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Biomedical subjects

A G Smals

Publications and source records attributed to A G Smals.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Systemic mastocytosis as a cause of osteoporosis].

Out of 21 male patients with osteoporosis who visited an outpatient clinic for endocrine diseases in two years (1994-1995), three had systemic mastocytosis as diagnosed histopathologically. Two of these had characteristic features of urticaria pigmentosa, consisting of multiple brown nodules on the skin of trunk and extremities, and a positive Darier sign. In all of them the excretion of the histamine metabolites methylhistamine and methylimidazoleacetic acid in a 24-hour urine specimen was increased. When osteoporosis is diagnosed in men or premenopausal women, underlying pathology could be considered. Cautious investigation of signs and symptoms of systemic mastocytosis in such patients might prove this disease be less rare than is often assumed.

Absorptiometry, Photon↗
PubMed1996

Number and percentage of NK-cells are decreased in growth hormone-deficient adults.

Snell-Bagg mice and Ames dwarf mice repeatedly show severe immunodeficiencies, affecting mostly the thymus- dependent lymphocyte system, probably caused by growth hormone deficiency. In growth hormone-deficient children contradictory data on the immune status have been reported. We investigated indices of cellular immunity in 22 adult patients with proven growth hormone deficiency in comparison to those in 100 health volunteers. Cellular immunity was assessed using total leukocyte count, percentage lymphocytes, and percentage and absolute numbers of CD3, CD4, CD8, CD19, and CD3-CD56+ (NK)-cells. Comparison revealed statistically significantly lower percentage and absolute number of NK-cells (P < 0.001). Except for a trend toward an increased CD4/CD8 ratio, no statistically significant differences for B- and T-lymphocytes could be observed. No correlation between the percentage and absolute number of NK-cells, on one hand, and the duration of growth hormone deficiency or prolactin level, on the other hand, could be demonstrated. In all these respects men did not differ from women. So, in growth hormone-deficient adults the percentage and absolute number of NK-cells are decreased.

Adolescent↗
PubMed1996

Kinetic analysis of steroid 5alpha-reductase activity at neutral pH in benign prostatic hyperplastic tissue: evidence for type I isozyme activity in the human prostate.

In human benign prostatic hyperplastic (BPH) tissue homogenates 5alpha-reduction of testosterone was examined at neutral pH. As Lineweaver-Burk and Eadie-Scatchard plots of estimated initial velocities against a wide range of substrate concentrations of 2 nM to 3.2 microM were non-linear, the existence of two 5alpha-reductase isozymes in this tissue was surmised. Indeed, enzyme parameters at pH 7.0 suggested the presence of two isozymes with affinity constants of 1995 and 11.8 nM, characteristic of the well established human steroid 5alpha-reductase isozymes type I and II, respectively. The physiological roles of these isozyme activities remain puzzling. The specific activities, Vmax, of these subtypes indicated an approx. 6-fold higher maximum velocity of type I than of type II 5alpha-reductase in the human hyperplastic prostate at this pH. In contrast, the efficiency ratios, Vmax/Km, demonstrated that the type II isozyme had a nearly 27 times higher potential in vivo activity than the type I isozyme, and is therefore most probably quantitatively responsible for dihydrotestosterone formation at physiological testosterone levels in this tissue at neutral pH. This is the first full paper on type I 5alpha-reductase activity in human BPH tissue.

Aged↗
PubMed1996

Kinetic analysis of rat steroid 5alpha-reductase activity in prostate and epididymis homogenates at neutral pH: evidence for type I activity in epididymis.

Immunocytochemical studies and mRNA measurements have shown that the rat epididymis--like the rat prostate--expresses both rat steroid 5alpha-reductase isozymes, i.e. type I and II. So far, enzyme activity measurements in rat epididymis homogenates, however, do not support the presence of type I 5alpha-reductase activity. Incubating homogenates of both tissues with a wide range of substrate concentrations, we were able to detect activity of both isozymes in rat prostate and epididymis tissues at neutral pH. In rat prostate the amount of type I activity, as measured by the Vmax at pH 7.0, exceeds that of type II 5alpha-reductase 50-fold. The efficiency ratio, Vmax/Km, of the type I isozyme accounts for 25% of the total in vivo potential activity. A possible anabolic role for the type I isozyme in rat prostate was thus surmised. In rat epididymis the Vmax of type I and type II 5alpha-reductase at pH 7.0 were similar. Comparison of the efficiency ratio Vmax/Km of either isozyme in the rat epididymis, however, suggested that the type II isozyme would play the major role in the 5alpha-reduction of testosterone at physiological concentrations and at neutral pH. The specific localization of the isozymes should be considered to allow for correct quantification of their in vivo contribution to dihydrotestosterone formation.

Animals↗
PubMed1996

3 Alpha-hydroxysteroid oxidoreductase activities in dihydrotestosterone degradation and back-formation in rat prostate and epididymis.

The metabolism of dihydrotestosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-Adiol) was assessed in full homogenates of rat prostate and epididymis. The major degradational route of DHT was catalysed by the enzyme(s) 3 alpha-hydroxysteroid oxidoreductase (HSOR). Enzyme kinetic characteristics Vmax, Km and Vmax/Km ratio, were obtained for the NADP(H)- and NAD(H)-dependent interconversion of DHT and 3 alpha-Adiol at pH 7.0 and at saturated co-factor concentration. For both the reduction of DHT and the oxidation of 3 alpha-Adiol, NAD(H) was the preferred co-factor when activities were rated by their Vmax and Vmax/Km ratio. Combining the data with the earlier established Vmax/Km ratios for the 5 alpha-reductase isozyme type I and II activities in rat prostate and epididymis indicated that DHT, at saturated co-factor concentrations, would not be sustained in either tissue considering the reported enzyme characteristics. The reported exclusive bioavailability of the co-factors NADPH and NAD+ in vivo, however, will direct the metabolic pathways in these tissues to sustain the formation of DHT.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Rat steroid 5 alpha-reductase kinetic characteristics: extreme pH-dependency of the type II isozyme in prostate and epididymis homogenates.

Reevaluating the assay for rat steroid 5 alpha-reductase isozymes in prostate and epididymis homogenates we encountered an extreme pH-dependency of the type II isozyme. The time-course of the metabolism of testosterone (T) to 17 beta-hydroxy-5 alpha-androstan-3-one (DHT) at acidic pH shows an initial burst when the homogenate is not brought to pH before the start of the incubation. Therefore, the rat type II 5 alpha-reductase isozyme does not follow Michaelian law under these conditions making a single time point measurement invalid. Assessing the pH-optimum of 5 alpha-reduction in both rat prostate and epididymis homogenates we found a strong substrate dependency: at high substrate concentrations a pH-optimum for the type II isozyme of pH 5.0 was found, whereas at lower concentrations pH 5.5 is optimal. Establishing Vmax (maximum velocities) and Km (affinity constants) for the 5 alpha-reduction of T at pH 4.5-8.0, the efficiency optimum Vmax/Km appeared to be pH 5.5 in both prostate and epididymis homogenates. Specifically at acidic pH these kinetic characteristics of the type II isozyme vary many-fold. Discrepancies in literature concerning 5 alpha-reductase characteristics can, at least in part, be attributed to the choice of optimal pH, or to pH shifts during the assay.

Animals↗
PubMed1995

Bone mineral density and bone turnover before and after surgical cure of Cushing's syndrome.

We measured bone mineral density (BMD) using dual-energy x-ray absorptiometry in 20 patients with Cushing's syndrome (CS) (14 pre- and 2 postmenopausal women, 4 men) before and in 18 of them also at regular intervals after surgical cure (median duration of follow-up, 36 months). In addition, in the premenopausal women with CS, fasting blood samples and 2-h fasting urine samples for measurement of biochemical parameters of bone and collagen metabolism were collected before and in 9 of them also at regular intervals during the first 2 yr after surgery. Marked osteopenia was present in most patients with active CS (Z-scores: lumbar spine -1.45 +/- 1.44 and femoral neck -1.50 +/- 1.02; mean +/- SD). No consistent change in BMD was observed at 3 and 6 months after surgery. Thereafter BMD increased considerably in almost all patients. For the 15 patients with a follow-up of at least 1 yr, Z-scores at the last evaluation were -0.65 +/- 1.27 for the lumbar spine and -0.98 +/- 1.02 for the femoral neck (both P < 0.002 compared with pretreatment values). In the premenopausal patients, the increase in BMD both in the lumbar spine and in the femoral neck at 24 months was inversely correlated with age (r = -0.733, P < 0.03, and r = -0.667, P < 0.05, respectively). Serum levels of osteocalcin, bone alkaline phosphatase, carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen, and the cross-linked telopeptide of type I collagen were not significantly different between the group of 14 premenopausal patients with active CS and a control group of 18 age-matched healthy premenopausal women. However, the urinary hydroxyproline/creatinine ratio was significantly higher in patients with CS (24.6 +/- 9.6 vs. 16.2 +/- 3.5 mumol/mmol, P < 0.01). In all 9 premenopausal patients, serum levels of osteocalcin increased considerably between 0 and 3 months (from 1.04 +/- 0.20 to 3.82 +/- 0.30 nmol/L) (mean +/- SEM, P < 0.0001), indicating a prompt increase of osteoblast activity. Also serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen, and cross-linked telopeptide of type I collagen, and the urinary hydroxyproline/creatinine ratio increased significantly between 0 and 3 months. Thereafter these levels decreased gradually. We conclude that marked osteopenia in the lumbar spine and femoral neck is present in most patients with active Cushing's syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Sudomotor function in human poikilothermia.

Hypohidrosis predisposes to hyperthermia and may indicate generalized thermoregulatory failure. To assess the sweating capacity in human poikilothermia, we performed a quantitative analysis of the central and peripheral sudomotor pathways in four women with acquired poikilothermia (aged 29 to 38 years) and nine controls. Heat challenge in a climatic chamber (ambient temperature 40 degrees C, 50% relative humidity) for 180 minutes revealed that both sweat secretion and evaporative weight loss were significantly lower in the patients than in the controls (p < 0.01). Temperature thresholds for thermal sweating were markedly elevated in at least two patients, whereas a third patient showed no sweating response. Stimulation of the eccrine sweat glands by intradermally injected acetylcholine during reduced core temperature (34.9 +/- 0.7 degrees C) revealed a significantly reduced sweating response in all patients (p < 0.01); the sudomotor response to pilocarpine iontophoresis was reduced or absent in three patients. We conclude that the generalized thermoregulatory sudomotor failure in these patients was attributable primarily to disorders of the central sudomotor drive; the impaired postganglionic sudomotor response is temperature related and possibly secondary to (long-standing) poikilothermia. Quantification of heat-dissipating capacity is pivotal for diagnosing severe thermolability and may help to prevent serious heat illness.

Acetylcholine↗
PubMed1994

Predictive value of luteinizing hormone releasing hormone (LHRH) bolus testing before and after 36-hour pulsatile LHRH administration in the differential diagnosis of constitutional delay of puberty and male hypogonadotropic hypogonadism.

Intravenous LHRH bolus testing (100 micrograms) after 36 h of pulsatile LHRH administration (5 micrograms/90 min) preliminary has been reported to allow complete differentiation between constitutional delay of puberty (DP) and hypogonadotropic hypogonadism (HH) in a small group of sexually immature patients. So far, these data have never been confirmed. To assess the discriminatory power of the test, 33 patients with a presumptive diagnosis of either DP (n = 17) or HH (n = 16), confirmed by clinical follow-up, were studied accordingly. Both groups of patients had similar mean basal LH and FSH levels (P > 0.10). The mean basal plasma testosterone level was three times higher in DP than in HH (4.2 +/- 1.0 vs. 1.4 +/- 0.2 nmol/L, P* < 0.001), but there was a wide overlap. In response to the first LHRH bolus test, the mean LH increment was significantly lower in HH than in DP patients (P < 0.001), but, in 44% of the patients, the values overlapped. The FSH increments were similar in HH and DP. Pulsatile LHRH administration for 36 h similarly increased LH levels in HH and DP to values (2.7 +/- 0.4 and 3.8 +/- 0.5, respectively) slightly higher than before (P < 0.01), but again, not statistically significantly different from each other. The mean testosterone levels increased 2-fold in both groups and remained significantly higher in DP than in HH (7.6 +/- 2.1 vs. 2.8 +/- 0.5 nmol/L P* < 0.05). The mean FSH levels after priming also rose, however, to levels significantly higher in HH than in DP (5.2 +/- 0.8 vs. 3.5 +/- 0.4, P* < 0.05). In HH the ratio of FSH to LH almost doubled, whereas it virtually remained unchanged in DP. LHRH bolus testing after LHRH priming evoked a significantly lower LH response in both HH and DP than before priming despite only slightly higher baseline LH values. The LH increment in HH was five times lower in HH than in DP. In any of the 16 HH patients, the LH increment was < or = 3 IU/L, whereas in 15 out of 17 DP patients the increase was higher (sensitivity of the test 100%, specificity 88%, and diagnostic efficiency 94% after LHRH priming against 56%, 94%, and 75% respectively, before LHRH priming.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

[Compared to whole body scanning thyroglobulin assay is reliable in the follow-up of thyroidectomized patients with thyroid carcinoma].

OBJECTIVE: To determine whether it is reliable to do thyroglobulin measurements during thyroid hormone substitution (Tg ON) alone or whether it is also necessary to do 131I total body scanning (TBS) and Tg measurements after withdrawal of thyroid hormone substitution (Tg OFF) in the follow-up of patients with differentiated thyroid carcinoma. DESIGN: Retrospective. SETTING: University Hospital Nijmegen. METHODS: 202 Patients (151 females and 51 males, mean age 50.6 years) with differentiated thyroid carcinoma were examined in the period 1970-90. All patients had undergone total thyroidectomy and if necessary 131I ablation. 27 Patients with Tg antibodies were excluded (13.4%). In 175 patients Tg OFF levels were compared with TBS and clinical and radiological data. In 81 of them Tg ON levels were also compared. RESULTS: Specificity of Tg OFF and Tg ON measurement was 83 and 88%. Sensitivity of Tg OFF and Tg ON measurement was 100 and 92%. In detecting local residual thyroid tissue Tg OFF was superior to Tg ON. In detecting metastases Tg OFF and Tg ON were both superior to TBS. CONCLUSION: In the follow-up of patients with differentiated thyroid carcinoma it is reliable to do Tg measurements during thyroid hormone suppression. When Tg ON is detectable (> 3 pmol/l) TBS and Tg OFF measurement and if necessary further investigations have to be performed.

Adolescent↗
PubMed1993

[Experiences with intracavernous auto-injection for the treatment of erection disorders].

We report on our experience with autoinjection therapy in 72 patients with erectile dysfunction. We analysed factors that have an impact on the outcome of autoinjection therapy, and we focused on psychological, sexological and relational issues. In 53 (74%) patients an organic aetiological factor was found. Although with the aid of injection 82% of the men were able to achieve an erection adequate for penetration, only 39% continued treatment beyond one year. Lowest drop-out rates were encountered among patients with diabetes mellitus and men without organic aetiology (50% and 53% respectively). The most important reason for discontinuation was lack of acceptance of autoinjection therapy by the partner. Other reasons were prolonged erection, haematomas, ineffectiveness and fear of self-injection. Although autoinjection provides a safe and effective long-term method for the treatment of erectile dysfunction, the drop-out rate is strikingly high. Apparently, the acceptance of the partner is the most important determinant of the result of autoinjection therapy. Therefore, the partner should be involved in the counselling and treatment from the beginning.

Adult↗
PubMed1993

Major contribution of the basic amino acid lysine at position 11 to the bioactivity of ACTH in purified isolated rat adrenocortical cells.

The contribution of the positive charge of lysine in position 11 of ACTH to the corticosteroidogenicity was tested in a purified isolated rat adrenal cell assay. ACTH analogues with Lys11 or Arg11 had the same bioactivity. Replacement of lysine by norleucine or protection of its positive charge diminished the potency by about a factor of 80. The extent of this reduction has been discussed in relation to the importance of the basic amino acid sequence 15-18 of the peptide. The result suggests a ten times higher contribution of Lys11 to the bioactivity of ACTH than the surmised potency of the individual amino acids present in the sequence 15-18.

Adrenal Cortex↗
PubMed1993

Increase of the proportion of corticosteroidogenic activity of ACTH versus immunoreactive ACTH in rat plasma extracts during stress.

The relationship between bioactive and immunoreactive adrenocorticotrophin (ACTH) was studied under various conditions. Rats were stressed by ether and the immunoreactive (I-ACTH) and bioactive (B-ACTH) ACTH levels were compared to the normal values obtained from "handled" rats. The bioactivity was determined by measuring the corticosteroid production in an isolated rat adrenal cell system. Stress exposure enhanced both the I-ACTH and B-ACTH levels. I-ACTH rose from 86.9 +/- 37.9 to 363 +/- 148.7 pg/ml, whereas the B-ACTH levels rose from 34.2 +/- 11.9 to 424.2 +/- 170.9 pg/ml. The bioactive to immunoreactive ratio (B/I ratio) was calculated as 0.47 +/- 0.13 in the control group and rose to the significantly higher value of 1.10 +/- 0.22 in the stressed rats. The conclusion is that under normal circumstances only about 50% of plasma immunoreactive ACTH shows corticosteroidogenic activity and that the B/I ACTH ratio might be a useful tool to estimate the physiological phase of the pituitary releasing activity.

Adrenal Cortex Hormones↗
PubMed1993

Multiple forms of bioactive and immunoreactive adrenocorticotropin in human pituitary and blood of patients with Nelson's syndrome.

A pool of human pituitaries obtained from allegedly healthy subjects (traffic victims) and plasma samples from patients with Nelson's syndrome were analyzed by high performance liquid chromatography, and the corticosteroidogenic bioactivity and ACTH immunoreactivity were measured. Three bioactive forms of ACTH were detected in plasma samples and pituitary extract. The major form (peak III) coeluted with human ACTH-(1-39), showed a bioactive to immunoreactive ratio (B/I ratio) of about 1, and represented about 80% of the total bioactivity in both the plasma samples and the pituitary extract. Peak I, with a B/I ratio greater than 1, represented about 5%, and peak II, with a highly variable B/I ratio, represented about 7% of the bioactivity in both the plasma and pituitary extracts. A fraction with a very low B/I ratio was found to coelute with corticotropin-like intermediate lobe peptide. These data suggest that in Nelson's syndrome, ACTH secretion by the pituitary gland does not differ from that in normal subjects, at least qualitatively.

Adrenocorticotropic Hormone↗
PubMed1993

Unpredictable hypersecretion of cortisol in Cushing's disease: detection by daily salivary cortisol measurements.

A 70-year-old man with mild signs and symptoms of Cushing's syndrome due to an ACTH-secreting pituitary adenoma is described. He had a completely unpredictable pattern of urinary excretion of cortisol; 24 h urine for determination of cortisol excretion was collected daily at home on 725 consecutive days. During this period there were eight episodes in which urinary cortisol excretion exceeded the upper limit of normal. Within these episodes the pattern of cortisol secretion was extremely unpredictable, with cortisol excretion ranging from normal to highly elevated. Using a Cluster Analysis Program 61 pulses of cortisol excretion were detected within the eight periods of cortisol hypersecretion. The interval between two pulses varied from 2 to 12 days. Between the periods of cortisol hypersecretion, urinary cortisol excretion was completely normal, lasting from 4 to 102 days. There was no difference in the clinical expression of Cushing's syndrome between the periods of elevated and normal urinary cortisol excretion. During the last 439 days of the observation, cortisol was also measured in saliva collected at home at 09.00 after an overnight fast. The salivary cortisol pattern closely resembled that of urinary cortisol excretion and there was a significant correlation between salivary cortisol levels and 24 h urinary cortisol excretion in the 24 h after (r = 0.42, p < 0.0001, Spearman) and before saliva collection (r = 0.44, p < 0.0001). On 71% of occasions cortisol peaks in saliva, as detected by the Cluster Analysis Program, coincided with urinary cortisol peaks. We conclude that daily measurement of cortisol in saliva, collected at home, is a convenient and reliable method for detecting intermittent hypercortisolism in patients with Cushing's syndrome.

Adenoma↗