Early rapid weight gain and current overweight in relation to asthma in adolescents born with very low birth weight

Early catch-up growth and subsequent overweight are suggested to be associated with later cardiovascular diseases and later type II diabetes. However, the impact of early catch-up growth and childhood overweight on the development of asthma has been less studied, particularly in children born with very low birth weight (VLBW). A birth cohort of 74 VLBW children (birth weight < or = 1500 g) was followed from birth and investigated on asthma at 12 yr of age. Early rapid weight gain was in one way defined as an increase of weight > or =1 standard deviation score (SDS) at 6 months of corrected postnatal age. Current overweight was defined by body mass index (BMI) exceeding 21.2 and 21.7 kg/m(2), respectively, for boys and girls at 12 yr of age. Current asthma was diagnosed by a pediatrician, according to asthma ever in combination with a positive response to hypertonic saline bronchial provocation test and/or wheeze at physical examination at 12 yr old. Being overweight at 12 yr of age was associated with an increased risk for current asthma in the VLBW children [crude odds ratio (OR): 5.5, 95% confidence interval (CI): 1.3-22.2]. After adjustment for early weight gain and neonatal risk, the OR of overweight increased nearly three times (adjusted OR: 15.3, 95% CI: 2.5-90.6). Early rapid weight gain seemed to be inversely associated with current asthma (adjusted OR: 0.49 for an increase of weight equal to 1 SDS, 95% CI: 0.23-1.02, p = 0.06). In addition, early rapid weight gain was inversely associated with the magnitude of bronchial responsiveness at 12 yr (coefficient -1.15, p < 0.01). There was a strong and positive association between overweight and asthma at 12 yr of age in the VLBW children. This strong association had been reduced by early rapid weight gain, possibly via the reduction of bronchial responsiveness.     

Effects of renin-angiotensin system blockade on macrophage infiltration in patients with hypertensive nephrosclerosis.

The mechanisms of hypertensive nephrosclerosis are not fully understood. In experimental models of the disease, inflammatory reactions such as macrophage infiltration play an important role. In human hypertensive nephrosclerosis, however, there have been few studies examining the role of inflammation histologically. We investigated whether the number of infiltrating macrophages was increased in human hypertensive nephrosclerosis, and evaluated the effects of a blockade of the renin-angiotensin system on clinical and histological findings. We examined macrophage infiltration using immunohistochemistry in renal biopsy specimens obtained from 16 patients with hypertensive nephrosclerosis, 5 patients with IgA nephropathy, 5 patients with membranous nephropathy, and 5 patients with minimal change nephrotic syndrome. The number of infiltrating macrophages in glomeruli was significantly larger in the patients with hypertensive nephrosclerosis than in those with minimal change nephrotic syndrome. The patients with hypertensive nephrosclerosis were divided into groups based on their use of antihypertensive agents at the time of renal biopsy. We investigated the effects of antihypertensive agents on clinical findings, macrophage infiltration, and monocyte chemoattractant protein-1 expression. There was no difference in clinical findings between the hypertensive groups. The numbers of infiltrating macrophages and monocyte chemoattractant protein-1-positive cells in glomeruli were significantly smaller in patients treated with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker, whereas calcium channel blockers had no influence on histological findings. In conclusion, inflammation is involved in the progression of human hypertensive nephrosclerosis and the inflammatory process is inhibited by blocking the renin-angiotensin system.     

Progressive supranuclear palsy with asymmetric lesions in the thalamus and cerebellum,with special reference to the unilateral predominance of many torpedoes

This report concerns a notable case of progressive supranuclear palsy exhibiting asymmetric dentate nucleus and thalamic degeneration with numerous torpedoes. The neuronal loss in the ventral lateral nucleus of the thalamus was predominant on the right side, while in the cerebellum, a quantitative study revealed the contralateral predominance of the neuronal loss in the dentate nuclei and torpedo formation, with preserved Purkinje cells. The abnormal tau-protein-related profiles in the two nuclei did not show any laterality in their distribution, indicating that the dentatothalamic tract may have been affected in a non-specific way in this case. In addition, the fact that the prominent sites of torpedo formation and loss of dentate nucleus neurons are identical supports the hypothesis that the torpedoes may be formed in association with neuronal loss in the dentate nucleus because of a plausible metabolic change in Purkinje cells through synaptic detachment of their axon terminals. Received: 4 January 1996 / Revised: 27 March 1996 / Accepted: 5 April 1996     

A case of pulmonary varices in which enhanced CT was useful for diagnosis]

A case of pulmonary varices in a 73-year-old female is presented. Routine chest X-ray revealed a mass in the right hilar region. CR tomogram showed a round, clearly defined mass at the right hilum. Computed tomography demonstrated marked enlargement of the proximal portion of the pulmonary vein at the entrance of the left atrium, which was suspected to be pulmonary varices. The diagnosis was confirmed by pulmonary angiography. During the arterial phase no abnormal findings were seen, but during the venous phase the veins of the right upper and middle lobes were found to be draining into the dilated pulmonary vein and then into the left atrium. Thus, the diagnosis of pulmonary varices was established. CT and angiography are the most useful methods for definitive diagnosis of pulmonary varices.     

Impaired cellular host defence in peritoneal dialysis by two granulocyte inhibitory proteins

Bacterial and fungal peritonitis is associated with a high riskof morbidity and mortality in patients undergoing continuousambulatory peritoneal dialysis (CAPD). Impaired cellular hostdefence in the peritoneal cavity underlies this risk. Two granulocyteinhibitory proteins with a molecular weight of 28000 dalton(GIP I) and about 9500 dalton (GIP II) with homology to light-chainproteins and beta respectively, were isolated from peritonealdialysis effluents. In vitro, both granulocyte inhibitory proteinsinhibit PMNL glucose uptake, phagocytosis and intracellularkilling of bacteria. The IC₅₀ of GIP I or GIP II required forinhibition of half-maximal FMLP-induced or PMA-stimulated PMNLfunction was found to be in the nanomolar range, suggestingvery specific inhibition. These data may explain, at least inpart, defective local cellular host defence in CAPD patients.     

Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus. III. Combined effects of arbekacin with cefotiam or cefuzonam]

Antibacterial effects of combination use of arbekacin (ABK) with cefotiam (CTM) or cefuzonam (CZON) were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and the following results were obtained. 1. Antibacterial effects of combinations of ABK with CTM and with CZON were equally potent against MRSA at clinically expected 1 MIC of ABK in blood. However, at a sub MIC of ABK the different effects were observed between the 2 combinations. The antibacterial effect of the former was strong and that of the latter was a little weak. 2. In either combination the potency of the antibacterial activity was less dependent on the concentration of CTM or CZON, but was strongly dependent on ABK concentrations. These results suggest that antibacterial effects of the combinations were highly dependent on antibacterial potency and concentration of ABK as previously reported for combinations of ABK with other drugs. 3. The combination use of ABK with CTM appears to be useful in cases of infection by MRSA alone while the combination use of ABK with CZON appears to be useful in cases of double infection with MRSA and Gram-negative bacterium.     

Different pattern of chromosomal allele loss in multiple hepatocellular carcinomas as evidence of their multifocal origin.

One of the most problematic aspects of surgery for hepatocellular carcinoma (HCC) is the frequent development of multiple tumors. Determination of the origin of multiple tumors, i.e., multifocal or metastatic, is important for predicting the clinical course of the disease after surgery. In order to clarify the origin of multiple tumors of HCC genetically, we examined patterns of loss of heterozygosity (LOH) on chromosome 16 for DNA isolated from 43 HCCs resected from 19 patients by analysis of restriction fragment length polymorphism. The cases were classified macro- and microscopically into 3 groups: multifocal origin; metastatic origin; and undetermined. Classification based on morphological features was shown to be well correlated with patterns of LOH in multiple tumors of HCC. Different patterns of LOH on chromosome 16 were detected in 8 of 11 patients with tumors of morphologically multifocal origin, whereas they were detected in none of 5 patients with tumors of morphologically metastatic origin. Among five patients with tumors of morphologically undetermined origin, a difference of LOH pattern among the tumors was detected in two, whereas in the other three, the pattern was identical between the tumors. A different pattern of LOH among HCCs arising in situ showed that they were composed of different clones, strongly suggesting their independent clonal origin and multifocal development. These results show that not only appropriate morphological observation but also examination of the LOH pattern on a particular chromosome is useful in diagnosis of multifocal HCC.     

Participation of rat liver cytochrome P450 2E1 in the activation of N-nitrosodimethylamine and N-nitrosodiethylamine to products genotoxic in an acetyltransferase-overexpressing Salmonella typhimurium strain (NM2009).

The possible roles of cytochrome P450 (P450) enzymes in the metabolic activation of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) by rat liver microsomes have been examined in a system containing the bacterial tester strain Salmonella typhimurium NM2009, a newly developed strain showing high O-acetyltransfer activities. The DNA-damaging activity could be determined by measuring expression of the umu gene in a plasmid containing the fused umuC-lacZ gene construct in the bacteria. The following lines of evidence support the view that both NDMA and NDEA are principally oxidized to reactive products by P450 2E1 in rat liver microsomes. First, NDMA and NDEA were activated by rat liver microsomes in a protein- and substrate-dependent manner and the former chemical was more active than the latter; both activities were induced in rats treated with P450 2E1 inducers such as ethanol, acetone and isoniazid and by starvation. Second, activation of NDMA and NDEA were both inhibited significantly by antibodies raised against rat P450 2E1 and by P450 2E1 inhibitors such as diethyldithiocarbamate and 4-methylpyrazole in rat liver microsomes. Finally, in reconstituted monooxygenase systems containing purified rat P450 enzymes, P450 2E1 gave the highest rates of the activation of both NDMA and NDEA; the addition of rabbit cytochrome b5 to the system caused about a 1.5-fold increase in both reactions. In separate experiments we also found that N-nitrosomethylacethoxymethylamine, a compound that reacts with DNA after ester cleavage, is more genotoxic in S.typhimurium NM2009 than in S.typhimurium NM2000, a strain that is defective in O-acetyltransferase activity. Part of the pathway involved in the activation of nitrosamines is suggested to be acetylation of alkyldiazohydroxides formed by P450 or acetylesterase, because the genotoxic activity of N-nitrosomethylacethoxymethylamine in S.typhimurium NM2009 could be inhibited by the O-acetyltransferase inhibitor pentachlorophenol. These results indicate that NDMA and NDEA are oxidized to gentoxoic products by rat liver microsomes and that a P450 2E1 enzyme plays a major role in the activation of these two potent carcinogens. The activation pathway of N-nitrosodialkylamines through acetylation by O-acetyltransferase has been proposed. This simple bacterial system for measuring genotoxicity should facilitate studies on the activation of N-nitroso alkylamines.