Immediate aspirin for suspected ischaemic stroke.
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Biomedical subjects
Publications and source records attributed to R Collins.
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Neutral glycolipid and ganglioside compositions were determined on 11 ependymal tumors, 12 medulloblastomas, 6 other neuronal tumors of the brain, 4 peripheral neuroblastomas, 1 cerebral primitive neuroectodermal tumor (PNET), and 1 PNET of the thoracic wall. Within the group of tumors that can demonstrate neuronal phenotypes, there was an association between the degree of neuronal differentiation usually demonstrated by these tumors and the proportions of both GD1a and 1b-pathway gangliosides. The amount of globoside also correlated with the amount of 1b pathway gangliosides. Patients with medulloblastomas whose 1b gangliosides made up over 15% of the total gangliosides survived longer that those with lower proportions of 1b gangliosides. The only gangliosides in the choroid plexus papilloma were GM3 and GD1a, but other ependymal tumors had significant amounts of GD1b and its metabolic precursors. Ependymoma and anaplastic ependymoma had similar neutral glycolipid compositions, which were different from subependymoma, which lacked ceramide monohexoside and ceramide dihexoside. These differences in glycolipid compositions suggest that there may be fundamental biological differences between these types of ependymal tumors.
OBJECTIVE: To compare the effectiveness of two widely used protocols for second-trimester screening for fetal trisomy 18. METHODS: Second-trimester screening results for 41,565 women were reviewed to determine whether pregnancies could be considered to be at high risk for trisomy 18. The screening test was considered positive if either maternal serum concentrations of alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (E3) fell below defined levels, or the second-trimester patient-specific risk (based on maternal age and serum analytes) was greater than 1:100. Detection rates, false-positive rates, and pregnancy outcomes for the two protocols were compared. RESULTS: The fixed-cutoff method showed a 23% detection rate and a 0.19% false-positive rate for trisomy 18. These low rates were in close agreement with a theoretical expectation for fixed-cutoff trisomy 18 screening. The risk-based approach resulted in a 69% detection rate and a 0.45% false-positive rate. Both methods identified pregnancies with other fetal anomalies. CONCLUSION: Overall, the risk-based method is more effective than the fixed-cutoff approach to trisomy 18 screening.
In this study we have developed a polymerase chain reaction-sequence-specific primer (PCR-SSP) or phototyping system to analyse the polymorphism of the human MICA gene locus. By scrutinising the reported MICA sequence variations in exons 2, 3 and 4 which encode the extracellular protein domains, we have selected and tested 20 MICA-specific primer mixes that should discriminate between the majority of homozygous and heterozygous combinations of MICA alleles 001-016. We have tested this scheme on DNA prepared from a large number of well-characterised tissue culture cell lines with previously reported MICA nucleotide sequences and found an excellent correlation with the observed PCR-SSP phototypes. We believe that this scheme can also be modified to detect new MICA alleles when they are characterised, as well as be incorporated into standard phototyping protocols to generate allele and haplotype profiles of both classical and non-classical HLA gene loci in test DNA samples.
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Allogeneic marrow transplantation offers curative therapy for patients with aplastic anemia. We analyzed retrospective results in 141 patients with severe aplastic anemia who received transplants between 1988 and 1995 from an unrelated volunteer donor identified through the National Marrow Donor Program (NMDP). All patients had failed one or more courses of immunosuppressive therapy. Of the patients, 121 (86%) received a radiation-containing conditioning regimen, and 20 (14%) were given chemotherapy only. Based on serologic human leukocyte antigen (HLA) typing (class I and II), 105 patients (74%) received HLA-matched marrow, and 36 (26%) received marrow mismatched for at least one HLA-A, -B, or -DR antigen. Allele-level (molecular) typing for HLA-DRB1 was available in 108 donor-recipient pairs; 77 patients received DRB -matched and 31 DRB1-mismatched transplants. All but 13% of patients were given a cyclosporine-containing regimen for graft-vs.-host disease (GVHD) prophylaxis, and 45 patients (32%) received marrow that was T cell-depleted. Among 131 evaluable patients, 116 (89%) achieved sustained engraftment and 15 (11%) did not. Among patients with engraftment, acute GVHD of grades II-IV developed in 60 patients (52%) and extensive chronic GVHD in 24 patients at risk (31%). Currently, 51 patients (36%) are surviving at 11-94 months (median 36) after transplantation. All but five have Karnofsky scores > or =80. Patients who received a serologically matched transplant fared somewhat better than did patients given a serologically mismatched transplant p = 0.03). Patients with donors matched by both serology and allele-level DRB1 typing had significantly better survival than DRB1-mismatched patients with 56 vs. 15% surviving at 3 years p = 0.001). Outcome in patients transplanted within 3 years of diagnosis was superior to that among patients transplanted with greater delay. Major causes of death were graft failure, GVHD, and infections. These data suggest that unrelated marrow transplantation offers successful therapy for a proportion of patients who have failed immunosuppressive therapy.
Surgical excision of an insulinoma results in dramatic reversal of hypoglycemic symptoms. Laparoscopic resection, if feasible, could reduce postoperative discomfort. Successful laparoscopic resection of an insulinoma is described. Preoperative studies failed to visualize the tumor; however, it was visualized and then imaged successfully during surgery. The operative approach described allows access to the entire pancreas and, therefore, may be useful for islet cell tumors at most sites in the gland. Based on this case and others in the literature, further efforts at laparoscopic pancreatic surgery are warranted.
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An international working party has conducted a study designed to select a suitable reference reagent for antihuman globulin, to replace those first made available in 1987. The chosen preparation contains levels of anti-IgG and anti-C3 (anti-C3c and anti-C3d) potency that are considered suitable to serve for reference when evaluating either polyspecific antihuman globulin reagents or those containing their separate monospecific components. The reference material is available in 2-ml freeze-dried aliquots from seven assigned distribution centres.
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When it comes to cosmetic or esthetic dentistry the old adage "beauty is in the eye of the beholder" should be a guiding principal when developing an outline of treatment for our patients. Frequently our patients come to us with requests for improving their smiles but uncertain as to exactly what they want or even worse that have expectations that we are unable to deliver. The path traveled from initial interviewing of the patient to completing each case can be fraught with pitfalls of disappointment unless a careful process of educating the patient and constant communication is followed.
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New mathematical models are formulated and analytical solutions are presented for the diffusional release of a solute from both non-erodible and biodegradable multi-layered slab matrices in which the initial drug loading c0 is greater than the solubility limit cs. A Stefan problem with moving boundaries results from this formulation. An inward moving diffusional front separates the reservoir (unextracted region) containing the undissolved drug from the partially extracted region. The cumulative mass released is determined as a function of time. The ultimate goal of such an investigation is to provide a reliable design tool for the fabrication of specialized implantable capsule/drug combinations to deliver prespecified and reproducible dosages over a wide spectrum of conditions and required durations of therapeutic treatment. Such a mathematical/computational tool may also prove effective in the prediction of suitable dosages for other drugs of differing chemical or molecular properties without additional elaborate animal testing.
A series of developmental stages of the platypus were examined to obtain an anatomical description of the development of the periphery of the electroreceptive system. Putative electroreceptors, composed of modified mucous glands, were observed to appear at 10 days post hatching (p.h.). The typical striped arrangement of peripheral electroreceptors in the platypus was seen at 12 days p.h. The arrangement of the stripes was modified during development with a range of additions and divisions of stripes occurring until the adult pattern is obtained, approximately 6 months p.h. After appearing at 10 days p.h., the number of electroreceptors increases rapidly until sometime between 24 and 28 days p.h. when there is massive death of electroreceptors, the number present at 28 days p.h. being 60% of the number present at 24 days p.h. This massive death of receptors is coincident with the appearance of other sensory structures in the epidermis of the bill skin, the push-rod mechanoreceptors and the sensory serous glands. Histological examination of a range of developmental stages demonstrated poorly differentiated innervation at 28 days p.h., which became differentiated and reached the adult configuration between 11 weeks p.h. and 6 months p.h., the time at which nestling platypuses leave the burrow. Lamination of the cells lining the duct of the electroreceptors showed a similar developmental profile. This study indicates that the electroreceptive system of the developing platypus is not functional, in a similar manner to the adult, until it is time for the platypus to leave the nesting burrow. However, the system may be functional in the developing platypus, and may be used speculatively in the location of the mammary region for suckling.
CONTEXT: A large number of epidemiologic studies have reported on associations between various "inflammatory" factors and coronary heart disease (CHD). OBJECTIVE: To assess the associations of blood levels of fibrinogen, C-reactive protein (CRP), and albumin and leukocyte count with the subsequent risk of CHD. DATA SOURCES: Meta-analyses of any long-term prospective studies of CHD published before 1998 on any of these 4 factors. Studies were identified by MEDLINE searches, scanning of relevant reference lists, hand searching of cardiology, epidemiology, and other relevant journals, and discussions with authors of relevant reports. STUDY SELECTION: All relevant studies identified were included. DATA EXTRACTION: The following information was abstracted from published reports (supplemented, in several cases, by the authors): size and type of cohort, mean age, mean duration of follow-up, assay methods, degree of adjustment for confounders, and relationship of CHD risk to the baseline assay results. DATA SYNTHESIS: For fibrinogen, with 4018 CHD cases in 18 studies, comparison of individuals in the top third with those in the bottom third of the baseline measurements yielded a combined risk ratio of 1.8 (95% confidence interval [CI], 1.6-2.0) associated with a difference in long-term usual mean fibrinogen levels of 2.9 pmol/L (0.1 g/dL) between the top and bottom thirds (10.3 vs 7.4 pmol/L [0.35 vs 0.25 g/dL]). For CRP, with 1053 CHD cases in 7 studies, the combined risk ratio of 1.7 (95% CI, 1.4-2.1) was associated with a difference of 1.4 mg/L (2.4 vs 1.0 mg/L). For albumin, with 3770 CHD cases in 8 studies, the combined risk ratio of 1.5 (95% CI, 1.3-1.7) was associated with a difference of 4 g/L (38 vs 42 g/L, ie, an inverse association). For leukocyte count, with 5337 CHD cases in the 7 largest studies, the combined risk ratio of 1.4 (95% CI, 1.3-1.5) was associated with a difference of 2.8 x 10(9)/L (8.4 vs 5.6 x 10(9)/L). Each of these overall results was highly significant (P<.0001). CONCLUSIONS: The published results from these prospective studies are remarkably consistent for each factor, indicating moderate but highly statistically significant associations with CHD. Hence, even though mechanisms that might account for these associations are not clear, further study of the relevance of these factors to the causation of CHD is warranted.
OBJECTIVE: To assess effects of intravenous streptokinase, one month of oral aspirin, or both, on long term survival after suspected acute myocardial infarction. DESIGN: Randomised, "2 x 2 factorial," placebo controlled trial. SETTING: 417 hospitals in 16 countries. SUBJECTS: 17 187 patients with suspected acute myocardial infarction randomised between March 1985 and December 1987. Follow up of vital status complete to at least 1 January 1990 for 95% of all patients and to mid-1997 for the 6213 patients in United Kingdom. INTERVENTIONS: Intravenous streptokinase (1.5 MU in 1 hour) and oral aspirin (162 mg daily for 1 month) versus matching placebos. MAIN OUTCOME MEASURES: Mortality from all causes during up to 10 years' follow up, with subgroup analyses based on 4 year follow up. RESULTS: After randomisation, 1841 deaths were recorded in days 0-35, 991 from day 36 to end of year 1, 1478 in years 2-4, and 1230 in years 5-10. Allocation to streptokinase was associated with 29 (95% confidence interval 20 to 38) fewer deaths per 1000 patients during days 0-35. This early benefit persisted (death rate ratio 0.98 (0.92 to 1.04) for additional deaths between day 36 and end of year 10), so that there were 28 (14 to 42) and 23 (2 to 44) fewer deaths per 1000 patients treated with streptokinase after 4 years and 10 years respectively. There was no evidence that absolute survival benefit increased with prolonged follow up among any category of patient, including those presenting early after symptoms started or with anterior ST elevation. Nor did the early benefits seem to be lost in any category (including those aged over 70). Allocation to one month of aspirin was associated with 26 (16 to 35) fewer deaths per 1000 during first 35 days, with little further benefit or loss during subsequent years (death rate ratio 0.99 (0.93 to 1.06) between day 36 and end of year 10). The early benefit obtained with combination of streptokinase and one month of aspirin also seemed to persist long term. CONCLUSIONS: The early survival advantages produced by fibrinolytic therapy and one month of aspirin started in acute myocardial infarction seem to be maintained for at least 10 years.
BACKGROUND: In previous studies, unadjusted comparisons of mortality and major morbidity after acute myocardial infarction have generally indicated that women have a poorer outcome than men. Much larger studies are needed, with more complete adjustment for coexisting conditions, to determine whether this difference is explained by the older age of the women studied or by the presence of other unfavorable prognostic factors, or both. METHODS: As part of the Third International Study of Infarct Survival (ISIS-3), information was collected on deaths during days 0 to 35 and on major clinical events during hospitalization up to day 35 for 9600 women and 26,480 men with suspected acute myocardial infarction who were considered to have a clear indication for fibrinolytic therapy. We compared the outcome among women and men, first without adjustment, then with adjustment for age, and finally with adjustment for other recorded baseline characteristics by means of multiple logistic regression. RESULTS: The unadjusted odds ratio for death among women as compared with men was 1.73 (95 percent confidence interval, 1.61 to 1.86). The women were significantly older than the men, and after adjustment for age the odds ratio was reduced markedly to 1.20 (95 percent confidence interval, 1.11 to 1.29). Adjustment for other differences in base-line clinical features further reduced the odds ratio to 1.14 (95 percent confidence interval, 1.05 to 1.23). Excesses in other major clinical events among women were generally reduced to a similar extent by adjustment. CONCLUSIONS: It seems likely that there is at most only a small independent association between female sex and early mortality and morbidity after suspected acute myocardial infarction.