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Biomedical subjects

S Morris

Publications and source records attributed to S Morris.

At least 91 records · Page 5Linked to original sources
PubMed1999

Childhood secondary (symptomatic) epilepsy, seizure control, and intellectual handicap in a nontropical region of South Africa.

PURPOSE: To determine the prevalence of secondary (symptomatic) epilepsy and to ascertain levels of seizure control and intellectual function in a clinic population of children drawn from a poor community in a temperate region of South Africa. METHODS: Detailed review of the records of every child with recurrent seizures who attended a special epilepsy outpatient clinic during 1995. RESULTS: A total of 1,017 children was studied. In 432 (43%), there was historic, clinical, and radiologic evidence to suggest that epilepsy was symptomatic of underlying brain damage or defect. Acceptable seizure control was maintained with a single standard anticonvulsant drug (AED) in 65% of cases. In the 6 months preceding the study, 37% of the subjects had remained seizure free. Forty-seven percent of the study population were considered to be of subnormal intelligence. CONCLUSIONS: In a children's hospital outpatient population in the Western Cape region of South Africa, the prevalence of secondary epilepsy is higher than is found in developed countries. There is need within the community for preventive measures aimed at reducing the prevalence of perinatal insults, meningitis, tuberculosis, neurocysticercosis, and cerebral trauma.

Adolescent↗
PubMed1999

Immunogenicity of DNA vaccines expressing tuberculosis proteins fused to tissue plasminogen activator signal sequences.

Novel tuberculosis DNA vaccines encoding native ESAT-6, MPT-64, KatG, or HBHA mycobacterial proteins or the same proteins fused to tissue plasminogen activator (TPA) signal sequences were evaluated for their capacity to elicit humoral, cell-mediated, and protective immune responses in vaccinated mice. While all eight plasmids induced specific humoral responses, the constructs expressing the TPA fusions generally evoked higher antibody responses in vaccinated hosts. Although most of the DNA vaccines tested induced a substantial gamma interferon response in the spleen, the antigen-specific lung responses were 2- to 10-fold lower than the splenic responses at the time of challenge. DNA vaccines encoding the ESAT-6, MPT-64, and KatG antigens fused to TPA signal sequences evoked significant protective responses in mice aerogenically challenged with low doses of Mycobacterium tuberculosis Erdman 17 to 21 days after the final immunization. However, the protective response induced by live Mycobacterium bovis BCG vaccine was greater than the response induced by any of the DNA vaccines tested. These results suggest that the tuberculosis DNA vaccines were able to elicit substantial immune responses in suitably vaccinated mice, but further refinements to the constructs or the use of alternative immunization strategies will be needed to improve the efficacy of these vaccine candidates.

Animals↗
PubMed1999

Changes in Rous sarcoma virus RNA secondary structure near the primer binding site upon tRNATrp primer annealing.

Predicted secondary-structure elements encompassing the primer binding site in the 5' untranslated region of Rous sarcoma virus (RSV) RNA play an integral role in multiple viral replications steps including reverse transcription, DNA integration, and RNA packaging (A. Aiyar, D. Cobrinik, Z. Ge, H. J. Kung, and J. Leis, J. Virol. 66:2464-2472, 1992; D. Cobrinik, A. Aiyar, Z. Ge, M. Katzman, H. Huang, and J. Leis, J. Virol. 65:3864-3872, 1991; J. T. Miller, Z. Ge, S. Morris, K. Das, and J. Leis, J. Virol. 71:7648-7656, 1997). These elements include the U5-Leader stem, U5-IR stem-loop, and U5-TPsiC interaction region. Limited digestion of the 5' untranslated region of wild-type and mutant RSV RNAs with structure- and/or sequence-specific RNases detects the presence of the U5-Leader stem and the U5-IR stem-loop. When a tRNATrp primer is annealed to wild-type RNAs in vitro, limited nuclease mapping indicates that the U5-IR stem becomes partially unwound. This is not observed when mutant RNAs with altered U5-IR stem-loop structures are substituted for wild-type RNAs. The U5-Leader stem also becomes destabilized when the tRNA primer is annealed to either wild-type or mutant RNA fragments. Nuclease mapping studies of tRNATrp, as well as the viral RNA, indicate that the U5-TPsiC helix does form in vitro upon primer annealing. Collectively, these data suggest that the various structural elements near the RSV primer binding site undergo significant changes during the process of primer annealing.

Animals↗
PubMed1999

Magnesium in drinking water supplies and mortality from acute myocardial infarction in north west England.

OBJECTIVES: To examine whether higher concentrations of magnesium in drinking water supplies are associated with lower mortality from acute myocardial infarction at a small area geographical level; to examine if the association is modified by age, sex, and socioeconomic deprivation. DESIGN: Small area geographical study using 13,794 census enumeration districts. Water constituent concentrations (magnesium, calcium, fluoride, lead) measured at water supply zone and assigned to enumeration districts. SETTING: 305 water supply zones in north west England. SUBJECTS: Resident population of 1,124,623 men and 1,372,036 women (1991 census) aged 45 years or more. MAIN OUTCOME MEASURE: Mortality from acute myocardial infarction, International Classification of Diseases, ninth revision (ICD-9) 410. Subsidiary analysis examined deaths from ischaemic heart disease, ICD 410-414. RESULTS: There were 21,339 male and 17,883 female deaths from acute myocardial infarction in 1990-92. Drinking water magnesium concentrations in water zones ranged from 2 mg/l to 111 mg/l (mean (SD) 19 (20) mg/l, median 12 mg/l); 24% of variation in magnesium concentrations was within zone and 76% was between zone. The relative risk of mortality from acute myocardial infarction (standardised for age, sex, and Carstairs deprivation quintile) for a quadrupling of magnesium concentrations in drinking water (for example, 20 mg/l v 5 mg/l) was 1.01 (95% confidence interval (CI) 0.99 to 1.03). When adjusted for north-south and east-west trends in mortality from acute myocardial infarction and for drinking water calcium, fluoride, and lead concentrations, this relative risk was 1.01 (95% CI 0.96 to 1.06). There was no evidence of a protective effect for acute myocardial infarction even among age, sex, and deprivation groups that were likely to be relatively magnesium deficient. For ischaemic heart disease mortality there was an apparent protective effect of magnesium and calcium (with calcium predominating in the joint model), but these were no longer significant when the geographical trends were incorporated. CONCLUSIONS: No evidence was found of an association between magnesium concentrations in drinking water supplies and mortality from acute myocardial infarction. These results do not support the hypothesis that magnesium is the key water factor in relation to mortality from heart disease.

Age Factors↗
PubMed1999

Choice of cost-effectiveness measure in the economic evaluation of cholesterol-modifying pharmacotherapy. An illustrative example focusing on the primary prevention of coronary heart disease in Canada.

OBJECTIVE: To evaluate the effect of using different cost-effectiveness measures in the economic evaluation of cholesterol-modifying pharmacotherapy. DESIGN AND SETTING: An economic model was used to examine the extent to which the relative cost effectiveness of cholesterol-modifying agents varies depending upon the cost-effectiveness measure used. The perspective taken was that of the Canadian public healthcare system. PATIENTS: Individuals without coronary heart disease (CHD) with low-density lipoprotein cholesterol (LDL-C) levels in excess of 190 mg/dl. INTERVENTIONS: Cholesterol-modifying pharmacotherapies available in Canada. MAIN OUTCOME MEASURES AND RESULTS: Cost per 1% reduction in LDL-C level; incremental cost per life-year gained; least-cost agent achieving the LDL-C reduction required to meet the target level of 160 mg/dl; incremental cost per life-year gained of agents reaching the target LDL-C level of 160 mg/dl relative to no therapy; incremental cost per life-year gained of agents achieving the target LDL-C level of 160 mg/dl relative to the least-cost agent reaching the target. Each cost-effectiveness measure had a different informational content to decision-makers, both in terms of the usefulness of the information they provided, and in terms of the extent to which they showed one agent to be more cost effective than another. The most cost-effective treatment regimens were fluvastatin 20 mg per day, fluvastatin 40 mg per day, atorvastatin 10 mg per day and atorvastatin 20 mg per day, depending on the pretreatment LDL-C level and the cost-effectiveness measure used. CONCLUSIONS: We recommend that the cost effectiveness of cholesterol-modifying pharmacotherapy be measured using incremental cost per life-year gained in reaching a predefined target LDL-C level.

Anticholesteremic Agents↗
PubMed1999

Serum cytosolic beta-glucosidase elevation and early ischemic injury to guinea pig small intestine.

BACKGROUND: The lack of an early, sensitive marker for intestinal ischemia has led to delay in diagnosis and worsended outcome for patients with acute onset of this condition. Our preliminary studies revealed that guinea pig cytosolic beta-glucosidase (CBG) is expressed predominantly in the small intestine, with lower levels in the liver and pancreas and undetectable levels in other organs. Cytosolic beta-glucosidase was investigated as a serum marker of small intestinal ischemia in a guinea pig model. METHODS: Guinea pigs underwent anesthesia, sham laparotomy, 30 minutes of mesenteric ischemia followed by 6 hours of reperfusion 6 hours of sustained mesenteric ischemia, or closed-loop small bowel obstruction. Serum samples were assayed for CBG activity. At the conclusion of the ischemia/reperfusion experiments, small bowel samples were assayed for residual enzyme activity, and paraffin sections were graded for the severity of histologic injury. RESULTS: Serum CBG activity rose rapidly after intestinal ischemia with and without reperfusion. Peak enzyme activities were elevated 23-fold for reperfused animals (P < .001) by 4 hours. For nonreperfused animals, peak serum CBG activities reached 29-fold above baseline and were significantly higher than the CBG activities of reperfused animals at 4 hours (P < .01) and at 6 hours (P < .05). Mucosal injury ranged from undetectable to moderate and corresponded in severity with both peak serum enzyme activity and decreased residual activity in the small bowel. In animals subjected to closed-loop obstruction, there was a mean increase of serum CBG of 9.2-fold from 4 to 6 hours after establishment of obstruction (P < .05). CONCLUSIONS: In the guinea pig model, CBG is a sensitive marker of ischemic injury caused by arterial occlusion or closed-loop obstruction of the small bowel.

Animals↗
PubMed1999

Type 1 diabetes in Thai children aged 0-14 years.

Fifty-nine patients were diagnosed with diabetes in the ten years from 1987 to 1996 in the Division of Endocrinology and Metabolism, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. All patients were less than fifteen years old. Fifty-five patients (93.3%) were type 1 diabetes, three (5%) were type 2 diabetes and MODY, and one (1.7%) was diabetes secondary to beta thalassemia major. Patients with type 2 diabetes, MODY, and secondary diabetes were excluded from this study, and fifty-five patients with type 1 diabetes were analysed. The aims of this study were to determine some of the general characteristics of Thai childhood type 1 diabetes and to see whether a seasonal variation is present. The results showed a female to male ratio of 1.39:1. The peak age at diagnosis was from 9 to 12 years. Seventy-seven per cent had diabetic ketoacidosis at the time of diagnosis. The majority of patients (93.9%) had a BMI of less than 20 kg/m2. A family history of diabetes was reported in 38 per cent but only 2 per cent were type 1 diabetes. We found a high prevalence of patients in the summer and winter seasons (35-48% and 37-50% respectively) and a lower prevalence in the rainy season (14.8-15%). These results are different from a previously reported study in 1984-1985 which found no differences in summer, winter, and rainy seasons. Further research study into Thai childhood type 1 diabetes is needed, especially the influence of seasonal factors, the incidence of the disease, and the significance of family history.

Adolescent↗
PubMed1999

Chronic widespread pain in the community: the influence of psychological symptoms and mental disorder on healthcare seeking behavior.

OBJECTIVE: To determine whether psychological symptoms and mental disorder are an intrinsic part of the chronic widespread pain syndrome or whether they have been observed in clinic attenders primarily because of their influence on the decision to seek a medical consultation. METHODS: A population survey of 1953 subjects was conducted in the Greater Manchester area of the United Kingdom. The survey included a postal questionnaire, and in a subgroup of respondents with high levels of distress, the presence of mental disorder was assessed by a semistructured standardized interview. Subjects with chronic widespread pain were classified according to whether they had sought a medical consultation for the reported pain ("consulters") or not ("nonconsulters"). RESULTS: In all, 252 subjects (13%) satisfied American College of Rheumatology criteria for chronic widespread pain, and of these 72% reported having consulted a general practitioner about this pain. There was a clear difference in levels of psychological distress, measured by the General Health Questionnaire (GHQ), between consulters, nonconsulters, and those with no pain. Consulters did not differ from nonconsulters in terms of levels of fatigue, social dysfunction, or number of somatic symptoms reported. Although consulters (among whom one in 4 had a mental disorder) were more likely to have a mental disorder than subjects without pain [OR = 4.9, 95% CI (2.6, 9.5)] the increase in risk comparing consulters to nonconsulters [OR = 2.1, 95% CI (0.7, 5.9)] and nonconsulters to subjects without pain [OR = 1.4, 95% CI (0.7, 2.6)] was not significant. CONCLUSION: The results suggest that psychological distress is associated with chronic widespread pain in addition to any effect on whether consultation is sought for symptoms. The finding that one-quarter of consulters to primary care with chronic widespread pain have a mental disorder should alert primary care physicians and rheumatologists to screen for mental disorder in this group.

Adolescent↗
PubMed1998

Relationship between auditory P300 amplitude and age of onset of schizophrenia in older patients.

Auditory P300 amplitude reductions are well-established in young adults with schizophrenia. Little is known, however, regarding the P300 in older schizophrenia patients, especially those with late onset. We studied 28 middle-aged and elderly (mean age = 62.7 years) patients [14 with early onset schizophrenia (EOS) and 14 with late onset schizophrenia (LOS)] and 14 normal comparison (NC) participants using an auditory oddball paradigm. Event-related potentials were recorded from 15 scalp electrodes and six non-scalp sites. There were no significant differences between EOS and LOS groups in neuroleptic dosage, symptom severity, reaction times, target-detection accuracy, or N100 and N200 ERP measures. The EOS, but not the LOS, group had significantly smaller auditory oddball P300 amplitudes than the NC group. Twelve of the 14 LOS patients had P300 amplitudes in the normal range. Smaller P300 amplitudes were associated with earlier age of onset (r = 0.48), longer duration of illness (r = -0.49) and more severe alogia (r = -0.50). We conclude that P300 abnormalities in schizophrenia may be a marker for a disease subtype with early onset and more severe information-processing deficits.

Age of Onset↗
PubMed1998

Red cell membrane fatty acids, cytosolic phospholipase-A2 and schizophrenia.

Forty subjects with schizophrenia and 40 age- and sex-matched controls were recruited, and blood samples were obtained for analysis of red cell membrane fatty acid composition by capillary gas chromatography. A blood sample was also taken from the same population to test for allelic association between schizophrenia and a polymorphism close to the promoter site of the cytosolic phospholipase-A2 gene which is mapped to chromosome 1q25. The schizophrenic population was heterogeneous with regards age, symptoms severity and treatment. A significantly higher percentage concentration of dihomogamma-linolenic acid (DGLA) was found in the red cell membranes of schizophrenics compared to matched controls. All other fatty acids examined showed no difference from the normal population. No correlation was found between any demographic factor, treatment variable, diet, drug use, alcohol or tobacco consumption which could explain the biochemical findings. A negative correlation was found between the concentration of DGLA in red blood cell (RBC) membranes and severity of symptoms of schizophrenia. In particular, there was a significant correlation (r = -0.41, p = 0.009) between DGLA percentage concentrations and 'disorganised' symptoms. No association was found between schizophrenia and alleles of the polymorphism near the phospholipase-A2 gene or between fatty acid concentrations and the presence of any particular alleles. This study therefore finds support for membrane phospholipid abnormalities in patients with schizophrenia and particular symptom clusters, but does not replicate a previous report of an allelic association between a polymorphism close to the site of the cytosolic phospholipase-A2 gene and schizophrenia.

Adult↗
PubMed1998

Unexplained physical symptoms in dental patients.

Physical symptoms for which there is no adequate organic pathology may be psychological in origin. The concept of somatisation described in this paper may be helpful in understanding these unexplained symptoms. Two case histories describe unusual physical symptoms that occurred following dental treatment and the role of somatisation in their development.

Adult↗
PubMed1998

A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder.

There are several lines of evidence which suggest that chromosome 4p may contain a major susceptibility locus for the functional psychoses. We previously reported a family (family 50) with cases of schizophrenia and schizoaffective disorder which gave maximum lod scores of 1.96 and 1.84 respectively with the markers D4S403 and a microsatellite near to DRD5 (DRD5-M). More recently Blackwood and co-workers described a family segregating bipolar and unipolar affective disorders which gives a maximum lod score of 4.1 with the marker D4S394, which lies 10 cM from D4S403. They obtained a combined maximum lod of 3.3 in their total sample of 12 bipolar families and found significant evidence of heterogeneity (chi 2 = 18.8, df = 2, P = 0.00008). Here we report the results of a linkage study of chromosome 4p markers in a sample of 24 multiply affected families with schizophrenia and related disorders. We obtained an overall maximum lod of 1.12 with D4S403 under both dominant and recessive modes of transmission, with no statistical support for heterogeneity within our sample. Examination of family by family data shows that only family 50 appears to show linkage at this locus. However, a discrepancy exists since our study examined families fulfilling criteria for a linkage study of schizophrenia while Blackwood et al examined families included in a genetic linkage study of bipolar disorder. This may be explained by the clinical features displayed by members of family 50, which show that all the affected members have some affective symptoms. It is therefore possible that a broad phenotype including unipolar depression, bipolar disorder, schizoaffective disorder and schizophrenia when accompanied by significant affective symptoms can result from mutations within a gene in this region. The dopamine D5 receptor gene lies within the region identified by the linkage studies and is therefore a major candidate for the putative disease gene. In family 50 we have looked for mutations of DRD5 by sequence analysis of the coding region and single stranded conformational polymorphism (SSCP) analysis of the promoter. SSCP analysis of the coding and promoter regions have also been carried out in unrelated cases of DSM-IIIR schizophrenia. Finally association studies of the (TC)n repeat in the promoter and schizophrenia, and DRD5-M and bipolar disorder were performed. These studies provided no further evidence supporting the possibility that mutations in DRD5 give rise to the linkage findings or are acting as susceptibility loci in schizophrenia or bipolar disorder.

Base Sequence↗
PubMed1998

All change: cancer services in transition.

The policy and health service background to this discussion are the radical changes in cancer services currently underway in the wake of the Calman-Hine Report and the wider changes ushered in by the NHS and Community Care Act 1990 (UK). Using the changing face of hospice care as the focus, the authors explore some of the potential issues and dilemmas involved in providing supportive care for cancer patients and their families. Three 'themes', or areas of concern, are highlighted: links between services, changing organizational factors, and increasing 'medical imperialism'. Potential benefits and drawbacks of the changing ethos and organizational structures are discussed. Interview data are used as 'triggers' for the presentation of the authors' own reflections on developments in the hospice and cancer services' arenas. The paper draws on interview data collected in the pilot phase of a 3-year study on the psycho-social needs of cancer patients and their informal carers in north-west England. Twenty-nine interviews were conducted with a range of professionals involved in the provision of cancer services in Lancaster and Kendal. In the spirit of 'gathering thoughts' and facilitating debate, a commentary on developments in the hospice sector is offered rather than any firm conclusion.

Health Care Reform↗
PubMed1998

Pupillary responses evoked during verbal fluency tasks indicate semantic network dysfunction in schizophrenia.

Pupillary responses, which index task controlled processing load, were recorded during semantic and phonemic fluency tasks to examine controlled search and automatic semantic network deficits in patients with schizophrenia. Word retrieval was more impaired on semantic than on phonemic fluency, but only during the first 15 seconds of trials. Pupillary dilation was greater on phonemic than on semantic fluency in nonpsychiatric participants but was greater on semantic than on phonemic fluency in the patients, during the first 15 seconds of trials. Thus, early in semantic fluency trials, patients with schizophrenia showed poorer word retrieval and abnormally high demand for frontal lobe controlled search processes, suggesting impairments in the temporal lobe automatic semantic memory processes that normally facilitate word retrieval.

Adult↗
PubMed1998

Expression of katG in Mycobacterium tuberculosis is associated with its growth and persistence in mice and guinea pigs.

The molecular mechanisms associated with the pathogenesis of tuberculosis are not well understood. The present study evaluated the role of catalase-peroxidase as a potential virulence factor for Mycobacterium tuberculosis. Growth and persistence of M. tuberculosis H37Rv in intravenously infected BALB/ c mice were compared with katG-deleted, isoniazid-resistant M. tuberculosis H37RVINHR. Transformation of M. tuberculosis H37Rv (TBkatG) or Mycobacterium intracellulare (MACkatG) genes into M. tuberculosis H37RvINHR restored its catalase-peroxidase activities and the ability of the recombinants to persist in spleens of mice and guinea pigs. Transformation with the TBkatG gene with the codon 463 R-->L mutation also restored catalase-peroxidase activity and enhanced persistence. However, transformants with the codon 275 T-->P mutant expressed low levels of enzymatic activity and failed to persist in guinea pig spleen, although they did survive in mouse tissues. These results indicate that KatG contributes to the ability of M. tuberculosis to grow and survive within the infected host tissues.

Animals↗
PubMed1998

Appropriate size and inflation of the laryngeal mask airway.

We have compared size 3 and size 4 laryngeal masks in 30 females and size 4 and size 5 in 30 males for success rate of insertion, incidence of airleak and pressure exerted on the pharynx. First, the ex vivo volume-pressure relationship of the mask was obtained. Second, after insertion of a mask, the cuff was inflated with the recommended maximum volume of air and intracuff pressure measured. Third, the incidence of airleak during a steady airway pressure of 18 cm H2O was noted. Fourth, the cuff was deflated until it just prevented airleak, and cuff pressure was measured. The mask was removed, the other size was inserted and the same procedure repeated. At the end of operation, final in vivo and ex vivo pressures were measured. The pressure exerted on the pharynx was calculated as the difference between ex vivo and in vivo intracuff pressures. It was always possible to insert both sizes in both sexes. In females, airleak occurred in 15 patients with the size 3 and in five patients with the size 4 (difference: P = 0.005) and in males, 21 patients with the size 4 and in four patients with the size 5 (P < 0.001). Removal of air to the minimum effective volume significantly decreased intracuff pressure and pressure on the pharynx; on removal of the mask, pressures were similar to, or lower than, initial pressures. Therefore, a larger mask (size 4 in females and size 5 in males) provided a better seal than a smaller size without producing higher pressures on the pharynx.

Adolescent↗