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Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 253 records · Page 14Linked to original sources
PubMed1995

[Tumor suppressor gen mutation in the germ line: its significance in familial and sporadic tumors].

Since the discovery of the retinoblastoma tumor suppressor gene many others have been described associated with a variety of different familial syndromes. These include the Li-Fraumeni syndrome, familial breast/ovarian cancer, multiple endocrine neoplasia (MEN1), neurofibromatosis 1 and 2, tuberous sclerosis and von Hippel-Lindau disease. Persons harboring a germ line mutation in a tumor suppressor gene are not born with disease, merely the predisposition to develop one. This is due to the fact that they have inherited only one functional copy compared to persons with no predisposition who have two copies. Germ line mutations have not to be inherited, they can result from a spontaneous mutation occurring during gametogenesis in one patient. Persons with an inherited or de-novo germ line mutation have similar risks to develop multiple cancer or to transmit the defective gene to their offspring. The genes can be analyzed by molecular genetic techniques allowing for a precise genetic diagnosis as well as reliable genetic counselling.

Eye Neoplasms↗
PubMed1995

Significance of conventional and new prognostic factors for locally confined renal cell carcinoma.

BACKGROUND: The prognosis of patients with locally confined renal cell carcinoma is variable. To improve the prognostic knowledge and select patients at high risk, additional prognostic parameters are needed. METHODS: The significance with respect to survival and tumor recurrence of "classic" and "new" prognostic parameters has been examined by following 41 patients with locally confined renal cell carcinoma after nephrectomy (mean follow-up, 5.2 years). The significance of histologic grade, tumor stage, Ki-67 index, proliferating cell nuclear antigen index, 3H-thymidine labeling index, tumor ploidy status, and tumor growth after xenotransplantation into nude mice (GAX range) was tested using the Kaplan-Meier plots by the log rank test or Tarone's test and also by the Cox multiple hazard regression analysis. RESULTS: Tumor stage (P < 0.0025), histologic grade (P < 0.005), Ki-67 index (P < 0.006), and GAX range (P < 0.00004) were found to be significant prognostic parameters for survival and tumor recurrence using single-factor analysis. Applying the multivariate analysis, the combination of the "new" factors, GAX range and Ki-67 index, resulted in even a higher prognostic relevance than the combination of the "classic" prognostic factors, tumor stage and histologic grade. The calculated prognostic index based on the results of the Cox analysis, which, except for stage and grade, included the Ki-67 index, was shown to be highly correlated with survival (P = 0.00002) and tumor recurrence (P = 0.0004). Its prognostic validity was studied with the receiver operating characteristics procedure and was found to be considerably superior to that of the two conventional prognosticators. CONCLUSIONS: The additional determination of the Ki-67 labeling index increases the prognostic assessment of patients with locally confined renal cell carcinoma.

Animals↗
PubMed1995

[Differential diagnosis of commonplace upper abdominal symptoms: hepatic echinococcosis].

A 17-year-old girl from Turkey had for 6 years been suffering from right-sided upper abdominal symptoms not usually related to food intake. Treatment of suspected gastritis remained ineffective. Laboratory tests were unremarkable, except for an accelerated erythrocyte sedimentation rate (12/30 mm), eosinophilia (6.4%) and albumin concentration of 52.6 g/l. Upper abdominal sonography revealed a cyst, about 10 cm in diameter, in the right liver lobe. Computed tomography showed the 8 x 8.5 cm cyst which was septated at its caudal portion and compressed the vena cava for 5.6 cm. The antibody titre against echinococcus antigen was 1:3200. At laparotomy the echinococcal cyst was found to have extended to the left adrenal gland, renal fat capsule and left part of the diaphragm. There was a pressure necrosis on the right lateral aspect of the vena cava. The affected parts were resected and the patient quickly recovered. Postoperative treatment consisted of the administration of mebendazole (1.5 g daily) for 18 months. The patient had come from an area where echinococcal infection is endemic. The disease could have been quickly and easily diagnosed and cured if sonography had been undertaken early, sparing the patient major surgery.

Adolescent↗
PubMed1995

Complete nucleotide sequences of 5'- and 3'-noncoding regions of both genome segments of different strains of infectious bursal disease virus.

The terminal sequences of both genomic dsRNA segments of different strains of infectious bursal disease virus were determined. Analysis of the linear sequences revealed in the 5'-noncoding region of both segments the presence of a 32-nucleotide sequence with motifs conserved between segments and serotypes. The 3'-noncoding regions showed a high degree of conservation within segment A or B, but differed between segments. Different inverted terminal repeats were detected in both segments. A sequence of 13 nucleotides found in the 5'-noncoding regions of both segments could function as a binding site for chicken 18 S rRNA. Secondary structure prediction of the different noncoding regions showed a high degree of similarity. Surprisingly, the predicted secondary structure of the 5'-noncoding region of segment A differed between serotypes. A possible influence of these different RNA structures on viral replication is discussed.

Animals↗
PubMed1995

Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer.

D-type cyclins are proto-oncogenic cell cycle regulators implicated in the pathogenesis of several types of cancer. Amplification of the cyclin D1 gene has been described in 30-50% of human head and neck squamous cell carcinoma (HNSCC). Using immunohistochemistry on archival specimens of human HNSCC and a mAb DCS-6, which is specific for cyclin D1, strong positivity was found in nuclei of 9 (17%) of 52, a moderately elevated signal in 16 (31%) of 52, and weak staining comparable with normal tissues in 27 (52%) of 52 patients. Immunoblotting analysis of five HNSCC-derived cell lines showed three distinct spectra of D-type cyclin proteins: cyclin D1 only (in UMSCC-2 and UMSCC-22b cell lines with 11q13 amplification), cyclins D1 and D3 (in HN5 and HN6), or cyclins D1, D2, and D3 (in UMSCC-1). Electroporation of neutralizing antibodies demonstrated requirement for cyclin D1 in cell cycle progression of all five HNSCC cell lines. Cyclin D2 was essential and showed a cooperative effect with cyclin D1 in positive regulation of G1 in UMSCC-1 cells. These data are consistent with the proposed oncogenic role of cyclin D1 in HNSCC and open up the way for immunohistochemical assessment of cyclin D1 aberrations in archival clinical specimens. It is also suggested that excessive levels of cyclin D1 alone or cooperative effects of several D-type cyclin proteins may lead to deregulation of G1 control in distinct subsets of human HNSCC. These results are discussed in the context of possible functional redundancy of D-type cyclins and the role of the D-type cyclin/p16-CDKN2/pRB pathway in tumorigenesis.

Carcinoma, Squamous Cell↗
PubMed1995

[Gene therapy and ethics].

Gene therapy represents a new strategy to treat human disorders. It was originally conceived as a cure for severe monogenetic disorders. Since its conception, the spectrum of possible application for gene therapy has been to include the treatment of acquired diseases, such as various forms of cancer and some viral infections, most notably human immune deficiency virus (HIV) and hepatitis B virus. Since somatic gene therapy does not cause substantially new ethical problems, it has gained broad approval. This is by no means the case with germ-line gene therapy. Practically all bodies who were evaluating the related ethical aspects wanted to ban its medical application on grounds of fundamental and pragmatic considerations. In this review, practical and ethical views concerning gene therapy are summarized which were presented at the "Junitagung 1994" of the Swiss Society for Biomedical Ethics in Basle.

Ethics, Medical↗
PubMed1995

[Intake of folic acid in the total daily diet--effect of food preparation on its folic acid content].

The folic acid content of total daily diet was determined by means of high-performance liquid chromatography (HPLC). The contents of tetrahydrofolic acid (THF), 5-methyl-THF and 5-formyl-THF were differentiated. The mean of the folic acid content of the total daily diet samples determined analytically was 205 +/- 60 micrograms and the mean of the individual ingredients of the samples was 401 +/- 78 micrograms, which implies that about 50% of folic acid is destroyed by common household food preparation methods. If the contents of pteroylglutamic acid (PteGlu) and 10-formyl-PteGlu (which cannot be determined analytically) are added, it can be assumed that the folic acid content with only be reduced by about 40%. THF and 5-methyl-THF proved to be less stable than 5-formyl-THF. The monoglutamate portion of the total folat content was higher in the total diet samples than in the individual foodstuffs as a consequence of the action of the enzyme "deconjugase" which is released when the matrix of food-stuffs is destroyed.

Chromatography, High Pressure Liquid↗
PubMed1995

Acute subdural haematoma from ruptured intracranial aneurysms.

Acute subdural haematoma (SDH) secondary to a ruptured intracranial aneurysm is a rare event. Out of a total of 292 patients with a verified aneurysm (period 1986-1992) in five cases SDH was the diagnosis on CT-evaluation. One patient was in such a bad condition that no treatment was indicated. The remaining four patients were operated on: craniotomy and haematoma evacuation in two cases, craniotomy for haematoma evacuation and aneurysm clipping in the other two cases. Two patients died and two achieved a good outcome.

Acute Disease↗
PubMed1995

A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients. A re-evaluation of the North American risperidone study.

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R2 = 0.50-0.51, p < 0.001). Only depressive symptoms did not contribute significantly to these results (p > 0.10). Path analysis showed that the greater mean change (p < 0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.

Antipsychotic Agents↗
PubMed1995

Close-meshed prevalence rates of different stages as a tool to uncover the rate of Alzheimer's disease-related neurofibrillary changes.

The speed of progression of Alzheimer's disease-related neurofibrillary changes is unknown. One reason for this is the impossibility to histopathologically follow-up one and the same individual over decades of their life. The present approach takes advantage of a recently introduced classification system which allows for a ranking of Alzheimer's disease-related neurofibrillary changes into six stages [Braak and Braak Acta Neuropath (1991) 82, 239-259] and analyses a staged sample of 887 brains obtained from routine autopsy. It sets out to interpret these cross-sectional data in dynamic longitudinal terms, in order to estimate the rate of passing through the various stages. The time needed to attain respective stages of pathology for 5% of a given cumulative sample is determined. The resulting fifth centiles are a measure of the average rate by which the disease-related changes progress assuming that the underlying stages represent a sequence of events and do not independently emerge. Advancing age and the prevalence of Alzheimer's disease-related changes of a given stage show a nonlinear positive correlation with only slight acceleration above the age of 65 years. Statistically, it takes at least 16 years from stage I to stage II, about 14 years pass by from stage II to III, 13 years from stage III to IV and five years from stage IV to V (= Alzheimer's disease) for 5% of a given cumulative sample. Thus, the deep roots of Alzheimer's disease-related neurofibrillary changes can be traced about 50 years back and may even extend into adolescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Circadian variations in antigen-specific proliferation of human T lymphocytes and correlation to cortisol production.

Cortisol is a well-known immunosuppressant when used therapeutically. The present investigation was set out to study if diurnal variations in endogenous cortisol production are reflected by changes in proliferative responses of human lymphocytes to either a mitogen (phytohemagglutinin-A, PHA) or an antigen (tetanus toxoid, TT) stimulus. The study included eight healthy volunteers. Blood was withdrawn at 0200, 0600, 1000, and 1800h for preparation of lymphocytes and determination of cortisol in plasma. Isolated cells were incubated without (baseline activity) or with inclusion of either 1 micrograms PHA or 10 micrograms TT. Proliferation was measured by labelling with 3H-thymidine for 16 h of culture. The cortisol plasma levels exhibited the well known diurnal variations with highest concentrations at 1000h and lowest levels at 0200h. Baseline activity or PHA stimulated cell proliferation did not show significant diurnal fluctuations. The response to TT, however, decreased by 38% between 0600 and 1000h (p = .01). Correlation analyses revealed that the reduction of the proliferative responses to TT correlated significantly (p < .05) with increases in cortisol plasma levels. It was concluded that diurnal fluctuations in the production of endogenous cortisol might be relevant for daytime dependent variations in immune responsiveness.

Adult↗
PubMed1995

[Color-coded duplex ultrasound of the vertebral artery: normal findings and pathologic findings in obstruction of the vertebral artery and remaining cerebral arteries].

AIM: The aim of this study was to determine normal values of flow velocities in the extracranial vertebral artery (VA) with regard to diameter of the VA, blood pressure and age. Hemodynamic changes in the VA in occlusive disease of the brain supplying arteries were also to be investigated. Based on the findings the clinical value of CCDS for the investigation of the VA were to be assessed. METHOD: The evaluation was carried out by a CCDS-scanner with a 7.5 MHz transducer in 85 normal individuals and in 166 patients with occlusive disease of the cerebral arteries. RESULTS: The average maximal systolic flow velocity was 59 +/- 17, time averaged maximal velocity 31 +/- 10 and enddiastolic velocity 19 +/- 8 cm/sec. Significantly reduced flow velocities were found in severely stenosed and in occluded VA increased flow velocities in VA serving as collateral pathway in higher grade obstructions of contralateral VA, ICA, and SCA. CONCLUSION: CCDS of the VA is a valuable tool in diagnosis of severe obstructions of the VA, but also for demonstration of collateral flow. Furthermore, cervical collateral pathways in severe obstruction of the VA-origin can be detected. Diagnosis of moderate stenosis of the ostium of the VA remains difficult.

Adolescent↗
PubMed1995

[Diabetes mellitus--an epidemiologic study of fertility, contraception and sterility].

MATERIAL AND METHODS: Data from 672 female patients with diabetes mellitus between 17 and 42 years of age were collected by questionnaire. Mean manifestation age was 19.9 years (min. 1, max. 38). RESULTS: 72.39% of the patients were treated with insulin; one third had successful pregnancies. Only one of ten diabetics delivered more than once after diabetes had become manifest. At the time of the study, 126 (19.1%) of the patients attempted pregnancy; about one-fifth of these for more than 2 years. Diabetes manifestation occurred significantly earlier in patients who did not achieve conception. Correlation between daily insulin dose and infertility was proved, whereas duration of diabetes had no significant influence on fertility. Habitual abortion was found in 0.62%, among nulliparous patients 1.64%, respectively. Contraception was performed in 64.2% (32.8% hormonal contraceptives, 18.6% IUD, 1.8% natural family planning, 11.0% tubal sterilisation or hysterectomy, 35.8% no contraception). 47% of the used oral contraceptives contained a reduced oestrogen dose (30 micrograms estradiol). In one third of the users, IUD were longer than 5 years in place. Tubal sterilisation was found in 69 (10.44%) of diabetic patients; in 51 cases before the age of 30 years. CONCLUSIONS: Contraceptive methods should be selected carefully. Diabetic patients unsuccessfully attempting pregnancy should be referred early to a centre for reproductive medicine.

Abortion, Habitual↗
PubMed1995

A controlled study of the efficacy and safety of mianserin and amitriptyline in depressive inpatients.

As with other second-generation antidepressants, the antidepressive efficacy of mianserin was investigated in double-blind control group studies, mostly under outpatient conditions. This study tested the antidepressive efficacy and safety of mianserin as compared to amitriptyline in a sample of 51 depressed inpatients suffering from major depression. No statistically significant difference was found with regard to the main efficacy outcome criterion, the HAMD. The tolerability results demonstrated a superiority of mianserin with respect to vegetative symptoms and especially with respect to dryness of the mouth.

Adult↗
PubMed1995

[Distortion product otoacoustic emissions (DPOAE) in chronic noise-induced hearing loss--recommendations for expert assessment].

The German guidelines for evaluation of chronic noise-induced hearing loss (NHL) require two special auditory tests besides pure tone and speech audiometry tests as proof of damage to the organum spirale. This requirement is the subject of controversy because of the subjective nature of the tests as well as the secondary ascending degeneration of neurons in cases of long-term NIHL. The application of otoacoustic emissions (OAE) could be a new starting point, independent of recruitment. DPOAE are preferable to TEOAE because they are frequency specific. For this reason, we carried out measurements of DPOAE in addition to the required tests on 33 patients (= 66 ears). The results are collected in four groups according to the pure-tone audiogram: a) slight b) typical, c) severe, d) no NIHL. The respective DP-Gram curves had typical features similar to the course of the pure-tone audiogram. The following conclusions are possible: a) in the frequency range up to 1 kHz, ambient noise often causes interference to the DP, b) in the frequency range from 1 kHz to the frequency of the steep pure-tone threshold decay clear DP amplitudes are seen, c) from a inner ear caused hearing loss of appr. 50 dB no DP are detectable, d) DP amplitudes are approximately inversely proportional to hearing loss, e) in severe NIHL (group C) or even slight conductive hearing loss (group D) no DP are found. Based on these results, we recommend including DPOAE as a further differential diagnostic test in the evaluation of NIHL.(ABSTRACT TRUNCATED AT 250 WORDS)

Audiometry, Pure-Tone↗
PubMed1995

Activities of trypsin and lipase in duodenal aspirates of preterm infants: influence of dietary protein and fat composition.

The influence of three different feeding regimens on the activities of pancreatic lipase and trypsin in duodenal aspirates and on fecal nitrogen and fat excretion was studied in 35 healthy preterm infants after a 2-wk feeding period. Eleven infants received a standard preterm formula (without long-chain polyunsaturated fatty acids), 12 were fed with an experimental formula that only differed from the standard formula in fat blend composition (with long-chain polyunsaturated fatty acids), and 12 infants received human milk fortified with protein and energy to have similar nitrogen and energy contents as the two formulas. There were no significant differences in duodenal trypsin activities among the groups. In the group fed the standard formula, lipase activity was significantly lower than in the group fed the experimental formula (standard formula group: 8.4 +/- 3.5 kU/L; experimental formula group: 13.8 +/- 4.8 kU/L; P < 0.05) but there was no significant difference between the experimental formula group and the human milk group (15.1 +/- 4.2 kU/L). Fecal nitrogen as well as fat excretion were similar in the three feeding groups. The data suggest that dietary fat composition can influence the postnatal development of duodenal lipase activity in preterm infants.

Dietary Fats↗
PubMed1995

Early and late pre-mRNA processing of budgerigar fledgling disease virus 1: identification of viral RNA 5' and 3' ends and internal splice junctions.

Budgerigar fledgling disease virus 1 (BFDV-1) is the first avian polyomavirus to be identified, and it possesses uncommon structural and biological properties. Here we present an analysis of the processed viral RNAs in infected chicken embryo fibroblast cells. Two early and 18 late BFDV-1 mRNAs were defined according to their 5' ends and internal splice patterns. In the early region of the genome an incomplete splice reaction covering 195 nt is responsible for creating two mRNAs that could encode small t and large T antigens, which would be initiated from a hypothetical early promoter, PE. The late mRNA 5' ends define two putative promoter regions (PL1 and PL2), 111 nt apart in the BFDV-1 genome non-coding region. The overall splicing pattern of the late mRNAs is further complicated by an alternative splice reaction of intron 2 (deletion of either 64 nt in intron 2a or of 256 nt in intron 2b) and a splice removing intron 3 (870 nt), resulting in deletion of most of the VP2-VP3 coding region. The positions of the late mRNA 5' ends and the splicing pattern indicate the existence of two open reading frames, putatively encoding two pairs of agnoproteins, in the 5' region of several late mRNAs. These mRNAs appear to be bicistronic and to encode one of the agnoproteins together with one of the viral coat proteins.

Animals↗