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Biomedical subjects

S Morgan

Publications and source records attributed to S Morgan.

At least 37 records · Page 2Linked to original sources

Diagnosing coeliac disease by rectal gluten challenge: a prospective study based on immunopathology, computerized image analysis and logistic regression analysis.

The purpose of this study was to evaluate the use of rectal gluten challenge in the diagnosis of coeliac disease. A total of 103 patients with features suggestive of this diagnosis were prospectively enrolled into the study; a diagnosis of coeliac disease was based on strictly defined criteria used in judging the proximal jejunal biopsy. On that basis, 45 out of the 103 patients were deemed to have coeliac disease. A slurry of gluten powder in physiological saline was introduced into the rectum, and biopsies taken before and at 2 h or 4 h after the challenge were examined immunohistochemically by computerized image analysis. Cell counts were analysed by logistic regression, and the best equations were obtained for each challenge group. The 2 h challenge yielded diagnostic sensitivity and specificity of 69.6% and 78.6% respectively. The 4 h challenge provided sensitivity and specificity of 100% and 100% respectively. These results were compared with other clinical diagnostic predictors,including anti-endomysial antibodies, which yielded diagnostic sensitivity and specificity of 70% and 98% respectively. It is concluded that a 4 h rectal challenge is a highly sensitive means of identifying gluten-sensitized individuals, and would be of particular value in cases showing negative antibody screening or equivocal biopsy appearances.

Adult↗

4-aminopyridine poisoning of crows in the Chicago area.

Poisoning of crows with the avicide 4-aminopyridine is reported. Seven crows had frequent vocalization and nervous signs; 6 died. Postmortem examination of 4 found evidence of trauma and corn-based bait present in the gastrointestinal tract. The bait contained 4-aminopyridine, a rapidly fatal nervous system toxin. When utilized by pest control professionals using manufacturer's recommendations, 4-aminopyridine has little risk of direct or relay toxicosis to non-target species. Treatment of exposed individuals involves symptomatic care and control of seizures.

4-Aminopyridine↗

The problems of aggression and violence for health-care staff.

Nurses frequently face violent and aggressive behaviour in the course of their daily work. Staff working in accident and emergency departments report the highest incidence of verbal and physical aggression and actual violence. This literature review examines the problem and highlights advice available on defusing potentially dangerous situations at work.

Aggression↗

Time- and space-resolved dynamic studies on ceramic and cementitious materials.

A review is given of the results and lessons arising from a sustained in situ diffraction study of the structure and performance of functional ceramic/cementitious materials in which synchrotron-based energy-dispersive diffraction has been the central under-pinning technique. Five particular points of discussion emerge: the demands on time resolution; the use of penetrating radiation for the in situ mode; the need for complementary techniques; re-analysing of data; spatially resolved diffraction: a new tomography. These aspects are discussed in turn using illustrative examples taken from the fields of cement hydration, clay intercalation, cation-exchanged zeolites, and particulate/fluid invasion into building and archaeological objects.

Journal Article↗

Evidence for resistance to MPTP in C57BL/6 x BALB/c F1 hybrids as compared with their progenitor strains.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is capable of producing a syndrome in mice which shares major characteristics with human Parkinson's disease. There is evidence for a genetic influence on the degree of damage exerted by MPTP, since different strains of mice can dramatically differ in their response to MPTP. We produced reciprocal F1 hybrids by crossbreeding the MPTP-susceptible C57BL/6 strain with resistant BALB/c. These hybrids were compared to the parental strains using neural and behavioral measures in order to characterize the genetic transmission of MPTP-susceptibility. The F1 generation as a whole had a lower depletion of neostriatal dopamine levels than even found in BALB/c. Furthermore, there was no significant loss of tyrosine hydroxylase-positive cells in the substantia nigra and quick recovery from deficits in motor behavior in F1, herein resembling BALB/c. We suggest that several loci are involved in susceptibility to MPTP, and that the trait is under control of recessive susceptibility and/or dominant resistance alleles, which interact in F1, leading to extremely low susceptibility.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Antithrombotic efficacy of RPR208566, a novel factor Xa inhibitor, in a rat model of carotid artery thrombosis.

Coagulation factor Xa is the sole enzyme responsible for activating the zymogen prothrombin to thrombin, resulting in fibrin generation, platelet activation, and subsequent thrombus formation. Our objective was to evaluate the antithrombotic efficacy of the novel factor Xa inhibitor, 2-(3-carbamimidoyl-benzyl)-3-[(3', 4'dimethoxy-biphenyl-4-carbonyl)-amino]-butyric acid methyl ester-trifluoroacetate (RPR208566), in a well-established rat model of arterial thrombosis, and to compare the results with those obtained with argatroban and heparin, direct and indirect inhibitors of thrombin, respectively. Thrombus formation was initiated by placing a filter paper saturated with FeCl(2) on the adventia of the carotid artery for 10 min. Time-to-occlusion was measured from initiation of injury until blood flow reached zero. Formed thrombi were removed and weighed 60 min after the placement of the filter paper. RPR208566, heparin, and argatroban dose-dependently increased time-to-occlusion and reduced thrombus mass. When administered at 500 microgram/kg+50 microgram/kg/min, RPR208566 prolonged time-to-occlusion to 56+/-4 min (vs. 18+/-2 min for vehicle) and reduced thrombus mass to 3.0+/-0.7 mg (vs. 7.3+/-0.6 mg for vehicle). The highest doses of argatroban (500 microgram/kg+50 microgram/kg/min) and heparin (300 U/kg+10 U/kg/min) increased time-to-occlusion to the maximum of 60 min and decreased thrombus mass to 5.5+/-0.8 and 2.6+/-0.3, respectively. The antithrombotic effects of heparin and argatroban at these doses were associated with increases in activated partial thromboplastin time of 5.6+/-0.9- and 2.9+/-0.3-fold over baseline, respectively. However, the highest dose of RPR208566 produced a modest 1.3+/-0.1-fold increase in activated partial thromboplastin time. These results indicate that factor Xa inhibition with compounds such as RPR208566 may be an attractive mechanism for novel antithrombotic drug therapy.

Amidines↗

Intraoperative cholangiography and postoperative pancreatitis.

BACKGROUND: It has been suggested that intraoperative cholangiography (IOC) can cause postoperative pancreatitis. METHODS: We studied the relationship between IOC and pancreatitis by reviewing the case histories of 500 patients (1992-97) who underwent cholecystectomy at our institution. In 82% of cases, the cholecystectomies were done laparoscopically, whereas, 7% were converted to an open procedure. An IOC was performed in 435/500, or 87%. During these studies, common bile duct (CBD) stones (or the possibility of a stone) were noted in 14% of the cases. An intraoperative CBD investigation was required in nine of 435 cases or 8.5%, while 28/435 (9.2%) underwent postoperative endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Follow-up was available in 90% of our patients (452/500). We found six cases of postoperative pancreatitis; only three of 452 (0.6%) occurred <1 year after cholecystectomy. None of these patients had a preoperative history of pancreatitis. In all six cases, there appeared to be an etiology for the pancreatitis unrelated to IOC. CONCLUSION: We could find no statistical association between IOC and postoperative pancreatitis. Postoperative pancreatitis is uncommon at our institution, where routine IOC is employed. Therefore, we conclude that IOC does not cause pancreatitis.

Adolescent↗

Hepatic stellate cells express the low affinity nerve growth factor receptor p75 and undergo apoptosis in response to nerve growth factor stimulation.

We have examined the expression of p75, a member of the TNF receptor superfamily in hepatic stellate cells (HSC) and pancreatic stellate cells (PSC). Activated HSC and PSC were demonstrated by Western blot analysis to express p75. p75 was immunolocalized to cells with a myofibroblast-like morphology in the fibrotic bands of six fibrotic and cirrhotic liver biopsies and three biopsies of fibrotic human pancreas. Immunostaining of parallel sections indicated that these cells were alpha-smooth muscle actin-positive, identifying them as activated HSC and PSC, respectively. HSC apoptosis in tissue culture in the presence of serum was quantified after addition of 0.1 to 100 ng/ml of nerve growth factor (NGF) a ligand for p75, by in situ counting of apoptotic bodies after addition of acridine orange. HSC demonstrated a significant increase in apoptosis in response to 100 ng/ml NGF (0.05 > P by Wilcoxon's rank; n = 7) after 24 hours. NGF 100 ng/ml had no effect on HSC proliferation, but reduced total HSC DNA by 19% relative to control after 24 hours (n = 3). These data demonstrate that activated HSC express p75 and respond to NGF stimulation by undergoing apoptosis. We therefore report p75 as a novel marker of activated HSC and suggest that signaling via ligand binding to p75 may provide a mechanism for selective apoptosis of HSC.

Animals↗

Patient satisfaction after carotid endarterectomy using a selective policy of local anesthesia.

BACKGROUND: Patient satisfaction after carotid endarterectomy has not been specifically studied or reported. Results of carotid endarterectomy using either local or general anesthesia have been widely reported, and outcomes are not significantly different for either technique. Patient satisfaction data were obtained in order to determine whether patients preferred one method of anesthesia over another. Data regarding outcome may be added to the surgical literature as benchmark data when comparing operative carotid endarterectomy to newer techniques. METHODS: During a 30-month period, 186 consecutive carotid endarterectomies were performed on 169 patients by a single surgeon with assistance from senior surgical residents. All patients were offered local anesthesia using a cervical block technique with intraoperative supplementation. Patients for whom local anesthesia was inappropriate or who declined were operated on using general endotracheal anesthesia. Results of operation were tabulated including indication for operation, method of anesthesia, intraoperative and postoperative complications, and mortality, and completion of a patient satisfaction survey form either on postoperative visit or by telephone questionnaire. RESULTS: Of 169 patients who underwent carotid endarterectomy, 151 (89%) completed the satisfaction survey form. One hundred fourteen (62%) had local anesthesia and 71 patients (38%) had general anesthesia. There was 1 stroke (0.5%) and 1 death (0.5%) in the series. Perioperative complications including temporary cranial nerve injury, neck hematoma, myocardial infarction, and restenosis were noted and not significantly different in either the general anesthesia or local anesthesia group. Patient satisfaction data including intraoperative discomfort, postoperative pain, attentiveness of the operating room staff, and length of stay were all tabulated. There was no statistically significant difference in satisfaction between the general anesthesia group and the local anesthesia group (chi-square and Fisher's exact test). Additionally, satisfaction with the procedure was extremely high. CONCLUSIONS: Patient outcome and perception of pain and recovery were not statistically significantly different in patients undergoing carotid endarterectomy using local anesthesia compared with general anesthesia. Overall patient satisfaction was extremely high. Patients should be offered carotid endarterectomy using an anesthesia technique with which the surgeon and patients are both comfortable, having confidence that the outcome is not related to anesthesia technique and that patients will be highly satisfied.

Aged↗

The use of zeolites as slow release anthelmintic carriers.

This work examines the ability of commercial zeolite Y to act as a slow release agent for a number of anthelmintic drugs. Administration to rats, dosed with Nippostrongylus brasiliensis, of pyrantel and/or fenbendazole and pigs, dosed with Ascaris and Oesophagostomum, of dichlorvos (DDVP) loaded onto zeolite Y was more successful in killing adult worms than administration of the pure drug alone. The zeolite Y was used as supplied for initial studies and then later dealuminated for further studies. The drug loadings were monitored by thermal analysis and the loaded zeolites were used in several field trials. The results indicate that zeolite Y is a suitable vehicle for the slow release of some anthelmintics. The slow release of drug from the zeolite matrix improved its efficacy.

Animals↗

MPTP susceptibility in the mouse: behavioral, neurochemical, and histological analysis of gender and strain differences.

To investigate the impact of strain and sex in the l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson's disease, C57BL/6 and BALB/c mice were treated with either systemic MPTP-HCl (4 x 15 mg/kg) or saline and were examined in a number of behavioral tests. Furthermore, neostriatal and ventral striatal monoamine contents were determined, and the numbers of tyrosine hydroxylase-immunostained cells were counted in the substantia nigra and ventral tegmental area. Open-field testing showed that locomotor activity was drastically reduced as an acute effect of MPTP in both strains; however, subsequent recovery to control levels was faster in BALB/c mice than in C57BL/6. Nest building also indicated strain-dependent effects, since it was delayed only in C57BL/6 mice treated with MPTP. The other tests (grip test, pole test, rotarod, elevated plus-maze), although partly sensitive for over-all strain or gender differences, turned out not to be useful to compare MPTP effects in these two strains. Neurochemically, MPTP led to more severe neostriatal dopamine depletions in C57BL/6 (-85%) than in BALB/c mice (-58%). Histologically, a loss of tyrosine hydroxylase immunoreactivity (-25%) was observed only in the substantia nigra of C57BL/6 animals. Thus, our analysis consistently showed that the C57BL/6 mouse strain is more susceptible to MPTP than the BALB/c strain. Sex differences in MPTP sensitivity were not observed in our mice. The implications of these findings for the search for genes related to susceptibility to neurodegeneration are discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

An outcome survey of psychology residency training program graduates of the University of Texas Houston Medical School.

A survey of 71 graduates of the psychology residency program at The University of Texas Houston Medical School and the Texas Research Institute of Mental Science indicated that two-thirds of the respondents were involved in private practice, conducting primarily individual therapy, with assessment also playing a major role in their practice. Managed care had the effect of placing limits on the numbers of sessions available to patients, reducing income, and increasing paperwork associated with practice. Implications for training during residency are that individual therapy, using focused short-term approaches, and assessment should continue to be the primary clinical experiences for trainees, and that there should also be training in the business aspect of practice, including marketing.

Adult↗

Synthesis, SAR and in vivo activity of novel thienopyridine sulfonamide pyrrolidinones as factor Xa inhibitors.

Thienopyridine sulfonamide pyrrolidinones were found to be potent and selective inhibitors of the coagulation cascade enzyme factor Xa. SAR studies led to several compounds that were selected for further in vivo investigation. These novel aryl binding pocket moieties represent a structural modification to a series of fXa inhibitors. Several compounds proved to be efficacious i.v. antithrombotic agents.

Animals↗

Prevalence and clinical characteristics of left ventricular dysfunction among elderly patients in general practice setting: cross sectional survey.

OBJECTIVE: To assess the prevalence and clinical characteristics of left ventricular dysfunction among elderly patients in the general practice setting by echocardiographic assessment of ventricular function. DESIGN: Cross sectional survey. SETTING: Four centre general practice in Poole, Dorset. SUBJECTS: 817 elderly patients aged 70-84 years. MAIN OUTCOMES: Echocardiographic assessment of left ventricular systolic function including measurement of ejection fraction by biplane summation method where possible, clinical symptoms, and signs of left ventricular dysfunction. RESULTS: The overall prevalence of left ventricular systolic dysfunction was 7.5% (95% confidence interval 5.8% to 9.5%); mild dysfunction (5.0%) was considerably more prevalent than moderate (1.6%) or severe dysfunction (0.7%). Measurement of ejection fraction was possible in 82% of patients (n=667): in patients categorised as having mild, moderate, or severe dysfunction, the mean ejection fraction was 48% (SD 12.0), 38% (8.1), and 26% (7.9) respectively. At all ages the prevalence was much higher in men than in women (odds ratio 5.1, 95% confidence interval 2.6 to 10.1). No clinical symptom or sign was both sensitive and specific. In around half the patients with ventricular dysfunction (52%, 32/61) heart failure had not been previously diagnosed. CONCLUSIONS: Unrecognised left ventricular dysfunction is a common problem in elderly patients in the general practice setting. Appropriate treatment with angiotensin converting enzyme inhibitors has the potential to reduce hospitalisation and mortality in these patients, but diagnosis should not be based on clinical history and examination alone. Screening is feasible in general practice, but it should not be implemented until the optimum method of identifying left ventricular dysfunction is clarified, and the cost effectiveness of screening has been shown.

Aged↗