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)

Proteinuria in benign nephrosclerosis.

Benign nephrosclerosis seldom is associated with significant proteinuria or reduced renal function. This study demonstrated that, despite the finding of benign nephrosclerosis on a renal biopsy specimen, concomitant proteinuria is predictive of a poor prognosis. Twelve patients, ranging in age from 24 to 59 years, with hypertension, proteinuria (greater than 1 g/d), and findings of benign nephrosclerosis on renal biopsy specimens were studied retrospectively. In three of these patients, the hypertension and proteinuria were diagnosed during pregnancy. Follow-up was possible in 11 patients. Nine patients became nephrotic in the course of their disease. Two patients had endstage renal disease and required maintenance dialysis treatment. Seven patients had decreased renal function as shown by the increase in serum creatinine levels. Thus, the combination of hypertension, proteinuria (greater than 1 g/d), and benign nephrosclerosis may be indicative of a progressive condition with a high percentage of patients having renal failure.

Ultrasonography in the diagnosis and follow-up of hepatic sinusoidal dilatation.

Hepatic sinusoidal dilatation is a rare complication of oral contraceptive use. A 29-year-old woman who had been taking oral contraceptive pills for eight years was found to have persistently elevated erythrocyte sedimentation rates and alkaline phosphatase levels, hepatomegaly, diffuse hepatic sinusoidal dilatation, and a large nonhomogeneous hyperechogenic lesion in the right hepatic lobe. The abdominal ultrasonogram, liver size, erythrocyte sedimentation rates, and alkaline phosphatase levels reverted to normal within 24 months after discontinuing oral contraceptives. This case should encourage the use of abdominal ultrasonography in detection and follow-up of hepatic sinusoidal dilatation.

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.

Unintentional weight loss. A retrospective analysis of 154 cases.

Unintentional weight loss (UWL) was documented in 154 patients (2.8%) admitted to an internal medicine department during a two-year period. A retrospective analysis of the clinical charts showed that more than one third (36.3%) were found to have a neoplasm, involving preponderantly the gastrointestinal tract. Patients with neoplasia were older and more frequently had abnormal physical findings and significantly lower values of serum albumin as well as higher values of alkaline phosphatase than other patients. Despite extensive investigations, in 36 patients (23.3%) UWL remained unexplained even after prolonged follow-up periods. The remaining 62 patients had a variety of disorders, preponderantly gastrointestinal tract (26 patients) and psychiatric (16 patients) diseases. Endocrinologic disorders such as diabetes mellitus and hyperthyroidism were relatively uncommon (3.8%). Unintentional weight loss is a relatively common problem in clinical practice. Familiarity with the spectrum of disorders associated with UWL as well as selected clinical and laboratory values may help in the initial examination of these patients.

Once-a-day pindolol in hypertension.

The possibility of using pindolol on a once-a-day schedule was investigated in the treatment of mild to moderate hypertension. Eighteen patients whose blood pressure responded satisfactorily to thrice-daily administration has a similar response to the single daily dose (p greater than 0.05). The advantages of once-daily pindolol therapy as well as some of the biochemical changes produced by the drug are commented upon.

Effects of pindolol on renal function.

Because beta blockers have been shown to reduce glomerular filtration rate (GFR), the renal effect of intravenous and prolonged oral administration of pindolol was examined in 10 patients with essential hypertension. Intravenous pindolol decreased inulin clearance from 99 to 94 ml/min/1.73 m2 (p < 0.005), and pulse rate from 75 to 69/min (p < 0.005). Blood pressure and filtration fraction were not changed. Oral pindolol (10 to 20 mg/day) for a mean of 6 mo resulted in a decrease in mean blood pressure from 124 to 111 mm Hg (p < 0.001), in mean pulse rate from 76 to 69/min (p < 0.005), and in mean plasma renin activity (PRA) from 0.9 to 0.29 ng/ml/hr (p < 0.05). Inulin clearance and filtration fraction did not change. At the end of oral therapy, intravenous pindolol induced a greater reduction in inulin clearance than in the first study. These observations indicate that intravenous pindolol induces a decrease in GFR probably secondary to hemodynamic effects. On the other hand, prolonged oral pindolol has no effect on GFR despite decreases in blood pressure, pulse rate, and PRA.

Effects of pindolol on renal function II. Effects on intravenous and prolonged oral dosing.

Effects of intravenous and long-term oral dosing with pindolol on renal function were examined in eight hypertensive patients with reduced renal function. (Inulin clearance ranged from 40.5 to 84.5 ml/min/1.73 m2.) Intravenous pindolol resulted in decreased mean heart rate (74.3 to 67 bpm) and decreased mean inulin clearance (66 to 60.5 ml/min/1.73 m2.) Blood pressure and renal plasma flow did not change significantly. Long-term oral pindolol depressed blood pressure and heart rate, but mean inulin clearance was unchanged and renal blood flow and plasma volume increased. A second intravenous pindolol dose, given while the patients were receiving oral doses, resulted in nonsignificant decreases in glomerular filtration rate and renal plasma flow, but no change in blood pressure and heart rate. We conclude that prolonged pindolol dosing in patients with reduced renal function had no effect on renal function. When the drug was given intravenously there were small decreases in glomerular filtration rate and renal plasma flow.

Elevation of serum potassium during beta blockade: absence of relationship to the renin-aldosterone system.

Eighteen patients with essential hypertension were treated in a single-blind, crossover study with pindolol and with propranolol. The two drugs were compared because of known differences between them on renin secretion. We noted that plasma renin activity and plasma aldosterone concentration were suppressed by propranolol but not by pindolol. Blood pressure was reduced about equally by both drugs. Serum potassium levels rose in 17 patients on pindolol (p < 0.001) and in 14 patients on propranolol (p = 0.08). Our data suggest that serum potassium elevations induced by beta blockade do not depend on the renin-angiotensin-aldosterone system. Alternative possibilities are discussed.

Effect of nifedipine and theophylline in asthma.

The effect of nifedipine, 10 mg po q.i.d. for 2 weeks, was studied in a randomized, double-blind, crossover trial in nine patients with asthma receiving theophylline. Nifedipine did not significantly affect the mean (+/- SD) morning peak expiratory flow rate (PEFR; 336 +/- 130 L/min for drug vs. 349 +/- 92 L/min for placebo), evening PEFR (393 +/- 69 L/min for drug vs. 367 +/- 66 L/min for placebo), symptom score (27.4% +/- 22.9% for drug vs. 33.8% +/- 26.4% for placebo), or the number of albuterol inhalations per day (5.8 +/- 3.5 for drug vs. 6.2 +/- 4.1 for placebo). Furthermore, there was no change in PEFR 30, 60, or 120 minutes after nifedipine dosing. Nifedipine did not significantly affect the steady-state serum theophylline trough levels (9.1 +/- 2.2 mg/ml for drug vs. 10.2 +/- 1.9 micrograms/ml for placebo) or the theophylline pharmacokinetic parameters, such as the elimination t1/2, peak serum concentration, time to peak, and AUC(0-24). We conclude that nifedipine has little, if any, effect on the clinical status, PEFR, or theophylline serum levels in patients with asthma who receive theophylline.

Reduction of serum theophylline levels by terbutaline in children with asthma.

We studied the effect of oral terbutaline on serum theophylline levels in 12 children with asthma. Sustained-release theophylline (10 mg/kg twice a day) was given with placebo or terbutaline (0.075 mg/kg three times a day) in a chronic, randomized, double-blind, crossover design. The trough serum theophylline concentration fell from 13.8 +/- 4.0 to 10.8 +/- 3.6 micrograms/ml and the peak expiratory flow rate increased from 285 +/- 30 to 310 +/- 29 L/min after terbutaline. Further investigation is needed to clarify the mechanism of action by which terbutaline decreases serum theophylline levels.

Hyperammonemia complicating mesenteric vein thrombosis.

Hyperammonemic coma developed in a 69-year-old woman with prolonged symptoms of abdominal pain, dysphagia, and fever. At laparotomy for an acute condition within the abdomen, mesenteric vein thrombosis was found and partial intestinal resection was performed. Following surgery, the patient regained consciousness and blood ammonia levels became normal. Hyperammonemia and coma complicating mesenteric vein thrombosis have not yet been described. Venous shunts are suggested as being responsible for this rare complication.

Lymphoma presenting with adrenal insufficiency. Adrenal enlargement on computed tomographic scanning as a clue to diagnosis.

A 73-year-old woman who presented with primary adrenal insufficiency and enlarged adrenal glands on computed tomographic scanning was ultimately found to have a large-cell lymphoma that had initially involved the adrenals and the stomach. A search of the English language medical literature revealed only seven other cases of lymphoma presenting with hypoadrenalism, none of which involved the stomach. As in this case, in most of those cases adrenal enlargement was documented on computed tomographic scanning. Despite its rare occurrence, lymphoma should be searched for in patients presenting with Addison's disease and enlarged adrenal glands.

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.

Clearance of Tc-99m DTPA in hemodialysis and peritoneal dialysis: concise communication.

The clearance of Tc-99m DTPA was studied in 14 patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). Mean Tc-99m DTPA clearance during HD was 37.8% +/- 10.1 of creatinine clearance. Mean Tc-99m DTPA clearance in PD was 65.1% +/- 10.3 of creatinine clearance. Tc-99m DTPA, with a larger molecular weight than that of creatinine, is cleared relatively better during PD than during HD. Thus Tc-99m DTPA may be used in the assessment of the effectiveness of different dialytic treatments for substances of similar molecular weight. In addition, our study shows that clearance of DTPA both in HD and PD is sufficiently high to allow the removal of this chelating agent in patients with renal failure.

Ethambutol-induced thrombocytopenia.

Extreme thrombocytopenia, purpura, and melena developed in a 71-year-old woman four days after ethambutol administration was started. The macrophage inhibition factor test was positive for ethambutol, and the thrombocytopenia subsided shortly after discontinuation of the drug therapy. The sequence of events in this patient suggests that, although previously unreported, thrombocytopenia should be added to the list of side effects of ethambutol.

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.

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.

Labetalol in the treatment of essential hypertension: a single-blind dose ranging study.

The hypotensive efficacy of labetalol was evaluated in 29 patients with essential hypertension in a single-blind dose ranging study. After a two-week period of placebo treatment, labetalol was given in oral doses of 0.6 g/d, 0.8 g/d, and 0.8 g/d combined with 25-50 mg/d of hydrochlorothiazide. Each regimen lasted four weeks. The decrease in blood pressure was dose dependent: 90% of patients showed a significant reduction in diastolic blood pressure and 75% showed a significant reduction in systolic blood pressure. In 69% of the patients, side effects of the drug were noted, and in five patients (17%), treatment was discontinued because of the side effects. Seven patients received labetalol intravenously before the oral treatment. Their heart rate and blood pressure reductions were similar to those found in patients only taking the medication orally. We conclude that labetalol is an efficient and safe antihypertensive agent in both oral and intravenous administration. However, the high incidence of side effects makes labetalol a drug of second choice in uncomplicated hypertensive patients.

Aquarium-borne Mycobacterium marinum skin infection. Report of a case and review of the literature.

A 33-year-old fish fancier developed a protracted skin infection that ultimately was found to be caused by Mycobacterium marinum. The organism was isolated from the lesion as well as from infected fish taken from his home aquarium. The lesion resolved after a six-week course of oral sulfamethoxazole and trimethoprim. Forty-four additional cases of culture-proved M marinum skin infections acquired from aquariums and reported in the English-language literature are reviewed. Almost universally, the lesions remained circumscribed and were either single nodular (14 patients) or multiple sporotrichoid (31 patients). Diagnosis was supported by acid-fast smears (15 patients) and isolation of the organism from skin lesions (43 patients) or from fish (two cases). In vitro studies, as well as clinical outcomes, suggest sulfamethoxazole-trimethoprim or ethambutol hydrochloride plus rifampin to be the drugs of choice.