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Biomedical subjects

J Müller

Publications and source records attributed to J Müller.

At least 73 records · Page 4Linked to original sources

A population-based study of thyroid function after radiotherapy and chemotherapy for a childhood brain tumor.

The effect of craniospinal irradiation (CSI) vs. cranial irradiation (CIR) only with or without chemotherapy (CT) on the hypothalamus/pituitary (HP) thyroid axis was assessed in a population-based study of patients treated for a childhood brain tumor not directly involving the HP axis. Thyroid function was evaluated and compared with that in healthy controls (n = 27), measuring TSH, free T4, total T4, total T3, and TRH. The biological effective dose (BED) of radiotherapy, determined for the HP region and spine and expressed in grays (Gy) as BED, gives a means of expressing the biological effects of different dosage schedules in a uniform way. Seventy-one children (45 males and 26 females), less than 15 yr of age when diagnosed between 1970-1997 in the eastern part of Denmark, were included. Twenty-nine had received CSI, and 42 had received CIR only. The median age at time of radiotherapy was 8.4 yr (range, 0.8-14.9). The median length of follow-up was 12.0 yr (range, 2.0-28.0). There was no significant difference between CSI and the CIR only patients with respect to median BED to the HP region. Primary hypothyroidism was found in 24%, of whom 71% had been treated with CSI and 29% with CIR only; 73% had compensated hypothyroidism, and 27% had overt primary hypothyroidism. Central hypothyroidism was found in 6%. Free T4 and total T3 were significantly lower in the CSI and CIR only groups compared with controls. As the CIR only group had significantly higher median basal TSH levels compared with controls and as the CSI compared with the CIR only group and controls had significantly higher median basal TSH levels, we speculate that this was probably due to scattered irradiation from both cranial and spinal fields to the thyroid gland. There was a significant relation between basal TSH and time of follow-up (r(s) = -0.39; P = 0.001). Stepwise backward multiple linear regression analysis showed that the best-fit model to predict basal TSH was free T4 (P < 0.0001), the length of follow-up (P = 0.02), and total T3 (P = 0.06). In contrast, age at radiotherapy, BED to the HP region and spine, and whether the patient had been treated with CT were not included in the model. The TRH test showed significantly exaggerated and prolonged TSH responses for the CSI and CIR only groups compared with controls, indicating HP dysfunction. In conclusion, these data suggest that both CSI and CIR for childhood brain tumor may affect the HP-thyroid axis, resulting in hypothyroidism. CT had no significant influence on HP-thyroid function. We recommend prolonged surveillance of pituitary-thyroid function in long-term survivors of childhood brain tumor and institution of thyroid hormone replacement if the levels of TSH and free T4 are above and below the normal range, respectively, to ensure normal growth and metabolism.

Adolescent↗

Assessment of the hypothalamo-pituitary-adrenal axis in patients treated with radiotherapy and chemotherapy for childhood brain tumor.

The impact of cranial irradiation (CIR) and chemotherapy on the hypothalamo-pituitary (HP)-adrenal (HPA) axis was assessed in a population-based follow-up study of patients treated for childhood brain tumor not directly involving the HP axis. HPA function was evaluated and compared with that in healthy controls (n = 17), measuring basal cortisol and the peak cortisol response to an insulin tolerance test (ITT) and an ACTH test(.) The cortisol cut-off level was 500 nmol/liter. The biological effective dose (BED) of radiotherapy was determined for the HP region and spine and was expressed in Gray units, as BED gives a means of expressing the biological effects of different dosage schedules in a uniform way. Seventy-three children (46 males and 27 females), less than 15 yr of age when diagnosed during 1970-1997 in the Eastern part of Denmark, were included. The median age at time of radiotherapy was 8.4 yr (range, 0.8-14.9). The median length of follow-up was 15 yr (range, 2-29). Fourteen patients (19%) had basal cortisol levels below 500 nmol/liter and did not respond with a peak cortisol above the cut-off level to either an ACTH test (30 or 60 min) or an ITT, and thus, they had insufficiency of the HPA axis. Even though a peak cortisol above 500 nmol/liter was reached in the rest of the cohort (n = 59) after either an ACTH test (30 or 60 min) or an ITT, they had significantly lower peak cortisol levels compared with controls (P = 0.0099). Thirteen patients failed the ACTH test (30 min), but passed the ACTH test (60 min), implying a risk of misinterpreting the cortisol capacity of the patient if only the ACTH test (30 min) is obtained. The basal cortisol levels and the cortisol levels in the ACTH test (30 min) and the ACTH test (60 min) were significantly lower in the patient group compared with controls. There was a significant correlation between the peak cortisol after the ITT compared with the peak cortisol after the ACTH test (30 or 60 min; r(s) = 0.56; P = 0.0006), but 48% failed the ITT, and there was discordance in 10 of 33 (30%) patients who passed the ACTH but failed the ITT, indicating the recommendation of continuous use of the ITT as the gold standard for evaluation of the HPA axis. Stepwise backward multiple linear regression analysis showed that the best-fit model to predict the peak cortisol level after an ITT included BED (P = 0.04) and length of follow-up (P = 0.06). In contrast, age at RT, chemotherapy, BED to the spine, and gender were not included in the model. In conclusion, these data suggest that CIR for a childhood brain tumor may affect the HPA axis, resulting in secondary adrenal insufficiency, whereas adjuvant chemotherapy does not seem to add to the deleterious effect of CIR. We recommend life-long surveillance of the HPA axis and performing regular ITTs.

Adolescent↗

[Molecular genetic diagnostics of some Daphnia species (Crustacea, Cladocera) from the Volga river].

Population genetic structure of the widespread Daphnia species from Kuibyshev and Saratov reservoirs was examined by use of RAPD-PCR technique with four mitochondrial DNA (16S rRNA) specific primers. One of the examined Daphnia clones from the Volga region appeared to be conspecific to the North American Daphnia galeata, while another clone was most likely a hybrid between D. galeata and D. cucullata.

Animals↗

The prevalence of primary dystonia in the general community.

The prevalence of primary dystonia was assessed in a random population sample of individuals aged 50 and over in Bruneck, South Tyrol. The diagnosis of primary dystonia was confirmed by videotaped review. Primary dystonia was present in 6 of 707 cases resulting in a prevalence rate of 732 per 100,000 (95% CI 319-1,564) in the general population aged 50 and over. Only two cases (33%) had been previously diagnosed. These results indicate that the true prevalence of primary dystonia is significantly higher than published rates.

Adult↗

Treatment of severe Candida infections in high-risk patients in Germany: consensus formed by a panel of interdisciplinary investigators.

Now that modern medicine can provide increasing chances of cure to patients with formerly incurable disorders, therapy-related complications play the key role in outcome. Thus, among opportunistic infections, severe candidiasis remains a challenge. A multidisciplinary panel of 20 investigators was formed to find a consensus on antifungal strategies for various underlying conditions in neutropenic and non-neutropenic patients. To record their preferences, the investigators used an anonymous voting system. Among antifungal agents, fluconazole emerged as the major alternative to the classic amphotericin B, being therapeutically at least equivalent but clearly less toxic. Factors that restrict the use of fluconazole include pretreatment with azoles, involvement of resistant species like Candida krusei, and an inability to exclude aspergillosis. Flucytosine can be reasonably combined with both amphotericin B and fluconazole. Within the limited antifungal armamentarium, amphotericin B lipid formulations and itraconazole also appear useful and require further investigation. The general consensus of the group is that antifungal agents should be administered at sufficient dosages, rather early, and often empirically.

Antifungal Agents↗

Biotransformation of trichloroethene by pure bacterial cultures.

From natural samples 11 isolates able to remove trichloroethene (CCl2CHCl) from an aqueous environment were obtained which were capable of cometabolic degradation of CCl2CHCl by an enzyme system for phenol degradation. At an initial CCl2CHCl concentration of 1 mg/L, the resting cells of particular cultures degraded 33-94% CCl2CHCl during 1 d and their transformation capacity ranged from 0.3 to 3.1 mg CCl2CHCl per g organic fraction. An analysis of a mixed phenol-fed culture with an excellent trichloroethene-degrading ability found a markedly minority isolate represented in the consortium to be responsible for this property. This culture degraded CCl2CHCl even at a low inoculum concentration and attained a transformation capacity of 14.7 mg CCl2CHCl per g. The increase in chloride concentration after degradation was quantitative when compared with the decrease in organically bound chlorine. The degree of CCl2CHCl degradation was affected by Me2S2; this substance can significantly reduce the degrading ability of some tested cultures (> 60%); however, it does not cause this inhibition with others.

Acinetobacter↗

[Dysequilibrium in idiopathic Parkinson disease. The effect of cerebrovascular comorbidity].

Disturbance of balance in idiopathic Parkinson's disease (IPD) has a significant effect on disability. Yet the underlying mechanisms and the contribution of age-associated comorbidity to dysequilibrium are unclear. In this study, static posturography was performed in 30 healthy controls and 40 patients with IPD. Comparison of sway during quiet stance did not show significant differences between patients and controls. Multiple linear regression analysis was used to identify factors responsible for the considerable interindividual variance in patients. Results of the pull test, CT-verified cerebral microangiopathy, dementia, and age were assessed, but only cerebrovascular comorbidity contributed significantly to variance. Apart from increased sway, patients with coinciding cerebral microangiopathy (n = 20) more frequently had a history of falls or pathological responses in the pull test. The present results suggest that cerebrovascular comorbidity enhances dysequilibrium in IPD. Pathological sway in IPD can indicate comorbidity and may have implications for further diagnostics.

Aged↗

The impact of blepharospasm and cervical dystonia on health-related quality of life and depression.

The aim of the study was to evaluate and compare health-related quality of life (HR-QoL) and depression in essential blepharospasm (BSP) and idiopathic cervical dystonia (CD), to identify the clinical and demographic factors associated with poor HR-QoL in both disorders and to analyse the effect of Botulinum Toxin A (BtxA) therapy. Two hundred-twenty consecutive patients with BSP (N = 89, 62 % women, mean age 64 years, mean disease duration 7 years) and CD (N = 131, 64 % women, mean age 53 years, mean disease duration 8 years) recruited from routine referrals to eight Austrian dystonia clinics were included. HR-QoL was measured by the Short Form 36 (SF-36) and depression by the Beck Depression Inventory (BDI). At baseline, patients with CD and BSP scored significantly worse in all eight SF-36 domains compared with an age-matched community sample. In addition, 47 % of patients with CD and 37 % of those with BSP were depressed. Women with BSP scored significantly lower in all SF-36 domains and were more depressed than male patients. In contrast, there was no significant effect of gender on HR-QoL and depression in CD. Neck pain had a significant impact on all SF-36 domains and represented the main determinant of depression in CD. Although BtxA therapy resulted in a significant improvement of clinical symptoms in BSP and CD, HR-QoL did not improve in BSP and only two of the eight SF-36 domains improved significantly in patients with CD. The present study for the first time demonstrated that BSP has a substantial impact on health status emphasizing the need for psychological support with interventions aimed at treating depression in these patients. Our results provide further evidence for the profound impact of CD on HR-QoL and indicate the importance of an adequate management of neck pain in addition to reducing the severity of dystonia in CD. The mismatch between objective BtxA derived improvement of dystonia and lack of change of HR-QoL as determined by the SF-36 illustrates the need for optimized disease specific quality of life rating scales in patients with craniocervical dystonia.

Aged↗

Botulinum toxin treatment in atypical parkinsonian disorders associated with disabling focal dystonia.

We investigated the efficacy of botulinum toxin A (BtxA) therapy in patients with atypical parkinsonian disorders (APD) exhibiting different types of disabling focal dystonia unresponsive to oral drug therapy. Eight patients with functionally disabling focal dystonia out of a series of 60 consecutive patients with APDs regularly treated at our outpatient movement disorders clinic were included. Patients were diagnosed according to established criteria and had disabling limb dystonia (n=4) or craniocervical dystonia (n=4) unresponsive to oral pharmacological treatment. Localization and dose of BtxA injections was determined individually based on clinical examination as well as EMG in patients with limb dystonia. BtxA reduced dystonic symptoms in all patients; only one developed a transient local side-effect. BtxA was particularly effective in the long-term treatment (up to 50 months) of blepharospasm associated with progressive supranuclear palsy (PSP). BtxA also alleviated PSP-associated retrocollis and orofacial dystonia with lower lip retraction associated with PSP and multiple system atrophy. BtxA treatment of limb dystonia in corticobasal degeneration (CBD) temporarily improved hand and arm function in early-disease stages while treatment in advanced stages reduced pain, facilitated hygiene and prevented secondary contractures. Limb dystonia was also alleviated by BtxA therapy in one patient with neuronal multisystem degeneration of undetermined cause. The results suggest that BtxA therapy may represent an effective means of alleviating disabling focal dystonia in different APDs. Particularly in early stage APD with disabling limb dystonia local BtxA injections may result in functional improvement.

Adult↗

[The Würzburg Ear Forms: a system to document surgery and follow-up evaluation].

BACKGROUND: About a decade ago a PC based system to document surgery and follow up evaluation was installed. At that time the wide spread DOS systems provided only inputs via the keyboard. However, we believed that to assure the system would be accepted by the user, a graphical user interface would be necessary. Such an interface provides greater user-comfort and ensures the validity of entered data. METHODS: A simple graphical platform was installed, which provided all the necessary functions without being too complex. Several forms were designed for data collection. The first form implemented was designed for ear surgery. It comprises 356 items. The relevant data in the form are selected by a mouse click from possible alternatives. Although a large number of items are provided, it takes only one to two minutes to fill in the form. RESULTS: At present, September 2001, the database contains 10 453 records related to ear operations, 9633 preoperative audiograms and the results from 16 140 follow up evaluations. A special language and an interpreter for analyzing the data were added to complete the system. CONCLUSIONS: The large number of cases stored in the database allows data analysis with a high level of statistical confidence for any conclusions based upon the data. It also allows investigations of the simultaneous influence of a large number of variables on the results.

Computer Graphics↗

[The Würzburg questionnaire for assessing the quality of hearing in CI-children (WH-CIK)].

BACKGROUND: The goal of this study was to compare the auditory behaviour of bilaterally implanted children while using both CIs to their auditory behaviour during the time when they were using one CI. METHODS: For this purpose a questionnaire looking at different aspects of hearing such as hearing in background noise, in complex listening situations and directional hearing was developed. The questionnaire was completed by the parents of 28 bilaterally implanted children. They were instructed to state their judgement on the behaviour of their children. The parents scaled their judgements using a method of extended category scaling similar to that applied in the loudness scaling with the Würzburg hearing field (WHF). Each of the five verbal categories was subdivided into 10 numerical subdivisions, so that the parents were able to express judgements lying between the different categories. RESULTS: Eight out of eleven items showed that hearing with bilateral CIs was significantly better than with one CI (p < 0,003). The two items, which did not show a significant difference between the two conditions were those related to the interest in auditory rehabilitation and to aversion to noise. CONCLUSIONS: The questionnaire has proven to be a useful instrument to assess the quality of hearing in children. The possibility of bilateral implantation should be considered during the decision process prior to implantation.

Adolescent↗

Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in dialysis patients, renal transplant recipients and healthy controls.

It has been suggested that infection with Chlamydia pneumoniae plays a role in the development and maintenance of atherosclerosis based on differences in the prevalence of antibodies against Chlamydia pneumoniae in patients with and without atherosclerotic lesions and on the presence of bacteria in atherosclerotic lesions. It is well known that patients undergoing chronic dialysis treatment and renal transplant recipients have a considerably increased risk of cardiovascular disease. In this study it is hypothesized that patients with these conditions have a higher prevalence of Chlamydia pneumoniae DNA in the white cells of the peripheral blood. Blood samples from 196 dialysis patients, 114 renal transplant recipients and 342 healthy controls were analysed with an in-house nested polymerase chain reaction (nPCR) and tested for the presence of Chlamydia pneumoniae DNA. The prevalence of Chlamydia pneumoniae DNA was significantly higher in dialysis patients (16.3%) than in healthy controls (8.5%, p < 0.01), whereas no significant difference was found between the prevalence in renal transplant recipients (9.6%) and healthy controls. The prevalence was not related to gender or age in either group, and it was the same in diabetics and non-diabetics. Dialysis patients have a higher prevalence of Chlamydia pneumoniae DNA than healthy controls. The lower prevalence of Chlamydia pneumoniae DNA in renal transplant recipients than in dialysis patients may be due to selection of dialysis patients with few or no cardiovascular complications for renal transplantation. Our results are consistent with the hypothesis that Chlamydia pneumoniae is associated with the pathogenesis of atherosclerosis.

Adult↗

Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient.

UNLABELLED: Treatment of allergic bronchopulmonary aspergillosis with itraconazole is becoming more widespread in chronic lung diseases. A considerable number of patients is concomitantly treated with topical or systemic glucocorticoids for anti-inflammatory effect. As azole compounds inhibit cytochrome P450 enzymes such as CYP3A isoforms, they may compromise the metabolic clearance of glucocorticoids, thereby causing serious adverse effects. A patient with cystic fibrosis is reported who developed iatrogenic Cushing's syndrome after long-term treatment with daily doses of 800 mg itraconazole and 1,600 microg budesonide. The patient experienced symptoms of striae, moon-face, increased facial hair growth, mood swings, headaches, weight gain, irregular menstruation despite oral contraceptives and increasing insulin requirement for diabetes mellitus. Endocrine investigations revealed total suppression of spontaneous and stimulated plasma cortisol and adrenocorticotropin. Discontinuation of both drugs led to an improvement in clinical symptoms and recovery of the pituitary-adrenal axis after 3 mo. CONCLUSION: This observation suggests that the metabolic clearance of buDesonide was compromised by itraconazole's inhibition of cytochrome P450 enzymes, especially the CYP3A isoforms, causing an elevation in systemic budesonide concentration. This provoked a complete suppression of the endogenous adrenal function, as well as iatrogenic Cushing's syndrome. Patients on combination therapy of itraconazole and budesonide inhalation should be monitored regularly for adrenal insufficiency. This may be the first indicator of increased systemic exogenous steroid concentration, before clinical signs of Cushing's syndrome emerge.

Adult↗