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Biomedical subjects

J Fletcher

Publications and source records attributed to J Fletcher.

At least 145 records · Page 8Linked to original sources

Resistance of Spiroplasma citri Lines to the Virus SVTS2 Is Associated with Integration of Viral DNA Sequences into Host Chromosomal and Extrachromosomal DNA.

Spiroplasmavirus SVTS2, isolated from Spiroplasma melliferum TS2, produces plaques when inoculated onto lawns of Spiroplasma citri M200H, a derivative of the type strain Maroc R8A2. S. citri strains MR2 and MR3, originally selected as colonies growing within plaques on a lawn of M200H inoculated with SVTS2, were resistant to SVTS2. Genomic DNA fingerprints and electrophoretic protein profiles of M200H, MR2, and MR3 were similar, but three proteins present in M200H were missing or significantly reduced in both resistant lines. None of these three polypeptides reacted with antiserum against S. citri membrane proteins, indicating that they probably are not surface-located virus receptors. Electroporation with SVTS2 DNA produced 1.5 x 10(sup5) transfectants per (mu)g of DNA in M200H but none in MR2 or MR3, suggesting that resistance may result from inhibition of viral replication. The digestion patterns of the extrachromosomal double-stranded (ds) DNA of these lines were similar. Three TaqI fragments of MR2 extrachromosomal DNA that were not present in M200H extrachromosomal DNA hybridized strongly to an SVTS2 probe, and two of these fragments plus an additional one hybridized with the MR3 extrachromosomal DNA, indicating that a fragment of SVTS2 DNA was present in the extrachromosomal ds DNA of MR2 and MR3 but not of M200H. When the restricted genomes of all three lines were probed with SVTS2 DNA, strong hybridization to two EcoRI fragments of chromosomal MR2 and MR3 DNA but not M200H DNA indicated that SVTS2 DNA had integrated into the genomes of MR2 and MR3 but not of M200H. When MR3 extrachromosomal ds DNA containing a 2.1-kb SVTS2 DNA fragment was transfected into M200H, the transformed spiroplasmas were resistant to SVTS2. These results suggest that SVTS2 DNA fragments, possibly integrated into the chromosomal or extrachromosomal DNA of a previously susceptible spiroplasma, may function as viral incompatibility elements, providing resistance to superinfection by SVTS2.

Journal Article↗

Traumatic carotid and vertebral artery dissection in a professional jockey: a cautionary tale.

Jockeys accept bony fractures and soft tissue injuries as occupational hazards. An average National Hunt jockey falls once in ten races with an injury rate of 4.25%. Head injury is a common cause of morbidity and the benefit of helmets is well recognized. Neck injuries are also common and usually musculoskeletal. Although rare, trauma to the neck arteries may go unnoticed yet have catastrophic consequences. Internal tears can allow arterial blood to dissect the layers of the arterial wall and obstruct the lumen. Severe obstruction may lead to cerebral ischaemia and infarction. An appreciation of the early clinical signs caused by this process may allow effective intervention. We report a case which illustrates these points.

Adult↗

Impaired polymorphonuclear neutrophil function in end-stage renal failure and its correction by continuous ambulatory peritoneal dialysis.

The polymorphonuclear neutrophil (PMN) function of 22 patients with end-stage renal failure (ESRF) was studied immediately before and 3 months after starting continuous ambulatory peritoneal dialysis (CAPD) and compared with a control group of healthy normal volunteers. The PMN functions studied were phagocytosis and killing of Staphylococcus epidermidis and respiratory burst activity. The results show that in the presence of normal pooled human serum PMN from patients with ESRF before CAPD treatment phagocytose bacteria normally, but have impaired killing. Before treatment, the PMN from patients with ESRF also showed an increase in both unstimulated and stimulated superoxide anion production. Abnormal PMN function was corrected by CAPD treatment, suggesting the involvement of a dialyzable toxin.

Acridines↗

Relationship between the provision of counselling and the prescribing of antidepressants, hypnotics and anxiolytics in general practice.

BACKGROUND: The provision of counselling in general practice is increasing, despite uncertainty concerning its effectiveness. Furthermore, the relationship between counselling and prescribing of antidepressants, hypnotics and anxiolytics in general practice is not known. AIM: This study set out to assess the relationship between provision of counselling and prescribing of antidepressants, hypnotics and anxiolytics in general practice. METHOD: An observational, cross-sectional study of general practices in Oxfordshire Family Health Services Authority was undertaken. Practices were surveyed on the availability of counselling services. The quantity and cost of prescribing of psychotropic drugs over one year (April 1992 to March 1993) were compared for practices with different levels of counselling provision. RESULTS: Of the 82 (96%) respondents, 74 (90%) referred patients for counselling; of these 74 practices, the highest levels of prescribing, in terms of number of items and net ingredient cost, were seen in those practices that employed a counsellor working on the premises. The lowest levels of prescribing were seen in those practices that referred their patients to a counsellor not working on the practice premises. CONCLUSION: The relationship between the provision of counselling and the level of prescribing of antidepressants, hypnotics and anxiolytics is complex. In this study lower levels of prescribing of these drugs in practices with higher provision of counselling were not observed.

Anti-Anxiety Agents↗

Fair warning.

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Adverse Drug Reaction Reporting Systems↗

Investigating the reliability and validity of the infrared tympanic thermometer: a learning experience.

This series of articles to date has discussed points that readers should be looking for when reading and critiquing a researcher article. This article presents a brief report of a research project investigating the reliability and validity of the infrared tympanic thermometer (ITT) in afebrile subjects. Using four subjects and 40 temperature diads, the ability of the ITT to predict the subjects' temperatures obtained with a mercury thermometer was very poor (regression coefficient = .39). Test-retest reliability using the same data set resulted in an equally poor correlation coefficient (r = .19). A critique of the methodology of the study is provided as a learning experience.

Humans↗

Inhibition of intimal hyperplasia and occlusion in Dacron graft with heparin and low molecular weight heparin.

OBJECTIVE: Intimal hyperplasia (IH) is a significant cause of late prosthetic graft occlusion. The influence of heparin and low molecular weight heparin (LMWH) on IH was studied in a sheep model. EXPERIMENTAL DESIGN: A gelatin sealed Dacron (Gelsoft) interposition vascular graft was placed end to end in sheep carotid artery. Standard heparin (SH) was administered in a dose of 7,500 units twice daily subcutaneously (n = 6). LMWH (enoxaparin) was administered in two dosages, a "low dose" of 2 mg/kg (n = 6) and a "high dose" of 5 mg/kg (n = 6) subcutaneously daily. A control group received a graft but no heparin (n = 6). At one month the animals were sacrificed and the grafts sectioned. An intimal measurement was obtained under light microscopy using an eyepiece graticule from a longitudinally sectioned graft. RESULTS: Controls occluded five grafts of six and recorded a mean intimal thickness of 2,510 micrometres, SH sheep occluded two with a mean thickness of 83 (p < 0.05), low dose enoxaparin sheep had no occlusions with a mean thickness of 73 (p < 0.001) and high dose enoxaparin sheep occluded one with a mean thickness of 225 (p < 0.01). The reduced occlusion rates were significant for the LMWH groups (p = 0.007 for low dose, p = 0.04 for high dose) but not for SH. There were no significant differences between treatment groups with respect to IH. CONCLUSIONS: In this sheep animal study, each of SH and two LMWH dose regimens resulted in a reduction in Dacron vascular graft occlusion rate and the development of IH, with the greatest effect seen in the low dose LMWH group.

Animals↗

Might history repeat itself?

Having recently moved into medical education, after spending many years in teacher education, the writer is struck by some parallels between the positions in which health and education now find themselves: subject to fundamental reform premised upon the creation of a social market and an extension to consumer choice, while discounting professional judgment. The paper analyses the implementation of teacher education reforms in the 1970s and 1980s, against a background of economic constraint. It then considers the recent reversal of those changes, as part of a wider reappraisal of social policy, heavily influenced by ideologies associated with the 'new right', which have underpinned reforms designed, in part, to curtail the traditional independence of professional groups and, in the name of greater accountability to consumers, substitute greater central control. Pre- and Post-Registration Education for health care professionals, now finds itself in a similar position to that which was evident in teacher education, when the writer joined. Since education and health both constitute major areas of social policy, the paper speculates whether the latter will, in the future, follow the same path as that described in relation to the former. In particular the control of the education of health care professionals is seen to be central to their ability to continue to offer reasoned critiques of political initiatives.

Education, Nursing↗

Non-Hodgkin's lymphoma in elderly patients: a phase II study of MCOP chemotherapy in patients aged 70 years or over with intermediate- or high-grade histology.

During the period 1 January 1988 to 31 July 1991, 74 patients were seen with intermediate- or high-grade non-Hodgkin's lymphoma who were aged 70 years or over. Of these 74 patients, 20 were treated with radiotherapy alone, and 46 were judged as suitable for treatment with the chemotherapy regime MCOP (mitoxantrone, cyclophosphamide, vincristine and prednisolone). Involved field radiotherapy (35-40 Gy in 20 fractions over 4 weeks) was given to 14 of the 21 patients with stage IA and IIA disease, and 6 of the 25 patients with stage III and IV disease after completion of chemotherapy. The complete response rate was 63% at the completion of all treatment (6 months), and 39% at 12 months. There were no treatment-related deaths, and the 3-year cause-specific survival was 26% (overall survival 21%). For patients aged 70-75 years, the 3-year cause-specific survival was 34% in comparison to 17% for those patients aged 76-93 years. The chemotherapy was well tolerated by those patients aged 70 years and over, 70% of the patients did not vomit and no patients had significant vincristine neuropathy. There were only four infections associated with neutropenia. All patients completing six cycles had moderate, patchy alopecia. This MCOP regime is suitable for patients aged 70 years and over with intermediate- and high-grade non-Hodgkin's lymphoma. The survival of patients is comparable to that obtained with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) with less apparent toxicity.

Aged↗

Analysis of radiocontrast-induced nephropathy by dual-labeled radionuclide clearance.

RATIONALE AND OBJECTIVES: This study was devised to develop a method of measuring the acute effects of radiocontrast media on renal function and assessing the relationship of the dose of radiocontrast media infused with the incidence of radiocontrast-induced renal failure. In addition, the drug adenosine phosphate-magnesium chloride (ATP-MgCl2) was evaluated as a renoprotective agent. METHODS: Eighteen patients with pre-existing renal impairment, (serum creatinine greater than 133 mumol/L) were randomized to receive a continuous infusion of ATP-MgCl2 or placebo before and during a radiocontrast procedure. Subjects were monitored with daily serum creatinine and with radionuclide renal clearance studies at baseline, during, and 24 hours after the radiocontrast procedure. RESULTS: There was an initial deterioration in renal clearance in the entire study group (from 44.2 +/- 4.6 to 32.6 +/- 3.9 mL/min, P = .001) which was independent of the dose of radiocontrast infused. There was a persistent deterioration in renal clearance only in those who received greater than 135 mL of contrast media (from 48.6 +/- 7.8 to 37.1 +/- 3.9 mL/min, P = .05). There also was an increase in serum creatinine that persisted only in those subjects who received greater than 135 mL of contrast media (230 +/- 27 to 283 +/- 44 mumol/L, P = .01). CONCLUSION: Persistent deterioration in renal function after radiocontrast administration appears to be dose-dependent and is not prevented by the use of ATP-MgCl2. Radionuclide techniques are useful in monitoring acute changes in renal function during radiocontrast procedures and may be of value in assessing renal impairment in future intervention studies.

Acute Kidney Injury↗

Evaluation of the efficacy of a redox agent in the treatment of chronic periodontitis.

A redox dye, methylene blue, was compared with subgingival root surface debridement and sterile water in the treatment of adult periodontitis. Plaque and gingival indices, bleeding on probing, and microbiological samples were obtained at baseline, and at 1, 4, 8 and 12 weeks following treatment. All subjects had matched pockets in each of the 4 quadrants, of 5 mm or more. One treatment consisted of 0.1% methylene blue gel irrigated professionally at 0, 1 and 4 weeks, and by subjects at days in between up to 4 weeks, at chosen sites within a randomly selected quadrant (split-mouth design). A 2nd treatment was sterile water irrigation as above. A 3rd quadrant received subgingival debridement, and sites in the 4th received methylene blue incorporated into a slow-release device of a biodegradable collagen alginate vicryl composite. All sites showed improvements in clinical and microbiological parameters. However, no statistically significant differences between treatment types were found for clinical measurements. Although plaque index tended to increase after week 1, gingival index was reduced, as was the papilla bleeding index. Probing depth reductions were approximately 1.2 mm for all treatments. Microbiological variables showed an increase in cocci and a decrease in motile organisms for all groups, the latter reaching statistical significance for subgingival debridement. The reductions in spirochaetes were significant for subgingival debridement and methylene blue by slow-release. Culture demonstrated an increase in the aerobe:anaerobe ratio for all groups, which was statistically significant initially (weeks 1 and 4) for subgingival debridement. Methylene blue was also effective statistically in improving this ratio, both by irrigation and slow-release (week 4). Methylene blue also significantly reduced the numbers of black-pigmented anaerobes during the trial period, both by irrigation and slow-release, which sterile water and subgingival debridement failed to do. No serious adverse experiences were seen, however, significantly greater morbidity was associated with subgingival debridement. These results clearly demonstrate that in altering the microflora to one that is more compatible with periodontal health, methylene blue treatment is comparable, or even better, than the currently standard treatment of subgingival debridement, and is better tolerated.

Adult↗

Primary and secondary granule release by polymorphonuclear leukocytes exposed to peritoneal dialysis effluent.

Peritoneal dialysis effluent from patients with end-stage renal failure contains a low-molecular-weight solute that inhibits the killing of phagocytosed Staphylococcus epidermidis by polymorphonuclear leukocytes (PMN). This observation has been investigated by using luciginen-enhanced chemiluminescence to measure PMN NADPH oxidase activity, CD11b/CD18 expression and lactoferrin release to measure secondary granule discharge, and cellular levels of beta-glucuronidase (EC 3.2.1.31) to measure changes in primary granules. Peritoneal dialysis effluent had no effect on the loss of intracellular beta-glucuronidase from normal unstimulated PMN or from PMN stimulated with S. epidermidis. It did, however, cause a concentration-dependent (0 to 70%; vol/vol) increase in expression of CD11b/CD18 and NADPH oxidase activity. CD11b/CD18 expression increased over 20 min before starting to plateau. Release of lactoferrin by the same cells demonstrated a strong positive correlation with integrin expression (P < 0.001, Spearman's rank correlation coefficient). When dialysis effluent-treated PMN were stimulated with formyl-methionylleucylphenylalanine, integrin expression, release of lactoferrin, and NADPH oxidase activity were greater than in PMN treated with formyl-methionylleucylphenylalanine alone. Under these conditions, a concentration-dependent increase in CD11b/ CD18 and lactoferrin release were observed only at a concentration between 0 and 30% (vol/vol) dialysis effluent, while a concentration-dependent increase in oxidase activity was seen at a concentration between 0 and 70% (vol/vol). The results suggest that dialysis effluent does not affect PMN primary granule release but does cause increased release of secondary granules and an increase in NADPH oxidase activity in both unstimulated and stimulated PMN.

CD11 Antigens↗

An eye-movement analysis of the effects of scotopic sensitivity correction on parsing and comprehension.

Does scotopic sensitivity correction enhance parsing and, thus, comprehension? Twenty-two readers with scotopic sensitivity (mean age = 20.3 yrs.; 40.9% male) parsed sentences under scotopic correction and control conditions. Measures included eye-movement indices of parsing and comprehension questions. Although eye movements suggested enhanced parsing, comprehension scores were not significantly improved with correction.

Adolescent↗

ChlVPP/PABlOE and radiotherapy in advanced Hodgkin's disease. The Central Lymphoma Group.

PURPOSE: The United Kingdom Central Lymphoma Group (CLG) has modified mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) by substituting mechlorethamine with chlorambucil and dacarbazine with etoposide in the treatment of patients with advanced Hodgkin's disease (HD). Prednisolone is included in the bleomycin-containing combination, and the vinca alkaloids have been switched to balance the myelotoxicity of the two component regimens. PATIENTS AND METHODS: The resulting ChlVPP/PABlOE regimen is as follows: on days 1 to 14, chlorambucil 6 mg/m2 orally, procarbazine 100 mg/m2 orally, and prednisolone 30 mg/m2 orally; on days 1 and 8, vinblastine 6 mg/m2 intravenously (i.v.); on day 29, doxorubicin 40 mg/m2 i.v.; on days 29 and 36, vincristine 1.4 mg/m2 (maximum, 2 mg) i.v., and bleomycin 10 mg/m2 i.v.; on days 30, 31, and 32, etoposide 200 mg/m2/d orally; on days 29 to 43, inclusive, prednisolone, 30 mg/m2 orally. The second full cycle restarts on day 50. Treatment continues to maximum response plus two full cycles, but with a minimum of three full cycles. Radiotherapy is administered, after chemotherapy, to sites of previously bulky disease. Since 1983, 216 patients with previously untreated, advanced Hodgkin's disease (HD) have entered this study. RESULTS: The complete remission (CR) rate after chemotherapy was 73% (95% confidence interval [CI], 67% to 79%), and after additional radiotherapy was 85% (95% CI, 80% to 90%). The failure-free survival (FFS) rate at 5 years was 68% (95% CI, 61% to 74%), and the overall actuarial survival at 5 years was 78% (95% CI, 72% to 84%). The CR rate in patients in the poorer prognostic categories was high: 81% in patients with albumin levels less than 37 g/L, 79% in patients older than 40 years of age, 84% in stages IIIB plus i.v. disease, and 79% in patients presenting with B symptoms. As expected, nausea and vomiting were not major problems, although infection, often in the context of myelosuppression, complicated almost half the cases, and 29% of patients required admission at some stage for treatment of infection. CONCLUSION: In this multicenter study, ChlVPP/PABlOE produced results comparable to those reported for MOPP/ABVD, but with less nausea and vomiting. Treatment duration was shorter than in the original MOPP/ABVD regimen, and than that used in the Cancer and Leukemia Group B (CALGB) trial. It will now be compared with PABlOE alone.

Adult↗