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Biomedical subjects

A Winder

Publications and source records attributed to A Winder.

36 records · Page 2Linked to original sources

DHICA oxidase activity of TRP1 and interactions with other melanogenic enzymes.

Tyrosinase-related protein 1 (TRP1) maps to the brown locus in mice. Although the specific function of TRP1 has been in dispute, mutations in its structural gene result in the formation of brown rather than black melanin. We have investigated the melanogenic function of TRP1 by using immune-affinity purification of the protein and also by using transfection of its gene into fibroblasts to study its characteristics. We show that TRP1 has the ability to oxidize DHICA, a melanogenic intermediate derived from DOPAchrome. In addition, TRP1 has the ability to interact with tyrosinase and significantly stabilize the latter's catalytic function.

Animals↗

The tyrosinase gene family--interactions of melanogenic proteins to regulate melanogenesis.

Several genes critical to the regulation of melanin production in mammals have recently been cloned and characterized. They map to the albino, brown, and slaty loci in mice, and encode proteins with similar structures and features, but with distinct catalytic capacities. The albino locus encodes tyrosinase, an enzyme with three distinct melanogenic functions, the brown locus encodes TRP1 (tyrosinase-related protein-1), and the slaty locus encodes TRP2, another tyrosinase related-protein. TRP2 functions as DOPAchrome tautomerase, an enzyme that preserves the carboxylic acid content of melanins, which would be spontaneously lost in its absence, while TRP1 is able to oxidize the DHICA produced by TRP2. In this study we have used three different systems (immune-affinity purified melanogenic enzymes, mutant melanocytes, and transfected cells) to examine the enzymatic interactions of these proteins, and their stabilization in a complex which significantly increases their physiological half-life. When extrapolated to the melanocyte, our results demonstrate the catalytic functions of these proteins and suggest how they might stably interact within a melanogenic complex in the melanosome to regulate the quantity and quality of melanin synthesized.

3T3 Cells↗

The effect of alpha-interferon on thymidine, uridine, and leucine uptake and ultrastructure of peripheral blood mononuclear cells from multiple myeloma patients.

The effect of IFN alpha-2b on thymidine, uridine, and leucine uptake was examined on peripheral blood mononuclear cells (PBMC) of healthy donors and 15 patients with multiple myeloma (MM). In addition, the surface ultrastructure of the cells incubated without or with IFN alpha-2b was examined with a scanning electron microscope. The results showed that IFN had no effect on thymidine, uridine, or leucine uptake of unstimulated MM and control PBMC. On the other hand IFN inhibited thymidine, and uridine uptake of PWM-stimulated MM PBMC, but had no effect on healthy donor stimulated PBMC. IFN inhibited also thymidine and uridine uptake in PHA-stimulated healthy donors and MM patients' PBMC. The cellular surface ultrastructure of MM lymphocytes incubated with 100 u/ml IFN showed disappearance of the microvilli and formation of cellular pits, whereas in healthy donor lymphocytes IFN caused flattening of microvilli.

Aged↗

A combined urodynamic and continence unit--a review of the first 19 years.

We have completed a 19-year audit of all patients referred to the urodynamic/continence unit since its inception in 1972 and their subsequent clinical management; a total of 20,437 patients were referred, increasing from 51 in the first year to 1564 in 1990. Although the annual number of referrals has remained constant for the last 8 years, the need for more complex urodynamic assessment such as video-cystourethrography has increased from 5% (56/1164) in 1981 to 25% (385/1564) in 1990. The number of out-patient attendances to medical, physiotherapy and continence clinics has also increased over that period. We conclude that the number of referrals represents increasing recognition of the value of urodynamic assessment. Accurate diagnosis leads to more effective treatment, whether surgical, medical or conservative. Some methods of diagnosis are complex and suitable only for a tertiary referral centre.

Ambulatory Care↗

Treatment of systemic lupus erythematosus by prolonged administration of high dose intravenous immunoglobulin: report of 2 cases.

Two patients with life threatening manifestations of systemic lupus erythematosus (SLE), unresponsive to corticosteroid and immunosuppressive therapy, were treated with high dose intravenous immunoglobulin (IVIG). Following IVIG therapy, lupus pneumonitis and encephalitis in the first patient, and lupus nephritis in the second patient, resolved. Continuous treatment with IVIG, every 4 weeks for up to 20 months induced a prolonged clinical and laboratory remission. Treatment with cytotoxic agents was stopped, and the dosage of corticosteroids lowered. Exacerbation of lupus nephritis occurred in the second patient after 10 months of IVIG therapy. We suggest that prolonged use of high dose IVIG may be a useful therapy for acute exacerbations of SLE and for inducing prolonged remissions.

Adult↗

Organising a continence advisory service.

Modern surgical techniques have greatly improved the treatment of incontinence, but there remains a large number of patients for whom conservative management will be necessary. This paper reports the appointment of a continence adviser 10 years ago, and describes the subsequent development of a District Continence Advisory Service. Experience has shown that this appointment is essential, not only in terms of facilitating the service, but also as a means of ensuring cost efficiency.

Community Health Nursing↗

Acetazolamide-responsive vestibulocerebellar syndrome: clinical and oculographic features.

Five patients who presented with long-standing episodic vertigo had ocular motor signs localizing to the vestibulocerebellum. In each patient, the episodic vertigo was either abolished or markedly decreased in frequency and severity with acetazolamide therapy. In 4, other family members had identical symptoms and signs. This syndrome is 1 of the few treatable causes of chronic episodic vertigo.

Acetazolamide↗

The persistence of neutralizing antibodies after revaccination against smallpox.

Persistence of neutralizing antibodies after revaccination against smallpox was studied. Single serum samples from 140 revaccinated donors were tested for neutralizing antibodies using the plaque reduction assay. The donors, aged 21-49 years at sampling, had been vaccinated in infancy and revaccinated at 8 and 18 years; they formed seven groups of 20 men each, revaccinated about 3, 5, 10, 15, 20, 25, and 30 years before sampling. The differences in mean titer among groups were insignificant (P greater than .01). The titer significantly decreased during the first 3 years after the revaccination but remained stable for at least 30 years thereafter (geometric mean titer, 10.5; 95% confidence interval, 6.8-16.4). The results suggest that there is probably no need for routine revaccinations beyond the primary and two revaccinations; nevertheless, persons at high risk should be revaccinated regardless of their vaccination status.

Adult↗

Serum gamma-aminobutyric acid (GABA) levels in patients with hepatic encephalopathy.

Serum levels of the potent inhibitory neurotransmitter gamma aminobutyric acid (GABA) were measured in 10 patients with chronic liver disease and hepatic encephalopathy, 11 patients with chronic liver disease and no evidence of hepatic encephalopathy, 7 patients with end-stage renal disease and 11 healthy volunteers. Serum GABA levels were elevated in all 10 patients with hepatic encephalopathy, 5/11 with liver disease and no encephalopathy and 4/7 renal disease patients. The mean serum GABA level for the encephalopathic patients (0.92 +/- 0.13 microM, mean +/- SEM) was significantly greater than the mean for liver disease patients without encephalopathy (0.48 +/- 0.05 microM, p less than 0.05), renal disease patients (0.46 +/- 0.04 microM, p less than 0.05) and healthy volunteers (0.39 +/- 0.03 microM, p less than 0.001). These results would tend to support the hypothesis that GABA may play a role in the pathogenesis of hepatic encephalopathy.

Ammonia↗

Secondary prevention and referral of elderly patients to a cardiovascular lipid service.

The burden of cardiovascular disease in the elderly has increased interest in lipid profiles which retain associations with outcome except at extreme age and for which management has benefits at least in secondary prevention. The source, clinical and laboratory background of 90 male and 120 female consecutive referrals age >70 years to a specialist cardiovascular lipid service have been analysed. Main sources were vascular surgery 47%, cardiology 9% and general practice 41% with 6% referred through routine health checks. Presenting lipids (mM: mean+/-S.D.) were: males: cholesterol 6.9+/-1.7, triglycerides 2.3+/-1.5, HDL 1.2+/-0.3; females: cholesterol 7.8+/-1.4, triglycerides 2.1+/-1.3, HDL 1.5+/-0.5, consistent with greater awareness of lipid-related problems in males but significant vascular disease in females. Secondary lipemia was defined in 131/210, 62.3% of patients (83 recognised before clinic presentation, 48 found at follow-up, mainly diabetes). Significant vascular disease was identified in 166/210 patients, significant other risk factors in another 35 patients. Levels of lipoprotein(a) were widely distributed for all groups, but elevated against population profiles for all groups with vascular disease. Referrals were monitored and not routinely accepted: reassuringly most then accepted were justified through atheroma-related disease and opportunities for secondary prevention, with little additional burden through untargeted routine health checks. Recognition of and management of secondary lipemia and obesity were however incomplete.

Journal Article↗

High-dose dexamethasone for splenectomy in patients with idiopathic thrombocytopenic purpura.

High-dose intravenous immune globulin (IV IgG) is currently the treatment of choice for patients with idiopathic thrombocytopenic purpura (ITP) who undergo splenectomy; however, this treatment is extremely expensive. We report on 13 ITP patients with severe thrombocytopenia (<20 x 10(9)/l) who were prepared for laparoscopic splenectomy with a 4-day oral course of high-dose (40 mg/day) dexamethasone (DEX). Four patients had an excellent response with platelet counts that increased to above 150 x 10(9)/l. Seven patients had a good response with a platelet count that increased to between 50 and 150 x 10(9)/l (median 121 x 10(9)/l). Two patients were resistant both to DEX and IV IgG. The operation was uneventful in all the patients, including the 2 who had resistant ITP and were operated on while their platelet count was very low (5 x 10(9)/l). Thus, high-dose DEX, which is an easy, effective and inexpensive treatment, is recommended for the preparation of ITP patients prior to splenectomy.

Administration, Oral↗

Indwelling catheters: practical guidelines for catheter blockage.

Catheterization is a medical decision and requires a team approach involving, where possible, the patient and carer, as well as those professionals administering care. Catheterization and subsequent effective catheter drainage is associated with many dangers and complications (Lowthian, 1998) and therefore the decision to catheterize someone should not be taken lightly. Catheterization should only be used in intractable incontinence when all other measures have been tried and proven to be ineffective. This article identifies some of the problems associated with the care of patients with indwelling catheters in the community setting, and examines the issues that can cause pain, distress and discomfort to patients. It looks at the various types of solutions to problems associated with catheterization. Case histories are used to illustrate the types of patients who may have been catheterized. It is hoped that nurses can learn from these examples, so that they will not only cope more effectively with these individuals, but also observe their own practice when initiating indwelling catheterization and developing care packages.

Aged↗

Devising an effective general nursing continence assessment tool.

Incontinence assessment forms are routinely used by nurses in order to implement the appropriate management, treatment and referral of patients suffering from bladder dysfunction. A thorough literature search using recognized databases revealed that no specific work has been carried out in respect of validating symptom scoring assessment tools for nurses. Validated symptom scores are available but these are generally used within specific areas of medicine, e.g. prostatic screening incorporates lower urinary tract symptom scores, and physiotherapy, to measure pelvic floor tone. This article examines the need for validity and symptom scoring within a general nursing incontinence assessment tool.

Documentation↗

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Humans↗