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Biomedical subjects

V Popovic

Publications and source records attributed to V Popovic.

At least 55 records · Page 3Linked to original sources
PubMed1996

Evaluation of pituitary GH reserve with GHRP-6.

GH releasing peptides (GHRPs) were developed before the isolation and identification of GH releasing hormone (GHRH) in 1982 yet the clinical era of the GHRPs began in 1988. Since then clinical studies have been greatly extended. We studied the effects of GHRPs on GH release as a function of age, metabolic status and in different neuroendocrine pathologies. The different mechanism of action of GHRPs versus GHRH and the site of action have been addressed. There is a large variability in the stimulatory action of GHRH contrasted with the reproducibility of action of GHRPs. In different metabolic states GH response after GHRH is more impaired than after GHRP-6. On the other hand in different neuroendocrine pathologies GH response after GHRP-6 is more impaired than after GHRH. Each secretagogue provides separate information on GH secretion, necessary not only for linear growth but for general metabolism.

Endocrine System Diseases↗
PubMed1995

The effect of sodium valproate on luteinizing hormone secretion in women with polycystic ovary disease.

The aim of this study was to examine whether modulation of the GABA-ergic system (with sodium valproate) affects gonadotropin secretory frequency and amplitude in women with polycystic ovarian syndrome (PCOS). Six women aged 25 +/- 2 years with diagnosed PCOS and six healthy women aged 26 +/- 2 years at day 7-11 of menstrual cycle were included in the study. Sodium valproate 1200 mg p.o./day (600 mg t.i.d.) was administered for five days in both groups. Efficacy of treatment was assessed in women with PCOS by measuring six hour LH pulsatility (every .10 min), and by GnRH tests before and after treatment. Basal serum steroids were assessed as well. Hormones were determined by radioimmunoassay and pulse detection was carried out by the program PULSAR. The administration of valproate did not change basal serum LH concentration (9.1 +/- 0.6 vs 9.0 +/- 0.8 IU/L p > 0.05) nor LH pulse frequency (7.3 +/- 0.5 vs 6.3 +/- 0.5 p > 0.05) or the LH pulse amplitude (3.0 +/- 0.5 vs 3.5 +/- 0.4 p > 0.05). LH response to GnRH (mean peak 43.6 +/- 5.2 vs 44.1 +/- 6.0 IU/L p > 0.05) did not change either. Valproate did not affect the LH secretory activity in women with PCOS. There was no change in FSH, and prolactin secretion. In five patients with PCOS valproate caused further increase in serum testosterone level but this did not reach significance in the group as a whole (5.6 +/- 1.0 vs 9.1 +/- 2.0 nmol/L p > 0.05).

Adult↗
PubMed1995

Growth hormone secretion after the administration of GHRP-6 or GHRH combined with GHRP-6 does not decline in late adulthood.

OBJECTIVE: Growth hormone (GH) secretion in middle and late adulthood declines with age. However, the precise mechanisms causing this impairment in GH release are unknown. His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose related and specific manner in several species, including man. In order to gain a further insight into disrupted GH secretion in late adulthood, we evaluated GH responses to GHRP-6 or GHRH, administered either alone or in combination, in healthy young and late adulthood groups of subjects. DESIGN: All subjects underwent three different tests carried out in random order and separated by at least one week. Tests were performed at 0900 h after an overnight fast. GHRH (100 micrograms), GHRP-6 (90 micrograms) either alone or in combination were administered as an i.v. bolus. SUBJECTS: Groups of healthy young (mean +/- SEM 22 +/- 1.1 years, n = 9) and older adult subjects (59.5 +/- 1.7 years, n = 9) were studied. MEASUREMENTS: Serum GH levels were measured by radioimmunoassay. RESULTS: In the group of young adult subjects the combined administration of GHRH and GHRP-6 elicited a greater GH increase than GHRH alone (F = 21.9, P < 0.001) or GHRP-6 alone (F = 6.2, P = 0.01). Similarly, the response to the combined stimuli was also greater than with GHRH alone (F = 21.8, P < 0.001) or GHRP-6 alone (F = 23.9, P < 0.001) in the late adulthood group of subjects. GH responses to GHRH were greater in younger than in older subjects (F = 3.45, P = 0.03). In contrast, GH responses to either GHRP-6 (F = 0.71, P = NS) or combined GHRH plus GHRP-6 administration (F = 0.68, P = NS) were not significantly different between the two groups. CONCLUSIONS: These data show that GH responses to GHRP-6 are much greater than to GHRH in late adulthood. The marked increase of plasma GH levels observed after administration of GHRP-6 alone or in combination with GHRH indicates that impaired GH secretion in late adulthood is a functional and potentially reversible state.

Adult↗
PubMed1995

Early hypotony after trabeculectomy.

The occurrence of early hypotony after trabeculectomy was analysed retrospectively in 60 glaucoma patients. Fifty-two per cent of the eyes had an intraocular pressure < or = 10 mmHg on the first postoperative day. In about one-third of the eyes, the intraocular pressure was < or = 5 mmHg at the first postoperative visit and in more than 70% of these eyes the hypotony was almost unchanged one week after operation. The hypotony one week after operation was not correlated to the age of the patients and the intraocular pressure at operation, nor to the glaucoma type, and showed no significant statistical dependence on the depth of anterior chamber and hyphema. The final untreated intraocular pressure and progression of the postoperative cataract were studied in four groups of patients, formed on the basis of the intraocular pressure level one week after operation: patients with marked hypotony, slight hypotony, normal pressure or with hypertension. The final untreated intraocular pressure in the eyes with early marked hypotony was not significantly different from the final untreated intraocular pressures in the slightly hypotonic and normotonic eyes. However, the untreated intraocular pressures in these three eye groups were significantly different from the untreated intraocular pressure in the eye group with hypertension. Fifty-two per cent of the eyes suffered from cataract progression during a mean follow-up period of 24 months. Postoperative cataract progression in the markedly hypotonic eyes was not significantly different from the cataract progression in the other groups of eyes.

Adult↗
PubMed1995

Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP-6 main action is exerted at the hypothalamic level.

GH-releasing peptide (GHRP-6; His-D Trp-Ala-Trp-D Phe-Lys-NH2) is a synthetic compound that releases GH in a specific and dose-related manner through mechanisms and a point of action that are mostly unknown but different from those of GHRH. In man, GHRP-6 is more efficacious than GHRH, and a striking synergistic action on GH release is observed when GHRP-6 and GHRH are administered simultaneously. Based on such a synergistic action, it has been hypothesized that GHRP-6 acts through a double mechanism by actions exerted both at the pituitary and hypothalamic levels. The aim of the present study was 2-fold: 1) to further characterize the mechanism of action and synergistic effects of GHRP-6; and 2) to study its action in patients with hypothalamopituitary disconnection. Twelve patients with different neuroendocrine pathologies leading to a state of hypothalamopituitary disconnection (functional stalk section) and 11 age- and sex-matched normal controls were studied. Each subject underwent 3 tests on separate occasions, being challenged with GHRH (100 micrograms, i.v.), GHRP-6 (90 micrograms, i.v.), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE, micrograms per L/120 min). In normal subjects GH secretion was 483.7 +/- 99.2 after GHRH, 1434.8 +/- 393.0 after GHRP-6, and 3771.5 +/- 399.6 after GHRH plus GHRP-6; the level of GH secreted after GHRH plus GHRP-6 treatment was significantly (P < 0.05) higher than after the arithmetic sum of GH levels after both compounds administered separately. In the group of patients with hypothalamopituitary disconnection, the level of GH secreted after GHRH was similar to that in controls (423.4 +/- 62.8); however, a complete blockade was observed after GHRP-6 (97.3 +/- 7.9), significantly (P < 0.05) lower than after GHRH as well as lower than the GHRP-6-induced GH release in control subjects (P < 0.01). After GHRH plus GHRP-6, the patients with hypothalamopituitary disconnection showed severely reduced secretion (745.3 +/- 67.6; P < 0.01 vs. controls), a value that was not significantly different from the arithmetic addition of levels produced by both compounds administered separately.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Growth hormone (GH) secretion in active acromegaly after the combined administration of GH-releasing hormone and GH-releasing peptide-6.

His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (called GHRP-6) is a synthetic compound that releases GH in a dose-related, specific, and nonspecies-specific manner, through mechanisms different from those of GHRH. Being, normally, more potent than GHRH, GHRP-6 shows a striking synergistic action when administered simultaneously with GHRH, although the mechanisms and point of action of such a potentiating effect are unknown. The aim of the present study was 2-fold: 1) to further characterize the actions and mechanisms of GHRP-6 as well as its synergistic effects, and 2) to study its actions in acromegalic patients. Eleven acromegalic patients and 12 normal subjects, age and sex matched as controls, underwent 3 tests each on separate occasions, being challenged with GHRH (100 micrograms, iv), GHRP-6 (90 micrograms, iv), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE; micrograms per L/120 min). In normal subjects, GH secretion was 686 +/- 227 after GHRH, 1787 +/- 510 after GHRP-6, and 4111 +/- 671 after GHRH plus GHRP-6; the level of GH secreted after GHRH plus GHRP-6 treatment was significantly (P < 0.05) higher than the arithmetic sum of GH levels after both compounds administered separately. In acromegalic patients, the level of GH secreted after GHRH was 1468 +/- 499, that after GHRP-6 was 2595 +/- 762, and that after GHRH plus GHRP-6 was 4949 +/- 1043; this last value was not significantly different from the arithmetical addition of levels produced by both compounds administered separately. These results indicate that GH-secreting pituitary adenomas respond surprisingly well to either GHRH or GHRP-6 despite being deprived for long periods (even years) of the physiological regulation exerted by the hypothalamus. In addition, the synergistic action of GHRH plus GHRP-6 was observed in normal subjects, but not in acromegalic patients. These results suggest that GHRP-6 does not need to operate through hypothalamic factors to exert its GH-releasing action, even for eliciting a greater response than GHRH. On the other hand, the synergistic effect of GHRH plus GHRP-6 appears to need the cooperation of the hypothalamus, but how this occurs is still undetermined.

Acromegaly↗
PubMed1993

Propofol anaesthesia reduces early postoperative emesis after paediatric strabismus surgery.

Propofol anaesthesia may reduce postoperative emesis. The purpose of this study was to compare the incidence of emesis after propofol anaesthesia with and without nitrous oxide, compared with thiopentone and halothane anaesthesia, in hospital and up to 24 hr postoperatively, in outpatient paediatric patients after strabismus surgery. Seventy-five ASA class I or II, unpremedicated patients, aged 2-12 yr were randomly assigned to one of three groups: Thiopentone, 6.0 mg.kg-1 i.v. induction followed by halothane and N2O/O2 for maintenance (T/H); propofol for induction, followed by propofol and oxygen for maintenance (P/O2); and propofol for i.v. induction, followed by propofol infusion and N2O/O2 for maintenance (P/N2O). All received vecuronium, controlled ventilation, and acetaminophen pr. Morphine was given as needed for postoperative analgesia. There were no differences in age, weight, number of eye muscles operated upon, duration of anaesthesia or surgery. The P/N2O group (255 +/- 80 micrograms.kg-1 x min-1) received less propofol than the P/O2 group (344 +/- 60 micrograms.kg-1 x min-1) (P < or = 0.0001) and had shorter extubation (P < 0.001) and recovery (P < 0.01) times. Emesis in the hospital, in both the P/N2O (4.0%) and P/O2 group (4.0%) was less than in the T/H group (32%) (P < 0.01). Antiemetics were required in four patients in the T/H group (16.0%). Overall emesis after surgery was not different among the groups: T/H (48%), P/O2 (28%) and P/N2O (42%). The use of propofol anaesthesia with and without N2O decreased only early emesis. This supports the concept of a short-acting, specific antiemetic effect of propofol.

Ambulatory Surgical Procedures↗
PubMed1993

Onset of maximum neuromuscular block following succinylcholine or vecuronium in four age groups.

BACKGROUND: Increasing age appears to be associated with a slower onset of neuromuscular blockade, but such an effect has not been studied with the same doses of the same drugs across pediatric and adult age groups. METHODS: The authors measured the evoked compound action potential of the adductor pollicis muscle in response to 0.1-Hz stimulation of the ulnar nerve, during fentanyl-thiopental-oxygen anesthesia, in 160 patients aged 1-3 yr, 3-10 yr, 20-40 yr, or 60-80 yr. Subparalyzing doses of vecuronium (0.03 mg/kg) or succinylcholine (0.3 mg/kg), or paralyzing doses of vecuronium (0.1 mg/kg) or succinylcholine (1.0 mg/kg), were administered to ten patients in each age group. RESULTS: Onset time, defined as the time from injection to maximum depression of response with a subparalyzing dose or the time from injection to ablation of visible response with a paralyzing dose, varied with age in all groups (P < 0.001). For 0.3 mg/kg succinylcholine, it increased from 49 +/- 6 s in 1-3-yr-old patients, to 104 +/- 9 s in 60-80-yr-old patients (P < 0.00001). For 0.03 mg/kg vecuronium, onset time was 3.6-5.9 times longer than for succinylcholine, increasing from 219 +/- 15 s in 3-10-yr-old patients to 473 +/- 30 s in 60-80-yr-old patients (P < 0.00001 by linear regression). For paralyzing doses, succinylcholine 1.0 mg/kg had an onset time of 58 +/- 7 s and 95 +/- 7 s, in 1-3-yr-old and 60-80-yr-old patients, respectively (P < 0.001). For 0.1 mg/kg vecuronium, onset time varied between 125 +/- 19 s in 1-3-yr-old patients to 295 +/- 31 s in 60-80-yr-old patients (P < 0.00001), and was 2.1-3.3 times longer than 1 mg/kg succinylcholine. CONCLUSIONS: Increasing age is associated with slower onset for both succinylcholine and vecuronium. When equipotent, subparalyzing doses of succinylcholine and vecuronium are compared, onset time is 4.5 times as long with vecuronium.

Adult↗
PubMed1993

Modulation by glucocorticoids of growth hormone secretion in patients with different pituitary tumors.

The acute administration of glucocorticoids is a new stimulus of growth hormone (GH) secretion in man. In order to ascertain its point of action, and also the suitability of this new test as a diagnostic tool in GH pathological states, 33 subjects were studied. Eight of them were normal controls, and 25 were patients with tumors affecting the hypothalamopituitary area. A glucocorticoid stimulus, dexamethasone 4 mg i.v. was administered at 0 min and GH levels (means +/- SEM, microgram/l) were measured during the following 5 h. In addition, GH-releasing hormone (GHRH) and clonidine were employed as either pituitary or hypothalamic GH stimuli. Dexamethasone administration to normal subjects did not alter GH levels in the first 2 h of the test. Afterwards, a GH peak was observed around the third hour, GH levels returning to basal ones thereafter. The dexamethasone-induced GH peak (6.7 +/- 1.5) and area under the curve (526 +/- 137) were lower than after GHRH (14.0 +/- 4.5 and 1,070 +/- 369, respectively). In the 14 acromegalic patients studied, the GHRH-induced GH net increase was similar to that observed in controls, while the placebo did not alter GH basal levels. An absence of hypothalamic control was evident because clonidine did not stimulate GH release. On the other hand, and contrary to normal subjects, dexamethasone strongly inhibited GH secretion, the values being significantly lower when calculated either as mean GH peak, or maximum GH increment (delta). The delta GH was -2.5 +/- 3.1 after placebo, +3.7 +/- 4.5 after clonidine, +17.0 +/- 3.3 after GHRH and -13.4 +/- 4.5 following dexamethasone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1992

Proceedings of the discussion, "Tolerability and safety of Sandostatin".

Side effects of octreotide may be local, biochemical, gastroenterological, or endocrinological. Local pain at the injection site occurs frequently, but rarely lasts more than 15 minutes and often resolves with continued therapy and may be improved if the vial is warmed prior to injection. No long-term hematological or biochemical abnormalities have been described. Despite initial diarrhea in some patients, no change in circulating fat-soluble vitamins has been consistently reported. Antibodies to octreotide have been described, but are rare. Abdominal pain or diarrhea can occur at the beginning of therapy. These symptoms rarely persist and are minimal if the injections are timed between meals, but this may increase the incidence of gallstones. Gallstones occur with increased frequency. Gastritis has been described as being an invariable consequence of long-term treatment with octreotide. We have found the incidence to be increased in patients on octreotide, but this is not invariable. Hypoglycemia may be exacerbated in some patients with insulinoma because of glucagon suppression. Small numbers of patients on octreotide for acromegaly have developed hypoglycemic. Conversely, carbohydrate tolerance may temporarily worsen because of insulin suppression and rarely oral hypoglycemia drug therapy may become necessary. Most frequently, carbohydrate tolerance does not deteriorate. In some patients with acromegaly, pituitary tumor size may continue to increase despite continued therapy. Last, there is the theoretical risk of addiction to a compound which may act through opiate receptors and considerably alleviates headache in some patients with pituitary tumor. Overall, despite the multiplicity of theoretical side effects, the majority of patients tolerate octreotide well, with no serious untoward effects.

Abdominal Pain↗
PubMed1992

Further evidence for differential regulation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH): increased FSH and decreased LH levels in a patient with familial pure gonadal dysgenesis.

There is experimental evidence that a portion of follicle-stimulating hormone (FSH) secretion is independent of hypothalamic influences. A 29 year old woman with familial pure gonadal dysgenesis developed myelodysplastic syndrome. Endocrine investigations showed discrepancy between serum FSH and luteinizing hormone (LH) levels. FSH levels remained elevated while LH levels decreased. The FSH to LH ratio was 10 (normal 2-2.5). The fall in LH is likely to be due to factor(s) involved directly and specifically in LH synthesis and release. Exogenous LH releasing hormone administration as well as hormonal replacement treatment increased LH levels. The FSH to LH ratio decreased to 7. This case supports the hypothesis of differential regulation of FSH and LH, and that FSH secretion is at least partly autonomous.

Adult↗
PubMed1991

Propofol and spontaneous movements: an EEG study.

Spontaneous movements during induction of anesthesia with propofol were studied in 21 children aged 6-12 yr. The children were randomly assigned to group A (propofol 3 mg.kg-1), B (propofol 5 mg.kg-1), or C (thiopental 5-7 mg.kg-1). A baseline electroencephalogram (EEG) was recorded during 10 min in children awake, supine with eyes closed and opened, and then from the beginning of induction until 5 min after tracheal intubation. Spontaneous movements were observed in all children in group A but only in 14% in groups B and C. The induction EEG sequences were similar for the three groups: after a mean latency of 12 s, the tracing showed an increase in frequency from 9 to 10 Hz (alpha waves) to more than 14 Hz (beta waves). This transition lasted approximately 2 s, followed by delta waves (2-3 Hz) that continued for 1-2 min. Finally, beta waves reappeared and progressively but incompletely replaced delta waves during the next 5 min. Neither spikes, spike-wave patterns, rhythmic theta waves, nor burst suppressions were observed. Spontaneous movements were recorded on videotape and analyzed after the completion of the study by a neurologist unaware of patient treatment. Videotape analysis of the periinduction period showed spontaneous movements to be dystonic and choreiform with flexion, twisting, or extension movements of all extremities. All movements occurred coincident with the appearance of delta waves on the EEG. Their dystonic nature and the absence of EEG abnormalities suggest a subcortical origin and argue against associated cortical epileptic activity.

Anesthesia↗
PubMed1991

GH response to growth hormone releasing hormone and hypoglycaemia is unaltered by high endogenous plasma calcitonin levels in patients with medullary thyroid carcinoma.

OBJECTIVE: As it has previously been reported that calcitonin suppresses stimulated growth hormone release, we have studied the serum growth hormone response to growth hormone releasing hormone and insulin-induced hypoglycaemia in patients with high calcitonin levels due to medullary carcinoma of the thyroid. DESIGN: Growth hormone releasing hormone (100 micrograms i.v.) and insulin (0.15 units/kg i.v.) were given and the growth hormone responses in the patients with medullary carcinoma of the thyroid and normal healthy controls were compared. PATIENTS: Eight with histologically confirmed medullary thyroid carcinoma, two females and six males, aged 21-77 years, were studied and compared with seven healthy age and sex matched controls. MEASUREMENTS: Growth hormone and calcitonin were measured. RESULTS: No significant difference was found between the growth hormone responses observed in patients with medullary carcinoma when compared with normal controls either after GHRH or during insulin-induced hypoglycaemia. CONCLUSION: We conclude that calcitonin does not alter the pituitary response to GHRH in medullary thyroid carcinoma and is unlikely to play an important role in regulating growth hormone secretion because calcitonin did not modify the release of growth hormone after insulin-induced hypoglycaemia.

Adult↗
PubMed1991

Long-term outcome following trabeculectomy: I Retrospective analysis of intraocular pressure regulation and cataract formation.

Decrease of intraocular pressure (IOP) and the occurrence of cataract were analysed in 75 patients of a community-based material followed for 6-12 years after trabeculectomy. IOP was controlled (less than or equal to 21 mmHg) with or without additional treatment in approximately 90% of the eyes, both at 5 years and at the last visit. The share of eyes requiring no medication for IOP control decreased linearly with time from approximately 90 to 60% between one and 10 years postoperatively. Thirty-eight per cent of the patients without cataract at the time of operation suffered from cataract development during follow-up. The prevalence of dense cataract producing severe visual loss at the last visit was 47%. The occurrence of cataract was correlated with the age of patients at operation. Cataract formation showed no relationship of statistical significance with preoperative treatment, with time since surgery, the magnitude of preoperative IOP and the reduction of postoperative IOP.

Aged↗