Effects of repeated doses of benzodiazepines on arterial blood gases and transcutaneous Po2

The effects of repeated doses of benzodiazepines, diazepam and midazolam in combination with meperidine on arterial blood gases and transcutaneous PO2 were studied in eight healthy volunteers. The study was designed to mimic a clinical situation. Initially two doses of either midazolam 0.05 mg/kg or diazepam in fat emulsion 0.15 mg/kg were given in a randomized crossover fashion with a 20-min interval, followed by meperidine 0.5 mg/kg another 20 min later. The opioid effects were then antagonized by naloxone 0.4 mg. The initial doses of benzodiazepines caused an increase in PaCO2 and a decrease in PaO2. The changes in PaO2 were of short duration and recovered to baseline levels between injections. However, they came sooner and were more pronounced after midazolam. The changes in PtcO2 paralleled those in PaO2. The PtcO2 index as a measure of cardiac output and peripheral blood flow adequacy was increased immediately after the first injection of midazolam but was otherwise not different from control. There were no differences between the drugs concerning PtcO2 index. PaCO2 increased after the first benzodiazepine injection and remained so throughout the study. Addition of meperidine caused only small changes in PaO2 and PaCO2. These changes were reversed by naloxone. In spite of different elimination kinetics there was no difference in the duration of respiratory depression between the two benzodiazepines.     

Presentation of growth velocities of rural Haitian children using smoothing spline techniques

The examination of monthly (or quarterly) increments in weight or length is important for assessing the nutritional and health status of children. Growth velocities are widely thought to be more important than actual weight or length measurements per se. However, there are no standards by which clinicians, researchers, or parents can gauge a child's growth. This paper describes a method for computing growth velocities (monthly increments) for physical growth measurements with substantial measurement error and irregular spacing over time. These features are characteristic of data collected in the field where conditions are less than ideal. The technique of smoothing by splines provides a powerful tool to deal with the variability and irregularity of the measurements. The technique consists of approximating the observed data by a smooth curve as a clinician might have drawn on the child's growth chart. Spline functions are particularly appropriate to describe bio-physical processes such as growth, for which no model can be postulated a priori. This paper describes how the technique was used for the analysis of a large data base collected on pre-school aged children in rural Haiti. The sex-specific length and weight velocities derived from the spline-smoothed data are presented as reference data for researchers and others interested in longitudinal growth of children in the Third World.     

Long term evaluation of the unilink anastomotic system. A study with light and scanning electron microscopy.

The long term effects of the Unilink mechanical microvascular anastomosis in terms of anastomotic patency and histological changes in the vessel wall were evaluated in 10 rabbits. Both carotid arteries and facial veins were divided and reanastomosed with the Unilink device. At death two years later all 40 anastomoses were fully patent, with histological changes similar to those described previously after 16 weeks, that is, normal endothelial lining, but almost total atrophy of the media at the anastomotic site. The thinning of the vessel wall at the anastomosis caused neither occlusions nor aneurysms during the observation period.     

Neuroendocrine Evidence for Reduced Dopamine Receptor Sensitivity in Alcoholism

Postsynaptic dopamine (DA) receptor sensitivity was assessed during abstinence in 15 male patients with alcohol dependence. The DA receptor sensitivity was evaluated using growth hormone (GH) responses to the DA receptor agonist apomorphine (0.18-0.24 mg intravenously). The patients were cared for in an alcoholism treatment unit for the 2 months prior to the investigation. They were carefully controlled for sobriety during this period. Thirteen healthy men were used as controls. The maximum GH responses to apomorphine were significantly reduced in patients compared with those in the control group. The patients had a significantly higher proportion of blunted GH responses. The findings suggest reduced postsynaptic DA, possibly D2, receptor sensitivity in abstinent alcoholics. The question whether this abnormal DA receptor status is genetically determined or acquired after long-term alcohol consumption remains to be addressed.     

In vivo motor effects of loperamide on the rat urinary bladder.

Bladder motility recordings were performed in anaesthetized rats and the effect of the peripherally active opiate agonist loperamide on urinary bladder function was studied. Regional intra-arterial administration of loperamide (0.01-2 mg kg-1) induced weak bladder contraction per se. Loperamide caused an effective dose-dependent inhibition of bladder motility induced by regional injection of the receptor agonists acetylcholine (ACh) and substance P (SP), as well as by peripheral motor nerve stimulation (PNS). Pretreatment with naloxone (0.5 mg kg-1) partially antagonized the inhibitory action of loperamide on the nerve-mediated detrusor contraction. However, the depression of the motor responses induced by the receptor agonists ACh and SP was not influenced. It is suggested that the demonstrated inhibitory effect of loperamide on bladder motility is partially mediated by peripheral opioid receptors. The main non-opioid part of the inhibition might be a direct smooth muscle action.     

Amounts and distribution of intracellular magnesium and calcium in pancreatic beta-cells

beta-Cell-rich pancreatic islets were incubated for 60-120 min in the presence of 1 mM or 20 mM glucose and analysed with regard to their contents of magnesium and calcium and how these elements were distributed among subcellular fractions. The islets contained 42 mmol magnesium per kg protein with as much as 70 mmol per kg protein in the microsomal fraction. Both the total amount and intracellular distribution of magnesium remained unaffected after raising the glucose concentration of the incubation medium. The islet content of calcium was twice as high as that of magnesium, the mitochondria and secretory granules accounting for most of the calcium in the sedimentable fractions. In both organelles a substantial fraction of calcium was exchangeable as indicated from the incorporation of 45Ca during 90 min of incubation of the islets. When raising the glucose concentration to 20 mM the percentage exchange of calcium increased from 10 to 27 in the mitochondria and from 13 to 28 in the secretory granules. The glucose stimulation of 45Ca uptake was not associated with a statistically significant increase in the total amounts of calcium. However, in addition to stimulating calcium/calcium exchange, it cannot be excluded that glucose also induces a net accumulation of intracellular calcium in the beta-cells.     

Daily versus thrice-weekly interferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected persons: a multicenter randomized controlled trial

Among HIV-infected persons, chronic hepatitis C virus (HCV) infection causes substantial morbidity and mortality. However, few studies have evaluated the safety and efficacy of interferon alfa (IFN) and ribavirin (RBV) therapy in co-infected persons. Accordingly, a randomized, controlled, open-label, multicenter trial was conducted to establish the safety, tolerability, and efficacy of IFN alfa-2b 3 mIU daily plus RBV 800 mg/d compared with IFN alfa-2b 3 mIU thrice weekly (TIW) plus RBV 800 mg/d in HCV treatment-naive, HIV-infected subjects with compensated liver disease and stable HIV disease. The primary endpoint was sustained virologic response (SVR), defined as an undetectable HCV RNA level 24 weeks after discontinuation of HCV therapy. At study entry, subjects in both groups were similar with respect to age, gender, HCV genotype, and HIV disease status. Of 180 randomized subjects, 162 received at least 1 dose of study medication, constituting the modified intention-to-treat population. After 12 weeks of therapy, 122 (75%) had serum HCV RNA levels assessed; of these subjects, early virologic response (undetectable HCV RNA or >2 log10 decrease from baseline) was observed in 33 (42%) and 13 (16%) of subjects taking daily and TIW IFN, respectively (P < 0.001). SVR was observed in 15 (19.0%) and 7 (8.4%) of subjects taking daily and TIW IFN, respectively (P = 0.05). Adverse events were similar in both groups. However, while no deaths or opportunistic infections were observed, nearly 30% of subjects stopped treatment due to adverse events and 7 subjects experienced a serious adverse event. In conclusion, SVR was achieved in 19% of HIV/HCV coinfected subjects treated with daily IFN plus RBV, but the effectiveness of therapy was substantially diminished by relatively high rates of treatment-related toxicity.     

Pharmacy protocol for adjusting patient-controlled analgesia

The use of patient-controlled analgesia (PCA) to manage pain post-operatively is becoming increasingly popular. The potential for pharmacist involvement is larger. Traditional areas of pharmacy involvement include PCA pump evaluation and selection, choice of narcotic-analgesic to be used, education of other health care professionals on PCA use, and development of PCA protocol guidelines. Monitoring post-operative pain and adjusting the PCA dosage are not traditional areas of pharmacist involvement. The purpose of this report is to describe a protocol which allows hospital pharmacists in an inpatient setting to adjust the PCA dose so that postoperative pain relief is maximized and sedation is minimized.     

The effect of lithium on amphetamine-induced locomotor stimulation

Rats were treated chronically with -methyl-p-tyrosine methyl-ester HCl (-MT) twice daily for 0–14 days. At 1 h after the (last) -MT injection, d-amphetamine sulphate was given and motor activity was measured in an ANIMEX activity meter for 4 h. Amphetamine-induced excitatory and stereotyped behaviour was scored according to a rating scale in a separate experiment. A single dose of -MT markedly reduced the activity response after amphetamine. After 1–3 days of -MT treatment, tolerance to its amphetamine-antagonistic affect started to develop, reaching a maximal degree after 7–14 days. The pattern of the amphetamine response, monophasic in control rats, became biphasic in the -MT tolerant rats with an early (at 0–1 h) and a late (2–4 h) peak of motor activity. The late peak appeared within 3 days, while the early peak appeared after 7 days of -MT treatment. The results on amphetamine-induced excitatory and stereotyped behaviour in essence agreed with the motor-activity data. It is concluded that tolerance to the amphetamine-antagonistic action of -MT is not complete. Its rate of development varies in a complex pattern, indicating the presence of more than one mechanism of tolerance.     

Pericardial tamponade caused by central venous catheters

Three cases of pericardial tamponade caused by central venous catheters are reported. Two essential factors have been recognized. First, the catheter material should be extremely soft and remain soft. Today the best material available seems to be a silicone rubber elastomer. Polyvinylchloride or polyethylene, which is widely used, is too rigid. These materials also contain phthalate esters to soften the plastic, and these softeners are gradually washed out into the bloodstream, rendering the catheters even more rigid in time. Second, a central venous catheter should enter the venous system proximal to the shoulder. When the catheter is inserted through a vein in the arm, the tip of the catheter will be able to progress 6–10 cm farther down in the venous system by extreme movements of the arm. This occurs regularly when a patient is turned in bed and his or her arm is elevated 108 at the shoulder. The internal jugular vein and the subclavian vein are the most suitable veins for catheterization. Veins in the arm should not be used.

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Résumé Trois cas de tamponade péricardique après cathétérisme veineux central sont rapportés cependant que deux causes particulières de ce type d'accident iatrogène ont été mises en évidence:-emploi d'un catheter rigide.-lieu inadéquat d'introduction de cet élément. En fait, le catheter doit Être souple et le rester, le meilleur matériaux étant représenté par le silicone. Le catheter en polyethylene largement employé est trop rigide, il contient également des éléments chimiques qui ont pour but de l'assouplir mais qui sont éliminés progressivement dans le sang.D'autre part le catheter doit Être introduit dans le système veineux a proximité de l'épaule. Quand il est mis en place au niveau du bras il peut progresser de 6 à 10 cm dans le système veineux sous l'impulsion des mouvements du membre supérieur. Ceci survient régulièrement quand le malade est retourné dans son lit et que le membre est ainsi levé à 180. La veine jugulaire interne ou la veine sous clavière représentent le meilleur lieu d'introduction du cath éter. Il ne faut jamais le mettre en place au niveau d'une veine brachiale.