Plasma glycohydrolase levels in patients with type 1 diabetes at onset and in subjects undergoing an intravenous glucose tolerance test.

The effect of hyperglycemia and insulin deficiency on the plasma level of lysosomal glycohydrolases, namely N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase, and alpha-D-glucosidase, was investigated. Two patient groups were assessed: (1) 28 children with type 1 diabetes at onset (fasting blood glucose, 444+/-154 mg/100 mL; hemoglobin A1c, 11.9%+/-2.4%; symptom duration, 15.9+/-8 days; and absence of complications), (2) 14 adult subjects undergoing an intravenous glucose tolerance test (IVGTT), consisting of 8 non-obese subjects (body mass index, 26+/-0.04 kg/m2; fasting blood glucose, 82+/-13 mg/100 mL; blood insulin, 6+/-0.04 mU/L) and 6 obese subjects (fasting blood glucose, 97+/-3.5 mg/100 mL; blood insulin, 27+/-6 mU/L, with normal oral glucose tolerance test). Enzyme activity was determined with the fluorimetric method. The mean level of all evaluated enzymes was significantly increased in patients with type 1 diabetes at diagnosis compared with normal controls. Increased enzyme levels were also detected in the group of adults undergoing an IVGTT in whom hyperglycemia was accompanied by insulin resistance (ie, obese subjects). Glycohydrolase abnormalities appear to be related to insulin deficiency rather than hyperglycemia. Lysosomal apparatus abnormalities seem to be an inherent feature of diabetes that is present at disease onset. The possible role of insulin in the regulation of plasma glycohydrolase levels is discussed.

Alterations in the activity of several glycohydrolases in red blood cell membrane from type 2 diabetes mellitus patients.

The erythrocyte membrane in 71 patients with type 2 diabetes mellitus was assessed for glycohydrolase activity: N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, alpha- and beta-D-galactosidase, alpha- and beta-D-glucosidase, alpha-D-mannosidase, and alpha-L-fucosidase. Only beta-D-glucuronidase, alpha-D-glucosidase, and beta-D-glucosidase showed markedly elevated levels with respect to the controls regardless of the presence of complications. Among the examined patients, those with good metabolic control (not yet submitted to any therapy) showed the same enzyme levels as the reference subjects, while the levels in patients with unsatisfactory metabolic control (treated with oral hypoglycemic and/or insulin) significantly differed from the control levels. For alpha-D-glucosidase and beta-glucosidase, a correlation with glycemia and the parameters of metabolic control was also evidenced. Alterations of beta-D-glucuronidase, alpha-D-glucosidase, and beta-D-glucosidase were also ascertained in the plasma of the same diabetic patients according to the literature; each enzyme correlated with the other, either in plasma or in the erythrocyte membrane. This study shows a correlation between plasma and erythrocyte membrane levels for these three enzymes. The strict parallelism of the glycohydrolases in the two different compartments provides a profile of these enzymes in the pathology of diabetes.

Abnormal response to exercise in middle-aged NIDDM patients with and without autonomic neuropathy.

The cardiovascular response to exercise in middle-aged non-insulin-dependent diabetes mellitus (NIDDM) patients and the potential role of clinical characteristics and autonomic function were evaluated. One hundred and eight NIDDM patients, aged 40-65 years, were compared with a control group of 112 subjects, matched by age, sex, physical fitness, and presence of hypertension. All subjects performed a maximal exercise test. The diabetic patients completed cardiovascular autonomic neuropathy (CAN) tests: deep breathing, postural hypotension and lying to standing. There were no significant differences in total work capacity, heart rate, and blood pressure, either at rest or at peak exercise between the two groups. Diabetic patients showed significantly lower values of systolic and diastolic blood pressure during exercise, significantly slower recovery of heart rate (at 5th minute the average values were 102.7 +/- 14.1 beats min-1 vs 91.9 +/- 11.1, p < 0.001); and significantly higher proportion of blunted increase of heart rate (9.2% vs 0.9%, p < 0.001) and systolic blood pressure (9.2% vs 0.7%, p < 0.001) during exercise. No correlation between the exercise results and the main clinical characteristic (presence of hypertension, BMI, duration of diabetes, treatment, microalbuminuria, total score of CAN) was observed. These findings suggest that the cardiovascular response to exercise could be impaired also in the absence of signs of CAN. This impairment was higher in patients showing a dysfunction of orthosympathetic activity.

Effects of ibopamine in combination with furosemide on renal function in patients with chronic congestive heart failure.

The effects of ibopamine and furosemide on renal function given alone and in combination at single doses were studied in 6 men and 6 women aged 45 to 73 years with chronic congestive heart failure of NYHA class II. After 3 days of dietary stabilization, the patients received either ibopamine 200 mg, furosemide 40 mg, or furosemide 40 mg plus ibopamine 200 mg with 2-day washout between treatments, according to a double-blind, balanced three-way crossover design using all possible treatment sequences. On each treatment day urine collections were performed at 2-hourly intervals from 2 h before to 6 h after dosing, and urine volume and Na+, K+, Cl-, and creatinine concentrations were measured for every period. The patients received a standardized breakfast 3 h before treatment and then were allowed 250 ml tap water to drink before starting each urine collection period. Venous blood samples were taken before breakfast and midway between each urine collection period for analysis of serum Na+, K+, Cl-, creatinine, and glucose. Heart rate, blood pressure, and physical signs were recorded 2, 1 h, immediately before, and then 0.5, 1, 2, 3, 4, 5, and 6 h after treatment. At the same times the patients were asked for any symptoms. The time course of the diuretic effect of furosemide 40 mg was consistent with the data reported by other authors.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum enzymes of lysosomal origin as indicators of the metabolic control in non-insulin-dependent diabetics.

Several lysosomal enzymes (beta-N-acetyl-D-glucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase, beta-D-galactosidase, alpha-D-glucosidase, beta-D-glucosidase, alpha-L-fucosidase and alpha-D-mannosidase) were determined in the serum of 54 non-insulin-dependent diabetics with different degrees of metabolic control and without complications and in 18 non-insulin-dependent diabetics with complications. The serum levels of beta-N-acetyl-D-glucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase, and alpha-D-mannosidase were significantly (p less than 0.01) higher in the diabetics without complications. The levels of beta-N-acetyl-D-glucosaminidase and beta-D-glucuronidase were inversely proportional to the degree of metabolic control, in a statistically significant manner. Moreover the levels of these enzymes decreased to normal values during a 2-month period of controlled oral hypoglycemic drug-diet therapy resulting in metabolic compensation. The presence of complications was indicated by a further increase of serum beta-N-acetyl-D-glucosaminidase and beta-D-glucuronidase; however the portion of lysosomal enzyme activities due to complications remained unchanged after controlled therapy aimed at compensating the metabolism. The conclusion is drawn that in non-insulin-dependent diabetics, as already shown for insulin dependent-diabetics, serum lysosomal enzymes, especially beta-N-acetyl-D-glucosaminidase and beta-D-glucuronidase, are good intraindividual indicators of the metabolic control of the disease.

[Cardiotoxicity of 5-fluorouracil. Personal cases and review of the literature]. / Cardiotossicità da 5-fluorouracile. Casistica personale e revisione della letteratura.

Two cases of 5-Fluorouracil (5FU) cardiotoxicity, chest pain with changes in ECG the former, and myocardial infarction the latter, are described. Review of literature shows the existence of 49 cases of cardiotoxicity due to 5FU (38 angina = 77.5% 8 myocardial infarction = 16.3%). This complication seems due to a "coronary toxicity" whose onset is very precocious and not dose-dependent. Since 5FU therapy could result very dangerous when cardiotoxicity occurs, it is strictly advisable to withdraw further administration of the drug. As a matter of fact 18 patients out of 21 who again were treated with 5FU, had more serious complications which resulted in 3 myocardial infarctions (2 deaths).

Retroperitoneal nodal aplasia, asplenia, chylous effusion and lymphatic dysplasia: an acquired immunodeficiency syndrome?

Two adult patients (one in Italy and the other in the USA) are described with similar findings of paraaortic nodal aplasia, asplenism, multiple serous and chylous effusions, and retroperitoneal lymphatic dysplasia. Although the clinical courses are incomplete, this unusual constellation of signs in the setting of normal peripheral lymph trunks suggest an acquired rather than inborn anomaly and possibly a variant acquired immunodeficiency syndrome.