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Biomedical subjects

J Müller

Publications and source records attributed to J Müller.

At least 199 records · Page 11Linked to original sources
PubMed2000

Serum inhibin A and inhibin B in central precocious puberty before and during treatment with GnRH agonists.

Serum levels of the gonadal hormones inhibin A and inhibin B are undetectable or low in prepubertal girls, and rise during puberty. In girls with central precocious puberty (CPP) the hypothalamic-pituitary-gonadal axis is prematurely activated, if the girl is thereafter treated with GnRH agonists both gonadotropins and estradiol levels become suppressed. We therefore investigated serum levels of inhibin A and inhibin B in girls with CPP at diagnosis and during treatment in order to test the hypothesis that inhibin secretion would increase and decrease in parallel with the activation and suppression of the hypothalamic-pituitary-gonadal axis. Serum levels of inhibin A and inhibin B were significantly (p < 0.0005) elevated in 42 girls at diagnosis of CPP (inhibin A: 7 pg/ml (<7--139), inhibin B: 80 pg/ml (<20--294) (median, range)) compared to levels in age-matched healthy schoolgirls (inhibin A: all values <7 pg/ml, inhibin B: 21 pg/ml (<20--122) (median, range)), but were appropriate for Tanner stage. During treatment with GnRH agonist (intranasal buserelin and oral cyproterone acetate, treatment group 1, n = 23, or triptorelin depot injections, treatment group 2, n = 19) levels of both hormones fell significantly (p = 0.002). There was a significantly (p = 0.003) greater fall in inhibin B levels during treatment in group 2 compared to group 1, with inhibin B levels now lying below (group 2: <20 pg/ml (<20--68)) rather than within (group 1: 34.5 pg/ml (<20--93)) the age-appropriate range. It is concluded that levels of inhibin A and inhibin B are elevated and suppressed in concert with activation and suppression of the hypothalamo-pituitary-gonadal axis in girls with CPP, supporting the concept that ovarian inhibin secretion is dynamically regulated by gonadotropin stimulation.

Buserelin↗
PubMed2000

Hydrothermal ablation. A new simple method for coagulating endometrium in patients with therapy-resistant recurring hypermenorrhea.

Hydrothermablation is a new method which could replace the electrosurgical method of endometrial ablation. Some prospective studies were carried out to assess efficacy, safety and tolerability of hydrothermablation in the treatment of recurrent menorrhagias. Hydrothermablation is an intervention with coagulation at the endometrium: temperature 90 degrees C and duration 10 min with simultaneous hysteroscopic control. In a follow-up of least 12 months, about 35% of the patients had an amenorrhea and the treatment was successful (reduction of pathological blood flow) in about 87% of the patients. Complications were vaginal burns in 2 cases. No other intra- or postoperative complications occurred. Hydrothermablation is a safe and effective method for treatment of recurrent menorrhagias. This method offers a simple possibility to perform endometrial ablation without extensive training of the surgeon and can contribute to avoid hysterectomy.

Adult↗
PubMed2000

Serum inhibin A and inhibin B in healthy prepubertal, pubertal, and adolescent girls and adult women: relation to age, stage of puberty, menstrual cycle, follicle-stimulating hormone, luteinizing hormone, and estradiol levels.

Biochemical assessment of gonadal function during maturation in girls and in adult women can be troublesome. With the recent advent of specific assays for the gonadal peptides inhibin A and inhibin B, it might be possible to achieve a clearer picture of events. We therefore determined serum levels of inhibin A, inhibin B, FSH, LH and estradiol in a cross-sectional study of 403 healthy schoolgirls (aged 6 -20 yr) in relation to age and stage of puberty and in 181 healthy nonpregnant women (aged 20-32 yr) in relation to stage of the menstrual cycle. In addition, inhibin A and inhibin B were measured daily throughout the menstrual cycle in 10 healthy adult women. Levels of inhibin B are low or undetectable in prepubertal girls (median, 26.5 pg/mL; 95% prediction interval, <20-100 pg/mL), increase sharply through pubertal stage II to peak in stage III (median, 84 pg/mL; 95% prediction interval, 28-227 pg/mL) and thereafter decline through pubertal stages IV and V. These changes presumably reflect increasing ovarian stimulation through early puberty, resulting in an increased number of developing follicles, follicles reaching a later stage of development before undergoing atresia, or both. Declining levels in late puberty and adulthood probably reflect the onset of the menstrual cycle and the subsequent appearance of the luteal phase, where inhibin B levels are low. Inhibin A levels are undetectable or very low in early puberty (median, <7 pg/mL; 95% prediction interval, <7-14) pg/mL), increasing gradually through pubertal stages to reach their highest values in adult women (median, 21.5 pg/mL; 95% prediction interval, <7-129 pg/mL). Levels of inhibin A greater than 19 pg/mL are only seen in postmenarcheal girls in puberty and in adult women, again consistent with inhibin A being primarily produced by the corpus luteum. Determining cut-off levels of serum inhibin B regarding whether a girl had entered puberty resulted in similar (low) sensitivities and specificities as those found for cut-off levels of LH or estradiol due to the large overlap between serum values in Tanner stages I and II. Correlations between inhibin A and inhibin B and FSH, LH, and estradiol within pubertal stages are presented. In early puberty both inhibin A and inhibin B correlated positively with LH and FSH. In late puberty inhibin A correlated negatively with FSH and did not correlate with LH; inhibin B still correlated positively with both FSH and LH, now most strongly with FSH. In adult women during the menstrual cycle, serum inhibin B levels increased during the follicular phase, indicating the greatest production by follicles in early stages of development. In contrast, serum inhibin A levels peaked during the luteal phase, indicating the greatest production by the corpus luteum. In conclusion, serum inhibin A and inhibin B levels in normal puberty in girls show consistency with our knowledge of the manner in which these hormones are secreted within the menstrual cycle in adult women. The presented reference values may be of use in the clinical evaluation of pubertal development in girls.

Adolescent↗
PubMed2000

Occurrence of gonadoblastoma in females with Turner syndrome and Y chromosome material: a population study.

The presence of Y chromosome material in patients with Turner syndrome is a risk factor for the development of gonadoblastoma. However, no cases with gonadoblastoma or other ovarian malignancies have been found in epidemiological studies of cancer, morbidity, or mortality in Turner syndrome. We examined 114 females with Turner syndrome for the presence of Y chromosome material by PCR. Initially, five different primer sets were used. Y Chromosome-positive individuals were further examined with an additional four primer sets. We found 14 (12.2%; 95% confidence interval, 6.9-19.7%) patients who had Y chromosome material. The karyotype in 7 of these patients did not suggest the presence of Y chromosome material. Seven of the patients had been ovariectomized before entering the study due to verified Y chromosome material, whereas three patients were operated upon after the DNA analysis. The histopathological evaluations showed that 1 of the 10 ovariectomized patients actually had a gonadoblastoma. The rest of the patients did not have gonadoblastoma or carcinoma in situ on histopathological evaluation. Three patients (age, >50 yr) positive for Y chromosome material chose not to have ovariectomy performed, and detailed ultrasonographies did not suggest the presence of gonadoblastoma. The frequency of Y chromosome material is high in Turner syndrome (12.2%), but the occurrence of gonadoblastoma among Y-positive patients seems to be low (7-10%), and the risk may have been overestimated in previous studies, perhaps due to problems with selection bias. This study emphasizes the need for prospective unbiased studies.

Adolescent↗
PubMed2000

Flock worker's lung: broadening the spectrum of clinicopathology, narrowing the spectrum of suspected etiologies.

STUDY OBJECTIVES: Workers in the nylon flocking industry recently have been found to be at increased risk of chronic nongranulomatous interstitial lung disease. Although a spectrum of cytologic and histopathologic abnormalities has been observed, nonspecific interstitial pneumonia, lymphoid nodules, and lymphocytic bronchiolitis predominated in the 19 previously reported cases of flock worker's lung. Here we describe five additional patients who appear to expand the histopathologic spectrum and add to the evidence suggesting a causative role for respirable-sized nylon fragments. METHODS: We studied all North American patients (n = 5) found in 1998 to satisfy our previous case definition of flock worker's lung. Two pulmonary pathologists independently reviewed each biopsy specimen. RESULTS: All five patients reported cough and dyspnea. Only one patient had crackles on chest auscultation. High-resolution CT scan, interpreted with attention to subtle ground-glass attenuation, remained a highly sensitive diagnostic test. Pulmonary function tests and plain chest radiograph were less sensitive. One patient's wedge biopsy showed previously described prototypical findings. Two others had transbronchial biopsies showing some of the same features. The fourth patient's wedge biopsy showed desquamative interstitial pneumonia. The fifth patient had bilateral synchronous adenocarcinoma but with radiographic evidence of diffuse interstitial fibrosis. These 5 patients and the 19 patients studied previously were exposed to nylon flock manufactured by a rarely used cutting technology. CONCLUSION: Findings in these five patients appear to broaden the spectrum of the clinicopathology of flock worker's lung and add to the evidence incriminating respirable-sized nylon particulates produced during the manufacture and use of rotary-cut nylon flock.

Adult↗
PubMed2000

Hormonal changes during GnRH analogue therapy in children with central precocious puberty.

Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of central precocious puberty (CPP) for more than 15 years. They are generally considered safe although data on potential long-term side effects are scarce. However, GnRHa therapy has profound effects on both the hypothalamopituitary-gonadal axis as well as on growth hormone (GH) secretion. Gonadal activity is increased in children with CPP; during GnRHa therapy secretion of gonadal hormones is suppressed as reflected by measurements of LH, FSH, and estradiol/testosterone. More recently, studies of levels of inhibin A and B as well as markers of androgen action such as SHBG and prostate specific antigen have demonstrated marked suppression of gonadal function possibly to infra-physiological levels. The possible long-term consequences of these observations have yet to be determined. Detailed analyses of the GH-IGF-I axis have revealed a decrease in levels of free, biologically active IGF-I during GnRHa treatment. These findings are in accord with the observed decrease in height velocity in children with CPP under treatment with GnRHa, and may also play a role in the relatively small gain in final height in most patients.

Androgens↗
PubMed2000

Molecular analysis of homeotic genes involved in barley development.

Ectopic expression of the barley homeobox gene BKn-3 conditions the development of epiphyllous flowers by de novo meristem formation. Various strategies are being described in an effort to identify genes whose products interact with the BKn-3 gene product or BKn-3 regulatory regions.

Chromosome Mapping↗
PubMed2000

[Advances and perspectives in mechanical heart assist].

Mechanical circulatory support devices were first developed to permanently replace the failing heart. Today, however, the majority of these devices are used as a mechanical bridge in patients awaiting heart transplantation. With this indication, important information on using mechanical assist devices has been assembled. We present our experience, which has been gained since 1987 in the area of patient selection, post-implant patient care and device maintenance. More than 450 patients have since been implanted with assist devices at our institution. Mechanical circulatory support may not only lead to recovery from secondary organ failure, but also to myocardial remodeling and recovery of the heart function in some patients. Additionally we report our experience with a newly developed implantable axial flow pump and discuss the possibility and costs of permanent support in some patients.

Adult↗
PubMed2000

[Asteroid bodies: host-pathogen reactions in mycoses].

A review of the literature on asteroid bodies (Splendore-Hoeppli phenomenon) as well as an immunoelectronmicroscopic study on asteroid bodies with Candida albicans and electronmicroscopic observations on asteroid bodies with Aspergillus are presented. The following definitions are proposed: Asteroid bodies with Candida albicans: precipitate consisting of fungal antigen and antibodies of host origin in light microscopically visible dimension deposited on the cell wall surface of Candida cells in parasitic condition. Asteroid bodies with Aspergillus: precipitate consisting of fungal antigen, antibodies of host origin and necrotic cellular detritus originated from cells of host defense, in light microscopically visible dimension, deposited on the cell wall surface of abortive Aspergillus cells, reduced in longitudinal growth, in parasitic condition.

Aspergillus↗
PubMed1999

[Safety and tolerance of single-dose botulinum toxin Type A treatment in 204 patients with spasticity and localized associated symptoms. Austrian and German botulinum toxin A spasticity study group].

High dose oral anti-spastic medication is effective in the treatment of spasticity but has the disadvantage of frequent systemic side effects such as drowsiness and general weakness. Therefore, neurolytic and chemodenervation procedures are further therapeutic options, especially in cases of local spasticity. Apart from phenol blocks with the risk of persisting painful dysesthesia, botulinum toxin type A (BtxA) appears to be a safe and effective treatment. In 204 patients (mean age, 41.5 years [range 3-91 years]) with acute (n = 29, mean duration of disease 2.9 months [range, 1-6 months]) and chronic (n = 175, mean duration of disease 111 months [range, 7-500 months]) spasticity due to stroke, traumatic brain and spinal injury and other lesions of the upper motor neuron, the effects of single-dose BtxA treatment were studied. An overall dose of 181.2 units [range, 15-600 units] of BtxA (Botox) was injected in a mean of 3.3 [1-14] muscles per patient. Results were assessed using a modified Rating of Response to BtxA (RRB, Brin et al. 1995). The RRB includes a pre- and post BtxA assessment of the severity of spasticity-associated problems (patient's self-assessment), a rating of the current percentage of normal function in the region of the body selected for BtxA and a global rating of changes induced by BtxA. 191 (93.6%) patients demonstrated improvement over a mean of 7.7 weeks [1-36]; no deterioration was observed. Mean overall severity and function improved significantly (p < 0.001). No systemic or severe side effects were registered. Only in 5.9% of the patients were mild (n = 10) or moderate (n = 2) reversible adverse events reported. We conclude that BtxA injections are safe and effective in the treatment of local spasticity.

Administration, Oral↗
PubMed1999

Agonist-like beta-adrenoceptor antibodies in heart failure.

Anti-beta1-adrenoceptor antibodies may play a harmful role, and the elimination of these antibodies could have beneficial effects for some patients with dilated cardiomyopathy. In vitro experiments showed that the antibody was able to influence the function of cultured cardiomyocytes. In these experiments, the antibody prevented the down-regulation of the beta-adrenoceptor-mediated chronotropic response. This lack of desensitization, which resulted in permanent stimulation, could also influence the Ca2+ homeostasis of cardiomyocytes. However, in longer-term (72 hours)-treated cells, the antibodies were able to decrease subtype-specific expression of the beta1 adrenoceptor. In animal experiments, it was shown that long-term immunization with a peptide corresponding to the second extracellular loop of the beta1 adrenoceptor induced a failing heart similar to that in dilated cardiomyopathy. In humans, we observed a remarkable correlation between disappearance of the antibodies and improvement of heart function. Furthermore, in anti-beta1-adrenoceptor-positive patients with dilated cardiomyopathy treated with the immunoadsorption technique, removal of the antibodies also led to improvement of cardiac function and quality of life. This finding indicates that autoimmune processes may be involved in some patients with dilated cardiomyopathy.

Adrenergic beta-Agonists↗
PubMed1999

Dosimetry and growth hormone deficiency following cranial irradiation of childhood brain tumors.

BACKGROUND: Dosimetry of the hypothalamus-pituitary (HP) region could allow prediction of the risk of growth hormone deficiency (GHD) following cranial irradiation. PROCEDURE: Nineteen children (15 boys) with a median age of 6.3 years (range 1.7-16.5) at the time of irradiation of a brain tumor not involving the HP axis were followed for 1.2-6.3 years (median 3.4) from radiotherapy (RT). The dose to a standardized anatomical model including the HP region was calculated from dose-volume histograms of 10% to 100% in steps of 10% of the HP model based on data from a computer-based treatment planning system. If GHD was suspected from insulin-like growth factor-I, serum insulin-like growth factor binding protein-3, and/or height velocity measurements, an arginine stimulation test was performed. GHD was defined by a peak GH <15mU/liter. RESULTS: Ten patients developed GHD 10-26 months from irradiation. Cox regression analysis identified the 90% dose-volume of the HP box as the strongest predictor of development of GHD (P = 0.03). The median dose to the 90% dose-volume of the HP region was 37.5 Gy (range 2. 3-55.3). The cumulated risk of GHD 2.5 years after radiotherapy for children receiving more than and less than 37.5 Gy to the HP region was 87% and 33%, respectively (P = 0.036). CONCLUSIONS: Dosimetry of a defined HP volume provides the opportunity to 1) calculate the exact dose delivered to this region, 2) predict the risk of GHD and, 3) in the future revise the treatment planning and thus reduce the risk of endocrine adverse effects.

Adolescent↗
PubMed1999

Genetic diagnosis of 21-hydroxylase deficiency: DGGE-based mutation scanning of CYP21.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is caused by mutations in the gene CYP21 encoding the enzyme steroid 21-hydroxylase. In addition to deletions, approximately 20 different point mutations have been reported, and still novel mutations are detected. This makes genetic diagnosis as well as carrier detection of 21-hydroxylase deficiency a complicated matter. We developed a simple nonradioactive assay based on the polymerase chain reaction (PCR) in combination with denaturing gradient gel electrophoresis (DGGE) to screen for mutations in the CYP21 gene. DGGE allows a fast scanning of PCR-amplified segments of genes for the presence or absence of any single base pair alterations. We have performed this technique on the coding sequence and intron-exon junctions of CYP21. Our results emphasize that this procedure constitutes a fast and reliable approach when performing diagnosis of 21-hydroxylase deficiency.

Adrenal Hyperplasia, Congenital↗
PubMed1999

Steroid 21-hydroxylase deficiency: mutational spectrum in Denmark, three novel mutations, and in vitro expression analysis.

We have investigated 68 unrelated 21-hydroxylase deficient Danish patients, representing 136 alleles, and determined the mutational spectrum of the CYP21 gene. The most frequent mutations detected were deletion of CYP21 and the splice mutation in intron 2 (I2-splice). Segregation analysis showed evidence of a de novo mutation in each of two patients. Three novel mutations were detected: G64E in exon 1, Q262X in exon 7, and A362V in exon 8. G64E and A362V were introduced in the CYP21 cDNA by in vitro site-directed mutagenesis, and the two corresponding proteins were transiently expressed in COS-7 cells. The activity of 21-hydroxylase was determined using the two hormone substrates 17-hydroxyprogesterone and progesterone. The analysis showed no enzyme activity for any of the substrates, a result that correlates well with the severity of the patients' disease.

Adrenal Hyperplasia, Congenital↗
PubMed1999

Worsening of motor performance in patients with Parkinson's disease following transdermal nicotine administration.

Nicotine has been reported to have positive effects on motor performance in patients with Parkinson's disease. In this study, motor performance was evaluated in 16 patients with idiopathic Parkinson's disease during a practical off-period using the motor part of the Unified Parkinson's Disease Rating Scale after 12 hours' exposure to a transdermal patch containing 35 mg nicotine or placebo. The study was performed using a double-blind crossover design. In contrast to previous reports, nicotine exposure was followed by a worsening of symptoms compared with placebo. A negative response to subthreshold dopaminergic stimulation, resulting from an inhibitory effect of low striatal dopamine concentrations acting on a subset of dopamine receptors, might possibly account for this finding.

Administration, Cutaneous↗
PubMed1999

Trick maneuvers in cervical dystonia: investigation of movement- and touch-related changes in polymyographic activity.

Antagonistic gestures or trick maneuvers are well-known clinical features to reduce or abolish dystonic posturing in cervical dystonia (CD). The maneuvers typically consist of a finger touch to the facial skin but their physiology remains unknown. To determine the temporal profile of geste maneuver performance, 25 patients with idiopathic CD were studied by means of polymyography of six cervical muscles prior to any botulinum toxin treatment. Two piezoelectric elements fixed to a fingertip of the hand involved in the trick maneuver and to the facial target region, respectively, were used to relate the essential points of the trick maneuver time course (start of geste-arm movement, facial contact, end of contact, end of movement) to changes in polymyographic activity. Thirteen patients (52%) showed marked reductions of electromyographic (EMG) activity (> or =50% in at least one muscle) during arm movement, definitely prior to contact between fingers and facial target area; in the remaining 12 patients (48%), geste-related EMG effects were confined to facial-finger contact. These results might indicate different physiological mechanisms in clinically indistinguishable antagonistic gestures.

Adult↗