Search PubMed⌕ Search

Biomedical subjects

A Watson

Publications and source records attributed to A Watson.

At least 163 records · Page 9Linked to original sources

Terbinafine in onychomycosis of the toenail: a novel treatment protocol.

BACKGROUND: Current treatment of onychomycosis of the toenail is poor and relapse is common. OBJECTIVE: Our purpose was to assess the efficacy and safety of oral terbinafine and placebo in onychomycosis of the toenail with the use of a novel treatment protocol. METHODS: This was a randomized, double-blind, 48-week study. Twelve weeks of terbinafine (250 mg daily) or placebo was followed by 12 weeks of observation. Responders received no further treatment and nonresponders were offered 12 weeks of terbinafine (250 mg daily) from week 28. RESULTS: Of 111 evaluable patients, 88% (49 of 56) of the patients given terbinafine and 29% (16 of 55) of the patients given placebo had a negative mycologic culture at week 24 (p < 0.001), 57% (32 of 56) of the terbinafine group and 6% (3 of 55) of the placebo group were responders (p < 0.001). By week 48, after the terbinafine nonresponders were given a second 12-week course of terbinafine, the overall mycologic cure rate for the patients given terbinafine was 94%. CONCLUSION: High mycologic cure rates in onychomycosis of the toenail can be achieved by terbinafine by this novel treatment regimen.

Adolescent↗

Persistent infection of macaques with simian-human immunodeficiency viruses.

Chimeric simian-human immunodeficiency viruses (SHIV) containing the human immunodeficiency virus type 1 (HIV-1) tat, rev, env, and, in some cases, vpu genes were inoculated into eight cynomolgus monkeys. Viruses could be consistently recovered from the CD8-depleted peripheral blood lymphocytes of all eight animals for at least 2 months. After this time, virus isolation varied among the animals, with viruses continuing to be isolated from some animals beyond 600 days after inoculation. The level of viral RNA in plasma during acute infection and the frequency of virus isolation after the initial 2-month period were higher for the Vpu-positive viruses. All of the animals remained clinically healthy, and the absolute numbers of CD4-positive lymphocytes were stable. Antibodies capable of neutralizing HIV-1 were generated at high titers in animals exhibiting the greatest consistency of virus isolation. Strain-specific HIV-1-neutralizing antibodies were initially elicited, and then more broadly neutralizing antibodies were elicited. env sequences from two viruses isolated more than a year after infection were analyzed. In the Vpu-negative SHIV, for which virus loads were lower, a small amount of env variation, which did not correspond to that found in natural HIV-1 variants, was observed. By contrast, in the Vpu-positive virus, which was consistently isolated from the host animal, extensive variation of the envelope glycoproteins in the defined variable gp120 regions was observed. Escape from neutralization by CD4 binding site monoclonal antibodies was observed for the viruses with the latter envelope glycoproteins, and the mechanism of escape appears to involve decreased binding of the antibody to the monomeric gp120 glycoproteins. The consistency with which SHIV infection of cynomolgus monkeys is initiated and the similarities in the neutralizing antibody response to SHIV and HIV-1 support the utility of this model system for the study of HIV-1 prophylaxis.

Acquired Immunodeficiency Syndrome↗

Nebulised amiloride in respiratory exacerbations of cystic fibrosis: a randomised controlled trial.

OBJECTIVE: To assess the benefit of nebulised amiloride added to the standard inpatient treatment of a respiratory exacerbation in cystic fibrosis. DESIGN: Prospective, randomised, double blind, placebo controlled trial. SUBJECTS: 27 cystic fibrosis patients (mean age 12.8 years). SETTING: Two hospitals in Leeds, UK. RESULTS: Both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) showed improvements over the course of treatment, although there was no difference in respiratory function between the two groups at any of three time periods during the study. The time to reach peak FVC was significantly reduced in the amiloride group (4.2 v 7.6 days; 95% CI 0.4 to 6.4 days), but not in the time to reach peak FEV1 (5.7 v 7.9 days; 95% CI -1.2 to 5.6 days). CONCLUSIONS: Amiloride did not result in a greater overall improvement in respiratory function. There was a suggestion that it may have an effect on the rate of improvement, and thus may possibly influence the duration of treatment. This hypothesis deserves further evaluation.

Adolescent↗

Prospects for the secondary prevention of colorectal cancer: screening by flexible sigmoidoscopy?

It may be useful to draw an analogy between the proposed screening programme for colorectal cancer and the cervical cancer screening programme. Both tumours show a spectrum of histological abnormalities consistent with a premalignant phase. The natural history of these premalignant lesions is poorly understood and although some will progress, if untreated, to invasive disease, most will not. Light microscopy cannot confidently distinguish which cases will progress and which will regress, and clinicians are therefore obliged to treat all. This will result in the destruction of many lesions of uncertain malignant potential. The secondary prevention of cervical cancer, although therapeutically efficacious, is inefficient. A lack of understanding of the natural history of intraepithelial neoplasia has frustrated attempts to develop rational referral criteria, and it is only now that the appropriate trials are being undertaken. The development of outpatient investigative and therapeutic procedures has resulted in many more women being referred for investigation and treatment, with predictable pressure on other services offered by gynaecologists, but no demonstrable saving of life. Similar uncertainties surround a screening programme for colorectal cancer. The principal concerns are not about the efficacy of polypectomy in interrupting the polyp cancer sequence, although uncertainties about the frequency with which cancer arises de novo do require that the effectiveness of this intervention is formally tested. Our major concerns are with compliance, and the management of the individual who tests positive--that is, who is found to have a distal polyp. Technological advances and operator enthusiasm may, as has happened with the cervical screening programme, lead to a relaxation in the indications for further investigation and treatment. Such a development would affect resources substantially if a population screening programme were in place. Nevertheless, there are grounds for believing that a screening programme for colorectal cancer, using sigmoidoscopy, might be successful in certain age groups if compliance was satisfactory. The scale of benefits may be comparable with those achieved by the breast screening programme. Our limited cost analysis, which relates to only to specific items of clinical activity, suggest that the mean cost for each case of cancer prevented will be about 8000 pounds sterling. These conclusions suggest that screening by flexible sigmoidoscopy merits serious consideration. It is also imperative, however, that consideration should be given to resolving some of the uncertainties about the clinical management and surveillance of those found to have distal polyps.

Age Factors↗

Recovery of human immunodeficiency virus from peritoneal dialysis effluent.

Increasing numbers of HIV-infected patients who have ESRD are being treated with continuous ambulatory peritoneal dialysis (CAPD). To investigate the potential infectious nature of peritoneal dialysate (PD), the peritoneal dialysis effluent was studied in 14 patients on CAPD who were known to be HIV antibody positive. Peripheral blood mononuclear cells and the sediment of PD were obtained from each patient and subjected to a qualitative microculture assay using a coculture of patient cells or PD fluid with peripheral blood mononuclear cells from non-HIV-infected individuals. Samples from the coculture were collected twice weekly for HIV P24 antigen determination as a marker of viral replication. PD, white blood cell and red blood cell counts, and peripheral blood CD4 lymphocyte counts were also measured. All 14 patients developed a positive blood culture by Day 3. Twelve of the 14 patients developed a positive PD fluid culture. The mean CD4 count was 310 cells/mm3. No patient had clinical or cellular evidence of peritonitis at the time of fluid sampling. These data indicate that peritoneal dialysis effluent from patients who are HIV antibody positive is potentially infectious.

Adult↗

Calcium promotes membrane association of reticulocyte 15-lipoxygenase.

The reticulocyte 15-lipoxygenase (linoleate:oxygen oxidoreductase, EC 1.13.11.12) is implicated in oxidative damage to reticulocyte mitochondria before their elimination by degradation during maturation to the erythrocyte. A proportion of the 15-lipoxygenase sediments with the mitochondrial-rich stromal fraction of density-gradient-fractionated rabbit reticulocytes suggesting a physical association with mitochondria before their elimination. Ca2+ promotes binding of reticulocyte 15-lipoxygenase to isolated rat liver and reticulocyte mitochondria and 15-lipoxygenase-mediated lipid peroxidation of mitochondrial lipids and free linoleic acid. Association of reticulocyte 15-lipoxygenase with isolated mitochondria is not simply a consequence of Ca(2+)-induced swelling, but implies that Ca2+ mediates translocation of soluble lipoxygenase to mitochondrial membranes. Therefore, Ca2+ may have an important physiological role in the regulation of 15-lipoxygenase-mediated targeting of reticulocyte mitochondria for degradation.

Animals↗

Properties of putative cardiac and non-cardiac neurones in the rat stellate ganglion.

Intracellular recordings were made from isolated left or right stellate ganglia of Wistar rats and the morphology of neurones studied after intracellular injection of hexammine cobaltic chloride or back-filling from the post-ganglionic nerve with cobalt lysine complex. The experiments attempted to identify the location, electrophysiological properties, morphology and chemosensitivity of putative cardiac neurones in the ganglion. These were identified by antidromic activation of the axon in a cardiac nerve and compared with neurones projecting towards the brachial plexus (non-cardiac neurones). Putative cardiac neurones were localized in the ganglion around the postganglionic nerve entry zone and showed considerable morphological diversity. They had complex dendritic trees with, on average, seven dendrites. They included both phasic and tonic neurones and were depolarized by muscarinic agonists, angiotensin and substance P; they invariably had a synaptic input from the sympathetic trunk and from a T1 or T2 ramus and, in 16% of cells, from a cardiac nerve. Non-cardiac neurones were more widely scattered through the stellate ganglion but were not clearly different in morphology, resting membrane potential or the proportion of phasic and tonic cells from putative cardiac neurones. They also showed depolarizing responses to muscarinic agonists, angiotensin and substance P. Angiotensin responses of stellate ganglion cells were blocked by the peptide antagonist, saralasin (1 microM).

Action Potentials↗

A meta-analysis of the therapeutic role of oil soluble contrast media at hysterosalpingography: a surprising result?

OBJECTIVE: To evaluate the therapeutic effect of oil-soluble contrast media compared with water-soluble contrast media after hysterosalpingography (HSG) in infertile couples. DESIGN: Meta-analysis of four randomized clinical trials (RCTs) and six nonrandomized controlled studies evaluating pregnancy rates after the use of oil- or water-soluble contrast media during HSG. SETTING: Institute of Epidemiology and Health Services Research, Leeds, United Kingdom. PATIENTS: Four identified RCTs studied 800 patients and six nonrandomized studies comprised an additional 1,806 patients, all experiencing primary or secondary infertility. INTERVENTION: Hysterosalpingography as part of infertility investigation. MAIN OUTCOME MEASURE: Pregnancy rates after HSG. RESULTS: Pregnancy rates were significantly higher in the oil-soluble contrast media group compared with the water-soluble contrast media group in the RCTs. Inclusion of the six nonrandomized studies did not alter this conclusion. This apparent benefit was greatest for patients with unexplained infertility. CONCLUSIONS: Oil-soluble contrast media have a therapeutic effect compared with water-soluble media and this effect is greatest for patients who have been diagnosed as having unexplained infertility. New techniques for the evaluation of tubal patency support the hypothesis that tubal "plugs" may be involved in proximal tubal blockage.

Clinical Trials as Topic↗

Public health medicine training and the NHS changes.

The current round of mergers between Health Authorities and Family Health Service Authorities (FHSAs), when set in the competitive context of markets, has profound implications for training in Public Health Medicine. This paper considers the phases in the management of change and the costs, benefits and principles for trainers, trainees and organisations as mergers take place. Particular emphasis is placed on understanding the motives of and learning from the change that is taking place.

Health Facility Merger↗

Information on which to base assessments of risk from environments contaminated with anthrax spores.

Although there has been a considerable amount of research conducted into Bacillus anthracis, the causative agent of anthrax, the data are widely disseminated in the scientific literature and are therefore not always easy to assimilate. In view of continuing concern about potential anthrax contamination in environmental materials and sites, this review brings together the currently available information relating to the health hazards from B. anthracis. The relevance of the available information for risk assessment purposes is assessed.

Animals↗

A comparison of amethocaine cream with lignocaine-prilocaine cream (EMLA) for reducing pain during retrobulbar injection.

A prospective, randomised, double-masked, placebo-controlled study was carried out on 169 patients undergoing cataract extraction to compare the topical anaesthetic cream amethocaine with EMLA (eutetic mixture of local anaesthetic, lignocaine and prilocaine) and placebo in reducing pain during retrobulbar injection. Fifty-eight patients received EMLA, 55 amethocaine and 56 the placebo. The pain was assessed objectively by the anaesthetist and subjectively by the patient. Significantly lower pain scores were observed in those patients who had amethocaine (p < 0.001) or EMLA (p < 0.005) in comparison with those who had placebo, but there was no statistical difference between amethocaine and EMLA (p > 0.1; t-test). No systemic or local side-effects were encountered in any group.

Aged↗

Cholecystokinin (CCK)-HIDA scintigraphy in patients with suspected gall-bladder dysfunction.

Cholecystokinin hepatobiliary (CCK-HIDA) scintigraphy is used to triage patients with chronic abdominal pain and suspected gall-bladder dysfunction. This study evaluates the predictive value of CCK-HIDA for clinical outcome after surgical and medical therapy. Fifty-six patients (45 females), mean age 43 +/- 9 years, with otherwise normal investigations, including normal ultrasound, fasted for more than 8h and then had 70MBq technetium-99m-EHIDA injected. One and a half hours later 15 ng/kg CCK was infused over 45 min. Seventy minutes dynamic imaging commenced 5 min prior to infusion. An abnormal gall-bladder ejection fraction (GBEF) was defined as < 50%. Patients were treated medically, or by cholecystectomy, depending on the surgeon's overall assessment, including results of the CCK-HIDA study. Patient status was then obtained in 51/56 patients at least 3 months after the scan or at least 1 month after surgery. All surgical specimens were reviewed independently for pathological changes of chronic acalculous cholecystitis. Of the 11 patients with an abnormal gall-bladder ejection fraction, nine (82%) underwent cholecystectomy, all of whom achieved total symptomatic cure, while two patients underwent other therapy, both of whom remained symptomatically unchanged. Of the 40 patients whose gall-bladder ejection fraction was normal, only five (12.5%) underwent cholecystectomy, of whom four were cured and one partially improved at follow up. Of the 35 patients with a normal gall-bladder ejection fraction and who underwent forms of therapy other than cholecystectomy, nine were cured symptomatically, 13 improved, 10 remained unchanged and three were symptomatically worse at follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Spontaneous intramural haematoma of the oesophagus: a report of three cases and review of the literature.

Spontaneous intramural haematoma of the oesophagus is an uncommon condition which may follow rapid increases in intra-oesophageal pressure and is predisposed to by coagulation disorders. The characteristic clinical presentation and findings at radiology and endoscopy frequently result in misdiagnosis and confusion with more sinister pathology. Awareness of the condition and conservative treatment with correction of coagulation abnormalities, when present, are the mainstays of management. Spontaneous resolution invariably occurs, and the condition is rarely fatal unless surgical treatment is attempted.

Aged↗