Angiotensin converting enzyme activity in the serum, lung and kidney of diabetic rats.

Diabetes Mellitus in its early stages, is associated with kidney enlargement and increased glomerular filtration rate in humans and in rats. The present study was designed to clarify the direct effect of diabetes on serum and tissue angiotensin converting enzyme (ACE) activity in streptozotocin-induced diabetic rats. Serum ACE activity, as determined using a radiometric assay, was significantly increased in the diabetic rats (n = 15) 14 days after induction of diabetes (670 +/- 31 vs. 506 +/- 14 nmol ml-1 min-1). Lung ACE activity, but not renal, was significantly elevated at 7 and 14 days by 29 and 46%, respectively. Plasma renin activity in the diabetic rats was decreased at 7 and 14 days by 41 and 78%, respectively. Incubations of lung slices in the presence of glucose at different concentrations did not affect in-vitro release of the enzyme. Administration of insulin (8 units kg-1) to diabetic rats (n = 6) on the 4th day for 11 days reduced ACE activity to values below control. Thus, serum and lung ACE activity is increased in the diabetic rat and reduced upon insulin treatment.

Pelger-Huët anomaly mimicking 'shift to the left'.

A case report is presented of an 83-year-old male patient with respiratory distress, body temperature of 38.5 degrees C, bilateral white infiltrates on chest X-ray and ECG showing acute myocardial infarction. Clinical evaluation led to the suspicion of severe infection accompanying lung congestion due to the infarction, mostly because his white blood cell differential count showed a persistent severe 'shift to the left'. Re-examination of his blood smear showed that the 'shift to the left' did not consist of band forms but of a 'Pelger-Huet' anomaly of the granulocytes. Recognition of this anomaly in the light of rapid clinical and radiological improvement precluded the administration of antibiotics for the diagnosis of severe infection with pulmonary involvement, which responded to diuretic therapy alone.

Management of congestive heart failure: neuroendocrine approach.

The term heart failure is a complex of clinical syndromes caused by "neuroendocrine" compensatory responses that are renal, neural, hormonal and hemodynamic in nature. Activation of these multiple systems--as a result of renin, angiotensin II and the action of circulatory catecholamines--causes the release of norepinephrine vasopressin and aldosterone. These responses contribute to the arteriolar constriction and salt and water retention that promote central pooling with an increase in pre- and afterload of the already failing heart, causing deterioration of the congestive heart failure (CHF). Therapy for this clinical syndrome is aimed at reducing both pre- and afterload with vasodilators, which produce a profoundly favorable effect on left ventricular performances. Beta blocking agents, which inhibit the increased sympathetic mediated vasoconstriction, up-regulate beta receptors and thus restore responsiveness to the failing heart. Inotropic agents, such as digitalis and amrinone/milrinone are reserved for patients with dilated failing heart and impaired systolic function; recently a synthetic atrial natriuretic factor has been developed for potential use in CHF. Ultrafiltration is also used in refractory preoperative CHF with cardiac abnormalities. Neuroendocrine responses to CHF are treated today directly by improving central hemodynamic imbalance in these patients.

Prostanoids and thromboxane production by renal brush border membrane.

It has been estimated that proximal tubule are responsible for about 7.5% of total kidney prostaglandin PGE2 production. In the present report we investigated the production of prostanoids and thromboxane by rabbit renal proximal tubule brush border membrane. PGF2 alpha was the major endogenous prostaglandin produced under basal condition. The addition of exogenous arachidonic acid increased only PGE2 production. No PGE2 production was found when vesicles were incubated with indomethacin or at 4 degrees C, suggesting the involvement of the PGH2 synthase and PGE2 isomerase enzymes. Addition of angiotensin II at 10(-6) and 10(-9) mol l-1 did not affect the endogenous PGE2 production by brush border membrane. Thus, results of our study demonstrates that the renal proximal tubule brush border membrane has the capacity to produce prostanoids and thromboxane.

Causes of death in patients with end-stage renal disease treated by dialysis in a center in Israel.

The causes of death in 84 end-stage renal failure patients, treated with dialysis, who died during a 66-month period were reviewed retrospectively. Cardiac and infectious diseases were the main cause of death (27% each). These two constituted 44% of causes of death in hemodialysis and 75% in continuous ambulatory peritoneal dialysis patients. Malignant disease (7%) and hyperkalemia (5%) were responsible for death only in hemodialysis patients. Patients who died following hyperkalemia were younger than 50 years old. Patients who died from malignant disease were dialyzed for more than 3 years. In summary, the mode of dialysis therapy, age at start of therapy, time on dialysis, and previous cardiac disease may play a role in determining the causes of death in dialysis patients.

Overdiagnosis of hypertension in the elderly.

Seventeen untreated and 36 treated hypertensives aged 65 years or more were referred to our clinic because of repeated values of systolic blood pressure > or = 160 mmHg and diastolic blood pressure > or = 95 mmHg. All 53 patients underwent 24h blood pressure monitoring during their customary daily activities. Eleven (65%) untreated and 23 (64%) treated patients were normotensive during their daily activities. Thus, ambulatory BP monitoring appears to be useful in the elderly hypertensive patients in detecting those whose BP is elevated only in the clinic. Ambulatory BP obtained outside the clinic may be useful in diagnostic and therapeutic decision-making in the elderly population.

Enhanced urinary albumin excretion after 35 weeks of gestation and during labour in normal pregnancy.

This study reports on the urinary albumin to creatinine ratio during normal pregnancy, with special emphasis on the pre-delivery and labour periods. Albumin was determined in single voided urine specimens obtained from healthy non-pregnant women (n = 16) and healthy pregnant women (n = 203; Groups A and B, 133 females examined during clinic visits and presentation at obstetric department; Group C, 70 females examined during labour) by radioimmunoassay (RIA). The mean ratio (+/- SD) for albumin/creatinine (A/Cr) in non-pregnant women was 1.46 +/- 0.32 mg mmol-1 Cr. Thus, 2.10 mg mmol-1 Cr (mean+2 SD) was considered to be the upper limit of normo-albuminuria. During pregnancy, 73% of the women (97 out of 133, Groups A and B) excreted less than or equal to 2.10 mg mmol-1 Cr. During the first 35 weeks of gestation, 30 of 34 pregnant women (88%) excreted less than or equal to 2.10 mg mmol-1 Cr, the mean being 0.93 +/- 0.64 mg mmol-1 Cr (median 1.0 mg mmol-1). During 36-42 weeks of gestation, the median A/Cr was 1.93 mg mmol-1 Cr (range 0.43-12.16) and 32 of 99 (32%) had values greater than 2.10 mg mmol-1 Cr, an increase of more than two-fold (p less than 0.031) compared with the first 35 weeks. During labour, 61% of non-haematuric urines (33 of 54, Group C) were greater than 2.10 mg mmol-1 Cr, being 125% greater (p less than 0.006) than that observed during pregnancy. Thus in normal pregnancy, A/Cr is increased during the late period of pregnancy and during labour.

Evaluation of clinic blood pressure measurements: assessment by daytime ambulatory blood pressure monitoring.

The clinical value of a set of three clinical blood pressure measurements as a predictor of daytime ambulatory hypertension was assessed by performing a set of clinical blood pressure measurements in 171 borderline hypertensives, and calculating their diagnostic accuracy, sensitivity, specificity and predictive value compared to the daytime average of ambulatory blood pressure monitoring. Diagnostic accuracy was 0.63, sensitivity was 81% and specificity was 47%. Positive and negative predictive values were 0.60 and 0.74, respectively. The set of clinical measurements detected 81% of hypertensives, but 36% of the population screened was mislabelled--48 patients (28%) as hypertensive and 15 (8%) as normotensive. A single set of clinic blood pressure measurements is quite sensitive for diagnosing daytime hypertension, although its accuracy, specificity and predictive value are low. The subpopulation incorrectly labelled as normotensive may have a different prognosis and merits further prospective study.

Seven years of left ventricular pacing due to malposition of pacing electrode.

The case report is presented of a patient in whom an uncomplicated left ventricular transvenous pacing produced right bundle branch block (RBBB). A diagnostic echocardiography, confirmed by cine cardiovascular computed tomography, showed that there was no rupture of the right ventricle and diagnosed a left ventricular pacing, due to malposition of the pacing electrode. The patient was treated with aspirin and dipyridamole during the last 6 years of follow-up, without any complications, including 1 year of pacing, prior to admission.

Long-term antihypertensive and renal effects of isradipine in hypertensive patients with normal and reduced renal function.

The long-term hemodynamic and antihypertensive effects of isradipine were investigated in 11 patients who had normal renal function and 9 who had reduced renal function. The dose regimen was 1.25-5 mg twice daily, depending on blood pressure response. After 24 weeks of active treatment, systolic/diastolic blood pressure decreased from 172/106 to 155/94 mm Hg (p less than 0.05) in the patients with normal renal function, and from 176/105 to 169/93 mm Hg (p less than 0.01) in those with impaired renal function. Contrary to the results of short-term treatment, no changes in inulin and p-aminohippuric acid (PAH) clearances were observed in either study group. There were no significant changes in plasma renin, aldosterone, glucose, or lipids, nor were these changes in protein excretion in either group; however, sodium excretion increased significantly in both groups. On the basis of our results, we conclude that isradipine has a place in the treatment of hypertensive patients with mild renal insufficiency.

Inhibition of angiotensin converting enzyme by ramipril in serum and tissue of man.

Studies in animal models have indicated that ramipril is a potent inhibitor of angiotensin converting enzyme (ACE) in serum and tissue. In our study, the normal range of ACE activity and the inhibitory effect of short-term oral administration of ramipril on ACE activity in human serum and tissue samples of renal cortex, heart and blood vessels were determined. ACE activity in the renal cortex (125.2 +/- 11.5 nmol/mg per min) was greater than 600 times that of the heart (0.20 +/- 0.01 nmol/mg per min), greater than 500 times that of the veins (0.23 +/- 0.09 nmol/mg per min) and greater than 150 times that of the arteries (0.80 +/- 0.23 nmol/mg per min). ACE activity in the renal cortex and arteries 2 h after last dosing was almost completely inhibited by ramipril whereas ACE activity in the veins and heart was inhibited to a lesser extent. Our results demonstrate in man, for the first time, an inhibition of tissue ACE following short-term oral treatment with an ACE inhibitor.

Transfusion reactions due to bacterial contamination of blood and blood products.

Bacterial infections transmitted by blood or blood products, although rare, remain a serious threat to the recipient of a transfusion. We report on five cases of adverse reactions due to bacterial contamination of blood products, and we review 76 similar cases reported in the English-language literature. Most cases (70%) have been reported from the United States. Various sources of contamination have been suggested, including infection in the donor and invasion of the blood product during the process of collection, preparation, and storage. Frequent clinical manifestations are fever (80%), chills (53%), hypotension (37%), and nausea or vomiting (26%). The overall mortality is 35% (28 of 81 patients). In 38 patients (47%) the adverse reactions have appeared during transfusion; in the others the interval between completion of the transfusion and appearance of symptoms has ranged from 15 minutes to 17 days. A wide spectrum of bacteria have been implicated as causes of adverse reactions, with Pseudomonas species involved in 28% of episodes. Many such reactions are probably misdiagnosed or overlooked, the result being underestimation of the extent of the problem.

Risk factors for development of diabetic nephropathy and retinopathy in Jewish IDDM patients.

Risk factors associated with diabetic microvascular complications, with special reference to ethnic origin, were looked for in 231 young Jewish insulin-dependent diabetes mellitus (IDDM) patients with duration of diabetes greater than or equal to 10 yr. Median age at diagnosis of diabetes was 9.2 yr (range 0.04-26.2 yr), and median duration of the disease was 15.3 yr (range 10.0-37.2 yr). Sixty-three percent of the patients were Ashkenazi Jews, and 37% were non-Ashkenazi Jews. HbA1 was evaluated every 3 mo in the last 10 yr of follow-up, and albumin excretion rate was tested in three 24-h urine collections. Direct and indirect ophthalmoscopy was performed every year since diagnosis of diabetes, and if retinal pathology was suspected, color photographs were taken. Microalbuminuria was detected in 31% and macroalbuminuria in 7% of the patients. Nonproliferative and proliferative retinopathy was found in 44 and 12% of the patients, respectively. On logistic regression analysis, two variables were significantly and independently associated with diabetic nephropathy--non-Ashkenazi origin and mean HbA1 values over the first 5 of 10 yr of follow-up. Variables significantly and independently related to diabetic retinopathy were non-Ashkenazi origin, mean HbA1 values over the last 10 yr of follow-up, and duration of diabetes. Because non-Ashkenazi Jews in Israel are of lower socioeconomic status than Ashkenazi Jews, we stratified our patients according to their socioeconomic parameters, median HbA1 values, and duration of diabetes. Non-Ashkenazi patients were at a higher risk to develop complications in all strata.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute antihypertensive and renal effects of isradipine in hypertensive patients with normal and reduced renal function.

The renal effects of a single oral dose of placebo v a new dihydropyridine calcium antagonist, isradipine, were investigated in 12 patients with mild-to-moderate essential hypertension. Six patients (group A) had normal creatinine concentrations greater than 1.6 mg/dL. Patients maintained a constant daily intake of approximately 120 mmol of sodium and 50 mmol of potassium. Measurements were taken at 30, 60, and 90 min after drug administration. Results indicated that isradipine at a dose of 5 mg once daily produced significant antihypertensive and renal responses. In conclusion, there is therapeutic benefit with isradipine independent of the status of renal function.

Urinary albumin excretion in the healthy population.

In the present study reference values for the albumin excretion rate (AER) and the albumin/creatinine ratio (A/C) in overnight 8-h urine collections (n = 73, group 1) and in 24-h urine collections (n = 25, group 2) were obtained from healthy, nondiabetic, normotensive volunteers. Furthermore, we examined the relationship of these values to age, sex and ethnic group. Albumin was determined by RIA. The mean (+/- SD) values obtained for AER and A/C in overnight urine collections were 6.5 +/- 3.8 mg/24 h and 6.7 +/- 3.6 micrograms/mg creatinine, respectively. These values were significantly lower (P less than 0.001) than the values obtained in 24-h urine collections (AER 11.6 +/- 4.7 mg/24 h and A/C 10.9 +/- 5.0 micrograms/mg creatinine). No difference in AER was observed when the subjects were divided into 10-year age-groups. AER in males was similar to that in females, and AER in European subjects was not different from values obtained for subjects of Oriental (Middle Eastern or North African) origin. Freezing urine specimens resulted in a 25% decrease in AER values. We recommend using freshly obtained 8-h or 24-h urine collections, and considering the excretion of 14 mg/24 h (10 micrograms/min) or 21 mg/24 h (15 micrograms/min), respectively, as the upper limit of normoalbuminuria.

Cyclosporin A treatment enhances angiotensin converting enzyme activity in lung and serum of rats.

Nephrotoxicity and arterial hypertension are the most common side effects of treatment with cyclosporin A (CSA). Its effects on angiotensin converting enzyme (ACE) activity in the renal cortex, lung and serum of nephrotoxic rats have been investigated. Wistar rats were treated with CSA (20 mg kg-1 day-1 i.p.) or vehicle (olive oil containing 10% ethanol) for 14 days. On day 15, the rats were killed and ACE activity determined by radiometric assay using [3H]hippuryl-glycyl-glycine as substrate. CSA treatment resulted in a decrease in creatinine clearance, urine flow and body weight and a significant increase in serum and lung ACE activities (436 +/- 9 vs 391 +/- 7 nmol mL-1 min-1, P less than 0.001; 184 +/- 8 vs 142 +/- 10 nmol mg-1 min-1 P less than 0.01, respectively). In contrast, renal cortex ACE activity was reduced in the CSA-treated rats (0.35 +/- 0.02 vs 0.51 +/- 0.02 nmol mg-1 min-1, P less than 0.01). ACE activities in the renal cortex and serum were not affected by treatment with gentamicin (80 mg kg-1 day-1) for 11 days. In rats treated simultaneously with CSA and captopril (50 mg kg-1 day-1) ACE activity in the serum, lung and renal cortex was inhibited by 95, 93 and 92%, respectively. These changes in ACE activity were associated with a decreased systolic blood pressure in the rats receiving CSA and captopril. Therefore, ACE activity in the serum and lung of CSA-treated rats was increased, while its activity in the renal cortex was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy and tolerability of nifedipine (NIF) and nisoldipine (NIS) both alone and combined with a beta-blocker in patients with essential hypertension: a multicenter, parallel-group study.

We have assessed the efficacy and tolerance of Nifedipine twice daily and Nisoldipine once daily, both alone and in combination with a beta-blocker in 171 essential hypertensives in a randomized parallel comparison fashion. Both drugs were equally effective in lowering blood pressure: 72.6% of the subjects on Nisoldipine and 80.5% of those on Nifedipine reached a supine diastolic blood pressure less than or equal to 90 mmHg. Spontaneously reported side effects were frequent but no biochemical, hematological or electrocardiographic abnormalities were detected.

Inadvertent sulfonylurea-induced hypoglycemia. A dangerous, but preventable condition.

Two patients with severe hypoglycemia due to inadvertent use of oral hypoglycemic agents are described. Unintentional substitution of tablets with sulfonylurea drugs was related in both cases to a similarity in shape and color of the pills. In one case glyburide was interchanged with an artificial sweetener, while in the other case chlorpropamide was dispensed by a pharmacist instead of quinidine bisulfate. To our knowledge, 20 similar cases have been reported in the medical literature. Most of them were attributed to sound-alike trade names of drugs. Inadvertent sulfonylurea-induced hypoglycemia has to be included in the differential diagnosis of severe unexplained hypoglycemia. This dangerous condition can be prevented by instructing patients to carefully identify their drugs, introducing typed prescription forms using generic names, and avoiding similar names and appearance of pills.