Pharmacokinetics of methylmethacrylate monomer during total hip replacement in man

Summary The concentration of methylmethacrylate monomer (MMA) in the blood stream after implantation of the components of 15 total hip prostheses using bone cement was determined in the pulmonary artery, the radial artery, and the superior vena cava after cement application, and correlated with the observed drop in blood pressure and the increase in the pulmonary arterial pressure. In all samples MMA was found. The values ranged from 0.02 g/ml to 59 gg/ml. The mean maximum value after implantation of the stem was measured to be 7.8g/ml in the pulmonary artery, 4.6 g/ml in the radial artery, and 1.75 g/ml in the superior vena cava. After implantation of the cup the values were clearly lower. The simultaneously recorded blood pressure decreased slightly during the first 3 min and then returned to previous values. The pulmonary arterial mean pressure increased from 18 to 20mmHg during the first 10 min. Although in some patients a drop in blood pressure started at the same time as MMA reached maximum values, high concentrations did not result in a greater effect on the circulatory parameters. Statistical analysis by the Spearman test revealed no correlation between MMA concentrations and the decrease in blood pressure or the increase in the pulmonary arterial pressure.

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Zusammenfassung Während der Implantation von fünfzehn Totalendoprothesen mit Knochenzement wurden die Konzentrationen von Methylmethacrylatmonomer (MMA) in der Arteria pulmonalis, der Arteria radialis and der Vena cava superior bestimmt und mit dem beobachteten Blutdruckabfall and dem Anstieg des pulmonalarteriellen Druckes korreliert. In den Proben konnten MMA-Konzentrationen zwischen 0,02 g/ml and 59 g/ml nachgewiesen werden. Die mittlere Maximalkonzentration betrug nach Implantation des Schaftes 7,8 g/ml in der Pulmonal-, 4,6 g/ml in der Radialarterie und 1,75 g/ml in der Vena cava superior. Die Konzentrationen nach Implantation der Pfanne waren deutlich geringer. Der gleichzeitig aufgezeichnete Blutdruck fiel geringgradig während der ersten drei Minuten and kehrte dann auf Ausgangswerte zuriick. Der pulmonalarterielle Mitteldruck stieg von 18 auf 20 mm Hg während der ersten zehn Minuten. Obwohl bei einigen Patienten der Blutdruckabfall mit dem Auftreten maximaler MMA-Konzentrationen zusammenfiel, hatten höhere MMA-Konzentrationen keinen größeren Effekt auf die zirkulatorischen Parameter. Bei der statistischen Analyse mit dem Spearman Test bestand keine statistische Korrelation zwischen den MMA-Konzentrationen und dem Abfall des Blutdruckes bzw. dem Anstieg des pulmonalarteriellen Druckes.

     

Association of ambient air‐pollution levels with acute asthma exacerbation among children in Singapore

BACKGROUND: Air-pollution levels have been shown to be associated with increased morbidity of respiratory diseases. METHODS: Data for ambient air-pollutant levels, meteorologic factors, and hospitalization or emergency room (ER) visits for acute asthma in Singapore children over a 5-year period (1990-4) were obtained and analyzed for associations by time-series methods. RESULTS: Throughout this period, the annual mean and 24-h mean levels for sulfur dioxide (SO2), nitrogen dioxide (NO2), and total suspended particles (TSP) and maximum 1-h daily average for ozone were generally within the air-quality guidelines established by the World Health Organization (WHO). However, positive correlation between levels of each of these pollutants and daily ER visits for asthma was observed in children aged 3-12 years, but not among adolescents and young adults (13-21 years old). The association with SO2 and TSP persisted after standardization for meteorologic and temporal variables. An adjusted increase in 2.9 ER visits for every 20 microg/m3 increase in atmospheric SO2 levels, lagged by 1 day, was observed on days when levels were above 68 microg/m3. With TSP, an adjusted increase of 5.80 ER visits for every 20 microg/m3 increase in its daily atmospheric levels, lagged by 1 day, was observed on days with levels above 73 microg/m3. Similar results were also obtained after controlling for autocorrelation by time-series analysis. CONCLUSIONS: These associations were observed even though the overall levels of all pollutants were generally within the air-quality guidelines established by the WHO. These findings suggest that asthmatic children are susceptible to increased levels of air pollutants, particularly SO2 and TSP, although the ambient levels are generally within "acceptable" ranges.     

Asymmetric distribution of calbindin-D28K in the ganglia habenulae of an elasmobranch fish

Summary Using an antibody raised against a purified chick duodenal vitamin D-dependent calcium-binding protein, the presence and distribution of calbindin has been studied immunohistochemically in the habenular ganglia of the dogfish. In the more developed left ganglion, a positive reaction was clearly observed in the neurons of the medial nucleus, whereas in the lateral nucleus, only some scarce, hardly immunostained cells appeared. In the neurons of the right habenula however, no immuno-reactivity was observed. The distribution of vitamin D-dependent calcium-binding protein in the dogfish habenulae is therefore asymmetrical. This may be due to differences in the neuronal activity between the two ganglia.     

Quantitation of 8 human herpesviruses in peripheral blood of human immunodeficiency virus-infected patients and healthy blood donors by polymerase chain reaction

Human herpesviruses are associated with morbidity and mortality in persons with compromised immune systems, including patients infected with human immunodeficiency virus (HIV). To investigate the basis for this association, the levels of all 8 human herpesviruses (herpes simplex virus, types 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6, human herpesvirus 7, and human herpesvirus 8) were measured with the quantitative polymerase chain reaction (PCR). Viral DNA was measured in the whole blood of 20 HIV-infected patients and compared with levels in 20 healthy blood donors. There was no significant difference in the frequency of virus detection of the 8 human herpesviruses between HIV-infected patients and healthy adults. These results indicate that HIV infection is not associated with a general increase in the circulating levels of human herpesviruses, and suggest that quantitative PCR analysis is superior to qualitative PCR analysis for detection of clinically relevant disease in HIV-infected patients.     

Lipoprotein(a) stimulates growth of human mesangial cells and induces activation of phospholipase C via pertussis toxin-sensitive G proteins

BACKGROUND: Renal disease is commonly associated with hyperlipidemia and correlates with glomerular accumulation of atherogenic lipoproteins, for example, lipoprotein(a) [Lp(a)], and mesangial hypercellularity. Specific binding of Lp(a) to mesangial cells and induction of c-myc and c-fos expression has been demonstrated. Therefore, in this study, we investigated a possible growth stimulatory effect and mode of action of Lp(a) in human mesangial cells. METHODS: Lp(a) was purified from the regenerate fluid of a dextran sulfate column-based low-density lipoprotein apheresis system. Human mesangial cells were isolated by a sequential sieving technique from patients undergoing tumor nephrectomy. DNA synthesis was measured by [3H]-thymidine incorporation. The intracellular calcium concentration ([Ca2+]i) was determined by Fura 2-fluorescence, and inositol 1,4,5-trisphosphate (1,4,5-IP3) concentration was measured by a radioreceptor assay. RESULTS: The data show that Lp(a) bound to the cells with a Kd of 17.0 micrograms/ml and increased DNA synthesis and cell proliferation. Lp(a) caused a rapid increase in 1,4,5-IP3 and [Ca2+]i via a pertussis toxin-sensitive mechanism. The phospholipase C (PLC) inhibitor U73122 abolished Lp(a)-induced cell proliferation. In contrast, vasopressin-induced increase in 1,4,5-IP3 and [Ca2+]i was pertussis toxin insensitive. CONCLUSION: This study revealed that Lp(a) stimulates growth of human mesangial cells. Lp(a)-induced signaling involves binding to a receptor and stimulation of PLC via Gi proteins. Stimulation of PLC appears to be essential for the growth stimulatory effect of Lp(a). Whether these effects of Lp(a) contribute to the pathophysiology of renal disease needs to be determined.     

Acute hemodynamic and renal effects of adrenomedullin in rats with aortocaval shunt

Heart failure is characterized by increased vascular resistance and water retention. Adrenomedullin is a peptide hormone with vasodilating and diuretic properties whose efficacy in heart failure has not been well established. We used an aortocaval shunt model of moderate heart failure in rats and infused increasing doses of adrenomedullin, both as bolus injections and 20-min infusions. In controls, a clear dose-dependent 4.8+/-1.0 to 13.6+/-2.3 mm Hg decrease in arterial blood pressure was observed after injection of 1 microg to 30 microg of adrenomedullin. In rats with aortocaval shunt, the hypotensive responses were significantly diminished. The urine flow rate, which was diminished at baseline in rats with aortocaval shunt, was increased and normalized by adrenomedullin administration. The glomerular filtration rate increased after infusion of adrenomedullin (0.5 microg/kg min(-1)) from 2.37+/-0.25 to 3.47+/-0.43 ml/min (P<0.01) in controls and from 1.79+/-0.33 to 2.58+/-0.49 (P<0.05) in rats with aortocaval shunt. Similarly, renal blood flow was significantly increased by adrenomedullin in both groups. Our results indicate a beneficial effect of adrenomedullin on renal function in rats with aortocaval shunt. These data suggest that adrenomedullin might be of potential therapeutic value in heart failure, without inordinately decreasing blood pressure.