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Biomedical subjects

S M Lewis

Publications and source records attributed to S M Lewis.

At least 73 records · Page 4Linked to original sources

A patent infarct-related artery is associated with reduced long-term mortality after percutaneous transluminal coronary angioplasty for postinfarction ischemia and an ejection fraction <50%.

BACKGROUND: Prognosis after myocardial infarction (MI) is influenced by the presence of post-MI ischemia and possibly the patency of the infarct-related artery. The purpose of this study was to compare long-term outcome (reinfarction and death) in patients with open versus closed coronary arteries after percutaneous transluminal coronary angioplasty performed for MI complicated by persistent ischemia. METHODS AND RESULTS: Between 1981 and 1989, 505 patients underwent percutaneous transluminal coronary angioplasty for post-MI ischemia at the Deaconess Hospital. Long-term incidence (mean follow-up, 34 months) of death, nonfatal reinfarction, repeated coronary angioplasty, and coronary bypass surgery was determined for 479 patients and then compared on the basis of the status of the artery, open versus closed, at the end of angioplasty. The 5-year Kaplan-Meier actuarial mortality rate was 4.9% for 456 patients with open infarct-related arteries and 19.4% for 23 patients with closed infarct-related arteries (P=.0008). Multivariate Cox proportional hazards analyses controlling for age, sex, number of diseased vessels, type and location of MI, and year of coronary angioplasty revealed a hazard ratio for death for closed compared with open arteries of 6.1 (95% CI, 1.8 to 20.0). Among patients with ejection fractions <50%, a closed artery was associated with a higher mortality (p=.0014) compared with patients with open arteries. The status of the artery was not associated with a difference in mortality in patients with ejection fractions > or = 50%. CONCLUSIONS: As open artery after coronary angioplasty for post-MI ischemia is associated with significantly lower long-term mortality, particularly in patients with ejection fractions <50%.

Adult↗

Routine perioperative dipyridamole 201Tl imaging in diabetic patients undergoing vascular surgery.

OBJECTIVE: To assess the utility of dipyridamole thallium testing in symptomatic and asymptomatic patients with diabetes undergoing vascular surgery. RESEARCH DESIGN AND METHODS: Dipyridamole 201Tl myocardial scintigraphy was performed preoperatively in 93 consecutive patients with diabetes undergoing peripheral vascular procedures. The utility of clinical and thallium variables in predicting cardiovascular complications was assessed. RESULTS: Two groups of patients were identified: group A (36 patients) without clinical evidence of cardiac disease and group B (57 patients) with clinical evidence of cardiac disease. Dipyridamole thallium scans were abnormal in 21 of 36 (58%) of group A patients compared with 53 of 57 (93%) of group B patients (P < 0.0001). Compared with group B patients with perfusion defects, group A patients with perfusion abnormalities tended to have fewer defects per scan (2.7 +/- 1.5 vs. 3.6 +/- 1.9, P = 0.05). No perioperative cardiac complications occurred in group A patients while perioperative cardiac complications occurred in 9 of 57 (16%, 95% CI 7-28%) group B patients (P = 0.01). For the entire study population, the complication rate was 10%. CONCLUSIONS: Diabetic individuals without clinical markers for coronary artery disease appear to be at low risk for adverse postoperative cardiac events after vascular surgery. Preoperative myocardial perfusion imaging may add little to cardiovascular risk assessment in this subgroup of patients with diabetes.

Aged↗

The impact of an integrated haematology screening system on laboratory practice.

The haematology laboratory of the Royal Postgraduate Medical School is required to handle an increasing workload with decreasing financial resources. An investment in technology was made in order to improve efficiency, meet future demands and to meet high technical standards. This required an increase in automation in the Full Blood Count section with staff redeployed into growth areas. The Sysmex HST 330, comprising an SE 9000 full blood count analyser, R 3000 reticulocyte counter, SP 1 film preparation unit, linked by a transport system was chosen as a comprehensive system. To fully exploit the reflex-testing capabilities and maximize the potential of the HST a computerized decision-making algorithm was developed. We have been able to evaluate the impact of a highly automated approach to FBC screening in a busy diagnostic laboratory.

Algorithms↗

Natural history of paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH), which is characterized by intravascular hemolysis and venous thrombosis, is an acquired clonal disorder associated with a somatic mutation in a totipotent hematopoietic stem cell. An understanding of the natural history of PNH is essential to improve therapy. METHODS: We have followed a group of 80 consecutive patients with PNH who were referred to Hammersmith Hospital, London, between 1940 and 1970. They were treated with supportive measures, such as oral anticoagulant therapy after established thromboses, and transfusions. RESULTS: The median age of the patients at the time of diagnosis was 42 years (range, 16 to 75), and the median survival after diagnosis was 10 years, with 22 patients (28 percent) surviving for 25 years. Sixty patients have died; 28 of the 48 patients for whom the cause of death is known died from either venous thrombosis or hemorrhage. Thirty-one patients (39 percent) had one or more episodes of venous thrombosis during their illness. Of the 35 patients who survived for 10 years or more, 12 had a spontaneous clinical recovery. No PNH-affected cells were found among the erythrocytes or neutrophils of the patients in prolonged remission, but a few PNH-affected lymphocytes were detectable in three of the four patients tested. Leukemia did not develop in any of the patients. CONCLUSIONS: PNH is a chronic disorder that curtails life. A spontaneous long-term remission can occur, which must be taken into account when considering potentially dangerous treatments, such as bone marrow transplantation. Platelet transfusions should be given, as appropriate, and long-term anticoagulation therapy should be considered for all patients.

Adolescent↗

Significance of location (anterior versus inferior) and type (Q-wave versus non-Q-wave) of acute myocardial infarction in patients undergoing percutaneous transluminal coronary angioplasty for postinfarction ischemia.

Predictors of increased risk for recurrent cardiac events and death after acute myocardial infarction include postinfarction myocardial ischemia, anterior location of the infarct, and non-Q-wave versus Q-wave infarction. Although coronary angioplasty is performed in patients with postinfarction ischemia to alleviate symptoms, the outcome according to location and type of infarction and the effect on prevention of subsequent myocardial infarction and death are not known. To determine if location and type of myocardial infarction provide prognostic information in patients with postinfarction ischemia, we analyzed morbidity and mortality during and after coronary angioplasty according to the location (anterior vs inferior) and type (Q-wave vs non-Q-wave) of myocardial infarction in 505 consecutive patients. The incidence of recurrent angina, repeat coronary angioplasty, coronary bypass surgery, reinfarction, and death during long-term follow-up after hospital discharge (mean 34 +/- 19 months) for the 440 patients with an initial successful angioplasty was also compared. During the procedure, there was no difference in the primary success rate or mortality among the different groups; however, more patients with anterior non-Q-wave myocardial infarction underwent emergent bypass grafting after unsuccessful coronary angioplasty (p = 0.001). Multivariate Cox proportional-hazards analyses controlling for age, gender, number of diseased vessels, location, type of infarction, and year of coronary angioplasty revealed that more patients with anterior infarction had > or = 1 cardiac event (repeat angioplasty, coronary artery bypass grafting, reinfarction, or death) than did those with inferior infarction (RR 1.80, 95% confidence interval [Ci] 1.22 to 2.65, p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Growth inhibition of human prostate tumor cells by an agonist of gonadotrophin-releasing hormone.

The effect of [D-Leu6,des-Gly-NH2(10),Proethylamide9]-GnRH, leuprolide, was determined for the human primary prostate tumor cell line ALVA-31 by in vitro mitogenic assays. Prostate tumor cell proliferation was inhibited up to 50% by leuprolide. Inhibition was not observed in parallel cultures treated with other low molecular weight bioactive peptides. The incorporation and metabolic reduction of testosterone was not affected by concentrations of leuprolide that were inhibitory in the mitogenic assay. Specific high-affinity binding of 125I-labeled leuprolide was also demonstrated on intact tumor cells with an estimated effective median dose (ED50) of < 1 x 10(-9)M. Inhibition of prostate tumor growth was further demonstrated in Balb/c athymic intact and castrate male mice bearing ALVA-31 tumor xenografts following chronic administration of leuprolide. These data clearly demonstrate that leuprolide can inhibit the growth of a human prostate carcinoma cell line. Studies conducted in castrate animals further suggest an alternative mechanism of growth inhibition that appears to be independent of the suppression of steroid hormone biosynthesis by LHRH analogues.

Animals↗

Requirements for controlled clinical trials of preoperative cardiovascular risk reduction.

Although controlled clinical trials have had a major impact in many areas of cardiovascular disease management, they have had little influence on preoperative cardiac risk reduction. Over the past 2 years, we have conducted the Reduction of Cardiac Operative Risk (RCOR) Trial, a pilot study designed to determine enrollment and event rates for a definitive trial evaluating a strategy to reduce cardiac risk associated with noncardiac surgery. This experience indicates that a successful, definitive trial will require recognition of the multiple questions to be answered, accurate identification of the study population, a large sample size, cooperation between internists, surgeons, and anesthesiologists, and strategies to minimize cost. The high costs and difficulties of such a trial are likely to be outweighed by the enormous benefit of identifying the proper strategy for the use of the expensive testing methods that are currently employed.

Cardiovascular Diseases↗

The effect of surveillance definitions on nosocomial urinary tract infection rates in a rehabilitation hospital.

This article presents original research findings to illustrate the influence of surveillance definitions on infection rate. Several definitions for urinary tract infection were applied to clinical and laboratory data from rehabilitation hospital patients, and the effect on sensitivity and specificity examined. We demonstrate that it is essential to take into account the influence of the surveillance definition when interpreting surveillance data, and the importance of ensuring that the surveillance definition is compatible with the surveillance objectives when selecting a definition. Surveillance definitions that serve well in one surveillance program may not serve well in another.

Cross Infection↗

Interpretation of measured red cell mass and plasma volume in adults: Expert Panel on Radionuclides of the International Council for Standardization in Haematology.

Four European centres provided height and weight data on 202 males and 204 females undergoing red cell mass (RCM) and plasma volume (PV) measurements. For these populations, the RCM and PV predictions by the various published methods were compared. It was shown clearly that predictions based solely on body weight were inappropriate, particularly because approximately half of the male and female populations could be regarded as overweight or obese. Although there was reasonable agreement in the prediction values given by the formulae based on both height and weight, it was not possible to establish which formulae could be recommended. For that reason, the published literature containing normal RCM and PV measurements were re-examined. RCM data for 283 males and 171 females and PV data for 100 males and 67 females were included. Measurements were standardized for variables such as trapped plasma in the PCV, exclusion of buffy coat in the PCV and calculation of PV at zero time. As a result of this analysis, prediction formulae based on surface area for RCM and PV with 98/99% reference ranges have been established.

Adult↗

Prospective evaluation of viable myocardium by quantitative dipyridamole-thallium-201 scintigraphy and radionuclide ventriculography.

Improvement of myocardial function is a major goal of coronary revascularization. Considerable interest remains in the preoperative identification of viable myocardium. We examined 26 consecutive patients with left ventricular dysfunction undergoing coronary artery bypass grafting. Serial dipyridamole-thallium imaging and radionuclide ventriculography was performed preoperatively and postoperatively. The relationship between preoperative and postoperative thallium perfusion and segmental wall motion was analyzed. The mean preoperative ejection fraction was 32 +/- 9 (21 to 51%) and increased to 41 +/- 12 (17 to 67%) postoperatively (p > 0.01). Seventy-seven percent of patients improved their global ejection fraction postoperatively by > 5%. Thallium perfusion improved postoperatively in 84% of reversible defects vs 63% of partially reversible defects and 35% of fixed defects. Segments with either reversible or partially reversible thallium defects showed an improved postoperative wall motion in 71% and 68%, respectively. Postoperative wall motion improved in 43% of fixed defects. Overall, 67% of hypokinetic segments showed improved postoperative wall motion while only 29% of akinetic or dyskinetic segments improved postoperatively. Preoperative thallium redistribution coupled with preserved wall motion was predictive of improvement in wall motion was predictive of improvement in wall motion postoperatively and indirectly indicates myocardial viability. However, 43% of fixed defects also showed improved postoperative wall motion. A significant improvement in global ejection fraction was found and could be predicted by a linear regression analysis utilizing clinical and thallium parameters.

Aged↗

A simple and reliable method for estimating haemoglobin.

A new colour scale has been advised for estimating haemoglobin levels by matching the blood samples with ten levels of haemoglobin (3, 4, 5, 6, 7, 8, 9, 10, 12, and 14 g/dl) on the scale. Preliminary results show good correlations with spectrophotometric readings. The new device is being field tested and if the initial promise is confirmed, will provide a simple and reliable method for estimating haemoglobin where laboratory facilities are not available.

Blood Chemical Analysis↗

Demand or ideation? Evidence from the Iranian marital fertility decline.

Is the onset of fertility decline caused by structural socioeconomic changes or by the transmission of new ideas? The decline of marital fertility in Iran provides a quasi-experimental setting for addressing this question. Massive economic growth started in 1955; measurable ideational changes took place in 1967. We argue that the decline is described more precisely by demand theory than by ideation theory. It began around 1959, just after the onset of massive economic growth but well before the ideational changes. It paralleled the rapid growth of participation in primary education, and we found no evidence that the 1967 events had any effect on the decline. More than one-quarter of the decline can be attributed to the reduction in child mortality, a key mechanism of demand theory. Several other findings support this main conclusion.

Adolescent↗

Quality assurance programmes in the United Kingdom.

Quality assurance in laboratory medicine includes: a) constant checking of test reliability by internal quality control (IQC), b) external quality assessment (EQA) by an independent agency to check performance of a number of laboratories at intervals in order to obtain a retrospective indication of their performance, and c) proficiency control by supervision of pre-test and post-test phases of laboratory work, from specimen collection to delivery of report to the clinician. In the UK the majority of laboratories are aware of the importance of IQC and to a greater or lesser extent they all perform some IQC procedures. These are briefly described, with special reference to the special requirements of haematology. A description is also given of the organizational structure of the EQA scheme which was established in the UK at a national level (UK NEQAS). This has an important role in ensuring good laboratory practice in both the national health service and the private sector.

Chemistry, Clinical↗

EQA for general haematology in the United Kingdom.

In the United Kingdom the national quality assessment scheme (NEQAS) in haematology organizes regular surveys for blood counts, blood films, reticulocyte counts, cytochemistry, identification of abnormal haemoglobins, HbA2 and HbF quantitation, G6PD screening tests, assays of serum vitamin B12, folate and ferritin. For most tests there has been significant reduction in inter-laboratory variance despite occasional blunders. This illustrates the role of NEQAS in improving the standard of laboratory practice in the UK. The problems in equating analysis of NEQAS survey materials with routine laboratory specimen are discussed.

Hematologic Tests↗

Joubert syndrome with congenital hepatic fibrosis: an entity in the spectrum of oculo-encephalo-hepato-renal disorders.

Joubert syndrome is an autosomal recessive inherited condition characterized by agenesis or hypoplasia of the cerebellar vermis, retinal dystrophy, chorioretinal colobomata, oculomotor abnormalities, episodic hyperpnea, ataxia, and mental retardation. Congenital hepatic fibrosis has not previously been described in Joubert syndrome. We report two unrelated children with Joubert syndrome and hepatosplenomegaly. On histopathological examination, both had congenital hepatic fibrosis. Both were also found to have congenital medullary cystic disease of the kidneys. Joubert syndrome appears to be one of a spectrum of congenital malformation syndromes involving the central nervous system, eye, liver and kidneys.

Abnormalities, Multiple↗

P nucleotide insertions and the resolution of hairpin DNA structures in mammalian cells.

Two lines of evidence point to a hairpin DNA intermediate in V(D)J joining (V, variable; D, diversity; J, joining) [Lieber, M.R. (1991) FASEB J. 4, 2934-2944]. One is the presence of P nucleotide insertions (short inverted-repeat sequence) in V(D)J junctions [Lafaille, J. J., DeCloux, A., Bonneville, M., Takagaki, Y. & Tonegawa, S. (1989) Cell 59, 859-870]; a second is the detection of site-specifically broken DNA molecules with covalently closed (hairpin) termini in thymus DNA [Roth, D. B., Menetski, J. P., Nakajima, P., Bosma, M. J. & Gellert, M. (1989) Cell 70, 983-991]. However, P nucleotide insertions could be generated in ways not involving a hairpin structure, and because physical evidence for hairpin-ended DNA fragments has been obtained only with mutant mice, there is some uncertainty regarding the role of hairpin molecules in the normal V(D)J joining pathway. To determine whether mammalian cells are capable of metabolizing this odd type of DNA terminus and whether, in doing so, junctions with P insertions are in fact created, a linear DNA molecule with a hairpin closure at each end was transfected into several murine cell lines. The hairpin-ended molecules were recircularized, and the junctions exhibited P insertions at a high frequency. This result directly links the presence of P insertions to a hairpin precursor, providing strong evidence for the notion that a hairpin DNA intermediate exists in V(D)J recombination. A comparison of hairpin end joining in various cells, including those derived from mice with the severe combined immunodeficiency (scid) mutation, is presented.

3T3 Cells↗

P nucleotides, hairpin DNA and V(D)J joining: making the connection.

The fine-structures of V(D)J joining products present a cache of information about the recombination process. Testable hypotheses with predictive value are beginning to provide a surprisingly detailed picture of the joining operation. Here, one feature of V(D)J junctions, the appearance of short palindromic inserts, is discussed, and experimental evidence in support of a joining model involving a hairpin-terminated DNA intermediate will be summarized.

Animals↗