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Biomedical subjects

M Nesović

Publications and source records attributed to M Nesović.

At least 19 recordsLinked to original sources

Effect of insulin sensitivity on pulsatile insulin secretion.

OBJECTIVE: The aim of the study was to determine whether derangements in insulin pulsatility are related to the presence of insulin resistance or whether these changes occur only in non-insulin-dependent diabetes mellitus (NIDDM). DESIGN AND METHODS: The study included 26 obese, 11 NIDDM and 10 control subjects. The obese group was divided into a low insulin (plasma insulin <20 mU/l, OLI, 14 subjects) and a high insulin (OHI, 12 subjects) group. For pulsatility analysis blood was sampled every 2 min for 90 min. Pulsatility analysis was carried out using the PulsDetekt program. The insulin secretion randomness was quantified using interpulse interval deviation (IpID) and approximate entropy (ApEn). ApEn and ApEn normalized by s.d. of the individual insulin time series (nApEn) were calculated. Lower values of ApEn and IpID indicate more regular secretion. Homeostasis model assessment (HOMA) was used to quantify insulin sensitivity. RESULTS: Insulin pulses were significantly less regular in the OHI and the NIDDM groups compared with the control and the OLI groups (control: ApEn 0.54+/-0.16, nApEn 0.69+/-0.19, IpID 2.53+/-0.99; OLI: ApEn 0.64+/-0.12, nApEn 0. 79+/-0.15, IpID 2.92+/-1.09; OHI: ApEn 0.88+/-0.07, nApEn 0.92+/-0. 07, IpID 3.95+/-0.84; NIDDM: ApEn 0.92+/-0.16, nApEn 0.99+/-0.09, IpID 4.41+/-0.53; means +/- s.d.). There was no difference in the pulse regularity between the OHI and the NIDDM groups. CONCLUSIONS: Decrease in insulin sensitivity was correlated with the reduction of insulin secretion regularity. Therefore irregular insulin secretion is related to a reduction in insulin sensitivity, and it is not unique to NIDDM.

Adult↗

Influence of three-week fasting on gonadotropin pulsatility in obese menstruating women.

OBJECTIVE: To evaluate the influence of three-week fasting on gonadotropin pulsatility in extremely obese women of reproductive age. DESIGN: Prospective study of 21-day fasting (400 kcal/day), under medical supervision. SUBJECTS: 20 females, average age of 35.1 +/- 5.9 y, and average BMI of 41.19 +/- 8.39 kg/m2, with regular menstrual cycles (26-34 days). The mean weight loss was 12.5 +/- 3.23 kg. MEASUREMENTS: Blood samples for LH and FSH were taken between 4th and 7th day of the menstrual cycle, before and in the first cycle immediately after weight reduction, for 6 h, starting at 09.00 with 10 min intersample intervals. Pulsatility analysis was done using Pulsar program. Statistical analysis was done using Wilcoxon's matched pairs signed ranking test and McNemar's test. RESULTS: There was no statistically significant difference (p > 0.05) in LH and FSH pulsatile secretion before and after diet including the number of pulses, amplitudes, interpulse intervals and peak lengths. There were no disturbances of menstrual cycle during or after the diet. CONCLUSION: These results suggest that a 21-day fast, accompanied with significant weight loss, does not affect gonadotropin pulse pattern in follicular phase and normal menstrual cycle length in extremely obese females of reproductive age, compared with the pattern before diet.

Adult↗

Microalbuminuria is associated with salt sensitivity in hypertensive patients.

We have investigated 59 patients with mild-to-moderate uncomplicated essential hypertension in order to estimate whether salt sensitivity is associated with greater urinary albumin excretion. Patients whose average mean blood pressure (BP) value on day 5 of the high-sodium regimen (300 mmol/l NaCl) exceeded 10 mm Hg or more than that on day 5 of the low-sodium regimen (40 mmol/l NaCl) were classified as salt sensitive. We have demonstrated that salt sensitive patients (n = 29) manifest greater urinary albumin excretion than salt resistant patients (51.5 +/- 15 vs 11.5 +/- 12.8 mg/24h). Hypertensive patients selected as salt sensitive had a longer duration of hypertension (87 +/- 62 vs 41.5 +/- 33.6 months); greater body mass index (BMI) (29.0 +/- 4.7 vs 24.7 +/- 3.6 kg/m2); lower urinary excretion of sodium after 3 days of sodium loading (172.1 +/- 23.3 vs 245.8 +/- 21.6 mmol/day); and slightly, but significantly higher mean BP (121.3 +/- 7.4 vs 115.3 +/- 5.3 mmHg) than salt resistant patients (n = 29). Nevertheless, there was no significant correlation between duration of hypertension and the degree of urinary albumin excretion in salt sensitive patients. On the other hand, a significant correlation was demonstrated in a group of salt resistant hypertensive patients, suggesting that salt sensitivity could be linked with an early tendency to abnormal albumin excretion, while in salt resistant patients it may depend on hypertension-related renal disfunction. Therefore, measurement of microalbuminuria in patients with essential hypertension can be a useful marker for salt sensitivity.

Adult↗

[The effect of cilazapril and prazosin on insulin sensitivity in patients with essential hypertension].

Two groups of drugs are actual for improving effects of insulin in vivo: alpha-1-adrenergic blockers and angiotensin-converting-enzyme-inhibitors. The objective of this study was to examine short-term effects of cilazapril and prazosin therapy on insulin sensitivity assessed by a 15' test of insulin tolerance of obese hypertensive persons. In groups of 8 patients insulin tolerance was tested prior to and 7 days after therapy by cilazapril dosed to 2.5 mg a day and prazosin 3 mean 1-2 mg a day. In this way satisfactory control of arterial tension was achieved. No significant changes of coefficient which enable assessment of insulin effects in vivo were established. However, in the group treated with cilazapril there were 6 out of 8 patients in whom coefficient increase was registered, so that among groups there was a significant difference in coefficient change in regard to therapy with better cilazapril effects.

Angiotensin-Converting Enzyme Inhibitors↗

[Free urinary cortisol in the diagnosis of hypercorticism].

24 hour urinary free cortisol has lower values in suspect obese patients compared to patients with Cushing's syndrome. The most favourable discriminatory border value of urinary cortisol is 100 micrograms/24 hours, giving the most valid differentiation of obese patients suspected for Cushing's syndrome from patients with hypercortisismus. Free cortisol has far expressive discriminatory value compared to 17-OHCS, and it is a good screening test in differential diagnosis of obese suspected patients from patients with Cushing's syndrome.

Cushing Syndrome↗

Daily profiles of aldosterone levels during normal, high and low sodium intake in patients with essential hypertension.

The episodic secretion of aldosterone depends on the dietary sodium intake, alterations in posture and follows ACTH circadian rhythm. Aldosterone daily profiles have been studied in 23 supine essential hypertensive patients on normal sodium intake. Secretory pulses at a frequency of two to five pulses per 12 hr have occurred, independent of PRA levels. Among 13 patients with normal PRA two lost pulsatility when sodium was loaded (10 g/24 hr) and the same happened with two others on sodium restricted diet (2 g/24 hr). These results suggest a profound effect of dietary sodium intake on the pulsatile pattern of aldosterone secretion, particularly in normal PRA essential hypertension.

Adult↗

How reliable is the euglycaemic hyperinsulinemic clamp test for the confirmation of autonomous endogenous hyperinsulinemia?

Inhibition of C-Peptide secretion by exogenous insulin was studied during euglycemic clamp in 13 patients with histologically verified causes of organic hyperinsulinaemia (10 with beta cell adenoma; 2 with beta cell carcinoma and 1 with beta cell hyperplasia) and in 10 healthy controls. Euglycemic clamps were performed using artificial endocrine pancreas (Clamp Mode 9:1) while insulin infusion (Humulin Normal-Lilly) rate was 0.1 U/kg BW/h. Blood samples for serum insulin (RIA INEP) and C-Peptide (RIA-Biodata) were taken at 0; 30; 60; 90 and 120 min. Statistical analysis was done using SPSS on IBM-PC with Wilcoxon sum rank test and one way ANOVA. All the patients were studied before the operation and in four of them clamp studies were repeated after the operation. Statistically significant suppression of C-Peptide values in 120 min was established in the control group (p less than 0.05) while there was no significant suppression in insulinoma group (p greater than 0.05), except in one patient with beta cell hyperplasia. Various types of responses (suppression, no change, paradoxical increase) were observed after the operation in the insulinoma group. Possible mechanisms and the meanings of the absence of insulin induced C-Peptide suppression in insulinoma group are discussed. It is concluded that euglycemic hyperinsulinemic clamp study could be useful and a complementary test to other established tests for the confirmation of the diagnosis of insulinoma. Further work on beta cell response after the operation in patients with insulinoma is necessary.

Adenoma↗

A comparison among the effectiveness of growth hormone suppression in active acromegaly of bromocriptine and long acting somatostatin analogue (SMS 201-995).

The aim of our study was to compare the effectiveness of bromocriptine vs. long acting somatostatin analogue (SMS 201-995) on growth hormone suppression in active acromegaly. A twenty year old female, student of law, was previously treated with Parlodel LA 50 mg i.m. injection and then with bromocriptine 30 mg orally for 2.5 years because of active acromegaly and very large intrasellar and suprasellar pituitary adenoma. She was partial bromocriptine responder with mean growth hormone levels prior the treatment 30 mU/L and after bromocriptine 13.7 mU/L and with gross tumor shrinkage. Since she failed to restore menstrual cycles, had clinical signs of the disease, she was taken off bromocriptine and treated with somatostatin analogue (SMS 201-995) 300 mcg s.c. daily and 400 mcg s.c. daily with mean growth hormone levels 10 mU/L. She was also treated with combined treatment (400 mcg s.c. SMS 201-995 plus 30 mg bromocriptine orally) and mean growth hormone levels were 11 mU/L. SMS 201-995 had a long lasting inhibitory effect on growth hormone secretion in acromegaly (p less than 0.01) but in comparison to daily growth hormone levels during bromocriptine treatment no difference was found (p greater than 0.01). Combined treatment with SMS 201-995 and bromocriptine did not achieve greater suppression of daily growth hormone levels than those achieved with SMS 201-995 alone (p greater than 0.1) or with bromocriptine alone (p greater than 0.05). No significant tumor shrinkage during chronic SMS treatment was seen. Severe clinical and biochemical signs of hypoglycaemia were registered on one occasion only during the first month of treatment with SMS 201-995.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

Hypersensitivity reaction with intravenous GnRH after pulsatile subcutaneous GnRH treatment in male hypogonadotrophic hypogonadism.

Chronic pulsatile subcutaneous administration of low doses of gonadotrophin releasing hormone (GnRH) is an effective therapy for men with hypogonadotrophic hypogonadism. Hypersensitivity reactions to GnRH are rare. We wish to report hypersensitivity reactions with intravenous GnRH after low dose subcutaneous pulsatile GnRH treatment in two men with hypogonadotrophic hypogonadism due to suprasellar disease.

Adolescent↗

Nicardipine versus nifedipine: multicentre controlled trial in essential hypertension.

Ninety-five hypertensive outpatients of both sexes, aged 23 to 65 years with diastolic blood pressures above 105 but below 120 mmHg (greater than 14.0 but less than 16.0 kPa), after one week on a placebo were randomly assigned either to nicardipine plus a placebo (40 mg/day - 48 patients) or nifedipine sustained-release plus a placebo (20 mg/day - 47 patients) for an additional six weeks. The study groups were homogeneous and comparable. After the run-in period the average blood pressure was 181 +/- 17/116 +/- 9 mmHg (24.1 +/- 2.3/15.5 +/- 1.2 kPa) in the nicardipine and 177 +/- 22/116 +/- 9 mmHg (23.6 +/- 2.9/15.5 +/- 1.2 kPa) in the nifedipine group (p greater than 0.10). In the acute oral test (nicardipine 40 mg to all the subjects; blood pressure measured at 30 min intervals during two hours) almost identical hypotensive effects within and between groups were observed (mean arterial pressure decrease of 11%, after 120 min; p less than 0.05). At the end of this trial blood pressure decreased further to 152 +/- 12/94 +/- 11 mgHg (20.3 +/- 1.6/12.5 +/- 1.5 kPa) (mean decrease of 20%; p less than 0.01) on nicardipine and to 145 +/- 12/94 +/- 11 mmHg (19.3 +/- 1.6/12.5 +/- 1.5 kPa) (mean decrease of 20%; p less than 0.01) on nifedipine. There were no significant changes in pulse rate. The observed between-group differences were trivial (p greater than 0.10). The laboratory data did not alter appreciably during this study. Three patients on nicardipine and four on nifedipine reported headache, palpitations and flushing: one patient on nicardipine and two on nifedipine were as a result excluded from the trial. It was concluded that nicardipine and nifedipine sustained-release were comparably effective and well-tolerated drugs suitable as the first-line agents for the management of mild to moderate hypertension.

Administration, Oral↗

The prolactin response to TRH and domperidone does not differentiate male hypothalamic hypogonadism and constitutional delay of puberty.

In order to test whether prolactin response to challenge with TRH and domperidone, dopamine receptor antagonist, is diagnostic for idiopathic hypothalamic hypogonadism (IHH) we studied 8 normal controls, 9 subjects with delayed sexual development and 6 patients with IHH. TRH test (200 micrograms i.v. bolus) and domperidone (10 mg i.v. bolus) were given on two different days. Prolactin (RIA-Biodata) was determined in blood samples during the test. The basal value of prolactin in subjects with delayed puberty and healthy controls did not differ from basal values of prolactin in patients with IHH. The peak elevation of prolactin after TRH in subjects with delayed puberty and healthy controls did not differ from that in patients with IHH. After successful treatment of one patient with IHH (Kallmann's syndrome) with pulsatile s.c. LHRH we did not find any change in the response of prolactin to TRH challenge after 1, 3 and 6 months of treatment, while prolactin response to domperidone increased. Prolactin responses to TRH and domperidone are not differential for the early diagnosis of IHH. Successful treatment of a patient with IHH did not change the response of prolactin to TRH, but increased prolactin response to domperidone possibly due to altered steroid milieu.

Adolescent↗

Chronic bromocriptine treatment and glucose intolerance in acromegaly.

Blood glucose, plasma GH, insulin and glucagon levels during OGTT before and after treatment with bromocriptine (20 - 40 mg daily 3 - 18 months) were studied in 12 nondiabetic acromegalics (NA) and 6 diabetic acromegalics (DA) not treated previously. There was no significant change in blood glucose levels before and after treatment in NA while blood glucose levels fell significantly in DA after treatment. Mean basal GH levels and after OGTT decreased significantly in NA group, while only in the 120 min of OGTT in DA group. There was no significant change in mean basal or glucose stimulated plasma insulin or glucagon levels before and after treatment in both non-diabetic and diabetic acromegalics. Normal glucagon levels in diabetic acromegalics prior to treatment is considered as relative hyperglucagonaemia which disappeared after treatment. We did not show that glucagon suppressibility after OGTT was reestablished after treatment with bromocriptine in non-diabetic and diabetic acromegalics. Other factors than changes in hormones should be considered as a cause of restored glucose tolerance.

Acromegaly↗