Prevalence of migraine in Noonan syndrome.

A randomized double-controlled trial involving 22 patients with Noonan syndrome (NS) and 22 normal individuals (control group) was carried out to determine the prevalence of migraine in patients with NS. The NS group consisted of 11 males aged 19.55 +/- 6.11 years and 11 females aged 18.81 +/- 5.47 years. The control group consisted of 11 males aged 19.55 +/- 6.6 years and 11 females aged 18.81 +/- 5.47 years. Seven NS-group patients reported migraine without aura (MO), and three reported probable MO (PMO). Taken together, these represent a prevalence of migraine in the NS group of 45.5%. Two control-group patients reported MO, a prevalence of 9.09%. The prevalence of migraine was significantly higher in the NS-group patients than in the controls (P < 0.005), suggesting a positive association between NS and migraine. Nevertheless, further studies are needed to confirm our findings.

Kidney transplantation improves the multidimensional quality of life.

INTRODUCTION: Quality of life is affected during any illness, especially chronic diseases, such as renal failure. OBJECTIVE: To evaluate the quality of life after kidney transplantation. METHODS: One hundred patients were interviewed (60 men, 40 women, mean age 36 +/- 10.4 years, median 35 years) from July to October 2000 using the multidimensional questionnaire WHOQL-Bref. RESULTS: Eighty-eight percent of patients were satisfied/very satisfied with their general health condition. Seventy-seven percent manifested a good capacity to carry out daily activities, and 75% considered themselves satisfied with their work capacity. Quality of life was considered "very good" or "good" among 80%, and "neither good nor bad" in 20%. None considered quality of life in general as "bad" or "very bad." Most (87%) were satisfied with their current condition and with themselves after the kidney transplant. CONCLUSION: Patients perceive kidney transplant as capable of improving their quality of life. The most important finding in this study is that the results of the physical and psychological domains did not show any significant difference. It was possible to conclude that the quality of life for most subjects is related to reduction or disappearance of the symptoms caused by the previous disease.

Role of Tamm-Horsfall protein and uromodulin in calcium oxalate crystallization.

One of the defenses against nephrolithiasis is provided by macromolecules that modulate the nucleation, growth, aggregation and retention of crystals in the kidneys. The aim of the present study was to determine the behavior of two of these proteins, Tamm-Horsfall and uromodulin, in calcium oxalate crystallization in vitro. We studied a group of 10 male stone formers who had formed at least one kidney stone composed of calcium oxalate. They were classified as having idiopathic nephrolithiasis and had no well-known metabolic risk factors involved in kidney stone pathogenesis. Ten normal men were used as controls, as was a group consisting of five normal women and another consisting of five pregnant women. Crystallization was induced by a fixed supersaturation of calcium oxalate and measured with a Coulter Counter. All findings were confirmed by light and scanning electron microscopy. The number of particulate material deposited from patients with Tamm-Horsfall protein was higher than that of the controls (P<0.001). However, Tamm-Horsfall protein decreased the particle diameter of the stone formers when analyzed by the mode of the volume distribution curve (P<0.002) (5.64 +/- 0.55 microm compared to 11.41 +/- 0.48 microm of uromodulin; 15.94 +/- 3.93 microm and 12.45 +/- 0.97 microm of normal men Tamm-Horsfall protein and uromodulin, respectively; 8.17 +/- 1.57 microm and 9.82 +/- 0.95 microm of normal women Tamm-Horsfall protein and uromodulin, respectively; 12.17 +/- 1.41 m and 12.99 +/- 0.51 microm of pregnant Tamm-Horsfall protein and uromodulin, respectively). Uromodulin produced fewer particles than Tamm-Horsfall protein in all groups. Nonetheless, the total volume of the crystals produced by uromodulin was higher than that produced by Tamm-Horsfall protein. Our results indicate a different effect of Tamm-Horsfall protein and uromodulin. This dual behavior suggests different functions. Tamm-Horsfall protein may act on nucleation and inhibit crystal aggregation, while uromodulin may promote aggregation of calcium oxalate crystals.

Role of Tamm-Horsfall protein and uromodulin in calcium oxalate crystallization

One of the defenses against nephrolithiasis is provided by macromolecules that modulate the nucleation, growth, aggregation and retention of crystals in the kidneys. The aim of the present study was to determine the behavior of two of these proteins, Tamm-Horsfall and uromodulin, in calcium oxalate crystallization in vitro. We studied a group of 10 male stone formers who had formed at least one kidney stone composed of calcium oxalate. They were classified as having idiopathic nephrolithiasis and had no well-known metabolic risk factors involved in kidney stone pathogenesis. Ten normal men were used as controls, as was a group consisting of five normal women and another consisting of five pregnant women. Crystallization was induced by a fixed supersaturation of calcium oxalate and measured with a Coulter Counter. All findings were confirmed by light and scanning electron microscopy. The number of particulate material deposited from patients with Tamm-Horsfall protein was higher than that of the controls (P<0.001). However, Tamm-Horsfall protein decreased the particle diameter of the stone formers when analyzed by the mode of the volume distribution curve (P<0.002) (5.64 ± 0.55 æm compared to 11.41 ± 0.48 æm of uromodulin; 15.94 ± 3.93 æm and 12.45 ± 0.97 æm of normal men Tamm-Horsfall protein and uromodulin, respectively; 8.17 ± 1.57 æm and 9.82 ± 0.95 æm of normal women Tamm-Horsfall protein and uromodulin, respectively; 12.17 ± 1.41 æm and 12.99 ± 0.51 æm of pregnant Tamm-Horsfall protein and uromodulin, respectively). Uromodulin produced fewer particles than Tamm-Horsfall protein in all groups. Nonetheless, the total volume of the crystals produced by uromodulin was higher than that produced by Tamm-Horsfall protein. Our results indicate a different effect of Tamm-Horsfall protein and uromodulin. This dual behavior suggests different functions. Tamm-Horsfall protein may act on nucleation and inhibit crystal aggregation, while uromodulin may promote aggregation of calcium oxalate crystals

Microalbuminuria and renal morphology in the evaluation of subclinical lupus nephritis.

AIM AND METHOD: In an attempt to evaluate subclinical lupus nephropathy, we analyzed the clinical characteristics, determined the albumin excretion rate (AER) by radioimmunoassay and performed renal biopsy in 30 patients with systemic lupus erythematosus (SLE) who had no clinical signs of renal involvement (no urinary sediment abnormalities, absence of proteinuria, serum creatinine <1.3 mg/dl). All biopsies were classified according to a modified classification proposed by the WHO. RESULTS: Fifteen cases (50%) had mesangial glomerulonephritis (MGN) type IIb, 12 had MGN type IIa and 3 patients showed no changes on light microscopy (LM) or on immunofluorescence (IF) (type I). Anti-IgM-fluorescent deposits were found in 83% of the renal biopsies, being associated with less heavily stained deposits of IgG, IgA and C3. Patients with MGN type IIb showed lower mean age when compared to those of MGN type IIa (26.04 years vs. 36.3 years) (p<0.029); those patients also presented disease duration of 4.8 years and their mean AER was 39.9 microg/min. Six of the patients (6 of 15, 40%) showed positive anti-dsDNA antibodies, in contrast to patients with MGN type IIa who did not show positive anti-dsDNA antibodies (p<0.002). The group with abnormal AER presented lower mean age (p<0.029) and lower C3 levels (p<0.0098) when compared to the group with normal AER. CONCLUSION: The results suggest the high prevalence of MGN type IIb and IgM deposits on IF, despite the paucity of clinical and laboratory data on these patients. Furthermore, there is an association between MGN type IIb and positive anti-dsDNA antibodies and a relationship between abnormal AER and low C3 levels. The level of AER could not determine the presence or absence of renal disease on LM or IF in this population.

Parenteral isradipine reduces blood pressure in hypertensive crisis.

The efficacy and tolerability of an infusion of isradipine, a calcium antagonist of the dihydropyridine type, were tested in patients in hypertensive crisis. Ten patients with symptomatic and significant elevations in blood pressure were infused for 12 h with isradipine at 1.2, 2.4, 4.8, and 7.2 micrograms/kg/h (3 h of each infusion level). No untoward effects or adverse reactions were noted. No alterations were observed on electrocardiographic tracings, and blood pressure was significantly reduced only at doses of 7.2 micrograms/kg/h. Thus, isradipine as an infusion is useful and safe for hypertensive crisis, starting at a rate of 7.2 micrograms/kg/h. Higher doses may yet prove to be safe, well tolerated, and even more efficacious.

Effects of a vasopressin antagonist with combined antipressor and antiantidiuretic activities in rats with left ventricular dysfunction.

These experiments assessed the hemodynamic and aquaretic effects of an arginine vasopressin (AVP) antagonist with dual V1V2-receptor inhibiting properties in rats with congestive heart failure resulting from ischemic cardiomyopathy. The compound d(CH2)5-D-Tyr(Et)VAVP was used in these studies. Rats with limited or extensive myocardial infarcts (i.e., with less than 50% or greater than 66% necrosis of the left ventricular wall, respectively, induced by left coronary ligation) and sham-operated controls received the AVP antagonist (100 micrograms/kg i.v.) 4 weeks later. This agent produced an 18% increase in cardiac output (p less than 0.05) and 13% decrease in systemic vascular resistance in the severely damaged rats, both changes being significantly different from those seen in the normal controls or the rats with limited infarcts. All animals exhibited increases in urinary output of 4-10-fold over baseline. We conclude that the hemodynamic and renal effects of this agent are beneficial in animals with left ventricular dysfunction.

Bradykinin antagonism and prostaglandins in blood pressure regulation.

These experiments were designed to analyze the interaction of a bradykinin antagonist with prostaglandins in blood pressure regulation of normotensive rats. Male Wistar rats, divided into three groups, received a 5-minute intra-arterial infusion of the bradykinin antagonist [( DArgo-Hyp3-Thi5,8-DPhe7]BK-TFA) at 250 micrograms/min. Groups were either intact rats (group I, n = 5), pretreated with indomethacin (group II, n = 10), or pretreated with both indomethacin and prazosin (group III, n = 8). The bradykinin antagonist infusion, which was shown to inhibit exogenous bradykinin by greater than 76% in intact animals, did not alter mean arterial pressure in group I rats despite a twofold increase in norepinephrine and a threefold increase in epinephrine. Group II rats presented a progressive increase in mean arterial pressure during the bradykinin antagonist infusion (14 +/- 3 mm Hg), with no statistically significant change in plasma catecholamines. Group III, with lower baseline mean arterial pressure due to alpha 1-adrenergic blockade, had an increase in mean arterial pressure comparable with group II during bradykinin antagonist infusion (22 +/- 5 mm Hg), confirming that this response was not sympathetically mediated. We conclude that in normotensive rats bradykinin plays a role in blood pressure regulation that is closely linked to that of prostaglandins and that points to a balance between these systems.

Renin-angiotensin and vasopressin in the development of salt-induced hypertension.

The purpose of this study was to assess the participation and interaction of the renin-angiotensin system and vasopressin in the early stages of the development of salt-induced hypertension. Subtotally nephrectomized rats, fed 1% saline, were treated over a 10-day period with either an antivasopressor V1 antagonist (by osmotic minipump) or an angiotensin converting enzyme inhibitor (either captopril or ramipril, given daily by oral gavage), or a combination of the two modes of treatment. Surprisingly, only ramipril (either alone or in combination with the V1 antagonist) could prevent the development of hypertension in these animals. Our data would not permit conclusion as to whether the different capacity of these agents to prevent salt-induced hypertension was due to a different degree of penetration into the central nervous system, or to some other property.

Regulation of renin gene expression in hypertensive rats.

A carboxy terminal renin complementary DNA (cDNA) clone from rat kidney was isolated, characterized, and used as a probe for renin messenger RNA (mRNA) quantification in normotensive and hypertensive rats. RNA blotting analysis detected renin mRNA in control kidney and brain. Deoxycorticosterone acetate (DOCA) and high salt (1%) treatment of experimental animals resulted in a greater than 95% decrease in the content of renin mRNA in the kidney, as compared with values in control rats receiving 0.4% NaCl in their diet. In contrast, high salt (1%) treatment alone caused only a twofold decrease in kidney renin mRNA content, as compared with values in controls. DOCA and low salt (0.04%) or low salt (0.04%) treatment alone caused a 1.5-fold increase in the kidney renin mRNA content, as compared with values in control rats. These results indicate that DOCA and salt have a synergistic effect in depressing renin mRNA levels in kidney. Clipping of the left renal artery caused a threefold increase in the steady state level of renin mRNA in the ischemic kidney and a 0.5-fold decrease in the hypertrophied kidney. The data are consistent with the hypothesis that blood pressure and other stimuli regulate the expression of the renin gene in vivo.

Acute effects of the new angiotensin-converting enzyme inhibitor cilazapril: a pilot study.

This study assesses the magnitude and duration of action of three different oral doses of the new orally active angiotensin-converting enzyme (ACE) inhibitor RO 312848 (cilazapril, Hoffman-LaRoche, Nutley, NJ) on blood pressure and plasma ACE levels. Twelve hypertensive patients were separated into two groups: Group A (n = 6) received two single daily doses of 5 and 10 mg, each preceded and followed by two placebo days, and Group B (n = 6) received 10 and 20 mg on an identical protocol. The onset and duration of an appreciable blood pressure lowering effects were at 2 hours and at least for 12 hours, respectively, whereas suppression of ACE levels occurred at 1 hour and lasted for more than 72 hours. Response of these two parameters was partial after 5 mg, but was maximal after 10 mg and did not increase further with the 20-mg dose. A 5-10 mg dose daily may be sufficient to maintain chronic blood pressure control with this agent, but long-term dose trials are necessary to establish its clinical utility.

Vascular and sympathoadrenal responses to bradykinin and a bradykinin analogue.

These experiments were designed to assess the interaction of bradykinin and its antagonist (Arg-Pro-Hyp-Gly-Phe-Ser-DPhe-Phe-Arg-trifluoroacetic acid) with the sympathoadrenal system. Three groups of male Wistar rats received 5-minute intra-arterial infusions of either dextrose (Group 1, n = 6), bradykinin, 250 micrograms/min (Group 2, n = 5), or bradykinin, 25 micrograms/min (Group 3, n = 4). Six other groups received a similar infusion of the bradykinin antagonist at 250 micrograms/min. They were either intact rats (Group 4, n = 10) or rats previously submitted to chemical sympathectomy (Group 5, n = 17), to adrenal enucleation (Group 6, n = 8), to combined alpha-adrenergic and beta-adrenergic blockade (Group 7, n = 7), to alpha 1-adrenergic receptor blockade (Group 8, n = 8), or to alpha 2-adrenergic receptor blockade (Group 9, n = 8). Bradykinin infusion produced a sustained fall in mean arterial pressure (MAP) in Groups 2 and 3 (by -48 +/- 3 and -36 +/- 7 mm Hg, respectively) associated with similar increases in plasma epinephrine levels (100-fold), and norepinephrine (sevenfold) as compared with Group 1. The bradykinin antagonist infusion in intact rats produced a 23 +/- 4 mm Hg rise in MAP associated with a sixfold increase in epinephrine and a twofold increase in norepinephrine. Group 5 rats with lower baseline catecholamine levels had an even larger MAP rise (30 +/- 6 mm Hg) accompanied by a rise in epinephrine and norepinephrine proportionally similar to that of intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of vasopressin in blood pressure maintenance in diabetic orthostatic hypotension.

The purpose of these studies was to assess the role of vasopressin in maintaining supine and upright blood pressures in hypertensive diabetic subjects. Patients with (n = 6) or without (n = 10) evidence of autonomic insufficiency had blood pressure and heart rate monitored before and after receiving an intravenous injection of 0.5 mg of a V1 vasopressin inhibitor. None of the patients had supine changes in blood pressure or heart rate. However, upon assuming the erect position, the six patients with preexisting orthostatic hypotension had an average blood pressure fall of 44 mm Hg after vasopressin inhibition (as opposed to 20 mm Hg before), accompanied by a modest rise in heart rate of 20 beats/min. Those without autonomic dysfunction were separated into two subgroups. Four developed an average fall in orthostatic blood pressure of 18 mm Hg after vasopressin inhibition, whereas the remaining six had no change. There were no distinguishing hormonal characteristics (vasopressin, renin, and catecholamine levels) between the groups, but in the patients with autonomic dysfunction, the renin level failed to rise when upright. We conclude that vasopressin plays an important role in preventing or minimizing orthostatic hypotension in diabetic patients. Its pressor contribution is crucial in those with autonomic insufficiency and impaired renin and sympathetic responses, in whom the pressor effectiveness of vasopressin is greatly enhanced.

Antihypertensive effectiveness of the nifedipine gastrointestinal therapeutic system.

The results of a multicenter trial conducted in order to determine the therapeutic efficacy of the gastrointestinal therapeutic system (GITS) formulation of nifedipine in comparison with hydrochlorothiazide and placebo in the management of mild to moderate essential hypertension are presented. During a one-week wash-out phase, antihypertensive therapy was discontinued in all patients. After a three-week single-blind placebo period, eligible patients were randomly assigned in a double-blind fashion to one of three treatment groups for a one-week titration period and a nine-week efficacy period. Patients received either nifedipine GITS, 30 or 60 mg daily; hydrochlorothiazide, 25 or 50 mg daily; or placebo. Sitting and standing blood pressures decreased by an average 11.6/10.4 and 10.8/10.8 mm Hg, respectively, with nifedipine GITS therapy, and 14.8/10.8 and 14.3/8.2 mm Hg, respectively, with hydrochlorothiazide therapy. Compared with placebo, these changes were highly significant for both sitting (p less than or equal to 0.005) and standing (p less than or equal to 0.02) measurements. Heart rate remained essentially unchanged in all three groups. It was therefore concluded that monotherapy with nifedipine GITS, at doses of 30 or 60 mg given once daily, effectively reduces blood pressure in patients with hypertension to a degree comparable with that seen in hydrochlorothiazide therapy.

The clonidine test for the diagnosis of pheochromocytoma: the usefulness of urinary metanephrine measurements.

1. The clonidine suppression of urinary metanephrines as a criterion for the diagnosis of pheochromocytoma is described. Twenty-four patients were divided into 3 groups: Group I, 10 patients with pheochromocytoma (confirmed by tomography and surgery); Group II, 9 patients with suspected pheochromocytoma (clinical evidence plus one mildly elevated value of urinary metanephrines, but with negative tomography); Group III, 5 patients with proven essential hypertension. 2. Urinary metanephrine levels were determined in urine collected before (basal) and 3 h after a single oral dose of clonidine (0.4 or 0.8 mg). 3. Mean basal urinary metanephrine levels were above normal for group I (9.2 +/- 2.2 micrograms/mg creatinine) and group II (2.2 +/- 0.3 micrograms/mg creatinine) but were within the normal range for group III (0.6 +/- 0.1 microgram/mg creatinine). After clonidine administration, urinary metanephrine levels remained elevated for all patients with pheochromocytoma but decreased to within the normal range for all but one patient in group II. The urinary metanephrine levels of group III were not significantly altered by clonidine. 4. These data demonstrate that, when monitored by the clonidine suppression test, urinary metanephrine levels are useful for the diagnosis of pheochromocytoma, permitting the differentiation of affected patients from those exhibiting essential hypertension and increased sympathetic drive.

Efficacy and tolerability of enalapril monotherapy in mild-to-moderate hypertension in older patients compared to younger patients.

In an eight-week, multicenter open-label study of enalapril monotherapy for mild-to-moderate essential hypertension, data for 115 of the 276 participants between the ages of 55 and 75 years (whites, n = 90; blacks, n = 25) were analyzed. These data were compared with similar data for the study subset of 92 younger patients between the ages of 21 and 45 years (whites, n = 58; blacks, n = 34). The most striking finding was the overall lack of significant differences in response between older and younger patients. There were, however, significant differences in response to therapy between the two racial groups studied. In the older group, normotension was achieved in 66% of white patients and 60% of black patients with a single daily dose of enalapril ranging from 5 to 40 mg; the group means, 13 +/- 1 mg in whites vs 22 +/- 2 mg in blacks, differed significantly (P less than 0.05). Thirty-one percent of older white patients attained normotension with a daily dosage of 5 mg, whereas only 4% of black patients in this age group did so. Only 4% of the older white patients but 24% of the older black patients reached the highest recommended daily dosage of 40 mg of enalapril. Adverse reactions occurred in 11% of the older white patients and 16% of the older black patients (a nonsignificant difference), consisting mostly of gastrointestinal discomfort, malaise, dizziness, and pruritus. There were no significant biochemical abnormalities, the only consistent change being a slight increase in mean plasma potassium from 4.34 to 4.45 mEq/L in older whites (P less than 0.05). Enalapril appeared to be generally effective and well tolerated in the management of mild-to-moderate hypertension in the older subset of patients in this study. Efficacy and tolerability data for older and younger patients were comparable.

Comparison of the hemodynamic effects of sodium acetate in euvolemic dogs and in dogs submitted to hemorrhagic shock.

We determined the dose-response relationship of systemic hemodynamics with graded intravenous infusions of sodium acetate (0.75, 1.50 and 3.00 microEq kg-1 min-1) in a group of dogs in the euvolemic state (N = 10) and in animals submitted to severe hemorrhagic shock (N = 7). Sodium acetate had a marked vasodilator effect on both groups, decreasing total peripheral resistance by 36.6% and 55.1%, respectively. Cardiac index increased simultaneously by 68.4% and 143.0%, respectively. Sodium acetate induced an approximate normalization of cardiac index and peripheral resistance at the highest infusion rate in the animals submitted to hemorrhagic shock. The normalization of cardiac output was due to a marked increase in heart rate in euvolemic dogs and to an increase in stroke volume in shocked animals. The hyperkinetic state of the circulation induced by the drug and a possible inotropic action of sodium acetate either direct or indirect could explain the different patterns of response.

Sodium acetate, an arterial vasodilator: haemodynamic characterisation in normal dogs.

Sodium acetate (SA) has been implicated in hypotensive episodes of haemodialysis because of its vasodilatory effects. The haemodynamic correlates of the changes in blood pressure, cardiac output (CO) and total peripheral resistance (TPR) are well known but the site of action of SA (i.e. arteriolar, venular or both) is not yet clarified. We thus studied the changes in CO, TPR and mean arterial pressure (MAP) induced by four graded doses of SA (0.034 to 0.300 mEq/kg/min) in seven normal dogs. To evaluate the site of vasodilation we also measured the changes in cardiopulmonary volume (CPV), mean pulmonary artery pressure (MPAP) and mean transit time (MTT). From control to the highest infusion rate, CO increased from 1.63 +/- 0.20 to 3.59 +/- 0.38L/min (p less than 0.001), TPR decreased from 78.2 +/- 11.3 to 36.4 +/- 4.8A.U. (p less than 0.001). MAP rose significantly from 107.2 +/- 4.0 to 116.5 +/- 8.5 mmHg (p less than 0.05) and stroke volume was maintained (17.2 +/- 2.3 to 19.6 +/- 2.1 ml, NS) in spite of the marked tachycardia observed (heart rate from 106.1 +/- 7.6 to 194.8 +/- 9.1bpm, p less than 0.001). This was associated with increases in MPAP (from 13.3 +/- 0.7 to 19.6 +/- 2.1mmHg, p less than 0.01) and CPV (from 195.0 +/- 21.3 to 224.4 +/- 24.3ml, p less than 0.01) and marked decrease in MTT (from 7.74 +/- 0.73 to 3.78 +/- 0.22 sec, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)