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J Hay

Publications and source records attributed to J Hay.

At least 55 records · Page 3Linked to original sources
PubMed1998

The varicella-zoster virus (VZV) open-reading frame 29 protein acts as a modulator of a late VZV gene promoter.

Transient expression assays have shown that the varicella-zoster virus (VZV) open-reading frame (ORF) 29 gene product can act as a modulator of VZV gene expression. The ORF 29 protein alone does not appear to have any effect on transcription; however, in its presence, changes in the level of reporter gene activity mediated by the VZV immediate early (IE) 62 major transactivator are seen. Increased expression was observed in human fibroblasts, MeWo cells, HeLa cells, and T cells. In contrast, the presence of the ORF 29 protein results in a down-regulation of IE62 activation in PC-12 rat neuronal cells. Competition filter binding assays indicate that the ORF 29 protein binds specifically to the glycoprotein I promoter. Since transcripts for ORF 29 and ORF 62 have been detected in latently infected ganglia, the gene regulatory properties of the ORF 29 protein may be relevant to maintenance or establishment of VZV latency.

Animals↗
PubMed1998

First International Pharmacoeconomic Conference on Alzheimer's Disease: report and summary.

The First International Pharmacoeconomic Conference on Alzheimer's Disease (AD) was held in Amsterdam in July 1998. The meeting was held under the auspices of the International Working Group for Harmonization of Dementia Drug Guidelines (http://dementia.ion.ucl.ac.uk/harmon), bringing together academics, clinicians, purchasers, and representatives from industry. Presentations were given on the methodology of pharmacoeconomic studies in AD, particularly focusing on caregiver burden, quality of life (QOL), and resource utilization. Three economic models of AD were presented based on data from the United States, Canada, and the United Kingdom. In two studies, these data were then used to model the cost-effectiveness and effect on cost of treatment with donepezil. Both studies suggested a possible cost advantage for the use of donepezil, when compared with no placebo or treatment, particularly when donepezil is used appropriately in mild-to-moderate AD. These data need to be interpreted with care, as none of the cost or utility information were collected during the clinical trials. Additional data from a 2-year clinical trial of selegiline and vitamin E suggest that cognitive measures may be poor predictors of economic outcome, which is better measured directly. Both economic models of donepezil rely on short-term cognitive data to predict long-term outcome, a methodf that may not be useful in predicting economic savings. The issues facing pharmacoeconomists, researchers, clinicians, and families in the future were addressed in a series of workshops using a method of strategic futuring. The workshops attempted to see 7 years into the future for a range of areas, including consumer and caregiver use of pharmacoeconomic data; early detection and prevention; Japanese perspectives; activities of daily life and what will be daily life activities; caregiver burden; QOL at the end of life; new uses for new information and communication technology in clinical research; and physicians' use of pharmacoeconomic data. A range of exciting futures were predicted, although common themes that arose when considering barriers to achieving these futures included cost, education, political will, confidentiality, privacy, and ethics. The first conference was deemed to have been a success, having attracted more than 160 delegates and many distinguished speaker. A second conference is planned for the year 2000. Over the next 2 years, research needs to be broadened particularly in the methodological areas of resource utilization, QOL, and caregiver burden. Data from clinical trials with relevant economic and QOL outcomes will be needed by purchasers if drug treatments for dementia are to gain widespread use. It is also hoped that the models described at the meeting may become more freely available to politicians, purchasers, clinicians, and caregivers to help them make better decisions about treatment.

Aged↗
PubMed1998

Antimicrobial management of presumed microbial keratitis: guidelines for treatment of central and peripheral ulcers.

AIMS: To determine the quantitative relation between the major risk factors for microbial keratitis of previous ocular surface disease and contact lens wear and central and peripheral infiltration, often associated with ulceration, in order to establish a rational chemotherapeutic management algorithm. METHODS: Data from 55 patients were collected over a 10 month period. All cases of presumed microbial keratitis where corneal scrapes had been subjected to microbiological examination were included. Risk factor data and laboratory outcome were recorded. Antimicrobial regimens used to treat each patient were documented. RESULTS: 57 episodes of presumed microbial keratitis were identified from 55 patients, 24 male and 31 female. There were 30 central infiltrates and 27 peripheral infiltrates of which 28 were culture positive (73% of central infiltrates, 22% of peripheral infiltrates). 26 patients had worn contact lenses of whom 12 had culture positive scrapes (9/14 for central infiltrates, 3/12 for peripheral infiltrates). 31 patients had an ocular surface disease of whom five previous herpes simplex virus keratitis patients developed secondary bacterial infection. Anterior chamber activity and an infiltrate size > or = 4 mm2 were more common with culture positive central infiltrates than peripheral infiltrates (chi 2 test = 11.98, p < 0.001). CONCLUSIONS: Predisposing factors for "presumed" microbial keratitis, either central or peripheral, were: ocular surface disease (26/57 = 45.6%), contact lens wear (26/57 = 45.6%), and previous trauma (5/57 = 8.8%). Larger ulceration (> or = 4 mm2) with inflammation was more often associated with positive culture results for central infiltration. None of these four variables (contact lens wear, ocular surface disease, ulcer size, anterior chamber activity) were of intrinsic value in predicting if a peripheral infiltrate would yield identifiable micro-organisms. Successful management of presumed microbial keratitis is aided by a logical approach to therapy, with the use of a defined algorithm of first and second line broad spectrum antimicrobials, for application at each stage of the investigative and treatment process considering central and peripheral infiltration separately.

Acanthamoeba Keratitis↗
PubMed1998

Determination of volumetric cerebrospinal fluid absorption into extracranial lymphatics in sheep.

We estimated the volumetric clearance of cerebrospinal fluid (CSF) through arachnoid villi and extracranial lymphatics in conscious sheep. Catheters were inserted into both lateral ventricles, the cisterna magna, multiple cervical lymphatics, thoracic duct, and jugular vein. Uncannulated cervical vessels were ligated. 125I-labeled human serum albumin (HSA) was administered into both lateral ventricles. 131I-HSA was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. From mass balance equations, total volumetric absorption of CSF averaged 3.37 +/- 0.38 ml/h, with 2.03 +/- 0.29 ml/h (approximately 60%) removed by arachnoid villi and 1.35 +/- 0.46 ml/h (approximately 40%) cleared by lymphatics. With projected estimates for noncannulated ducts, total CSF absorption increased to 3.89 +/- 0.33 ml/h, with 1.86 +/- 0.49 ml/h (48%) absorbed by lymphatics. Additionally, we calculated total CSF drainage to be 3.48 +/- 0.52 ml/h, with 54 and 46% removed by arachnoid villi and lymphatics, respectively, using previously published mass transport data from our group. We employed estimates of CSF tracer concentrations that were extrapolated from relationships observed in the study reported here. We conclude that 40-48% of the total volume of CSF absorbed from the cranial compartment is removed by extracranial lymphatic vessels.

Animals↗
PubMed1998

Raised intracranial pressure increases CSF drainage through arachnoid villi and extracranial lymphatics.

We demonstrated previously that about one-half of cerebrospinal fluid (CSF) removed from the cranial vault was cleared by extracranial lymphatic vessels. In this report we test the hypothesis that lymphatic drainage of CSF increases as intracranial pressure (ICP) is elevated in anesthetized sheep. Catheters were inserted into both lateral ventricles, cisterna magna, cervical lymphatics, and jugular vein. A ventriculocisternal perfusion system was employed to regulate CSF pressures and to deliver a protein tracer (125I-labeled human serum albumin) into the CSF compartment. 131I-labeled human serum albumin was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. ICP was controlled by adjusting the height of the inflow reservoir and the cisterna magna outflow catheter appropriately. The experimental design consisted of a 3-h period of lower pressure followed by a 3-h period of higher pressure in the same animal (10-20 or 20-30 cmH2O). We determined that incremental changes in ICP were associated with higher CSF transport through lymphatic and arachnoid villi routes in all eight animals tested (P = 0.004).

Animals↗
PubMed1998

Sclerosing encapsulating peritonitis: early and late results of surgical management in 32 cases. French Associations for Surgical Research.

OBJECTIVE: To propose guidelines for treatment based on the study of early and late outcome after various surgical procedures for sclerosing encapsulating peritonitis (SEP). PRIMARY BACKGROUND DATA: SEP is rare. The main complication is intestinal obstruction. Ideal treatment is resection of the membrane, whenever possible. Mortality and morbidity, however, have not been well analyzed. METHODS: The case records and histopathological reports of 32 operated cases of SEP (18 centers during 16 years) were retrospectively studied. Patients underwent four types of procedures: group 1 (n = 5), membrane resection; group 2 (n = 12), enterolysis with partial excision of the membrane; group 3 (n = 7), intestinal resection, and group 4 (n = 8), exploratory laparotomy only. Five cases were considered as idiopathic. Medical and surgical antecedent history for the 27 other cases (6 patients had associations) included laparotomy for carcinoma (n = 14) or benign disorders (n = 5), beta-blocker treatment (n = 4), cirrhotic ascites (n = 4), generalized peritonitis (n = 3) and continuous ambulatory peritoneal dialysis (n = 3). Indications for operation included subacute (n = 22) or acute intestinal obstruction (n = 6), abdominal mass (n = 8), other clinical presentations (n = 4) and asymptomatic SEP discovered during surgery for portacaval shunt (n = 1). Seven patients had two associated clinical presentations. All cirrhotic patients with ascites and the asymptomatic patient were in group 4. None of the imaging techniques (plain radiograms, barium follow-through, sonograms and CT scans) were formally contributive to the preoperative diagnosis of SEP. RESULTS: In group 1, both complicated patients, one with an inadvertent intraoperative intestinal wound, the other with a postoperative intestinal leak, healed uneventfully. In group 2, 4 inadvertent intraoperative intestinal wounds led to 4 postoperative leaks with 3 consequent deaths. One further patient died of persistent intestinal obstruction. In group 3, 1 inadvertent intestinal intraoperative wound healed uneventfully and 2 deaths, one due to persistent intestinal obstruction associated with anastomotic leakage and the other due to ventricular fibrillation, were noted. In group 4, there were no intraoperative wounds, no postoperative morbidity or deaths. The median follow-up was 49.5 months (range 4-142 months). Seven patients (1 or 2 in each group) experienced transient episodes of subacute intestinal obstruction between 1 month and 6 years after discharge, none of which required a repeat operation. Eight patients (in all groups) died of their initial cancer between 4 and 75 months after discharge. CONCLUSIONS: Our results suggest that: (1) resection of the membrane should be attempted when feasible; (2) in case of inadvertent intestinal wound(s), the most proximal one should be brought out as a stoma, and partial resections should not be anastomosed primarily, but (3) no surgical treatment is required in ascites, asymptomatic SEP or subacute intestinal obstruction.

Adult↗
PubMed1997

The use of exfoliative cell samples to map clonal genetic alterations in the oral epithelium of high-risk patients.

Although it is widely accepted that clonal genetic alterations are an essential component of tumor progression, little is known of the distribution of such changes in high-risk lesions or how such clones are altered over time. We explored the feasibility of using exfoliative cells collected by scraping the mucosal surface to detect allelic loss in oral lesions of 22 patients (14 squamous cell carcinomas, 2 carcinomas in situ, and 6 dysplasias). The data show that the patterns of allelic loss observed in these samples closely represent those observed in biopsies of the same region. Furthermore, early indications are that this approach can be used to detect recurrent outgrowth of clones of altered cells in patients after therapy.

Adult↗
PubMed1997

Colonization of transplant unit water supplies with Legionella and protozoa: precautions required to reduce the risk of legionellosis.

Organ transplant recipients and other immunosuppressed patients are known to be at increased risk of nosocomial Legionnaires' disease. Although the ecology of Legionella in hospital water storage and distribution systems (including a protozoonotic relationship with free-living protozoa) has been well documented, little is known regarding the quality of water supplied to high-risk units. Hot- and cold-water samples (two first draw and one run to waste for 5 min) were taken from 69 (85%) of the 81 United Kingdom organ transplant units (31 renal, 24 bone marrow, nine cardiopulmonary and five liver transplant units) and cultured for Legionella and protozoa. Legionella spp. were isolated from the water supplies of 38 (55%) units and Legionella pneumophila from 31 (45%). The blue-white fluorescent group of Legionella (Legionella gormanii, Legionella bozemanii and others) was isolated from 18 (26%) units. Free-living protozoa were isolated from 47 units (68%) and genera of the protozoa known to permit the intracellular growth of Legionella (PGIGL), from 40 units (58%). Possible associations between Legionella and the variables Protozoa; PGIGL; water pH; and circulating water temperature (recorded after running to waste for 5 min) were examined by logistic regression analysis. In cold-water supplies, a significant association was found between the isolation of Legionella and PGIGL (P = 0.032; OR = 1.81; 95% CI 1.1-3.1). In hot-water supplies, an inverse association was found between the isolation of Legionella and circulating water temperature (P = 0.034; OR = 1.0719 per degree C; 95% CI 1.0052-1.1432). (We failed to isolate Legionella when the circulating hot water was > 58 degrees C. No other associations were significant. We recommend the active surveillance of water quality in high-risk patient areas, and that transplant units, either with a history of nosocomial Legionnaires' disease, or where active surveillance indicates a persistently high Legionella colony count, take remedial action. The quality of cold water may be improved by provision of a dedicated supply taken directly from the incoming mains; and of hot water by the use of a dedicated calorifier, able to maintain a minimum circulating hot water return temperature of 60 degrees C.

Cross Infection↗
PubMed1997

Lymphatic drainage of the CNS: effects of lymphatic diversion/ligation on CSF protein transport to plasma.

The plasma recovery of an intraventricularly administered protein was compared before and after lymph diversion/ligation in the same conscious sheep to determine the relative roles of arachnoid villi and lymphatics in the clearance of a cerebral spinal fluid tracer. 125I-human serum albumin was injected into both lateral ventricles, and venous blood was sampled. One day later, multiple cervical vessels and the thoracic duct were cannulated for lymph collection. Uncannulated vessels were ligated. The experiment was repeated with 131I-human serum albumin as the tracer. Before lymph diversion/ligation, the time-averaged tracer transport into the plasma was 6.4 +/- 1.0%/h, with an average 6-h plasma recovery of 38.2 +/- 5.7% (percentage of injected dose). After lymph diversion/ligation, the values dropped to 2.9 +/- 0.5%/h and 17.7 +/- 2.7%, respectively. The collected lymph contained 8.7 +/- 2.6% of the tracer. No significant differences were observed in sham-operated animals. In conclusion, extracranial lymphatic vessels in sheep transport approximately one-half of the protein tracer from the cerebral spinal fluid compartment into plasma.

Animals↗
PubMed1996

Sweet's syndrome in a patient with oral cancer associated with radiotherapy.

Approximately 10-20% of the reported patients with acute febrile neutrophilic dermatosis (Sweet's syndrome) have an associated neoplasm. Oral findings of Sweet's syndrome are rarely reported, and no cases in patients with oral cancer have been reported to date. This report describes the clinico- and histopathological findings of Sweet's syndrome in a patient with oral cancer, treated with radiotherapy. After 10 fractions of external beam radiotherapy, treatment was interrupted because of severe oral mucositis which extended beyond the radiation fields. Two days later the patient developed multiple tender skin lesions and the diagnosis Sweet's syndrome was made. Skin and oral lesions resolved without additional treatment and did not recur upon resuming radiotherapy. As suggested in previous case reports, tumour antigens might play a role in the development of Sweet's syndrome. In this case, irradiation therapy may also have been a trigger for this syndrome.

Carcinoma, Squamous Cell↗
PubMed1996

Amebic keratitis in a wearer of disposable contact lenses due to a mixed Vahlkampfia and Hartmannella infection.

PURPOSE: To support the hypothesis that Acanthamoeba is not a unique cause of amebic keratitis, we report a case of amebic keratitis in which viable Acanthamoeba could not be isolated from corneal tissue. Vahlkampfia and Hartmannella, two other genera of free-living ameba, were isolated, however, using prolonged culture. METHODS: A 24-year-old wearer of soft contact lenses had keratitis. Extensive histologic and microbiologic investigations were performed on corneal scrape, biopsy, and keratoplasty tissue. Contact lenses, storage case, and the home water supply, where contact lens hygiene was practiced, were examined for the presence of micro-organisms. RESULTS: No viruses, pathogenic bacteria, or fungi were detected from corneal tissue samples. Amebae were observed using light and electron microscopy, but these could not be unequivocally classified using immunocytochemical staining. Viable Vahlkampfia and Hartmannella, but no Acanthamoeba, were isolated from the corneal biopsy sample. Indirect immunofluorescence with a range of polyclonal rabbit antisera raised against axenically cultivated stains of the three amebal genera was unhelpful because of cross-reactivity. A diverse range of micro-organisms was present within the storage case, including the three amebal species. Amebic cysts also were associated with the contact lens. CONCLUSION: A mixed non-Acanthamoeba amebic keratitis has been identified in a wearer of soft contact lenses where lack of storage case hygiene provided the opportunity for the free-living protozoa Vahlkampfia and Hartmannella to be introduced to the ocular surface. When Acanthamoeba-like keratitis occurs, but where Acanthamoeba cannot be isolated using conventional laboratory culture methods, alternate means should be used to identify other amebae that may be present. Polyclonal immunofluorescent antibody staining was unreliable for generic identification of pathogenic free-living amebae in corneal tissue.

Adult↗