Losartan but not verapamil inhibits angiotensin II-induced tissue endothelin-1 increase: role of blood pressure and endothelial function

Endothelin partially mediates angiotensin (Ang) II-induced vascular changes in vivo. This study investigated the effects of the angiotensin type 1 receptor antagonist losartan and the calcium channel blocker verapamil on vascular reactivity and tissue endothelin-1 levels in aortas of Wistar-Kyoto rats treated for 2 weeks with Ang II (200 ng x kg(-1) x min(-1)). Ang II increased systolic blood pressure (39+/-4 mm Hg, P<0.05). Concomitant treatment with losartan abolished the Ang II-induced pressure increase (P<0.05), whereas verapamil reduced it only partially (P<0.05). In the aortas of rats with Ang II-induced hypertension, tissue endothelin-1 content was increased threefold and contractions to endothelin-1 were impaired (P<0.05). Interestingly, these alterations were normalized by losartan (P<0.05) but not by verapamil. Hence, there was a strong, negative correlation between contractions to endothelin-1 and tissue endothelin-1 content (r=-0.733, P<0.0001). In contrast, both antihypertensive drugs normalized impaired endothelium-dependent relaxations to acetylcholine and reduced the sensitivity of vascular smooth muscle to sodium nitroprusside compared with Ang II-treated rats (P<0.05). Ang II-induced hypertension enhanced endothelium-dependent contractions to acetylcholine, and these were normalized by either drug. In conclusion, these findings suggest that long-term treatment with Ang II modulates endothelin-1 protein expression in the rat aorta. Although both antihypertensive agents lowered blood pressure and normalized endothelial function, only losartan prevented the increase in tissue endothelin-1 content, suggesting that angiotensin type 1 receptor antagonists but not calcium antagonists modulate tissue endothelin-1 in vivo.     

Identification and characterization of the KlCMD1 gene encoding Kluyveromyces lactis calmodulin

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major cause of morbidity and death after lung transplantation. Therapy has focused on augmented immunosuppression with a variety of agents. Although transient responses are often achieved, sustained remission has been unusual. The outcome of cytolytic therapy for BOS at our center has been analyzed and is reported. METHODS: Between July 1988 and July 1994, 233 patients underwent lung transplantation at Barnes-Jewish Hospital. Among 207 recipients (88.8%) who survived more than 3 months, 81 recipients (39%) had development of BOS; 48 of these patients underwent 64 courses of treatment with a cytolytic agent (antilymphocyte globulin, antithymocyte globulin, or OKT3 monoclonal antibody). The cases of BOS were retrospectively analyzed to determine the impact of cytolytic therapy. RESULTS: The 4-year survival rate was significantly greater in recipients without BOS than in those with BOS (82.8% vs 46.0%; p < .05). Various clinical factors, including diagnosis, forced expiratory volume in 1 second at onset of BOS, presence or absence of pathologically proven bronchiolitis obliterans, type of transplant operation, cytomegalovirus serologic status, and cytomegalovirus pneumonia, were examined, but no significant predictor of survival after the development of BOS was discerned. The mean decrement in forced expiratory volume in 1 second was significantly reduced by cytolytic therapy (-23.5% +/- 2.3% in the 3 months before therapy vs -9.9% +/- 3.5% in the 3 months after the therapy; p < .002). Nevertheless, the stage of BOS progressed over time in spite of therapy in most cases, and only 4 recipients (4.9%) with BOS remained in a lower BOS stage 2 years after treatment. CONCLUSIONS: Recipients with BOS had a significantly lower survival rate than recipients without BOS. No predictor of survival after the onset of BOS was identified. Although cytolytic therapy decreased the rate of decline in pulmonary function in the 3 months after treatment, the stage of BOS ultimately progressed in most patients.     

Pancreatic pseudocysts associated with chronic pancreatitis--early and late results of 1367 operations

The authors hereby review the data of 1367 operations for pancreatic pseudocysts. The surgical procedures of choice in particular pancreatic pathologies are analysed in the light of early morbidity and mortality, as well as long term follow-up results. The best operations for pancreatic pseudocysts have been the internal drainage procedures, which resolve the pathological alterations without the necessity of pancreatic resection. The treatment of chronic pancreatitis may require combined surgical procedure, such as cysto-Wirsungo-gastrostomy. The pancreatic resections performed for the treatment of small pseudocysts in the pancreatic head have been superseded by the less invasive blunt, forced cysto-duodenostomies, representing better results secondary to the smaller perioperative risk for the patient. The cyst-to-stomach and cyst-to-duodenum internal drainage techniques are just as effective, but with shorter operation time, than the Roux-en-Y cysto-jejunostomies.     

Effect of chronic nitric oxide deficiency on angiotensin II-induced hypertrophy of rat basilar artery

BACKGROUND AND PURPOSE: Although in vitro studies suggest that nitric oxide has an inhibitory effect on cellular proliferation and migration, in vivo experiments failed to support this conclusion. The present study was designed to determine the effect of endogenous nitric oxide on angiotensin II-induced hypertrophy of small arteries in vivo. METHODS: Angiotensin II (200 ng/kg per minute), alone or in combination with N(omega)-nitro-L-arginine methyl ester (L-NAME) (60 mg/kg per day), was administered for 2 weeks in normotensive rats. Basilar arteries were harvested, and their geometry was determined in perfused and pressurized conditions. RESULTS: Angiotensin II increased media thickness, media-lumen ratio, and cross-sectional area of the arteries, confirming the presence of hypertrophic remodeling. The concomitant administration of L-NAME, an inhibitor of nitric oxide synthesis, prevented vascular hypertrophy. The remodeling of the basilar artery geometry in the combined treatment was of eutrophic nature, similar to that observed with the administration of L-NAME alone. CONCLUSIONS: Our results suggest that endogenous nitric oxide does not inhibit angiotensin II-induced vascular hypertrophy in vivo. Nitric oxide may even be a necessary factor for hypertrophy to develop.     

A Ser315Thr substitution in KatG is predominant in genetically heterogeneous multidrug-resistant Mycobacterium tuberculosis isolates originating from the St. Petersburg area in Russia

Parts of katG and rpoB from 27 Russian Mycobacterium tuberculosis isolates were sequenced to detect mutations causing resistance to isoniazid (INH) and rifampin (RMP), respectively. All 24 INH-resistant isolates had a mutated katG, and 22 of them (91.7%) carried a mutation coding for a Ser315Thr shift. An rpoB mutation was noted for each of the 21 RMP-resistant isolates, with Ser531Leu being the most prevalent change encoded. Only two isolates had identical IS6110 fingerprints.     

Regional hip blockade. A simplified technique for the relief of intractable osteoarthritic pain

A regional anaesthetic technique is described using a blind anatomical approach to the obturator nerve and nerve to quadratus femoris, as a means of alleviating the disabling pain of chronic osteoarthritis of the hip, when arthroplasty is not available.     

Recurrent abdominal pain during childhood

RAP offers a complex and often confusing array of symptoms and diagnostic possibilities. This may be due to its unique age of presentation, its inherent somatic and cognitive developmental issues, or the physiology of abdominal pain itself. A careful examination of the historic and physical findings should produce a therapeutic plan that addresses somatic, psychological, and environmental aspects of the child. This process will avoid overly simplistic and premature misdiagnosis or potentially unnecessary investigations that convey a sense of disinterest, haste, and disbelief in the problem. The successful management of RAP lies in the recognition that serious underlying disease frequently is not present and that time usually is on our side. It is the process of continued and thoughtful evaluation and reassurance over time that counts.