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A G Smals

Publications and source records attributed to A G Smals.

At least 73 records · Page 4Linked to original sources
PubMed1990

Differential metabolism of pregnenolone by testicular homogenates of humans and two species of macaques. Lack of synthesis of the human sex pheromone precursor 5,16-androstadien-3 beta-ol in nonhuman primates.

In previous reports we described the early time sequence in in vitro [4-14C] pregnenolone metabolism in human and rat testicular homogenates and, apart from a difference in the preferred route of the conversion of pregnenolone to testosterone, we demonstrated the presence of delta 16-synthetase activity in human but not in rat testes. In the study of testicular function higher monkeys are increasingly used as a model for human reproduction. The availability of testes from 2 different species of macaques (rhesus and crab eating monkeys) enabled us to compare the in vitro metabolism of pregnenolone in these testes with human testes. The pattern obtained in both monkey species were very similar, but completely different from those found in man. The delta 4 pathway was the preferred route for the conversion of pregnenolone to testosterone in the monkeys tested, the delta 5 pathway in the humans. delta 16-Synthetase activity, a prerequisite for the synthesis of the sex pheromone precursors 5,16-androstadien-3 beta-ol and 4,16-androstadien-3-one, was clearly measurable in the human but not in the monkey testicular homogenates. So far, man and boar are the only species harbouring delta 16-synthetase activity in their testes. These in vitro data indicate that the nonhuman primates studied are not suitable models for the study of human testicular function.

Androstenols↗
PubMed1990

Postprandial exocrine pancreatic function during long-term treatment with the somatostatin analogue SMS 201-995 in acromegalic patients.

Long-term treatment with the somatostatin analogue SMS 201-995 (SMS) might impair exocrine pancreatic function, secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP), and pancreatic size. In five acromegalics on chronic treatment with SMS, we investigated postprandial 6-h urinary excretion of p-aminobenzoic acid (PABA) and p-aminosalicylic acid (PAS) after s.c. injection of 100 micrograms SMS or placebo and after ingestion of 2 mmol nBT-PABA and 2 mmol PAS. In the acromegalics, urinary PABA/PAS ratio (reflecting exocrine pancreatic function) after SMS was similar to that after placebo (P greater than 0.10) and higher than in healthy volunteers (n = 8, P = 0.05). The initial inhibition of plasma CCK secretion by SMS was cancelled during the 3rd h after the meal, whereas PP release remained completely abolished. Pancreatic size as measured by ultrasonography, was not reduced in seven acromegalics compared with 14 healthy volunteers. It is concluded that despite a blunted release of the trophic hormone CCK, long-term treatment with SMS 201-995 neither induces an abnormally small pancreas nor deterioration of postprandial exocrine pancreatic function in patients with acromegaly.

4-Aminobenzoic Acid↗
PubMed1990

Pancreatic exocrine and gallbladder function during long-term treatment with octreotide (SMS 201-995).

Since octreotide (SMS 201-995, Sandostatin; Sandoz Pharmaceuticals) is a potent inhibitor of pancreatic exocrine secretion and gallbladder contraction, long-term treatment with this drug may theoretically result in impaired pancreatic function and gallstones. However, we observed excellent pancreatic exocrine function--as assessed by the PABA/PAS test--in acromegalics who received octreotide treatment for more than 6 months. Plasma cholecystokinin showed a significant, although blunted, postprandial response, which exceeded the threshold for gallbladder contraction in healthy controls. Remarkably, postprandial gallbladder contraction was completely abolished for at least 2 h during octreotide treatment. In contrast to other studies, none of 16 acromegalic patients on long-term octreotide treatment developed gallstones. Although the incidence of gallstones in patients on long-term octreotide treatment may be increased, the risk seems to be variable.

4-Aminobenzoic Acid↗
PubMed1990

Lack of antibody formation during long-term subcutaneous treatment with the somatostatin analogue octreotide in acromegaly.

Serum samples from 13 patients with active acromegaly on long-term sc treatment with octreotide (SMS 201-995, 1-36 months, mean daily dose 285 micrograms) were taken 12 h after the injection of their regular evening doses. Octreotide assay was performed using 125I-Tyr-SMS and a polyclonal rabbit anti-serum. For assessment of antibody formation both serum coated charcoal adsorption (adsorption of free octreotide) and polyethylene glycol precipitation (precipitation of IgG complexes) were used. The mean binding percentage in the patients proved to be similar to that of 5 healthy volunteers (p greater than 0.10). No specific binding was detected, whatever method used. No correlation was found between the binding percentages and octreotide serum levels, duration of octreotide treatment or daily octreotide dose (p greater than 0.10). These results strongly suggest that clinically relevant endogenous antibody formation is not a frequent event during long-term sc treatment of acromegalic patients with octreotide.

Acromegaly↗
PubMed1990

Concentrations of total and free dehydroepiandrosterone in plasma and dehydroepiandrosterone in saliva of normal and hirsute women under basal conditions and during administration of dexamethasone/synthetic corticotropin.

Using a specific and sensitive radioimmunoassay involving extraction with diethyl ether and chromatographic separation of steroids, we measured concentrations of salivary and plasma dehydroepiandrosterone (DHEA) in 22 women with normal ovulatory cycles (ages 18-45 years). Salivary DHEA values closely correlated with total and free DHEA in plasma. In the follicular phase the mean concentrations of salivary and plasma free DHEA were virtually equal [mean (SD): 0.61 (0.32) and 0.56 (0.34) nmol/L, respectively]. In the luteal phase, salivary DHEA slightly exceeded the plasma free DHEA [0.68 (0.40) vs 0.56 (0.38) nmol/L, P less than 0.01]. Also, during combined dexamethasone/synthetic corticotropin administration in 25 patients with androgenizing disorders and in 10 normal subjects (each in the follicular and luteal phases), the concentration of DHEA in saliva strongly correlated with total and free DHEA in plasma. During these dynamic tests, the mean concentrations of free DHEA in plasma and salivary DHEA in the hirsute women were significantly higher than the mean concentrations in the control women at all times before and after corticotropin infusion (P less than 0.05- less than 0.0001). In contrast, plasma total DHEA in patients exceeded nonhirsute values only at 15 min after corticotropin administration. In six of 25 patients total DHEA during combined administration of dexamethasone/synthetic corticotropin exceeded normal values by at least 2 SD. The response of salivary and free DHEA to synthetic corticotropin in this subgroup was also excessive.

Adrenocorticotropic Hormone↗
PubMed1989

Does SMS 201-995 normalize growth hormone secretion in acromegaly? GH day profiles and GH concentrations after oral glucose loading.

GH secretion in acromegaly was studied in 8 patients before and during treatment with SMS 201-995, a somatostatin analogue, 100 micrograms twice daily, by evaluating GH day profiles and GH suppressibility after oral glucose tolerance tests (OGTT). Normalization of GH secretion, estimated by OGTT, was only observed in the three patients who had a decrease in plasma GH to less than 2 micrograms/l after SMS 201-995 injection, and who had the lowest mean plasma GH levels during the day and the largest percent decline of mean plasma GH levels. We conclude that real normalization of GH secretion during SMS 201-995 therapy only occurs in a subset of patients. The data illustrate that the applicability of the generally held cut-off value of 5 micrograms/l, between normal and abnormal plasma GH, has to be reconsidered in the case of chronic intermittent subcutaneous therapy with SMS 201-995.

Acromegaly↗
PubMed1989

The mechanism of the synthesis of 16-androstenes in human testicular homogenates.

The biochemical pathway leading to the 16-unsaturated C19 steroids--known as sex pheromone (precursors) in pig and man--is still a matter of dispute. In the 16-ene-synthetase process, via which 5,16-androstadien-3 beta-ol (ADL) or 4,16-androstadien-3-one (ADN) are biosynthesized from pregnenolone (P5) or progesterone (P4), a number of 2 or even 3 step conversions have been suggested in porcine tests, including 20 beta-reduction, 21-hydroxylation and 16,17-dehydrogenation. Studying the 16-ene-synthetase reaction in human testicular homogenates, we adduced evidence for the hypothesis that ADL is synthesized from P5 in a single step, not requiring separate intermediates. Our proposal for the 16-ene-synthetase mechanism also explains why, at least in our hands, synthesis of ADL is always accompanied by co-synthesis of its satellite 5-androstene-3 beta,17 alpha-diol (epiA5): both steroids are synthesized as a mere consequence of the fact that the proposed elimination and substitution reactions for the synthesis of ADL and epiA5, respectively, are competitive processes.

Androstenes↗
PubMed1989

The bioactivity of immunoreactive adrenocorticotrophin in human blood is dependent on the secretory state of the pituitary gland.

A highly sensitive bioassay, using preincubated purified isolated rat adrenal cells, has been developed for measuring plasma ACTH. This bioassay enables detection of ACTH in plasma of about 0.9 pmol/l. Bioactive ACTH (B-ACTH) plasma levels were determined during insulin-induced hypoglycaemia in 12 female subjects and the values were compared with immunoreactive ACTH (I-ACTH) levels. The mean (+/- SD) basal B-ACTH level amounted to 1.7 +/- 0.8 pmol/l, the mean I-ACTH to 2.9 +/- 1.4 pmol/l. The highest mean B-ACTH plasma value was found 30 min after insulin injection: 14.7 +/- 15.7 pmol/l (I-ACTH: 12.8 +/- 9.9 pmol/l). By 90 min the B-ACTH level had returned to baseline (1.6 +/- 0.8 pmol/l), whereas the I-ACTH level was still significantly higher (5.4 +/- 2.7 pmol/l) than at time zero. Remarkably, the B-ACTH to I-ACTH ratio (B/I ratio) showed a biphasic profile during the insulin tolerance test, the ratio increasing from 0.60 +/- 0.77 at time zero to 1.08 +/- 0.35 at the ACTH peak, and decreasing after that to a lower value of 0.33 +/- 0.11 at 90 min. From these results it is concluded: (1) in the morning hours a considerable amount of circulating I-ACTH has no steroidogenic activity; (2) the B/I ratio temporarily increases immediately after insulin injection but gradually decreases afterwards to values half the baseline level at 90 min. Whereas this decrease at 90 min can be explained by differences in disappearance rates, the increase of B-ACTH relative to I-ACTH at 30 min indicates that estimations of immunoreactive ACTH reflect the biological activity of newly released ACTH with greater precision than at steady state level. Thus, the B/I-ACTH ratio can be used as a tool for measuring the state of the pituitary releasing activity.

Adrenocorticotropic Hormone↗
PubMed1989

Postprandial gallbladder motility during long term treatment with the long-acting somatostatin analog SMS 201-995 in acromegaly.

The effects on gallbladder motility of long term treatment with the somatostatin analog SMS 201-995 (SMS) were studied in five patients with acromegaly treated for 6-32 months with 200-300 micrograms SMS daily. SMS (100 micrograms) or placebo was injected sc 45 min before a standard breakfast. Gallbladder volume (ultrasonography), plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured until 120 min after the meal. SMS completely suppressed the postprandial gallbladder contraction, despite a blunted, though still statistically significant, increase in plasma CCK from 1.6 +/- 0.2 pmol/L to an average of 3.7 +/- 1.7 pmol/L (P less than 0.01). The postprandial plasma PP peak after placebo was replaced by a slight but statistically significant decrease after SMS (P less than 0.05). A statistically significant correlation between the plasma CCK values and corresponding gallbladder volumes was seen only after placebo injection, not in the SMS study. We conclude that during long term treatment of acromegalics with SMS, an injection of 100 micrograms, sc, completely abolishes gallbladder contraction for at least 2 h after a standard breakfast, despite blunted, but still significant, CCK release. The data suggest a decreased sensitivity of the gallbladder to endogenous CCK during long term treatment with SMS. Careful control of patients with respect to the formation of gallstones is recommended.

Acromegaly↗
PubMed1989

Predictive factors for initial cure and relapse rate after pituitary surgery for Cushing's disease.

Twenty-seven patients with Cushing's disease underwent transsphenoidal pituitary surgery. After the operation 16 patients were cured, and 11 remained hypercortisolemic. In the cured patients a significantly lower incidence of paradoxical responsiveness to TRH or to LRH was found preoperatively (1 of 16) than in the failures (6 of 11; P less than 0.02, by Fisher's chi 2 test). Furthermore, responsiveness of cortisol to CRH administration was significantly lower in the failures [maximum, 0.30 +/- 0.10 mumol/L (10.8 +/- 3.6 micrograms/dL) vs. 0.50 +/- 0.07 mumol/L (18.1 +/- 2.5 micrograms/dL) in the cured patients; P less than 0.05]. There were no differences in basal plasma cortisol levels, ACTH levels, or suppressibility by dexamethasone between the 2 groups. In the 16 patients who were cured initially, 4 patients relapsed after a mean period of 4 yr. These 4 patients had significantly higher basal cortisol levels postoperatively than those who remained in remission [0.14 +/- 0.03 mumol/L (5.1 +/- 0.8 micrograms/dL) vs. 0.04 +/- 0.01 mumol/L (1.4 +/- 0.3 micrograms/dL); P less than 0.01]. Cortisol responses to CRH after the operation positively correlated with the basal cortisol levels at that time (P less than 0.05, by Spearman's rank correlation test; r = 0.64), thus, the relapsing patients had higher cortisol responses to CRH than patients who stayed in remission [maximum response, 0.31 +/- 0.07 (11.2 +/- 2.5 micrograms/dL) vs. 0.12 +/- 0.03 mumol/L (4.3 +/- 1.1 microgram/dL), respectively; P less than 0.05]. We conclude that 1) patients responding paradoxically to TRH and/or LRH have a lower chance of being cured after pituitary surgery; and 2) patients with higher cortisol levels (greater than 0.10 mumol/L; 3.6 micrograms/dL) after being cured initially have a higher chance of recurrence of their disease.

Adenoma↗
PubMed1989

Single-dose response study of the somatostatin analogue octreotide in acromegaly.

The recommended dosage schedules for intermittent sc therapy with the somatostatin analogue octreotide in acromegaly vary widely, from 100 to 1500 micrograms daily. As acute administration of octreotide has been shown to predict its long-term response, we performed a single-dose response study in 5 patients with active acromegaly using doses of 25, 50, 100, 200 and 400 micrograms octreotide as well as a placebo injection. Plasma GH of 2 patients did not normalize after any of the injections, but nadir plasma GH overall gradually decreased as doses were increased from 25 to 400 micrograms. The 400 micrograms octreotide dose was superior with regard to the duration of plasma GH suppression to below 5 micrograms/l or 25% of the basal GH level, the mean GH as a percentage of the basal level over the first 4 and 8 h, and the integrated reduction of plasma GH during the first 4 and 8 h. The postprandial integrated insulin secretion during the first 3 h after injection of the octapeptide was significantly lower after 50, 100 and 400 micrograms than after the placebo injection. The mean plasma glucose as a percentage of the basal level during the first 8 h was significantly higher after octreotide after the 200 and 400 micrograms injections. Minor adverse events were seen in 2 patients after injection of 200 and 400 micrograms octreotide. Within the limitations of this single-dose response study it was concluded that injection of 400 micrograms octreotide yields the best results with regard to suppression of GH secretion, whereas the 50, 100 and 200 micrograms doses are superior to 25 micrograms, but do not differ from each other.

Acromegaly↗
PubMed1989

Pseudogout attacks after successful treatment of hyperparathyroidism.

Two patients developed pseudogout attacks during treatment for hyperparathyroidism, the first shortly after surgery and the second during medical treatment of her hypercalcaemia. From our observations in these patients and from data in the literature, we conclude that pseudogout attacks following parathyroidectomy in patients with chondrocalcinosis are caused by the decrease in the serum calcium levels and not by the major surgical procedure itself.

Aged↗
PubMed1988

The melanotropin potentiating factor and beta-endorphin do not modulate the alpha-melanotropin-or adrenocorticotropin-induced corticosteroidogenesis in purified isolated rat adrenal cells.

The ability of two pro-opiomelanocortin-derived peptides, the melanotropin potentiating factor (MPF) and beta-endorphin (beta EP), to affect corticosteroid production was studied in purified isolated rat adrenal cells. Addition of MPF or beta EP, in doses from 5 pg to 5 micrograms, alone did not result in a corticosterone production. Furthermore, no effect of MPF or beta EP in doses from 5 pg to as high as 5 micrograms for both peptides upon the ACTH or alpha-MSH-induced corticosteroidogenesis was observed (p greater than 0.1). It is concluded that both MPF and beta EP do not influence the steroidogenic activity in the adrenal gland. Use of these peptides for discrimination of the ACTH/alpha-MSH receptor interactions is suggested.

Adrenal Glands↗
PubMed1988

Adjuvant chemotherapy in premenopausal patients with primary breast cancer; relation to drug-induced amenorrhoea, age and the progesterone receptor status of the tumour.

Adjuvant chemotherapy with cyclophosphamide, 5-fluorouracil and methotrexate (CMF)-induced permanent ovarian suppression in 47 of 77 (61%) premenopausal patients with axillary node positive breast cancer. After a median observation time of 37 months the relapse-free and overall survival times were significantly longer for patients with permanent amenorrhoea. A strongly positive correlation between CMF-induced amenorrhoea and age of the patients, as well as between age and the tumour PgR status, was found. The induction of ovarian suppression predominantly occurs in patients with PgR positive tumours and may add an endocrine effect to the cytotoxic action of adjuvant chemotherapy in this particular group of older premenopausal women.

Adult↗
PubMed1988

Sex difference in the relation between sellar volume and basal and GH-releasing hormone stimulated GH in acromegaly.

Sellar volume and both basal (r = +0.54, P less than 0.02) and GHRH-stimulated (r = +0.41, P less than 0.05) GH levels were directly correlated in a group of 28 patients with acromegaly as were the latter indices (r = +0.82, P less than 0.001). By subdividing the patients according to sex, a close relation between sellar size and both basal (r = +0.77, P less than 0.02) and stimulated GH (r = +0.71, P less than 0.02) was found only in the men, not in the women (r = +0.12 and r = +0.02, respectively, P greater than 0.10). The presence of a tight relation between sellar volume and basal and GHRH stimulated GH levels in male patients with acromegaly and its complete absence in women are equally intriguing and await further elucidation. A modulating role of gonadal steroids in the genesis of this sex differences remain to be assessed.

Acromegaly↗
PubMed1988

Which factors predict the results of pituitary surgery in acromegaly?

Thirty-one patients with acromegaly who underwent pituitary surgery were investigated for possible predictive factors of the surgical outcome. The patients were divided into two groups: those whose GH levels normalized (less than 5 micrograms/l) after operation, group A (N = 18), and those whose GH levels remained elevated, group B (N = 13). There were no differences in age, sex distribution and sellar volume between both groups. There was a tendency to a higher incidence of supra-sellar extension of the pituitary tumor in group B (P less than 0.10). The basal GH levels in group A (38 +/- 5 micrograms/l) before operation were significantly lower than in group B (100 +/- 22 micrograms/l, P less than 0.002). Somatomedin C levels after the operation were significantly lower in group A than in group B (P less than 0.05) and were more often in the normal range (P less than 0.05). No differences were found in the occurrence of paradoxical GH responses to TRH and/or to GnRH between the groups and neither were there any differences in GH responses to GHRH and to bromocriptine between the groups. The sensitivity to SRIH tended to be higher in group A. After operation, the paradoxical GH response to TRH disappeared in 7 out of 10 patients and to GnRH in 2 out of 5 patients of group A, whereas in group B this anomaly persisted in all 9 after TRH and all 3 patients after GnRH. Hypopituitarism developed in only 5 out of the 31 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗