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ISSN 2320-5407 International Journal of Advanced Research (2015), Volume 3, Issue 3, 689-696
689
Journal homepage: http://www.journalijar.com INTERNATIONAL JOURNAL
OF ADVANCED RESEARCH
RESEARCH ARTICLE
Effect of extracorporeal shock wave therapy on skin blood perfusion in patients with
diabetic foot: Randomized controlled trial.
Mohamed Ibrahim Ahmed Ibrahim Mabrouk1, Nagwa Mohamed Badr2, Mona Mohamed Taha3, Ahmed
Mohamed Fathi El Shiwi4, Ashraf Abdelaal Mohamed Abdelaal5, Shymaa Mohamed Ali6, Alaa Mohamed
Abd El Hamed7
1 M.Sc. in Physical Therapy for Cardiovascular /Respiratory Disorder and Geriatrics, General Organization of The
Teatching Hospitals and Institutes (National Heart Institute), Egypt.
2, 3,5,6 Department of Physical Therapy for Cardiovascular/Respiratory Disorder and Geriatrics, Faculty of Physical
Therapy, Cairo University.
4 Department of Physical Therapy for Musculoskeletal Disorders and its Surgery, Faculty of Physical Therapy, Cairo
University.
7 Department of Internal Medicine, Faculty of Medicine, Cairo University.
Manuscript Info Abstract
Manuscript History:
Received: 11 January 2015
Final Accepted: 25 February 2015
Published Online: March 2015
Key words:
Extracorporeal Shockwave, Blood
Perfusion, Diabetic Foot
*Corresponding Author
Mohamed Ibrahim Ahmed
Ibrahim Mabrouk
Introduction: Diabetes mellitus (DM) is associated with serious
microvascular complications, which have significant impact on patient's
quality of life, morbidity, and mortality. Aim: The aim of this study was to
investigate the effect of extracorporeal shock wave therapy (ESWT) on blood
perfusion of diabetic foot in patients with type 2 diabetes mellitus (T2DM).
Methods: Thirty patients with T2DM, aged 40 to 55 years and were
randomly assigned into group-A (study group) received ESWT (3000 shock,
1000/session, 3 sessions, 2 weeks a part, 0.32mJ/mm2) in addition to oral
hypoglycemic drugs or group-B (control group) received oral hypoglycemic
drugs only. Maximum skin blood perfusion (SBP max), minimum skin blood
perfusion (SBP min), and basal mean changes of perfusion (BMCP) of the
legs were evaluated at the beginning and after four weeks for both groups.
Results: SBP min, SBP max and BMCP were evaluated before and after the
study. At the end of the study; SBP min and percentage of improvement (%)
for the groups-A and B were 9.9±2.7 (44.93%) and 7.25±3.44 (0.93%)
respectively. SBP max and (%) for the groups-A and B were 25.19 ± 4.14,
(15.62%), 22.17 ± 2.52, (0.12%) respectively. BMCP and (%) for the groups-
A and B were 15.37±2.64 (16.09%) and 12.73± 2.49 (0.29%) respectively
(P<0.05). Conclusion: ESWT is effective in increasing blood perfusion and
microcirculation in diabetic foot of patient with T2DMP.
Copy Right, IJAR, 2015,. All rights reserved
INTRODUCTION
Diabetes mellitus (DM); a metabolic disorder characterized by defects in insulin secretion/ action or both; is
accompanied with long-term dysfunction of various organs, especially blood vessels (American Diabetes
Association, 2005). The rapid rise in the incidence of DM and its related complications is an alarming concern to
health care professionals (Wu et al., 2007). Diabetes becomes one of the most common chronic non-communicable
diseases, the global prevalence of DM in 2000 was estimated at 131 million and is expected to reach 366 million by
2030 (Wild S et al., 2004).
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690
With its wide-spread prevalence; 90% to 95% of patients with DM have type 2 diabetes mellitus (T2DM). The
incidence of T2DM is expected to continue rising because of the globally prevailing inactive life style. T2DM-
related micro or macrovascular complications are frequently associated with disability and mortality (Creager et al.,
2003) and impaired patient's quality of life (Viberti, 2005).
Lower limb diabetic ischemia is a serious complication that can lead significant pathologic consequences including
ulceration, infection, destruction of deep tissues and amputation (Khalifa et al., 2009).These consequences, if
ignored, take continuous serial and sequential pattern because patients with diabetes have diminished ability to
establish collateral circulation (Gayle et al., 1998). Risk of peripheral arterial disease (PAD) is increased by age and
duration of diabetes, with "the below knee vessels" are the most affected site (American Diabetes Association,
2003a).
Diabetic foot and lower limb disorders share large proportion of morbidity in patients with T2DM, the matter that
arises the need for effective foot care interventions for those patients (Reiberet al., 1995).Prevention and early
intervention is a cornerstone in management of T2DM related PAD because the process of improving the circulatory
health of the extremity with bad and deteriorated status is costly and time consuming (Rodrigues and Mitta, 2011).
Rapid changes in diagnostic, treatments and vascular services procedures are associated with the emergence of new
interventions that resulted in considerable variation in practice (NICE 2012). The non-invasive techniques play an
important role in PAD evaluation and management when utilized in evaluation of vascular status health (Rodrigues
and Mitta, 2011). Noninvasive blood flow evaluative measures are usually preferable, Laser Doppler Flowmetry
(LDF) can be efficiently used to evaluate skin microcirculation and perfusion in patients with T2DM (Núńez et al.,
2004).
Shock waves (SW) are sound waves generated by a vibration-creating source, characterized by a very high pressure
amplitude (up to 1000 bar/100 MPa), very short pulse length in the range of 300 ns and extremely short pulse rise
time of around 10 ns(Jankovic, 2011), transported through tissue via fluid and solid particles interaction (Perez et
al., 2003). Extracorporeal shock waves Therapy (ESWT) have been used for the treatment of number of
musculoskeletal disorders (Furia, 2006), dermatological disorders, poorly healing burns and diabetic leg wounds.
ESWT can successfully improve blood supply and tissues metabolic processes and hence stimulates biological
regeneration processes and long-term healing (Jankovic, 2011).
Material and Methods
Subjects
Forty patients diagnosed with T2DM were evaluated for eligibility for this study, of them; thirty patients (17 male
(57%) and 13 female (43%)) with T2DM were eligible for the study. Patients were recruited from the outpatient
clinic of Kasr Al-Aini Hospital. All evaluative and treatment procedures were applied in the outpatient clinic of the
Al-Aguza Physical Rehabilitation Center, Army Hospital, Egypt. All patients fulfilled the inclusion criteria of the
study and had no exclusion criteria. This study was carried out according to the principles of the Declaration of
Helsinki 1975, revised Hong Kong 1989 and was approved by the corresponding department council and ethics
committee.
Inclusion criteria:
The inclusion criteria were as follows: Age from 40-55 years old, established T2DM for 10-15 years duration, Under
tight medical control, treatment only with oral hypoglycemic agents (not taking insulin), and an inactive previous
lifestyle for at least the previous 6 months.
Exclusion Criteria:
Age over 55 or less than 40 years, pregnant women, smoking, history of serious cerebrovascular or cardiovascular
diseases that could affect patient safety and continuity of the study, existent of chronic respiratory or
cardiopulmonary disorders and sever current lower extremity symptoms.
The study protocol was explained in details for every patient before the initial assessment. All patients were
informed about the purpose, nature of the study and a written informed consent was obtained before participation in
the study; giving agreement to participation and publication of the results of the study. Initial medical screening was
performed for each patient by the physician; clinical history was documented for all participants with particular
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attention to identify any long-term complications of diabetes. All participants were asked to continue their
pharmacological regimen, regular diet, normal daily activities and lifestyle throughout the study.
Patients were randomly assigned into two groups through two stages by a person who did not share any other part of
the study. First; eligible patients who fulfilled the inclusion criteria were initially recorded. Second; after medical
counseling; patients were randomly assigned into either group-A; study group (n=15; received ESWT plus oral
hypoglycemic medications or group-B; control group (n=15; received oral hypoglycemic medications only) through
opening an opaque envelope prepared by an independent person with random number generation.
Evaluation:
Patients in both groups underwent an identical battery of tests; pre and post-study evaluations. All evaluative and
treatment procedures were conducted at the same time of the day (between 9-11 am). Surrounding environment was
controlled to be the same for all patients throughout the study. Evaluated variables include maximum skin blood
perfusion (SBP max), minimum skin blood perfusion (SBP min), and basal mean changes of perfusion (BMCP) of
the lower extremity, all variable were evaluated at the beginning and after four weeks for both groups. Weight in Kg
and height in cm were also evaluated using a standard laboratory scale. Involvement and assessment of the patients
was conducted after agreement of their physician.
Evaluation of the skin blood flow by Laser Doppler:
While assuming supine lying position for at least 5 min (IN WHICH patient was asked to remain as motionless as
possible); skin blood flow was evaluated for each patient using (Laser Doppler FlowmetryPeriflux system 5001
(LDF), Perimed, Sweden). After proper cleaning of the pulp of the great toe, The Laser Doppler probe was
positioned on the pulp of the right great toe that the tip touched the tissue without over pressure to prevent the false
measurements. A combined laser Doppler and thermostatic probe was used for local heat provocation while blood
perfusion was measured.
Interventions:
Each group adhered to the prescribed regimen throughout the study. After the physician permission; group-A; study
group (n=15; received ESWT "3000 shock, 1000/session, 3 sessions, 2 weeks a part, 0.32mJ/mm2" plus oral
hypoglycemic medications, while group-B; control group (n=15; received oral hypoglycemic medications only). No
adverse events were recorded throughout the study. ESWT treatment was applied after proper cleaning of the lower
leg and foot by alcohol, while the patient assumed relaxed supine lying position.
The ESWT was applied perpendicular to the skin using The Orthospec ESWT (Medispec LTD, Germantown, MD,
USA). The ESWT pattern of application was adjusted to cover the width of the area from above the malleoli till tip
of the big toes then to the plantar aspect. ESWT was applied on the dorsal, plantar and lateral surface of the right
ankle and foot. ESWT was applied in form of 3000 shocks (1000 shock/session, 2 week apart for 3 sessions).
The ESWT treatment was performed using an electrohydraulic, or "spark-gap", method of creating therapeutic
shockwaves, according to previously mentioned procedure in which the used portable shockwave generator targeted
the shockwaves to a 35-mm diameter therapy zone that enables shockwaves of sufficient energy to be delivered to
the tissues in a single therapeutic session (Malay et al., 2006).
Statistical analysis
All data were examined using SPSS version 16.0. Data were collected and statistically analyzed using pre and post
study T-test to test hypothesis and to control both within and between variabilities. All results were shown as means
and standard deviations (SD), and a p-value less than 0.05 was considered as a statistically significant value.
Result
For this study, forty patients with T2DM were evaluated for eligibility for this study. Of these; thirty patients were
eligible and included. In the baseline (pre-treatment) evaluation; results revealed that there were statistically non-
significant differences between the two groups (study group; group-A and control group; group-B) before treatment
(pre-test values) in the demographic characteristics including age, height, weight, BMI, FBG, HbA1c and average
duration of T2DM among both groups, (table I); P < 0.05.
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Table I: Demographic data of participants in both groups (pre- study).
Variables
Study group (group-A;
n=15)
Control group
(group-B; n=15)
T value
P value☼
Age (year)
50.4 ± 3.09
50.93 ± 3.39
0.45
0.66٭٭
Height (m)
170.78 ± 6.6
171.13 ± 4.88
0.13
0.9٭٭
Weight (kg)
78.33 ± 7.14
79.07 ± 9.28
0.24
0.81٭٭
BMI (Kg/m2)
36.23 ± 6.07
38.27 ± 8.47
0.76
0.46٭٭
Fasting blood glucose
(mmol/L)
173.6 ± 23.88
166.8 ± 22.57
0.801
0.43٭٭
☼Level of significance at P<0.05.٭ = significant ٭٭ = non-significant
Within groups
Post-study results revealed that there were significant increase in mean values of maximum skin blood perfusion
(SBP max), minimum skin blood perfusion (SBP min), and basal mean changes of perfusion (BMCP) of the lower
extremity within group-A, compared with non-significant increase in the same measured variables within group-B
(P < 0.05), (Table II).
Between groups:
Post-study results of between groups' comparisons revealed that there were significant differences in mean values of
SBP min, SBP max and BMCP of the lower extremity (P < 0.05) (Table II), (Figure 1).
Table II. Within and between groups' comparisons of SBP min, SBP max and BMCP mean values (T & P
values).
Variable
Group
Pre
Post
T & P values
SBP min
Study group
7.23 ± 2.71
9.9±2.66
10.84, 3.42-8 ٭
Control group
7.21 ± 3.46
7.25±3.44
1.47, 1.64٭٭
T & P values
0.02, 0.99 ٭٭
2.36, 0.03 ٭
SBP max
Study group
21.95±4.22
25.19±4.14
-9.9-, 1.05 -7٭
Control group
22.15±2.52
22.17±2.52
-1.08-, 0.301 ٭٭
T & P values
-0.16-, 0.88 ٭٭
2.41, 0.02٭
BMCP
Study group
13.29±2.44
15.37±2.64
-11.7-, 1.29 -8٭
Control group
12.71±2.55
12.73± 2.49
-0.94-, 0.36 ٭٭
T & P values
0.64, 0.53 ٭٭
2.82, 0.01 ٭
Minimum skin blood perfusion (SBP min), Maximum skin blood perfusion (SBP max), and basal mean changes of
perfusion (BMCP) of the lower extremity.
Level of significance at P<0.05.٭= significant ٭٭= non-significant
Minimum skin blood perfusion (SBP min) evaluation:
The pre and post-study mean values of (SBP min) are reported in table II. By comparing the mean values of (SBP
min) at pre and post-study evaluations for study and control groups; there was statistically significant increase in
(SBP min) by about 44.9% for study group, and non-significant increase by about 0.93 % for control group (Figure
1).
Maximum skin blood perfusion (SBP max) evaluation:
The pre and post-study mean values of (SBP max) are reported in table II. By comparing the mean values of (SBP
max) at pre and post-study evaluations for study and control groups; there was statistically significant increase in
(SBP max) by about 15.62% for study group, and non-significant increase by about 0.12 % for control group
(Figure 1).
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Basal Mean Changes of Perfusion (BMCP) of the lower extremity evaluation:
The pre and post-study mean values of (BMCP) are reported in table II. By comparing the mean values of (BMCP)
at pre and post-study evaluations for study and control groups; there was statistically significant increase in (SBP
max) by about 16.09 % for study group, and non-significant increase by about 0.29 % for control group (Figure 1).
Figure (1): Mean valuesof Minimum skin blood perfusion (SBP min), Maximum skin blood perfusion (SBP max),
and basal mean changes of perfusion (BMCP) of the lower extremity for both groups.
Discussion
Patients with T2DM have an increased incidence of atheroscleroticcardiovascular and peripheral vascular disorders
(American Diabetes Association, 2003b). Diabetics are at great risk of morbidity and mortality from
cardiovascular disease; the leading cause of death among diabetic people (American Diabetes Association, 2010).
Therefore, efforts to prevent and/ or reduce diabetes- related complications by introduction of preventive or
therapeutic measures into the treatment program must be a primary interest when caring for the diabetic patients
(Abdelaal et al., 2013).
Foot problems are the most common reasons for hospitalization of patients with T2DM. Gangrene and amputation
pose a major burden both to the patient and to the health care system. Impaired blood supply is considered among
the most important risk factors for foot ulceration and gangrene (Urbani et al., 2004).T2DM Accompanied vascular
complications and abnormal endothelial function in patients with T2DM are considered among the main causes of
morbidity and mortality. A high percentage of endothelial- damage markers are detected in diabetic subjects;
0
5
10
15
20
25
30
SBP min (
Pre(
SBP min
(Post (
SBP max (
Pre(
SBP max (
Post(
BMCP
(Pre(
BMCP
(Post(
7.23
9.9
21.95
25.19
13.29
15.37
7.21
7.25
22.15
22.17
12.71
12.73
Flux
Study group
Control group
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especially those with microvascular complications (Regla et al., 2001). With type 2 diabetes, the maintenance of
skin blood flow is imperative to promote effective healing and prevent ulcerations in the skin (Kilo et al., 2000).
Recently, there has been an increase in the clinical application of shock wave therapy in various fields. The rational
for the use of ESWT in patients with T2DM is based on stimulation of neovascularization and pain relief (Maier et
al., 2002), with minimal side effects that may include local bruising or short duration swelling and tenderness
(Lebrun, 2005). This study was designed to explore the effect of ESWT on blood flow in patients with T2DM. A
comparison was conducted between 2 groups of patients with T2DM (study and control groups). The results of this
study revealed that ESWT significantly increases blood flow and perfusion in patients with T2DM.
In the present study, we found that application of ESWT lead to a significant increase in Minimum skin blood
perfusion (SBP min), Maximum skin blood perfusion (SBP max) and Basal Mean Changes of Perfusion (BMCP) of
the lower extremity as measured by laser Doppler flowmetry. Treatment with ESWT has been prescribed in many
other cases, resulting in many favorable outcomes. ESWT fasten burn wound healing rate and perfusion in patients
with deep partial full thickness burn. ESWT objectively increases perfusion to the ischemic tissue, stimulates growth
factors, decreases inflammation and accelerate healing (Arno et al., 2010).
Results of our study were consistent with previous studies reported that optimal dosage of ESWT treatment
positively affects flab ischemic zone increasing tissue perfusion, suppressing inflammatory response, increasing
tissue perfection which leads to enhance tissue healing and improve function and vitality (Kuo et al., 2007).
Another study stated that ESWT suppresses the early pro-inflammatory immune response, significantly blunts
polymorphonuclear neutrophil and macrophage infiltration, attenuates acute pro-inflammatory cytokine expression
and extracellular matrix proteolytic activity and hence protects against additional capillary endothelial and skin
damage (Davis et al., 2009).
The beneficial effects of application of ESWT can be further explained on the basis of possible molecular
mechanism of the anti-inflammatory action of ESWT treatment. ESWT can increase neuronal nitric oxide synthase
(nNOS) activity and basal nitric oxide (NO) production. Furthermore; ESWT reverts the decrease of nNOS activity
and NO production induced by a mixture of lipopolysaccharides (LPS), interferon-γ (IFN-γ) plus tumour necrosis
factor a (TNF-a). Additionally; NO is important for vasodilation, angiogenesis and neurotransmission. ESWT can
effectively enhance endothelial NOS (eNOS) activity in endothelial cells (Ciampa et al., 2005). Application of
ECSWT proved to be effective in reducing the amount of exudates, increasing percentage of granulation tissue
compared with fibrino-necrotic tissue. ESWT therapy is a safe, feasible and cost-effective treatment for the lower
extremities disorders and ulcers (Saggini et al., 2008).
Results of the current study were consistence with results obtained from a study conducted by Wang et al., to
evaluate the effect of Low-energy ESWT on stimulating the blood flow and revascularization of injured tissue.
Application of ESWT enhanced the process of neovascularization at the bone-tendon injured site (Wang and Chen,
2002). ESWT can significantly improve blood supply and tissue regeneration through stimulating production and
expression of angiogenesis-related markers including endothelial nitric oxide synthase (eNOS), vessel endothelial
growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) (Wang et al., 2003). Furthermore; application
of ESWT can relieve joints symptoms through altering focal circulation and soft tissue regeneration (Hsu et al.,
2008).
Beneficial ESWT effects observed in our study can be explained on basis that ESWT application creates little
tunnels through which new blood vessels can grow, and so stimulating an increased blood flow to the area.
Additionally; ESWT application stimulates release of local endorphins and provides local anesthetic effect(Tassery
and Allaire, 2003).
Conclusion
ESWT is safe and effective and adjunctive modality to other therapeutic procedures described for management of
circulatory disturbances usually encountered in patients with T2DM. Results of this study have clinical significance
to physical therapists dealing with patients with T2DM. The utilized ESWT program in this study can be easily and
safely applied in clinical practice settings and serve as an adjunctive treatment protocol to prevent complications and
improve lower limb circulation in patients with T2DM.
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References
Abdelaal, A.A., Elsisi H.F., and Alayat M.S. (2013). Lipid profile and hemodynamic response to exercise therapy
in type 2 diabetic pre-hypertensive patients: A follow up randomized controlled trial. Jokull Journal. 63 (5): 290-
308.
American Diabetes Association(2003a). Peripheral Arterial Disease in People with Diabetes.Diabetes Care. 26:
3333-3341.
American Diabetes Association.(2003b). Report of the Expert Committee on the Diagnosis and Classification of
Diabetes Mellitus.Diabetes Care. 26:S5-S20.
American Diabetes Association.(2005). Diagnosis and Classification of Diabetes Mellitus.(Position
statement).Diabetes Care. 28: S37-S42.
American Diabetes Association.(2010). Diagnosis and classification of diabetes mellitus.Diabetes Care.
33(Supplement 1): S62-S69.
Arno, A., Garcia, O., Hernan, I., Sancho, J., Acosta, A. and Barret, J.P. (2010).Extra corporeal shock waves a
new non-surgical method to treat severe burns. Burn. 80(25): 119-129.
Ciampa, A.R., Prati, A.C., Amelio, E., Cavalieri, E., Persichini, T., Colasanti, M., Musci, G., Marlinghaus, E.,
Suruki, H. and Mariotto, S. (2005). Nitric oxide mediates anti-inflammatory action of extracorporeal shock waves.
FEBS letters 579 (19): 6839-6845.
Colberg, S.R., Stansberry, K.B., McNitt, P.M. and Vinik, A.I. (2002).Chronic exercise is associated with
enhanced cutaneous blood flow in type 2 diabetes. Journal of Diabetes and Its Complications. 16:139-145.
Creager, M., Lüscher, T., Cosentioo, F. and Beckman, J. (2003).Diabetes and Vascular Disease:
Pathophysiology, Clinical Consequences, and Medical Therapy: Part I. Circulation. 108:1527.
Davis, T.A., Stojadinovic, A., Amare, K., Anam, M., Naik, S., Peoples, E.E., Tadaki, D. and Elster, E.A.
(2009). Extra corporeal shockwave therapy suppresses the acute early pro-inflammatory immune response to a
severe cutaneous burn injury. Int. Wound Journal. 6: 11-21.
Furia, J.P. (2006). High energy extracorporeal shock wave therapy for insertionalachillistendionpathy.AmJ sports
Med. 34: 733-740.
Gayle, R., Benjamin, A.L., and Gary, N.G. (1998).The burden of diabetic foot ulcers.The American Journal of
Surgery. 176 (Suppl 2A): 65-105.
Hsu, C., Wang, D., Tseng, K., Fong, Y., Hsu, H. and Jim, Y. (2008).Extra corporeal shock wave therapy for
calcifying tendonitis of the shoulder.Journal of shoulder and elbow surgery. 17 (1): 55-59.
Jankovic, D. (2011). Case study: shock waves treatment of diabetic gangrene. Int Wound J. 8:206-209.
Khalifa, A.A., Gueret, G., Badra, A., and Gouny, P. (2009). Diabetic Critical Ischemia of Lower Limbs : Distal
Arterial Revascularisation. ActaChir Belg. 109: 321-326.
Kilo, S., Berghoff, M., Hilz, M. and Freeman R. (2000).Neural and endothelial control of microcirculation in
diabetic peripheral neuropathy.Neurology. 54: 1246-1252.
Kuo, Y-R., Wu, W-S., Hsieh, Y-L., Wang, F-S., Wang, C-T., Chiang, Y-C.and Wang, C-J. (2007). Extra
corporeal shockwave enhance extended skin flap tissue survival increase of topical blood perfusion and associated
with suppression of tissue pro-inflammation. Journal of surgical research. 143 (2): 385-392.
Lebrun, C. (2005).Understanding shock wave therapy for the treatment of bone and tendon pain.Sportline. 1 (20):
1-4.
Maier, M., Miler, S., Writz, D.C., Rompe, J.D. and Schritr, C. (2002). Basic research of the applying
extracorporeal shock waves on the musculoskeletal system.An assessment of current status.Orthopedec. 31: 667-
677.
Malay, D.S., Pressman, M.M., Assili, A. and Kline, J.T. (2006).Extracorporeal shock wave therapy versus
placebo for the treatment of chronic proximal fasciitis.The journal of foot and ankle surgery. 45 (4): 196-209.
ISSN 2320-5407 International Journal of Advanced Research (2015), Volume 3, Issue 3, 689-696
696
National Institute for Health and Clinical Excellence.(2012) (NICE 2012).Lower limb peripheral arterial disease:
diagnosis and management: guidance. NICE clinical guideline 147. nice.org.uk/cg147.
Núńez, S., Nogueira, G., Ribeiro, M. and Lage-Marques, G. (2004).He-Ne laser effects on blood
microcirculation during wound healing.Lasers in Surgery and Medicine. 35:363-368.
Perez, M., Weiner, R. and Gilley, J.C. (2003).Extracorporeal shock wave therapy for the planter
facilities.Clin.Podiatr. Med. Surg.20: 333-346.
Regla, M., Mateo, J., Cauxas, A. and Perer, A. (2001). Physical training decreases plasma thrombomodulin in
type 1 and type 2 diabetic patients. Diabetologia. 4:693-699.
Reiber, G.E., Boyko, E.J., and Smith, D.G. (1995).Lower extremity foot ulcers and amputations in diabetes. In:
National Diabetes Data Group, National Institutes of Health, National Institute of Diabetes and Digestive and
Kidney Diseases. Diabetes in America. 2nd ed. Bethesda (MD): p. 409-28.
Rodrigues, J., and Mitta, N. (2011). Diabetic Foot and Gangrene, Gangrene - Current Concepts and Management
Options, Dr. Alexander Vitin (Ed.), pp. 122-143. Available from: http://www.intechopen.com/books/gangrene-
current-concepts-and management-options/diabetic-foot-andgangrene.
Saggini, R., Figus, A., Troccola, A., Cacco, V., Saggini, A. and Scuderi, N. (2008). Extracorporeal shock wave
therapy for management of chronic ulcers in the lower extremities.Ultrasound in medicine and biology. 34 (8):
1261-1271.
Tassery, F. and Allaire, T. (2003).Radial shock wave therapy for the treatment of lower limbs.FIBA Assist
Magazine. 3: 57-58.
Urbani, V., Stefanovska, A., Bernjak, A., Juvan, K. and Kocijani, A. (2004).Skin Blood Flow in the Upper and
Lower Extremities of Diabetic Patients with and without Autonomic Neuropathy. J Vasc Res. 41:535-545.
Viberti, G. (2005). Thiazolidinediones-benefits on microvascular complications of type 2 diabetes.J-Diabetes-
Complications. 19 (3): 168-177.
Wang, C-J., and Chen, H-S.(2002). Shock wave therapy for patients with lateral epicondylitis of the
elbow.American Journal of Sports Medicine. 30 (3): 422-425.
Wang, F.S., Yang, K.D., Kuo, Y.R., Wang, C.J., Sheen-Chen, S.M., Huang, H.C. and Chen, Y.J. (2003).
Morphogenetic proteins in extra corporeal shock wave promoted healing of segmental defect. Bone. 32 (4): 387-
396.
Wild, S., Roglic, G., Green, A. et al. (2004). Global prevalence of diabetes: estimates for the year 2000 and
projections for 2030. Diabetes Care. 27: 1047-53.
Wu, S.C,, Driver, V.R., Wrobel, J.S., and Armstrong, D.G. (2007). Foot ulcers in the diabetic patient, prevention
and treatment.Vasc Health Risk Manag. 3(1):65-76.
