Biomedical subjects
Publications and source records attributed to A Beck.
The two geminal ethyl groups in the succinic acid moiety of CGP57698 (4-[3-(7-fluoro-2-quinolinyl-methoxy)phenyl-amino]-2,2-diethyl-4-oxo- butanoic acid) are responsible for the high in vitro and in vivo potency of this peptidoleukotriene antagonist of the quinoline type. The synthesis and structure activity relationships of CGP57698 and its analogs are described.
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Black-Caribbean patients are more often admitted compulsorily to psychiatric wards than patients from other ethnic groups. We tested the hypothesis that perceived ethnicity of a patient had no independent effect on the risk of compulsory admission. For all consecutive admissions over a 6-month period to acute psychiatric wards in Nottingham, medical officers responsible for the decision to admit completed a questionnaire recording clinical details of the patients and reasons for admission. The results showed that 43.2% of Black-Caribbean patients and 18.8% of White patients were admitted compulsorily (unadjusted odds ratio 3.29, 95% CI 1.71-6.33). Perceived ethnicity (Black-Caribbean) was significantly associated with being young, receiving a diagnosis of psychosis, and being perceived to be at a risk of violent acting out. A forced entry logistic regression model was used to adjust for hypothesised confounding variables such as age, sex, diagnosis, risk, socio-economic status and level of social support. A diagnosis of psychosis, risk of committing violence and being Black-Caribbean had independent effects on the risk of being compulsorily detained. The odds ratio for compulsory detention of Black-Caribbean patients was 2.16 (95% CI 1.03-4.52) after adjusting for the hypothesised confounding variables.
We used a standardized bicycle ergometry protocol with a stepwise increasing workload (30-100 W) to evaluate various metabolic factors for the diagnosis and metabolic monitoring of mitochondrial encephalomyopathies. All patients (n = 9) showed pathological venous lactate/pyruvate (L/P) ratios, which normalized in three patients after 6 months of coenzyme Q10 (CoQ) therapy. Thus, the L/P ratio proved to be the clinically most useful parameter in the evaluation and monitoring of mitochondrial diseases, showing higher sensitivity than lactate measurements only. CoQ may exert a favourable effect in some patients with mitochondrial diseases.
We used equilibrium binding analysis to characterize the agonist binding properties of six different rat neuronal nicotinic receptor subunit combinations expressed in Xenopus laevis oocytes. The alpha4beta2 receptor bound [3H]cytisine with a Kdapp of 0.74 +/- 0. 14 nM. The rank order of Kiapp values of additional nicotinic ligands, determined in competition assays, was cytisine < nicotine < acetylcholine < carbachol < curare. These pharmacological properties of alpha4beta2 expressed in oocytes are comparable to published values for the high affinity cytisine binding site in rat brain (alpha4beta2), demonstrating that rat neuronal nicotinic receptors expressed in X. laevis oocytes display appropriate pharmacological properties. Use of [3H]epibatidine allowed detailed characterization of multiple neuronal nicotinic receptor subunit combinations. Kdapp values for [3H]epibatidine binding were 10 pM for alpha2beta2, 87 pM for alpha2beta4, 14 pM for alpha3beta2, 300 pM for alpha3beta4, 30 pM for alpha4beta2, and 85 pM for alpha4beta4. Affinities for six additional agonists (acetylcholine, anabasine, cytisine, 1, 1-dimethyl-4-phenylpiperazinium, lobeline, and nicotine) were determined in competition assays. The beta2-containing receptors had consistently higher affinities for these agonists than did beta4-containing receptors. Particularly striking examples are the affinities displayed by alpha2beta2 and alpha2beta4, which differ in 1,1-dimethyl-4-phenylpiperazinium, nicotine, lobeline, and acetylcholine affinity by 120-, 86-, 85-, and 61-fold, respectively. Although smaller differences in affinity could be ascribed to different alpha subunits, the major factor in determining agonist affinity was the nature of the beta subunit.
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Deformation due to growth disturbance after epiphyseal fractures around the knee may involve more than the primarily injured epiphysis, as spontaneous corrective growth of the opposite epiphyseal plate can take place in an attempt to maintain overall alignment of the leg. As a result, there will be an inclination in the knee joint line if corrective osteotomy is only performed for the primary angulation. We report two cases of this complex deformity in which corrective osteotomies of both the distal femur and the proximal tibia were performed, resulting in correct alignment of the overall leg axis and knee joint axis.
OBJECTIVE: To determine whether a schedule of fewer prenatal visits than traditional for women with low-risk pregnancies lead to additional medical services outside prescribed prenatal care. METHODS: In a randomized, controlled trial conducted within a group-model health maintenance organization, we studied 2328 pregnant women judged to be a low risk of adverse perinatal outcomes. After risk assessment and consent, women were assigned to an experimental (nine visits) or a control (14 visits) schedule, with additional visits if requested either by providers after identifying risks or by women seeking additional services. We recorded whether women underwent maternal serum alpha-fetoprotein screening, obstetric ultrasound examinations at 15-24 weeks' gestation, hematocrit testing after 20 weeks, and diabetic screening. We also noted visits to nonobstetric care providers or our emergency care center, telephone calls, and hospitalizations. RESULTS: We found no significant differences between the two groups for prenatal blood tests, visits to nonobstetric providers or to the emergency care center, telephone calls from patients, or hospital admissions. A significantly greater percentage of women underwent ultrasound examinations at 15-24 weeks in the control group compared with the experimental group (57.3% and 53.1%, respectively; P = .045). CONCLUSION: The reduction in prenatal visits achieved using the experimental schedule was not accompanied by an increase in the use of other medical services compared with the routine schedule. The use of the schedule proposed by the Expert Panel on the Content of Prenatal Care improved the efficiency of delivery of prenatal care to low-risk women.
OBJECTIVE: To compare the impact of group outpatient visits to traditional "physician-patient dyad" care among older chronically ill HMO members on health services utilization and cost, self-reported health status, and patient and physician satisfaction. DESIGN: A 1-year randomized trial. SETTING: A group model HMO in the Denver Metropolitan area. PARTICIPANTS: Three hundred twenty-one members aged 65 and older, randomized to a group visit intervention (n = 160) or to usual care (n = 161). INTERVENTION: Patients with high health services utilization and one or more chronic conditions had monthly group visits with their primary care physician and nurse. Visits included health education, prevention measures, opportunities for socialization, mutual support, and for one-to-one consultations with their physician, where necessary. MEASUREMENTS: Health services utilization and associated cost, health status, and patient and physician satisfaction. RESULTS: Outcome measures obtained after a 1-year follow-up period showed that group participants had fewer emergency room visits (P = .009), visits to subspecialists (P = .028), and repeat hospital admissions per patient (P = .051). Group participants made more visits (P = .021) and calls (P = .038) to nurses than control group patients and fewer calls to physicians (P = .019). In addition, a greater percentage of group participants received influenza and pneumonia vaccinations (P < .001). Group participants had greater overall satisfaction with care (P = .019), and participating physicians reported higher levels of satisfaction with the groups than with individual care. No differences were observed between groups on self-reported health and functional status. Cost of care per member per month was $14.79 less for the group participants. CONCLUSIONS: Group visits for chronically ill patients reduce repeat hospital admissions and emergency care use, reduce cost of care, deliver certain preventive services more effectively, and increase patient and physician satisfaction.
BACKGROUND: Although modern psychiatric services seek alternatives to hospitalisation wherever appropriate, the national trend toward higher bed occupancies on acute psychiatric wards has refocused attention on community-based alternatives and methods of assessing reed for acute care. METHOD: We surveyed key decision makers in a community-oriented district service with a low acute psychiatric bed to population ratio, in order to examine alternatives to hospitalisation in a cohort of consecutive admissions over a six-month period. RESULTS: Alternatives to acute ward hospitalisation were identified for 29% of admissions, and for 42% of those with an admission duration of more than 60 days. Residential options were chosen more often than intensive community support. Simulated bed day savings were considerable. CONCLUSIONS: In a community-oriented service, key decision-makers could identify further alternatives to acute ward hospitalisation, although relatively few non-residential, community support options were chosen. Although this methodology has limitations, data based upon keyworker judgements probably have greater local 'ownership', and the option appraisal process itself may challenge stereotyped patterns of resource use.
OBJECTIVE: The effect of varying mineral intakes on total body bone mass accretion during the first year of life in healthy full-term infants is unknown. The purpose of this study was to determine whether total body bone mass accretion during the first year of life was influenced by the calcium and phosphorus intake of an infant and whether early differences in bone accretion persist through 1 year of age. DESIGN: This prospective, randomized trial was conducted in two phases. In phase I, 67 infants were randomized within the first 2 weeks of life into either a low (439 mg of calcium per liter and 240 mg of phosphorus per liter) or moderate (510 mg of calcium per liter and 390 mg of phosphorus per liter) mineral-containing formula feeding group. An additional group of 34 human milk-fed (low mineral) infants also was enrolled. Phase II involved an additional randomization of all infants at 6 months of age into moderate-mineral formula (see above), high-mineral formula (1350 mg of calcium per liter and 900 mg of phosphorus per liter), or cow milk (1230 mg of calcium per liter and 960 mg of phosphorus per liter) feeding group. Anthropometric measurements, nutrient intake, and total body bone mineral content (BMC) by dual-energy x-ray absorptiometry were measured at 1, 3, 6, 9, and 12 months. RESULTS: During the first 6 months, the moderate-mineral group had a greater increase in weight (3.42 +/- 0.62 kg) compared with the human milk group (2.93 +/- 0.56 kg); the low-mineral group (3.19 +/- 0.62 kg) was intermediate. Bone mass accretion differed in a similar direction, with the moderate-mineral feeding group having a greater increase than the human milk group and the low-mineral group being intermediate of the two. Including weight, length, and bone area as covariates, both the low-mineral formula- and human milk-fed groups had similar BMC, which was lower than that of the moderate-mineral group at 3 and 6 months of age. Adjusted mean BMC values for the moderate-mineral formula-fed group compared with the low-mineral formula- and human milk-fed groups were 127.8 +/- 1.5 (SEM) g vs 119. 2 +/- 1.5 and 122.1 +/- 1.4 g, respectively, at 3 months of age and 168.7 +/- 2.5 g vs 157.6 +/- 2.5 and 158.7 +/- 2.4 g, respectively, at 6 months of age. The BMC at 6 months of age among the formula-fed infants was correlated with both average dietary phosphorus intake (r = .592) and average daily calcium intake (r = .620) during the first 6 months. The relationships between BMC and these minerals remained significant even after controlling for caloric intake. It was not possible to determine the independent effects of dietary calcium and phosphorus on BMC because of the strong correlation of these minerals with each other. Despite significant differences in both calcium and phosphorus intakes during the second 6 months of life, there were no differences in growth parameters or bone mass accretion. Means for BMC, adjusted for body weight, length, and bone area, were not significantly different among feeding groups at either 9 or 12 months of age. Adjusted means were 199 +/- 2 (SEM) and 237 +/- 3 g at 9 and 12 months of age for infants receiving moderate-mineral formula; 198 +/- 2 and 236 +/- 3 g at 9 and 12 months of age for infants receiving the high-mineral formulas and 202 +/- 5 and 233 +/- 5 g at 9 and 12 months of age for infants receiving cow milk. The gain in bone mass during the second 6 months differed by the first 6-month feeding group; mean changes in BMC between 6 and 12 months, adjusted for changes in weight, length, and bone area, were greater in human milk-fed infants than in either the low- or moderate-mineral-containing formula groups: 81 +/- 16 g in human milk-fed infants and 73 +/- 15 and 71 +/- 15 g in the low- and moderate-mineral formula groups, respectively. Infants fed whole cow milk during the second 6 months were excluded from this analysis because of the small number of infants completing the study. By 12 months of age t
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OBJECTIVES: In 1989, the Expert Panel on the Content of Prenatal Care established guidelines on the timing and content of prenatal care, including a schedule consisting of fewer prenatal visits than traditionally provided, for women at low risk of adverse perinatal outcomes. We tested the hypothesis that there are no significant increases in adverse perinatal outcomes when low-risk women are seen in a prenatal care visit schedule of fewer visits than routinely advised. DESIGN: Randomized controlled trial. SETTING: Group-model health maintenance organization. PATIENTS: A total of 2764 pregnant women, judged to be at low risk of adverse perinatal outcomes. INTERVENTIONS: Following risk assessment, participants were randomly assigned to an experimental schedule (nine visits) or a control schedule (14 visits) with additional visits as indicated or as desired by the patient. MAIN OUTCOME MEASURES: Preterm delivery, preeclampsia, cesarean delivery, low birth weight and patient's satisfaction with care. RESULTS: On average, there were 2.7 fewer visits observed in the experimental group than in the control group. There were no significant increases in the main outcomes of the experimental group; preterm delivery (relative risk [RR], 1.08; 95% confidence interval [CI], 0.92 to 1.27; P = .19), preeclampsia (RR, 0.94; 95% CI, 0.78 to 1.14, P = .74), cesarean delivery (RR, 1.04; 95% CI, 0.93 to 1.17; P = .25), and low birth weight (RR, 0.94; 95% CI, 0.78 to 1.12; P = .76). There were no differences between the two groups in patients' satisfaction with quality of prenatal care. CONCLUSION: In this study, good perinatal outcomes and patient satisfaction were maintained when the prenatal visit schedule proposed by the Expert Panel on the Content of Prenatal Care was observed.
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OBJECTIVE: Our purpose was to determine whether nonclosure of the visceral peritoneum at low transverse cesarean delivery has advantages over suture peritonization with regard to postoperative morbidity. STUDY DESIGN: A prospective randomized trial of 549 women undergoing cesarean section was carried out; 262 were randomized to nonclosure and 287 to closure of the visceral peritoneum. Perioperative, intraoperative, and postoperative management decisions were made without reference to treatment groups. Statistical analysis compared intraoperative and postoperative outcome between the two groups. RESULTS: Operating and anesthesia times were significantly shorter in patients receiving nonclosure. The incidence of febrile morbidity and cystitis and the need for antibiotics and narcotics were all significantly greater when the peritoneum was closed. Hospital stay was significantly shorter after nonclosure. CONCLUSION: Nonclosure of the visceral peritoneum is associated with lower febrile and infectious morbidity. Routine closure of the visceral peritoneum should be abandoned at cesarean delivery.
In recent years a variety of studies have been carried out to compare the accuracy (generally expressed in terms of sensitivity and specificity) of commercially available anti-HTLV tests. None of these studies were performed in Brazil or in any other South American country. During the characterization of our Brazilian reference panel we evaluated the sensitivities and specificities of the Abbott HTLV EIA (100%; 89.7%) and the Biochrom HTLV-1/-2 ELISA (100%; 42.4%). Our conclusion was that both assays may be problematic in terms of correctly identifying HTLV-negative sera. We therefore adjusted the cut-off values using receiver operating characteristics (ROC). ROC analysis, which involves calculating sensitivity and specificity for several cut-off values, can be used to ascertain the co-variation in the specificity and sensitivity of any assay giving quantitative results. The optimum cut-off value for the assay in a given study population is the point that gives highest possible sensitivity in conjunction with a small false-positive fraction. Using the HTLV-1/-2 Western blot as the "gold standard", we were able to improve the specificity of the Biochrom HTLV-1/-2 assay to 95% without affecting its sensitivity of 100%. However, it seems that when using the Biochrom HTLV-1/-2 ELISA, there may be problems in separating positive and negative sera. In the case of the Abbott HTLV EIA, our ROC analysis revealed that the cut-off value suggested by the manufacturer was nearly identical to the optimum cut-off value. Adjustment will affect neither sensitivity nor specificity. However, a slight adjustment of the cut-off value result in a clearer separation of the positive and negative populations. Furthermore, we assume that this adjustment will help to avoid false-positive results when larger serum panels are investigated. Further investigations will show whether or not this problem is linked to the geographical regions where the test is performed (e.g. polyclonal stimulation due to parasitic infections in tropical countries).
The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X-linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide-exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.