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Biomedical subjects

G Webster

Publications and source records attributed to G Webster.

At least 37 records · Page 2Linked to original sources
PubMed1999

Finasteride in the treatment of men with frontal male pattern hair loss.

BACKGROUND: Finasteride, a specific inhibitor of type II 5alpha-reductase, decreases serum and scalp dihydrotestosterone and has been shown to be effective in men with vertex male pattern hair loss. OBJECTIVE: This study evaluated the efficacy of finasteride 1 mg/day in men with frontal (anterior/mid) scalp hair thinning. METHODS: This was a 1-year, double-blind, placebo-controlled study followed by a 1-year open extension. Efficacy was assessed by hair counts (1 cm2 circular area), patient and investigator assessments, and global photographic review. RESULTS: There was a significant increase in hair count in the frontal scalp of finasteride-treated patients (P < .001), as well as significant improvements in patient, investigator, and global photographic assessments. Efficacy was maintained or improved throughout the second year of the study. Finasteride was generally well tolerated. CONCLUSION: In men with hair loss in the anterior/mid area of the scalp, finasteride 1 mg/day slowed hair loss and increased hair growth.

5-alpha Reductase Inhibitors↗
PubMed1999

Predictors of a favorable response to alpha interferon therapy for hepatitis C.

The most consistently identified predictive factors for a response to both IFN-alpha monotherapy and IFN-alpha in combination with ribavirin are a low HCV RNA level, the absence of fibrosis, infection with HCV genotype 2 and 3, and a prolonged duration of treatment. In addition, an early response to IFN-alpha predicts response to IFN-alpha monotherapy but not necessarily to combination therapy. There does not appear to be any major gain in treating IFN-naive patients with HCV genotype 2 or 3 infection with a combination of IFN-alpha and ribavirin for longer than 6 months. The identification of these predictive factors has allowed improvement in study design and assessment and may provide a patient with an idea of the likelihood of response, making possible a more informed decision regarding treatment. At present, none of these factors, either alone or in combination, completely predicts response to IFN-alpha. Thus, individual patients should not be denied treatment on the basis of these factors.

Alanine Transaminase↗
PubMed1999

Relationship and family breakdown following acquired brain injury: the role of the rehabilitation team.

Although the literature documents the considerable problems acquired brain injury causes for the survivor's family and close relationships, and the corresponding significantly inflated rate of separation and divorce, few papers offer practical solutions. The objective of this paper is to respond to this gap in the literature by presenting some of the problems raised for the rehabilitation team when a family separates, and some suggestions for ways in which these problems could be overcome. The literature is reviewed briefly, followed by reflections and suggestions which are based on this review and on clinical experience. The discussion indicates that there are a number of practical dilemmas raised for the rehabilitation team when a family already involved in the rehabilitation process starts to break up. Some specific suggestions for addressing these issues are made; further research is needed to evaluate their effectiveness.

Brain Injuries↗
PubMed1998

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail.

BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of fungal infections. OBJECTIVE: The purpose of this study was to assess the safety and efficacy of oral fluconazole 150, 300, and 450 mg administered once weekly compared with placebo in the treatment of distal subungual onychomycosis of the fingernail caused by dermatophytes. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study enrolling 349 patients with onychomycosis of the fingernails. Clinical and mycologic efficacy as well as measures of safety were assessed monthly for a maximum of 9 months of treatment, with additional safety visits occurring at weeks 2 and 6. For inclusion, patients were required to have clinically and mycologically documented onychomycosis of the fingernail caused by dermatophytes with at least 25% involvement of the target fingernail. After end of therapy, patients with improved or cured fingernails entered a blinded 6-month follow-up without drug treatment during which efficacy was assessed every 2 months. Efficacy was assessed by clinical (visual) and mycologic (microscopic and culture) measures. Clinical measures included assessments of the percentage of target nail involvement, measurement of the distance from the nail fold to the proximal onychomycotic border, and signs and symptoms of onychomycosis. RESULTS: Fluconazole was significantly superior to placebo in eradicating clinical and mycologic symptoms of onychomycosis, both at the end of active treatment and at 6 months after treatment (p=0.0001 for all efficacy measures). At the end of therapy, 91% to 100% of patients in the fluconazole groups were judged clinical successes, defined as reduction of the affected area of the target nail to less than 25% or cure, compared with 8% for placebo. Clinical cure rates at end of therapy were 76%, 85%, and 90% for fluconazole 150, 300, and 450 mg, respectively, compared with 3% for placebo. These clinical success and cure rates were largely maintained or improved during follow-up. Clinical relapse in cured patients during the follow-up period was very low (1.5% to 3.3%). Fluconazole demonstrated mycologic eradication rates of 89% to 100% at the end of treatment and 90% to 99% at the end of follow-up; for placebo the rates were 8% and 12%, respectively. CONCLUSION: Fluconazole administered once weekly is safe and effective in eradicating distal subungual onychomycosis of the fingernail caused by dermatophytes.

Adolescent↗
PubMed1998

Pharmacokinetics of three once-weekly dosages of fluconazole (150, 300, or 450 mg) in distal subungual onychomycosis of the fingernail.

BACKGROUND: Fluconazole has proven to be safe and effective for a variety of superficial and systemic fungal infections. Preliminary analysis of extensive Phase III studies suggests that it is very effective for the treatment of onychomycosis. Its pharmacokinetic properties, including low molecular weight and high water-solubility, suggest a unique ability to penetrate the nail. This feature is likely to account in part for fluconazole's effectiveness in the treatment of onychomycosis. OBJECTIVE: Determinations of plasma and fingernail concentrations of fluconazole were performed as part of a larger study comparing the safety and efficacy of once-weekly fluconazole (150, 300, and 450 mg) to placebo in the treatment of distal subungual onychomycosis of the fingernails caused by dermatophytes. The relationship between fluconazole concentrations and efficacy was also examined. METHODS: Pharmacokinetic studies were performed by means of plasma and fingernail samples from 133 patients, a subset of 349 patients participating in a double-blind, placebo-controlled clinical trial of fluconazole administered in once-weekly doses of 150, 300, or 450 mg until cure of onychomycosis or for a maximum of 9 months. Blood and fingernail samples for pharmacokinetic analysis were taken at baseline, at week 2, and at monthly intervals during the treatment phase of the study. Patients considered clinically cured or improved also participated in a 6-month follow-up study. During this phase, patients were monitored and samples taken every 2 months. RESULTS: Significant amounts of fluconazole were detected in the earliest fingernail samples taken (after 2 weeks of treatment). After two weekly doses, 30% to 33% of steady-state concentrations had been achieved in healthy nails and 22% to 29% in affected nails. Steady state was achieved in 3 to 5 months. Fluconazole concentration in nails as well as plasma followed dose-proportional pharmacokinetics. Nail:plasma ratios in affected nails were 0.4 to 0.6 at 2 weeks and 1.7 to 1.8 at 6 months. Fluconazole concentrations fell slowly after drug discontinuation and were still detectable 4 months after end of treatment. A statistically significant correlation was found between steady-state concentration and clinical and global outcomes. CONCLUSION: Fluconazole rapidly penetrates the fingernail, where it is retained at detectable levels for at least 4 months after drug discontinuation. A significant correlation exists between fluconazole concentration in the fingernails and clinical and global outcomes.

Adult↗
PubMed1997

A common core for binding single-stranded DNA: structural comparison of the single-stranded DNA-binding proteins (SSB) from E. coli and human mitochondria.

The crystal structure of the DNA-binding domain of E. coli SSB (EcoSSB) has been determined to a resolution of 2.5 A. This is the first reported structure of a prokaryotic SSB. The structure of the DNA-binding domain of the E. coli protein is compared to that of the human mitochondrial SSB (HsmtSSB). In spite of the relatively low sequence identity between them, the two proteins display a high degree of structural similarity. EcoSSB crystallises with two dimers in the asymmetric unit, unlike HsmtSSB which contains only a dimer. This is probably a consequence of the different polypeptide chain lengths in the EcoSSB heterotetramer. Crucial differences in the dimer-dimer interface of EcoSSB may account for the inability of EcoSSB and HsmtSSB to form cross-species heterotetramers, in contrast to many bacterial SSBs.

Crystallography, X-Ray↗
PubMed1997

Skewed T-cell receptor Vbeta8.2 expression in transgenic CD2-myc induced thymic lymphoma: a role for antigen stimulation in tumour development?

Transgenic mice expressing the c-myc proto-oncogene under the control of the CD2-dominant control region show stochastic development of mainly clonal thymic lymphoma with long latency, indicating that cooperative events are needed for the development of the fully malignant phenotype. Previous studies have suggested that T-cell receptor-associated signals can contribute to tumour development. We have therefore used this transgenic model of T-cell transformation to determine whether antigen-specific responses could constitute an epigenetic event in lymphomagenesis. The T-cell receptor (TcR) repertoires of lymphoma clones were analysed with a panel of monoclonal antibodies (Abs) recognizing TcR Vbeta chains. The Vbeta repertoire of tumour clones arising in these mice was non-random with overrepresentation of Vbeta8.2 TcR species. The majority of Vbeta8.2+ clones were of a mature CD3+ CD8 single-positive (SP) phenotype. The biased TcR usage, together with a mature cell phenotype is consistent with the hypothesis that TcR-mediated signals cooperate with activated myc during T-cell transformation.

Animals↗
PubMed1997

Specific flavonoids promote intercellular root colonization of Arabidopsis thaliana by Azorhizobium caulinodans ORS571.

The ability of Azorhizobium caulinodans ORS571 and other diazotrophic bacteria to internally colonize roots of Arabidopsis thaliana has been studied. Strains tagged with lacZ or gusA reporter genes were used, and the principal colonization sites were found to be the points of emergence of lateral roots, lateral root cracks (LRCs). High frequencies of colonization were found; 63 to 100% of plants were colonized by ORS571, and 100% of plants were colonized by Herbaspirillum seropedicae. After LRCs were colonized, bacteria moved into intercellular spaces between the cortical and endodermal cell layers. Specific flavonoids, naringenin and daidzein, at 5 x 10(-5) M, significantly promoted colonization by ORS571. By using a nodC and a nodD mutant of ORS571, it was shown that neither Nod factors nor NodD are involved in colonization or flavonoid stimulation of colonization. Flavonoids did not appear to be stimulating LRC colonization by their activity as nutritional factors. LRC and intercellular colonization by H. seropedicae was stimulated by naringenin and daidzein at the same concentration that stimulated colonization by ORS571.

Arabidopsis↗
PubMed1994

Collateral growth between left internal mammary and left anterior descending coronary arteries following coronary artery bypass surgery.

A case is described in which new collateral vessels grew between the left internal mammary artery and the left anterior descending coronary artery following coronary artery bypass surgery. Collateralization of the coronary arteries by extra-cardiac arteries has not been previously described following bypass surgery and may have implications for the mechanisms of angiogenesis.

Adult↗
PubMed1994

The selenium metabolite selenodiglutathione induces p53 and apoptosis: relevance to the chemopreventive effects of selenium?

Selenodiglutathione (SDG), the initial metabolite of selenite, is shown to be a more powerful inhibitor of cell growth in vitro than selenite itself. This has been established both with mouse erythroleukaemia (MEL) cells and an ovarian cell line (A2780) which is known to contain wild-type p53. Other seleno-compounds, such as selenomethyl selenocysteine (SMS) and dimethyl selenoxide (DMS), which are potent chemopreventive agents and are known to be metabolized to methylated selenium derivatives directly rather than via SDG, are also growth inhibitory to both MEL and A2780 cells, although less so than SDG or selenite. However, cells growth-inhibited by DMS are more viable than cells growth-inhibited to the same extent by SDG or selenite, suggesting that the methylated seleno-compounds may inhibit cell growth in a different manner from that of SDG or selenite. Our studies of the mechanism of growth inhibition by SDG, have established two facts. First, SDG induces p53 protein levels in cells that contain wild-type p53 (A2780 cells), suggesting that SDG induces the DNA damage-recognition pathway. Secondly, SDG induces apoptosis in MEL cells, as judged by flow cytometry and formation of nucleosomal DNA ladders. However, since p53 mutations have been found to be targetted events in all MEL cells examined, our evidence suggests that induction of apoptosis by SDG is not absolutely dependent on the p53 response pathway.

Animals↗
PubMed1994

Allergy to gloves. Case report.

The risk of contracting infectious diseases from patients with either serious or even fatal consequences has led to considerable changes in dental practice in the last few years. A key step in infection control is to prevent contact between the dentist's skin and the patient's blood and saliva by wearing gloves. The practice initially requires some patients and tolerance but then has few disadvantages. This paper reports a case where there were adverse effects to the patient from the dentist wearing gloves.

Aged↗
PubMed1993

A quantitatively controlled method to study prospectively interstitial cystitis and demonstrate the efficacy of pentosanpolysulfate.

A randomized, prospective, double-blind, placebo-controlled study was conducted at 7 clinical centers on 148 patients. Patients received orally either 100 mg. pentosanpolysulfate (a synthetic polysaccharide) 3 times per day or a placebo. Of the patients on drug therapy 32% showed significant improvement compared to 16% of those on placebo (p = 0.01). This study provides a model to assess this disease quantitatively in a prospective manner using a method whereby the patients globally assess their symptoms as either worse or improved by 0, 25, 50, 75 or 100%. Patients on drug therapy also experienced a significant decrease in pain and urgency (p = 0.04 and 0.01) on analogue scales when compared to placebo and also more drug patients showed an average increase of more than 20 ml. in voided volume than did placebo patients (p = 0.02). All adverse effects were minor, with 7 in the drug group and 10 in the placebo group. The results support the concept that some patients with the interstitial cystitis syndrome may have abnormal bladder surface glycosaminoglycans.

Aged↗
PubMed1992

Acute tonsillectomy in the management of infectious mononucleosis.

Life-threatening upper airway obstruction can be caused by tonsillopharyngitis secondary to infectious mononucleosis (IM). The administration of corticosteroids, emergency tracheostomy and acute tonsillectomy have been advocated as ways of managing this problem. In a series of 25 patients admitted over a five-year period with IM, 15 were judged to have symptoms severe enough to warrant the administration of corticosteroids. Six of these 15 patients had little improvement in their condition and thus underwent acute tonsillectomy. There were no significant complications of this surgery. A further three patients who received corticosteroids required tonsillectomy for recurrent tonsillitis later in the study period. By contrast, only one of the ten patients who did not receive corticosteroids subsequently required tonsillectomy. Acute tonsillectomy is of value in selected cases of IM tonsillopharyngitis. It may decrease the morbidity of recurrent tonsillitis after IM, in addition to averting the immediate risk of respiratory obstruction.

Acute Disease↗