More trouble with ethics committees.
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Ethics Committees↗
Biomedical subjects
A Cohen
Publications and source records attributed to A Cohen.
Maternal intrapartum temperature elevation as a risk factor for cesarean delivery and assisted vaginal delivery.
OBJECTIVES: This study investigated the association of intrapartum temperature elevation with cesarean delivery and assisted vaginal delivery. METHODS: Participants were 1233 nulliparous women with singleton, term pregnancies in vertex presentations who had spontaneous labors and were afebrile (temperature: 99.5 degrees F [37.5 degrees C]) at admission for delivery. Rates of cesarean and assisted vaginal deliveries according to highest intrapartum temperature were examined by epidural status. RESULTS: Women with maximum intrapartum temperatures higher than 99.5 degrees F were 3 times as likely to experience cesarean (25.2% vs 7.2%) or assisted vaginal delivery (25.2% vs 8.5%). The association was present in epidural users and nonusers and persisted after birthweight, epidural use, and labor length had been controlled. In adjusted analyses, temperature elevation was associated with a doubling in the risk of cesarean delivery (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5, 3.4) and assisted vaginal delivery (OR = 2.1, 95% CI = 1.4, 3.1). CONCLUSIONS: Modest temperature elevation developing during labor was associated with higher rates of cesarean and assisted vaginal deliveries. More frequent temperature elevation among women with epidural analgesia may explain in part the higher rates of cesarean and assisted vaginal deliveries observed with epidural use.
Adult↗
Correlational cuing as a function of target complexity and target-flanker similarity.
It is generally assumed that the correlational cuing effect (CE) between targets and correlated flankers is due to learning association between the flankers and their correlated responses. The present study challenges this view. Experiment 1 shows that the CE for targets composed of color is eliminated as soon as the correlation is removed. Experiment 2 shows that the CE during training is not due to association of the flankers with responses. Experiment 3 shows that at least some of the CE during training with the correlation is due to repetition priming of the display. Experiment 4 replicates the results of Experiment 1 for orientation targets. In Experiments 5-7, more typical tasks with letter targets are examined, and it is demonstrated that preexperimental similarity between targets and correlated flankers is crucial. The CE for correlated but dissimilar target-flanker pairs, similar to that for color and orientation targets, is confined to on-line processes that occur during training. The CE is transferred, however, for correlated and similar target-flanker pairs. We propose that, at least for the simple stimulus to response mapping used in our study, the CE is not due to learning at all. Instead it is due to (1) on-line processes, such as repetition priming, that occur during training with the correlation and (2) a regular flanker effect (see, e.g., B. A. Eriksen & C. W. Eriksen, 1974) that occurs for similar target-flanker pairs.
Adult↗
Intra- and cross-dimensional visual search for single-feature targets.
Cross-dimensional visual search for single-feature targets that differed from the distractors along two dimensions (color and orientation) was compared with intradimensional search for targets that differed from the distractors along a single dimension (either orientation or color). The design of the first three experiments differed from those of previous studies in that participants were required to respond differently to each of the targets. Experiments 1-3 were similar except that in Experiment 1, the distractors were homogeneous; in Experiment 2, two types of distractors were used in equal proportions; and in Experiment 3, two types of distractors were used but one of the distractors was a singleton. The findings, contrary to those of previous studies, revealed that cross-dimensional search is at least as efficient and for some targets even more efficient than intradimensional search. These results suggest that the details of stimulus-to-response mapping are essential in comparing intra- and cross-dimensional tasks. Experiment 4 used a priming design and did not support an explanation based on grouping processes. We outline an explanation for all the findings based on a recent cross-dimensional response selection model by Cohen and Shoup (1997).
Adult↗
Analysis of forces developed during mechanical preparation of extracted teeth using Profile NiTi rotary instruments.
AIM: The aim of this study was to analyse the vertical forces and torque developed in the root canal system of extracted teeth during mechanical preparation using ProFile NiTi instruments. METHODOLOGY: Instrument wear and fracture is in great part due to the repeated application of forces and torque during the course of root-canal preparation but research into the direct relationship has been hampered by the lack of adequate measuring devices. Measurements of these forces and torque were made with a new force analyser device, the Endographe, that was equipped with a holder to record and generate graphs of the vertical forces and torque exerted during the preparations. These preparations was performed by endodontists or students either with a series of instruments of increasing size or with the crown-down pressureless technique. RESULTS: The mean values for the endodontists of the generated vertical forces and torque varied, respectively, from 4 to 6N and from 7.105 to 12.105 Nm for the step-back technique and from 2.9 to 4.2 N and from 18.105 to 20.105 Nm for the crown-down technique. This suggested that the crown-down technique generated lower stresses (lower torque and lower vertical forces), although these findings also depend on the shape of individual canals. The students initially showed wide variations in generated forces, with significantly lower vertical force the torque values. By the end of the experimental sessions their values were similar to those of the endodontists, which indicated improvement in the efficiency of manipulation. CONCLUSIONS: Further work is needed to investigate the relationship between the force and the torque data from this study and the incidence of instrument fracture with the two techniques, as the clinical implications are considerable. It must be noted, however, that the Endographe is unable to take into account the cutting efficiency of the instruments. The use of graphs provides a new approach to the analysis of mechanical preparation.
Analysis of Variance↗
Paclitaxel, UFT, and calcium folinate in metastatic breast cancer.
This is a phase I dose-escalation study of uracil and tegafur (in a molar ratio of 4:1 [UFT]) administered in combination with calcium folinate and paclitaxel in metastatic breast cancer. This trial was initiated to 1) determine the maximum tolerated dose and dose-limiting toxicities of UFT plus calcium folinate (Orzel) administered three times per day for 21 days in combination with paclitaxel; and 2) define the appropriate dose for phase II testing. Thus far, 14 patients have been accrued to three dose levels. Two patients developed dose-limiting toxicities at dose level 3. One patient experienced grade 3 hypotension. A second patient experienced grade 3 vomiting, grade 4 diarrhea, and severe hand-foot syndrome. Two partial responses and one complete response have been observed. Early trends suggest that this regimen is active in metastatic breast cancer and is well tolerated. Completion of this study is anticipated in 1999.
Adult↗
Independence in instrumental activities of daily living and its effect on mortality.
Factors relating to six-year mortality in a representative sample of seventy-year-old Jerusalem residents (N = 605) were investigated using logistic regression techniques. Around 16.3% of the study population died during the six-year post-interview period. Bivariate analysis found elevated mortality related to being male, having more than one IADL dysfunction, more than two ADL dysfunctions, financial problems, no social support in times of emergencies, bad self-rated health status, cognitive impairment, confinement to bed during the fortnight prior to interview, and lack of regular exercise. Logistic regression controlling for gender, various clinical diagnoses, financial state, social support and smoking status showed IADL (ROR = 4.57, 95% CI 1.51, 13.90), cognitive impairment (ROR = 3.99, 95% CI 1.85, 8.59) and having been bed-sick a week or more during the preceding fortnight (ROR = 6.60, 95% CI 1.00, 43.86) to be independent predictors of mortality. All persons who had a cognitive problem and were dysfunctional in more than two IADL categories, and 93.8% of persons who had been bed-sick and had more than one IADL dysfunction died during the study period. Combined measures of these three easily obtainable variables could prove a cheap and efficient method of identifying at-risk elderly persons in order to provide them with specific programs aimed at decreasing functional decline, and hence mortality.
Activities of Daily Living↗
[Appetite suppressants and heart valve disorders].
Serotoninergic appetite-suppressant drugs, fenfluramine and dexfenfluramine, were withdrawn from the market in September 1997 on account of two major cardiopulmonary complications: primary pulmonary hypertension and valvular regurgitation. The valvular heart diseases involve mainly left-sided valves, and contrary to physiological valvular regurgitations, they appear mostly on the aortic valve. Prolonged exposure (> 3 months) appears to confer a higher risk of cardiac valve involvement. Pathological features are similar to carcinoid or ergot alkaloid-induced valve diseases, and suggest a common pathophysiological mechanism which would also explain pulmonary hypertension by the toxic effect of high levels of circulating serotonin. After the first reports documenting a dramatically high prevalence of valvular side effects (up to 33% according to the Food and Drug Administration), recent studies reported a lower prevalence and severity. The long-term outcome and the real incidence are unknown and require further research and epidemiological data. A clinical survey of the patients exposed to serotoninergic appetite-suppressants is necessary, to be repeated 6 to 8 months later in the absence of an initial cardiac murmur. Doppler echocardiographic examination should be performed after prolonged exposure (> 3 months) or a high dosage of these drugs, in circumstances such as the presence of cardiovascular symptoms, a cardiac murmur, or an uncertain cardiac examination because of weight of patients.
Adult↗
[Recommendations of the French Society of Cardiology concerning indications for Doppler echocardiography].
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Cardiovascular Diseases↗
Pharmacokinetics of a recombinant modified amino terminal fragment of bactericidal/permeability-increasing protein (rBPI21) in healthy volunteers.
Phase I pharmacokinetic and safety studies were conducted in healthy volunteers with rBPI21, a recombinant protein derived from the amino terminal domain of human bactericidal/permeability-increasing protein. rBPI21 was administered as a 30-minute infusion at doses of 0.25 to 4 mg/kg or as a 24- to 48-hour infusion at doses of 2 to 8 mg/kg. For the 30-minute infusions, the clearance of rBPI21 decreased with increasing dose from 8.4 mL/min/kg at 0.25 mg/kg to 3.3 mL/min/kg at 4 mg/kg. For rBPI21 infused over 24 to 48 hours the clearance was 10 to 11 mL/min/kg. The concentration-time profile of rBPI21 was well described by a three-compartmental model with parallel first-order and Michaelis-Menten (saturable) elimination. This model for the clearance of rBPI21 has been useful in estimating starting doses for therapeutic clinical trials.
Adolescent↗
Mental health services--primary concerns for the future.
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Family Practice↗
[Ultrasonographic imaging of superior sagittal thrombosis].
Ultrasonographic findings of superior sagittal sinus thrombosis include dilated and hyperechoic sinus (direct imaging of the thrombus). No flow should be demonstrated by the various Doppler techniques. In the deeper sinuses, if the thrombus can not be visualized after a negative Doppler study, MR imaging is recommended. Recanalization and reflow can be demonstrated on follow-up study.
Humans↗
Transient cardiac expression of constitutively active Galphaq leads to hypertrophy and dilated cardiomyopathy by calcineurin-dependent and independent pathways.
Cardiac hypertrophy and dilatation can result from stimulation of signal transduction pathways mediated by heterotrimeric G proteins, especially Gq, whose alpha subunit activates phospholipase Cbeta (PLCbeta). We now report that transient, modest expression of a hemagglutinin (HA) epitope-tagged, constitutively active mutant of the Gq alpha subunit (HAalpha*q) in hearts of transgenic mice is sufficient to induce cardiac hypertrophy and dilatation that continue to progress after the initiating stimulus becomes undetectable. At 2 weeks, HAalpha*q protein is expressed at less than 50% of endogenous alphaq/11, and the transgenic hearts are essentially normal morphologically. Although HAalpha*q protein declines at 4 weeks and is undetectable by 10 weeks, the animals develop cardiac hypertrophy and dilatation and die between 8 and 30 weeks in heart failure. As the pathology develops, endogenous alphaq/11 rises (2.9-fold in atria; 1.8-fold in ventricles). At 2 weeks, basal PLC activity is increased 9- to 10-fold in atria but not ventricles. By 10 weeks, it is elevated in both, presumably because of the rise in endogenous alphaq/11. We conclude that the pathological changes initiated by early, transient HAalpha*q expression are maintained in part by compensatory changes in signal transduction and other pathways. Cyclosporin A (CsA) prevents hypertrophy caused by activation of calcineurin [Molkentin, J. D., Lu, J.-R., Antos, C. L., Markham, B., Richardson, J., Robbins, J., Grant, S. R. & Olson, E. N. (1998) Cell 93, 215-228]. Because HAalpha*q acts upstream of calcineurin, we hypothesized that HAalpha*q might initiate additional pathways leading to hypertrophy and dilatation. Treating HAalpha*q mice with CsA diminished some, but not all, aspects of the hypertrophic phenotype, suggesting that multiple pathways are involved.
Animals↗
Effect of deletion of the major brain G-protein alpha subunit (alpha(o)) on coordination of G-protein subunits and on adenylyl cyclase activity.
Heterotrimeric G-proteins, composed of alpha and betagamma subunits, transmit signals from cell-surface receptors to cellular effectors and ion channels. Cellular responses to receptor agonists depend on not only the type and amount of G-protein subunits expressed but also the ratio of alpha and betagamma subunits. Thus far, little is known about how the amounts of alpha and betagamma subunits are coordinated. Targeted disruption of the alpha(o) gene leads to loss of both isoforms of alpha(o), the most abundant alpha subunit in the brain. We demonstrate that loss of alpha(o) protein in the brain is accompanied by a reduction of beta protein to 32+/-2% (n = 4) of wild type. Sucrose density gradient experiments show that all of the betagamma remaining in the brains of alpha(o)-/- mice sediments as a heterotrimer (s20,w = 4.4 S, n = 2), with no detectable free alpha or betagamma subunits. Thus, the level of the remaining betagamma subunits matches that of the remaining alpha subunits. Protein levels of alpha subunits other than alpha(o) are unchanged, suggesting that they are controlled independently. Coordination of betagamma to alpha occurs posttranscriptionally because the mRNA level of the predominant beta1 subtype in the brains of alpha(o)-/- mice was unchanged. Adenylyl cyclase can be positively or negatively regulated by betagamma. Because the level of other alpha subunits is unchanged and alpha(o) itself has little or no effect on adenylyl cyclase, we could examine how a large change in the level of betagamma affects this enzyme. Surprisingly, we could not detect any difference in the adenylyl cyclase activity between brain membranes from wild-type and alpha(o)-/- mice. We propose that alpha(o) and its associated betagamma are sequestered in a distinct pool of membranes that does not contribute to the regulation of adenylyl cyclase.
Adenylyl Cyclases↗
A week in the life of a hospital.
The same urgency and intellect that America's teaching hospitals apply to saving lives is now also going into saving the institutions themselves. All across the country, academic medical centers are trying to figure out how to marry progress with profits. At the Duke University Medical Center, TIME visits the front line in the war between money and medicine.
Budgets↗
Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is implicated in reorganizing the actin cytoskeleton.
The p21-activated protein kinases (PAKs) are activated through direct interaction with the GTPases Rac and Cdc42Hs, which are implicated in the control of the mitogen-activated protein kinase (MAP kinase) c-Jun N-terminal kinase (JNK) and the reorganization of the actin cytoskeleton [1-3]. The exact role of the PAK proteins in these signaling pathways is not entirely clear. To elucidate the biological function of Pak2 and to identify its molecular targets, we used a novel two-hybrid system, the Ras recruitment system (RRS), that aims to detect protein-protein interactions at the inner surface of the plasma membrane (described in the accompanying paper by Broder et al. [4]). The Pak2 regulatory domain (PakR) was fused at the carboxyl terminus of a RasL61 mutant protein and screened against a myristoylated rat pituitary cDNA library. Four clones were identified that interact specifically with PakR and three were subsequently shown to encode a previously unknown homologue of the GTPase Cdc42Hs. This approximately 36 kDa protein, designated Chp, exhibits an overall sequence identity to Cdc42Hs of approximately 52%. Chp contains two additional sequences at the amino and carboxyl termini that are not found in any known GTPase. The amino terminus contains a polyproline sequence, typically found in Src homology 3 (SH3)-binding domains, and the carboxyl terminus appears to be important for Pak2 binding. Results from the microinjection of Chp into cells implicated Chp in the induction of lamellipodia and showed that Chp activates the JNK MAP kinase cascade.
Actins↗
Right ventricular infarction.
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Echocardiography↗