PubMed Health⌕ Search

Biomedical subjects

M Tenenhaus

Publications and source records attributed to M Tenenhaus.

23 records · Page 2Linked to original sources

Use of the repeated cross-over design in assessing bioequivalence: (within and between subjects variability - Schuirmann Confidence Intervals estimation).

In 1992, the Division of Bioequivalence in the Office of Generic Drugs published a guide to Statistical procedures for bioequivalence studies using a standard two-treatments cross-over design (1). This paper describes the application of the guidelines to a practical protocol and the recent Proc MIXED (SAS) will be shown to be much more convenient than the traditional Proc GLM for theoretical and practical reasons (correct estimation of residuals, analysis of the within-subjects variation, direct calculation of the Schuirmann 90% Confidence Intervals). This new procedure was applied to a study protocol on riluzole (Rilutek) including a replicate design with the within-subject and between-subject variances being estimated on Cmax and AUC biopharmaceutic parameters.

Administration, Oral↗

Effects of high-dose vitamin C administration on bacterial translocation and lung neutrophil sequestration in burned mice.

Severe burn injury produces shock and induces acute gastrointestinal derangements that may disrupt mucosal integrity and facilitate bacterial translocation (BT) to mesenteric lymph nodes, accompanied by endotoxemia. Antioxidant treatments may be beneficial after shock by acting as scavenger agents for highly reactive oxygen intermediates. We studied the effects of high dosages of vitamin C, a water-soluble antioxidant, on the incidence of BT and on levels of lung myeloperoxidase in burned mice. Myeloperoxidase is primarily found in neutrophils, and levels of myeloperoxidase in tissues reflect neutrophil sequestration. The doses of vitamin C used were equivalent on a weight basis to 1 gm/hr administered to humans over a 24-hour period, doses that have shown efficacy in improvement of resuscitation in other experimental burn models and currently are being used in clinical trials in patients with burns. Mice were anesthetized and received 32% total body surface area, full-thickness burn injury to the dorsum, followed by injection of 1 ml of Ringer's lactate (RL) for resuscitation. Mice were divided into three groups: (1) unburned, received anesthesia and RL injections; (2) burned, received vitamin C (14 mg/kg/hr) in 1 ml RL by intraperitoneal injection immediately after burn and via subcutaneous injection (0.5 ml) at 6 and 12 hours after burn; (3) burned, received identical injections of RL alone (control animals). Mesenteric lymph nodes were removed by use of sterile technique at 24 hours after burn and cultured; any growth was considered evidence of BT. The incidence of BT in burned mice was not altered by administration of vitamin C (normal, 10% BT; burn, 41.37% BT; burn+vitamin C, 45.83% BT). Similarly, burned animals that received vitamin C or RL alone did not differ in the levels of myeloperoxidase in the lungs (normal, 0.015 +/- 0.003 U/gm; burn, 0.2231 +/- 0.029 U/gm; burn+vitamin C, 0.281 +/- 0.041 U/gm).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗

Effects of recombinant bactericidal, permeability-increasing protein on bacterial translocation and pulmonary neutrophil sequestration in burned mice.

Burn injury induces bacterial translocation (BT) from the gut in multiple animal models. Etiologic factors contributing to BT may be an ischemia-reperfusion injury to the gut, the release of inflammatory cytokines, oxygen metabolites and other mediators, and cytotoxic effects mediated by endotoxin (lipopolysaccharide). Bactericidal, permeability-increasing protein is a neutrophil granule protein with potent bactericidal and lipopolysaccharide-neutralizing activities. The use of this protein has not been previously reported in a burn-injury model. The purpose of this study was to determine whether recombinant bactericidal, permeability-increasing protein (rBPI23) affects the incidence of BT and myeloperoxidase content in lung tissue (a measure of leukocyte sequestration) in a burn-injury model. Mice received a 32% total body surface area, full-thickness, scald burn, and 10 mg/kg body weight rBPI23 in saline solution was given by intraperitoneal injection at 0, 3, and 6 hours after the burn. Control animals received intraperitoneal saline solution only. All animals received a total of 1 ml saline solution intraperitoneally immediately after burn injury for fluid resuscitation. At 24 hours after burn injury, mesenteric lymph nodes (MLN) were harvested, homogenized, and plated. Lung tissue was harvested and assayed for myeloperoxidase. Burned mice treated with rBPI23 had significantly (p = 0.005, Fisher's Exact Test, two-tailed) decreased incidence of BT, compared to burned mouse controls. Leukosequestration into lung tissues was not affected by rBPI23. Postburn administration of rBPI23 reduces but does not abolish the incidence of BT after burn injury in mice, perhaps by reducing intestinal injury during burn shock and the ischemia-reperfusion period by inhibiting the effects of lipopolysaccharide. An alternate explanation may be that rBPI23 could increase clearance and killing of bacteria by host defenses.

Animals↗

A comparison of the outgrowth potentials of split-thickness skin grafts sectioned by scalpel, mechanical mesher, and CO2 laser.

Mechanical meshers that press blades through immobilized skin are routinely used to expand split-thickness skin grafts, and scanned incisional lasers are currently under investigation for the same purpose. However, in contrast to the atraumatic wound edge that is created on these grafts by a sliding scalpel blade, the skin "crushing" and skin coagulation that can occur with the use of mechanical meshers and lasers are thought to reduce the outgrowth potential of the epidermis. With the use of an in vitro explant outgrowth system, epithelialization derived from wound edges that were created by a scalpel, a mechanical mesher, and a CO2 laser at various settings was studied. The area of epithelialization around skin explants was not significantly different for skin bridges produced by scalpel cuts and those produced by the skin mesher, and histologic sections demonstrated similar epiboly-growth under these explants. In contrast, wounds created with the CO2 laser showed impaired epithelialization. Incisions were made at several power settings, ranging from 11 passes at 4 mW to 1 pass at 24 mW. Only minor differences were demonstrated, with the lower laser power yielding slightly better results. Recruitment of keratinocytes into the proliferative state, as assessed by bromodeoxyuridine incorporation, was equivalent for scalpel and mesh cut skin. This data does not support concerns about decreased graft viability resulting from the crushing blade action used by mechanical meshers. The possibility of cutting and meshing skin grafts with lasers of the far-infrared and mid-infrared light spectrum are discussed.

Humans↗

Daily variations in skin surface properties using mixed model methodology.

In order to explore the variations over the course of a day in certain skin biophysical properties, a study was conducted on 8 female volunteers. An assessment of several skin biophysical properties was carried out on the face and the volar forearm every 4 h over a period of 48 h. The biophysical parameters were assessed on the face for sebum secretion, skin surface pH, skin colour, transepidermal water loss, capacitance and skin surface temperature. The same parameters were measured on the volar forearm (excepted for sebum secretion). A statistical analysis based on mixed effect models was conducted. Four models, with different covariance structures, were successively tested. The analysis allowed us to identify a structure that repeated itself over time in the same way over each 24-hour period for capacitance on the forearm and for sebum secretion, skin surface pH and skin colour (L* and a* parameters) on the face. Mixed effect methodology is a powerful tool to analyse longitudinal data involving correlations among repeated measurements made on the same subject.

Adult↗