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Biomedical subjects

C Walker

Publications and source records attributed to C Walker.

At least 109 records · Page 6Linked to original sources

An equine herpesvirus 1 mutant with a lacZ insertion between open reading frames 62 and 63 is replication competent and causes disease in the murine respiratory model.

An equine herpesvirus 1 (EHV-1) mutant was constructed by inserting a lacZ expression cassette into the intergenic region upstream of gene 62 (glycoprotein L; gL) and downstream of gene 63 (a homologue of the herpes simplex virus transcriptional activator ICP0). The recombinant lacZ62/63-EHV-1 had similar growth kinetics in cell culture to those of the parental wild type (wt) virus, with indistinguishable cytopathic effects and plaque morphology. Reverse transcriptase PCR confirmed that the lacZ insertion did not interfere with transcription of gL and immunoblot analysis indicated there was no modification to late gene expression as monitored by synthesis of EHV-1 glycoproteins C and D. The parental EHV-1 isolate HVS25A used here had almost identical nucleotide sequence to that published for isolate Ab4, in a 1200 bp region surrounding the insert, but lacked a HindIII site corresponding to Ab4 position 109,048. The lacZ62/63-EHV-1 caused respiratory disease in BALB/c mice with clinical signs, histopathology and virus titres in lungs throughout days 1-5 post infection similar to those induced by wt EHV-1. X-gal staining for beta-galactosidase expression in murine lungs clearly demonstrated EHV-1 infection in cells of the bronchiolar epithelium and pulmonary parenchyma, with a peak of infection evident at day 2 post infection, when up to 50% of bronchioles demonstrated blue-staining and thus virus-infected epithelial cells. The construction of this replication competent virus carrying a reporter gene identifies a site for insertion of foreign genes and will facilitate studies on the pathogenesis of EHV-1.

Animals↗

Balance in the cat: role of the tail and effects of sacrocaudal transection.

To determine whether the tail of the domestic cat plays a role in balance during locomotion, four cats were trained to traverse a narrow beam. To challenge balancing ability, a sudden lateral displacement was imparted to the beam as the subject was crossing. Freeze-frame videotape analysis revealed that cats responded to beam movement by rapidly moving the tail in the opposite direction. Adjustment of the tail contributed to realignment of the hips over the beam and enabled the animal to remain aboard the beam. Following complete sacrocaudal spinal transection, that eliminated supraspinal control to only the tail, cats fell significantly more often in response to movements of the beam. The importance of the cat's tail for balance, and the utility of this system for modeling functional consequences of spinal cord injury and therapeutic interventions, are discussed.

Animals↗

Using remote sensing to predict outbreaks of Oestrus ovis in Namibia.

The Directorate of Veterinary Services of the Ministry of Agriculture, Water and Rural Development of Namibia issues warnings to farmers in the south of the country about the likelihood of infestation of small-stock by the nasal bot fly, Oestrus ovis. Farmers can then treat their stock at the most appropriate time. The O. ovis puparia develop at shallow depths in the soil and the timing of emergence is directly dependent on climate conditions, specifically the number of degree-days above a particular threshold soil temperature. Based on temperature measurements from only a few stations scattered throughout the country, the veterinary department warnings lack precision in space and time. This paper presents an attempt to support the programme of warnings with accumulated temperature information from Meteosat satellite images, in order to strengthen predictions of the time of emergence in specific places, and to improve the precision and reliability of warnings given to farmers.

Animals↗

Primary and challenge infection of mice with equine herpesvirus 1, strain HSV25A.

Clinical signs, haematology, lymphocyte subset analysis, viral clearance, lung histopathology and humoral and cell-mediated (CMI) immune responses were monitored throughout the acute and convalescent phases of infection in groups of BALB/c mice infected intranasally with equine herpesvirus 1 (EHV-1), strain HSV25A. Primary infection caused a leucocytosis due to a neutrophilia during days 1 and 2 post-infection (pi) and a B lymphocytosis at day 1 pi. Serum ELISA antibodies were detected by 7 days pi and neutralising antibodies by 2 weeks pi. Mice infected with EHV-1 were not protected against disease when challenged with EHV-1 12 weeks later. However, viral clearance from lungs was significantly faster and the antibody response was markedly enhanced within the first few days of challenge infection. A CMI response was detected by 5 days after primary infection, but the level of responsiveness was not increased by challenge infection, although the lungs of challenged mice had markedly increased numbers of mononuclear cells around blood vessels and bronchioles. Specific antibodies to glycoprotein (g) B were detected by 2 weeks pi, 4 weeks earlier than the detection of antibodies to gC and 10 weeks before those to gD. The primary response was relatively short-lived with neither ELISA antibody nor lymphocyte proliferation was evident by 6 months pi.

Animals↗

Funding Melbourne's hospitals: some historical moments.

In 1993 the Victorian Government introduced casemix funding as part of its restructure of the public hospital system. Casemix funding provides a new basis for government funding according to outcomes. At the same time, restructure of hospitals allows for a reconsideration of who is eligible to use them. Historical research into the growth of the public hospital system in Melbourne shows that attempts to reform the hospital system are as old as the system itself. This paper argues that the views of hospitals in funding crises and the solutions that are recommended have more to do with the politics of the day than the economics of running hospitals.

Cost Control↗

Genetic analysis of chromosomal rearrangements in the cyclops region of the zebrafish genome.

Genetic screens in zebrafish have provided mutations in hundreds of genes with essential functions in the developing embryo. To investigate the possible uses of chromosomal rearrangements in the analysis of these mutations, we genetically characterized three gamma-ray induced alleles of cyclops (cyc), a gene required for development of midline structures. We show that cyc maps near one end of Linkage Group 12 (LG 12) and that this region is involved in a reciprocal translocation with LG 2 in one gamma-ray induced mutation, cyc(b213). The translocated segments together cover approximately 5% of the genetic map, and we show that this rearrangement is useful for mapping cloned genes that reside in the affected chromosomal regions. The other two alleles, cyc(b16) and cyc(b229), have deletions in the distal region of LG 12. Interestingly, both of these mutations suppress recombination between genetic markers in LG 12, including markers at a distance from the deletion. This observation raises the possibility that these deletions affect a site required for meiotic recombination on the LG 12 chromosome. The cyc(b16) and cyc(b229) mutations may be useful for balancing other lethal mutations located in the distal region of LG 12. These results show that chromosomal rearrangements can provide useful resources for mapping and genetic analyses in zebrafish.

Alleles↗

A randomized trial of mobilization of peripheral blood stem cells with cyclophosphamide, etoposide, and granulocyte colony-stimulating factor with or without cisplatin in patients with malignant lymphoma receiving high-dose chemotherapy.

The purpose of this study was to evaluate the addition of cisplatin to cyclophosphamide, etoposide, and granulocyte colony-stimulating factor (G-CSF) for the mobilization of peripheral blood stem cells (PBSC). Eighty-one patients with malignant lymphoma were randomized to receive either cyclophosphamide 4 g/m2 and etoposide 600 mg/m2 (CE), and G-CSF 6 microg/kg/day (n = 41), or the same drugs with cisplatin 105 mg/m2 (CEP; n = 40) followed by collection of PBSC. Seventy-eight of 81 patients (96%) had apheresis performed and 70 (86%) received high-dose chemotherapy (HDC) with PBSC support. The median number of CD34+ cells collected after CE was 19.77 compared with 9.39 x 10(6)/kg after CEP (p = 0.09). More patients receiving CEP had grade 3-4 gastrointestinal (p = 0.03) and neurologic toxicities (p = 0.05), had significant delays in recovery of neutrophils (p = 0.0001) and platelets (p = 0.009), and received more red blood cell (p = 0.03) and platelet (p = 0.08) transfusions than patients receiving CE. There were no significant differences in treatment-related deaths, relapse, survival, or event-free survival between patients receiving CE or CEP when all 81 patients or the 70 patients receiving HDC were evaluated. It was concluded that the addition of cisplatin to CE did not improve CD34+ cell yields, was associated with more morbidity and resource utilization, and was not associated with improvement in outcomes.

Adult↗

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Humans↗

Kid-1 expression is high in differentiated renal proximal tubule cells and suppressed in cyst epithelia.

The cDNA coding for the transcriptional repressor protein Kid-1 was cloned in a screen for zinc finger proteins, which are regulated during renal development and after renal ischemia. Kid-1 mRNA levels increase in the course of postnatal renal development and decrease after acute renal injury caused by ischemia or administration of folic acid. We have raised a monoclonal anti-Kid-1 antibody and demonstrate that the Kid-1 protein is strongly expressed in the proximal tubule of the adult rat kidney. During nephron development, the Kid-1 protein appears after the S-shaped body stage concomitantly with the brush-border enzyme alkaline phosphatase. In two animal models of polycystic kidney disease, the expression of Kid-1 is downregulated. The loss of expression of Kid-1 in cyst wall cells correlates with the loss of alkaline phosphatase histochemical staining. Kid-1 mRNA levels are also reduced in rodent renal cell carcinomas, another condition characterized by epithelial cell dedifferentiation and increased proliferation. We propose that Kid-1 plays an important role during the differentiation of the proximal tubule.

Aging↗

13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies for ecotoxicity.

There is growing public pressure to minimize the use of vertebrates in ecotoxicity testing; therefore, effective alternatives to toxicity tests causing suffering are being sought. This report discusses alternatives and differs in some respects from the reports of the other three groups because the primary concern is with harmful effects of chemicals at the level of population and above rather than with harmful effects upon individuals. It is concluded that progress toward the objective of minimizing testing that causes suffering would be served by the following initiatives--a clearer definition of goals and strategies when undertaking testing procedures; development of alternative assays, including in vitro test systems, that are based on new technology; development of nondestructive assays for vertebrates (e.g., biomarkers) that do not cause suffering; selection of most appropriate species, strains, and developmental stages for testing procedures (but no additional species for basic testing); better integrated and more flexible testing procedures incorporating biomarker responses, ecophysiological concepts, and ecological end points (progress in this direction depends upon expert judgment). In general, testing procedures could be made more realistic, taking into account problems with mixtures, and with volatile or insoluble chemicals.

Animal Testing Alternatives↗

Low-level chromosome 12 amplification in a primary lipoma of the lung: evidence for a pathogenetic relationship with common adipose tissue tumors.

Cytogenetic analysis of a primary lipoma of the lung removed from a 56-year-old woman revealed the presence of a supernumerary marker chromosome in all metaphase cells analyzed; namely, 47,XX,+mar. To the best of our knowledge, this is the first cytogenetic description of a primary lipoma of lung. Genetic analysis of intramuscular lipoma, atypical lipoma, and well-differentiated liposarcoma have revealed the presence of one to three supernumerary ring or giant marker chromosomes composed of chromosome 12 segments as the characteristic anomaly. The marker chromosome in the present case was shown to be composed entirely of chromosome 12 material by subsequent analysis with a chromosome 12-specific paint probe and fluorescence in situ hybridization. Thus, analogous to intramuscular lipoma, atypical lipoma, and well-differentiated liposarcoma, extra chromosome 12 material is present. These findings support a pathogenetic relationship between this lipoma of unusual anatomic location and common adipose tissue tumors.

Chromosome Aberrations↗

Allergic rhinitis history as a predictor of other future disqualifying otorhinolaryngological defects.

BACKGROUND: Problems with the otorhinolaryngological system represent the largest category of pilot referrals for specialist assessment and possible waiver recommendation in the U.S. Navy. Most of these referrals deal with allergic rhinitis (AR). Approximately 3% of all Naval aircrew have a waiver for AR. This paper tests the hypothesis that the identification of a history of AR is a predictor for the development of future disqualifying otorhinolaryngological (ear, nose, and throat, or ENT) diseases such as chronic sinusitis, alternobaric disease, conductive hearing loss, or the need for various surgical procedures (i.e., Caldwell Luc antrostomy, myringotomy, polypectomy, mastoidectomy, and functional endoscopic sinus surgery. METHODS: The U.S. Navy Aviation Medical Data Retrieval System (AMDRS) was searched for aircrew who were diagnosed only with AR in 1988. These aircrew were matched with a control group from the 1988 database who had no diagnoses of AR or any of the other disqualifying ENT diseases. The AR cohort and controls had their physical examinations up to 1995 assessed to see if any of the disqualifying ENT conditions had developed. RESULTS: There was a statistically significant increase in the number of identifiable chronic sinusitis cases but there was no significant relationship between an AR history and the development of any of the other ENT disease categories. CONCLUSION: Based on the study findings, it is doubtful that uncomplicated AR as an isolated historical diagnosis should be disqualifying for either candidate or designated aircrew.

Aerospace Medicine↗

Ankle fractures in diabetics.

Ankle fractures are common and good results are expected. Insulin dependent diabetes mellitus is also common, and long-standing disease is associated with peripheral neuropathy. A trauma unit will inevitably receive patients with both problems. We describe two salutary lessons and suggest how our experience with diabetic neuroarthropathy might be avoided.

Ankle Injuries↗

A Canadian hospital-based HIV/hepatitis C look-back notification program.

OBJECTIVE: To describe the process used to notify pediatric patients who received transfusions of blood or blood products at our institution before donor blood was routinely screened for antibodies to HIV (1985) and hepatitis C virus (1990), and to evaluate the effectiveness of the notification program. DESIGN: Patients who had received transfusions were identified through the hospital's medical records and the records from the Transfusion Medicine Laboratory. Patients were contacted by registered mail to provide notification of transfusion. A questionnaire was included with the notification to obtain information about the patient's awareness of the transfusion and whether he or she had undergone or planned to undergo testing for HIV and hepatitis C virus. SETTING: Tertiary care university-affiliated teaching hospital in Hamilton, Ont. PATIENTS: Patients 16 years of age or younger who had received blood products between February 1978 and November 1985. Patients who had received only albumin or immune serum globulin were not included as these products were not associated with viral transmission in Canada. RESULTS: Notification letters were sent to 1546 patients. Of these letters 522 (33.8%) were returned undelivered. Of the 1024 patients contacted 493 (48.1%) responded to the questionnaire, of whom 157 (31.8%) were not aware of their transfusion. A total of 130 (26.4%) of the respondents had already undergone testing for HIV, and 342 (69.4%) indicated that they would undergo such testing as a result of the notification. In contrast, only 30 (6.3%) of 474 respondents had undergone testing for hepatitis C virus, but 425 (89.7%) indicated that they would undergo such testing. Overall, the patients' response to the notification was neutral or positive; however, a number of patients expressed dissatisfaction and anxiety. CONCLUSIONS: The high proportion of patients who were unaware that they had undergone transfusion and who decided to undergo testing for HIV and hepatitis C virus as a result of notification supports the use of notification programs such as this one.

Adolescent↗

Helicobacter pylori eradication using a 7-day regimen of low-dose clarithromycin, lansoprazole and amoxycillin.

AIM: To evaluate the efficacy of a 7-day regimen of clarithromycin 250 mg b.d., amoxycillin 1 g b.d., and lansoprazole 30 mg b.d. as a treatment for Helicobacter pylori infection. METHODS: H. pylori status of dyspeptic patients was assessed by 13C-urea breath test and at endoscopy by histology, culture and rapid urease testing of gastric biopsies. Fifty-one H. pylori-positive patients were treated with the above regimen. H. pylori status was reassessed by 13C-urea breath test not less than 28 days after completing treatment. Adverse events and compliance were evaluated. RESULTS: On an intention-to-treat basis. H. pylori infection was cured in 77% (95% CI: 65-88%) of patients. Minor side-effects including diarrhoea, nausea and taste disturbance were reported by 64% of patients. Ninety-five per cent of patients consumed > 95% of tablets. Metronidazole resistance was 29% but all cultures were sensitive to amoxycillin and clarithromycin. CONCLUSION: This 7-day treatment with low-dose clarithromycin was moderately effective in curing H. pylori infection. Although compliance was excellent, there was a high frequency of minor adverse events.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Weight changes and serum sodium concentrations after an ultradistance multisport triathlon.

OBJECTIVE: This study describes the incidence of hyponatremia and the weight changes during an ultradistance multisport triathlon. DESIGN: Descriptive research. SETTING: A 1-day triathlon in which each athlete kayaks 67 km, cycles 148 km, and runs 23.8 km. PARTICIPANTS: Forty-eight athletes competing in the race were studied. INTERVENTIONS: None. MAIN OUTCOME MEASURES: All subjects were weighed before the race and on completion of the race. A blood sample for serum sodium was taken at the finish of the race. RESULTS: The mean weight change over the course of the race was a loss of 2.5 kg (SD +/- 1.7, n = 48), or a mean percentage loss of body weight of 3.1% (SD +/- 2.07). This was highly statistically significant (p < 0.0001) using the Student paired t test. No athletes gained weight, and six athletes maintained their same weight. Only one athlete was hyponatremic (Na = 134 mEq/L). This athlete maintained his weight over the course of the race and he did not seek medical attention. The mean serum sodium concentration at the end of the race was 139.3 mEq/L (SD = 2.28, n = 47). There was a significant correlation (r = 0.30, p = 0.04) between sodium levels and weight change during the race: the greater the weight loss, the higher the serum sodium concentration. There was no significant correlation between the degree of weight loss and athletes' finishing times (r = 0.11, p = 0.45). CONCLUSIONS: Symptomatic hyponatremia did not occur in the 1996 Coast to Coast multisport triathlon, although one athlete had borderline hyponatremia. Athletes lose significant amounts of weight over the course of this multisport event, but nevertheless manage to complete the race.

Adult↗