BIOCHEMICAL CORRECTION IN THE SYNDROME OF HYPERTENSION AND HYPERKALAEMIA BY SEVERE DIETARY SALT RESTRICTION SUGGESTS RENIN-ALDOSTERONE SUPPRESSION CRITICAL IN PATHOPHYSIOLOGY

1. Plasma potassium and chloride concentrations were raised and plasma renin activity, aldosterone, bicarbonate and arterial pH were reduced in two brothers with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome), on unrestricted or moderately restricted sodium diets. 2. These abnormalities were corrected in both patients within 10 days of severe sodium restriction. 3. Pressor sensitivity to cold and angiotensin II decreased on low sodium diet, associated with a fall in blood pressure. 4. Increasing distal tubular sodium delivery by infusion of normal saline increased fractional excretion of potassium when aldosterone had been stimulated by severely restricted sodium diet, but not when aldosterone levels were low on unrestricted sodium diet. 5. These findings are consistent with excessive sodium reabsorption as the primary renal lesion in Gordon's syndrome, leading to volume expansion and suppression of renin and aldosterone. Severe dietary sodium restriction leading to volume contraction, by stimulating renin and aldosterone and promoting kaliuresis, corrects the abnormalities.     

RENIN GENE POLYMORPHISM ASSOCIATED WITH ALDOSTERONE RESPONSIVENESS TO THE RENINANGIOTENSIN SYSTEM IN PATIENTS WITH ALDOSTERONE-PRODUCING ADENOMAS

1. Aldosterone levels in patients with unilateral aldosterone-producing adenomas may be responsive or unresponsive to the renin-angiotensin system, with the former often previously misdiagnosed as bilateral adrenal hyperplasia. 2. In tumours from patients in the responsive subgroup, renin mRNA is expressed in greater amounts than in tumours from patients in the unresponsive subgroup, or in normal adrenals. 3. We compared the frequency of four renin gene polymorphisms in peripheral blood DNA from the two subgroups and found significant associations between BglI, TaqI and HinfI restriction fragment length polymorphisms (RFLP) and aldosterone responsiveness. 4. Allelic variation in the constitutive renin gene was associated with a specific cause of hypertension.     

Increased cerebral blood flow after brain arteriovenous malformation resection is substantially independent of changes in cardiac output

Brain arteriovenous malformation (BAVM) resection can result in an acute increase in cerebral blood flow (CBF) of unclear etiology. This observational study investigated the relationship between changes in CBF and cardiac output (CO) in patients undergoing microsurgical resection of BAVMs. In 20 patients undergoing a BAVM resection during an isoflurane-based anesthesia, we measured CBF and systemic cardiovascular parameters immediately before and after BAVM resection. CBF was measured on the hemisphere ipsilateral to the lesions and on the contralateral side, using intravenous cold 133Xe washout. Cardiac output was measured using thermodilution technique via a pulmonary artery catheter. There was an increase in global CBF after resection (25 +/- 8 versus 31 +/- 13 mL/100 g/min, preresection versus postresection, mean +/- SD, P =.002), ipsilateral CBF (25 +/- 8 versus 31 +/- 13 mL/100 g/min, P =.002), and contralateral CBF (24 +/- 7 versus 30 +/- 13 mL/100 g/min, P =.003). There was no change in CO, mean systemic arterial pressure, central venous pressure, or pulmonary artery diastolic pressure. The change in CBFGLOBAL was not correlated with changes in CO (r =.154, P =.517). BAVM resection resulted in global increases in CBF that was not substantially related to changes in CO or other systemic parameters.     

Predictors and impact of aneurysm rebleeding after subarachnoid hemorrhage

BACKGROUND: Aneurysm rebleeding has historically been an important cause of mortality after subarachnoid hemorrhage (SAH). OBJECTIVE: To describe the frequency and impact of rebleeding in the modern era of aneurysm care, which emphasizes early surgical or endovascular treatment. DESIGN: Inception cohort. SETTING: Tertiary care medical center. PATIENTS: A total of 574 patients enrolled in the Columbia University SAH Outcomes Project between August 1996 and June 2002. Early aneurysm repair was performed whenever feasible. MAIN OUTCOME MEASURES: Rebleeding was defined by prespecified clinical and radiographic criteria, excluding prehospital, intraprocedural, and postrepair events. Functional outcome was assessed at 3 months with the modified Rankin Scale. Multiple logistic regression was used to identify predictors of rebleeding, poor functional outcome, and mortality. RESULTS: Rebleeding occurred in 40 (6.9%) of the 574 patients; most cases (73%) occurred within 3 days of ictus. Hunt-Hess grade on admission (odds ratio [OR], 1.92 per grade; 95% confidence interval [CI], 1.33-2.75; P<.001) and maximal aneurysm diameter (OR, 1.07/mm; 95% CI, 1.01-1.13; P = .005) were independent predictors of rebleeding. After controlling for Hunt-Hess grade and aneurysm size, rebleeding was associated with a markedly reduced chance of survival with functional independence (modified Rankin Scale score, 相似文献   

ALDOSTERONE-PRODUCING ADENOMAS RESPONSIVE TO ANGIOTENSIN POSE PROBLEMS IN DIAGNOSIS

1. A subgroup of patients with aldosterone-producing adenoma (APA) have been identified who lack many of the biochemical features regarded as characteristic of APA and used to distinguish APA from bilateral adrenal hyperplasia. 2. In these patients, aldosterone is responsive to infused angiotensin II (angiotensin-responsive APA), which explains their uncharacteristic responses to upright posture, saline infusion and fludrocortisone acetate administration. 3. The angiotensin-responsiveness of these patients may derive from the contralateral adrenal gland, since renin levels are less completely suppressed in angiotensin-responsive APA than in angiotensin-unresponsive APA. 4. However, while the excretion of 18-oxo-cortisol was consistently increased in angiotensin-unresponsive APA, it was normal in angiotensin-responsive APA, consistent with biochemical and biosynthetic distinctiveness residing in the tumours. 5. Angiotensin-responsive APA should always be considered as an alternative diagnosis to bilateral hyperplasia causing primary aldosteronism.     

The syndrome of hypertension and hyperkalemia with normal GFR (Gordon's syndrome): is there increased proximal sodium reabsorption?

The syndrome of hypertension and hyperkalemia, hyperchloremic acidosis with normal glomerular filtration rate (Gordon's syndrome) is characterised by volume expansion, suppressed renin and reduced mineralocorticoid-induced renal clearance of potassium. The clinical and biochemical defects are aggravated by high salt diet and corrected by low salt diet, leading to the hypothesis of excessive sodium reabsorption in the nephron proximal to where aldosterone acts. In this study, we used lithium clearance as a marker of proximal sodium reabsorption in three patients with Gordon's syndrome, in order to further localise the site in the nephron of defective sodium handling. Fractional excretion of lithium was decreased, and absolute and fractional proximal reabsorption of sodium was increased compared to normal controls. In addition, absolute distal reabsorption of sodium was decreased, consistent with decreased mineralocorticoid activity. Fractional excretion of potassium was markedly decreased and did not rise with increased distal delivery of sodium during saline infusion. However, after severe dietary sodium restriction had elevated plasma aldosterone (lowering plasma potassium levels to normal), fractional excretion of potassium was raised by saline infusion. Reduced lithium clearance in patients with Gordon's syndrome supports the hypothesis of increased proximal sodium reabsorption in this condition.     

AN ASSOCIATION OF PRIMARY ALDOSTERONISM AND ADRENALINE-SECRETING PHAEOCHROMOCYTOMA

1. Two patients with adrenaline-only secreting phaeochromocytomas and primary aldosteronism were studied. 2. Urinary adrenaline levels were raised and plasma adrenaline was not suppressed normally following administration of clonidine. Plasma aldosterone to plasma renin activity ratios were repeatedly elevated. 3. Both had large intra-adrenal phaeochromocytomas visible on computerized tomography (CT) scanning. Surrounding adrenal cortical tissue contained an adenoma in one and nodular hyperplasia in the other. 4. Following removal of the adrenal gland containing the phaeochromocytoma, plasma and urinary adrenaline levels, and plasma aldosterone to plasma renin activity ratios returned to normal. 5. Adrenaline-only secreting phaeochromocytomas and primary aldosteronism have been rarely diagnosed even as separate entities, but reliable screening tests are now available. 6. Simultaneous presence of these two conditions of hormone excess is probably a chance occurrence. Alternatively, there may be a genetic predisposition to endocrine dysplasia, or an interaction between the contiguous medullary and cortical tissues, particularly after the normal architecture has been disturbed by an enlarging phaeochromocytoma.