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Biomedical subjects

M Hanumadass

Publications and source records attributed to M Hanumadass.

At least 19 recordsLinked to original sources

Long-term outcome of xenogenic dermal matrix implantation in immunocompetent rats.

BACKGROUND: Acellular dermal matrix (ADM) has been used successfully in the treatment of full-thickness skin injuries as an allogenic dermal substitute. To assess the efficacy of xenogenic ADM in such wounds, we examined the long-term wound healing and immunological responses to porcine ADM in a rat model. MATERIALS AND METHODS: Xenogenic and allogenic ADMs were produced by treating porcine (fresh or cryopreserved) or rat skin with dispase and Triton X-100. Full-thickness skin defects on the rat dorsum were implanted with porcine or rat ADMs and overlaid with split-thickness skin grafts (STSGs). Wounds were evaluated grossly and immunologically at 1, 6, and 12 months after surgery. RESULTS: Extensive wound contraction was seen in wounds implanted with porcine ADM, but healing was significantly (P < 0.01) better in the rat ADM or STSG groups at 6 and 12 months postsurgery. Sera obtained from porcine ADM-implanted rats reacted strongly with porcine ADM and specifically with the papillary dermis and basal lamina. One month postsurgery, extensive inflammation but few intact mast cells were seen in wounds implanted with porcine ADM and significant (P < 0.02) levels of residual porcine ADM were detectable immunologically. Little inflammation was evident in the STSG or rat ADM groups at any time. Significant lymphocyte proliferation (P < 0.05) occurred in the 6- and 12-month groups in response to porcine, but not rat, ADM. CONCLUSIONS: In wounds implanted with xenogenic ADM, a short-lived acute inflammatory response, long-lasting humoral and cell-mediated immune responses, and generally poor wound healing were observed.

Animals↗

Use of porcine acellular dermal matrix as a dermal substitute in rats.

OBJECTIVE: To examine porcine acellular dermal matrix (ADM) as a xenogenic dermal substitute in a rat model. SUMMARY BACKGROUND DATA: Acellular dermal matrix has been used in the treatment of full-thickness skin injuries as an allogenic dermal substitute providing a stable wound base in human and animal studies. METHODS: Xenogenic and allogenic ADMs were produced by treating porcine or rat skin with Dispase and Triton X-100. Full-thickness skin defects (225 mm2) were created on the dorsum of rats (n = 29), porcine or rat ADMs were implanted in them, and these were overlain with ultrathin split-thickness skin grafts (STSGs). In two adjacent wounds, 0.005- or 0.017-inch-thick autografts were implanted. In other experiments, the antimicrobial agent used during ADM processing (azide or a mixture of antibiotics) and the orientation of the implanted ADM (papillary or reticular side of ADM facing the STSG) were studied. Grafts were evaluated grossly and histologically for 30 days after surgery. RESULTS: Significant wound contraction was seen at 14, 20, and 30 days after surgery in wounds receiving xenogenic ADM, allogenic ADM, and thin STSGs. Contraction of wounds containing xenogenic ADM was significantly greater than that of wounds containing allogenic ADM at 30 days after surgery. Graft take was poor in wounds containing xenogenic ADM and moderately good in those containing allogenic ADM. Wound healing was not significantly affected by the antimicrobial agent used during ADM preparation or by the ADM orientation. CONCLUSION: Dispase-Triton-treated allogenic ADM was useful as a dermal substitute in full-thickness skin defects, but healing with xenogenic ADM was poor.

Animals↗

Characterization of acellular dermal matrices (ADMs) prepared by two different methods.

The efficacy of acellular dermal matrix (ADM) in the treatment of full-thickness skin injuries as a dermal substitute depends on its low antigenicity, capacity for rapid vascularization, and stability as a dermal template. These properties will be determined largely by the final composition of the ADM. We have treated human skin with either Dispase followed by Triton X-100 detergent or NaCl followed by SDS detergent, cryosectioned the resulting ADMs, and then characterized them immunohistochemically. Staining for cell-associated antigens (HLA-ABC, HLA-DR, vimentin, desmin, talin), extracellular matrix components (chondroitin sulfate, fibronectin, laminin, vitronectin, hyaluronic acid), elastin, and collagen type VII was dramatically reduced or absent from ADMs prepared by both methods. However, significant amounts of elastin, keratan sulfate, laminin, and collagen types III and IV were still observed in both ADMs. Both methods of ADM preparation resulted in extensive extraction of both cellular and extracellular components of the skin but retention of the basic dermal architecture. In general, ADM prepared by the NaCl-SDS method retained larger amounts of each antigen than did that prepared by the Dispase-Triton method. This was most evident for laminin and type VII collagen but larger amounts of type IV collagen, fibronectin, desmin, elastin, and HLA-DR were also evident in the NaCl-SDS ADM.

Cytoskeletal Proteins↗

Silver sulfadiazine induced Clostridium difficile toxic megacolon in a burn patient: case report.

A 53 yr old diabetic male presented with a 34% total body surface area (TBSA) deep partial- and full-thickness burns. On post burn days 4 and 9, all of his burns were excised and grafted. Although he had only been treated with topical antibiotics, he developed Clostridium difficile colitis after his second surgery that progressed to Toxic Megacolon and perforation. The incidence and treatment of Toxic Megacolon secondary to C. difficile is reviewed. Early diagnosis and treatment with colonoscopic decompression may obviate the need for surgery.

Anti-Infective Agents, Local↗

Reduced resuscitation fluid volume for second-degree burns with delayed initiation of ascorbic acid therapy.

BACKGROUND: Oxygen radicals may play an important role in injury due to thermal burns. High-dose antioxidant ascorbic acid (vitamin C, Cenolete, Abbott Laboratory, Abbott Park, Ill) therapy reduces edema of burned and unburned tissue, lipid peroxidation, and subsequent resuscitation fluid volume requirement in experimental burn models. OBJECTIVE: To determine the hemodynamic effects of delayed initiation (2 hours after injury) of antioxidant therapy in patients with second-degree burns. DESIGN: Experimental study. MATERIALS AND INTERVENTION: Burns over 70% of body surface area were produced by subxiphoid immersion of 12 guinea pigs in 100 degrees C water for 3 seconds. The animals were resuscitated with Ringer's lactated solution according to the Parkland formula (4 mL/kg for 1% of burned body surface area during the first 24 hours) from 0.5 to 2 hours following injury, after which the resuscitation fluid volume was reduced to 25% of the Parkland formula. Animals received Ringer's lactated solution to which ascorbic acid (340 mg/kg during the first 24 hours) was added (vitamin C group [n = 6]) or Ringer's lactated solution only (control group [n = 6]). MEASUREMENTS: Heart rates, mean arterial blood pressure, cardiac output, hematocrit level, and water content in burned and unburned tissue were measured before injury and at intervals thereafter. RESULTS: There were no significant differences in heart rates (P = .29) and blood pressures (P = .53) between the 2 groups throughout the 24-hour study period. No animal died. The vitamin C group showed significantly lower hematocrit levels (P < .05) and significantly higher cardiac output values (P < .05) at 7 hours following burn injury and at intervals thereafter (P < .001). CONCLUSION: With delayed initiation of high-dose ascorbic acid therapy, the 24-hour fluid resuscitation volume was reduced to 32.5% of the Parkland formula, while maintaining adequate cardiac output values.

Animals↗

Dispase/detergent treated dermal matrix as a dermal substitute.

A method for preparing acellular allogeneic dermal matrix (ADM) and its effectiveness as a dermal substitute are described. Treatment of rat skin with Dispase followed by Triton X-100 completely removed cellular components from the dermis. Subcutaneously implanted ADM evoked no immunological reaction and 20 weeks after implantation, the size of the implanted ADM was reduced to about 60 per cent of its original area. ADM became completely vascularized within 2 weeks after implantation into full thickness skin defects in the rat and inhibited extensive wound contracture. A second layer of ADM placed onto the implanted ADM served as an excellent dressing, providing mechanical protection and permitting vascularization of the underlying implant. Onlay skin autografts placed onto vascularized allogeneic ADM showed good survival when the skin was grafted more than 1 week after ADM implantation. Dispase/detergent treated ADM derived from animal or human skin may be useful in full thickness skin defects providing a vascularized bed for subsequent epidermal coverage.

Animals↗

Nosocomial infections in a burn intensive care unit.

Although many studies have reviewed burn wound infections (BWIs) in burn patients, few have prospectively surveyed other nosocomial infections. Seriously burned patients are clearly at increased risk for infection due to the nature of the burn injury itself, immunocompromising effects of burn injury, prolonged hospital stays, and invasive diagnostic and therapeutic procedures. Over 6 months, we prospectively reviewed all patients admitted to our burn intensive care unit (BICU) for nosocomial infections. We used standard CDC definitions of nosocomial infections (NIs). Because we had previously documented a high incidence of nosocomial pneumonias in these patients, we were particularly interested in determining risk factors for nosocomial pneumonia. The total census during the study period was 57. There were 40 discharges and deaths. Surveillance demonstrated 36 nosocomial infections in 26 patients, for a total of 90 nosocomial infections per 100 discharges and deaths, or 32.3 NIs/1000 patient days. Infections included 22 pneumonias, 10 urinary tract infections, two bacteraemias, one BWI and one episode of cellulitis. Intubation was strongly associated with nosocomial infection, particularly with pneumonia, BWI and bacteraemia. Sixty per cent of all patients were intubated at some time during their BICU stay, but 88 per cent of those who developed a nosocomial infection were intubated (P < 0.001). Inhalation injury was less significant than intubation in the development of nosocomial infection. All patients who developed pneumonia or a BWI were intubated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

High-dose vitamin C therapy for extensive deep dermal burns.

We studied the haemodynamic effects of antioxidant therapy with high-dose vitamin C administration (170 mg/kg/24 h) in guinea-pigs with 70 per cent body surface area deep dermal burns. The animals were divided into three groups of six animals each. Group 1 was resuscitated with Ringer's lactate solution according to the Parkland formula; group 2 with 25 per cent of the Parkland formula with vitamin C; and group 3 with 25 per cent of the Parkland formula without vitamin C. There were no significant differences in heart rates or in blood pressures between the groups throughout the 24-h study period. Group 3 showed significantly higher haematocrit values at 3 h postburn and thereafter as compared with those of group 2. The cardiac output values of group 2 were significantly higher than those of group 3, but equivalent to those of group 1. The water content of the burned skin in group 2 was significantly lower than that in the other groups, indicating that increased postburn capillary permeability was minimized by the administration of vitamin C. With adjuvant high-dose vitamin C administration, we were able to reduce the 24-h resuscitation fluid volume from 4 ml/kg/per cent burn to 1 ml/kg/per cent burn, while maintaining adequate cardiac output.

Animals↗

Early coverage of deep hand burns with groin flaps.

Deep burns of the hands require skin flap coverage in order to protect the exposed vital structures. The groin flap is a safe and effective method of obtaining early closure of these defects. We have used groin flaps to cover deep hand burn defects in nine patients. In each case, groin flaps effectively covered the various defects, such as the volar aspect of the wrist, dorsum of the hand, first web space, thumb, and fingers.

Adult↗

Classification and surgical correction of postburn axillary contractures.

Postburn axillary contractures should be surgically corrected as soon as the diagnosis has been established in order to avoid deeper tissue involvement. We have classified axillary contractures based upon local anatomic conditions and present procedures for correction of each type that we find most suitable. Type I contractures are characterized by a linear web at either axillary fold with minimal adjacent scarring. A double Z-plasty with Y-V advancement is the procedure of choice. Type II contractures involve either axillary fold, with adjacent skin scarring. A double incisional release on both sides of the hair-bearing area is the procedure of choice. Type III contractures are characterized by linear webs at both axillary folds without involvement of the adjacent skin. The procedure of choice in these cases is a double incisional release. Type IV axillary contractures involve the hair-bearing area and the periaxillary region. This diffuse scar contracture is best treated by a single incisional release.

Axilla↗

Serious wound infections in burned patients.

Wound infections are a major problem in burned patients. To determine the rate of wound infection associated with initial wound size and the amount of open full-thickness wound, we prospectively studied all patients admitted within 1 week of burn injury during a 2-year period using weekly wound cultures. Wounds were treated with topical silver sulfadiazine and occlusive dressings. Burn wound excision and immediate grafting were initiated during the first postburn week. One thousand five hundred twenty-three patient weeks (483 patients) were evaluated. Serious burn wound infections developed during 55/185 patient weeks (42.3%) when the initial total burn (ITB) was greater than 40% body surface area (BSA). This decreased to 27/304 (8.9%) when the ITB was 21% to 40% and 60/1034 (5.8%) when the ITB was less than 20% BSA. Burn wound infections developed during 57/211 patient weeks (27.0%) when the initial full-thickness burn (IFB) was greater than 20% BSA. The rate of wound infection decreased to 73/776 (9.4%) when the IFB was 1% to 20% and to 12/536 (2.2%) when no IFB was present. We further analyzed the prevalence of serious wound infections in relation to the open wound size during the hospital course. Wound infections occurred during 47 of 96 patient weeks (49.0%) when the current full-thickness wound was greater than 10% BSA. The infection rate decreased to 76 of 594 (12.8%) and 17 of 833 patient weeks (2.0%) when the remaining full-thickness wound was reduced to 1% to 10% and less than 1% BSA, respectively (p less than 0.05). Early wound closure would appear to reduce the risk of serious wound infections, especially in patients with full-thickness burns.

Adolescent↗

The importance of burn wound size in determining the optimal calorie:nitrogen ratio.

Calorie requirements in hypermetabolic burned patients have been established based on burn size and patient weight. However, the requirement for nitrogen (N), especially with variable open wound sizes, is not clear. Thirty-six adult burned patients were fed with diets containing two different calorie to N (kcal:N) ratios--150:1 (group 1) and 100:1 (group 2)--and N balance was studied with wounds of different sizes. Calorie requirements were calculated with the Curreri formula (25 cal X weight (kg) + 40 Cal X % body surface area [BSA] burned). Daily N balance was calculated from total N intake less total N output (estimated by adding 4 gm to the measured 24-hour urea N production). The data were selected on 233 patient-days when actual calorie intakes were 100% to 150% of the calculated requirement. For a wound size of 1% to 10% BSA, group 1 patients had an N balance of +2.33 gm/day and group 2, +5.54 gm/day. For a wound size of 11% to 30% BSA, N balance was +0.13 and +3.49 gm/day, respectively. For a wound size of 31% to 60% BSA, N balance was -3.38 and +3.88 gm/day, respectively. The traditional 150:1 kcal:N ratio may be adequate for patients with open wounds of less than 10% BSA. Patients with greater than 10% BSA open wounds require a dietary regimen containing a nonprotein kcal: N ratio of 100:1 in order to achieve positive N balance.

Adult↗

The effect of burn wound size on ureagenesis and nitrogen balance.

Hypermetabolic burn patients are frequently in negative nitrogen balance despite provision of estimated caloric needs. We studied 18 thermally injured adult patients in order to evaluate the relationship of burn wound size to urea production and nitrogen balance. We selected data from 147 patient-days when the patients received 100 +/- 25% of their estimated caloric needs. Three significantly different burn size groups (by body surface area [BSA]) were identified by calculation of the catabolic index (CI): group 1, 0-10% BSA (CI = -0.1); group 2, 11-30% BSA (CI = 6.4); and group 3,31-60% BSA (CI = 10.5). The urine urea nitrogen (UUN) for groups 1,2, and 3 was 11.1, 18.9, and 25.3 gm/day, and nitrogen balance was 1.0, -3.9, and -5.8 gm/day, respectively. When nitrogen was given in a calorie:nitrogen ratio of 150:1, only those patients in group I were able to achieve positive balance. We conclude that large burn wounds are associated with increased ureagenesis and impaired nitrogen retention. The protein intake, at the customary calorie:nitrogen ratio of 150:1, may not provide adequate nitrogen to achieve equilibrium, even when energy demands have been met, in patients with burn wounds greater than 10% BSA.

Adult↗

Effects of cimetidine on fluid requirement during resuscitation of third-degree burns.

Seventy percent body surface area third-degree burns were produced in four groups of six guinea pigs each, after which all were resuscitated with Ringer's lactate solution. Group 1 received 4 ml/kg/%burn. Group 2 received 1 ml/kg/%burn with cimetidine, which was begun at 0.5 hours after burn injury. Group 3 received 1 ml/kg/%burn with cimetidine, which was begun at 1 hour after burn injury. Group 4 received 1 ml/kg/%burn without cimetidine. There were no significant differences among any of the groups in blood pressures or heart rates during the study period. Group 4 showed significantly higher hematocrit values than group 2 at 4 hours after burn injury and thereafter. The cardiac outputs of group 2 were the same statistically as those of group 1. The cardiac outputs of group 3 were significantly lower than those that received cimetidine early (group 2), though still higher than those of the 1 ml control group (group 4) at 4 hours after burn injury and thereafter. At 24 hours after burn injury, the water content of the burned skin of group 2 was significantly lower than that of the other groups. We conclude that in third-degree burns, cimetidine therapy can effectively reduce burn edema and the amount of required resuscitation fluid. Early administration is better than late administration of cimetidine.

Administration, Cutaneous↗

Reduced fluid volume requirement for resuscitation of third-degree burns with high-dose vitamin C.

The effects of high-dose vitamin C therapy (170 mg, 340 mg, and 680 mg/kg/day) were evaluated in 70% body surface area third-degree burns in guinea pigs that were resuscitated with 1 ml/kg/%burn Ringer's lactate solution. The water content measurements of the burned skin at 24 hours after burn injury in the vitamin C-treated groups were significantly lower than those of the control group (1 ml/kg/%burn) and those of the standard resuscitation group (4 ml/kg/%burn). The cardiac outputs in the group that received 340 mg vitamin C were significantly higher than those of the control group but not significantly different than those of the standard therapy group at 2 hours after burn injury and thereafter. In comparison with the regimen of 340 mg vitamin C, the regimen of 680 mg vitamin C was no more beneficial, and the regimen of 170 mg was less effective. With administration of adjuvant high-dose vitamin C, we were able to reduce the total 24-hour resuscitation volume from 4 ml/kg/%burn to 1 ml/kg/%burn, while a comparable cardiac output was maintained.

Animals↗

Effects of high-dose vitamin C administration on postburn microvascular fluid and protein flux.

The effects of vitamin C treatment (14 mg/kg/hr) on burn injury were evaluated in the hind paws of 12 mongrel dogs. A lymph duct above one hind paw of each dog was cannulated. Hourly lymph flow rates (QL) and plasma and lymph total protein concentrations were measured before the burn injury and for 6 hours after the burn injury. Data from 24 paws were divided into four groups: nonburn without treatment, nonburn with treatment, burn without treatment, and burn with treatment. The nonburn groups showed no significant differences in QL or in total protein flux. In the burn groups the postburn hourly QL increased by sevenfold in the nontreatment group and only by threefold in the treatment group, whereas the postburn hourly total protein flux increased by fifteenfold and fivefold, respectively. We conclude that administration of high-dose vitamin C reduces early postburn microvascular leakage of fluid and protein.

Animals↗

How long do we need to give antioxidant therapy during resuscitation when its administration is delayed for two hours?

Twenty-four guinea pigs with third-degree burns over 70% of the body surface area were divided equally into four groups. All animals received Ringer's lactate (R/L) beginning 30 minutes after burn injury. Group 1 received R/L without vitamin C beginning 2 hours after burn injury. Groups 2, 3, and 4 received R/L with vitamin C until 4, 8, and 24 hours after burn injury, respectively. Beginning 3 1/2 hours after burn injury the hourly fluid volume was reduced to 25% of the Parkland formula calculation. The hourly sodium and fluid intake in each group was the same. Groups 1 and 2 demonstrated higher hematocrit and lower cardiac output values as compared with those values for group 3, indicating hypovolemia and hemoconcentration in these groups. Group 3 showed hematocrit and cardiac output values equivalent to those values for group 4. We conclude that high-dose vitamin C must be given until 8 hours after burn injury to maintain adequate hemodynamic stability in the presence of a reduced resuscitation fluid volume.

Analysis of Variance↗

The effects of high-dose vitamin C therapy on postburn lipid peroxidation.

The effects of vitamin C treatment (14 mg/kg/hr) on postburn lipid peroxidation were evaluated in 12 dogs. A lymph duct above the ankle was cannulated bilaterally. Hourly lymph flow rates, plasma and lymph total protein concentrations, and plasma and lymph malondialdehyde concentrations were measured before the burn injury and for 24 hours after the burn injury. Four groups were employed: nonburn without treatment, nonburn with vitamin C treatment, burn without treatment, and burn with vitamin C treatment. The nonburn groups showed no significant differences in lymph flow rates, total protein flux, or lymph malondialdehyde level. In the burn groups the postburn hourly lymph flow rate increased by 850% without treatment and by 500% with vitamin C treatment, whereas the postburn hourly total protein flux increased by fiftyfold and twentyfold, respectively. There was a significant reduction in the postburn lymph malondialdehyde level in the group treated with vitamin C as compared with the nontreatment group. We conclude that high-dose vitamin C administration diminishes early postburn lipid peroxidation and reduces microvascular leakage of fluid and protein.

Animals↗