached conventional significance in both groups only in response to handgrip
exercise. Pressor responses to exercise and stress, as tested in the study,
were
concluded to be normal in insulin-dependent diabetic patients without
complications due to their disease. Thus, diabetics respond the same as non-
diabetics to the stressors, which suggests a potential benefit for treating
diabetecs with isometric exercise, since the rise in BP during the isometric
contractions is the physiological signal that leads to the adaptive response
of
lower BP over time with repeated isometric training.
[00174] Further studies have likewise concluded that resistance training
(i.e.,
isometric exercise) improves metabolic features and insulin sensitivity, and
reduces abdominal fat in type 2 diabetic patients. For example, Bacchi E, et
al.,
Metabolic Effects of Aerobic Training and Resistance Training in Type 2
Diabetic
Subjects: A randomized controlled trial (the RAED2 study), Diabetes Care. 2012
Feb 16, [Epub ahead of print], (incorporated by reference herein in its
entirety),
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assessed differences between the effects of aerobic and resistance training on
HbA(1c) (primary outcome) and several metabolic risk factors in subjects with
type 2 diabetes, and to identify predictors of exercise-induced metabolic
improvement. As is known, HbA(1c) is a form of hemoglobin that identifies
average glucose in blood plasma over time, i.e. months.
[00175] In the study, type 2 diabetic patients (n = 40) were randomly assigned
to aerobic training or resistance training. Before and after 4 months of
intervention, metabolic phenotypes (including HbA(1c), glucose clamp-measured
insulin sensitivity, and oral glucose tolerance test-assessed f3-cell
function), body
composition by dual-energy X-ray absorptiometry, visceral (VAT) and
subcutaneous (SAT) adipose tissue by magnetic resonance imaging,
cardiorespiratory fitness, and muscular strength were measured. After
training,
increase in peak oxygen consumption (V0(2peak)) was greater in the aerobic
group (time-by-group interaction P = 0.045), whereas increase in strength was
greater in the resistance group (time-by-group interaction P <0.0001). HbA(1c)
was similarly reduced in both groups (-0.40% [95% CI -0.61 to -0.18] vs. -
0.35%
(-0.59 to -0.101, respectively). Total and truncal fat, VAT, and SAT were also
similarly reduced in both groups, whereas insulin sensitivity and lean limb
mass
were similarly increased. (3-Cell function showed no significant changes. In
multivariate analyses, improvement in HbA(1c) after training was independently
predicted by baseline HbA(1c) and by changes in VO(2peak) and truncal fat.
Thus, resistance training, similarly to aerobic training, improves metabolic
features and insulin sensitivity and reduces abdominal fat in type 2 diabetic
patients. Other studies have shown similar results (e.g., see Lambemd S., et
al.,
Contractile activity of human skeletal muscle cells prevents insulin
resistance by
inhibiting pro-inflammatory signalling pathways, Diabetologia. 2012 Jan 27,
[Epub ahead of print], incorporated by reference herein in its entirety).
[00176] As described above, there are several metabolic links between
diabetes and obesity. Put simply, if insulin resistance is high, glucose sugar
is
not metabolized and glucose and other sugars are readily converted to fats and
stored. The studies cited herein use various methods of enhancing or blocking
some of these interconnected metabolic pathways to illustrate the effects of
exercise on skeletal muscle. Several of the recent studies included isometric
contractions, voluntary or electrically induced, which makes it easier to
connect
or extrapolate from "rhythmic" contraction studies.
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[00177] Other studies have elucidated the role and effect of certain factors
on
insulin sensitivity and signaling, even in aged animals. For example, Wenz T.,
et
al., Increased muscle PGC-1alpha expression protects from sarcopenia and
metabolic disease during aging, Proc Natl Acad Sci U S A. 2009 Dec
1;106(48):20405-10. Epub 2009 Nov 16, incorporated by reference herein in its
entirety, notes that aging is a major risk factor for metabolic disease and
loss of
skeletal muscle mass and strength, a condition known as sarcopenia. Both
conditions present a major health burden to the elderly population. Wenz et
at.
analyzed the effect of mildly increased PGC-1alpha expression in skeletal
muscle during aging, and found that transgenic MCK-PGC-1alpha animals had
preserved mitochondrial function, neuromuscular junctions, and muscle
integrity
during aging. Increased PGC-1alpha levels in skeletal muscle prevented muscle
wasting by reducing apoptosis, autophagy, and proteasome degradation. The
preservation of muscle integrity and function in MCK-PGC-1alpha animals
resulted in significantly improved whole-body health; both the loss of bone
mineral density and the increase of systemic chronic inflammation, observed
during normal aging, were prevented. Importantly, MCK-PGC-1alpha animals
also showed improved metabolic responses as evident by increased insulin
sensitivity and insulin signaling in aged mice. These results of Wenz et at.
highlight the importance of intact muscle function and metabolism for whole-
body
homeostasis and indicate that modulation of PGC-1alpha levels in skeletal
muscle presents an avenue for the prevention and treatment of a group of age-
related disorders.
[00178] Still other studies have examined the effect of exercise on insulin
action. For example, Vind BF, et at., Impaired insulin-induced site-specific
phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle
of type 2 diabetes patients is restored by endurance exercise-training,
Diabetologia. 2011 Jan;54(1):157-67, Epub 2010 Oct 13, (incorporated by
reference herein in its entirety), notes that phosphorylation of TBC1 domain
family, member 4 (TBC1D4) is, at present, the most distal insulin receptor
signalling event linked to glucose transport, and examines insulin action on
site-
specific phosphorylation of TBC1D4 and the effect of exercise training on
insulin
action and signalling to TBC1D4 in skeletal muscle from type 2 diabetic
patients.
[00179] In the study, during a 3 h euglycaemic-hyperinsulinaemic (80 mU min-1
m-2) clamp, Vind et al. obtained M. vastus tateralis biopsies from 13 obese
type 2
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diabetic and 13 obese, non-diabetic control individuals before and after 10
weeks
of endurance exercise-training. Before training, reductions in insulin-
stimulated
R (d), together with impaired insulin-stimulated glycogen synthase fractional
velocity, Akt Thr3 8 phosphorylation and phosphorylation of TBC1D4 at Ser318,
Ser588 and Ser751 were observed in skeletal muscle from diabetic patients.
Exercise-training normalized insulin-induced TBC1D4 phosphorylation in
diabetic
patients. This happened independently of increased TBC1D4 protein content, but
exercise-training did not normalize Akt phosphorylation in diabetic patients.
In
both groups, training-induced improvements in insulin-stimulated R(d) (-20%)
were associated with increased muscle protein content of Akt, TBC1D4, a2-
AMP-activated kinase (AMPK), glycogen synthase, hexokinase II and GLUT4
(20-75%).
[00180] Thus, it was concluded that impaired insulin-induced site-specific
TBC1D4 phosphorylation may contribute to skeletal muscle insulin resistance in
type 2 diabetes. And the mechanisms by which exercise-training improves
insulin sensitivity in type 2 diabetes may involve augmented signalling of
TBC1D4 and increased skeletal muscle content of key insulin signalling and
effector proteins, e.g., Akt, TBC1D4, AMPK, glycogen synthase, GLUT4 and
hexokinase
[00181] Finally, as noted, there is an intimate link between obesity and
diabetes. Problems with obesity, and the aspect of the present invention for
treating obesity with isometric exercise is discussed above. Part of that
discussion focuses on the FOXC2 gene and a newly revealed hormone, irisin
(see, Cederberg A, et al., FOXC2 is a winged helix gene that counteracts
obesity, hypertriglyceridemia, and diet-induced insulin resistance, Cell. 2001
Sep
7;106(5):563-73; and BostrOm P., et al., A PGC1-a-dependent myokine that
drives brown-fat-like development of white fat and thermogenesis, Nature. 2012
Jan 11;481(7382):463-8. doi: 10.1038/nature10777). Another aspect of the
present invention contemplates many of the therapeutic benefits of this
hormone
(and its isometric exercise-induced secretion) also being used as a therapy
for
diabetes.
[00182] Thus, like the method of the present invention for lowering the
resting
systolic and diastolic blood pressures of patients (described above), another
aspect of the present invention includes a method for treating diabetes via
isometric exercise. This method may begin with a determination of the maximal
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isometric force which can be exerted by a patient with any given muscle (e.g.,
skeletal muscle or group of muscles) of such patient. The determined maximal
isometric force is recorded. The patient, then, is periodically permitted to
intermittently engage in isometric contraction of the given muscle at a
fractional
level of the maximal force determined for a given contraction duration
followed
by a given resting duration. A perceptible indicia correlative to the
isometric force
exerted by the given muscle is displayed to the patient so that the patient
can
sustain the given fractional level of maximal force.
1001831 A representative procedure for a patient to follow includes the
patient
exerting a force with a selected muscle or muscle group to about 50%±5% of
the previously determined maximal isometric force (of that muscle or muscle
group) and holding that 50% force for 45 seconds; resting for one minute; and
then repeating multiple times. The particular muscle or muscle group may be
selected based upon the treatment desired. For example, the method may
include exerting a squeezing force with either hand equal to about 50%±5%
of
the previously determined maximal isometric force and holding that 50% force
for
45 seconds; resting for one minute; exerting a force with the other hand equal
to
50% of the maximum for 45 seconds; resting one minute; exerting a force of 50%
of maximum for 45 seconds again with the first hand; resting one minute; and
exerting a force of 50% for 45 seconds again with the second hand. This
completes the isometric exercise for that day. The same procedure may be
followed by the patient multiple days (e.g., at least five days per week). It
will be
recognized by those of ordinary skill in the art that the use of "hand" for
the
muscle group is exemplary.
100184] Thus, the isometric component of exercise alone can be used to
stimulate NO production to increase arterial diameter and treat diabetes, by
following a simple, yet effective, regimen that includes exerting fractional
isometric force by any given muscle (for present purposes, "muscle" includes
any skeletal muscle or group of muscles) for a given duration followed by a
given
duration of resting. This sequence is repeated several times (say, from about
3
to 6 times) and the entire regimen is repeated several times per week (say,
from
about 3 to 7 times per week). Since the regimen takes only several minutes per
day to complete, it is believed that patients will be better able to stay with
the
program and, thus, receive long term benefits in treating diabetes. Moreover,
since the patient exerts only a fraction of the maximal force of the given
muscle,
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the patient's blood pressure during the exercise protocol does not rise to
unacceptably high values whereat the patient's health would be at risk.
[00185] An important aspect of the therapeutic method associated with the
instrument of the invention resides in the limiting of user performance to
carry out
the regimen of trials. In this regard, the instrument is programmed to perform
only within predetermined and mandated test limits. Each therapeutic regimen
is
based upon an initial evaluation of the maximum gripping force capability of
the
user. Under that limitation, target load factors, hold on target load
intervals,
intervening rest intervals and trial repetition numbers may be elected only
from
pre-established and mandated memory retained ranges. The program also
nominates rest intervals and hold on target intervals in correspondence with
user
elected target force factors. Thus, valuable strength recovery and development
may be achieved but only within safe limits.
[00186] Additionally, the instrument is employable as a therapeutic device.
First a protocol is nominated by prescribing nominal parameters of the effort.
Each isometric regimen is controlled initially by requiring that a maximum
grip
strength be established for each individual patient or user. Then, the
practitioner
may elect parameters of grip force and timing under mandated memory
contained parameter limits. Accordingly, the user will be unable to carry out
strength enhancement therapies which would otherwise constitute an excessive
grip force regimen. For carrying out the noted diagnostic procedures as well
as
therapy activities, the grip widthwise extent is variable from 17/8 inches to
27/8
inches, such variation being adjustable in 1/2 inch increments. This is in
keeping
with standardized diagnostic practices. Further with respect to diagnostic
procedures, the display or readout of the instrument can be adjusted with
respect
to the grip structuring such that only the practitioner or therapist may
observe the
data which is being developed during a diagnostic protocol.
[00187] More particular description of examples of protocols are shown in FIG.
19, (described in greater detail above), which presents a flow diagram that
outlines the methodology achieving this safe utilization of isometric
exercises.
[00188] While the various aspects of the present invention have been
disclosed by reference to the details of various embodiments of the invention,
it
is to be understood that the disclosure is intended as an illustrative rather
than in
a limiting sense, as it is contemplated that modifications will readily occur
to
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those skilled in the art, within the spirit of the invention and the scope of
the
appended claims.
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