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Biomedical subjects

A G Smals

Publications and source records attributed to A G Smals.

At least 19 recordsLinked to original sources
PubMed1992

Postprandial gallbladder motility and plasma cholecystokinin at regular time intervals after injection of octreotide in acromegalics on long-term treatment.

The increased risk of gallstone formation in acromegalics treated with the somatostatin analog octreotide has been related to an impaired gallbladder emptying. To determine the duration of these inhibitory effects, meal-stimulated gallbladder motility, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured in five acromegalics treated for 6-32 months with 200-300 micrograms octreotide daily. Meal tests were performed 45 min, 8 hr and two weeks after the last 100-micrograms subcutaneous dose. Results were compared with those in normal subjects. Integrated postprandial gallbladder contraction (-125 +/- 194 cm3/120 min) and integrated PP secretion (-0.1 +/- 0.2 nmol/liter/120 min) were completely suppressed in the 45-min study, but significantly improved (P < 0.05) when measured 8 hr (1376 +/- 322 cm3/120 min and 3.0 +/- 1.0 nmol/liter/120 min) and two weeks (1437 +/- 263 cm3/120 min and 10.6 +/- 1.6 nmol/liter/120 min) after the last dose of octreotide. The integrated gallbladder contraction in acromegalics at 8 hr was comparable to that at two weeks and to that in normal subjects, but the integrated PP response at 8 hr was significantly smaller (P < 0.05 vs two weeks and vs normals). Integrated plasma CCK secretion at 45 min (0.13 +/- 0.06 nmol/liter/120 min) was not statistically significantly different from the response at 8 hr (0.15 +/- 0.02 nmol/liter/120 min) and from that in normal subjects, but it was significantly increased at two weeks after cessation of octreotide (P < 0.05 vs 45 min and 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1992

Adrenocortical function: an indicator of severity of disease and survival in chronic critically ill patients.

Plasma cortisol levels and modified Apache II (Apache IIm-stay) severity of disease scores were determined at weekly intervals in 159 patients who were treated for at least 7 days at the Critical Care Unit of our hospital. The mean (+/- SD) plasma cortisol level (0.60 +/- 0.28 mumol/l) was clearly elevated in these patients. The highest plasma cortisol levels were measured in patients treated with vasoactive drugs (0.76 +/- 0.39 mumol/l). Non-survivors (n = 36) had a significantly higher mean plasma cortisol level and Apache IIm-stay score than survivors (respectively 0.78 +/- 0.40 vs. 0.54 +/- 0.21 mumol/l; p less than 0.0003 and 12.6 +/- 4.8 vs. 7.3 +/- 4.1; p less than 0.0001). A significant correlation was found between the individual weekly plasma cortisol levels and the Apache IIm-stay scores (r = 0.41; p less than 0.0001), especially in the subgroup of patients, who never received glucocorticoids during their stay at the ICU (r = 0.51; p less than 0.0001). During the 14-month study period only two patients showed a clinical picture of adrenocortical insufficiency and a blunted response of cortisol to 0.25 mg synthetic ACTH(1-24). In conclusion, our data suggest that a high plasma cortisol level, like a high Apache IIm-stay score, indicates severity of disease and poor survival in critically ill patients. De novo adrenocortical insufficiency is rare and therefore routine screening of adrenocortical function is superfluous.

Adolescent↗
PubMed1992

Human breast cancer: survival from first metastasis. Breast Cancer Study Group.

Survival from the detection of first metastasis (SAM) was analyzed in a single center series of 258 patients with advanced breast cancer. During the 15 year period covered by this study 230 patients died, 215 of their disease. The overall median SAM was 28 months. Univariate analysis of SAM stratified by first dominant site of metastasis, estrogen receptor status (ER), progesterone receptor status (PgR), tumor size, axillary lymph node status, patient age, menopausal status, and disease-free interval (DFI) showed the first dominant site of metastasis, ER, PgR, and axillary lymph node status to be significantly associated with SAM. Patients with visceral metastasis as first dominant site of metastasis had significantly shorter survival than those with either bone or soft tissue metastasis, median SAM 16 vs. 34 vs. 41 months respectively (P less than 0.001). SAM also differed according to the steroid hormone receptor status of the primary tumor: median SAM 34 and 33 months for patients with ER-positive or patients with PgR-positive tumors against 14 months for patients with ER-negative or with PgR-negative tumors (P less than 0.001). Patients with axillary lymph node involvement at primary disease had a shorter SAM than those without, median SAM 24 vs. 35 months (P = 0.006). No association between SAM and either tumor size, patient age, menopausal status, or DFI could be observed. Multivariate analysis including first dominant site of metastasis, ER, PgR, and axillary lymph node status showed the first dominant site of metastasis, ER, and axillary lymph node status to be independently associated with SAM.

Adult↗
PubMed1992

Electrocardiographic changes during steady mild hypothermia and normothermia in patients with poikilothermia.

1. ECG changes observed in short-term induced and accidental hypothermia are well known. To assess the influence of steady-state spontaneous hypothermia on the ECG, we subjected four patients with acquired poikilothermia (severe thermolability) to 24 h ECG recording, exercise testing and thermal stress. 2. Twenty-four hour Holter monitoring showed a significant reduction in heart rate and a prolongation of the QT interval during steady-state mild hypothermia (rectal temperature 33.9 +/- 0.7 degrees C, mean +/- SD) compared with during normothermia; no significant changes occurred in the PR interval, QRS complex and QTc interval (QT interval corrected for heart rate). 3. Unlike during normothermia, during steady hypothermia atrioventricular Wenckebach blocks were observed in two patients, whereas another patient showed markedly more atrioventricular Wenckebach blocks during hypothermia. 4. During steady hypothermia the heart rate variability was significantly enhanced in comparison with normothermia. 5. Exercise tolerance was similar during mild hypothermia and normothermia. 6. Heat exposure (ambient temperature 40 degrees C) induced significantly greater changes in rectal temperature, heart rate and PR interval, QRS complex and QT interval in the patients than in the control subjects (n = 8). 7. The present study reveals that even mild steady spontaneous hypothermia can elicit ECG changes, presumably mediated by relatively enhanced cardiac vagal tone. Hence, spontaneous abnormalities in core temperature should be taken into account in interpreting the ECG in clinical practice.

Adult↗
PubMed1992

Chronic stimulation of the pituitary-adrenal axis in rats by interleukin-1 beta infusion: in vivo and in vitro studies.

It has been shown that acute administration of interleukin-1 (IL-1) to rats elicits a transitory increase in plasma ACTH and corticosterone (B) levels. To investigate the effects of chronic administration of IL-1 on plasma ACTH and B levels, in the present study rats were equipped with Alzet osmotic minipumps loaded with either IL-1 (delivery rate 0.5, 2.0, or 4.0 micrograms/24 h, ip, for 1 week) or saline. At the end of the treatment the rats were decapitated, the adrenals were weighed, and the in vitro release of beta-endorphin (beta E) by the anterior pituitary and that of B by the adrenal gland were measured. Continuous administration of 2.0 and 4.0 micrograms IL-1/24 h resulted in a persistent increase in plasma ACTH and B concentrations compared to the levels in saline-infused rats, with peak levels on the first day of administration. In addition, adrenal weights of IL-1 rats were significantly higher than those of saline rats. The 4.0-micrograms IL-1/day in vivo treatment induced an increase in spontaneous in vitro secretion of beta E and B, while the in vitro responses of the pituitary (to CRF) and the adrenal (to ACTH) of animals treated in vivo with IL-1 were significantly diminished. IL-1 at a dose of 0.5 microgram failed to affect plasma ACTH and B values, adrenal weight, and in vitro beta E and B secretion. Chronic infusion of rats with 4.0 micrograms IL-1/day induced prolonged fever, whereas at lower doses of IL-1 (2.0 and 0.5 micrograms), temperatures were elevated only on the first 2 days of infusion. IL-1 at doses of 2.0 and 4.0 micrograms/day induced suppression of body weight gain on the first 2 days of the treatment period compared to saline treatment. Plasma norepinephrine and/or epinephrine concentrations were raised only on day 1 of the 2.0- and 4.0-micrograms IL-1 experiments. Thus, the observed effects of IL-1 on the hypothalamo-pituitary-adrenal axis probably do not result merely from stress induced by the treatment. Taken together, our data show the potential of IL-1 to induce a dose-dependent and long term activation of the pituitary-adrenal axis.

Adrenal Glands↗
PubMed1992

Continuous infusion of interleukin-1 beta induces a nonthyroidal illness syndrome in the rat.

We studied the effects of continuous administration of recombinant human interleukin-1 beta (IL-1) on pituitary-thyroid function. Rats were equipped with minipumps loaded with either IL-1 (delivery rate, 0.5, 2.0, or 4.0 micrograms/day, ip, for 1 week) or saline. Infusion of 2.0 and 4.0 micrograms IL-1/day caused a significant decrease in plasma free T4 levels during the first 2-4 days, whereas plasma total T4 levels and T4 binding were significantly lowered throughout the week of the study. The infusion of 0.5 micrograms IL-1/day did not significantly change plasma TSH or total and free T4 levels. During the infusion of 2.0 micrograms IL-1/day, the decrease in plasma free T4 levels was paralleled by a significant decline in plasma TSH values and an impaired TSH responsiveness to TRH administration on the second day of infusion. IL-1 (2.0 micrograms/day) treatment significantly lowered plasma levels of T4-binding prealbumin, whereas it did not influence the plasma T3/T4 ratio or hepatic 5'-deiodinase activity. Plasma rT3 levels remained undetectable in both control and IL-1-treated rats. Chronic infusion of rats with 4.0 micrograms IL-1/day induced prolonged fever, whereas at the lower doses of IL-1, temperatures were elevated only on the first 2 days. IL-1 at doses of 2.0 and 4.0 micrograms/day induced a transient decrease in food intake and a suppression of body weight gain. Restriction of food consumption to the level observed in the 2.0 micrograms IL-1 experiment caused small decreases in T3, total and free T4, and TSH levels compared to those in ad libitum fed rats, but had no effects on T4 binding. We conclude that 1) continuous infusion of rats with 2.0 and 4.0 micrograms IL-1/day induces changes in thyroid economy commonly seen during infectious diseases and other systemic illnesses in rats [decreased plasma levels of TSH, T3, and (free) T4; diminished T4 binding; and decreased plasma T4-binding prealbumin levels], 2) the decrease in food intake during IL-1 treatment cannot completely explain the observed changes in thyroid hormone and TSH levels; and 3) it is highly unlikely that the decrease in thyroid hormone binding during chronic IL-1 infusion is caused by decreased food intake. Further studies are needed to clarify whether the observed alterations in thyroid economy during IL-1 infusion reflect direct effects of IL-1 per se or indirect effects caused by the mild illness induced by the cytokine.

Analysis of Variance↗
PubMed1992

Body weight and/or endogenous estradiol as determinants of cortical bone mass and bone loss in healthy early postmenopausal women.

The objective was to study the independent relationships of body mass index and endogenous estradiol to cortical bone mineral density and the rate of cortical bone loss at the radius in healthy early postmenopausal women. Fifty-one healthy early postmenopausal women (aged 58-66 years) participated. The women were a subset of a population participating in a 10-year longitudinal study to elucidate the influence of dietary calcium on the rate of cortical bone loss. Cortical bone mineral density at the radius, body weight and body height were measured annually (1979-89). Concentrations of sex steroids were measured in serum samples collected during the last year of follow-up (1989). Endogenous estradiol levels, although significantly positively correlated with body mass index, were not independently related to bone mass indices of the radius. Body mass index, on the other hand, was found to be positively related to cortical bone mineral density and negatively to the rate of bone loss, even after adjustments had been made for confounding factors. Our results suggest that the level of total estradiol is not an important determinant of cortical bone mass indices in healthy early postmenopausal women. Other factors of overweight such as mechanical loading may be important.

Aged↗
PubMed1992

TSH-dependent production of T4 and T3 by metastases of a thyroid carcinoma.

A patient with T4 and T3 production by metastases of a follicular thyroid carcinoma leading to TSH suppression is described. During a period of three years, plasma T4, T3 and TSH levels were measured in the substitution-free periods before the successive iodine-131 retention measurements and iodine-131 therapies, when the patient was at least two weeks without thyroid hormones. From the presented data it can be derived that the production of thyroid hormones by metastases was enhanced by endogenous TSH.

Adenocarcinoma↗
PubMed1992

Low ratio of androstenedione to testosterone in plasma and saliva of hirsute women.

To gain insight into the passage of androstenedione (A4) through the salivary gland, we measured concentrations of plasma total (TA4), free (FA4), and salivary (SA4) androstenedione during administration of dexamethasone and synthetic corticotropin to control subjects and hirsute women and compared these data with plasma total (TT), free (FT), and salivary testosterone (ST) concentrations. TA4 and FA4 were significantly lower in control subjects throughout (0, 15, 45, and 75 min) (P less than 0.05). SA4 in control subjects was significantly lower only in the follicular phase at 0 and 15 min. There was no significant difference between the increments in SA4 in response to corticotropin. The concentration of SA4 in the control women at 0 min was not significantly different from the concentration of FA4. At 45 and 75 min after corticotropin administration, however, SA4 was slightly higher than FA4 (P less than 0.01). In hirsute women, however, the concentration of SA4 was significantly lower than FA4 at all times (P less than 0.05). TT, FT, and ST concentrations were about twofold higher in the hirsute women than in control subjects throughout. In both groups, ST concentrations were three times as high as FT concentrations (P less than 0.001). The SA4:ST ratio was significantly lower than the FA4:FT ratio in both groups (P less than 0.001) because of higher ST than FT concentrations and similar or even lower SA4 concentrations in both groups. Both FA4:FT and SA4:ST ratios were lower in hirsute women, except for the FA4:FT ratio in control subjects in the luteal phase. Our data are compatible with 17-hydroxysteroid oxidoreductase activity in the salivary gland. If the difference in the ratios of A4 to T between hirsute women and control subjects is attributed to this hypothetical enzymatic activity, it would suggest a more rapid conversion of A4 to T in the hirsute group.

Adrenocorticotropic Hormone↗
PubMed1991

Steroid hormone receptor activity of primary human breast cancer and pattern of first metastasis. The Breast Cancer Study Group.

A series of 258 breast cancer patients with known estrogen receptor (ER) status of the primary tumour who subsequently developed metastases were reviewed for site of first metastasis. In 188 cases progesterone receptor (PgR) data were also available. Univariate analysis showed metastatic patterns to differ statistically significantly related to ER status and (less pronounced) PgR status of the primary tumour. Patients with ER-positive tumours had bone metastases three times more often than patients with ER-negative tumours. With respect to PgR-positive and PgR-negative tumours this frequency differed by a factor of two. With regard to visceral metastases ER and PgR status were equally potent prognosticators, patients with receptor negative tumours having a 50% higher frequency of visceral metastasis than patients with receptor positive tumours. Assessment of metastatic patterns in relation to combined receptor status did not substantially enhance the discriminatory value of ER and PgR when assessed separately. Multivariate analysis showed that the observed differences in metastatic patterns were all attributable to differences in the ER status of the primary tumour, and were not influenced by age, menopausal status, axillary lymph node involvement, duration of disease-free interval (DFI), mode of postoperative treatment, or the PgR status of the primary tumour.

Abdominal Neoplasms↗
PubMed1991

16-Ene-steroids in the human testis.

Incubation of human testicular homogenates with [4-14C]pregnenolone gave substantial amounts of an unknown metabolite within 1 min, reaching plateau values of 17-23% of total radioactivity added within 5 min. Mass spectrometry of the metabolite showed it to be identical to the boar sex pheromone precursor androsta-5, 16-diene-3 beta-ol (ADL). In cell cultures the major source of ADL and its dehydrogenated metabolite androsta-4, 16-diene-3-one (ADN) was the Leydig cell. In rat and monkey testicular homogenates 16-ene-synthetase activity, a prerequisite for the synthesis of ADL and ADN, was completely lacking, limiting the presence of 16-androstenes to boars and men. In contrast to boars, however, in the human testis no 5 alpha-reductase activity was found and consequently no 5 alpha-reduced-16-androstenes, e.g. androstenol (AL, musk like) and androstenone (AN, urine like), known sex pheromones in pigs. As both sex pheromones have been identified in urine, plasma, sweat and saliva of men and (especially hirsute) women we hypothesize that AL and AN are synthesized from ADL via ADN peripherically in tissues rich in 5 alpha-reductase, i.e. skin, axillary sweat glands and probably also the salivary glands. So far, there is some evidence that both sex pheromones may have similar functions in humans as in boars.

Age Factors↗
PubMed1991

The HMG-CoA reductase inhibitor simvastatin suppresses human testicular testosterone synthesis in vitro by a selective inhibitory effect on 17-ketosteroid-oxidoreductase enzyme activity.

In concentrations probably exceeding those achieved in vivo, the cholesterol lowering compound simvastatin was found to suppress the synthesis of the androgens androstenediol and testosterone in vitro by human testicular homogenates. It was demonstrated that simvastatin in addition to its known inhibitory effect on HMG-CoA reductase activity, also affects the later steps of testicular steroidogenesis by selectively inhibiting the 17-ketosteroid-oxidoreductase catalyzed conversion of dehydroepiandrosterone and androstenedione to androstenediol and testosterone respectively. There was no effect of simvastatin on the Cytochrome P-450-dependent microsomal enzymes. Although in doses conventionally used in the treatment of hypercholesterolemia, simvastatin does not affect testicular steroidogenesis, at higher doses--especially when inadvertently administered during early pregnancy--adverse effects on normal testosterone biosynthesis and thereby fetal development should be considered.

17-Hydroxysteroid Dehydrogenases↗
PubMed1991

Poikilothermia in man: pathophysiology and clinical implications.

Poikilothermia, the inability to maintain a constant core temperature independent of ambient temperature, markedly influences both the mental and physical function of affected patients; furthermore, prolonged hypothermia can induce numerous complications. To establish the pathophysiology of thermoregulation underlying poikilothermia in man, we compared 4 women with acquired poikilothermia, with 9 female control subjects. The activity of the main thermoregulatory effector mechanisms was assessed in a thermoneutral environment, and during subsequent cold stress and heat exposure. At thermoneutrality the patients had a significantly lower rectal temperature and resting metabolic rate compared with the controls; no patient showed peripheral vasoconstriction or shivering. Cooling revealed markedly reduced peripheral vasoconstriction in 3 patients and failure of the metabolic response in 2 patients; unlike controls, no patient exhibited shivering. Heat challenge revealed severely reduced capacity for heat dissipation in all patients. We conclude that in patients with poikilothermia, the mechanisms for both heat conservation and heat dissipation are seriously attenuated. Careful monitoring of the core temperature and adequate measures to maintain normothermia are of great importance in patients with poikilothermia in order to provide adequate treatment, improve the quality of life, and prevent serious complications.

Adipose Tissue↗
PubMed1991

Favourable response of a virilizing adrenocortical carcinoma to preoperative treatment with ketoconazole and postoperative chemotherapy.

A 25-year-old woman presented with an extensive adrenocortical carcinoma with severe virilization and mild Cushing's syndrome. In the tumour there was a primacy of the P450C17 (17,20-lyase) over the P450C21 (21-hydroxylase) route, favouring the synthesis of androgens over corticoids. Preoperatively, the patient was treated with the antimycotic agent ketoconazole, a known inhibitor of steroid synthesis, at a dose of 600 mg/day and after a week 1200 mg/day, to reduce operation risks and to achieve a better metabolic control. This treatment markedly decreased hyperandrogenism and normalized the hypercortisolism. The main effect of ketoconazole was at the 17,20-lyase level and probably at a locus prior in steroidogenesis, i.e. at the P450SCC and/or 17 alpha-hydroxylase level. In contrast with other studies no effect at all was seen on the 11-hydroxylase activity of P450C11. After removal of a massive adrenal carcinoma, extending into the vena cava, vena cava resection and hemihepatectomy because of liver invasion, plasma cortisol and androgen values normalized. Despite adjuvant chemotherapy with o,p'-dichlor-diphenyl-dichloretan (4000 mg daily) hyperandrogenism soon recurred and lung metastases became manifest. Within 2 months after starting combined chemotherapy with 5-fluorouracil, cisplatin, and doxorubicin lung metastases almost completely disappeared with clinical and biochemical resolution of the hyperandrogenic state.

Adrenal Cortex Neoplasms↗
PubMed1991

Aseptic bone necrosis in patients on glucocorticoid replacement therapy.

The incidence of aseptic bone necrosis in 167 patients on glucocorticoid replacement therapy in our hospital was found to be 2.4% (4 patients). The diagnosis was made 16 months to five years after initiation of the therapy. A review of eight other cases reported in the literature is presented. The incidence of aseptic bone necrosis in patients on glucocorticoid replacement therapy seems much higher than might be expected. It is suggested that the dose of glucocorticoid substitution therapy be established individually at the lowest acceptable level.

Adult↗
PubMed1991

Concentrations of salivary testosterone and plasma total, non-sex-hormone-binding globulin-bound, and free testosterone in normal and hirsute women during administration of dexamethasone/synthetic corticotropin.

Preliminary data indicate that the concentration of circulating cortisol may affect the binding of testosterone to plasma proteins. This interdependency was evaluated by the assessment of plasma cortisol, salivary (ST) and plasma total testosterone (TT), testosterone not bound to sex-hormone-binding globulin (n-SHBGT), and free testosterone (FT) in normal and in hyperandrogenemic women during combined dexamethasone/synthetic corticotropin administration. The concentrations of TT, FT, and ST significantly increased (P less than 0.001) during this dynamic test both in the controls and in hirsute women. Remarkably, however, n-SHBGT remained virtually unchanged in normal women in the follicular phase, decreasing in the luteal phase, and decreasing even more markedly in the hirsute women. Both the normal and the hirsute women showed a statistically significant negative correlation between the percentage of n-SHBGT and plasma total cortisol (P less than 0.001). The apparent decrease of n-SHBGT was the result of displacement of T from corticosteroid-binding globulin (CBG) by the increase in cortisol after the infusion of synthetic corticotropin: the CBG-bound T was measured as n-SHBGT because CBG was not precipitated with 50% saturated ammonium sulfate. Our results indicate that ST or FT better represents the clinical status of androgenicity than does n-SHBGT, as assessed by ammonium sulfate precipitation, because n-SHBGT also depends on the concentration of cortisol.

Adrenocorticotropic Hormone↗
PubMed1990

[Fine-needle biopsy of cold thyroid nodules].

In retrospect we analysed 175 fine needle aspiration biopsies, performed on 154 patients with a palpable, solitary, 'cold', thyroid nodule. In contrast to conventional diagnostic methods such as ultrasound and scintigraphy fine needle aspiration is a highly specific method for the detection of thyroid cancer. We found a significant difference in the frequency of thyroid carcinoma between patients operated because of cytological diagnosis and patients operated because of clinical suspicion of cancer, 44% and 20% respectively. We conclude that fine needle aspiration is a major step forward in the evaluation of solitary thyroid nodules.

Adolescent↗