Search PubMed⌕ Search

Biomedical subjects

A G Smals

Publications and source records attributed to A G Smals.

At least 127 records · Page 7Linked to original sources
PubMed1984

Concordance and discordance of estrogen and progesterone receptor content in sequential biopsies of patients with advanced breast cancer: relation to survival.

In 75 patients with advanced breast cancer, sequential biopsies were analyzed for estrogen receptor (ER). In 50 of these patients progesterone receptor (PgR) was also measured. All pairs of biopsies met the following criteria: (i) interval between the two biopsies: at least 6 weeks; (ii) biopsies performed at least 6 weeks after stopping endocrine therapy; and (iii) concordant histology. Discordance in ER was found in 14 of 75 patients (18.7%); PgR was discordant in 14 of 50 patients (28.0%). No significant differences were found between concordant and discordant groups of patients in age at first diagnosis, menopausal state, diameter of the primary tumor, time interval between the two biopsies and intervening therapy. The initial ER level in patients whose ER changed from positive to negative was significantly lower than in patients whose ER remained positive. PgR levels exhibited a rise only when ER rose at the same time. Sequential assays have increased the prognostic significance of ER and as a consequence the estimated survival time for patients whose tumors were ER-negative in both biopsies was significantly shorter than for patients whose tumors were ER-negative in only one of the two biopsies. We found no prognostic significance for PgR in either single measurements or repeated biopsies.

Adult↗
PubMed1984

Differential effect of luteinizing hormone-releasing hormone infusion on testicular steroids in normal men and patients with idiopathic oligospermia.

Basal serum gonadotropin levels in 11 oligospermic men were significantly higher than in 9 euspermic control subjects, although most were still in the normal range. Basal serum testosterone (T), 17-hydroxyprogesterone (17-OHP), and estradiol levels and their ratios did not differ significantly. Continuous luteinizing hormone-releasing hormone (LH-RH) infusion (1 microgram/minute for 180 minutes) during integrated blood sampling evoked similar gonadotropin responses in both groups but had a differential effect on T: in the control subjects T increased (P less than 0.01) within 15 minutes to 1.5 times baseline, whereas in the oligospermic men T decreased (P less than 0.01). From 60 minutes on, however, T also significantly rose in the oligospermic men, but the maximum increment was about half lower (P less than 0.01) than in the euspermic men, despite virtually similar rises in 17-OHP. Only in the oligospermic men did the 17-OHP/T ratio increase (P less than 0.02) during LH-RH, which is compatible with the occurrence of a 17,20-lyase block. Serum estradiol did not increase in either group. In conclusion, continuous LH-RH infusion uncovers an intrinsic difference in acute Leydig cell stimulation between euspermic and oligospermic men.

Adult↗
PubMed1984

Differential effects of ovine and human corticotrophin-releasing factor in human subjects.

Ten healthy subjects received 200 micrograms of human CRF (hCRF) and 200 micrograms of ovine CRF (oCRF) as an intravenous bolus injection on two different occasions. After hCRF plasma ACTH levels rose significantly (P less than 0.0005, by Friedman's nonparametric analysis of variance) from a basal value of 35 +/- 3 pg/ml (mean +/- SEM) to a peak value of 80 +/- 7 pg/ml 30 min after hCRF administration. This ACTH response was followed by a rise in plasma cortisol levels (P less than 0.0005, by Friedman's test) from a baseline value of 0.32 +/- 0.03 mumol/l to a peak value of 0.56 +/- 0.02 mumol/l 60 min after hCRF. Ovine CRF elicited similar rises in the plasma ACTH and cortisol levels. However, as derived from the faster rate of decline of ACTH and cortisol after hCRF than after oCRF, human CRF had a significantly shorter duration of action than ovine CRF in humans. Human CRF not only stimulated ACTH release by the human pituitary gland but also prolactin release. After hCRF administration prolactin levels rose significantly (P less than 0.005, by Friedman's test) from a basal value of 179 +/- 18 mU/l to a peak value of 288 +/- 34 mU/l at 10 min.

Adolescent↗
PubMed1984

Growth hormone responsiveness to human pancreatic growth hormone releasing factor in acromegaly: modulatory effects of basal hormone levels and of concomitant somatostatin administration.

Human pancreatic growth hormone releasing factor 1-44 (hpGRF), 100 micrograms was administered as an i.v. bolus injection to eleven patients with acromegaly. The mean serum growth hormone (GH) levels rose (P less than 0.001) from 54 +/- 20 ng/ml to 215 +/- 126 ng/ml (+/- SEM) 20 min after the injection. Although the maximum response of GH levels was highly variable it correlated positively with the individual GH levels (P less than 0.01, Rs = +0.80). Thus the higher the GH levels, the greater the responsiveness to hpGRF. Administration of somatostatin (SRIF), 300 micrograms/h, lowered basal GH levels from 76 +/- 38 ng/ml to 13 +/- 5 ng/ml (P less than 0.01) after 1 h. hpGRF administration during concomitant SRIF infusion also led to highly variable growth hormone responses. The maximum GH responses again correlated positively with the GH level before hpGRF after 1 h of SRIF administration (P less than 0.05, Rs = +0.79). GH responses to hpGRF were completely blocked by SRIF in three out of four patients whose GH levels decreased to normal levels during SRIF infusion. Our data illustrate that the pituitary in acromegaly is normally responsive to both SRIF and hpGRF but at a higher setting of basal GH levels.

Acromegaly↗
PubMed1984

Plasma adrenocorticotropin, cortisol, and aldosterone responses to corticotropin-releasing factor: modulatory effect of basal cortisol levels.

Two hundred micrograms of corticotropin-releasing factor (CRF) were administered as an iv bolus injection to 10 normal subjects (5 men and 5 women). Mean plasma ACTH levels rose significantly (P less than 0.0005, by Friedman's nonparametric analysis of variance) from a basal value of 27 +/- 5 pg/ml (mean +/- SEM) to a peak value of 63 +/- 8 pg/ml 30 min after CRF administration. This ACTH response was followed by a rise in plasma mean cortisol levels (P less than 0.0005, by Friedman's test) from a baseline value of 12.3 +/- 1.4 micrograms/100 ml to a peak value of 21.0 +/- 0.7 micrograms/100 ml 60 min after CRF and a rise in mean plasma aldosterone levels from a basal value of 13 +/- 2 ng/100 ml to a peak value of 23 +/- 2 ng/100 ml. There was no significant difference between men and women in the responsiveness of ACTH, cortisol, and aldosterone to CRF administration. The individual basal cortisol levels were highly significantly and negatively correlated with the areas under the individual ACTH curves (r = -0.76; P less than 0.005, by Pearson's correlation test) and cortisol curves (r = -0.91; P less than 0.001, by Pearson's test). These data suggest a modulatory effect of physiological cortisol levels on the response of the pituitary-adrenal axis to CRF.

Adolescent↗
PubMed1984

Macronodular adrenocortical hyperplasia in long-standing Cushing's disease.

Clinical and biochemical findings in 13 patients (11 women and 2 men) with macronodular adrenocortical hyperplasia (MNH; nodule size, greater than 0.5 to 5.3 cm) were compared with those of 18 patients (15 women and 3 men) with Cushing's disease and diffuse (n = 9) or micronodular (n = 9) hyperplasia (DH). All were bilaterally adrenalectomized for their hypercorticism. The clinical picture was almost identical in both groups, except for greater frequency of hypertension (13 of 13 vs. 10 of 18; P less than 0.05), alopecia (4 of 11 vs. 0 of 15; P less than 0.05), and scintigraphic lateralization (6 of 7 vs. 1 of 7; P less than 0.05) in the MNH group than in the DH group. The sella turcica was enlarged in 30% of the patients in both groups. Patients with MNH were significantly older than DH patients [43.5 +/- 7.8 (mean +/- SD) vs. 31.7 +/- 10.1 yr; P less than 0.005] and had a 3-fold longer duration of disease (7.8 +/- 4.6 vs. 2.0 +/- 1.1 yr; P less than 0.001) than those with DH. The mean plasma ACTH and cortisol levels and urinary 17-hydroxycorticosteroid excretion were elevated in both MNH and DH patients and responded similarly to specific (corticotropin-releasing hormone and metyrapone) and nonspecific (TRH and LHRH) stimuli. However, dexamethasone suppressibility and the stimulatory effect of ACTH on adrenocortical function were less in the MNH than in the DH group or its subgroups, suggesting a greater degree of adrenal autonomy in the former. Adrenal weight in MNH (15.8 +/- 12.1 g each) was almost twice as high as in DH (8.2 +/- 2.0 g) patients and positively correlated with the duration of the disease. The data suggest that MNH may be a result of long-standing Cushing's disease with varying degrees of pituitary dependence and adrenocortical autonomy, which may lead to confusing biochemical and radiological findings. Bilateral adrenalectomy, rather than hypophysectomy, is the treatment of choice in MNH.

Adrenal Cortex↗
PubMed1984

Differential effect of single high dose and divided small dose administration of human chorionic gonadotropin on Leydig cell steroidogenic desensitization.

This study compared the effect of a single high dose of hCG (1500 IU) with that of the same dose administered in multiple small doses (300 IU, once daily for 5 days) on Leydig cell steroidogenesis. Administration of a single high dose of hCG to seven healthy men raised the mean plasma testosterone (T) level to peak levels 2.1 +/- 0.2 (SEM) X the baseline value at 48 h. Thereafter plasma T decreased to below normal (0.7 +/- 0.1 X baseline) 7 days after the injection. The mean 17-hydroxyprogesterone (17-OHP) level peaked at 24 h (2.5 +/- 0.2 X baseline) and then also fell to a nadir value of 0.6 +/- 0.2 X baseline on day 7. Reflecting the early accumulation of 17-OHP over T, the 17 OHP/T ratio reached its maximum (1.6 +/- 0.1 X baseline) at 24 h at the same time when plasma estradiol [(E2) 4.4 +/- 0.6 X baseline] and the ratio E2/T (2.7 +/- 0.3 X baseline) achieved their maximal values. Administration of 1500 IU hCG in five divided doses of 300 IU daily increased the mean plasma T levels to peak value of 2.1 +/- 0.2 X baseline at 5 days and the levels remained elevated thereafter. The response of T as reflected by the area under the curve was almost twice as great as in the single dose study (2844 +/- 360 vs. 1647 +/- 214). In contrast to the single high dose experiment, mean plasma 17-OHP levels in the divided dose protocol did not peak at 24 h but only gradually increased. As the increase of T exceeded the 17-OHP increase at almost all time intervals, no accumulation of 17-OHP over T occurred as in the single dose experiment. Instead the 17-OHP/T ratio fell to a nadir value of 0.6 +/- 0.1 X baseline on day 7. The initial E2 peak was absent in the divided dose protocol and the E2/T ratio only marginally increased. Considering both experiments together a close relation was found between the hCG-induced increases in E2 and 17-OHP (r = +0.88, P less than 0.001), as well as the ratio 17 OHP/T (r = +0.64, P less than 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1983

Pyridoxine treatment does not prevent homocystinemia after methionine loading in adult homocystinuria patients.

Fasting homocystinemia in homocystinuria due to cystathionine synthase deficiency reportedly disappears on high-dose pyridoxine treatment. This does not necessarily reflect normal tolerance to methionine. The present study compares the effects of oral methionine loading on homocystine, cystine, and homocysteine-cysteine disulphide profiles in 8 adult homozygous homocystinuria patients on and off pyridoxine treatment and in 20 controls. Pyridoxine nearly normalized fasting serum amino acid levels. Nevertheless, with a similar methionine load the patient's homocystine levels on and off treatment rose and the cystine levels decreased, reflecting the ongoing formation of the homocysteine-cysteine disulphide in the presence of impaired transsulphuration of homocysteine. In the controls homocystinemia remained virtually absent and cystine transiently rose which indicates normal transsulphuration. On treatment methionine loading evoked a brisk rise of the homocysteine-cysteine disulphide levels to values equal to those off treatment, when these levels virtually plateaued after the load. Thus, pyridoxine treatment attenuates the biochemical abnormalities in the fasting patients but leaves their impaired capacity to handle major methionine loads essentially unchanged.

Adult↗
PubMed1983

Testosterone and delta 4-androstenedione in the saliva of patients with Klinefelter's syndrome.

This study compares salivary and total plasma levels of testosterone and androstenedione in healthy controls and chromatin positive patients with Klinefelter's syndrome. The mean plasma testosterone level in fifteen Klinefelter patients was significantly lower than in ten control subjects, but the mean androstenedione levels were similar. Saliva of the normal men and patients with Klinefelter's syndrome did not differ significantly in binding potency for testosterone or androstenedione. The mean salivary testosterone level in the Klinefelter patients was significantly lower than in the controls but again salivary androstenedione levels were similar. Although testosterone as well as androstenedione showed a fair correlation between the salivary and plasma concentrations, preliminary data suggested that salivary testosterone levels better characterize the clinical state of androgenicity than do plasma levels. When salivary testosterone and androstenedione were expressed as a percentage of total steroid levels in plasma, the ratios for both steroids were similar in Klinefelter patients and healthy controls and closely approximated to the reported percentages of free steroid levels in plasma. The absolute salivary testosterone concentrations also were almost identical to the reported free plasma hormone levels. Together the data provide indirect evidence that in Klinefelter patients testosterone and androstenedione binding in plasma and saliva does not differ from that in normal men, and measurement of salivary steroids, by reflecting their free hormone concentration in plasma, may be useful in evaluating endocrine function in both health and disease.

Adult↗
PubMed1983

Unique efficiency of methionine metabolism in premenopausal women may protect against vascular disease in the reproductive years.

Premenopausal women develop occlusive artery disease less frequently than postmenopausal women. In coronary heart disease, higher blood levels of homocysteine-cysteine mixed disulphide have been reported. Therefore, in healthy subjects, we studied the role of menopausal status in the transsulphuration of methionine in 10 premenopausal and 10 postmenopausal women. To exclude the role of aging, we compared these results with those in 10 younger and 10 older men of comparable age groups. An oral methionine load (0.1 g/kg of body weight) was administered after overnight fasting. Before and during 8 h, thereafter, serum levels of methionine, homocystine, and homocysteine-cysteine mixed disulphide were measured. In the fasting state, serum methionine levels were similar in the premenopausal women and both groups of men. Postmenopausal women had significantly lower fasting levels. Peak levels and clearances of methionine after loading did not differ between the groups. In the fasting state, homocystine was never detectable; yet, after methionine loading, slight homocystinemia was present in 12 out of 20 men, and was more pronounced in all postmenopausal women. However, homocystinemia did not occur in any of the premenopausal women after loading. Fasting serum homocysteine-cysteine mixed disulphide levels did not differ between both groups of men and postmenopausal women. In premenopausal women, both fasting and postloading disulphide levels were significantly lower than in any other group. We conclude that premenopausal women have a unique efficiency of methionine handling, and thereby are preserved against the accumulation of homocysteine after methionine loading. We speculate that this phenomenon might account for the lower incidence of vascular disease in women in the reproductive life cycle.

Adult↗
PubMed1983

Responsiveness of the hypophyseal-adrenocortical axis to corticotropin-releasing factor in pituitary-dependent Cushing's disease.

Corticotropin-releasing factor [(CRF) 200 micrograms] was administered iv to five patients with classical pituitary-dependent Cushing's disease and to five normal subjects. In both groups no changes were observed in the plasma concentrations of hGH, PRL, TSH, LH, or FSH. In the normal subjects plasma ACTH levels rose from 41 +/- 9 (SEM) pg/ml to 87 +/- 28 pg/ml after 60 min (P less than 0.01) and plasma cortisol levels from 0.30 +/- 0.06 mumol/liter (8.0 +/- 0.2 micrograms/dl) to 0.53 +/- 0.07 mumol/liter (14.2 +/- 0.2 micrograms/dl) after 60 min (P less than 0.001). In the patients with classical Cushing's disease plasma ACTH levels increased from 109 +/- 23 to 281 +/- 78 pg/ml after 30 min (P less than 0.01) and plasma cortisol levels from 0.45 +/- 0.06 mumol/liter (12.0 +/- 0.2 micrograms/dl) to 1.02 +/- 0.21 mumol/liter (27.2 +/- 0.6 micrograms/dl) after 120 min (P less than 0.005). The absolute increments of ACTH and cortisol levels in the patients with Cushing's disease were significantly (P less than 0.02 and P less than 0.05, respectively) higher than in the normal subjects. In individual patients, however, CRF responses were rather variable; three of the patients had ACTH or cortisol increases within the mean +/- SD of the responses of the control subjects. In another patient with Cushing's disease due to bilateral macro- and micronodular adrenocortical hyperplasia, who had nonsuppressible circulating ACTH and cortisol levels, unresponsiveness to CRF was shown. These results indicate that testing the pituitary-adrenocortical axis of patients with Cushing's disease may reveal hyperresponsiveness, normal responsiveness, and even unresponsiveness.

Adrenal Cortex↗
PubMed1983

Accurate measurements of the lower leg length and the ulnar length and its application in short term growth measurement.

A new method of lower leg measurement for the determination of endochondral growth has been described quite different from the techniques commonly utilized. Endochondral growth of the lower leg can now be detected after one week (in provided case) the growth is at least 0.15 mm. The results of the lower leg measurement were compared with those of the ulnar length measurements in a four months lasting longitudinal growth study on twenty-one normal growing children. It appeared that the new lower leg length measuring technique with a margin of error in hundreds of millimeters is even more sensitive than the ulnar length measuring technique and a substantial improvement to conventional measuring methods in which the error fault is commonly expressed in millimeters. The new technique is especially suited for the assessment of short term growth in children whose ulnar length can not be measured accurately enough. Short term growth can now be followed in children from about the age of two years without using X-rays. This new technique permits: 1. Short term growth studies; 2. Studies of drug effects on tibia in single individuals within short time intervals; 3. Comparison of the growth in length of the lower leg and the ulna within time intervals as short as three weeks. 4. Studies in biorhythms of the lower leg length.

Adolescent↗