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Biomedical subjects

R Walker

Publications and source records attributed to R Walker.

At least 181 records · Page 10Linked to original sources

Influencing prescribing in primary care: a comparison of two different prescribing feedback methods.

This study evaluated two different methods of providing practice-based, antibiotic prescribing feedback to general practitioners (GPs). The impact of face-to-face prescribing discussion visits led by a pharmaceutical prescribing adviser were compared to the provision of practice specific prescribing analysis workbooks. Sixty-six practices within one Family Health Services Authority were randomly stratified into one of two groups (Group 1: visits; Group 2: workbooks). The 23 practices who did not wish to participate were used as a self selected control group (Group 3). Twelve months after the start of the programme, visits were extended to Group 2 and Group 3. Prescribing patterns were evaluated using five prescribing indicators, before and at 12 and 24 months after the start of the programme. Analysis of practice prescribing patterns at 12-months demonstrated that the desired changes in the selected five indicators were greater in Group 1 than Group 2 or Group 3; changes were statistically significant for indicators 5, 4 and 2 in each group, respectively. After 24 months all groups demonstrated significant changes in five indicators. Face-to-face visits proved the most successful of the two methods to influence GP prescribing, although the workbook promoted more change than that seen in the control group.

Anti-Bacterial Agents↗

Cardiff puerperal mood and hormone study. III. Postnatal depression at 5 to 6 weeks postpartum, and its hormonal correlates across the peripartum period.

BACKGROUND: We assessed associations of mood at 5-6 weeks postpartum with peripartum saliva cortisol and progesterone profiles. METHOD: A prospective study involved 120 primiparous women free of major marital, socioeconomic and health problems, who collected saliva twice daily from 2 weeks before delivery to day 35 postpartum. This allowed intensive characterisation of cortisol and progesterone profiles. At the conclusion of the study, mood was assessed according to standard criteria. RESULTS: Seven women developed major depression according to DSM-III-R criteria. No associations emerged between progesterone and mood at 5 to 6 weeks. Lower levels of evening cortisol in the immediate peripartum period, were associated with postnatal depression. CONCLUSION: The study provides no support for the treatment strategy of progesterone augmentation following delivery, as a prophylactic against postnatal depression. The HPA axis and its associations with postnatal mood warrants further investigation.

Adolescent↗

Functional studies of epidermal Langerhans cells and blood monocytes in HIV-infected persons.

APC dysfunction may be important in immune dysregulation associated with HIV disease. Langerhans cells, epidermal APC, can be infected with HIV, although their function in HIV-infected persons has not been studied. Therefore, we studied the immunologic function of Langerhans cells, in parallel with blood APC (enriched for monocytes/macrophages (M phi) function, in 21 HIV-seropositive (HIV+) and 21 HIV-seronegative volunteers, including three monozygotic twin pairs discordant for HIV serology. Langerhans cells from HIV+ patients were quantitatively normal and expressed normal levels of HLA-DR. However, Langerhans cells from AIDS patients and M phi from both AIDS and HIV+ non-AIDS patients stimulated allogeneic T cells less well compared with control APC. In addition, decreased recall Ag- and mitogen-induced T cell responsiveness was observed in HIV+ patients using either autologous Langerhans cells or autologous M phi as APC/accessory cells. Interestingly, Langerhans cells and M phi isolated from HIV+ twins (CD4+ cell counts of 181, 271, and 562/mm3) were able to present recall Ag normally to HIV-uninfected syngeneic T cells. In summary, APC from HIV+ patients were impaired in their ability to generate a primary immune response (i.e., alloantigen-induced T cell stimulation), but they retained the ability to generate a secondary immune response (i.e., recall Ag-induced syngeneic T cell stimulation). Thus, these findings suggest that defects in secondary immune responses commonly observed in HIV disease are dependent on T cell dysfunction alone, whereas defective primary immune responses may be secondary to both T cell and APC dysfunction.

Adult↗

Allelic imbalance on chromosome 1 in human breast cancer. I. Minisatellite and RFLP analysis.

In order to characterise the role of chromosome 1 more fully in breast cancer, polymorphic markers mapping along the length of the whole chromosome were used to assess a panel of 71 tumour-lymphocyte pairs for allelic imbalance. Complex patterns of alterations were established that are consistent with cytogenetic data in the literature. Deletion mapping of individuals with loss of heterozygosity identified five independent smallest common regions of deletion, two of which are novel. There are also three discrete regions showing a gain in copy number of one homologue. The two arms of the chromosome may be subject to different events; the short arm primarily undergoes interstitial deletions, whereas the long arm is subject to whole arm events (as both gains and losses) as well as regional deletions.

Alleles↗

Loss of heterozygosity on the X chromosome in human breast cancer.

The analysis of loss of heterozygosity (LOH) in tumours can be a powerful tool for mapping the sites of tumour suppressor genes in the human genome. A panel of breast cancer patients was assembled as pairs of tumour and lymphocyte DNA samples and LOH studies carried out by Southern hybridisation with polymorphic loci mapping to the X chromosome with appropriate controls. Deletion mapping revealed a high frequency of small regionalised deletions, defining at least three independent regions, one of which is particularly well mapped to a 500 kb stretch of DNA in the distal portion of the pseudoautosomal region of Xp. A second region has been identified within the pseudoautosomal region close to the pseudoautosomal boundary, and there is a third discrete site of loss on distal Xq. Perturbations of sequences at these regions represent independent events in a number of patients. This study represents the first detailed analysis of LOH on the X chromosome in human breast tumours, the results of which indicate that at least three regions of this chromosome are involved in the disease.

Alleles↗

Microvenous thrombosis rates following anastomosis with vein grafting and a knotted suture.

An experimental microvenous thrombosis model was developed combining vein grafting in femoral vein defects with exaggerated vessel injuries using a knotted suture in the vessel repair. The rat femoral vein grafts were separately subjected to injuries caused by an anastomosis performed with a suture knotted with eight half-hitches at the distal anastomosis (upstream), the proximal anastomosis (downstream), and both anastomotic sites. These groups were compared to vein grafting done with a standard suture. Vessel patency was assessed at 20 min and 24 hr, and the thrombus component was histologically analyzed at 24 hr after the procedures. One hundred percent of control vein grafts were patent at 24 hr. All experimental groups had significantly decreased patency at 24 hr (P < 0.001). Among the experimental groups, knotted suture anastomoses at both anastomoses produced significantly lower patency (13.3%, P < 0.05) than knotted suture anastomoses at distal anastomoses. Histological analyses of thrombosed grafts showed that a large amount of thrombocyte deposition and inflammatory cells were noted at both anastomotic sites in the vein grafts with a knotted suture at the distal anastomosis and in the grafts with a knotted suture at both anastomoses. Thrombocyte deposition and inflammatory cells were seen only at the site of proximal anastomosis when using a knotted suture at the proximal anastomosis site alone. This study demonstrated that quantified microvenous thrombosis can be produced by exaggerating vessel injuries with a knotted suture in a vein graft model. This thrombosis model can be used to study the effects of antithrombogenic agents.

Anastomosis, Surgical↗

Independent contributions of the orienting of attention, fixation offset and bilateral stimulation on human saccadic latencies.

In a series of experiments we examined the effects of the endogenous orienting of visual attention on human saccade latency. Three separate manipulations were performed: the orienting of visual attention, the prior offset of fixation (gap paradigm) and the bilateral presentation of saccade targets. Each of these manipulations was shown to make an independent contribution to saccade latency. In experiments 1 and 2 subjects were instructed to orient their attention covertly to a location by a verbal pre-cue; targets could appear in the attended hemifield (valid) or in the non-attended hemifield (invalid) together with a no-instruction (neutral) condition. Saccades were made under fixation gap and overlap conditions, to either single target or two bilaterally presented targets which appeared at equal and opposite eccentricities in both hemifields. The results showed a large increase (cost) of saccade latency to invalid targets and a small non-significant decrease (benefit) of saccade latency to valid targets. The cost associated with invalid targets replicates the "meridan crossing effect" shown in manual reaction time experiments and is consistent with the hemifield inhibition and premotor models of attentional orienting. The use of a "gap" procedure produced a generalised facilitation of saccade latency, which was not modified by the prior orienting of visual attention. The magnitude of the gap effect was similar for saccades made to attended and non-attended stimulis. This suggests that the gap effect may be due to ocular motor disengagement, or a warning signal effect, rather than to the prior disengagement of visual attention. When two targets were presented simultaneously, one in each hemifield, saccade latency was slowed compared with the single target condition. The magnitude of this slowing was unaffected by the prior orienting of visual attention or by the fixation condition. The slowing was examined in more detail in experiment 3, by presenting targets with brief offset delays. The latency increase was maximal if the two targets were presented simultaneously and decreased if the distractor appeared at short intervals (20-80 ms) before or after the saccade target onset. If the non-attended stimulus was presented at greater intervals (160, 240 ms) before the saccade target, then a facilitation effect was observed. This demonstrates that the onset of a distractor in the non-attended hemifield can have both an inhibitory and a facilitatory effect on a saccade production.

Attention↗

Confirmation of the copy number of chromosome 1 in interphase nuclei from paraffin sections of breast tumours by fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) was used to establish the copy number of chromosome 1 in a set of nine breast tumours in which the chromosome had previously been shown to have undergone a variety of rearrangements by loss of heterozygosity studies. In each case, FISH with satellite III DNA from chromosome 1q12 confirmed the results obtained by Southern hybridization. Importantly, in all five cases with rearrangements thought not to involve the centromeric region, FISH showed that the events had not disrupted the gross chromosome structure. This study highlights the potential of using the two techniques together to obtain a clearer picture of both large- and small-scale alterations to chromosomes in solid tumours.

Alleles↗

Stimulation of rat hepatic UDP-glucuronosyl transferase activity following treatment with green tea.

Studies were conducted to investigate whether aqueous extracts of green tea, administered to rats at concentrations consumed by humans, could influence the phase II conjugation reactions in the liver, and so contribute to its established anticarcinogenic activity. Exposure of rats to green tea (2.5%, w/v), as the sole drinking fluid, for 4 wk did not influence sulfotransferase, epoxide hydrolase nor glutathione S-transferase activities. UDP glucuronosyl transferase activity, when determined using 2-aminophenol as the substrate, was increased by 100% following treatment with tea. Finally, green tea had no effect on the enzymes affording protection against reactive oxygen species, namely catalase, glutathione peroxidase and superoxide dismutase. It is postulated that the enhanced glucuronidation may contribute to the anticarcinogenic effect of green tea by facilitating the metabolism of chemical carcinogens into inactive, readily excretable products.

Aminophenols↗

Spontaneous sustained ventricular tachycardia in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) Trial.

OBJECTIVES: We compared the QRS waveforms of the initial and subsequent complexes of spontaneous sustained monomorphic ventricular tachycardia and the rhythm induced at electrophysiologic study to test the theory that premature ventricular complexes "trigger" spontaneous ventricular tachycardia and that a stable substrate exists such that the spontaneous arrhythmia can be reproduced at electrophysiologic study. BACKGROUND: Failure rates have been high in several recent studies in which prevention of ventricular tachyarrhythmias was guided by suppression of premature ventricular complexes or induced ventricular tachycardias. METHODS: Digital waveform analysis was used to distinguish events of ventricular tachycardia initiated by configurationally distinct, possibly triggering, complexes (type 1) from events in which the initial QRS waveforms were identical to subsequent complexes, suggesting no requirement for premature ventricular beats (type 2). RESULTS: Of 1,102 episodes of spontaneous ventricular tachycardia, 73 (6.6%) were type 1; 1,012 were type 2 (91.8%); and 17 (1.5%) were uncertain. Of 59 patients only 14 (24%) had only type 1 episodes (group 1), whereas 37 patients (63%) had predominantly type 2 events (group 2) (p < 0.0001). Sustained ventricular tachycardia was inducible in all group 1 patients, and in most (57%) the induced rhythm was similar to the spontaneous rhythm. Ventricular tachycardia could not be induced in 7 patients from group 2 (19%), and in 18 patients (49%) the induced and spontaneous rhythms were dissimilar. Recurrence of arrhythmia rates differed according to the guidance method in group 2. CONCLUSIONS: Discrepancies between observed and predicted modes of initiation of ventricular tachycardia and between spontaneous and induced rhythms could result in inappropriate guidance and subsequent failure of antiarrhythmic treatment.

Aged↗

Community-based health care: a different approach to health outcomes.

Health sector organisations are undergoing a period of fundamental change. One set of changes is about increasing the capacity of the system to provide integrated client care. This paper discusses the practices that community health care workers have used to approach some basic issues of service integration. Although the discussion is about practices in community health, the issues are important for health care providers, managers and policy-makers throughout the health care system.

Australia↗

A study of bovine tuberculosis in domestic animals and wildlife in the MacKenzie Basin and surrounding areas using DNA fingerprinting.

The MacKenzie Basin, an area of about 5150 km2 in the South Island of New Zealand, was free of bovine tuberculosis prior to 1980. During the next 13 years, the majority of the cattle and deer herds in this area became infected with Mycobacterium bovis. The history of infection in the MacKenzie Basin has all the characteristics of a newly developed region of endemic tuberculosis with a wildlife reservoir of M. bovis. Tuberculous possums and ferrets were found in the MacKenzie Basin and both may have been a source of infection for domestic animals. DNA fingerprinting of 125 isolates of M. bovis from domestic animals and wildlife by restriction endonuclease analysis revealed two major groups of isolates. The same groups were identified using IS6110 as a DNA probe. Restriction endonuclease analysis enabled one group to be subdivided into seven restriction types and the other group into eight types. Mycobacterium bovis isolates with the most common restriction types were present in both domestic animals and wildlife, indicating that infection had spread between these two groups of animals. DNA fingerprinting also revealed that M. bovis was introduced into the MacKenzie Basin from at least two distinct sources. Furthermore, DNA finger-printing was able to identify probable sources of infection.

Journal Article↗

Safety and feasibility of renal blood flow determination during kidney transplant surgery with perfusion ultrasonography.

Contrast-enhanced perfusion patterns of newly transplanted kidneys were determined in 10 patients. Albumin-stabilized sonicated microspheres were injected into the iliac-renal artery of the transplanted kidney while continuous two-dimensional ultrasound images were recorded. Doppler derived resistance index (RI) of the transplanted kidney's blood flow before injection of contrast (0.68 +/- 0.8) did not differ significantly from RI measured immediately after injection (0.72 +/- 0.13) or RI 24 h after surgery (0.69 +/- 0.11). Heart rate, mean arterial pressure, central venous pressure, and electrocardiogram (ECG) signs for ischemia did not change during contrast injections. Renal scintigraphy and renal biopsy revealed acute tubular necrosis and/or rejection in two patients at 24-48 h. Videodensitometry was used to assess the ratio of inner to outer peak pixel intensity from the recorded tomographic images in six patients. In both patients with acute rejection, the inner to outer cortex peak pixel intensity was greater than 1, whereas it was less than 1 in the remaining four patients with normal postoperative renal function. Visual scores (0-3) of contrast enhancement for three doses of Albunex were evaluated (0.5 mL, 1.0 mL, 2.0 mL). Two milliliters always enabled perfusion assessment. In seven patients the identical dose of Albunex was injected immediately before and 30 s after 2 mg of verapamil was injected directly into the renal artery at the time of surgery. The contrast enhancement score before verapamil (1.4 +/- 0.6) was significantly less than the enhancement score after (2.1 +/- 0.6), implying greater renal blood flow after verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evaluation of changes in skeletal muscle blood flow in the dog with contrast ultrasonography.

Intraoperative methods to assess skeletal muscle blood flow or muscle-flap perfusion during vascular reconstructive surgery are limited. At present, techniques enable only anatomic identification of the degree of patency of large vessels. We report here the first use of ultrasonography to assess dynamic changes in skeletal muscle perfusion. Baseline blood flow in the adductor muscle group of the hindlimbs of seven dogs was measured with an electromagnetic flow probe and with contrast ultrasound using the contrast agent Albunex. Blood flow was manipulated in each dog pharmacologically with random administration of intraarterial injections of Neo-Synephrine and papaverine. After each change in blood flow detected by electromagnetic flow probe, flow also was assessed qualitatively by four independent observers who graded video-recorded contrast enhancement in the muscle group on a 0 to 4 scale. Videodensitometry also was used to generate time versus intensity curves in the adductor muscle region of interest. Peak pixel intensity was determined during each flow condition. A total of 21 flow measurements were made with each assessment scheme (electromagnetic flow probe, video enhancement, videodensitometry) for each condition (7 control, 7 papaverine, 7 Neo-Synephrine). Changes in blood flow assessed by video enhancement scores and changes in peak pixel intensity correlated with changes measured by electromagnetic flow probe (r = 0.84 and 0.66, respectively). We conclude that contrast ultrasound may be used to detect changes in skeletal muscle perfusion intraoperatively. Measures of muscle perfused by visual inspection of contrast enhancement and videodensitometric data were in agreement with direct measurements of changes in skeletal muscle blood flow.

Animals↗

Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity.

The Vpr accessory gene product of human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus is believed to play a role in permitting entry of the viral core into the nucleus of nondividing cells. A second role for Vpr was recently suggested by Rogel et al. (M. E. Rogel, L. I. Wu, and M. Emerman, J. Virol. 69:882-888, 1995), who showed that Vpr prevents the establishment in vitro of chronically infected HIV producer cell lines, apparently by causing infected cells to arrest in the G2/M phase of the cell cycle. In cycling cells, progression from G2 to M phase is driven by activation of the p34cdc2/cyclin B complex, an event caused, in part, by dephosphorylation of two regulatory amino acids of p34cdc2 (Thr-14 and Tyr-15). We show here that Vpr arrests the cell cycle in G2 by preventing the activation of the p34cdc2/cyclin B complex. Vpr expression in cells caused p34cdc2 to remain in the phosphorylated, inactive state, p34cdc2/cyclin B complexes immunoprecipitated from cells expressing Vpr were almost completely inactive in a histone H1 kinase assay. Coexpression of a constitutively active mutant p34cdc2 molecule with Vpr relieved the G2 arrest. These findings strongly suggest that Vpr arrests cells in G2 by preventing the activation of the p34cdc2/cyclin B complex that is required for entry into M phase. In vivo, Vpr might, by preventing p34cdc2 activation, delay or prevent apoptosis of infected cells. This would increase the amount of virus each infected cell produced.

CDC2 Protein Kinase↗