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Lack of interaction between two antihistamines, mizolastine and cetirizine, and ethanol in psychomotor and driving performance in healthy subjects.

The pharmacodynamic interaction between mizolastine, a new H1 antihistamine, and ethanol was assessed in a randomized, double-blind, three-way crossover, placebo-controlled study. Eighteen healthy young male volunteers received mizolastine 10 mg, or cetirizine 10 mg or placebo once daily for 7 days with a 1-week wash-out interval. An oral dose of ethanol or ethanol placebo, given 2 h after dosing on days 5 or 7 of each treatment period, was administered to achieve a peak blood alcohol concentration (BAC) of 0.7 g/l then maintained for 1 h by two further doses of ethanol. Driving ability and psychomotor performance were evaluated using actual and simulated driving tests, critical flicker fusion threshold (CFF), adaptive tracking and divided attention (DAT) tasks. Ethanol produced a significant decrement in all tasks up to 5.5 h after administration: an increase in steering movements of 4.6, in lateral deviation of 0.45 m, in braking reaction time of 80 ms, in driving test and DAT performance of + 3.2; and a decrease in CFF and in tracking speed of 2.6 m.s-1. Neither mizolastine nor cetirizine significantly impaired driving ability or arousal (CFF) compared with the placebo. However, both drugs significantly impaired DAT performance 6:00 h post-dose (increase of + 2.1 for mizolastine and + 2.4 for cetirizine). The tracking speed was significantly decreased 7:50 h after mizolastine administration (-1.3 m.s-1) and more consistently from 1:30 to 7:50 h after cetirizine administration (-1.4 m.s-1). No significant adverse interaction, i.e. potentiation, occurred between ethanol and either antihistamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prospective associations between lateralised brain function and immune status in HIV infection: analysis of EEG, cognition and mood over 30 months.

Prospective relations between individual differences in both lateralised neuro-psychophysiological functions and mood ratings with immune status (CD4 and CD8 counts) were examined in asymptomatic HIV-positive men (n = 27) over thirty months. They participated in a controlled study of zidovudine versus placebo (results published elsewhere). Measures included EEG spectra, neuropsychological tests and mood ratings. A model of reciprocal lateralised influences on the immune system was tested whereby patients with left superior to right hemispheric functions were predicted to show a less deleterious outcome than those with the opposite asymmetry pattern. Prospective relations with immune status were found in the EEG with lateralised theta, alpha and beta activity; among cognitive measures with word fluency, semantic processing, and lateralised motor and recognition memory (word/face) processes; with mood ratings including depression, confusion and the total mood score. The nature of the effects supported the laterality predictions. These unique data, showing that neuro-psychophysiological factors in HIV+ but otherwise healthy subjects predict immune competence and compromise present 2-3 years later, warrant replication in a larger cohort.

Adult↗

An experimental randomized study of five different ventilatory modes in a piglet model of severe respiratory distress.

OBJECTIVES: To characterize different modes of pressure- or volume-controlled mechanical ventilation with respect to their short-term effects on oxygen delivery (DO2). Furthermore to investigate whether such differences are caused by differences in pulmonary gas exchange or by airway-pressure-mediated effects on the central hemodynamics. DESIGN: After inducing severe respiratory distress in piglets by removing surfactant, 5 ventilatory modes were randomly and sequentially applied to each animal. SETTING: Experimental laboratory of a university department of Anesthesiology and Intensive Care. ANIMALS: 15 piglets after repeated bronchoalveolar lavage. INTERVENTIONS: Volume-controlled intermittent positive-pressure ventilation (IPPV) with either 8 or 15 cmH2O PEEP; pressure-controlled inverse ratio ventilation (IRV); pressure-controlled high-frequency positive-pressure ventilation (HFPPV) and pressure-controlled high frequency ventilation with inspiratory pulses superimposed (combined high frequency ventilation, CHFV). The prefix (L) indicates that lavage has been performed. MEASUREMENTS AND RESULTS: Measurements of gas exchange, airway pressures, hemodynamics, functional residual capacity (using the SF6 method), intrathoracic fluid volumes (using a double-indicator dilution technique) and metabolism were performed during ventilatory and hemodynamic steady state. The peak inspiratory pressures (PIP) were significantly higher in the volume-controlled low frequency modes (43 cmH2O for L-IPPV-8 and L-IPPV-15) than in the pressure-controlled modes (39 cmH2O for L-IRV, 35 cmH2O for L-HFPPV and 33 cmH2O for L-CHFV, with PIP in the high-frequency modes being significantly lower than in inverse ratio ventilation). The mean airway pressure (MPAW) after lavage was highest with L-IRV (26 cmH2O). In the ventilatory modes with a PEEP > 8 cmH2O PaO2 did not differ significantly and beyond this "opening threshold" MPAW did not further improve PaO2. Central hemodynamics were depressed by increasing airway pressures. This is especially true for L-IRV in which we found the highest MPAW and at the same time the lowest stroke index (74% of IPPV). CONCLUSIONS: In this model, as far as oxygenation is concerned, it does not matter in which specific way the airway pressures are produced. As far as oxygen transport is concerned, i.e. aiming at increasing DO2, we conclude that optimizing the circulatory status must take into account the circulatory influence of different modes of positive pressure ventilation.

Airway Resistance↗

Changes over time in blood lipids and their correlates in Polish rural and urban populations: the Poland-United States Collaborative Study in cardiopulmonary disease epidemiology.

PURPOSE: The purpose of this manuscript is to examine changes in blood lipid levels and related factors between 1983 and 1987 in two selected Polish populations, to evaluate these changes and their association with other coronary heart disease (CHD) risk factors, and to examine the nutrient intake changes for consistency with observed lipid changes. METHODS: Men and women, aged 35-64 were screened from Warsaw and rural Tarnobrzeg province, Poland-the Pol-MONICA screening sites. An independent random sample of 5132 screened in 1983-84 and a second independent random sample of 2596 screened in 1987-88 were compared. A 25% cohort of the 1983-84 sample was also rescreened in 1987-88 (n = 1236) and 24-hour dietary recall information on this cohort was used to evaluate nutrient intake changes and their relationship to the lipid changes. RESULTS: For the random samples, the total cholesterol increased by 5.1 mg/dL (rural) and by 7.9 mg/dL (urban) for women; there were no significant changes among men. Low-density lipoprotein cholesterol (LDL-C) increased for all site and gender subgroups by 5.4-8.7 mg/dL. Among rural men and women, high-density lipoprotein cholesterol (HDL-C) decreased by 3.4 and 3.3 mg/dL, respectively, whereas it increased by 3.3 mg/dL among urban women and did not change among urban men. Total triglycerides (TG) increased by 9.5 mg/dL for rural men, with no significant change for rural women. For urban men and women, TG decreased by 29.5 and 21.8 mg/dL respectively. In the cohort, changes in dietary intake (decreases in energy from fat, Keys index and increases in the polyunsaturated to saturated fats ratio) were related to a decrease in TC at both sites and to a decrease or smaller increase in LDL-C for rural men. CONCLUSIONS: The observed changes were generally unfavorable, with a decrease in the proportion of persons with desirable lipid levels. At both sites nutritional changes were favorable, including a drop in total energy intake. Less pronounced were changes in percentages of total energy from fats, where the only significant decrease was for rural women; however, improvements in dietary fat composition and declines in cholesterol consumption were found. These favorable changes in diet were not strong enough or were not in effect long enough to counter the unfavorable changes in blood lipids.

Adult↗

Microbial fermentative preparation of L-[15N2]lysine and its tracer: application to serum amino acid kinetic studies.

The microorganism Brevibacterium flavum 21129 has been used to produce multigram batches of L-[15N2]lysine of high purity and isotopic enrichment by supplementation of the growth medium with (15NH4)2SO4 of 98.0 atom% excess. The doubly 15N-labeled lysine can be detected at dilutions 10 times greater than singly labeled lysine when isotope dilution curves are analyzed by gas chromatography-mass spectrometry. This enhanced sensitivity permits kinetic measurements of plasma free-lysine isotope content over a 300-fold dilution during 6 h following a single oral bolus of 5 mg/kg body wt. This inexpensive preparation method lends itself to the production of highly useful biochemical compounds for kinetic studies of human nutrition.

Absorption↗

Reduction in the incidence of alveolar osteitis in patients treated with the SaliCept patch, containing Acemannan hydrogel.

PURPOSE: In the present study, we compared the incidence of alveolar osteitis (AO) in patients treated with either clindamycin-soaked Gelfoam (Pharmacia and Upjohn Co, Kalamazoo, MI) or SaliCept Patches (Carrington Laboratories, Inc, Irving, TX). The SaliCept Patch is a freeze-dried pledget that contains Acemannan Hydrogel (Carrington Laboratories) obtained from the clear inner gel of Aloe vera L. PATIENTS AND METHODS: A retrospective evaluation was performed of the records of 587 patients (1,031 sockets) whose extraction sites had been treated with clindamycin-soaked Gelfoam. A prospective trial was conducted in which 607 patients (1,064 sockets) had 2 SaliCept Patches placed immediately after extraction. The same surgeon treated all patients. RESULTS: Analysis restricted to mandibular third molar sites showed that 78 of 975 sites (8.0%) in the Gelfoam group developed AO, whereas only 11 of 958 sites (1.1%) in the SaliCept group developed AO (P <.0001). Further analysis of all extraction sites revealed that the incidence of AO in the Gelfoam group was 7.6% compared with 1.1% in the SaliCept-treated group (P <.0001). CONCLUSIONS: The study results suggest that the SaliCept Patch significantly reduces the incidence of AO compared with clindamycin-soaked Gelfoam.

Adolescent↗

Persistent social class mortality differences in New Zealand men aged 15-64: an analysis of mortality during 1995-97.

OBJECTIVE: Social class mortality differences in New Zealand men aged 15-64 years have previously been examined for the periods 1975-77 and 1985-87 using the Elley-Irving social class scale. The objective was to repeat these analyses for 1995-97 in order to examine time trends, and to assess current social class patterns of mortality. METHODS: Age-standardised mortality rates were calculated for each social class and a weighted estimate of the social class mortality gradient was obtained. RESULTS: Male mortality declined 21% between 1985-87 and 1995-97, but the social class mortality differences have not diminished and may have even increased. The Relative Index of Inequality has increased from 1.8 in 1975-77 to 2.1 in 1985-87 and 2.3 in 1995-97. Unlike previous analyses, the relative social class mortality gradient was just as strong in the older age groups as in the younger age groups, indicating that the possible increase in social class gradient has largely occurred in the older age groups. CONCLUSIONS: These findings indicate that the potential to address the excess preventable mortality caused by socio-economic factors has not been fully realised in New Zealand. IMPLICATIONS: Social class analyses identify groups in the community that have an excess mortality that is potentially preventable. There are still major social class differences in mortality in New Zealand, and these differences may even have increased. It is important that these patterns are taken into account in public health planning and that further research is conducted to identify the mechanisms by which these differences occur.

Adolescent↗

Relief of bileduct obstruction by the percutaneous transhepatic insertion of an endoprosthesis.

Benign and malignant biliary strictures can be treated by the percutaneous transhepatic insertion of an endoprosthesis. We report the use of this technique in 44 patients, with a detailed description of the procedure. Insertion was successful in 41, three of whom later had elective surgery, and one, emergency laparotomy for biliary peritonitis. This patient died post-operatively. Cholestasis was relieved in 31 of the remaining 37 patients. Complications occurred in four. Twelve patients, all with malignant disease, died within 30 days of the procedure. The percutaneous insertion of a biliary endoprosthesis is a valuable alternative to surgery in selected patients. Complications can occur, and the prognosis depends on the nature of the underlying disease.

Adult↗

Determination of the enantiomers of ketamine and norketamine in human plasma by enantioselective liquid chromatography-mass spectrometry.

A sensitive enantioselective liquid chromatographic assay with mass spectrometric detection has been developed and validated for the simultaneous determination of plasma concentrations of (R)- and (S)-ketamine, and (R)- and (S)-norketamine. The compounds were extracted from human plasma using solid-phase extraction and then directly injected into the LC-MS system for detection and quantification. Enantioselective separations were achieved on a liquid chromatographic chiral stationary phase based upon immobilized alpha(1)-acid glycoprotein (the Chiral AGP column). The separations were achieved using a mobile phase composed of 2-propanol-ammonium acetate buffer (10 mM, pH 7.6) (6:94, v/v), a flow-rate of 0.5 ml/min and a temperature of 25 degrees C. Under these conditions, the analysis time was 20 min. Detection of the ketamine, norketamine and bromoketamine (internal standard) enantiomers was achieved using selected ion monitoring at m/z 238.1, 224.1 and 284.0, respectively. Extracted calibration curves were linear from 1 to 125 ng/ml per enantiomer for each analyte with correlation coefficients better than 0.9993 and intra- and inter-day RSDs of less than 8.0%. The method was applied to samples from a clinical study of ketamine in pain management.

Calibration↗

Effects of sarcomere length and temperature on the rate of ATP utilisation by rabbit psoas muscle fibres.

1. The steady state rate of ATP utilisation by single permeabilised fibres from rabbit psoas muscle immersed in silicone oil was measured using a linked enzyme assay that coupled ADP production to the oxidation of NADH.2. At sarcomere length 2.5 microm, at 10 degrees C, the rate of ATP utilisation in relaxing conditions was 6 +/- 1 microM s-1 (mean +/- S.E.M., n = 8 fibres); during isometric contraction it was 310 +/- 10 microM s-1 (mean +/- S.E.M., n = 11). Assuming a myosin active site concentration of 150 microM, these values correspond to rates of ATP utilisation per active site of about 0.04 and 2.1 s-1, respectively. 3. The rate of ATP utilisation in relaxing conditions was independent of sarcomere length in the range 2.5-4.0 microm. The rate of ATP utilisation during isometric contraction had a dependence on resting sarcomere length similar to that of isometric force in the range 2.5-4.0 microm, but was less strongly dependent on sarcomere length than was isometric force in the range 1.5-2.5 microm. 4. The rate of ATP utilisation in relaxing conditions had a Q10 of 2.5 in the temperature range 7-25 degrees C, but this increased to 9.7 in the range 25-35 degrees C, suggesting that some active force may have been generated in relaxing solution at temperatures above 25 degrees C. 5. The rate of ATP utilisation during isometric contraction had a Q10 of 3.6 throughout the temperature range 7-25 degrees C; this was similar to the Q10 for isometric force at low temperature (3.5 at 7-10 degrees C) but much larger than that for isometric force at higher temperature (1.3 at 20-25 degrees C). 6. Application of the NADH-linked assay to single muscle fibres in oil improves the effective sensitivity and time resolution of the method, and allows continuous measurements of the rate of ADP production during active contraction.

Adenosine Triphosphate↗

Atresia revisited: two basic patterns of atresia of bovine antral follicles.

Our observations of bovine follicles indicated that the original histological classifications of atresia were inaccurate. A detailed histological, ultrastructural and immunohistochemical study of antral follicles from bovine ovaries collected from an abattoir and from animals whose large follicles had been monitored by ultrasonography was conducted to investigate this further. Nidogen and CD68 were immunolocalized to observe the follicular basal lamina and macrophages, respectively. In randomly collected ovaries, approximately one quarter of all antral follicles were undergoing antral atresia, as designated in this study. Antral atresia was characterized by early destruction of the layers of the membrana granulosa closest to the antrum, whereas the most basal cells remained intact. Numerous pyknotic nuclei were observed in the most antral layers and in the antrum close to the membrana granulosa. This is the classic description of atretic follicles and was observed at all sizes of follicle development and almost universally in large follicles (> 5 mm in diameter), including dominant follicles. Basal atretic follicles, as designated in this study, were almost as prevalent as the antral atretic follicles, and were characterized by initial destruction of the most basal layer of granulosa cells, whereas the cells in the most antral layers remained associated with each other and were predominantly healthy. Pyknotic nuclei and the nuclei of dying basal cells budded into apoptotic bodies were observed rarely. The basal lamina of basal atretic follicles was often breached by macrophages, which were phagocytosing dying basal granulosa cells. The theca was characterized by an increased deposition of collagen, and the cells were orientated randomly, rather than lying parallel to the membrana granulosa as in healthy follicles. Basal atresia occurred in small (< 5 mm in diameter) follicles only. Importantly, these basal atretic follicles were originally identified incorrectly in the literature. Thus, on the basis of the results of this study and another on the expression of steroidogenic enzymes in atretic follicles, it is suggested that the standard biochemical methods for measuring steroid hormone concentrations in follicular fluids to assess atresia should be re-evaluated.

Animals↗

Attenuation of lung reperfusion injury by modified ventilation and reperfusion techniques.

BACKGROUND: High ventilation and perfusion pressures after lung transplantation may have deleterious effects. We hypothesized that using combined protective approaches for ventilation and perfusion would be optimal for reducing injury and improving function after ischemia-reperfusion. METHODS: Using an isolated, blood-perfused, rabbit lung model, lungs underwent 120 minutes of reperfusion either immediately (Sham) or after 18 hours of cold ischemia (IR). Groups Sham-P and IR-P underwent protective ventilation and reperfusion, and Groups Sham-C and IR-C underwent conventional ventilation and reperfusion. Protective ventilation involved gradually increasing the flow rate during 5 minutes to 1.8 liters/min, and conventional ventilation entailed immediate initiation of flow at 1.8 liters/min. Protective reperfusion involved gradually increasing perfusion during 5 minutes to 60 ml/min, and conventional reperfusion entailed immediate perfusion at 60 ml/min. Two other groups underwent either protective ventilation with conventional perfusion or vice versa. Airway pressure, pulmonary artery pressure, and arterial blood gases were measured throughout reperfusion. Wet/dry weight, highest oxygenation index, and bronchoalveolar lavage (BAL) protein were also measured. RESULTS: Protective ventilation and perfusion after ischemia (IR-P) resulted in significant improvements in lung function as measured by increased Po(2) and decreased Pco(2), airway pressure, and highest oxygenation index compared with conventional reperfusion (IR-C). Injury was significantly reduced in IR-P lungs as measured by reduced edema (wet/dry weight) and vascular leakage (BAL protein). In most cases, IR-P lungs performed better, with less injury than protective ventilation or perfusion alone. CONCLUSIONS: This protective approach of ventilation and perfusion after ischemia may improve lung function after transplantation, a simple method that could easily be applied clinically.

Administration, Inhalation↗

Percutaneous nephrostomy in paediatrics.

Percutaneous nephrostomy has been performed on 18 kidneys in 16 children with an age range of 1 day old to 14 years. The indications and techniques for percutaneous nephrostomy are described, the results are documented, and the effects of the procedure on the management of these patients are discussed. It is shown that percutaneous nephrostomy in paediatrics is a safe and reliable method for draining renal collecting systems in order to relieve obstruction, to assess renal function and to drain pyonephroses.

Child↗

Ntau-methylhistidine in human skeletal and smooth muscle proteins.

1. Fifteen pieces of rectus abdominus muscle and fifteen pieces of taenia muscle were removed from patients undergoing various surgical procedures. 2. The muscles were extracted, hydrolysed and the content of Ntau-methylhistidine was measured. 3. The rectus muscles contained 3.13 +/- 0.7 mumols Ntau-methylhistidine/g fat-free dry solid and the taenia muscles 2.4 +/- 0.6 mumols/g fat-free dry solid. There was a statistically significant difference (P less than 0.05) between these values using the Student's unpaired tau test, although this could have been due to contamination of the taenia muscles with connective tissue. 4. The muscle content of Ntau-methylhistidine was at least 40% higher than the only other reported value and therefore the method of calculating muscle protein breakdown based on Ntau-methylhistidine excretion requires revision.

Aged↗

Reagents for measuring intracellular enzyme activity with flow cytometry.

The line of enzyme substrates described, together with the flow cytometer, bring a simplified method of measuring intracellular enzyme activity to the research laboratory. They are optimized for use in flow cytometry but can also be adapted to other fluorescent detection methods (e.g., spectrofluorometry, fluorescent microscopy, and image analysis) (Figure 5). The large number of enzymes that can be measured with the reagents (currently 37), together with the automation and multiparametric capabilities of flow cytometry, offer many advantages over conventional methods of cell characterization. They also expand the potential of functional assays for studying many normal physiological and disease processes.

Animals↗

Neurophysiological evaluation of zidovudine in asymptomatic HIV-1 infection: a longitudinal placebo-controlled study.

The effect of early antiretroviral medication with zidovudine on neurophysiological functions was evaluated in subjects with asymptomatic HIV-1 infection. Patients were recruited participants of a larger double-blind randomised placebo-controlled treatment trial with zidovudine (Concorde). The main outcome measures included: quantitative electroencephalography (QEEG), auditory event-related potentials (AEP) and pattern-reversal visual evoked potentials (PRVEP), as well as standard clinical, virological and immunological markers. No significant impairment and no difference between treatment groups was found in visual P100 latency and auditory long-latency P3 responses which is in agreement with the absence of neurological and neuropsychological impairment over the study period. Significant treatment effects were revealed by quantitative electroencephalography (QEEG). While the placebo group showed a significant increase in delta and theta slow frequency QEEG activity over the study period, slow wave amplitude remained unchanged in the zidovudine group after a mean follow-up period of 28 months. In summary, the data provide evidence for a low level neuropathological process in asymptomatic HIV-1 infection which can be effectively suppressed by antiretroviral medication.

Adult↗