Biomedical subjects
J Ryan
Publications and source records attributed to J Ryan.
A survey of tick-borne bacteria and protozoa in naturally exposed dogs from Israel.
Antibody reactivity against seven bacterial or protozoal pathogens was measured in sera derived from 40 dogs suspected of a tick-borne disease. Sera from 73% (29/40) of the dogs reacted with three or more test antigens. Seroreactivity was most prevalent to Babesia canis antigen (90%) followed by Babesia gibsoni (75%), Ehrlichia canis (63%), Rickettsia conorii--Moroccan strain (58%), Rickettsia conorii--Israeli strain no. 2 (28%), Borrelia burgdorferi (10%) or Bartonella vinsonii (berkhoffii) (10%). Seroconversion documented in seven dogs, supported an acute phase diagnosis of ehrlichiosis in four dogs, R. conorii infection in three dogs and babesiosis in one dog. In the remaining dogs, correlation of clinical abnormalities with increased seroreactivity was not established through the design of this study. Although Lyme borreliosis has not been reported in people in Israel, Western blot analysis for antibodies reactive to B. burgdorferi identified genus-specific antiflagellin antibodies indicating that dogs in Israel are exposed to a Borrelia species. Identification of species-specific seroreactivity was not possible and infection with a Borrelia species other than B. burgdorferi is likely. Seroreactivity to B. vinsonii (berkhoffii) in dogs outside the USA is reported here for the first time.
Interleukin-4 receptor signalling mechanisms and their biological significance.
These studies describe key elements of the means through which the IL-4 receptor transduces functions of IL-4 and show relationships between these biochemical events and the major biological consequences of IL-4 action. In large measure, the control of IL-4-mediated growth and gene activation are segregated to different regions of the cytosolic domain of the receptor. These regions function by interacting with specific signaling molecules, leading to the activation of these molecules and the intracellular signaling pathways that result in the observed biological effects of IL-4.
Biochemical and catalytic properties of an endoxylanase purified from the culture filtrate of Thermomyces lanuginosus ATCC 46882.
An endoxylanase (1,4-beta-D-xylan xylanohydrolase, EC 3.2.1.8) from the culture filtrates of T. lanuginosus ATCC 46882 was purified to homogeneity by DEAE-Sepharose and Bio-Gel P-30 column chromatographies. The purified endoxylanase had a specific activity of 888.8 mumol min-1 mg-1 protein and accounted for approximately 30% of the total protein secreted by this fungus. The molecular mass of native (non-denatured) and denatured endoxylanase were 26.3 and 25.7 kD as, respectively. Endoxylanase had a pI of 3.7 and was optimally active between pH 6.0-6.5 and at 75 degrees C. The enzyme showed > 50% of its original activity between pH 5.5-9.0 and at 85 degrees C. The pH and temperature stability studies revealed that this endoxylanase was almost completely stable between pH 5.0-9.0 and up to 60 degrees C for 5 h and at pH 10.0 up to 55 degrees C for 5 h. Thin-layer chromatography (TLC) analysis showed that endoxylanase released mainly xylose (Xyl) and xylobiose (Xyl2) from beechwood 4-O-methyl-D-glucuronoxylan, O-acetyl-4-O-methyl-D-glucuronoxylan and rhodymenan (a beta-(1-->3)-beta(1-->4)-xylan). Also, the enzyme released an acidic xylo-oligosaccharide from 4-O-methyl-D-glucuronoxylan, and an isomeric xylotetraose and an isomeric xylopentaose from rhodymenan. The enzyme hydrolysed [1-3H]-xylo-oligosaccharides in an endofashion, but the hydrolysis of [1-3H]-xylotriose appeared to proceed via transglycosylation. since the xylobiose was the predominant product. Endoxylanase was not active on pNPX and pNPC at 40 and 100 mM for up to 6 h, but showed some activity toward pNPX at 100 mM after 20-24 h. The results suggested that the endoxylanase from T. lanuginosus belongs to family 11.
Epilepsy in the accident and emergency department--developing a code of safe practice for adult patients. South East and South West Thames Accident and Emergency Specialty Sub-committees.
OBJECTIVES: To benchmark current practice in the management of adult patients presenting with seizures to the accident and emergency (A&E) departments by performing a comparative interdepartmental audit. To assess the quality and degree of completeness of documentation in A&E records and to develop a proforma for the documentation of any case presenting with a seizure which would incorporate management guidelines for use by A&E doctors. METHODS: This was a retrospective, criterion based audit carried out in 12 A&E departments in the South Thames region. It involved 1200 adult patients who presented to A&E departments after a seizure. The degree of completeness of A&E records was assessed using criteria identified by A&E consultants and neurologists. Guidelines for use in the management of patients with seizures have been produced. RESULTS: Important aspects of the history and examination were frequently unrecorded in patients' notes. The recording of vital signs was particularly poor. A diversity of practice was shown between the departments that were audited and the number of investigations performed in each department varied considerably. Hospital admissions for patients with first seizures varied widely between departments, ranging from between 34.6% to 91.7% of cases. Documentation of advice given to patients about driving was evident in just 0.9% of cases. CONCLUSIONS: Wide interdepartmental variation exists in both the quality of information recorded in A&E records and in the management of patients. Deficiencies could be minimised and potential improvements in the quality of documentation might be achieved by the introduction of a structured proforma incorporating pre-defined management guidelines.
What goes wrong at a disaster or major incident?
From a receiving hospital's perspective a major incident is 'an accident about to happen'. The potential for chaos is present at every phase. This short paper describes in a chronological fashion the common traps and pitfalls and how to avoid them.
Straddle injuries--is current practice safe?
Genital injuries may be markers of sexual abuse and child protection issues should be considered when case present. This study evaluates the quality of history taking and the physical examination of children who present with straddle injuries to an accident and emergency department. A retrospective analysis of the accident and emergency case notes of children who presented over a 12-month period with straddle injuries was undertaken. A scoring system of risk factors was devised to help identify children at risk of sexual abuse and applied to the case notes. The results showed that the documentation of injuries was inadequate in the majority of cases, increasing the risk that cases of sexual abuse may be missed. Core questions which aid in the selection of children who require further evaluation have previously been identified. Utilizing the information from our findings we have devised a protocol for the assessment of children with straddle injuries which includes an action plan for the management of such cases.
A controlled trial of an educational program to prevent low back injuries.
BACKGROUND: Low back injuries are common and costly, accounting for 15 to 25 percent of injuries covered by workers' compensation and 30 to 40 percent of the payments made under that program. The high costs of injury, the lack of effective treatment. and the evidence that there are behavioral risk factors have led to widespread use of employee education programs that teach safe lifting and handling. The effectiveness of those programs, however, has received little rigorous evaluation. METHODS: We evaluated an educational program designed to prevent low back injury in a randomized, controlled trial involving about 4000 postal workers. The program, similar to that in wide use in so-called back schools, was taught by experienced physical therapists. Work units of workers and supervisors were trained in a two-session back school (three hours of training), followed by three to four reinforcement sessions over the succeeding few years. Injured subjects (from both the intervention and the control groups) were randomized a second time to receive either training or no training after their return to work. RESULTS: Physical therapists trained 2534 postal workers and 134 supervisors. Over 5.5 years of follow-up, 360 workers reported low back injuries, for a rate of 21.2 injuries per 1000 worker-years of risk. The median time off from work per injury was 14 days (range, 0 to 1717); the median cost was $204 (range, zero to $190,380). After their return to work, 75 workers were injured again. Our comparison of the intervention and control groups found that the education program did not reduce the rate of low back injury, the median cost per injury, the time off from work per injury, the rate of related musculoskeletal injuries, or the rate of repeated injury after return to work; only the subjects' knowledge of safe behavior was increased by the training. CONCLUSIONS: A large-scale, randomized, controlled trial of an educational program to prevent work-associated low back injury found no long-term benefits associated with training.
In differentiated CD4+ T cells, interleukin 4 production is cytokine-autonomous, whereas interferon gamma production is cytokine-dependent.
CD4+ T cells from T cell receptor transgenic mice that have been vigorously primed to be interleukin (IL)-4 producers (T(H2) cells) are capable of producing IL-4 even if restimulated in the absence of IL-4 and in the presence of IL-12. T cells vigorously primed in the absence of IL-4 (T(H1) cells) fail to produce IL-4 even if restimulated under conditions that would cause a naive T cell to produce IL-4. In contrast, interferon gamma (IFN-gamma) production is highly cytokine-regulated. T cells primed in the presence of IL-4 develop into IFN-gamma producers if IFN-gamma is included in the priming culture and if the cells are challenged in the presence of IL-12, presumably reflecting the role of IFN-gamma in inducing responsiveness to IL-12. Cells primed in the absence of IL-4 become highly responsive to IL-12 if IFN-gamma is included in the priming culture, and these cells are excellent IFN-gamma producers upon challenge; IL-12 considerably enhances their production of IFN-gamma. If cells are primed in the absence of IL-4 and IFN-gamma, they show very weak responsiveness to IL-12 as determined by STAT-4 activation. However, these cells acquire IL-12 responsiveness if cultured with IFN-gamma for a period as short as 4 hr. Thereafter, they produce large amounts of IFN-gamma upon challenge with antigen in the presence of IL-12. These results indicate that in primed CD4+ T cells, IL-4 production is largely cytokine-autonomous, whereas IFN-gamma production is highly cytokine-regulated.
L-arginine prevents cyclosporin A-induced pulmonary vascular dysfunction.
BACKGROUND: Cyclosporin A is known to alter endothelium-dependent responses to different agonists. Few data are available concerning the effect of cyclosporin A on the pulmonary vascular bed. METHODS: The endothelium-dependent responses to acetylcholine (20 micrograms), bradykinin (5 micrograms), and substance P (5 micrograms) were investigated in a dog model of left lung autoperfusion at constant flow. RESULTS: The vasodilator response to bradykinin and substance P was significantly decreased with cyclosporin A (20 mg) administration. The average decreases in pulmonary arterial pressure with bradykinin were 5.4 +/- 1.5 mm Hg and 2.4 +/- 0.4 mm Hg before and after cyclosporin A administration, respectively (p = 0.04). The average decreases in pulmonary arterial pressure with substance P were 4.4 +/- 1.0 mm Hg and 1.8 +/- 0.5 mm Hg before and after cyclosporin A administration, respectively (p = 0.04). The responses to acetylcholine and the endothelium-independent relaxing agent nitroglycerin were not significantly affected by cyclosporin A. The effects of cyclosporin A on endothelium-dependent responses to bradykinin and substance P were overcome by the administration of L-arginine (200 mg/kg intravenously). The decreased response to bradykinin and substance P after cyclosporin A administration was not significantly affected by indomethacin, a cyclooxygenase inhibitor. The pulmonary angiotensin-converting enzyme activity was also measured using [3H]benzoyl-phenylalanyl-glycyl-proline, an inactive angiotensin-converting enzyme substrate. There was an average [3H]benzoyl-phenylalanyl-glycyl-proline hydrolysis of 54% +/- 2% and 55% +/- 2% before and after cyclosporin A administration, respectively (not significant). CONCLUSIONS: The present study suggests that cyclosporin A selectively decreases endothelium-dependent responses to bradykinin and substance P without affecting the cyclic guanosine monophosphate-dependent pathway in the canine pulmonary vascular bed. The decreased endothelium-dependent responses to bradykinin and substance P are not related to increased angiotensin-converting enzyme activity. The toxic effect of cyclosporin A on endothelium-dependent responses is reversible by the administration of L-arginine, a source of substrate for nitric oxide.
Studies on the production of galactomannanase by thermophilic fungi.
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Bilateral locked posterior shoulder dislocation in a footballer.
Posterior dislocation of the shoulder is an uncommon injury, accounting for between 2% and 4% of all shoulder dislocations. It occurs most frequently in patients following convulsions or direct anterior force to the shoulder. It is a particularly uncommon injury in sport. This paper reports an unusual case of bilateal locked posteriorly dislocated shoulders in a previously healthy young man who fell while playing football.
How good are doctors at estimating children's weight?
OBJECTIVE: (1) To see whether children are weighted before drugs are prescribed in an accident and emergency (A&E) department; (2) to assess how safe it is for doctors to guess children's weight if they prescribe "by eye". METHODS: An audit of 100 sets of notes was performed to see if children were weighed before drugs were prescribed. A&E senior house officers were asked to estimate the weight of 75 children aged 12 years and under. RESULTS: Children were weighed before prescribing in only two out of 100 cases. The mean difference between the actual and estimated weights was -0.21 (not significantly different from zero: P = 0.40); 95% of the estimates were within two standard deviations of the mean difference. The percentage difference between the actual and estimated weight varied between overestimates of 300% and underestimates of nearly 100%. CONCLUSIONS: The average guess of doctors as a group was approximately correct. However, there was a wide range of estimates for individuals. If the child's weight is guessed, the doctor could risk under- or overprescribing analgesia, sedation, or intravenous fluids. Given the wide range of estimates, actual weights are required for accurate prescribing. Prescribing on an age basis may be acceptable for drugs such as paracetamol or amoxycillin, but it is imperative to prescribe on a mg/kg basis for opiates, sedatives, and intravenous fluids because of the large variation in weight that can occur for a single age.
Lipopolysaccharide induces cell shrinkage in rabbit ventricular cardiac myocytes.
The effects of 10 ng/ml of lipopolysaccharide (LPS) on cell volume were examined in rabbit left ventricular myocytes. The myocytes were isolated with depyrogenated digestive enzymes (< 0.7 ng/ml of LPS) to minimize tolerance. Myocyte cross-sectional area (CSA) did not change after 1 h of LPS. However after 8 h, the CSA decreased to 0.93 +/- 0.01 (SE) of the baseline CSA (time = 0) in 19 LPS-exposed myocytes compared with 1.00 +/- 0.01 in 13 control myocytes (P = 0.0015). LPS-induced cell shrinkage was completely blocked by coincubation with 1 mM N-monomethyl-L-arginine, indicating a nitric oxide-mediated mechanism. Cardiac guanosine 3',5'-cyclic monophosphate (cGMP) did not change after 1 h but increased 6 h after LPS (548 +/- 31 vs. 312 +/- 20 fmol/mg protein in control cells; P < 0.05). After 8 h, bumetanide (10 microM for 30 min), a Na+/K+/2Cl- cotransport inhibitor, decreased the CSA in 15 control myocytes to 0.92 +/- 0.02 of the baseline CSA. However, in 19 myocytes with a CSA of 0.93 +/- 0.01 of baseline after 8 h of LPS, the addition of bumetanide caused no additional cell shrinkage. We conclude that low levels of LPS increase cardiac cGMP to inhibit Na+/K+/2Cl- cotransport, causing significant cell shrinkage in cardiac myocytes.
Massive bone allografts for limb salvage.
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Alcohol consumption and blood pressure in recently hospitalised patients.
One-thousand-four-hundred-and-fifty-three patients admitted to a teaching hospital, haemodynamically stable and not severely ill nor in significant pain, were interviewed within 48 h of admission and demographic data and a detailed drinking history were obtained. Supine blood pressures (BP) were recorded on the day following admission. The mean age of the population was 60.5 +/- 19.9 years (range 16-99 years) and the mean reported alcohol consumption was 67.8 +/- 273 g/week (range 0-6125 g/ week). Thirty-six percent of patients were currently receiving antihypertensive drug therapy. On multivariant analysis, reported alcohol intake was not significantly related to systolic BP (beta = 0.000, p = 0.902) or diastolic BP (beta = 0.028, p = 0.281). Age (beta = 0.331, p = 0.0001) and body weight (beta = 0.121, p = 0.0002) were significant independent predictors of systolic BP, and body weight was a significant independent predictor of diastolic blood pressure (beta = 0.207, p < 0.0001). A relationship between alcohol consumption and blood pressure was not apparent in this population of patients following admission to hospital. A positive association between alcohol consumption and blood pressure may not be a universal finding and may be contributed to by a "white coat" effect.