HLA and longevity

One hundred fifty-five healthy nonagenarians, 55 men and 100 women, all French Caucasians, were phenotyped for alleles of the A, B, C, DR loci of the HLA complex. The observed HLA antigen frequencies were compared to those of a control series of 133 males and 179 females whose ages ranged from 10 to 50 years. When comparing the total young and elderly series, no significant differences were observed with respect to HLA antigen distribution or heterozygosity at any of the loci. When taking sex difference into account, however, an excess of the Cw1 antigen was found in the group of elderly females (p < 0.001) and an excess of the Cw7 antigen in the group of elderly males (p < 0.001). Of particular significance was the fact that Cw7 belonged in this instance to a phenotypic combination (and most probably to the corresponding haplotype) A1/Cw7/B8/DR3 which was found significantly increased in male nonagenarians (p < 0.001). These results support the hypothesis that certain HLA haplotypes are associated with survival advantage.     

Peripheral vascular disease: correlation of MR imaging and angiography

The capability of magnetic resonance (MR) imaging for detecting aortic, iliac, and femoral stenoses and occlusions was evaluated. Multisection spin-echo studies at 0.35 tesla were obtained of the infrarenal aorta to the femoral bifurcation in 24 patients, all of whom had undergone intraarterial angiography within 14 days of imaging. Transaxial MR images were compared with the angiograms. Arterial stenoses and occlusions in these vessels detected by MR imaging correlated with angiographic findings in 91% of the instances. Protrusional atherosclerotic plaques and occlusions and stenoses in the aortoiliac region were demonstrated accurately on MR images; complications of previous vascular surgery, such as aneurysms at sites of previous anastomoses or endarterectomy, were also identified. Due to the limited spatial resolution, MR images failed to demonstrate some femoral stenoses. MR imaging may be used for evaluation of aortoiliac vascular disease and for follow-up study after surgical revascularization. However, the limited spatial resolution, noncomposite display of the aortoiliofemoral circulation, and lack of evaluation of peripheral runoff provided by current MR imaging techniques militate against its replacing angiography prior to vascular intervention.     

Acute changes in cyclic AMP levels of certain brain areas following intraventricular injection of renin in rats

Actions of the central angiotensin system on brain cAMP concentrations were studied after intraventricular injection of renin. Biosynthesis of endogenous brain angiotensin II was stimulated by 0.1 U renin and the blood pressure was elevated 40 min after the application.Stimulation of the brain angiotensin system affected cAMP metabolism in several brain areas, mostly expressed as decreased cAMP levels.Significant decreases in cAMP concentrations were found in the cerebral cortex, hippocampus, basal ganglia, various hypothalamic nuclei, substantia nigra, central grey matter and in the locus coeruleus.The unchanged cAMP levels in the nucleus of the solitary tract might indicate that intraventricular injection of renin induced an acute blood pressure elevation which is not associated with changes in the cAMP system in the primary baroreceptor area.     

3 cases of mucoepidermoid bronchial malignant tumors

Mucoepidermoid tumors of the lung are extremely uncommon. Like the considerably more common mucoepidermoid tumors of the salivary glands, their histology is characterized by two components: a glandular mucoid element and an epidermoid element. The degree of malignancy is still a subject of discussion, but as with mucoepidermoid tumors of the salivary glands, mucoepidermoid carcinomas of the bronchus may be of either high or low-grade malignancy. The three cases reported here were of high-grade malignancy and metastasized irrespective of the degree of cellular differenciation. We have concluded that mucoepidermoid lung tumors should be considered as malignant lesions and the treatment has to consist in radical resection.     

Lack of detectable N-nitroso-N-methyl-N-cyclohexylamine in humans after administration of bromhexine

The possible formation of N-nitroso-N-methyl-N-cyclohexylamine (NMCA) from the drug bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) and nitrite was investigated in humans using three different approaches: 1. analysis on metabolites of NMCA in human urine; 2. analysis on NMCA in human gastric juice; 3. in vitro incubation of human gastric juice with therapeutic bromhexine doses. Diet given to volunteers was varied during these investigations with respect to nitrate content. Experiments with a maximum load of 200 mg nitrate to stimulate nitrite formation were performed. Results of in vivo experiments did not indicate any formation of NMCA. In one out of 39 ex-vivo/in-vitro experiments (with a load of 100 mg nitrate in drinking water) 0.5 ng NMCA/ml gastric juice could be detected which is near the detection limit. Finally, this study showed that bromhexine is not secreted by saliva. This allows to conclude that nitrite and bromhexine do not reach the stomach simultaneously over a longer period of time. In consequence, medication with bromhexine is not regarded to represent a risk due to nitrosamine formation.