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Biomedical subjects

V Plavsić

Publications and source records attributed to V Plavsić.

At least 19 recordsLinked to original sources

Xerostomia in patients with triple A syndrome--a newly recognised finding.

Triple A syndrome is characterised by achalasia, alacrima, adrenal insufficiency and progressive neurological abnormalities including impaired autonomic nervous function. We present five patients with triple A syndrome in whom we describe xerostomia for the first time, a symptom which was presumed to be practically exclusive to Sjøgren syndrome and familial dysautonomia. Conclusion We recommend the investigation of salivation in all patients with triple A syndrome and treatment of xerostomia in order to ease swallowing. Further, our results corroborate earlier doubts that some patients with Sjøgren syndrome, especially those with the so-called "achalasia sicca" syndrome and adrenocortical insufficiency, actually had triple A syndrome. Therefore, adrenocortical function should be assessed in all patients with Sjøgren syndrome, particularly in those with difficulties in swallowing, because even latent adrenocortical insufficiency could be life-threatening for these patients in stressful situations.

Adolescent↗

Clinical and morphological features of undifferentiated monomorphous GH/TSH-secreting pituitary adenoma.

A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.

Adenoma↗

Nevo syndrome.

We report on a patient with Nevo syndrome manifesting intrauterine and postpartum overgrowth, accelerated osseous maturation, dolichocephaly, highly arched palate, large, low-set ears, cryptorchidism, delayed neuropsychological development, hypotonia, adema, contractures of the hands and feet, a single a transverse palmar crease, and tapering digits. After meningococcal sepsis at age 6 months, he remained decerebrate. Thereafter, overgrowth and especially weight gain were extremely accelerated until his death at age 18 months, at which time his height was 103 cm and his weight was 23 kg. In addition to low plasma concentrations of growth hormone and insulin-like growth factor, severe insulin resistance was observed. It is presumed that a selective defect in insulin-stimulated glucose uptake, with preservation of anabolic effect, was one of the causes of his "overgrowth without growth hormone," at least in the last 12 months of life after severe brain damage.

Blood Glucose↗

Analysis of the in vitro secretory activity of human pituitary adenomas: modification of corticotropin release from adenoma tissue explant cultures by addition of a human plasma ultrafiltrate bioactive fraction.

The lack of control of tumour behaviour is manifested in different ways, depending primarily on the type of tumour. This results in numerous problems of tumour diagnosis and therapy. In the case of "benign" tumours, like pituitary adenomas, in vitro studies are often used for evaluation of the tumour. The use of tissue explant cultures of human pituitary adenomas and the comparison of the feature of cultured tumours with their behaviour in vivo showed that corticotropin is released not only from the tumours associated with Cushing's disease, but also from clinically non-functioning tumours. Hence, it was supposed that the release of corticotropin in vivo from non-secreting tumours is probably under the influence of certain neuroendocrine and/or systemic humoral factors. To test this possibility, samples of 22 tumours were cultured in plain culture medium or in the presence of the "human plasma ultrafiltrate bioactive fraction" (tentatively termed as TBP) prepared by anion-exchange chromatography. In the presence of TBP the release of corticotropin was strongly inhibited in adenomas showing relatively high spontaneous secreting activity in vitro (> 200 ng/l in 24 hours), while immunohistochemistry of these tumours indicated accumulation of corticotropin inside the cells. In contrast, TBP stimulated corticotropin release from tumours that showed relatively low basic corticotropin release (< 200 ng/l in 24 hours), with no obvious change in cellular corticotropin immunoreactivity. Such a dual activity of TBP was not observed for 8 samples of adenomas cultured in the presence of surrounding pituitary tissue, probably because TBP did not affect corticotropin secretion by the normal pituitary cells (as indicated by immunohistochemistry). From these results, it appears that TBP could be one of the humoral factors involved in the regulation of corticotropin release from pituitary adenoma tissue. Its possible involvement in the regulation of corticotropin release from normal pituitary tissue, however, is uncertain.

Adenoma↗

[Biosynthesis of steroids in the adrenal gland].

Cholesterol and steroid hormone biosynthesis, enzymes which catalyze each step in the biosynthesis, their localization and the genes that encode them are presented. The simplified mechanism of the enzyme cytochrome P450 action is described. It comprises alternative oxidation and reduction of flavoprotein adrenodoxin reductase, adrenodoxin and cytochrome P450. delta 4 and delta 5 pathways for androgen biosynthesis and an alternative biosynthetic pathway for aldosterone and cortisol biosynthesis are also described.

Adrenal Cortex Hormones↗

Effects of ritanserin, a specific serotonin-S2 receptor antagonist, on the release of anterior pituitary hormones during insulin-induced hypoglycemia in normal humans.

The role of serotonin in the insulin hypoglycemia (IH) stimulated secretion of prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH) and cortisol (F) was studied in a group of 12 normal subjects during the control period after placebo and a consecutive six-day treatment with 20 mg ritanserin (RIT) per day. RIT failed to affect the baseline levels of all the four hormones as well as the PRL response to IH (p > 0.5). The serum GH response to IH was moderately diminished after RIT, the reduction of integrated trapezoidal area under hormone curves (nAUC) being 50.7% +/- 6.9% (p < 0.005). Furthermore, RIT was found to slightly decrease the plasma ACTH response to IH, the reduction of nAUC being 36.3% +/- 2.6% (p < 0.005). Decrease in the corresponding plasma F response to IH was accompanied by 29.1% +/- 2.4% reduction of nAUC (p < 0.005). According to our results, serotonin-S2 receptors appeared to be moderately involved in IH-induced release of GH, but slightly in that of ACTH, leaving unaffected that of PRL.

Adult↗

Effects of ritanserin, a novel serotonin-S2 receptor antagonist, on the secretion of pituitary hormones in normal humans.

The availability of a new potent and selective serotonin-S2 antagonist, ritanserin (RIT), encouraged us to further investigate the effect of serotonin on the basal secretion of anterior pituitary hormones in normal humans. Administered in a single 30-mg dose to group 1 consisting of 10 normal women, RIT failed to affect the baseline LH, FSH, GH or TSH levels. In group 2 consisting of 20 normal subjects (ten males and ten females), the same dose of RIT decreased in parallel both ACTH and cortisol levels but only at 180 min. Group 3 consisting of 8 normal men was studied on three separate occasions seven days apart: each subject received graded doses of 10 mg, 20 mg and 30 mg RIT. The mean baseline PRL concentration at 180 min as well as the net integrated area under the hormone curve (nAUC) decreased only after the highest dose, while the baseline cortisol concentrations at 180 min as well as the corresponding nAUC values displayed a clear dose-dependent response. The findings indicated the serotonin-S2 receptors to be only partially involved in the basal secretion of ACTH in normal humans.

Adolescent↗

Effect of propranolol on urinary prostaglandin E2 excretion and renal interlobar arterial blood flow after furosemide administration in patients with hepatic cirrhosis.

The effect of propranolol on furosemide-stimulated urinary prostaglandin E2 (PGE2) excretion and renal blood flow was evaluated in 12 patients with alcoholic liver cirrhosis. Plasma and urine were collected before and 60 min after furosemide 20 mgI with or without propranolol pretreatment, and plasma renin activity (PRA), plasma aldosterone concentration (PAC), urinary excretion of PGE2 and sodium were determined. The renal interlobar arterial Pulsatility Index (PI), as an index of resistance to blood flow, was also determined before and 60 min after furosemide administration with and without propranolol pretreatment, by using a duplex Doppler ultrasound (Hitachi EUB 565). Urine volume and sodium excretion after furosemide administration were not influenced by the propranolol pretreatment. Furosemide administration significantly increased urinary PGE2 excretion, PRA and PAC, and these effects were significantly reduced by propranolol. Furosemide administration with or without propranolol significantly reduced renal interlobar arterial PI, the average reduction in PI being significantly lower after furosemide administration with propranolol pretreatment. The results demonstrate that propranolol pretreatment significantly influenced the furosemide-induced increase in urinary PGE2 excretion and renal interlobar arterial blood flow in cirrhotic patients.

Adult↗

Adrenocorticotropic hormone insensitivity associated with autonomic nervous system disorders.

Five children with adrenocorticotropic hormone (ACTH) insensitivity associated with autonomic nervous system disorders are described. At the time of diagnosis, four of them had osteoporosis. The fifth patient died and skeletal roentgenograms were not done. Osteoporosis was subsequently discovered in one of our previously reported patients with ACTH insensitivity. We assume that osteoporosis is, at least partly, the result of decreased adrenal androgen production. Human leucocyte antigen typing failed to establish any linkage.

Adrenal Cortex Function Tests↗

An update on the frequency of nonclassic deficiency of adrenal 21-hydroxylase in the Yugoslav population.

Nonclassic steroid 21-hydroxylase deficiency is an attentuated adrenal enzyme defect that is commonly the basis of hyperandrogenic syndromes. Inherited as an autosomal recessive trait, it is known to occur with high frequency in the general population and with increased frequency in a number of ethnic groups, including the Yugoslav population. Following expansion of the original data on 21 families in Croatia to a total of 49 Croatian and Serbian families, we establish that this enzymatic disorder is increased in this Slavic population and provide an updated estimate for the gene frequency of 0.092 (0.035-0.149). Also in keeping with earlier reports, we continue to note the absence of association between nonclassic 21-hydroxylase deficiency occurring among Yugoslavs and HLA-B14; DR1.

17-alpha-Hydroxyprogesterone↗

Some aspects of adrenocortical stress response following stroke.

Stress response measured as the cortisol secretion rate as well as urinary 17 oxogenic steroid (17 OGS) and 17 oxosteroid (17 OS) excretion was investigated in a group of 28 patients with stroke (11 with hypertensive intracerebral hemorrhage and 17 with ischemic cerebrovascular insult). Significantly higher cortisol secretion values were found in the group of patients who died (p less than 0.01). Similarly, the first day urinary 17 OGS excretion pointed to the greater adrenocortical response in patients who died (p less than 0.05). Urinary 17 OS excretion was normal or below normal in the majority of patients and no difference was found between either male or female patients who survived or died. Our findings indicate that adrenocortical changes which maximize the production of cortisol are operative soon after the onset of stroke. The cortisol secretion rate appeared to be a good indicator of the severity of the stress caused by stroke and may be useful in predicting the prognosis of the illness.

17-Hydroxycorticosteroids↗

Absent spermatogenesis despite early bilateral orchidopexy in 17-ketoreductase deficiency.

We describe a 26-year-old patient with 17-ketoreductase deficiency who was raised as a male from 8 months and whose left testis was brought down at the age of 2.5 years and the right testis at the age of 4. Despite the early orchidopexy and not significantly decreased serum testosterone, he was sterile, and biopsy of the testes at the age of 26 revealed absence of spermatogenesis. This case indicates that the absence of spermatogonia in previously reported patients whose testes remained undescended until a later age could not be attributed solely to cryptorchidism. We suggest that decreased intratesticular testosterone due to steroidogenic defect in the developing testis mainly contributes to the arrest of spermatogenesis.

17-Hydroxysteroid Dehydrogenases↗

'Cryptic' form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in the Yugoslav population.

Five individuals with the asymptomatic, 'non-classical', 'cryptic' form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OH) deficiency from 5 unrelated families were discovered during hormonal studies and HLA-typing performed in a series of 24 families with CAH due to 21-OH deficiency. Four of the 5 individuals with the 'cryptic' form of CAH belong to families where the index case was a patient with the classical form of CAH due to 21-OH deficiency. The fifth one originated from a family where the index case was a girl with the 'non-classical', 'late-onset' form of the disease. All the 5 individuals had no clinical symptoms in spite of clearcut biochemical signs of 21-OH deficiency: increased 17-OH-progesterone (17-OHP), dehydroepiandrosterone and androstenedione levels, particularly after ACTH-stimulation. The 17-OHP response upon ACTH stimulation of heterozygotes for this 'non-classical' form of 21-OH deficiency did not differ from the response of heterozygous individuals for the classical form of the disease. The results of this study confirm the hypothesis that individuals with the 'cryptic' form of CAH due to 21-OH deficiency are genetic compounds bearing one allele for the severe, classical form, and on the homologous locus, another one for the mild 'non-classical' form of CAH due to 21-OH deficiency. Their genotype was 21-OH severe/21-OH mild.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗