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Biomedical subjects

R Watson

Publications and source records attributed to R Watson.

At least 19 recordsLinked to original sources

A novel gene cluster in Fusarium graminearum contains a gene that contributes to butenolide synthesis.

The development of expressed sequence tag (EST) databases, directed transformation and a sequenced genome has facilitated the functional analysis of Fusarium graminearum genes. Extensive analysis of 10,397 ESTs, derived from thirteen cDNA libraries of F. graminearum grown under diverse conditions, identified a novel cluster of eight genes (gene loci fg08077-fg08084) located within a 17kb region of genomic sequence contig 1.324. The expression of these genes is concomitantly up-regulated under growth conditions that promote mycotoxin production. Gene disruption and add-back experiments followed by metabolite analysis of the transformants indicated that one of the genes, fg08079, is involved in butenolide synthesis. The mycotoxin butenolide is produced by several Fusarium species and has been suggested, but not proven, to be associated with tall fescue toxicoses in grazing cattle. This is the first report of the identification of a gene involved in the biosynthetic pathway of butenolide.

4-Butyrolactone↗

Increasing the confidence of nursing staff to address the sexual health needs of people living with HIV: the use of motivational interviewing.

The need to promote safer sexual behaviour has taken on new urgency in the UK because of large increases in the number of sexually transmitted infections (STIs). The sexual health needs of people living with HIV and AIDS (PLHA) also require attention as part of health promotion efforts. Many sexual health clinics are however struggling with high demand and limited resources. Within this context, this paper describes an innovate attempt at STI prevention with PLHA. Specifically, nursing staff were trained in the use of motivational interviewing to address sexual health issues and safer sexual behaviour in PLHA. We describe the training package and the impact upon participants. We conclude that by providing a positive training experience, front-line health staff that see the highest volume of PLHA with repeat STIs, can be assisted in developing their skills and confidence in prevention work with clients.

Clinical Competence↗

Isolated donor specific alloantibody-mediated rejection after ABO compatible liver transplantation.

Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d.

ABO Blood-Group System↗

Refocusing health promotion for syphilis prevention: results of a case-control study of men who have sex with men on England's south coast.

BACKGROUND: Prevention interventions have had little impact on syphilis outbreaks among men who have sex with men (MSM) and diagnosis rates continue to rise rapidly. Detailed studies of the determinants of syphilis transmission are needed to inform new prevention interventions. OBJECTIVE: To investigate factors associated with recent syphilis diagnosis and recommend strategies for improved prevention interventions. METHODS: A case-control study of MSM attending genitourinary medicine (GUM) and HIV outpatient clinics. Cases were MSM testing positive for early syphilis, based on either laboratory or microscopy results, with those testing negative being controls. All participants completed the same anonymous questionnaire covering demographics, lifestyle, sexual behaviour, and sexual partnerships. RESULTS: 50 cases and 108 controls returned questionnaires. Syphilis diagnosis was significantly associated with sexually transmitted infection history, recent recreational drug use, receptive anal sex practices, but not insertive ones, higher numbers of oral sex partners, but not specific oral sex practices. Overall, there were no differences between HIV positive and HIV negative/untested men in reporting of sexual behaviours or partnership combinations. The use of public sex settings (backrooms, saunas, "cruising grounds," etc) was reported by 68% of all participants and not significantly associated with syphilis diagnosis. CONCLUSIONS: Many key behavioural and partnership risk factors for syphilis are also risk behaviours for HIV transmission and point to the need for integrated strategies that tackle the two infections together. Simplified procedures for syphilis screening should be available in GUM clinical settings, along with targeted community outreach prevention interventions.

Adult↗

The management of basal cell carcinomas.

The mortality and morbidity associated with basal cell carcinoma (BCC) is low. However, BCCs represent a significant burden to the health service due to their high and increasing incidence. This audit was designed to examine the management of BCCs by a dermatology department and to highlight deficiencies in the service offered to patients. The mean intervals between the first dermatology clinic visit and definitive treatment by the dermatology and the plastic surgery departments were 62 and 129 days respectively. Factors contributing to the delay included the frequent use of diagnostic incisional biopsies and the high referral rate from dermatology to the department of plastic and reconstructive surgery. In 90% of cases the dermatologist made an accurate clinical diagnosis. Despite this, diagnostic biopsies were performed in 72% of cases, often necessitating additional hospital visits. Forty three percent of cases were treated definitively by dermatology, whereas over 50% were referred to the department of plastic surgery. A number of changes are planned or are in process as a consequence of the audit.

Adult↗

Alpha7-acetylcholine receptor antibodies in two patients with Rasmussen encephalitis.

Rasmussen encephalitis (RE) sera were screened for antibodies to human alpha7 nicotinic acetylcholine receptors (nAChRs) using electrophysiology, calcium imaging, and ligand binding assays. Sera from two of nine patients with RE blocked ACh-induced currents through alpha7 nAChRs and the ACh-induced rise in intracellular free calcium ([Ca2+]i) and inhibited (125)I-alpha-bungarotoxin binding in cells expressing alpha7 nAChRs. Thus, the alpha7 nAChR is a potential target for pathogenic antibodies in patients with RE.

Adolescent↗

Immunohistochemical expression of vascular endothelial growth factor and microvessel counting as prognostic indicators in node-negative colorectal cancer.

This manuscript reports a carefully controlled study of patients with Dukes B colorectal cancer (Dukes stage A, n=12 and Dukes stage B, n=44). Immunohistochemistry has been used to demonstrate reactivity for vascular endothelial growth factor (VEGF), and to measure levels of microvessel density (MVD) in order to assess the relationship of tumor angiogenesis with clinical outcome. Immunohistochemistry was performed using antibodies to VEGF and CD34 (for intratumoral vessel identification) and counting was performed at the invasive margin of the tumor. Results showed that for Dukes stage A patients 4/12 died of their disease, none of whose tumor was VEGF positive. In contrast, 2 patients who survived were positive for VEGF cytoplasmically, but neither showed increased tumor MVD. In Dukes B patients 10/44 died, 5 of whose tumor demonstrated VEGF reactivity, both in malignant cells and in tumor vascular endothelium. MVD ranged from 11 to 53 (median 28) for Dukes A cases and from 9 to 69 (median 32.5) for the Dukes B group. Kaplan-Meier plots and log rank test statistics for Dukes B patients demonstrated that VEGF reactivity in cells, and in tumor vascular endothelium was correlated with survival (p=0.047 and p < or = 0.06, respectively). There was a significant relationship between the presence of VEGF reactivity on vascular endothelium and outcome by Fisher's exact test (p=0.018). Similarly, by the same test VEGF positivity was significantly correlated with patient mortality (p=0.032). The presence of endothelial VEGF reactivity correlated with VEGF in malignant cells (p=0.0001) by Mann-Whitney U test and a significant inverse relationship between vessel density and patient survival was demonstrated (p = 0.019). The finding that in Dukes B patients MVD was inversely correlated with mortality supports the hypothesis that a low microvascular count is predicted close to the invasive margin, where VEGF expression is upregulated in response to hypoxia, induced by a lack of a functional vasculature. These data will be used to identify cohorts of patients who have a high risk of relapse and can be selected for adjuvant therapies such as VEGF antibody or antitumor antibody-directed therapy.

Adult↗

Community based syphilis screening: feasibility, acceptability, and effectiveness in case finding.

OBJECTIVES: To investigate the feasibility and acceptability of implementing community based syphilis screening using different sample collection techniques, and its effectiveness in screening at-risk populations and identifying new syphilis cases. METHODS: Two phases of syphilis screening were conducted in venues frequented by men who have sex with men (MSM). Phase 1 used venepuncture and phase 2 a validated saliva test. Evaluation used quantitative data from testers, venues and the local genitourinary medicine (GUM) clinic, and qualitative data from venue and programme staff. RESULTS: 1090 MSM were tested over 7 weeks. 62% of testers had not attended a GUM clinic in the past year. 64% of testers reported > or = 2 sexual contacts in the past 90 days and 11% reported > or = 10. Similar diagnosis rates were recorded for phase 1 (1.4%) and phase 2 (1.8%). There was greater uptake of testing with the saliva test in saunas during phase 2. CONCLUSIONS: Syphilis screening in gay venues is feasible and acceptable to at-risk MSM, and reaches a group not routinely accessing GUM services. The low case detection for syphilis suggest this approach, while unlikely to contain outbreaks, may be more useful if combined with screening for other sexually transmitted infections and effective health promotion strategies.

Adult↗

Localization of organelle proteins by isotope tagging (LOPIT).

We describe a proteomics method for determining the subcellular localization of membrane proteins. Organelles are partially separated using centrifugation through self-generating density gradients. Proteins from each organelle co-fractionate and therefore exhibit similar distributions in the gradient. Protein distributions can be determined through a series of pair-wise comparisons of gradient fractions, using cleavable ICAT to enable relative quantitation of protein levels by MS. The localization of novel proteins is determined using multivariate data analysis techniques to match their distributions to those of proteins that are known to reside in specific organelles. Using this approach, we have simultaneously demonstrated the localization of membrane proteins in both the endoplasmic reticulum and the Golgi apparatus in Arabidopsis. Localization of organelle proteins by isotope tagging is a new tool for high-throughput protein localization, which is applicable to a wide range of research areas such as the study of organelle function and protein trafficking.

Arabidopsis↗

Absence of antibodies to glutamate receptor type 3 (GluR3) in Rasmussen encephalitis.

OBJECTIVE: To determine the prevalence of serum antibodies to the ionotropic glutamate receptor 3 (GluR3) in patients with Rasmussen encephalitis (RE), a severe epileptic disorder, and to compare with serum from control subjects and patients with intractable epilepsy (IE). METHODS: The authors looked for serum immunoglobulin (Ig) G antibodies to GluR3 in 30 patients with RE, including two patients who had plasma exchange and 12 who had been treated with IV Igs with varying results, and 49 patients with IE and 23 healthy individuals, using ELISA with GluR3B peptide, Western blot analysis of recombinant full-length GluR3, immunoprecipitation of [35S]- and [125I]-labeled GluR3 extracellular domains, immunohistochemistry on rat brain sections, and electrophysiology of GluR3 expressed in Xenopus oocytes. RESULTS: Low levels of antibodies to the GluR3B peptide were detected using ELISA in only 4 of the 79 patients with epilepsy (2 with RE and 2 with IE); binding to GluR3B in other sera was shown to be nonspecific. One other patient with IE had antibodies to recombinant GluR3 on Western blot analysis. However, none of the sera tested precipitated either the [35S]- or the [125I]-labeled GluR3 domains; none bound to rat brain sections in a manner similar to rabbit antibodies to GluR3; and none of the nine sera tested affected the electrophysiologic function of GluR3. CONCLUSIONS: GluR3 antibodies were only infrequently found in Rasmussen encephalitis or intractable epilepsy.

Adolescent↗

The impact of care on carers of patients treated for aneurysmal subarachnoid haemorrhage.

Over the last decade there has been an increasing awareness that psychosocial problems may persist in patients who have made apparently good recoveries after aneurysmal subarachnoid haemorrhage (ASAH). The caregivers of these patients are often relatives and it is becoming apparent that these carers frequently suffer psychosocial stress with associated morbidity. Previous studies have looked primarily at patients and few have included carers. We exclusively studied carers using simple validated questionnaires. We measured the effect on general and psychosocial health of the carers of patients treated for ASAH, 2-3 years after discharge. The majority of the carers (88.1%) were close relatives; 53.8% were experiencing social or emotional stress and 46.4% of these felt completely overwhelmed. The level of stress correlated positively with management complications, but not site of aneurysm or other aspects of treatment. We conclude that there is an argument for priority assistance for those carers predicted to be vulnerable to stress.

Caregivers↗

Multiphasic helical computerized tomography for the assessment of microscopic hematuria: a prospective study.

PURPOSE: We evaluated multiphasic helical computed tomography for the detection and characterization of lesions responsible for hematuria not diagnosed on prior urological surveillance studies. MATERIALS AND METHODS: A total of 393 men and 207 women with recurrent microscopic hematuria but negative urological surveillance studies were examined at 4 participating institutions by multiphasic helical computerized tomography, consisting of pre-enhancement, arterial corticomedullary, parenchymal and excretory phase sequences generating 2 to 5 mm slices through the kidney and lower pelvis. RESULTS: The cause of microscopic hematuria was established in 256 of 600 patients with prior negative urological surveillance examinations with 0.91 sensitivity and 0.94 specificity. The diagnosis was correct in all subsequently proven cases of calculous and renal vascular disease. A total of 67 of 70 inflammatory kidney lesions, 24 of 25 renal neoplasms, 15 of 16 bladder neoplasms, 27 of 35 inflammatory bladder conditions and 21 of 23 ureteral lesions were also correctly diagnosed. The diagnosis of renal medullary and papillary necrosis, and neoplastic lesions of the kidney and bladder allowed the early institution of medical therapy or appropriate surgery. CONCLUSIONS: Multiphasic helical computerized tomography diagnosed lesions responsible for microhematuria in 42.6% of 600 patients with negative urological surveillance examinations. This relatively low cost and low co-morbidity examination is advocated for patients with negative urological surveillance examinations or even as a first examination.

Adult↗

Efficacy of pulsed-dye laser for viral warts--an internal audit.

Pulsed-dye laser (PDL) surgery is a recognized treatment of viral warts. Initial studies in 1993 by Tan et al achieved a 72% cure rate for 39 patients after a mean of 1.68 treatments. Since then, conflicting response rates ranging from 47-95% have been reported. The records of 44 patients, who attended the Laser Unit at St. James's Hospital between January 1999 to June 2000, were reviewed. Follow-up was conducted by telephone interview or questionnaire. Twenty-eight (64%) patients identified for the study responded. The average number of treatments was 4 (range 1-12) and mean treatment intervals were 4.9 weeks (3-10). Our results showed 64% complete clearance of all the areas treated, and 46% complete clearance of the 13 areas identified as recalcitrant. Rates for complete clearance varied with anatomic site: 73% for the face, 68% for the hands, and 40% for feet. Seventy-eight percent (7/9) of periungal warts completely cleared, and 70% (7/10) mosaic warts cleared. Twenty-five percent of the patients complained of severe pain during treatment. Post-operative complications were few, and rarely affected the patients' lifestyle. The recurrence of warts, in weeks to months following the last treatment, was reported by 36% of the patients. Seventy-nine percent of patients were satisfied with the treatment they were given. PDL may be useful in treatment of refractory warts in selected patient populations. The study identified a need to address pain control in a significant number of patients.

Adolescent↗

Towards sustainability in world fisheries.

Fisheries have rarely been 'sustainable'. Rather, fishing has induced serial depletions, long masked by improved technology, geographic expansion and exploitation of previously spurned species lower in the food web. With global catches declining since the late 1980s, continuation of present trends will lead to supply shortfall, for which aquaculture cannot be expected to compensate, and may well exacerbate. Reducing fishing capacity to appropriate levels will require strong reductions of subsidies. Zoning the oceans into unfished marine reserves and areas with limited levels of fishing effort would allow sustainable fisheries, based on resources embedded in functional, diverse ecosystems.

Animals↗

Inflammatory bowel disease: developing a short disease specific scale to measure health related quality of life.

AIM: To report on the preliminary development of a short scale, the Edinburgh inflammatory bowel disease questionnaire (EIBDQ) to measure disease specific aspects of inflammatory bowel disease (IBD) in terms of both physical impact and health related quality of life (HRQoL) consequences. METHODS: A survey of individuals with Crohn's disease (n=50), ulcerative colitis (n=50) and psoriatic arthritis (n=28) was carried out using the EIBDQ. The data were subject to factor analysis in order to investigate underlying dimension of the EIBDQ which were then analysed for internal consistency. Data for disease specific aspects of the EIBDQ were compared between IBD patients and psoriatic arthritis patients using contingency tables and the underlying dimension of the EIBDQ were correlated with measures of quality of life and psychological morbidity and a disease specific measure. RESULTS: There are three underlying dimensions to the EIBDQ: a disease specific factor, a bowel specific factor and an information factor. The disease specific factor and the bowel specific factor are internally consistent and correlate with other measures of disease activity, quality of life and psychological morbidity. The EIBDQ is able to discriminate between IBD and another inflammatory disease: psoriatic arthritis. CONCLUSION: The EIBDQ is a reliable and valid instrument for measuring disease specific aspects of IBD but further development is required.

Arthritis, Psoriatic↗

Influence of harvest date and light integral on the development of strawberry flavour compounds.

Strawberries cv. Elsanta were grown in peat bags in a glasshouse and subjected to three shading levels (0%, 25%, 47%) for 2 weeks, commencing 1 week prior to first fruit ripening. Fruit was harvested at five intervals and analysed using Atmospheric Pressure Chemical Ionization (APCI) and direct liquid-mass spectrometry techniques. Thirteen volatiles implicated in strawberry flavour and three non-volatiles, sucrose, glucose and citric acid, were measured. Highly significant differences in volatile and non-volatile concentrations existed between harvest dates. Shading had a significant effect on hexanal, hexenal, ethyl methyl butyrate, and methyl butyrate concentrations at some harvests. In general, at each harvest the higher the level of shading the lower the level of the volatile in the fruit. Sucrose concentration showed a decrease throughout the harvest period, whereas glucose and citric acid showed less clear trends. Shading had a significant effect on glucose and sucrose concentrations. Some possible reasons for the variability in strawberry flavour are discussed.

Carbohydrate Metabolism↗