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Biomedical subjects

V Marshall

Publications and source records attributed to V Marshall.

At least 19 recordsLinked to original sources
PubMed2006

Safety profile of repaglinide as used in general practice in England: results of a prescription-event monitoring study.

Repaglinide is a prandial glucose regulator indicated for management of type 2 diabetes. This post-marketing study used the observational cohort technique of prescription-event monitoring (PEM) to monitor safety of repaglinide prescribed in primary care in England. Patients were identified from dispensed prescriptions issued by general practitioners (GPs) between December 1998 and January 2001. Demographic and clinical event data were collected from questionnaires posted to GPs at least six months after the date of first prescription for each patient. The cohort consisted of 5731 patients [median age 60 (IQR 51-68), 49.9% male]. Event incidence densities (IDs) [no. 1st reports/1000 patient-months of exposure] were calculated for all events reported. The most frequently recorded clinical events in the first month were diarrhoea (ID(1) 10.3), malaise/lassitude (ID(1) 8.1) and nausea/vomiting (ID(1) 7.9). The most frequently reported reason for stopping was 'not effective' (647), with the most common clinical reasons being diarrhoea (60), malaise/lassitude (55) and intolerance (54). One hundred and thirteen adverse drug reactions (ADRs) were reported, with the most frequently specified being diarrhoea (10), abdominal pain (10) and nausea/vomiting (9). We concluded that repaglinide is generally well tolerated when used in general practice in England and did not identify any serious unrecognised adverse events.

Aged↗
PubMed2001

Biosynthesis, characterisation, and design of bacterial exopolysaccharides from lactic acid bacteria.

Lactic acid bacteria (LAB) are characterised by their conversion of a large proportion of their carbon feed, fermentable sugars, to lactic acid. However, in addition to lactic acid production, the LAB are able to divert a small proportion of fermentable sugars towards the biosynthesis of exopolysaccharides (EPSs) that are independent of the cell surface and cell wall material. These microbial EPSs when suspended or dissolved in aqueous solution provide thickening and gelling properties, and, as such, there is great interest in using EPSs from food grade microorganisms (such as the LAB that are traditionally used for food fermentations) for use as thickening agents. The current review includes a brief summary of the recent literature describing features of the biosynthetic pathways leading to EPS production. Many aspects of EPS biosynthesis in LAB are still not fully understood and a number of inferences are made regarding the similarity of the pathway to those involved in the synthesis of other cell polysaccharides, e.g., cell wall components. The main body of the review will cover practical aspects concerned with the isolation and characterisation of EPS structures. In the last couple of years, a substantial number of structures have been published and a summary of the common elements of these structures is included as is a suggestion for a system for representing structures. A brief highlight of the attempts that are being made to design 'tailor'-made polysaccharides using genetic modification and control of metabolic flux is presented.

Journal Article↗
PubMed2000

Human herpesvirus 8 in Brazilian Amerindians: a hyperendemic population with a new subtype.

Human herpesvirus 8 (HHV-8) epidemiology in Brazilian Amerindians was studied. Use of an immunofluorescence (IFA) test for latent antibody demonstrated that the prevalence of HHV-8 in 781 Amerindians of diverse tribes (overall, 53% prevalence) was not related to language group or sex but rather increased gradually from 41% in children <10 years of age to 65% in adults >/=30 years of age. In IFA-positive subjects, HHV-8 DNA was detected in 3 (16%) of 19 mononuclear cell samples from peripheral blood and in 1 of 16 saliva samples. The sequences of conserved ORF22 and K6 genes were typical of HHV-8, but the variable K1 gene sequences were only 70%-75% identical to other known HHV-8 strains. Thus, a new HHV-8 subtype, E, is hyperendemic in Brazilian Amerindians, although Kaposi's sarcoma has not been reported. Transmission is probably oral rather than sexual. The limited genetic pool in isolated groups may permit more frequent transmission of a virus with a low prevalence in heterogeneous populations.

Adolescent↗
PubMed2000

Activity of thalidomide in AIDS-related Kaposi's sarcoma.

PURPOSE: To assess the toxicity and activity of oral thalidomide in Kaposi's sarcoma (KS) in a phase II dose-escalation study. PATIENTS AND METHODS: Human immunodeficiency virus (HIV)-seropositive patients with biopsy-confirmed KS that progressed over the 2 months before enrollment received an initial dose of 200 mg/d of oral thalidomide in a phase II study. The dose was increased to a maximum of 1,000 mg/d for up to 1 year. Anti-HIV therapy was maintained during the study period. Toxicity, tumor response, immunologic and angiogenic factors, and virologic parameters were assessed. RESULTS: Twenty patients aged 29 to 49 years with a median CD4 count of 246 cells/mm(3) (range, 14 to 646 cells/mm(3)) were enrolled. All patients were assessable for toxicity, and 17 for response. Drowsiness in nine and depression in seven patients were the most frequent toxicities observed. Eight (47%; 95% confidence interval [CI], 23% to 72%) of the 17 assessable patients achieved a partial response, and an additional two patients had stable disease. Based on all 20 patients treated, the response rate was 40% (95% CI, 19% to 64%). The median thalidomide dose at the time of response was 500 mg/d (range, 400 to 1,000 mg/d). The median duration of drug treatment was 6.3 months, and the median time to progression was 7.3 months. CONCLUSION: Oral thalidomide was tolerated in this population at doses up to 1,000 mg/d for as long as 12 months and was found to induce clinically meaningful anti-KS responses in a sizable subset of the patients. Additional studies of this agent in KS are warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Comparison of UW solution and St. Thomas' solution in the rat: importance of potassium concentration.

BACKGROUND: University of Wisconsin solution (UW) is in limited clinical use for heart transplantation, but there are doubts about its efficacy and concerns about the effect of its high K+ concentration on endothelium. St. Thomas' solution with or without aspartate is widely used and is of proven efficacy. METHODS: Using a modified (starch-free) variant of UW (MUW) we studied: (1) recovery of function with UW compared with aspartate-containing St. Thomas' solution; (2) effect of elevation of K+ in St. Thomas' solution to the level in UW; and (3) effect of reduction of K+ in UW and addition of Ca2+ or aspartate. Isolated rat hearts underwent 7 hours of arrest at 1 degrees C using MUW with or without 20 mmol/L aspartate or using aspartate-containing St. Thomas' solution. RESULTS: Functional recovery with MUW (51.8% +/- 2.5%) was superior to that with aspartate-containing St. Thomas' solution (37.1% +/- 4.3%; p < 0.01). Addition of aspartate to MUW had no effect. During 6 hours of arrest, lowering the K+ in MUW from 125 mmol/L to 20 mmol/L reduced functional recovery from 59.9% +/- 4.2% to 42.3% +/- 4.3% (p < 0.01). The addition of 1 mmol/L Ca2+ had no effect. Elevation of K+ in St. Thomas' solution produced more rapid arrest but no improvement in recovery. CONCLUSIONS: The protective effect of starch-free UW is greater (+13%) than that of aspartate-enriched St. Thomas' solution. Reduction of K+ in UW to lessen possible deleterious effects would decrease its protective effect by about 30% to a level comparable with that of St. Thomas' solution.

Animals↗
PubMed1996

Bilateral orchidectomy and flutamide versus orchidectomy alone in newly diagnosed patients with metastatic carcinoma of the prostate--an Australian multicentre trial.

OBJECTIVES: To investigate the hypothesis that maximal androgen blockade improves the outcome of patients with metastatic prostate cancer. PATIENTS AND METHODS: A total of 222 previously untreated patients with metastatic prostatic cancer were entered into a randomized, double-blind, placebo-controlled trial of bilateral orchidectomy with or without androgen blockade (112 receiving flutamide and 110 a placebo) which commenced in 1985 in four Australian centres. The characteristics of the patients, e.g. age, performance status, the presence of bone pain, duration of disease and the use of prior radiation, were well balanced between the groups. Patients commenced the protocol therapy with flutamide or placebo within the 7 days preceding surgery and continued this medication for a minimum of 2 years, unless there was unequivocal evidence of tumour progression. RESULTS: Apart from a difference in grade 3 or 4 gastrointestinal toxicities between the flutamide and placebo arms (13% and 3%, respectively), serious or life-threatening toxicities were uncommon and equally balanced. The assessment of response in six patients (three in each arm) was inevaluable. The objective response rates were 45% and 56% in the flutamide and placebo arms, respectively. There was no difference in survival between the treatments. CONCLUSIONS: This study was not sufficiently powerful to detect small differences in outcome (although the trend in survival favoured the placebo arm) but nevertheless failed to show any benefit for maximal androgen blockade over orchidectomy in this group of patients.

Aged↗
PubMed1994

Plasmodium falciparum: extensive polymorphism in merozoite surface antigen 2 alleles in an area with endemic malaria in Papua New Guinea.

Plasmodium falciparum: Extensive polymorphism in merozoite surface antigen 2 alleles in an area with endemic malaria in Papua New Guinea. Experimental Parasitology 79, 106-116. The prevalence of Plasmodium falciparum in 304 individuals from two villages in Papua New Guinea has been determined by PCR amplification of the gene encoding the merozoite surface antigen 2 (MSA2). Forty-seven percent of the blood samples were positive for P. falciparum. The MSA2 alleles of this parasite population were characterized by PCR-RFLP genotyping. In 144 P. falciparum infections 38 different MSA2 alleles were found. The most common allele (22%) was a variant of FC27. Further alleles, found in the study area, were IC1, KF1916, and MAD71. In addition to these previously described alleles, 33 novel variant forms of MSA2 were detected, most of which were represented at very low frequency in the study population. MSA2 genotyping of a local P. falciparum population revealed an unexpected amount of genetic heterogeneity. The diversity is mostly due to variation in the repeat region resulting in length polymorphism that can be easily detected by PCR-RFLP.

Adolescent↗
PubMed1992

Psychologic distress during the menopausal years in women attending a menopause clinic.

OBJECTIVE: This study measures psychologic distress in women attending a menopause clinic to determine if significant differences exist between peri-menopausal and menopausal women. METHOD: Consecutive women attending a university hospital menopause clinic were administered the Brief Symptom Inventory (BSI) and a study questionnaire to determine menopausal symptoms, menstrual cycle status, and use of hormone replacement therapy (HRT). The BSI results were compared between menopausal and perimenopausal women, and to a normative sample of middle-aged women who were nonpatients. RESULTS: Two hundred and fifty-nine menopause clinic women completed the questionnaire: 113 perimenopausal and 146 menopausal women. There was significantly greater psychologic distress on the BSI among perimenopausal as compared to menopausal women on the global severity index, and each of the anxiety, hostility, somatization, depression, paranoid, and psychoticism subscales. Perimenopausal women met BSI caseness severity criteria significantly more often than did menopausal women on the global severity index, and on the subscales for depression, anxiety, and psychoticism. On the BSI, menopausal women showed results similar to those of a normative sample of nonpatient middle-aged women. CONCLUSIONS: Perimenopausal women attending menopause clinics have significantly higher levels of psychologic distress meeting case severity criteria on the BSI. Further research is warranted to define the subgroups of perimenopausal women who are at increased risk, in the hopes of developing effective interventions.

Adaptation, Psychological↗
PubMed1989

The influence of Org 10172, an antithrombotic heparinoid, on urinary blood loss after transurethral prostatectomy.

We have measured the effects of Org 10172 (a mixture of naturally occurring glycosaminoglycans derived from hog intestinal mucosa) on blood loss after transurethral prostatectomy (TURP), using doses which are likely to prevent postoperative venous thrombosis (VT). 48 patients entered a double-blind randomised pilot study: 18 were given subcutaneous (sc) injections of a placebo and 30 received sc Org 10172 (750 anti-Xa units/day, 500 units twice daily (bid), or 750 units bid, starting just before TURP and continued until discharge; 10 patients per group). No Org 10172 regimen increased peroperative blood loss but all caused a similar trend towards increased urinary bleeding after surgery. Since there was no apparent dose effect gradient, it was decided to pool the data from all three dosing blocks: this analysis showed that Org 10172 increased geometric mean blood loss during the first 2 days after surgery from 10.4 gm hemoglobin (Hgb; range = 3.2-71) to 20.5 gm Hgb (range = 1.9-147) (p = .005), an effect which retained its significance after allowing for two other major determinants of postoperative bleeding, the weight of prostate resected and the length of surgery, and also when pooling was restricted to the twice daily Org 10172 injection groups and their corresponding controls. Bleeding was not severe, but our results indicate a need for caution when considering the use of Org 10172 in this setting.

Aged↗
PubMed1989

An examination of loneliness among elderly Canadian seasonal residents in Florida.

As part of a larger study focusing on different facets of the lives of 2,731 older Canadians who seasonally reside in Florida, we investigated primarily the extent of family and friendship contacts and the loneliness expressed by these older Canadians. The data were collected using a questionnaire that was distributed and returned by mail. The sample was taken from the subscription list of a newspaper in Florida that was a subsidiary of a large Canadian newspaper. The results show a population that was relatively young, married, in generally good health, and with rather extensive contacts with family and friends while residing in Florida. Nevertheless, more than a fifth indicated they were at least somewhat lonely. Results, using discriminate function analysis, showed that those more lonely were younger, female, less educated, not married, in poorer physical health, had fewer Florida friends, and had more children who lived near them in Canada, but fewer children who lived near them in the United States. Implications of the results are discussed.

Age Factors↗
PubMed1988

Multiple sclerosis is a chronic central nervous system infection by a spirochetal agent.

Multiple Sclerosis (MS) is a chronic central nervous system (CNS) infection similar to Lyme Disease or Neurosyphilis in its latency period, pathogenesis, symptoms, histopathology and chronic CNS involvement. It does not have as yet a fully identified spirochetal etiological agent. Much research and clinical support for this hypothesis was published before 1954 and is based on silver staining of neural lesions, animal isolation of the etiologic agent and the characteristic symptoms and pathogenesis of the disease. If this hypothesis is correct, the disease should be treatable with antibacterial agents that penetrate the CNS (such as high dose antibiotics), diagnosible by specific immunological tests, and preventable by early treatment or by the use of vaccines in high risk populations.

Animals↗