Rapid degradation of endothelin-1 by an enzyme released by the rat isolated perfused mesentery.

1. In vivo the effects of endothelin-1 (ET-1) are limited by its rapid removal from the circulation and possibly by its metabolism by enzymes such as neutral endopeptidase 24.11, deamidase or carboxypeptidase A. Here, using as a model the isolated perfused mesenteric arterial bed of the rat, we have examined the involvements of these enzymatic activities in the vascular responses to ET-1. 2. Samples of Krebs buffer which had been recirculated through the mesenteric arterial bed for 30 min rapidly destroyed the activity of ET-1 as assessed either by bioassay on rings of rat thoracic aorta or by high performance liquid chromatography (h.p.l.c.). For instance, after 15 min incubation with the recirculated-Krebs solution (recirc-K) the contraction induced by 3 x 10(-9) M ET-1 was reduced by more than 90%. Contractions induced by sarafotoxin 6b (3 x 10(-9) M) were similarly suppressed by preincubation with recirc-K whereas those to Arg-vasopressin (3 x 10(-9) M) were unaffected. 3. The degradation of ET-1 by recirc-K was prevented by 1,10-phenanthroline (10(-3) M), abolished by heating the recirc-K solution to 90 degrees C for 15 min, and reduced by EGTA (5 x 10(-3) M) or ET-1(16-21) (10(-5) M). For instance, in the presence of ET-1(16-21) (n = 6) the contraction induced by ET-1 was reduced by only 40% after 15 min incubation with recirc-K buffer.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

Transnasal jet ventilation is a useful adjunct to teach fibreoptic intubation: a preliminary report

PURPOSE: Fibreoptic intubation (FOI) has become an essential technique in the anesthetic management of patients with difficult airways. Unfortunately, residents may graduate from anesthesiology training programs with insufficient skills in FOI. To enhance resident proficiency at FOI without compromising patient comfort or safety, the technique of transnasal jet ventilation-assisted FOI was developed. This report describes our initial experience with this technique. METHODS: Sixty-four patients scheduled for oromaxillofacial surgery under nasal endotracheal anesthesia were recruited. Twenty-eight residents at all levels of training performed FOI through the patient's right nostril after the induction of general anesthesia and neuromuscular blockade. Oxygenation and ventilation were maintained by a faculty anesthesiologist using a Sanders device to deliver a jet of oxygen through a nasal trumpet placed in the patient's left nostril. The time from induction until completion of the FOI was recorded. Residents were subsequently queried about the educational benefit of the technique using a standardized questionnaire. RESULTS: All residents were able to successfully intubate all patients in this study. Thirteen residents successfully performed intubations on three or more occasions with 70% performing the technique faster on the third trial than on the first. No evidence of hypoxemia, gastric distension, pneumothorax, hemodynamic instability or recall was observed. All respondents to the questionnaire reported that the technique was useful as an educational tool and recommended its use with other residents. CONCLUSION: Transnasal jet ventilation-assisted FOI is a useful method to train residents in FOI while maximizing patient comfort and safety.     

Biochemical actions of chronic ethanol exposure in the mesolimbic dopamine system

In previous studies, we have demonstrated that chronic administration of morphine or cocaine produces some common biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc), components of the mesolimbic dopamine system implicated in the reinforcing actions of these and other drugs of abuse. Since this neural pathway is also implicated in the reinforcing actions of ethanol, it was of interest to determine whether chronic ethanol exposure results in similar biochemical adaptations. Indeed, as seen for chronic morphine and cocaine treatments, we show here that chronic ethanol treatment increased levels of tyrosine hydroxylase and glial fibrillary acidic protein immunoreactivity, and decreases levels of neurofilament protein immunoreactivity, in the VTA. Also like morphine and cocaine, ethanol increases levels of cyclic AMP-dependent protein kinase activity in the NAc. These actions of ethanol required long-term exposure to the drug, and were in most cases not seen in the substantia nigra or caudate-putamen, components of the nigrostriatal dopamine system studied for comparison. Altered levels of tyrosine hydroxylase in catecholaminergic cells frequently reflect altered states of activation of the cells. Moreover, increasing evidence indicates that ethanol produces many of its acute effects on the brain by regulating NMDA glutamate and GAB_A receptors. We therefore examined the influence of chronic ethanol treatment on levels of expression of specific glutamate and GABA receptor subunits in the VTA. It was found that long-term, but not short-term, ethanol exposure increased levels of immunoreactivity of the NMDARl subunit, an obligatory component of NMDA glutamate receptors, and of the Glu Rl subunit, a component of many AMPA glutamate receptors; but at the same time, long-term ethanol exposure decreased immunoreactivity levels of the α1 subunit of the GABA_A receptor complex. These changes are consistent with an increased state of activation of VTA neurons inferred from the observed increase intyrosine hydroxylase (TH) expression. These results demonstrate that chronic ethanol exposure results in several biochemical adaptations in the mesolimbic dopamine system, which may underlie prominent changes in the structural and functional properties of this neural pathway related to alcohol abuse and alcoholism. © 1995 Wiley-Liss, Inc.     

Renal vein renin analysis: Limitations of its use in predicting benefit from percutaneous angioplasty

Two hundred forty-four consecutive patients (mean age 61 years), including 123 who had technically valid renal vein renin (RVR) analysis and 121 without RVR data, underwent technically successful percutaneous renal artery angioplasty (PTRA). They were retrospectively examined to evaluate the utility of RVR analysis in identifying renal hypertension (RVH), predicting benefit from PTRA, and determining if the lack of knowledge of renin levels significantly affected clinical outcome after PTRA. Abnormal RVR values were associated with clinical benefit after PTRA in 62 of 93 patients (67% sensitivity, 20% specificity, 72% positive predictive value). Clinical improvement following PTRA occurred in 31 of 37 patients with normal pre-PTRA RVR values (16% negative predictive value). RVR analysis correctly identified 86 of 117 patients with renovascular hypertension (74% sensitivity, 16% negative predictive value). Improved blood pressure (BP) control occurred in 72% with abnormal RVR analysis and 66% of the 121 patients without RVR data (p>0.1). We conclude that the very low negative predictive value significantly limited the use of RVR analysis in this elderly (mean age 60 years) patient population with a high incidence of mild renal functional impairment (mean serum creatinine 1.4 mg/dl) and bilateral renal artery stenosis (38%). The lack of pre-PTRA renin data did not significantly affect clinical outcome. If RVR data were relied upon as the exclusive selection criterion in patients of this type, many would be prevented from having the benefit of cure or improvement by PTRA.     

Dega-Osteotomie bei Hüftgelenkdysplasie

Zusammenfassung Operationsziel überdachung des Femurkopfes bei Hüftgelenkdysplasie. Indikationen Dysplastisches Acetabulum bei Patienten mit neuromuskul?ren und nichtneuromuskul?ren Erkrankungen. übergro?es, flaches Acetabulum. Fehlen einer lateralen und kranialen überdachung. Kontraindikationen Y-Fuge geschlossen, Wachstum abgeschlossen. Stark verformter Femurkopf. Operationstechnik Modifizierter Zugang nach Salter/Smith-Petersen. Freilegung und Teilung der Apophyse des Beckenkammes mit einem Messer. Freilegung der Darmbeinschaufel. Osteotomie der ?u?eren Wand des Iliums; sie wird vorsichtig mit Hilfe eines gebogenen mei?els nach unten gebogen und in dieser Stellung durch Einsetzen von trikortikalen Beckenkammsp?nen gehalten. Eine Osteosynthese ist nicht notwendig. Becken-Bein-Gipsverband mit Einschlu? des gegenseitigen Oberschenkels für sechs Wochen. Ergebnisse Zwischen 1987 und 1997 wurden 26 Hüften von 23 Patienten operiert. überwiegend handelte es sich um Kinder mit spastischen Paresen. Folgende zus?tzliche Eingriffe wurden vorgenommen: Offene Reposition zehnmal, Femurosteotomie 18mal und Tenotomien sowie Muskelabl?sungen 15mal. Der Durchschnittswert des azetabul?ren Index verbesserte sich von 32° auf 22°, der durchschnittliche Wert des Kopfzentrum-Pfannenrand-Winkels von −25° auf 22° und der durchschnittliche Migrationsindex von 62% auf 69%. Als Komplikationen wurden beobachtet: eine erneute Subluxation, ein frühzeitiger Verschlu? des Y-Knorpels, eine Fraktur des anderen Femur, einmal heterotope Ossifikationen und einmal eine Infektion der Harnwege.