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Biomedical subjects

J Fletcher

Publications and source records attributed to J Fletcher.

At least 37 records · Page 2Linked to original sources
PubMed2001

Attenuation of ketamine effects by nimodipine pretreatment in recovering ethanol dependent men: psychopharmacologic implications of the interaction of NMDA and L-type calcium channel antagonists.

Ketamine blocks the calcium channel associated with N-methyl-D-aspartate (NMDA) glutamate receptors. It has transient behavioral effects in healthy humans that resemble aspects of schizophrenia, dissociative disorders, and ethanol intoxication. Ethanol is an antagonist of both NMDA receptors and L-type voltage-sensitive calcium channels (VSCC) and it has minimal psychotogenic activity in humans. A double-blind placebo-controlled study was conducted that evaluated whether pretreatment with the L-type VSCC antagonist, nimodipine, 90 mg D, modulated ketamine response (bolus 0.26 mg/kg, infusion of 0.65 mg/kg/hr) in 26 ethanol-dependent inpatients who were sober for at least one month prior to testing. This study found that nimodipine reduced the capacity of ketamine to induce psychosis, negative symptoms, altered perception, dysphoria, verbal fluency impairment, and learning deficits. Nimodipine improved memory function, but had no other intrinsic behavioral activity in this patient group. Nimodipine pretreatment attenuated the perceived similarity of ketamine effects to ethanol as well as ketamine-induced euphoria and sedation. However, nimodipine did not reduce the stimulant effects of ketamine. These data suggest that antagonism of L-type VSCCs attenuates the behavioral effects of NMDA antagonists in humans. They support the continued evaluation of nimodipine in the treatment of neuropsychiatric disorders. They also suggest that drugs, such as ethanol, that combine NMDA and L-type VSCC antagonism may have enhanced tolerability without attenuation of their stimulant effects.

Adult↗
PubMed2001

Correlation between patients' satisfaction and objective measurement of knee stability after ACL reconstruction using a patellar tendon autograft.

We evaluated the relationship between patients' satisfaction and objective measurements of knee stability after reconstruction of the ACL using a patellar tendon autograft. An examination of 59 patients 2-7 years after surgery was carried out. Assessment was made by the Knee and Osteoarthritis Outcome Score for patient satisfaction, a modified International Knee Documentation Committee form for clinical knee stability and a Telos stress radiography for PA stability. The results show that patients' satisfaction was much greater than the objective evaluation would suggest. We conclude that documenting mechanical knee stability alone is inadequate for follow-up studies and a questionnaire assessing patient satisfaction should be added.

Anterior Cruciate Ligament↗
PubMed2001

Deletion of the alpha(1,3)galactosyl transferase (GGTA1) gene and the prion protein (PrP) gene in sheep.

Nuclear transfer offers a cell-based route for producing precise genetic modifications in a range of animal species. Using sheep, we report reproducible targeted gene deletion at two independent loci in fetal fibro-blasts. Vital regions were deleted from the alpha(1,3)galactosyl transferase (GGTA1) gene, which may account for the hyperacute rejection of xenografted organs, and from the prion protein (PrP) gene, which is directly associated with spongiform encephalopathies in humans and animals. Reconstructed embryos were prepared using cultures of targeted or nontargeted donor cells. Eight pregnancies were maintained to term and four PrP-/+ lambs were born. Although three of these perished soon after birth, one survived for 12 days. These data show that lambs carrying targeted gene deletions can be generated by nuclear transfer.

Animals↗
PubMed2001

Community nurses', home carers' and patients' perceptions of factors affecting venous leg ulcer recurrence and management of services.

AIM: This study examines the feasibility of utilizing social service home carers (SSHC) to provide a collaborative approach with community nurses for the provision of leg ulcer aftercare in four National Health Service (NHS) Trusts. The purpose of this study was to gain insight into what community nurses and people with healed venous leg ulcers felt influenced leg ulcer recurrence. BACKGROUND: Studies have demonstrated that provision of community-based leg ulcer clinics has improved healing rates of venous leg ulcers, yet recurrence remains a problem. The reasons for this are far from clear, and further research is required before unequivocal support can be given to one approach to the provision of care for this client group. Collaborative approaches to the provision of leg ulcer aftercare are beginning to receive more attention. It has been recognized that social service health carers could be co-opted to provide essential aftercare once healing has occurred, although the logistics of this approach have not been fully explored. METHODS: This study was conducted in four NHS Trusts. Stage one used focus groups to explore the perceptions of district nurses (n = 15) and social service health carers (n = 15) of a leg ulcer shared care project and to gain insight into factors that they felt influenced recurrence. The second stage used semistructured interviews (n = 12) to explore the perceptions that people with healed leg ulcers have about factors influencing ulcer recurrence. FINDINGS: Key themes emerging from this study were: health promotion is perceived by community nurses and patients to be ineffective and leg ulcer aftercare services are fragmented. Organizational factors such as time constraints and limited resources were cited by community nurses and home carers as being responsible for high leg ulcer recurrence rates. Community nurses expressed a desire to delegate preventative aspects of leg ulcer care to home carers rather than participate in health promotion strategies to support healing behaviours. CONCLUSIONS: A strategy aimed at supporting healing behaviour in elderly people has the potential to reduce the recurrence of leg ulceration and improve quality of life. The findings suggest that such a strategy needs to rationalize delivery of leg ulcer aftercare to provide seamless care. It needs to improve carers' and patients' understanding of factors influencing leg ulcer recurrence and facilitate development of a more balanced professional--patient relationship.

Adult↗
PubMed2001

Changing government, changing cultures? Moving the quality agenda towards effective processes to counterbalance performance outcomes.

This paper begins by identifying current government initiatives to tabulate performance in the National Health Service by the identification and codification of selected clinical indicators, and notes the ambivalence as to whether effectiveness is to be seen on financial or qualitative terms. It continues by reviewing official and academic definitions of effectiveness, and discovers a similar lack of consensus. It then moves on to consider the concept of effectiveness in another public utility -- education. A distinction is drawn between effectiveness as a measure of institutional outcome and as a key factor influencing institutional process. The factors that promote effectiveness in education are identified and exemplified. The paper concludes by reflecting on the steps necessary if such processes are to be adopted in the management of the National Health Service, and notes that the new 'National Plan' offers, at least in theory, an ideal context for a collective effort to enhance effectiveness processes in the health service, in which managers can play a decisive role.

Cost Control↗
PubMed2001

Unbuffered highly acidic gastric juice exists at the gastroesophageal junction after a meal.

BACKGROUND & AIMS: Gastroesophageal reflux typically occurs after meals. During dual gastric and esophageal pH monitoring, we observed that postprandial refluxate was often more acidic than the gastric contents. This study aimed to investigate this phenomenon. METHODS: Dual gastric and esophageal pH tracings were analyzed from 40 dyspeptic patients. Dual pH electrode pull-through studies were performed in healthy volunteers to document regional variation in intragastric pH under both fasting and postprandial conditions. The squamocolumnar junction was identified using radio-opaque endoscopic clips. We also examined in vitro partitioning of gastric juice added to a homogenized fatty meal. RESULTS: The dual pH traces confirmed that esophageal refluxate was frequently more acidic than the body of the stomach after meals but not during fasting. The pull-through studies showed a pocket of acid at the gastroesophageal junction that escaped the buffering effect of meals, remaining highly acidic (median pH 1.6) compared with the body of the stomach (pH 4.7; P < 0.001). This proximal acid pocket extended from the cardia across the squamocolumnar junction 1.8 cm into the distal esophagus. The in vitro studies showed that acidic gastric juice could partition on top of a homogenized fatty meal. CONCLUSIONS: After eating, highly acidic unbuffered gastric juice is present at the gastroesophageal squamocolumnar junction and is likely to contribute to the high prevalence of disease at this site.

Adult↗
PubMed2001

Gene targeting in primary fetal fibroblasts from sheep and pig.

Nuclear transfer offers a new cell-based route for introducing precise genetic modifications in a range of animal species. However, significant challenges, such as establishment of somatic gene targeting techniques, must be overcome before the technology can be applied routinely. In this report, we describe targeted deletion at the GGTA1 (alpha 1,3-galactosyl transferase) and PrP (prion protein) loci in primary fibroblasts from livestock. We place particular emphasis on the growth characteristics of the primary cell cultures, since these are key to determining success.

Animals↗
PubMed2001

The anti-inflammatory effects of circulating fatty acids in obstructive jaundice: similarities with pregnancy-induced immunosuppression.

Rheumatoid arthritis (RA) is ameliorated during both obstructive jaundice and pregnancy. Previous studies of polymorphonuclear leukocyte (PMN) function during pregnancy have shown reductions in the stimulated release of arachidonic acid (AA) and leukotriene B4 (LTB4), and lower NADPH oxidase activity. These changes may account for the amelioration of RA. The cause of this reduction in PMN function appears to be a progressive change in circulating fatty acids (FA), with a reduction in polyunsaturated FA, predominantly AA. The NADPH oxidase responsible for the respiratory burst has a direct requirement for polyunsaturated FA, particularly AA. We investigated whether the same changes in PMN function and FA, occur during obstructive jaundice. Patients with biliary obstructions were investigated before and after surgical correction (n=14). Obstructive jaundice caused significant changes in the proportions of serum and cellular FA. There was a striking reduction in polyunsaturated FA, particularly AA (48% in serum, p<0.001; 42% in PMNs, p<0.001) and an increase in mono-unsaturated oleic acid (24% in serum, p<0.001; 15% in PMNs, p<0.005). Similar changes occurred in mononuclear cell FA. Jaundice also caused a significant reduction in PMN function. Respiratory burst activity was reduced by between 32% and 38% in response to physiological and non-physiological stimuli, and there were similar significant reductions in the release of AA and LTB4. These changes in stimulated PMN function were evident whether or not the cells were first primed with tumour necrosis factor alpha (TNFalpha). Incubation of PMNs from healthy donors in pooled serum from patients with obstructive jaundice caused a reduction of 32% in cellular AA and 38% in NADPH oxidase activity. These findings support the idea that circulating FA can regulate PMN inflammatory responsiveness. The FA-induced attenuation in PMN activity in both jaundice and pregnancy may explain their ameliorating effects upon RA.

Adult↗
PubMed2001

Identification of the exported proteins of the oral opportunistic pathogen Actinobacillus actinomycetemcomitans by using alkaline phosphatase fusions.

A phoA fusion library of Actinobacillus actinomycetemcomitans genomic DNA has been screened to identify genes encoding exported and secreted proteins. A total of 8,000 colonies were screened, and 80 positive colonies were detected. From these, 48 genes were identified with (i) more than half having homology to known or hypothetical Haemophilus influenzae genes, (ii) 14 having no ascribed function, and (iii) 4 having very limited or no homology to known genes. The proteins encoded by these genes may, by virtue of their presence on the cell surface, be novel virulence determinants.

Aggregatibacter actinomycetemcomitans↗
PubMed2001

Comparison of two methods for serotyping Campylobacter spp.

Two serotyping schemes (Penner and Laboratory of Enteric Pathogens [LEP]) based on soluble heat-stable antigens were used to analyze 3,788 Campylobacter sp. isolates. A significant percentage (36.6%) was untypeable using LEP serotyping; greater cross-reaction was also observed. The relative discrimination capabilities of the techniques were similar. Penner serotyping fulfils more of the requisite criteria for typing methods.

Antigens, Bacterial↗
PubMed2001

Termination of pregnancy: patients' perceptions of care.

BACKGROUND: Little is known about women's perceptions of care in termination of pregnancy (TOP). Developing an understanding of how care is experienced is crucial to improvements in services. METHOD: Two hundred and eight women undergoing either a medical or surgical TOP reported on their perspectives of the experience and the care received. A mix of questionnaire and open questions analysed by content analysis was used. Women reported on the aspects which were most stressful, helped them to feel more relaxed, were unexpected in some way, and also on the provision of information and on the quality of staff care. RESULTS: The most stressful aspects for the medical group related to the physical and emotional aspects of the process, whilst for the surgical group it concerned waiting in hospital for the operation. Whilst little was unexpected for the surgical group, many aspects came as a surprise to the medical group. Seeing the foetus was particularly difficult. All information provided was viewed as helpful, with greater information required about the phase following termination. Care from staff was rated positively, although areas for improvement in terms of opportunity to ask questions and ensuring concerns were dealt with were identified. Caring and non-judgemental staff attitudes were viewed as particularly important in helping women to feel as relaxed as possible in a potentially stressful situation. CONCLUSION: Surgical termination schedules should avoid a long waiting time once the woman has been admitted. More adequate preparation is required for those having medical termination so that they have realistic expectations of what will happen, including the possibility of seeing the foetus. More attention to information about the time following termination, including possible emotional responses, is needed. The importance of positive staff attitudes in the quality of care is emphasised.

Abortion, Legal↗
PubMed2001

Sexually transmitted infections in primary care: a need for education.

General practitioners and practice nurses require the clinical skills that will enable them to detect sexually transmitted infections in the context of a shift to having no, or insidious symptoms. They need to be able to confirm the diagnosis and have clear models for management and referral. Primary care and genitourinary medicine need to work more closely together to increase mutual understanding and clarify the issues which surround referral and attendance. Sexual health risk assessment through the investigation of sexual history is a helpful way forward in both differential diagnosis and in targeting sexual health promotion and care. Many aspects of these clinical skills are specific to the primary care context. There is a need for improved undergraduate, postgraduate, and in-service training. Multidisciplinary educational approaches are ideal for the subject of sexual health. Primary care groups offer a potential way forward to help develop quality in primary care and some are developing health improvement programmes that aim to address sexual health issues.

Ambulatory Care↗
PubMed2001

Effects of angiotensin II (AT1) receptor blockade on cardiac vagal control in heart failure.

The objective of the present study was to determine the autonomic effects of angiotensin II (AT(1)) receptor blocker therapy in heart failure. In a randomized double-blind cross-over study, we compared the effects of candesartan and placebo on baroreflex sensitivity and on heart rate variability at rest, during stress and during 24 h monitoring. Acute effects were assessed 4 h after oral candesartan (8 mg) and chronic effects after 4 weeks of treatment (dose titrated to 16 mg daily). The study group comprised 21 patients with heart failure [mean (S.E.M.) ejection fraction 33% (1%)], in the absence of angiotensin-converting enzyme (ACE) inhibitor therapy. We found that acute candesartan was not different from placebo in its effects on blood pressure or mean RR interval. Chronic candesartan significantly reduced blood pressure [placebo, 137 (3)/82 (3) mmHg; candesartan, 121 (4)/75 (2) mmHg; P<0.001; values are mean (S.E.M.)], but had no effect on mean RR interval [placebo, 857 (25) ms; candesartan, 857 (21) ms]. Compared with placebo there were no significant effects of acute or chronic candesartan on heart rate variability in the time domain and no consistent effects in the frequency domain. Baroreflex sensitivity assessed by the phenylephrine bolus method was significantly increased after chronic candesartan [placebo, 3.5 (0.5) ms/mmHg; candesartan, 4.8 (0.7) ms/mmHg; P<0.05], although there were no changes in cross-spectral baroreflex sensitivity. Thus, in contrast with previous results with ACE inhibitors, angiotensin II receptor blockade in heart failure did not increase heart rate variability, and there was no consistent effect on baroreflex sensitivity.

Aged↗