Search PubMed⌕ Search

Biomedical subjects

S Morgan

Publications and source records attributed to S Morgan.

At least 37 records · Page 2Linked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

Comparison of visual and computerized interpretation of nonstress test results in a randomized controlled trial.

OBJECTIVE: This study tested the null hypothesis that the number of fetal surveillance tests and perinatal outcomes would not differ statistically between pregnancies randomized to visual or computerized interpretation of antepartum nonstress test results. STUDY DESIGN: A prospective, randomized controlled trial was conducted, which required a sample size of 404 patients. By using a random-number table with assignment codes concealed in opaque envelopes, half of the patients were randomized to computerized interpretation of nonstress test results and half to standard visual interpretation of nonstress test results. The amount of antepartum testing and the perinatal outcome were measured and compared between the groups. Logistic regression analysis was used to control for maternal risk factors while morbidity differences between the 2 groups were assessed. RESULTS: The 2 randomized groups were similar at baseline, but the computerized interpretation group had significantly fewer biophysical profiles compared with the visual interpretation group (1.3 +/- 1.8 vs 1.9 +/- 2.1; P =.002). The patients in the computerized interpretation group spent less time per test than patients in the visual interpretation group (12 vs 20 minutes; P =.038). After the 5 pregnancies with congenital anomalies were excluded, the overall perinatal outcome was similar in the 2 groups. The computerized interpretation group, however, had a slightly lower proportion of infants who required >/=2 days of neonatal intensive care (7.4% vs 12.4%; P =.086; odds ratio, 0.56; 95% confidence interval, 0.29-1.09). The average number of neonatal intensive care days was also slightly lower in the computerized interpretation group (0.4 vs 0.9; P =.105). Neither of these variables was statistically significant. CONCLUSIONS: Computerized interpretation of nonstress test results is associated with fewer additional fetal surveillance examinations, less time spent in testing, and a similar length of stay in the neonatal intensive care unit compared with standard visual interpretation.

Adult↗
PubMed1999

MRI of the lumbar intervertebral disc.

The lumbar spine is one of the commonest regions of the body imaged with MRI. Various pathological processes can involve the lumbar intervertebral disc, including degeneration, infection and trauma and these may present with a variety of signal intensity and morphological changes as depicted by MRI. The aim of this pictorial review is to illustrate these abnormalities and discuss their clinical relevance where appropriate.

Humans↗
PubMed1999

A mutation within exon 14 of the TGFBI (BIGH3) gene on chromosome 5q31 causes an asymmetric, late-onset form of lattice corneal dystrophy.

PURPOSE: Two forms of autosomal-dominant lattice corneal dystrophy (LCD), types I and IIIA, have previously been shown to be caused by different mutations within the transforming growth factor, beta-induced (TGFBI) gene. A clinical and molecular analysis of three unrelated kindreds with a clinically distinct late-onset LCD was undertaken to determine whether this phenotype is also caused by mutations within the TGFBI gene. DESIGN: Experimental study. PARTICIPANTS: Thirty-two members of three kindreds with corneal dystrophy. DNA from 100 normal control subjects was used as a control population. METHODS: Members of three kindreds with LCD were examined clinically, and blood samples were taken for DNA analysis. Mutation analysis was undertaken on all individuals for the coding region of the TGFBI gene by means of polymerase chain reaction (PCR) followed by single-stranded conformation polymorphism/heteroduplex analysis, subcloning, and sequencing. MAIN OUTCOME MEASURES: Detection of mutations within the TGFBI gene. RESULTS: Clinical examination revealed a form of LCD that was bilateral in all but one case, with onset around the fourth to fifth decade. The majority of cases showed significant asymmetry, and in one case there was evidence of onset directly after minor superficial corneal trauma. Molecular analysis in all families demonstrated sequence changes within exon 14 of the TGFBI gene on chromosome 5q31, at codon 622 in family 3, and at codon 626 in families 1 and 2, which are presumed to be responsible for the disease. CONCLUSIONS: Previously, a late-onset form of LCD, termed IIIA, was shown to be caused by a P501T mutation in exon 11 of TGFBI. The authors present the first description of mutations in exon 14 of TGFBI causing an LCD, also of late onset. Although the condition presented is morphologically and histopathologically typical of an isolated lattice dystrophy, the age of onset and clinical course is not typical of type I, III, or IIIA lattice dystrophy. This, in conjunction with recent developments in our understanding of the molecular genetics of these disorders, calls into question the usefulness and validity of the current classification of the isolated lattice dystrophies.

Adult↗
PubMed1999

Evaluation of tube coagulase and a fluorogenic substrate for rapid detection of methicillin-resistant Staphylococcus aureus from selective enrichment broth in an outbreak of EMRSA 15.

We investigated the use of tube coagulase and a fluorescent substrate, N-t-BOC-val-pro-arg-7-amido-4-methylcoumarin for the rapid detection of MRSA in selective broth enrichment cultures during an outbreak. These methods were compared with direct plating of swabs and plating a selective broth enrichment culture using 200 screening swabs collected from forty patients during the investigation of an outbreak of E-MRSA 15. Overall 66 swabs were positive for MRSA following subculture of broth enrichment culture. Direct plating detected 25 (38%) positives, tube coagulase 37 (56%), and fluorescent substrate 49 (74%) respectively, although nine of the 49 turned out to be false reactions. When detection from individual patients was analyzed, selective broth subculture identified 28 patients colonized with MRSA. Direct plating detected only 12 (43%) of these patients. The tube coagulase and fluorescence methods detected MRSA in 17 (60%) and 19 (68%) patients respectively. The tube coagulase method was found to be 100% specific for MRSA suggesting its use as a rapid method for the detection of MRSA from selective enrichment broth.

Bacteriological Techniques↗
PubMed1999

Accuracy and reproducibility of one-day disposable contact lenses.

One-day disposable contact lenses are experiencing rapid market growth in certain markets, such as the United Kingdom. Because of the huge numbers of lenses required to satisfy this modality of wear, both practitioners and patients need to be reassured about the quality of these products. Analysis of the accuracy and reproducibility of each of three currently available 1-day disposable lenses was conducted with respect to the following lens parameters: total diameter, back optic zone radius, center thickness, water content, and back vertex power. Fourteen of the 15 parameters measured (three lenses x five parameters per lens) were found to fall within ISO-defined tolerances. Reproducibility was similar for the three lens types and was considered clinically acceptable. Practitioners and patients can be confident that the current generation of 1-day disposable lenses can be relied on to give consistent ocular and visual performance.

Journal Article↗