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Biomedical subjects

R S Rees

Publications and source records attributed to R S Rees.

68 records · Page 4Linked to original sources

Interaction of brown recluse spider venom on cell membranes: the inciting mechanism?

The venom from the brown recluse spider, Loxosceles reclusa, contains one or more factors which produce skin necrosis. A dermonecrotic factor with sphingomyelinase D activity was purified from the spider's venom sacs which produced skin necrosis when injected intradermally in rabbits. Adsorption of the dermonecrotic activity occurred following incubation with isolated membranes from different cell types or different species in a dose-responsive fashion. Since injection of the complex in rabbits produced skin necrosis, a specific antibody that inhibits the dermonecrotic activity and sphingomyelinase activity was used to identify the venom fraction on the plasma membrane of erythrocytes with electron microscopy. Initiation of cutaneous inflammatory reaction may result from high-affinity interaction of a venom component in the brown recluse spider venom and cell membranes.

Adsorption↗

Venous endothelial changes after experimental cooling of free flaps.

The free epigastric rabbit flap was used to observe morphological alterations in the microvasculature following prolonged hypothermic ischemic intervals. Free flaps were raised, cooled 1-6 days, and reanastomosed. The epigastric artery, vein, and dermal vessels were examined by electron microscopy. Efforts to keep flap tissues in the cold less than or equal to 5 days were successful (85% of flaps survived following reanastomosis N = 15). Flap failures were accompanied by extensive disruption to the endothelial cells of the epigastric vein. The findings support the efficacy of a cooling period less than or equal to 5 days for free flaps. The morphological alterations in the venous endothelium of the flap also suggest a plausible explanation for flap failures which occur in spite of patent anastomotic sites.

Animals↗

Becaplermin gel in the treatment of pressure ulcers: a phase II randomized, double-blind, placebo-controlled study.

Pressure ulcers are associated with significant rates of morbidity and mortality, particularly in the geriatric and spinal cord-injured populations. Newer pharmacologically active therapies include the use of topically applied recombinant human platelet-derived growth factor-BB (becaplermin), the active ingredient in REGRANEX) (becaplermin) Gel 0.01%, which has been approved in the United States for treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. In this study, the efficacy of becaplermin gel in the treatment of chronic full thickness pressure ulcers was compared with that of placebo gel. A total of 124 adults (>/= 18 years of age) with pressure ulcers were assigned randomly to receive topical treatment with becaplermin gel 100 microg/g (n = 31) or 300 microg/g (n = 32) once daily alternated with placebo gel every 12 hours, becaplermin gel 100 microg/g twice daily (n = 30), or placebo (sodium carboxymethylcellulose) gel (n = 31) twice daily until complete healing was achieved or for 16 weeks. All treatment groups received a standardized regimen of good wound care throughout the study period. Study endpoints were the incidence of complete healing, the incidence of >/= 90% healing, and the relative ulcer volume at endpoint (endpoint/baseline). Once-daily treatment of chronic pressure ulcers with becaplermin gel 100 microg/g or 300 microg/g significantly increased the incidences of complete and >/= 90% healing and significantly reduced the median relative ulcer volume at endpoint compared with that of placebo gel (p < 0.025 for all comparisons). Becaplermin gel 300 microg/g did not result in a significantly greater incidence of healing than that observed with 100 microg/g. Treatment with becaplermin gel was generally well tolerated and the incidence of adverse events was similar among treatment groups. In conclusion, once-daily application of becaplermin gel is efficacious in the treatment of chronic full thickness pressure ulcers.

Administration, Cutaneous↗

Use of a cell-based interactive wound dressing to enhance healing of excisional wounds in nude mice.

The need to have viable, metabolically active cells to heal wounds is well recognized, because there is clear evidence that cellular dysfunction delays healing. This suggests that addition of metabolically active cells to a delayed healing tissue could enhance the healing of the tissue. Therefore, we examined the ability of an interactive wound dressing composed of human keratinocytes or fibroblasts grown on microporous bio-reactor beads and placed into a polyethylene bag to facilitate the delayed healing of wounds in nude mice. A 1 x 1 cm wound was made on the backs of nude mice, and the dressing with or without viable cells was placed on the wound for 8 to 24 days, with dressing changes every other day. Wound area and time to heal measurements were compared after various interventions including freeze-thawing. The data shows that the interactive wound dressing was more effective than the control dressings (p<0.05) and that keratinocytes were more effective than fibroblasts in wound healing (p<0.05). Freezing-thawing of the interactive wound dressings destroyed the activity of the dressing. Studies examining cells using a live/dead viability assay showed that both keratinocytes and fibroblasts were alive after 2 days on the mice. Surprisingly, human fibroblasts appeared to exhibit bridging behavior that is indicative of fibroblast proliferation. We conclude that a simple interactive wound dressing using either keratinocytes or fibroblasts can enhance the healing of wounds in nude mice.

Animals↗

Noninvasive measurement of an index of renal blood flow.

A new technique for the noninvasive measurement of an index of renal blood flow is described. The method utilizes ultrasound determined renal volume and radionuclide assessment of the mean transit time of a pertechnetate bolus through the kidneys. From this information a value for flow is calculated according to compartmental analysis principles. There is good correlation between renal blood flow estimated by this technique and that determined by microsphere injection, r = 0.96.

Animals↗

In vivo validation of MR velocity imaging.

Calculations of left ventricular stroke volume obtained by summing the areas of multiple contiguous transverse magnetic resonance (MR) slices in systole and diastole using a spin echo sequence have been compared in 10 healthy volunteers with the stroke output derived from velocity maps in the ascending aorta using a field even-echo rephasing sequence. The results gave a correlation coefficient of 0.97 (p less than 0.001) and a standard error of estimate of 3.2 ml. Velocity maps have also been obtained in the pulmonary artery, the descending aorta, and the superior vena cava. The accuracy of this technique and the theoretical limitations of MR measurements have implications for the earlier detection of atheroma in the coronary and other arteries.

Aorta↗

TGF-beta3 in the treatment of pressure ulcers: a preliminary report.

OBJECTIVE: To determine the safety, tolerability, and efficacy of TGF-beta3 in the treatment of chronic, nonhealing pressure ulcers. DESIGN: A subset analysis of data from a randomized, blind, parallel, placebo-controlled trial involving 270 patients. SETTING: University of Michigan Wound Care Center. PATIENTS: A total of 14 patients (6 women and 8 men aged > or = 18 years) with pressure ulcers were randomly assigned to 1 of 3 groups to receive once daily topical application of recombinant TGF-beta3 or placebo gel for a period of no more than 16 weeks. Group 1 (n=4) received 1.0 microg/cm2 of TGF-beta3, Group 2 (n=5) received 2.5 microg/cm2 of TGF-beta3, and Group 3 (n=5) received placebo gel. All subjects received standardized wound care as well. Weekly evaluations were performed for efficacy, determined by relative wound surface areas and volumes, and were compared with initial baseline values and safety parameters. MAIN OUTCOME MEASURE: Reduction in pressure ulcer area and volume. MAIN RESULTS: Group 2 had a significantly increased rate of wound healing at the fourth visit (P<.05). No significant difference was observed in the healing rate among the groups at the termination of the study. Treatment with TGF-beta3 was well tolerated and there were no significant adverse reactions. CONCLUSION: The findings of this study indicate that the topical application of TGF-beta3 is safe and useful in the treatment of pressure ulcers and is most effective at the earliest stages of therapy.

Administration, Topical↗

Osteomyelitis related to pressure ulcers: the cost of neglect.

Twelve patients with documented chronic osteomyelitis of the pelvis resulting from truncal pressure ulcers were examined retrospectively to identify the cost of treatment for this significant health care problem. The retrospective review of each case spanned an 18-month period--6 months prior to the initial positive bone biopsy to 1 year following bone biopsy. The financial charges associated with treatment of osteomyelitis were identified using the University of Michigan Health System's databases for hospital charges, professional charges, and pharmacy charges. Prior treatment of these patients included surgical debridement of the pressure ulcer, pelvic bone biopsy, and culture-specific antibiotic therapy. The total charges for this group of 12 patients was $715,204, or an average charge of $59,600 per patient. Each patient was hospitalized, with hospitalization charges of $587,212, or an average of $48,934 per patient. Pharmacy charges for culture-specific antibiotics totaled $85,217 for the 12 patients. Six of 8 flap repairs achieved successful surgical closure of the pressure ulcer (75%) postantibiotic therapy. Surgery charges are not included in the totals.

Adult↗