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The diabetic foot. General considerations and proposal of a new therapeutic and preventive approach
Abstract
The treatment of the diabetic foot is a common and sometimes difficult problem. The treatment of the characteristic lesions of the diabetic foot involves many forms of therapy: these include contact dressings and topical treatments. The different therapies that have been applied do not often give satisfactory results. Therefore, for this purpose, we have studied the effect of biostimulation of wound-healing by utilising the CO2 laser together with the action of the KTP laser on 25 patients (11 females and 14 males), all suffering from diabetes mellitus with polyneuropathic ulcers of the foot. Low out-put laser irradiation may stimulate granulation tissue and collagen production in fibroblasts. Many studies observed a regeneration of microcirculation in the ulcer and a regeneration of lymphatic circulation. The laser irradiation method produces a sterilizing effect from bacteria that over-infect the diabetic ulcer too. Each patient underwent a surgical treatment of the edges of the ulcers with CO2 and KTP laser (wavelength 532 nm) focused, and a combined phototherapy (CO2 laser and afterwards KTP laser, defocused). The irradiation was carried out through laser beam (by optic fiber for KTP) manually directed, until all of the ulcer surface became irradiated. On the skin around the ulcer, an omental derived cream (fractionated porcine omental lipid extracts) was daily applied, independently from the laser treatment, to evaluate the angiogenic effect of this substance.(ABSTRACT TRUNCATED AT 250 WORDS)
... ~ 459 ~ Other risk factors for DFU's include male sex, smoking, poor glycemic control, previous risk of ulcer or amputations [4] . Newer and recent modality of treatment of DFU's are ultrasound therapy, laser therapy, photo biomodulation, electrical stimulation, growth factor applications, hyper baric oxygen therapy (HBOT), Platelet Rich Plasma (PRP) application and vacuum assisted wound closure therapy (VAC) [5,6] . The common complication of diabetes includes foot problems, which is the most common cause of non -traumatic limb amputations [19] . ...
Introduction: Foot ulcers are serious complication of Diabetes Mellitus and are known to be resistant to conventional treatments. They may end in severe complications like amputations if not treated wisely at the earliest. Foot ulcers affect 10-25% of Diabetic patients. Management of a Diabetic Foot Ulcer (DFU) is often a challenging problem. Healing of these ulcers often takes a long time and may need one or more methods of treatment. In particular Vacuum assisted wound closure (VAC) therapy has gained popularity for treatment of chronic and complex wounds in patients with Diabetes.
Aims and Objectives: To evaluate the efficacy of vacuum assisted wound closure (VAC) therapy for the treatment of diabetic foot ulcers.
Materials and Methods: This is a prospective observational study done in Department of Plastic Surgery in Rajah Muthiah Medical College, Annamalainagar, Chidambaram from January 2016 – December 2018 with a total of 30 patients with diabetic foot ulcers. All these patients after admission were started on medical treatment for control of diabetes and antibiotics for infection. They were subjected to wound debridement followed by VAC dressing. The VAC dressing was continued till the ulcer bed developed healthy granulation tissue and ready for definitive procedure like grafting or flap cover. Initial wound surface area and the resultant wound surface area after VAC therapy, duration of hospital stay and procedure done for DFU’s were recorded and statistical analysis was done using paired ‘T’ test to compare wound surface area before and after VAC therapy.
Result: This study showed that mean initial wound surface area of 30 patients before VAC therapy was 103.07 cms and after VAC therapy there was significant reduction in wound size to 94.53 cms over a mean duration of 31.9 days. There was statistically reduction in wound size of 9.53 cms. This significantly increased the wound bed granulation tissue and good percentage of graft and flap take up. The daily requirement of antibiotic and analgesic was also reduced. Duration of hospital stay was also reduced due to faster wound healing. There was overall reduction in pain and further complications like amputations were avoided thereby increasing the patients compliance.
Conclusion: VAC therapy is newer and a safe method of treatment for Diabetic Foot Ulcers. There is faster wound healing, good graft and flap take with minimal or no complications.
... Most of these drugs are regularly related with systemic aftereffect and do not retard advancement of the neuropathy [11]. Non pharmacological method of treatment includes Acupuncture, Transcutaneous electrical nerve stimulation (TENS) infrared [12,13] and low level laser therapy. ...
Background: Low Level Laser Therapy (LLLT) is an emerging treatment modality for management of
neuropathic pain. It works by triggering biochemical changes with in cells.
Objective: This systematic review focused on finding evidence on the effectiveness of LLLT on treatment
of painful diabetic neuropathy.
Methods: We conducted a systematic review (PubMed, Web of Science, CINAHL and Cochrane) to find the evidence on effectiveness of LLLT on treatment of painful diabetic neuropathy. Randomized and nonrandomized
studies were included in the review.
Results: A total of 627 studies were screened. After the exclusion criteria (duplicate, animal studies, LLLT
for treating other neuralgias) 6 studies were included in the study. The outcome measure that was considered were the difference in pain score and nerve conduction velocity test and quality of life
questionnaire.
Conclusion: The evidence obtained shows LLLT has a positive effect in controlling diabetic neuropathic
pain.
... When traditional wound care methods fail, alternative treatments are needed to prevent chronic ulcer complications, such as amputation. CO 2 laser can be a valid alternative to traditional surgery because of its versatility (possibility of non-vital tissue vaporization, cutting, hemostasis, controlling local infection [1,2] in the treatment of skin ulcers, as described in several case reports [2][3][4][5][6][7][8][9] and in a randomized clinical trial on decubitus ulcers [1]. ...
AimThe treatment of foot ulcers with exposed bone is challenging, because of the risk of infection and of difficulties in the development of granulation tissue. A CO2 laser beam could be used to produce discontinuities in periosteum, allowing the exposure of blood containing multipotent stem cells, capable of initiating the healing process. The local application of platelet-rich plasma (PRP) has been proposed as a therapeutic tool for accelerating healing in foot ulcers, including those in patients with diabetes. Aim of the present pilot, proof-of-concept study is the assessment of the therapeutic potential of CO2 laser treatment, either alone or combined with PRP, in the treatment of diabetic foot ulcers with exposed bone. Methods
We performed a pilot, uncontrolled 3-month observation study on a consecutive series of 9 type two diabetic patients and foot ulcers with exposed bone. A CO2-laser was used for producing nine discontinuities on periosteum for each cm2, by directing the focused laser beam on the bone until bleeding. The procedure was repeated up to 6 times, at a distance of 1 week and ulcers assessed weekly until the end of the study (3 months). In the last 5 of the 14 patients, the treatment described above was associated with PRP. ResultsOf the nine patients treated, four healed, and one more patient developed granulation tissue covering entirely bone surface. Out of the four patients who did not heal, one underwent minor amputation. Among the five patients treated with a combination of CO2 laser and PRP, two healed within 3 months, and two more patients developed granulation tissue covering entirely bone surface; the fifth patient did not show any improvement and underwent amputation. Conclusions
The present pilot experience represents a novelty in this field showing a possible use of CO2-laser in the treatment of diabetic foot ulcers.
... Non-healing DFUs are resistant to conventional treatment [19]. Several adjuvant therapies which have been tried to stimulate healing process are ultrasound, laser therapy and other forms of photobiomodulation, electrical stimulation, hyperbaric oxygen and vacuum-assisted closure [20,21]. Although laser therapy has been investigated since the 1990s for possible improvements in the healing of wounds [22][23][24][25][26][27][28][29][30][31], lack of reproducible results [32,33] have hampered its widespread use. ...
Foot ulcers are serious complications of diabetes mellitus (DM) and are known to be resistant to conventional treatment. This study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) for the treatment of diabetic foot ulcers in a tertiary care centre (Department of Surgery, Mahatma Gandhi Memorial Medical College and Maharaja Yashwantrao Hospital, A.B. Road, Indore). A total of 30 patients with type 2 DM having Meggitt-Wagner grade I foot ulcers of more than 6 weeks duration with negative culture were studied. Patients were randomized into two groups of 15 each. Patients in study group received LLLT (660 ± 20 nm, 3 J/cm²) along with conventional therapy and those in control group were treated with conventional therapy alone. The primary outcome measure was the absolute and relative wound size reduction at 2 weeks compared to the baseline parameter. Percentage ulcer area reduction was 37 ± 9% in the LLLT group and 15 ± 5.4% in the control group (p < 0.001). For ∼75% of wounds of the treatment group, wound area reduction of 30–50% was observed. In contrast, for the control group, ∼80% of wounds showed a wound area reduction of <20% on day 15. Further, the wounds with initial wound area 1000–2000 mm² seems to have better final outcome than the groups with larger areas. The treated groups showed higher amount of granulation than the control group. The results suggest that LLLT is beneficial as an adjunct to conventional therapy in the treatment of diabetic foot ulcers.
... Topical use of POL in cream formulation has demonstrated that this product could be an effective emollient and moisturizing therapeutic strategy in subjects with marked xerosis and at high risk of skin damage such as pressure sore. Rinaldi et al. [16] evaluated 25 diabetic patients with neuropathic ulcers and severe skin dystrophy in a controlled left-vs-right side study design. The skin areas surrounding the necrotic tissues were treated with POL cream on the other side, used as a control, with hyaluronic acid. ...
Background: Skin dryness is commonly observed in diabetic patients. Purified Omental lipids (POL) are considered an effective emollient and hydrating topical product in subjects at risk of skin fissuring and damage. In addition, topical POL could express a wound-healing and skin regenerative effect.
Aim: We evaluated the efficacy of topical 25% concentrated POL product (P.O.L. cream; Difa Cooper, Italy) (POL-C) in Type 2 diabetic patients with (YES-C) or without (NO-C) vascular or neurological complications in comparison with non-treated healthy volunteers. Presence of vascular or neurological ulcers was an exclusion criterion.
Methods: We assessed the efficacy of POL-C on skin hydration and skin integrity in a prospective, evaluatorblinded controlled study in 30 type II diabetic patients (YES-C: n=15) (NO-C: n=15), aged 40–75 years, treated with POL-C twice daily for 3 months. Ten subjects, matched for age and sex, without diabetes, formed the control group. Primary outcomes were the Dryness Area Severity Index (DASI) Score evaluating xerosis, erythema, scaling and skin fissuration (minimum-maximum score values: 4-20) and Patient-Assessed Skin Score (PASS) evaluating dryness, itching and irritation (minimum-maximum score values: 3-15). DASI score was evaluated at baseline, after 1 and 3 months by an investigator unaware of treatment allocation (patients or controls) and unaware of the type of diabetes (with or without complications). PASS scores were collected at the same study times in YES-C and NO-C only groups.
Results: One subject (YES-C group) dropped out prematurely from the trial. At baseline mean(SD) DASI score was 7.4 (2.5) in YES-C group, 4.9 (0.7) in NO-C group and 5.0 (0.7) in control subjects. DASI score in YES-C was significantly higher in comparison with NO-C and control groups. POL induced significantly DASI score reductions in both diabetic patients’ groups at month 1 and month 3 (p < 0.001) in comparison with baseline values. At month 3, DASI score was 4.5 (1.5) in YES-C and 4.1 (0.3) in NO-C. PASS score was significant reduced in comparison with baseline in YES-C group (from 5.2 to 3.5; p=0.02) and in NO-C group (from 3.7 to 3.0; p=0-05). The product was well tolerated.
Conclusion: In diabetic subjects, skin xerosis is significantly worse in the presence of vascular or neuropathy in comparison with diabetic subjects without complication and in comparison with matched healthy control subjects. The use of POL cream improves and normalizes skin xerosis both assessed by the investigator or by the subject with a clinical effect correlated with the baseline level of skin dryness severity. Application of Purified Omental Lipids cream increases skin hydration and relieves the condition of skin dryness in Type 2 diabetic patients with or without complications.
... Non-healing DFUs are resistant to conventional treatment [7]. Several adjuvant therapies which have been tried to stimulate healing process are ultrasound, laser therapy, and other forms of photobiomodulation, electrical stimulation, hyperbaric oxygen, and vacuumassisted closure [8,9]. ...
Unlabelled:
Foot ulcers are serious complications of Diabetes Mellitus (DM) and are known to be resistant to conventional treatment. They may herald severe complications if not treated wisely. Electromagnetic radiations in the form of photons are delivered to the ulcers in laser form to stimulate healing. This study was conducted to evaluate the efficacy of Low Level Laser Therapy (LLLT) in diabetic ulcer healing dynamics. To determine mean percentage reduction of wound area in study and control groups.
Settings:
KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belgaum.
Study design:
Randomized-Control Study.
Methods:
A total of 68 patients with Type 2 DM having Meggitt-Wagner Grade I foot ulcers of atleast more than 4 weeks duration, less than 6 × 6 cm(2) with negative culture were studied. Patients were randomized into two groups of 34 each. Patients in study group received LLLT with conventional therapy and those in control group were treated with conventional therapy alone. Healing or percentage reduction in ulcer area over a period of 15 days after commencement of treatment was recorded.
Statistical analysis:
Unpaired Student T Test and Mann Whitney U test. Mean age of the patients was 50.94 years in control group and 54.35 years in study group (p = 0.065). There was no significant difference between control and study group with respect to mean FBS and HbA1c levels (p > 0.05), suggesting no biochemical differences between two groups. Initial ulcer area was 2608.03 mm(2) in study group and 2747.17 mm(2) in control group (p = 0.361). Final ulcer area was 1564.79 mm(2) in study group and 2424.75 mm(2) in control group (p = 0.361). Percentage ulcer area reduction was 40.24 ± 6.30 mm(2) in study group and 11.87 ± 4.28 mm(2) in control group (p < 0.001, Z = 7.08). Low Level Laser Therapy is beneficial as an adjunct to conventional therapy in the treatment of diabetic foot ulcers (DFU).
... One of these modes of treatment is low output laser therapy 9 . It has been extensively investigated in experimental animals with favourable results 10 , 11 , 12 , 13 In humans, several case studies 14 , 15 and outcome studies 16 , 17 , 18 have been done, but randomized controlled trials have yet to be carried out. ...
The aim of this study was to assess the effects of low output laser therapy as an adjuvant treatment in grade 1 diabetic foot ulcers. Methods: Sixteen patients were randomly divided equally into two groups. Group A had daily dressing only, while group B had low output laser therapy instituted five days a week in addition to daily dressing. Serial measurement of the ulcer was done weekly using digital photography and analyzed. Results: The rate of healing in group A was 10.42 mm2/week, and in group B was 66.14mm2/week. The difference in the rate of healing was statistically significant, p<0.05. Conclusion: Laser therapy as an adjuvant treatment accelerates diabetic ulcer healing by six times in a six week period.
Objectives
Treating chronic cutaneous wounds is challenging, and debridement is a central concept in treating them. Studies have shown that CO2 laser debridement can control local infection and promote the wound healing process. The present study aimed to investigate the efficacy and safety of fully ablative CO2 laser debridement compared to routine surgical debridement in the treatment of chronic wounds.
Methods
The retrospective cohort study was conducted on patients with chronic (>1 month) cutaneous wounds (≥1 cm²) between December 1, 2017, and December 1, 2020, in the Wound Healing Center at Shanghai Ruijin Hospital, China. Patients treated with CO2 laser debridement with a DEKA SmartXide2 C80 (DEKA) (the CO2 laser group) were compared with matched control patients with similar baseline characteristics who had undergone routine surgical debridement (the routine group). The primary outcome was time-to-heal (days) for chronic wounds in two groups, and secondary outcomes included the wound area and BWAT (Bates–Jensen wound assessment tool) score before treatment, and at 1, 2, 3, and 4 weeks after treatment.
Results
The study included 164 patients (82 in the CO2 laser group and 82 matched in the routine group). The time-to-heal for patients in the CO2 laser group (41.30 ± 17.11) was significantly shorter than that of the patients in the routine group (48.51 ± 24.32) (p = 0.015). At 3 and 4 weeks after treatment, the absolute wound area of the CO2 laser group was significantly smaller than that of the routine group. Also, the CO2 laser group exhibited a significantly lower relative area at 2, 3, and 4 weeks after treatment. The CO2 laser group yielded significantly lower BWAT scores at 2, 3, and 4 weeks after treatment. Additionally, the relative BWAT score was significantly lower in the CO2 laser group than the relative scores in the routine group at 2, 3, and 4 weeks after treatment. No adverse events related to the treatments were observed in either group during the study period.
Conclusions
The present study has shown that fully ablative CO2 laser debridement has several advantages over routine sharp surgical debridement. It is superior at ameliorating wound status and reducing wound area, and it also significantly reduces the time-to-heal for chronic wounds, without causing any adverse events.
The omentum is a large peritoneal fold. Its main function is to protect abdominal organs, exerting a defensive action against infective agents. The tissue promotes repair after several types of injury. An extensive vascularisation is the key characteristic of this tissue and the omentum has the highest level of production and content of vascular endothelial growth factor (VEGF). A component of omentum is the lipid compound, which carries out important activities for the organism. Omentum is rich in neutral glycerides, phospholipids, glycolipids and gangliosides. Dermatological products containing purified omental lipids are commercially available and topical omental extracts have been useful in the softening, moisturising and smoothing of skin. Animal-derived omental lipids could be use in topical products with different textures (creams, fluids, emulsions and cleansers) and at different concentrations (10–25%) for the treatment of fragile skin or skin conditions causing risk of ulcer formation. This review summarises the pharmacological rationale of purified omental lipids in topical formulations for use in fragile skin conditions, the clinical efficacy data available in the scientific literature and the potential future perspectives. Efficacy of topical purified omental lipids have been demonstrated in numerous clinical controlled trials involving a total of 320 subjects. These studies demonstrated that this product helps prevent the formation of pressure ulcers (PU) in hospitalised high-risk subjects, improves wound healing process, normalises skin hydration in diabetic subjects with moderate-severe skin xerosis and improve the clinical evolution of diabetic foot. Therefore, purified omental lipid could be an effective tool for the management of fragile skin and the skin at high risk of PU formation.
Objectives : One of major complications of diabetes, diabetic ulcer is also one of the main reasons for amputation, and the prevalence rate is 4-10%. Laser therapy is widely used for leg ulcer and diabetic ulcer, and it is known to improve wound epithelialization, cellular content, and collagen deposition. The purpose of this study is to investigate the properties of the laser and the spectrum of laser instruments for diabetic ulcer. Methods : We performed literature search using the PubMed, Cochrane, CINAHL and Web of science for the data in English. In addition, other databases were checked for different languages such as OASIS and NDSL for the literature in Korean, CNKI in Chinese, and CiNii and J-STAGE written in Japanese. We excluded all review article and experimental studies, and only clinical studies using laser or light emitting diode (LED) for diabetic ulcer were selected. Results : A total twenty papers were selected. Different light sources were used as follows: LED, HeNe, InGaAlP, GaAlAs, GaAs, CO2, and KTP. The number of LED studies was 9, and HeNe laser was 7, and InGaAlP and GaAlAs laser was 2, GaAs, CO2, and KTP laser was 1 for each. Various energy density of the clinical study were reported. Conclusions : It is suggested that to select appropriate laser type and give the adequate output power to treat diabetic ulcer. Further evaluation and research for the condition of laser therapy to treat diabetic ulcers are warranted.
Il potenziamento della capacità proliferativa dei cheratinociti della cute sana che circonda l´ulcera è uno degli obiettivi del trattamento locale; infatti studi recentissimi x-y-z hanno dimostrato che tale capacità non è affatto ridotta, si ha una proliferazione e una migrazione in senso orizzontale che viene ulteriormente accelerata creando un ambiente ideale “ambiente umido”. La presenza inoltre dei fattori di crescita sul fondo della lesione permette una maggiore rapidità dei processi riparativi. Da qui si evince l´importanza di una gestione corretta della cute peri-lesionale che la si può raffigurare come il “nostro ponte” che porta alla guarigione dell´ulcera. E’ stato dimostrato che i lipidi purificati di omento hanno un’attività angiogenica1-2-3-4 migliorando il microcircolo e l’ossigenazione dei tessuti, e aumentano la proliferazione e migrazione dei cheratinociti 5-6. In più, data la composizione lipidica, svolgono un’importante attività emolliente e protettiva. In questa ottica il loro impiego nella gestione della cute peri-lesionale potrebbe risultare un importante supporto al trattamento terapeutico
Se estudió el efecto angiogénico y la composición de proteínas y lípidos del omentum humano a partir de la inoculación intraestromal en la córnea de conejo de los extractos obtenidos tras homogeneizar el material biológico. Se encontraron valores muy bajos de proteínas y muy elevados de triglicéridos fundamentalmente en el extracto 2 de origen lipídico. En relación con la vascularización, ésta se logró con mayor intensidad en la córnea de los animales que se inocularon con el extracto 2.It was studied the angiogenic effect and the composition of proteins and lipids of the human omemtum by the intrastromal inoculation into the rabbit's cornea of the extracts obtained after homogenizing the biological material. Extremely low values of proteins and very high values of triglycerides were found mainly in the extract 2 of lipidic origin. Regarding vascularization, it was attained with greater intensity in the cornea of those animals that were inoculated the extract 2.
conclusion:
Measurement of tcPO2 was shown to be a reliable assay with reproducible results
Assays were well accepted by patients, although it took some time to stabilise the curve
Assays may suit measurement of the effect on WH, applying different types of dressings
To determine the effect of carbon dioxide laser microsurgery in the treatment of intractable chronic myringitis (CM).
Retrospective 10-year case note review.
Tertiary referral hospital.
We reviewed retrospective case notes for 30 treated ears in 29 consecutive patients with CM (ie, loss of the tympanic membrane for longer than 1 month, refractory to conservative medical treatment) who underwent carbon dioxide laser microsurgery between 1995 and 2004, excluding patients who had undergone previous otologic surgery such as tympanoplasty.
Carbon dioxide laser microsurgery for resurfacing the nonepithelialized tympanic membrane was performed using local anesthesia.
Resolution of disease in the affected tympanic membrane.
Of 30 affected ears, 22 demonstrated total resolution of CM, 7 demonstrated partial resolution, and the status of 1 ear remained unchanged at the end of follow-up (mean,19.7 months). Revision laser therapy was performed in 3 ears, resulting in total resolution of disease in 1 ear. Time to total resolution of disease ranged from 1 to 16 months (mean, 2.95 months).
We used carbon dioxide laser microsurgery to treat intractable primary CM and describe its efficacy in a retrospective review of laser resurfacing covering 10 years. We believe that laser microsurgery has the advantages of less invasiveness and higher applicability compared with aggressive surgical treatment. In patients with CM refractory to conservative medical treatment, carbon dioxide laser microsurgery could be an effective alternative when aggressive surgical procedures are not under consideration.
The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to encourage communication of the very best cancer research from laboratories and clinics in all countries. The breadth of its coverage, its editorial independence and it consistent high standards, have made BJC one of the world's premier general cancer journals. Its increasing popularity is reflected by a steadily rising impact factor.
Since the first ruby laser was made in 1960, multiple applications of lasers have been identified. The special burning, coagulating, and vaporizing effects of high output lasers, together with their easy manipulation using optical systems, have resulted in extensive medical use. Additionally, there is much interest in the nonthermic effects of lasers in photodynamic tumor therapy and in biostimulation.
• Three topical antibiotics and four antiseptics (1% povidone-iodine, 0.25% acetic acid, 3% hydrogen peroxide, and 0.5% sodium hypochlorite) were directly applied to cultured human fibroblasts to quantitatively assess their cytotoxicity. The four antiseptics were found to be cytotoxic; all of the cytotoxic agents except hydrogen peroxide were subsequently found to adversely affect wound healing in an animal model. Comparison of bactericidal and cytotoxic effects of serial dilutions of these four topical agents indicated the cellular toxicity of hydrogen peroxide and acetic acid exceeded their bactericidal potency. Bactericidal noncytotoxic dilutions of povidone-iodine and sodium hypochlorite were identified. These experiments provide evidence that 1% povidone-iodine, 3% hydrogen peroxide, 0.5% sodium hypochlorite, and 0.25% acetic acid are unsuitable for use in wound care. This sequence of experiments could be used to identify bactericidal, noncytotoxic agents prior to their clinical use.(Arch Surg 1985;120:267-270)
Casts were made of the vascular lumen of 20 successive extremities amputated for gangrene. Half of the patients were diabetic. All nondiabetics had arteriosclerotic vascular disease plus acute occlusion. Only one diabetic had an acute episode. There was no significant difference in age, blood pressure, or digital blood flow between the two groups. Diabetics had somewhat greater occlusion of the calf vessels and less occlusion in the foot than nondiabetics; the overall extent of large artery occlusion was equal in the two groups. There was no increase in small vessel occlusion with diabetes. Small vessel occlusions were present in all areas of muscle and skin examined. The findings indicate that: (1) very extensive occlusion must be present to result in necrosis; (2) in nondiabetics, amputation was required only when sudden occlusion was superimposed on previous occlusive disease; (3) both large and small vessels are occluded to about the same extent in diabetics and nondiabetics when amputation is required, and (4) either diabetes or sudden occlusion in conjunction with chronic vascular disease can result in insufficient collateral flow and subsequent death of tissues.
Placing the omentum on the brain surface by surgical transposition or transplantation will result in the development of numerous neovascular connections between these two structures. This phenomenon occurs even in the absence of cerebral ischemia, which raised the question as to whether an angiogenic factor was causing the response. A lipid material obtained from the omentum contains a potent angiogenic factor extractable in a chloroform-methanol solvent mixture. Angiogenesis created by this material was observed in the rabbit cornea after only a single injection of the substance. The angiogenic material obtained from the omentum is abundant in supply. This important characteristic offers promise for the purification and identification of its structure, which should allow for extensive animal and clinical studies dealing with the development or inhibition of angiogenesis.
(JAMA 1984;252:2034-2036)
This article has no abstract; the first 100 words appear below.
For almost 50 years, since insulin therapy was initiated, proponents of "rigid," "tight" or "chemical" control have quoted retrospective evidence of decreased or delayed nephropathy and retinopathy as glucose levels are brought by therapy toward the normal range. Opponents to this hypothesis have pointed to the problems of complications in many of these patients with supposedly better control of the disease, to the emotional and socioeconomic conflicts that often resulted from the demands of rigorous control, to the frequent difficulties with hypoglycemic reactions, and, recently, to the University Group Diabetes Project.¹,² Five years ago, in a review of 300 reports . . .
George F. Cahill, Jr., M.D.
Harvard Medical School Boston, MA 02115
Donnell D. Etzwiler, M.D.
University of Minnesota Medical School Minneapolis, MN 55455
Norbert Freinkel, M.D.
Northwestern University Medical School Chicago, IL 60611
To determine possible mechanisms by which omental pedicles protect bronchial anastomoses from ischemia, we studied the angiogenic potential of a lipid extract of omentum. A rabbit cornea model was used to quantify neovascularization produced by methanol-chloroform extract of homogenized autologous omentum or perirenal fat. In 22 anesthetized rabbits, 10 microliters of omental lipid extract was injected into the cornea. In each animal the opposite eye was used as a control and was injected with a similar volume of extract prepared from perirenal fat. The side of injection of autologous omental fat was randomized and was not known to the investigator who assessed neovascularization on days 4, 7, 14, and 21 after injection. Neovascularization was recorded on microphotography and quantified by a point-counting method. Four days after injection, neovascularization in corneas injected with autologous omental fat was significantly (p less than 0.05) greater than in control corneas for all indices of neovascularization including total point count, which was three times greater than control. The angiogenic effect diminished with time, and by 21 days after injection corneal neovascularization was comparable for the two groups. Our results suggest that the lipid fraction of omentum has angiogenic activity that may stimulate neovascularization in ischemic tissues. Lack of sustained activity may be due to washout by neovessels or local tissue metabolism.
Three topical antibiotics and four antiseptics (1% povidone-iodine, 0.25% acetic acid, 3% hydrogen peroxide, and 0.5% sodium hypochlorite) were directly applied to cultured human fibroblasts to quantitatively assess their cytotoxicity. The four antiseptics were found to be cytotoxic; all of the cytotoxic agents except hydrogen peroxide were subsequently found to adversely affect wound healing in an animal model. Comparison of bactericidal and cytotoxic effects of serial dilutions of these four topical agents indicated the cellular toxicity of hydrogen peroxide and acetic acid exceeded their bactericidal potency. Bactericidal noncytotoxic dilutions of povidone-iodine and sodium hypochlorite were identified. These experiments provide evidence that 1% povidone-iodine, 3% hydrogen peroxide, 0.5% sodium hypochlorite, and 0.25% acetic acid are unsuitable for use in wound care. This sequence of experiments could be used to identify bactericidal, noncytotoxic agents prior to their clinical use.
The effects of several antiseptic agents on granulation tissue were studied using rabbit ear chambers as models of the healing wound. This enabled us to study dynamically the action of these agents on the microcirculation of the wound. All the agents tested caused some adverse effect, but in the cases of hypochlorite antiseptics Eusol and Chloramine T, blood flow in the capillary circulation of the granulation tissue ceased and the process of repair was subsequently delayed. A laser Doppler flowmeter was used to measure these changes in local perfusion which reflected the toxic effects seen on microscopy of the ear chamber.
The effects and possible mechanisms of distant acute sterile inflammation, distant acute bacterial infection, local infection, and systemic infection on early wound healing were investigated in rats. Abdominal and gastric wounds and peritoneal defects were created in rats with turpentine aseptic abscess, Pseudomonas aeruginosa muscle abscess, or transient bacteremia. Mechanical, biochemical, histologic, and bacteriologic aspects of the wounds were studied. Distant sterile inflammation, distant bacterial infection, and transient bacteremia have a marked inhibitory effect on early healing of the skin, muscle, stomach, and peritoneum. This is a systemic effect which apparently is not related to low plasma protein level or early colonization of the wounds by the bacteria.
Five hundred and fifteen amputations were performed on 320 patients in a 5 yr period. The 30 day operative mortality rate was 35%. The mortality rate among those with diabetes was 34%. In those patients without diabetes undergoing amputation for arteriosclerotic disease, the mortality rate was 45%. Myocardial infarction or pulmonary embolus was uniformly fatal in the postoperative period and must be prevented. Prompt, rapidly performed open amputation permitted a significant salvage to below knee stumps. Disarticulations or open amputations are more efficacious than refrigeration in resuscitating the toxic patient. Immediate fitting of a prosthesis may be of great benefit in the rehabilitation of the patient, but judgment must be exercised in selecting the patient for this procedure.
Human amnio-chorionic membranes and placenta maintained in culture release factors with angiogenic and mitogenic capacities at concentrations corresponding to nanogram amounts of protein. Angiogenic activity of amnio-chorion and placenta-conditioned media was assessed by their ability to stimulate neovascularisation in the dorsal subcutaneous fascia in the rat and the chorio-allantoic membrane in the chick embryo. Mitogenic characteristics were assessed by their ability to initiate DNA synthesis in cells at resting state, unstimulated peripheral blood lymphocytes and serum-deprived 3T3 fibroblasts. These growth promoting factors can be isolated from amnio-chorion and placenta-conditioned media mostly as factor-protein complexes of high molecular weight (higher than 100000 daltons) by gel filtration, and dissociated by magnesium chloride in components of low molecular weight including molecules readily diffusable through dialysis membranes of 2000 molecular weight cutoff. Presence of angiogenic and mitogenic factors in amnio-chorion suggests they might play a role in wound healing when amniotic membranes are used as biological dressings, besides the role they may play, in conjunction with placental factors, in embryonic and foetal development.
Placing the omentum on the brain surface by surgical transposition or transplantation will result in the development of numerous neovascular connections between these two structures. This phenomenon occurs even in the absence of cerebral ischemia, which raised the question as to whether an angiogenic factor was causing the response. A lipid material obtained from the omentum contains a potent angiogenic factor extractable in a chloroform-methanol solvent mixture. Angiogenesis created by this material was observed in the rabbit cornea after only a single injection of the substance. The angiogenic material obtained from the omentum is abundant in supply. This important characteristic offers promise for the purification and identification of its structure, which should allow for extensive animal and clinical studies dealing with the development or inhibition of angiogenesis.
A variety of conditions was selected for inclusion in this and the following chapter on metabolic and collagen-vascular diseases. They range from the common to the rare. Diseases were selected because their only skin manifestation occurs on the lower extremities or because their expression on the legs and feet is an important component of the disease process. Many of these cutaneous signs are of great concern to the patient and provide valuable diagnostic and prognostic clues for the physician. The treatment of many of these dermatologic changes represents difficult therapeutic challenges for physicians in all fields of medicine.
When cultured in a hypoxic environment similar to that found in the center of a wound, macrophages secreted active angiogenesis factor into the medium. Under conditions similar to those of well-oxygenated tissue, macrophages did not secrete active angiogenesis factor. Macrophages that secreted the factor at hypoxic conditions stopped secreting it when returned to room air. Thus the control of angiogenesis in wound healing may be the result of macrophages responding to tissue oxygen tension without the necessity of interacting with other cell types or biochemical signals.
Cutaneous Laser Therapy: Principles and Methods
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Laser biostimulation in Wound-Healing Laser in General Surgery The effect of an-tiseptics on the healing wound: a study using the rabbit ear chamber
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Mester A.F. and Mester, A. (1989) Laser biostimulation in Wound-Healing. In: Stephen N. Joffe (Ed.), Laser in General Surgery, Williams & Wilkins, Baltimore. Brennan, S.S. and Leaper, D.J. (1985) The effect of an-tiseptics on the healing wound: a study using the rabbit ear chamber. Br. J. Surg. 72, 780-782.
Increased vascular perfusion after administration of an omental lipid fraction
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Harry, S., Goldsmith, M.D. et al. (1986) Increased vascu-lar perfusion after administration of an omental lipid frac-tion. Surgery Gynecol. Obstet. 162, 579-583.
Lipid angiogenic factor from omentum Angiogenic and growth factors in human amnio-chorion and placenta
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Harry, S., Goldsmith, M.D. et al. (1984) Lipid angiogenic factor from omentum. J. Am. Med. Assoc. 252, No. 15. Burgos, H. (1983) Angiogenic and growth factors in human amnio-chorion and placenta. Eur. J. Clin. Invest. 13, 289-296.
Common Foot Dis-orders: Diagnosis and Management. Churchill Liv-ingstone
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Neale, D. and Adams, I.M. (1989) Common Foot Dis-orders: Diagnosis and Management. Churchill Liv-ingstone, New York.
Clinical Diabetes: Modem Manage-ment
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Podolosky, J. (1980) Clinical Diabetes: Modem Manage-ment. New York: Appleton -Century Crofts, pp. 522-530.
Laser in dermatology (Editorial)
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Arndt, K. (1982) Laser in dermatology (Editorial). Arch. Dermatol. 118, 293-295.
Cutaneous Laser Therapy: Principles and Methods.
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Topical antimicrobial toxicity.
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Evaluation of porcine omental extract in wound healing using ultrasound in normal volunteers
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Complications of diabetes
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Neuropathic ulcers in diabetes mellitus
- Pomeraze
Cutaneous Laser Therapy: Principles and Methods
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Microcirculation and diabetic foot
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