Prediction of cure of hypertension in atherosclerotic renal artery stenosis

We analysed the outcome of 63 consecutive, adequate interventions for atherosclerotic renal artery stenosis and hypertension: 34 patients had percutaneous transluminal renal angioplasty, and 29 had surgical correction. Hypertension was cured in 21% of patients and improved in 47%, but 32% failed to respond. We analyzed clinical variables predictive of cure. Duration of hypertension, level of diastolic blood pressure, and sex were found to be predictive of cure. The highest probability of cure was found in men with a duration of hypertension of less than 10 years and an initial diastolic blood pressure of greater than 80 mm Hg. Use of these clinical variables in a tree-based model correctly classified 80% of cases, with a sensitivity of 92% and a specificity of 77%. We conclude that a tree-based clinical algorithm based on only three clinical criteria correctly predicted cure of hypertension in most patients with renal artery stenosis and may be useful in decision making. A prospective analysis will be required to evaluate the clinical validity of the algorithm.     

Cilazapril reverses endothelium-dependent vasodilator response to acetylcholine in mesenteric artery from spontaneously hypertensive rats

This study was designed to evaluate the effect of chronic treatment with cilazapril on vascular reactivity of aorta and mesenteric artery from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Cilazapril (5 mg/kg), an angiotensin converting enzyme inhibitor, was injected intraperitoneally twice a day for 4 weeks. Results demonstrated that acetylcholine (ACh)-induced relaxation in aorta and mesenteric artery from SHR was significantly less than that from WKY, cilazapril-treated WKY, and SHR. The impairment of ACh-induced relaxation in SHR was significantly reversed after cilazapril treatment and there were no significant differences among WKY, cilazapril-treated WKY, and SHR. Meanwhile, both N omega-nitro-L-arginine (LNNA; 10(-4) mol/L) and methylene blue (MB; 10(-5) mol/L) completely blocked the vasodilator response to ACh in aorta but only partly inhibited in mesenteric artery from WKY, cilazapril-treated WKY, and SHR. These LNNA- and MB-resistant vasodilator responses to ACh in mesenteric artery were only slightly inhibited by TEA (10(-3) mol/L) but not by indomethacin (5 x 10(-6) mol/L). These findings suggest that there may be an unidentified endothelium-dependent relaxing factor(s) (EDRF), which exists in the endothelium and may participate in the modulation of blood pressure in SHR. Results further demonstrate that the antihypertensive effect of cilazapril may be partly mediated by the reversing function of endothelium to release EDRF and LNNA-resistant, unidentified relaxing factor(s).     

New technique for knife and radial keratotomy

Low-flow (1 litre min-1) sevoflurane anaesthesia was used in 16 patients undergoing laparoscopic cholecystectomy (group LSC, n = 8) or tympanoplasty (group TP, n = 8), and concentrations of sevoflurane degradation products were measured. Degradation products in the circuit were measured hourly, and end-tidal carbon dioxide concentration, inspired and end-tidal sevoflurane concentrations, and carbon dioxide elimination were monitored. The only degradation product detected was CF2=C(CF3)-O-CH2F (compound A). The mean maximum concentrations of compound A were 21.6 (SEM 1.6) ppm and 19.6 (0.8) ppm in the LSC and TP groups, respectively (ns). The maximum temperatures of soda lime were 46.4 (0.5) degrees C and 44.8 (0.5) degrees C, respectively (P < 0.05). Hourly end-tidal sevoflurane concentrations and concentrations of sevoflurane degradation products were the same for both groups. Carbon dioxide elimination was the same for both groups 1 h after the start of anaesthesia, but was higher in group LSC after 2 h (P < 0.05). Intraperitoneal carbon dioxide insufflation associated with laparoscopic cholecystectomy had no effect on the concentration of sevoflurane degradation products.     

Video-assisted thoracoscopic surgery for pneumothorax

A 28-year-old Japanese woman who suffered from mononeuritis multiplex was admitted to our hospital. Serological study revealed cryoglobulinemia (type III), hypocomplementemia, high titers of rheumatoid factor (RF), and positive antihepatitis C virus (HCV) antibody. Nerve conduction velocities were slower in sensory nerves than in motor nerves. Biopsied sural nerve showed a marked decrease of myelinated fibers but no evidence of angitis. She received plasma exchange and cryoglobulinpheresis over a period of 2 months with approximately 2.0 L (40 ml/kg) of plasma replaced in each procedure. Both plasma exchange and cryoglobulinpheresis alleviated clinical symptoms, and nerve conduction velocities were improved in several nerves. The serum cryoglobulin level was markedly reduced after the treatment together with the recovery of the C4 level. Thus, complements appeared to be consumed in large quantities in the presence of cryoglobulinemia in this patient. Efficacy of cryoglobulinpheresis indicates the possibility that cryoglobulins produced in association with HCV infection played a role in damaging the nerve directly through the activation of the complement system.     

Further observations on enterovirus infection in specific-pathogen-free turkey poults

To evaluate sites of enterovirus replication and to characterize the resulting lesions, twenty 4-day-old specific-pathogen-free (SPF) turkey poults were orally inoculated with an enterovirus. Twenty uninoculated SPF poults served as controls. Inoculated poults were depressed, had ruffled feathers, watery droppings, and pasted vents. Gross lesions were dilated thin-walled ceca with foamy yellow fluid. Immune electron microscopy of the gastrointestinal tract contents revealed an enterovirus with an average diameter of 23.5 nm. Immunoperoxidase and indirect immunofluorescent antibody assays revealed intracytoplasmic staining in enterocytes of the duodenum, jejunum, and ileum. This correlated with the scanning electron microscopy findings, which showed the most lesions in the jejunum and ileum. The ileum had prominent cell outlines because of rounded, distinct, bulging epithelial cells. Histopathology revealed slight shortening of villi and increased crypt depth in the intestines of inoculated poults. Our findings indicate that the small intestine is the site of turkey enterovirus replication, and the gross and microscopic changes observed are determined to result from viral damage to the enterocytes.     

Inhibitory effects of antisense oligodeoxynucleotides targeting c-myc mRNA on smooth muscle cell proliferation and migration

Smooth muscle cell (SMC) proliferation and migration play pivotal roles in restenosis following angioplasty. c-myc is an immediate early response gene induced by various mitogens, and several lines of evidence derived from experiments using transformed or hematopoietic cell lines, or transgenic mice, suggest its protein product plays a role in numerous signaling transduction pathways, including those modulating cell division. We therefore reasoned that a strategy employing oligodeoxynucleotides (ODNs) complementary to c-myc mRNA (antisense ODNs) might be potent inhibitors of SMC proliferation and, perhaps, of SMC migration. To evaluate this concept, we tested several antisense ODNs targeted to c-myc mRNA (15- or 18-mer ODNs complementary to different c-myc mRNA sequences) by introducing them individually into the medium of cultured rat aortic SMCs. Phosphoroamidate-modified ODNs were employed to retard degradation. Antisense ODNs inhibited, in a concentration-dependent manner, SMC proliferation and SMC migration. Maximal inhibitory effect was 50% for proliferation and > 90% for migration. These effects were associated with decreased SMC expression of c-myc-encoded protein by Western immunoblotting and immunocytochemical staining. ODNs with the same nucleotides but a scrambled sequence caused no effect. These results indicate that the c-myc gene product is involved in the signal transduction pathways mediating SMC proliferation and migration in the in vitro model we employed. The results also suggest a potential role of antisense strategies designed to inhibit c-myc expression for the prevention of coronary restenosis.     

Characterization of DNA adducts formed by anti-benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide

The anti-11,12-dihydrodiol 13,14-epoxide of benzo[g]chrysene, a fjord-region-containing hydrocarbon, was found to react with DNA in vitro to yield, as the major product, an adduct in which the epoxide of the 11R, 12S, 13S, 14R enantiomer was opened trans by the amino group of deoxyadenosine. The structures of this adduct and other deoxyadenosine and deoxyguanosine adducts were established by spectroscopic methods. In reactions with deoxyguanylic acid, a product tentatively identified as a 7-substituted guanine was also detected. The mutagenic properties of this dihydrodiol epoxide in shuttle vector pSP189 showed that mutation at AT pairs accounted for 39% of base change mutations whereas chemical findings indicated that about 60% of adducts formed in calf thymus DNA involved adenines. Since calf thymus DNA is 56% AT and the target supF gene is 41% AT, the findings represent a fairly close relationship between adduct formation and mutagenic response. Overall, the chemical and mutagenic selectivities for the two purine bases in DNA were similar, though not identical, to those for the only other fjord-region-containing hydrocarbon studied in depth, i.e., benzo[c]phenanthrene. A major difference for these two hydrocarbon derivatives, however, is that benzo[c]phenanthrene dihydrodiol epoxides react to much higher extents (approximately 4-fold) with DNA than did the benzo[g]chrysene derivative.