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Biomedical subjects

D Klingmüller

Publications and source records attributed to D Klingmüller.

At least 55 records · Page 3Linked to original sources

A comparison of different methods for diagnosing acromegaly.

OBJECTIVE: The present study was designed to assess the diagnostic value of different single measurements in comparison to the classic time-consuming method, the oral glucose tolerance test (OGTT), in acromegaly. DESIGN, PATIENTS AND MEASUREMENTS: IGF-I, free IGF-I, 24-hour-urinary GH (uGH), serum IGFBP-3 and 24-hour-urinary IGFBP-3 (uIGFBP-3) were measured in 12 patients with untreated active acromegaly, in 29 patients who had been treated but were not cured, in 13 patients with cured acromegaly and in 14 healthy control subjects, and compared with the results of the OGTT. RESULTS: In all patients with active acromegaly, whether they had been treated or not, nadir GH in OGTT was > 3 mU/l, whereas nadir GH was < 1.8 mU/l in the cured patients and the control subjects. In patients with untreated active acromegaly IGF-I, free IGF-I, uGH and IGFBP-3, but not uIGFBP-3, were significantly higher than in healthy individuals (P < 0.0001). Only IGF-I values did not overlap with the control group. In those patients with acromegaly who had been treated but not cured these parameters overlapped with the control group. In patients with acromegaly there was a significant correlation between nadir GH levels in OGTT and IGF-I (r = 0.71), free IGF-I (r = 0.76), IGFBP-3 (t = 0.73) and uGH (r = 0.81) (P < 0.0001), but no correlation with uIGFBP-3. CONCLUSIONS: Only be means of the OGTT could patients with active acromegaly be completely distinguished from the control subjects and from cured patients. IGF-I, free IGF-I, IGFBP-3 and uGH were useful in the diagnosis of acromegaly, but of limited value in the follow-up of acromegalic patients after treatment. The determination of free IGF-I, which has yet not been investigated in acromegaly, offered no advantage over that of total IGF-I and IGFBP-3; uIGFBP-3 was not useful in the diagnosis of acromegaly.

Acromegaly↗

Inhibin B in men with normal and disturbed spermatogenesis.

Inhibin, a dimeric gonadal glycoprotein, inhibits the production and/or secretion of follicle stimulating hormone (FSH). The major species currently recognized are inhibin A (alphabeta A subunit) and inhibin B (alphabeta B subunit). In men, inhibin B seems to be the physiologically important form of inhibin. Therefore we measured serum inhibin B using a new two-site immunoenzymatic assay in 14 men (mean +/- SEM age, 34.5 +/- 0.7 years) with sperm counts >20 x 10(6)/ ml, in 35 men (mean +/- SEM age, 36.4 +/- 1.3 years) with oligozoospermia (sperm count <20 x 10(6)/ml) and in men with azoospermia (three orchidectomized men, three men with Klinefelter's syndrome, 10 men with Kallmann's syndrome). We compared inhibin B concentrations with serum FSH and sperm concentrations. In men with normal sperm concentrations (44.7 +/- 6.4 x 10(6)/ml), the concentration of inhibin was 223 +/- 18 pg/ml and of FSH 5.0 +/- 0.7 IU/l; in patients with low sperm concentrations (3.7 +/- 0.8 x 10(6)/ml), the concentration of inhibin B was 107 +/- 12 pg/ml and of FSH 12.2 +/- 1.5 IU/l. In all patients, except those with hypogonadotrophic hypogonadism, the relationship between inhibin B and FSH concentrations was inverse (r = -0.69, P < 0.0001). In all patients the sperm concentration was positively correlated with inhibin B concentrations (r = 0.70, P < 0.0001) and negatively correlated with FSH concentrations (r = -0.37, P < 0.01). We conclude that inhibin B may be a marker of exocrine testicular function and could offer improved diagnosis and treatment modalities for male infertility.

Adult↗

Gonadal function of patients treated with cisplatin based chemotherapy for germ cell cancer.

PURPOSE: The cure rate of patients with germ cell cancer of the testis has considerably improved since the introduction of cisplatin based chemotherapy. Because these patients are in their reproductive years and because some of them will be infertile after treatment, the effects of cytotoxic treatment on gonadal function are investigated by hormonal evaluations. MATERIALS AND METHODS: In a transversal trial, luteinizing hormone, follicle-stimulating hormone and testosterone were determined radioimmunologically in serum samples of 232 patients with germ cell tumors after unilateral orchiectomy (patient age 18 to 64 years) up to 153 months after chemotherapy. Additionally, 51 of these patients were investigated in a longitudinal trial before and up to 5 years after chemotherapy. All patients received at least 2 courses of different cisplatin based chemotherapy regimens: cisplatin/vinblastine/bleomycin, cisplatin/vinblastine/bleomycin/ifosfamide, cisplatin/etoposide/bleomycin, cisplatin/vinblastine/bleomycin/ifosfamide/etoposide. Additionally, 11 patients with germ cell tumors (age 22 to 38 years, stage I) were investigated within the first year after orchiectomy and retroperitoneal lymphadenectomy but without chemotherapy. RESULTS: In the transversal trial, 24 of 73 patients investigated during the first year after chemotherapy showed elevated luteinizing hormone concentrations, 5 had subnormal serum testosterone and 65 had elevated serum follicle-stimulating hormone, reflecting spermatogenesis deficits. In 28 patients studied longer than 8 years after chemotherapy (median followup 8.5 years, range 8.0 to 12.6), luteinizing hormone increased after chemotherapy and 60 months after treatment, and follicle-stimulating hormone was elevated in 1 patient, follicle-stimulating hormone was increased in 18 and testosterone was subnormal in 1. Patients without chemotherapy treatment showed gonadotropin and testosterone within normal range and 3 patients had elevated serum follicle-stimulating hormone. In the longitudinal study, mean serum luteinizing hormone plus or minus standard deviation (3.45 +/- 0.05 IU/l.), follicle-stimulating hormone (7.79 +/- 0.13 IU/l.) and testosterone (18.6 +/- 0.17 nmol./l.) were within the normal range before chemotherapy; serum follicle-stimulating hormone was still significantly elevated (16.9 +/- 0.71 IU/l., 19 cases, p < 0.001). Mean luteinizing hormone and testosterone levels were within the normal range, but 60 months after therapy the testosterone-to-luteinizing hormone ratio was still lower than before treatment (p < 0.05). CONCLUSIONS: In patients with germ cell tumors, a compensated insufficiency of the function of the Leydig cells was still observed up to 60 months after chemotherapy. Of these patients 68% showed elevated follicle-stimulating hormone levels, which reflected a functional insufficiency of the Sertoli cells with impaired spermatogenesis. This study shows that impairment of germinative functions is more severe and protracted than the impairment of the endocrine functions.

Adolescent↗

Testicular dysfunction in adrenomyeloneuropathy.

Adrenomyeloneuropathy (AMN) is a disorder due to a disturbance in the peroxisomal beta-oxidation of saturated very long chain fatty acids. It is characterized by symptoms of the nervous as well as the endocrine systems, especially the adrenal cortex and the gonads. We investigated the testicular function in 49 male AMN patients aged 36.2 +/- 1.5 years (range, 18.5-59 years). Twenty-four of these patients were suffering from adrenocortical insufficiency. Twenty-five AMN patients showed neurological symptoms without 'Addison's disease'. To register the frequency and the degree of gonadal impairment, LH and FSH, testosterone, free testosterone and inhibin-B were determined. Gonadotropin concentrations were significantly higher in AMN patients than in healthy controls (LH, 8.0 +/- 1.2 vs 2.77 +/- 0.11 IU/l; FSH, 10.1 +/- 1.6 vs 4.0 +/- 0.17 IU/l; P < 0.001). Serum LH was elevated in 31 patients (63.3%); 28 patients (57.1%) showed elevated serum FSH indicating deficient spermatogenesis. Mean testosterone did not differ significantly between patients and healthy controls, but mean free testosterone was significantly lower in patients than in controls (16.3 +/- 1.0 vs 28.5 +/- 1.68 pg/ml, P < 0.002). Inhibin-B concentrations did not differ between AMN patients and healthy men. The testosterone/LH ratio reflecting an impairment of the Leydig cells was significantly lower in AMN patients than in controls (P < 0.01). An impairment of the Leydig cells and/or of the Sertoli cells was evident in 81.6% of AMN patients. Twenty-one of thirty-nine patients (53.8%) admitted erectile dysfunction. These data indicate that endocrine dysfunction in AMN is not only confined to adrenocortical functions, but testicular dysfunctions also frequently occur, thus permitting the term 'adreno-testiculo-myelo-neuropathy'.

Adolescent↗

[Scintigraphy of the parathyroid glands with 99mTc-MIBI].

AIM: Since about 3 years 99mTc-MIBI is used instead of 201Tl/99mTc subtraction scintigraphy for the localization of parathyroid involvement in hyperparathyroidism (HPT). The sensitivity of the new method was evaluated. PATIENTS AND METHODS: 24 patients aged between 28 and 83 years with surgically confirmed primary HPT were studied. Planar images were acquired 15 minutes and 3 hours after tracer injection. Additionally, in 9 patients dynamic images were obtained for 2 hours to study tracer kinetics. RESULTS: 19 out of 24 adenomas (79%) were identified correctly with 99mTc-MIBI. CONCLUSION: The sensitivity of the scintigraphy using 99mTc-MIBI is in the range of the 201Tl/99mTc subtraction scintigraphy. Because of the superior logistic and the lower radiation exposure, 99mTc-MIBI can replace the 201Tl/99mTc scintigraphy in the preoperative diagnostic assessment.

Adenoma↗

Clinical significance of serum S100 in metastatic malignant melanoma.

The clinical significance of serum S100 was assessed in comparison to neuron-specific enolase (NSE) in 126 patients with malignant melanoma: 80 patients with clinical stage I/II, 23 patients with stage III and 23 patients with stage IV according to the criteria of the American Joint Committee on Cancer (AJCC). Using cut-off values of 0.15 micrograms/l for S100 and 12.5 micrograms/l for NSE, the sensitivity was found to be 1.3% (1/80) for S100 and 8.75% (7/80) for NSE in patients with stage I/II, 8.7% (2/23) for S100 and 13% (8/23) for NSE in patients with stage III, and 73.9% (17/23) for S100 and 34.8% (8/23) for NSE in patients with stage IV disease (P < 0.05). In 6 patients with stage III/IV tumours, serial measurement of serum S100 and NSE was performed. A rise of serum S100 indicated progression of the disease; a decline indicated response to treatment. Our preliminary results support the value of serum S100 as an adjunct to the clinical staging and monitoring of metastatic malignant melanoma.

Adult↗

Clinical significance of serum S100 in metastatic malignant melanoma.

The clinical significance of serum S100 was assessed in comparison to neuron-specific enolase (NSE) in 126 patients with malignant melanoma: 80 patients with clinical stage I/II, 23 patients with stage III and 23 patients with stage IV according to the criteria of the American Joint Committee on Cancer (AJCC). Using cut-off values of 0.15 microgram/l for S100 and 12.5 micrograms/l for NSE, the sensitivity was found to be 1.3% (1/80) for S100 and 8.75% (7/80) for NSE in patients with stage I/II, 8.7% (2/23) for S100 and 13% (8/23) for NSE in patients with stage III, and 73.9% (17/23) for S100 and 34.8% (8/23) for NSE in patients with stage IV disease (P < 0.05). In 6 patients with stage III/IV tumours, serial measurement of serum S100 and NSE was performed. A rise of serum S100 indicated progression of the disease; a decline indicated response to treatment. Our preliminary results support the value of serum S100 as an adjunct to the clinical staging and monitoring of metastatic malignant melanoma.

Aged↗

Effects of the gonadotropin-releasing-hormone agonist, D-Trp-6-GnRH, on prolactin secretion in healthy young men.

The objective of this study was to examine the changes in basal plasma gonadotropin, alpha-subunit, sex steroids, and prolactin levels and the prolactin and luteinizing hormone (LH) secretion pattern before, during and 161 days after treatment with a depot preparation of D-Trp-6-GnRH in young men. Gonadotropins, alpha-subunit, sex steroids, and prolactin were measured in pooled plasma samples. Additionally, before treatment, several times during its course and on day 161 after treatment, blood samples were drawn for 8 h every 15 min for prolactin and LH measurements. After initial stimulation of the pituitary, administration of a depot preparation of D-Trp-6-GnRH resulted in a constant decrease in gonadotropin and sex steroid concentrations with LH and testosterone concentrations remaining within the limits of prepubertal levels from days 16 to 48. Alpha-Subunit concentrations (0.4 +/- 0.09 IU/l; mean +/- SE) increased after application of D-Trp-6-GnRH, and remained elevated until day 48. Basal prolactin levels (3.5 +/- 0.25 microgram/l) did not change significantly during treatment but afterwards increased consistently with maximal levels at day 141 (15.3 +/- 3.8 microgram/l); they had decreased at day 161 to 10.3 +/- 1.8 microgram/l which is significantly higher than before treatment (p < 0.05). On day 161, prolactin pulse amplitude was significantly higher than before and during treatment (p<0.05), while no significant changes in pulse frequency occurred. No significant temporal coupling between LH and prolactin release could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Immunoreactive inhibin concentrations in human gonads and adrenals during the first years of life.

We determined immunoreactive inhibin (irINH) concentration in the gonads and adrenals of healthy children (0-75 months) who had died suddenly. Testicular irINH peaked in the first 3 months of life with a significant drop in the 4th month (p < 0.05). In ovarian tissue, irINH was significantly lower than in the testes (p < 0.001) with highest levels during the first 4 months of life parallel to the highest estradiol concentrations. A significant correlation between gonadal testosterone/estradiol and irINH was observed. In adrenal tissue, irINH levels were significantly lower than in the gonads without sex-specific differences.

Adrenal Glands↗

Opiate antagonists in erectile dysfunction: a possible new treatment option? Results of a pilot study with naltrexone.

Opioids have an inhibitory effect on sexual functions in both animals and humans. Twenty patients with idiopathic, nonvascular, nonneurogenic erectile dysfunction were treated with the opiate receptor antagonist naltrexone in a randomized, placebo-controlled, double-blind study for 8 weeks. Libido and frequency of sexual intercourse were not significantly altered, but early-morning erections increased significantly under naltrexone therapy. This response was not related to levels of androgens or gonadotropins, neither was it dose dependent. There was no change in any of the measured parameters under placebo. Further clinical studies with the substance should be conducted to evaluate its possible role in the oral treatment of male impotence.

Adult↗

Attempted protection of spermatogenesis from irradiation in patients with seminoma by D-Tryptophan-6 luteinizing hormone releasing hormone.

Possible protective effects of D-Tryptophan-6 luteinizing hormone releasing hormone (D-Trp-6-LH-RH) against irradiation-induced testicular damage were investigated for the first time in patients with seminoma. After unilateral orchiectomy 12 men were allocated to receive the long-acting gonadotropin releasing hormone (GnRH) agonist D-Trp-6-LH-RH prior to and for the duration of radiotherapy. Eight patients with the same disease served as a control group. In contrast to several trials to protect spermatogenesis from chemotherapy by GnRH agonists, we first suppressed the pituitary-testicular axis before starting the treatment. As a new schedule this adjuvant GnRH agonist treatment was combined with cyproterone acetate for the first 20 days to diminish the amount and the duration of the initial stimulation of gonadotropins and testosterone. Irradiation started after suppression of the pituitary-gonadal axis. In all patients luteinizing hormone and testosterone were completely suppressed throughout the treatment compared to the controls, whereas the initial suppression of follicle-stimulating hormone was not completely maintained until radiotherapy was completed. At the follow-up at 18 months after completion of therapy, all patients reached their initial concentration of gonadotropins, testosterone, and motile spermatozoa independently of D-Trp-6-LH-RH treatment. With the dose and schedule investigated, the GnRH agonist showed no protective effects against testicular damage caused by radiotherapy.

Adult↗

Serum prolactin response to repetitive epileptic seizures.

We measured postictal prolactin (PRL) levels during repetitive seizures in 14 patients (10 men and 4 women) suffering from epilepsy with focal and/or secondarily generalized seizures. Between two and six seizures occurred per patient (mean 2.7). The interveral between seizures was 15 min and 8 h 40 min (mean 3 h 32 min). Five of the 14 patients showed a marked postictal PRL rise after each seizure (i.e. concentrations above 700 microU/ml for women, 500 microU/ml for men). In the remaining 9 patients there was no detectable rise in PRL. A decrease in PRL did not occur in any of the 14 patients. In those patients who had shown a marked PRL increase after the first seizure, the PRL continued to rise in subsequent seizures. Unlike previous investigations, these results show that repetitive epileptic seizures are not necessarily followed by a decrease in postictal PRL levels. A decrease in PRL response is known to occur if there is progression to status epilepticus.

Adolescent↗

[Suppression of endogenous LH increase in ovarian stimulation with the GnRH antagonist Cetrorelix].

Surges of LH in serum, which result in luteinization, but occur prematurely with respect to the diameter of the leading follicle, frustrate attemps to induce multiple follicular maturation for in-vitro fertilisation in a number of women. We examined the possibility of blocking premature LH-surges by the administration of Cetrorelix, a potent antagonist of gonadotrophin releasing hormone. Twenty patients, who had repeatedly shown premature LH surges, were treated with human menopausal gonadotrophins from the 2nd day onwards. From the 7th day until the induction of ovulation by HCG, the GNRH-antagonist Cetrorelix was given daily. HCG was injected when the dominant follicle had reached the diameter of at least 18 mm and oestradiol levels were above 300 pg for each follicle and more than 15 mm. Oocyte collection was performed 36 hours later by transvaginal ultrasound puncture, followed by IVF and embryo transfer. The hormone profiles of these patients and the results of in-vitro fertilisation and embryo transfer are discussed. It could be demonstrated in this study, that combined treatment with gonadotrophins and the GNRH-antagonist seems to be a promising method for ovarian stimulation in patients, who frequently exhibit premature LH discharges and therefore fail to complete treatment.

Adult↗

Suppression of the endogenous luteinizing hormone surge by the gonadotrophin-releasing hormone antagonist Cetrorelix during ovarian stimulation.

Surges of luteinizing hormone (LH) that result in luteinization but occur prematurely with respect to the diameter of the leading follicle, prevent attempts to induce multiple follicular maturation for in-vitro fertilization (IVF) in a significant number of women. We examined the possibility of blocking premature LH surges by the administration of Cetrorelix, a potent antagonist of gonadotrophin-releasing hormone (GnRH), in a study including 20 patients, some of whom had previously shown premature LH surges. All patients were treated with human menopausal gonadotrophins (HMG) starting on day 2. From day 7 until the induction of ovulation by human chorionic gonadotrophin (HCG) the GnRH antagonist Cetrorelix was given daily. HCG was injected when the dominant follicle had reached a diameter of > or = 18 mm and oestradiol concentration was > 300 pg/ml for each follicle having a diameter of > 15 mm. Oocyte collection was performed 36 h later by transvaginal ultrasound puncture, followed by IVF and embryo transfer. The hormone profiles of these patients and the results of IVF and embryo transfer are comparable to those treated with GnRH agonists and HMG. However, less time and especially less HMG is needed in comparison to patients stimulated with a long agonist protocol. Hence, treatment with Cetrorelix proved to be much more comfortable for the patient. In this study we showed that combined treatment with gonadotrophins and the GnRH antagonist Cetrorelix is a promising method for ovarian stimulation in patients who frequently exhibit premature LH surges and therefore fail to complete treatment.

Adult↗

Secretion pattern of immunoreactive inhibin in men.

Chronological changes in serum concentrations of inhibin, a gonadal glycoprotein hormone, were studied in healthy male volunteers (age 24-27 years). Secretion profiles of immunoreactive inhibin (ir-inhibin) were compared with those of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. Blood samples were collected every 15 min for 24 h. Serum inhibin concentrations were measured by a two-site immunoenzymatic assay with antibodies raised against distinct epitopes of the recombinant 1-32 amino acids of the alpha-subunit of human inhibin. The normal range for men was 0.79-3.1 U/l x 10(-3), the sensitivity of the assay was 0.1 U/l x 10(-3) (cv: within-assay, 6.8%; between-assay, 8.2%). Luteinizing hormone and FSH were measured by immunoradiometric assay and testosterone by radioimmunoassay. Secretion profiles of inhibin and testosterone were tested for diurnal variations by cosinor rhythmometry. Highest ir-inhibin concentrations were observed in the morning at 08.00 h, with peak values of 2.45-3.20 U/l x 10(-3). During the evening and the night, ir-inhibin levels were relatively low; lowest concentrations were observed between 01.00 h and 02.00 h at night: 1.20-1.86 U/l x 10(-3). Highest testosterone levels were observed in the morning (20.5-36.6 pmol/l), lowest concentrations were detected at night (7.35-12.6 pmol/l). Cosinor rhythmometry supported the suggestion that there is a clear circadian secretion of ir-inhibin and testosterone, respectively. The secretion pattern of ir-inhibin was analyzed by the Cluster pulse analysis computed algorithm, which identified four to seven inhibin pulses per day, depending on the person under observation.2+ volunteers follow a clear diurnal rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗