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Biomedical subjects

B D Wilson

Publications and source records attributed to B D Wilson.

At least 19 recordsLinked to original sources

Photodynamic therapy in the treatment of Bowen's disease.

BACKGROUND: The treatment of Bowen's disease in anatomically difficult areas or especially large lesions can challenge accepted modalities of treatment. OBJECTIVE: The purpose of this study was to illustrate the effectiveness of photodynamic therapy in the treatment of Bowen's disease. In addition, photodynamic therapy may be used as adjuvant therapy for difficult lesions. METHODS: Six patients with Bowen's disease in various anatomic sites were treated with photodynamic therapy. Four were in a difficult anatomic site, or were especially large, or both. Photofrin, 1.0 mg/kg, was administered intravenously and laser treatment was given approximately 48 hours later with the argon dye laser. Light was administered at a wavelength of 630 nm and the light dose ranged from 185 to 250 joules/cm2. Treatment was given by surface radiation only. RESULTS: Eight lesions were treated. All showed a complete response at 3 months (100%) and continue to show a complete response at 6 and 12 months. Morbidity was low; the most significant side effects were moderate pain and edema. Healing time varied depending on the size of the lesion. CONCLUSION: Photodynamic therapy is an effective and useful alternative for Bowen's disease, especially those lesions in anatomically difficult areas or those that are especially large.

Adult

Regulation of endothelial cell protein C activation by native and oxidized low density lipoprotein.

The effects of native LDL and Ox-LDL and HDL on endothelial cell protein C activation were examined. Ox-LDL, which is postulated to contribute to cardiovascular disease, markedly suppressed activation of protein C, an important vascular anticoagulant activity. This effect was seen with both human venous and arterial endothelial cells. Endothelial cells modified LDL to a form that reduced protein C activation, an effect prevented by the anti-oxidant, probucol. Endothelial cells are known to express the acetyl LDL (scavenger) receptor, which binds chemically modified and Ox-LDL. The effect of Ox-LDL on protein C activation does not appear to result from uptake via the acetyl LDL receptor, since a known scavenger receptor antagonist (fucoidin) did not inhibit the oxidized LDL effect. In contrast to the results with Ox-LDL, native LDL and both native and oxidized HDL increased protein C activation. These data indicate that native and modified lipoproteins regulate blood coagulation by affecting vascular anticoagulant activity and suggest mechanisms that may link modified lipoproteins with both vascular disease and thrombosis.

Cells, Cultured

Photodynamic therapy for the treatment of basal cell carcinoma.

BACKGROUND: Photodynamic therapy is an investigational method for the treatment of a variety of solid tumors. The purpose of this study was to determine the optimum factors and illustrate the effectiveness of photodynamic therapy in the treatment of basal cell carcinomas. This was a prospective study in which patients presenting with primary or recurrent basal cell tumors, particularly but not exclusively widespread tumors or large single tumors, were offered the option of photodynamic therapy in their treatment regimen. RESULTS: Patients were administered 1 mg/kg of a photosensitizer (Photofrin II). Light doses (630 nm) ranged from 72 to 288 J/cm2. A total of 37 patients with 151 sites were treated in this study. A complete response rate of 88% was achieved with one application. Morbidity was low; the most significant side effects were moderate pain and edema. CONCLUSIONS: Photodynamic therapy is a modality that offers localized treatment of primary or recurrent nonmelanoma skin cancer. By applying reciprocal doses of photosensitizer and light, the efficacy of photodynamic therapy in the treatment of skin lesions is demonstrated achieving significant light penetration into tissue with a high complete response rate of the lesions and acceptable normal tissue response.

Basal Cell Carcinoma

The cost benefit of rehabilitation of injured workers in New Zealand.

A multidisciplinary rehabilitation centre was established to address the needs of people with mild to moderate disability who had not worked for prolonged periods of time. A fitness based programme assisted 10 of the 20 who had been off work for more than six months to return to activity. Six and eighteen month follow up confirmed the durability of placement of most workers who had returned to work, and that projected benefits were achieved. Benefits were defined as savings in earnings related compensation (ERC), and compared to the costs of establishing and running the centre. Sensitivity analysis ascribing between 100% and 50% of benefit to the programme showed a positive benefit cost ratio, with benefits discounted at a rate of 10% over 10 years. With 75% ascribed, the project produced benefit cost ratio of about 1.5:1 in the first year, 2.8:1 in the second year, and rising to 6.2:1 in the fifth year and 10:1 by the tenth year. With only 50% ascribed, the benefit over the same times was 1.0:1, 1.9:1, 4.1:1 and 6.7:1 by the tenth year. These calculations probably underestimate true benefits.

Adult

Oxidized low-density lipoprotein increases cultured human endothelial cell tissue factor activity and reduces protein C activation.

Increasing evidence suggests that the formation of oxidized low-density lipoprotein (Ox-LDL) in vivo is associated with the development of atherosclerotic vascular disease. We investigated the effects of Ox-LDL on two vascular endothelial cell coagulant properties, tissue factor expression, and protein C activation. The Ox-LDL increased human arterial and venous endothelial cell tissue factor activity, with 100 micrograms/ml of Ox-LDL increasing factor activity fourfold. Native LDL modified by incubation with cultured human arterial and venous endothelial cells also induced endothelial cell tissue factor activity. This modification was blocked by coincubation with the antioxidants, probucol or ascorbic acid. It was determined, based on inhibition by known scavenger receptor antagonists (fucoidin, dextran sulfate), that binding of Ox-LDL via the acetyl LDL (scavenger) receptor was partially responsible for the increase in tissue factor expression. Whereas endothelial cell tissue factor expression was increased by incubation with Ox-LDL, protein C activation was reduced approximately 80% by incubating cultured endothelial cells with Ox-LDL. The effect of Ox-LDL on protein C activation was not inhibited by antagonists to the scavenger receptor. These data indicating that an atherogenic lipoprotein can regulate key vascular coagulant activities provide an additional link between vascular disease and thrombosis.

Anticoagulants

Localization of endogenous beta-galactoside-binding lectin as a means to distinguish malignant from benign skin tissue.

The immunolocalization of a 30-kd endogenous lectin, referred to as galaptin, was studied in various skin tumor types. Basal cell carcinomas expressed little or no galaptin, whereas nonmalignant basaloid cells, squamous cell carcinomas, melanoma, nevi, and stroma showed more prominent galaptin immunostaining. Therefore, the immunodetection of galaptin may aid the dermatopathologist in difficult histologic diagnosis.

Biomarkers, Tumor

Amiodarone-induced pulmonary inflammation. Correlation with drug dose and lung levels of drug, metabolite, and phospholipid.

To investigate the hypotheses that amiodarone-induced pulmonary inflammation may be related to direct drug toxicity, groups of 10 or more Wistar rats were fed amiodarone by gavage at concentrations of 175, 300, 400, and 500 mg/kg/day, or vehicle alone. After 6 wk of drug feeding, the rats were examined for histologic and cellular evidence of pulmonary inflammation. In addition, the amounts of amiodarone, the major metabolite of amiodarone N-desethylamiodarone (N-des), and phospholipid in the lungs were determined. We found that rats fed 175 mg/kg of amiodarone were essentially no different from control animals. The 175 mg/kg group had normal lung histologies, no change in lavage cell counts or differential counts, and very little amiodarone, N-des, or phospholipid in the lungs. In contrast, the three high-dose groups had abnormal lung histologies along with increases in lavage cell counts and change in differential counts. There were also significant increases in the amounts of amiodarone, N-des, and phospholipid in the lung. We conclude that the development of amiodarone-induced pulmonary inflammation is dose dependent, and that there is a direct correlation between the amount of amiodarone, N-des, and phospholipid in the lung with the development of inflammation. It therefore appears that the drug is directly toxic to lung tissue.

Amiodarone

The rehabilitation of injured workers in New Zealand: a pilot study.

At the request of the local office of the Accident Compensation Corporation (ACC) we established a centre which offered a multidisciplinary rehabilitation programme consisting of a full assessment and an eight week individually planned and monitored fitness programme. The clients progressed to occupational therapy, work trials, and later to paid work. The programme included education about back care and health maintenance, and relaxation techniques. Of the 48 injured people who attended the centre, 37 were assessed as suitable to enter the programme, and 32 people took part. Outcome, measured as return to work or change in assessed fitness to work, was not related to age, sex, marital status, length of time since accident, or work category. Only 25% of workers returned to jobs in medium or heavy manual work. Sickness impact profile total and physical scores improved over the programme, but did not correlate significantly with return to work or fitness for work. Client perception of benefit was not significantly related to outcome. We analysed data from the 20 clients with claims longer than 6 months separately because matched case controls could not be provided by the ACC. Six months after completion of the programme, four were in paid employment, four in prolonged work trials, one in a job partly paid by the ACC, and one setting up his own business. Their return to the work force demonstrated the effectiveness of the centre in restoring people to function after prolonged periods of inactivity.

Accidents, Occupational

Pulmonary accumulation of amiodarone and N-desethylamiodarone. Relationship to the development of pulmonary toxicity.

To investigate the relationship between the amount of amiodarone and the major metabolite N-desethylamiodarone found in the lung with the development of toxicity, Fischer 344 and Wistar rats were given 175 mg/kg/day of drug by gavage. After 1, 3, 6, and 12 wk of drug feeding, both stains were examined for histologic evidence of pulmonary inflammation and for changes in lavage cell counts and differentials. The amounts of amiodarone and N-desethylamiodarone in the lungs were determined using high performance liquid chromatography. We found that in drug-fed Wistar rats the lavage differentials were unchanged, lavage cell counts were decreased compared with those in control rats, and the lungs appeared normal except for some foamy macrophages. Wistar rats also had low levels of amiodarone and metabolite in both lung tissue and cells. In contrast, Fischer rats had an increase in lavage lymphocytes, neutrophils, and macrophages compared with that in control rats and abnormal lung histologies. Also, there was much more drug and metabolite in the lungs than the amounts found in Wistar rats. Because Fischer rats had more metabolite than amiodarone in the lung and the reverse was true in Wistar rats, the in vitro cytotoxicity of amiodarone and N-desethylamiodarone were compared. We found that N-desethylamiodarone was significantly more cytotoxic than amiodarone to both fibroblasts and endothelial cells. We conclude that there is a relationship between the amounts of drug and metabolite in the lung and the development of pulmonary inflammation, and that N-desethylamiodarone may be more cytotoxic than amiodarone.

Amiodarone

Experimental values of the ionization constants for L-3,5-di-iodotyrosine and a model for ionic interactions of thyroid hormone (T3) and its nuclear receptor.

Ionization characteristics of L-3,5-di-iodotyrosine have been measured under various conditions. These data, which correct an erroneous report of pK3 in the literature, have been used to estimate the ionization constants of the thyroid hormone L-3',3,5-tri-iodothyronine (T3). On this basis a reinterpretation has been made of the pH-dependent binding of the hormone to its solubilized rat liver nuclear receptor (Wilson BD and Gent WL, Biochem J 232: 663-667, 1985). The interaction may depend on the ionization of the phenolic group of T3 and an acidic group (pK'7.6) in the receptor site, leading to the formation of a hydrogen bond between the two groups. The changes of the number of binding sites with pH must then result independently from alterations in the conformation of the receptor protein.

Diiodothyronines

Amiodarone-induced pulmonary toxicity in the rat.

A rat model of amiodarone-induced pulmonary toxicity is described. The rats were fed, by gavage, 175 mg/kg/day of amiodarone hydrochloride suspended in methyl cellulose. Controls received methyl cellulose alone. Groups of rats were examined after 1, 3, 6, 9, and 12 weeks of feeding. We found that drug-fed rats had significantly more macrophages, neutrophils, and lymphocytes in the bronchoalveolar lavage (BAL). The early increase in cellularity was due to an increase in macrophages, and the macrophage count peaked after 6 weeks of drug treatment. The number of neutrophils in the experimental animals remained high throughout the course of the experiment. An increasing number of lymphocytes was seen in the BAL between 6 and 12 weeks of drug treatment. Protein in the lavage fluid was significantly elevated after 12 weeks of amiodarone exposure. Histologic sections were abnormal after 3 weeks of drug treatment, characterized by interstitial thickening with accumulation of mononuclear cells and alveoli packed with large foamy macrophages. There was only minimal evidence of fibrosis. This model appears to be very similar to human amiodarone-induced pulmonary toxicity and should be useful for the study of the pathogenesis of amiodarone-induced toxicity.

Administration, Oral

Does amiodarone inhibit T3 binding to solubilized nuclear receptors in vitro?

One of the proposed mechanisms of action of amiodarone is by interfering with T3-receptor interactions. However, reports in the literature on this matter are contradictory and, in an attempt to resolve these contradictions, the effects of amiodarone on T3 binding to solubilized nuclear receptors from rat liver were investigated. A drug concentration-related competitive inhibition of T3 binding occurred in the presence of considerable amiodarone precipitation. Measurement of the proportion of soluble amiodarone over the range where significant inhibition of T3 binding was observed, revealed that the soluble amiodarone decreased over this range. Since the amiodarone preparation was free of any contaminant, these findings suggested that a product generated from amiodarone during incubation was responsible for the inhibition. HPLC analysis of the soluble amiodarone fraction indicated that, during incubation, two substances were generated from the parent compound. However, only the concentration of one of the substances continually increased whereas the other decreased with increasing concentrations of amiodarone added to the samples. These findings suggest that the inhibition of T3 binding to solubilized nuclear receptors in the presence of amiodarone results from the generation of a specific product from the amiodarone under certain conditions during incubation.

Amiodarone

Neutrophil accumulation and cutaneous responses in experimental cutaneous candidiasis of genetically complement-deficient mice.

Mice deficient in the fifth component of complement were studied for their ability to respond to and clear experimental cutaneous Candida albicans infections. The complement-deficient animals took longer to clear the infections and developed a significantly greater delayed hypersensitivity response to Candida than did normal animals. However, although the serum of the complement-deficient animals was incapable of generating in vitro chemotactic activity for neutrophils after appropriate stimulation, the epidermal neutrophilic infiltrate in the Candida-infected skin of these animals was equivalent to that in the normal animals. The progression of the infection, including the early relocation of the invading Candida pseudohyphae to a more superficial site in the stratum corneum and the thickening of the epidermis itself, was also similar in the complement-deficient and normal animals. Therefore, although mice lacking the fifth complement component cannot generate complement-derived serum chemotactic factors and are somewhat less efficient in clearing experimental cutaneous candidiasis, the accumulation of neutrophils in the Candida-infected skin of these animals and their initial cutaneous responses to the infections are normal.

Abscess

Inhibition of prostaglandin biosynthesis by etodolac. I. Selective activities in arthritis.

Etodolac is the first anti-inflammatory drug belonging to the tetrahydropyranoindole class. In contrast to several other common anti-inflammatory drugs, etodolac exhibited an unusually high potency as an inhibitor of established adjuvant arthritis relative to its activity against carrageenan paw edema in the rat. This phenomenon led us to investigate whether the ability of NSAIDs to inhibit prostaglandin biosynthesis differed between cultures of macrophages, which are present in inflammatory exudates, and cultures of synoviocytes and chondrocytes, which contribute to inflammation of the articulating joint. Although other anti-inflammatory drugs were found to be equally active in all three cell types, etodolac was found to be much more effective on the cells of the joint than on the macrophage. This differential activity may be responsible for the striking efficacy of etodolac as an anti-arthritic drug.

Acetates

Forces exerted during exercises on the uneven bars.

The purposes of this study were (1) to develop a technique to measure the force exerted on uneven bars during a gymnast's performance, and (2) to determine the magnitudes of the maximum forces exerted on the bars during normal use. Strain gages, a UV recorder, and motion-picture cameras were used to record the forces exerted against the bars and the motions with which they were associated. Three college gymnasts were used as subjects. Each performed several repetitions of an exercise sequence judged to result in the maximum loading of the bars she might produce under normal conditions. The maximum forces recorded were 3500 N (low bar) and 2140 N (high bar). These values were recorded during a sharp impact between the subject's thighs and the bar during the passage of the subject beneath the bar in a giant swing, respectively. Making due allowance for possible measurement error and for the estimated effects of the bars being used by gymnasts of greater mass than those in this study, it was concluded that bars should be designed to withstand repeated loads of at least 4205 N.

Adult