Weight percentile at birth. I. Clinical data of pregnancy and relevance for early childhood development

The influence of the weight percentile at birth on childhood development was examined in a prospective study of 847 singleton pregnancies. In the first two years of life significant relationships between the birth weight percentiles and the infant's development could be proven, while at the age of four social factors were predominant. Though various clinical data in pregnancy and delivery were related to fetal growth, such as weight of the mother, previous abortions and diseases, additional biochemical and biophysical information is desirable for early recognition of intrauterine growth disorders.     

Development of the laws of war as they pertain to medical units and their personnel.

International law provides certain protections for medical units and their personnel during times of war. This was not always the case, but protections were gradually added and finally codified in the Geneva Conventions. The development of these protections is traced from early recorded history to modern times, and the limitations and obligations placed on medical units and medical personnel by international law are examined.     

Local interaction of apoptotic hepatocytes and Kupffer cells in a rat model of systemic endotoxemia

Aim: There is strong evidence that hepatocellular apoptosis is not only initiated by circulating blood cells which become adherent within the endotoxemic liver, but also contributes to further sustain the inflammatory cell-cell response. Methods: Because previous studies assumed the importance of the role of cellular cross-talk in mediating inflammatory liver injury, we herein examined the activation of Kupffer cells (KCs) and their spatial coincidence with intrahepatic leukocyte adherence and hepatocellular apoptosis at 6 h after intraperitoneal exposure of rats with lipopolysaccharide (10 mg/kg). Results: In vivo multifluorescence microscopy revealed liver injury including nutritive perfusion failure, tissue hypoxia, leukocyte accumulation, as well as KC activation and parenchymal apoptotic cell death. Detailed spatial analysis revealed frequent colocalization of activated KCs with apoptotic hepatocytes. Colocalization was absent in saline-treated controls.Colocalization was confirmed by histochemistry, which showed ED1-positive KCs neighboring and engulfing TUNEL-positive hepatocytes. Colocalization of KCs with leukocytes ranged between 4% and 5% and did not increase in endotoxemic animals. Taken together, the present results indicate that apoptotic cell death of hepatocytes may stimulate phagocytosis by neighboring KCs. Direct KC-leukocyte contact seems not to be mandatory for cellular communication in the process of hepatocellular apoptosis. Conclusion: With respect to the fundamental importance of cell apoptosis, improved knowledge of these cell-cell interactions might allow the development of new therapeutic strategies through the regulation of apoptotic cell death.     

Checklist for the qualitative evaluation of clinical studies with particular focus on external validity and model validity

Background  

It is often stated that external validity is not sufficiently considered in the assessment of clinical studies. Although tools for its evaluation have been established, there is a lack of awareness of their significance and application. In this article, a comprehensive checklist is presented addressing these relevant criteria.     

Lymph vessel expansion and function in the development of hepatic fibrosis and cirrhosis.

The process of lymph vessel expansion and function in the development of CCl4-induced hepatic fibrosis and cirrhosis was studied using intravital fluorescence microscopy of the rat liver. The unique aspect of our approach was the use of high molecular fluorescein-isothiocyanate-labeled dextran (MW, 150,000) as fluorescent marker, which allowed for simultaneous assessment of both 1) the macromolecular blood hepatocytic exchange from the sinusoidal microvasculature (extra-/intrasinusoidal gray level intensity at 1, 3, 5, and 10 minutes after intravenous injection) and 2) the hepatic lymph system. In animals exposed with CCl4 up to 4 weeks, macromolecular trans-sinusoidal exchange was found progressively delayed. This was strongly associated with lymph vessel expansion and function, as indicated by a continuous increase of lymph vessel density and area. Delay of macromolecular exchange and lymph vessel expansion was found not further enhanced at fibrotic and cirrhotic stages of 8- and 12-week CCl4-exposed livers. Linear regression analysis revealed a strong negative correlation between lymphatic network density development and macromolecular trans-sinusoidal exchange (r2 = 0.99; P < 0.01). Thus, our study provides for the first time direct evidence for the pivotal role of lymphatic function for macromolecular transport in case of deteriorated sinusoidal hepatocellular exchange capacity.     

Cell surface and nuclear changes during TNF-α-induced apoptosis in WEHI 164 murine fibrosarcoma cells

 Tumour necrosis factor (TNF)-α-induced apoptosis is associated with several nuclear and cell surface alterations, in particular with the condensation of chromatin and the fragmentation of the cell nucleus, formation of blebs on the cell surface and breakdown of the plasma membrane. However, there is little information about the relationship between the cell surface alterations and the nuclear changes during apoptosis. To study this, cultured WEHI cells were exposed to TNF-α over different time periods. The cytological changes were studied using a correlative approach, which allowed observation of the same cell consecutively under light, scanning and transmission electron microscopy. The earliest sign of cell alteration was a reduction of the number of microvilli after 15 min of TNF-α exposure. This reaction was reversible (reappearance of microvilli) and took place during the first hour, in which neither nuclear alterations nor plasma membrane breakdown were observed. The changes in the nucleus began with condensation of chromatin after approximately 1 h of TNF-α-exposure. After 4–5 h the microvilli disappeared again, particularly in areas where the formation of blebs (blebbing) was observed. Strikingly, cell surface alterations (bleb formation) were detected only in those cells that presented with condensed chromatin, and not in cells with a normal chromatin pattern, proving at least a close correlation between nuclear and cell surface changes during the process of apoptosis. Received: 7 October 1997 / Accepted: 23 March 1998     

Up-regulation of endothelial nitric oxide synthase inhibits pulmonary leukocyte migration following lung ischemia-reperfusion in mice

Endogenous nitric oxide (NO) is known to modulate post-ischemic inflammatory response in various organs. However, the role of nitric oxide synthase isoforms (NOS) in mediating pulmonary post-ischemic inflammatory response is poorly understood. We therefore studied post-ischemic endothelial adhesion molecule expression and leukocyte migration in endothelial NOS knockout (eNOS-KO) mice subjected to pulmonary ischemia and reperfusion in vivo. Under anesthesia and mechanical ventilation, the left pulmonary hilum in wild-type (WT) and eNOS-KO mice was clamped for 1 hour, followed by reperfusion for up to 24 hours. In WT mice, we observed a selective up-regulation of both eNOS mRNA and protein in lung tissue, while inducible NOS (iNOS) and neuronal NOS (nNOS) remained unchanged. Survival in eNOS-KO mice was reduced due to severe pulmonary edema, underlining an increased susceptibility to ischemia-reperfusion (I/R) injury. Interstitial tissue infiltration by CD18- and CD11a-positive white blood cells as well as lung tissue water content peaked at 5 hours of reperfusion and were found significantly higher than in WT mice. Enhanced leukocyte-endothelial interaction was associated with pronounced up-regulation of vascular cell adhesion molecule (VCAM) in eNOS-KO mice during post-ischemic reperfusion. We conclude that eNOS attenuates post-ischemic inflammatory injury to the lung most probably via inhibition of endothelial adhesion molecule expression.     

Effect of bezafibrate during 4.5 years of treatment of hyperlipoproteinaemia

Bezafibrate in a dosage of 200 mg 3 times daily was given to 24 patients with type II A (n = 8), II B (n = 1) and IV (n = 15) hyperlipoproteinaemia for 4.5 years. In type II A the content of total cholesterol and that of low density lipoprotein in serum decreased by 10-23 and 11-34 percent over the years compared to pretreatment. In type IV the content of total triglycerides and that of very low density lipoprotein decreased by 28-39 and 38-52 percent, respectively, over the years. High density lipoprotein cholesterol increased in both types. The "atherogenic index" was reduced by the drug. The effect remained through the 4.5 years of treatment. Compliance to the drug was good. Changes in safety laboratory parameters were minor and reversible. No subjective side-effects occurred and no cases of gallbladder disease or cancer were noted. It is concluded that bezafibrate is a safe, convenient and effective serum lipid-lowering drug suitable for the use in primary and secondary prevention of atherosclerotic disease.