Biomedical subjects

W G Payne

Publications and source records attributed to W G Payne.

11 recordsLinked to original sources

PubMed2001

Long-term outcome study of growth factor-treated pressure ulcers.

BACKGROUND: Exogenous application of growth factors have been reported in an attempt to accelerate healing of chronic wounds. Most of the trials were of brief duration with short to no follow-up periods. Long-term outcome studies are sparse for pressure ulcer therapies with success rates around 30% for both operative and nonoperative treatments. METHODS: Follow-up evaluations were performed serially up to 12 months for patients completing a 35 day blinded, placebo-controlled cytokine clinical trial of pressure ulcers. RESULTS: Fifty-four of 61 patients completed the follow-up period with 68.5% of the patients (37 of 54) being healed after 1 year. Of patients healing > or =85% during the active treatment phase, 84.6% were healed after 1 year compared with 61% of those that healed <85% during treatment (P <0.05). CONCLUSION: Long-term outcome was better in this growth factor trial than with surgical or standard nonoperative treatment of pressure ulcers. Since only patients receiving exogenously applied cytokines achieved >85% closure during the treatment phase of the trial, the excellent long-term outcome appears attributable to the cytokine therapy.

Administration, Topical↗

PubMed2001

Biotransformation, excretion kinetics, and tissue distribution of an N-pyrrolo[1,2-c]imidazolylphenyl sulfonamide herbicide in rats.

TY029, an N-pyrrolo[1,2-c]imidazolylphenyl sulfonamide herbicide, controls economically important weeds through inhibition of protoporphyrinogen oxygenase. Due to the potential for exposure to this compound in food and animal feed items, a rat metabolism study was required to define the biotransformation of this compound. Animals were exposed to single 50- and 2-mg/kg doses of TY029 [hydantoin-5-(14)C] by oral gavage. About 90% of the administered dose was excreted within 96 h after oral administration. Excretion plateaued after 48 h, and the cumulative sum of urinary or fecal excretion after 48 h was less than 5% of the orally administered dose. TY029 yielded seven major metabolites. While some metabolites were formed by epimerization around chiral centers, others were generated through hydrolytic bond cleavage and hydroxylations and subsequent oxidation of hydroxyl groups to carboxylic acids. One metabolite, about 6.1% of the dose, was observed only in the urine from low-dose female rats. This metabolite was characterized as a glutamate conjugate of an extensively oxidized analog of TY029. With the exception of the glutamate conjugate, the same metabolites were observed in the excreta of all dose groups. However, the relative ratios of the metabolites were different between various dose groups.

Animals↗

PubMed2001

Desmoplastic melanoma.

Desmoplastic melanoma is an uncommonly encountered variant of malignant melanoma. Three histological subtypes exist: desmoplastic, neurotropic, and neural transforming. Desmoplastic melanoma commonly presents in conjunction with existing melanocytic lesions or as an amelanotic firm nodule. Local recurrences are common. Thirty patients over a 6-year period were treated at our institution for desmoplastic melanoma. All lesions were treated with local excision. Local recurrence occurred in seven patients (23%) and was treated by aggressive re-excision in each instance. Clinical regional metastasis (lymph nodal basins) were detected in two patients (6%). Distant metastasis (lung) developed in two patients (6%). Twenty-three patients (76%) were found to have desmoplastic subtype, whereas five (17%) had neurotropic subtype. Six patients (20%) had associated pigmented melanotic lesions. Average length of follow-up has been 18 months. Overall survival is 96 per cent. Presentations and histologic diagnosis can sometimes be difficult and misleading. Treatment is aggressive local excision with follow-up necessary to detect resectable recurrent lesions.

Adult↗

PubMed2001

Cytokine manipulation of explanted Dupuytren's affected human palmar fascia.

INTRODUCTION: Dupuytren's disease plagues human hands and digits producing fibrotic nodules and fascial cords with resultant debilitating flexion contracture deformities. Interest in this condition is great but because the disease is specific to humans and study has been hampered by the lack of an in vivo model. By utilizing an in vivo "nude" rat model it is possible to maintain and study explanted Dupuytren's contracted palmar fascia for prolonged periods of time. MATERIALS AND METHODS: Human specimens were divided into four, one for in vitro analysis, and three for model explantation. The explanted tissue was perfused with either transforming growth factor beta-2 (TGFbeta2), its antibody, or a control vehicle. Explant biopsies were obtained at 30 and 60 days and compared to tissue prior to explantation. Immunohistochemistry of collagen I and III, DNA synthesis, protein production, and fibroblast kinetics were serially determined. RESULTS: Perfusion of explanted Dupuytren's tissue by TGFbeta2 upregulated collagen I and III from biopsies obtained from the explants at 30 days when compared to vehicle control (P < 0.001). Perfusion with antibody prevented this upregulation when compared to vehicle control (P < 0.001). Cell cultures derived from fibroblasts obtained from biopsies of the explants perfused with TGFbeta2 increased DNA synthesis, protein production and fibroblast kinetics. CONCLUSION: These findings paralleled those from other fibroproliferative disorders suggesting a role for TGFbeta2 in the pathogenesis of Dupuytren's contracture as well as possible novel treatment approaches.

Analysis of Variance↗

PubMed2000

Overexpression of transforming growth factor beta-2 and its receptor in rhinophyma: an alternative mechanism of pathobiology.

Proliferative scarring is one of the clinical features of rhinophyma. The following study was undertaken to test the authors' hypothesis that fibrosis might also play an important role in the pathobiology of rhinophyma. The rhinophyma specimens were obtained from 5 white men (mean age, 67.8 years). Normal skin biopsies near benign facial lesions from 5 additional white men of similar age were obtained to serve as controls. Peroxidase-labeled immunohistochemical staining was performed in the rhinophyma and normal skin specimens for the presence of transforming growth factor (TGF) beta-2 and/or TGF-beta II receptor. Histological slides were then measured for the intensity of staining for TGF-beta2 and TGF-beta II receptor using a computer-aided imaging system. The dermis of the rhinophyma tissue displayed stronger immunoreactivity of TGF-beta2 (p = 0.014) and TGF-beta II receptor (p = 0.006) compared with the normal skin. The results of this study demonstrate the overexpression of the fibrogenic protein TGF-beta 2 and TGF-beta II receptor in rhinophyma tissues. These findings support the authors' hypothesis that fibrosis may also play an important role in the pathobiology of rhinophyma.

Aged↗

PubMed2000

Sequential cytokine therapy for pressure ulcers: clinical and mechanistic response.

OBJECTIVE: To compare the healing response of sequential topically applied cytokines to that of each cytokine alone and to a placebo in pressure ulcers, and to evaluate the molecular and cellular responses. SUMMARY BACKGROUND DATA: Because of a deficiency of cytokine growth factors in chronic wounds and the reversal of impaired healing in animal models, pressure ulcer trials have been performed with several exogenously applied growth factors. Because single-factor therapy has not been uniformly successful, combination or sequential cytokine therapy has been proposed. Laboratory data have suggested that sequential treatment with granulocyte-macrophage/colony-stimulating factor (GM-CSF)/basic fibroblast growth factor (bFGF) might augment the previously reported effect of bFGF alone. METHODS: A masked, randomized pressure ulcer trial was performed comparing sequential GM-CSF/bFGF therapy with that of each cytokine alone and with placebo during a 35-day period. The primary measure was wound volume decrease over time. Cytokine wound levels and mRNA levels were serially determined. Fibroblast-populated collagen lattices (FPCLs) were constructed from serial fibroblast biopsies. Cellular ultrastructure was evaluated by electron microscopy. Changes in ease of surgical closure and its relative cost were determined. RESULTS: Ulcers treated with cytokines had greater closure than those in placebo-treated patients. Patients treated with bFGF alone did the best, followed by the GM-CSF/bFGF group. Patients treated with GM-CSF or bFGF had higher levels of their respective cytokine after treatment. Patients with the greatest amount of healing showed higher levels of platelet-derived growth factor (PDGF) on day 10 and transforming growth factor beta (TGFbeta1) on day 36. Message for the bFGF gene was upregulated after treatment with exogenous bFGF, suggesting autoinduction of the cytokine. FPCLs did not mimic the wound responses. Ultrastructure of wound biopsies showed response to bFGF. Treatment with any of the cytokines improved the wound by allowing easier wound closure. This was most marked for the bFGF-alone treatment, with a cost savings of $9,000 to $9,200. CONCLUSIONS: Treatment with bFGF resulted in significantly greater healing than the other treatments in this trial. The clinical response appeared to be related to upregulation of the bFGF message and to increased levels of PDGF-AB, bFGF, and TGFbeta1 in the wounds and changes in ultrastructure. The resultant improvements could be correlated with cost savings.

Double-Blind Method↗

PubMed1999

Maintenance of wound bacterial balance.

BACKGROUND: There is a critical number of bacteria above which tissue responds with infection. This balance of 10(5) or fewer bacteria/g tissue is also required for wound healing to proceed normally. This study evaluated whether a chronic wound once in bacterial balance can maintain that balance over time. METHODS: Serial biopsies for bacterial analyses were obtained weekly during a blinded, placebo-controlled cytokine clinical trial of pressure ulcers. To enter the trial ulcers had to be debrided and have a bacterial count of 10(5) or fewer bacteria/g tissue with no beta-hemolytic streptococci. RESULTS: In all, 96% of cultures (350/363) remained at <10(2) bacteria/g tissue over the 5-week trial; 3% had 10(2) to 10(5), and only 1% had >10(5) bacteria/g tissue. CONCLUSION: Chronic pressure ulcers, once debrided and brought into bacterial balance, will remain in bacterial balance if cared for and kept free of necrotic tissue.

Biopsy↗

PubMed1995

Dethiobiotin synthetase: the carbonylation of 7,8-diaminonanoic acid proceeds regiospecifically via the N7-carbamate.

Dethiobiotin synthetase (DTBS) catalyzes the penultimate step in biotin biosynthesis, the formation of the ureido ring of dethiobiotin from (7R,8S)-7,8-diaminononanoic acid (7,8-diaminopelargonic acid, DAPA), CO2, and ATP. Solutions of DAPA at neutral pH readily formed a mixture of the N7- and N8-carbamates in the presence of CO2. However, four lines of evidence together indicated that only the N7-carbamate of DAPA was an intermediate in the reaction catalyzed by DTBS. (1) Addition of diazomethane to mixtures of DAPA and [14C]CO2 yielded a mixture of the N7- and N8-methyl carbamate esters, consistent with carbamate formation in free solution. In the presence of excess DTBS (over DAPA), the ratio of N7:N8-methyl carbamate esters recovered was roughly doubled, suggesting that the enzyme preferentially bound the N7-DAPA-carbamate. (2) Both N7- and N8-DAPA-carbamates were observed directly by 1H and 13C NMR in solutions containing DAPA and [13C]CO2. In the presence of excess DTBS (over DAPA) only one carbamate was observed, showing that carbamate binding to the enzyme was regiospecific. 13C NMR of mixtures containing enzyme, [7-15N]DAPA, and [13C]CO2 showed that the enzyme-bound carbamate was at N7 of DAPA. In addition, pulse-chase experiments showed that the binary complex of DTBS and N7-DAPA-carbamate became kinetically committed upon addition of MgATP. (3) The N7-DAPA-carbamate mimic, 3-(1-aminoethyl)nonanedioic acid, in which the carbamate nitrogen was replaced with a methylene group, cyclized to the corresponding lactam in the presence of DTBS and ATP; ADP and P(i) were also formed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Diamino↗

PubMed1995

Combined laparoscopic and endoscopic approach to resection of gastric leiomyoma.

Gastric leiomyoma is an uncommonly found entity. Most leiomyomas are asymptomatic and are found at autopsy or on abdominal exploration for other reasons. Indications for resection include large size and symptoms of compression, obstruction, or hemorrhage. The traditional surgical approach consists of laparotomy and resection. This article describes a technique for minimally invasive resection using a combined laparoscopic and endoscopic approach.

Aged↗

PubMed1995

Endoscopic basket impaction.

Endoscopic Retrograde Cholangiopancreatography (ERCP) is an indispensable tool for imaging the pancreatico-biliary tree, and in treating diseases of the pancreatic and biliary systems. ERCP plays a primary role in the management of choledocholithiasis, both in diagnosis and treatment. Complications occur infrequently and can usually be treated nonoperatively. An unusual complication of ERCP and an impacted stone retrieval basket are presented and discussed along with review of the medical literature.

Catheterization↗

PubMed1994

Extramammary Paget's disease of the scrotum.

This case report describes a patient with extramamary Paget's disease of the scrotum. Treatment consisted of excision and primary closure with local advancement flaps. A review of the literature and treatment of extramammary Paget's disease are discussed.

Aged↗