Increased bone turnover during the third trimester of pregnancy and decreased bone mineral density after parturition in adolescents as compared to age-matched control patients.

To evaluate the impact of pregnancy on bone, we studied bone turnover at the first (T1) and third (T3) trimester of gestation in 58 adolescents and 28 healthy adolescents who had never been pregnant. Total body (TB) and lumbar spine (LS) bone mineral density (BMD) and body composition were evaluated by dual-energy X-ray absorptiometry in all control patients (C) and after parturition in 28 pregnant patients (G). Paired and unpaired t tests, Mann-Whitney and Pearson correlation tests were used. Bone turnover markers were above the reference range for adult women in more than 80% of the adolescents, with no difference between C and G patients at T1. Increase in urinary N-telopeptide crosslinks of type I collagen and serum bone-specific alkaline phosphatase, markers of bone turnover, was seen during pregnancy ( p < 0.0001). Body composition did not differ between groups, but LS BMD, percentage of expected LS BMD, LS Z-score, percentage of expected TB BMD and TB Z-score were lower in G than C patients ( p < 0.05). TB BMD was positively correlated with LS BMD (r2 = 0.52). The inverse correlations between bone markers and LS BMD suggest that the increased bone turnover during pregnancy probably explains the low bone density after parturition. The impact on future peak bone mass must be studied.     

Determinants of left ventricular systolic function recovery after an acute coronary syndrome.

INTRODUCTION: Ischemic heart disease is a major cause of heart failure in western societies. However, the factors that may influence left ventricular function (LVF) recovery after an acute coronary syndrome (ACS) are still unclear. OBJECTIVE: To identify variables that may influence LVF evolution one year after ACS. METHODS: 104 patients hospitalized with ACS between 7/1/2001 and 12/31/2002 and with systolic dysfunction--defined as an echocardiographic ejection fraction (EF) < or = 45%--were randomly allocated to a planned coronary follow-up program (FUP) or a general cardiology clinic (GC); patients from both groups were also randomly referred to a structured cardiac rehabilitation program (CRP). EF was re-assessed at one year. We compared differences between patients who recovered left ventricular function (EF > 45%; group 1) and those who did not (group 2). RESULTS: One year after discharge, 44.2% of the patients had recovered function. There were no significant differences between the groups in gender (77.7 vs. 76.5% male), age (56 vs. 59 years), hypertension, diabetes, dyslipidemia, smoking habits or family history. A previous history of cardiovascular events was more frequent in group 2 (11.1% vs. 35.3%, p = 0.03). Cardiac catheterization was performed before discharge in 88.8% and 88.2% in groups 1 and 2 respectively (p = NS); no differences were found in coronary anatomy between the two groups. Angioplasty was performed in 54.2% in group 1 and 50% in group 2 (p = NS). There were no differences in the use of angiotensin-converting enzyme inhibitors (83.3% vs. 87.5%), beta-blockers (87.5% vs. 87.5%), nitrates (37.5% vs. 33.3%), aspirin (95.8% vs. 95.8%), statins (79.1% vs. 75%) or diuretics (20.8% vs. 45.8%). There was no significant difference in LVF recovery between patients randomized to FUP or GC (38.5% vs. 54.5%). 87.5% of patients who completed the CRP had normal EF at one year compared to 32.7% of patients not referred to the program (p = 0.009). Although EF improved in both groups, this improvement was greater in patients who completed a CRP (EF 8% vs. 5%, p = 0.003). CONCLUSION: A previous cardiovascular event and completion of a CRP were the only variables that influenced LVF recovery. Thus, enrollment in a CRP, in addition to standard therapy, could be an important therapeutic measure in patients with systolic dysfunction after ACS; our data suggest that these programs should be more widely used.     

Evidence of lowest brain penetration of an antiemetic drug, metopimazine, compared to domperidone, metoclopramide and chlorpromazine, using an in vitro model of the blood-brain barrier.

PURPOSE: The objective of the current study was to determine the ability of some antiemetic compounds to cross the blood-brain barrier (BBB) and thereby to determine possible side effects of compounds for the central nervous system (CNS). METHODS: We compared the brain penetration of some antiemetic compounds using an in vitro BBB model consisting in brain capillary endothelial cells co-cultured with primary rat glial cells. RESULTS: This study clearly demonstrated that the metopimazine metabolite, metopimazine acid, has a very low brain penetration, lower than metopimazine and even less than the other antiemetic compounds tested in this study. CONCLUSIONS: The poor brain penetration of metopimazine acid, metopimazine biodisponible form, seems very likely related to the clinically observed difference in therapeutic and safety profile.     

Discriminative conditioning-related slow potential and single-unit responses in the frontal cortex of urethane-anesthetized rats

A model is described for obtaining long-term and stable discriminative conditioning-related slow-potential and single-unit responses from the frontal cortex of urethane-anesthetized rats. Responses were recorded and analyzed to reinforced (rewarding medial forebrain bundle stimulation) and non-reinforced tone cues. In the present study, cortical event-related slow potentials provided an adequate index of the level of discriminative conditioning. Single-unit response patterns are described for 57 neurons which demonstrated a discriminative response to either the reinforced or non-reinforced tone cue.     

Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B

Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, K_i, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.     

Pain levels experienced with activities after cardiac surgery.

BACKGROUND: Acute pain is common after cardiac surgery and can keep patients from participating in activities that prevent postoperative complications. Accurate assessment and understanding of pain are vital for providing satisfactory pain control and optimizing recovery. OBJECTIVES: To describe pain levels for 5 activities expected of patients after cardiac surgery on postoperative days 1 to 6 and changes in pain levels after chest tube removal and extubation. METHODS: Adults who underwent cardiac surgery were asked to rate the pain associated with various types of activities on postoperative days 1 to 6. Pain levels were compared by postoperative day, activity, and type of cardiac surgery. Pain scores before and after chest tube removal and extubation also were analyzed. RESULTS: Pain scores were higher on earlier postoperative days. The order of overall pain scores among activities (P < .01) from highest to lowest was coughing, moving or turning in bed, getting up, deep breathing or using the incentive spirometer, and resting. Changes in pain reported with coughing (P = .03) and deep breathing or using the incentive spirometer (P = .005) differed significantly over time between surgery groups. After chest tubes were discontinued, patients had lower pain levels at rest (P = .01), with coughing (P = .05), and when getting up (P = .03). CONCLUSIONS: Pain relief is an important outcome of care. A comprehensive, individualized assessment of pain that incorporates activity levels is necessary to promote satisfactory management of pain.     

Quantitative immunoblotting assay of blood coagulation factor XII

The immunoblotting technique was applied to the study of Factor XII (F.XII) in plasma. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of whole plasma followed by electroblotting of the electropherograms to nitrocellulose (NC) membranes and immunologic detection by a double antibody technique was used. ¹²⁵-F.XII was transferred to the NC membrane in amounts proportional to the amount applied to the gel provided that a constant amount of carrier protein was present. Based on this, a quantitative assay was developed using either normal plasma or F.XII dilutions in F.XII-deficient plasma as standards. The measurement of F.XII antigen by immunoblotting was reproducible and gave values similar to those obtained by radial immunodiffusion. Two normal plasma pools contained 26 and 29 μ/ml of F.XII according to the immunoblotting assay. Compared to other immunoassays, immunoblotting has the advantage of directly estimating the apparent molecular weight (MW) of the protein of interest. Thus, we could confirm the normal apparent MW (80,000) of a F.XII-like molecule previously isolated from a cross reacting material (CRM)-positive F.XII-deficient plasma. None of eight CRM-negative F.XII-deficient plasmas showed an 80,000 MW immunoreactive molecule. However, five of these eight plasmas had a faint autoradiographic band at 115,000 MW that was similarly seen in only three out of 43 individual normal plasmas. The nature of this 115,000 MW band remains to be defined.     

A model-based detector of vertex waves and K complexes in sleep electroencephalogram.

A model of sleep phasic events such as vertex waves, K complexes, delta waves and sleep spindles is proposed. It consists of feedback loops that are driven by white noise (simulating tonic delta and sigma activity) and by isolated random impulses, simulating vertex waves or K complexes, depending on the background tonic activity. A model-based method for the detection of sleep phasic events was implemented in a personal computer. Its performance was investigated using simulated and real whole-night EEG signals. The method was able to detect K complexes and vertex waves in a reliable way in spite of their variable shapes and in the presence of a variety of background activities. The detector appears to have superior performance to those so far reported in the literature. The performance of the detector was also compared to that of an electroencephalographer using normal sleep EEG records of 8 h duration from 6 subjects. The performance was satisfactory both in terms of accuracy and reliability. The problem of detecting K complexes in stages 3 and 4 of sleep is discussed.     

Experience of a combined apheresis, blood collection, and blood transfusion unit in a large tertiary care medical center

The Barnes Hospital Apheresis Blood Collection and Blood Transfusion Unit is part of Barns Hospital Blood Bank. Because of its size and complexity, we report our experience which may be useful to administrators and physicians involved in the planning or management of similar services. From 1985 through 1988 we collected platelets from 1,976 different donors, the majority of which (87%) were community donors. Sixty-nine percent of 1,976 donors donated in 1988 an average of 4.9 times. Of 6,568 apheresis products collected. 1.1% were discarded because of positive screening tests and 0.7% were discarded because of outdating or presence of fibrin clot. In 1988 a total of nine cell separators were used. All donor apheresis were done with seven blood separators, and on average a separator produced an apheresis product every 4.5 worked hours. All therapeutic apheresis (338) were done on two separators. Most of them (88%) were performed during work hours. In 1988 donor and therapeutic apheresis were done by 17 1/2 full-time employees (FTEs) during work hours. Considering the Workload Unit Value per procedure given by the College of American Pathologists (CAP) and that each FTE worked 1,864 hours per year, the worked hour productivity for donor and therapeutic apheresis was 78.2%. Blood collections, therapeutic bleeds, and outpatient transfusions (1,127, 114 and 1,745 respectively) were accomplished by two FTEs, for a worked hour productivity of 35.5%. Because 95.1% of total worked units was produced by efficient donor and therapeutic apheresis activities, overall efficiency remained high at 73.8%.