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Biomedical subjects

J Müller

Publications and source records attributed to J Müller.

At least 433 records · Page 24Linked to original sources

Intramyocardial electrogram recordings for diagnosis and therapy monitoring of cardiac allograft rejection.

The registration of intramyocardial ECG amplitudes (IMEG) is a non-invasive diagnostic method of monitoring cardiac allograft rejection. In order to detect possible sources of error IMEG signals were recorded in heterotopic neck hearts in ten beagle dogs. Immunosuppression was based on cyclosporin A. The rejection process was followed by IMEG registrations as well as by serial myocardial biopsies. Intramyocardial electrogram recordings were made via three unipolar and three bipolar leads obtained from screw-in electrodes in both ventricles and the apex of the allograft. A 10% voltage drop was used as an indicator of rejection. In four dogs, the first rejection episode was treated with methyl-prednisolone and the therapy's success was monitored by IMEG and repeat biopsy. At autopsy the histology of each electrode circumference was correlated with the corresponding IMEG. The average sensitivity of a single lead was not acceptable (unipolar: 28%, bipolar: 47%). When the voltages of different leads were summed up the sensitivity rose to 43% (3 x unipolar), 85% (3 x bipolar) and 100% (all leads). During rejection therapy the IMEG recovered within 24-48 h. We conclude that in moderate allograft rejection (grade 2/3a ISHT classification), the rejection-related changes of intramyocardial ECG voltage amplitude (IMEG) seem to follow a "focal pattern" similar to the histology. Therefore the recording of several, preferably bipolar, electrode configurations appears to enhance adequate diagnostic reliability.

Animals↗

Effects of the novel acetylcholinesterase inhibitor SDZ ENA 713 on sleep in man.

A novel brain-selective acetylcholinesterase inhibitor, SDZ ENA 713, is under development for the treatment of dementia of the Alzheimer type. To determine the threshold dose for central activity, single doses of the compound were administered to 20 young male volunteers in a double-blind cross-over design and the effects on the sleep electroencephalography studied. The first group of eight volunteers received in random order: placebo, 0.5 mg; and 1 mg SDZ ENA 713. The second group of 12 volunteers received: placebo, 1.3 mg; and 2 mg SDZ ENA 713. Sleep quality was not affected by the study medication, which was well tolerated by all subjects. A statistically significant increase in rapid-eye movement sleep density was observed after doses of 1 mg, 1.3 mg, and 2 mg. Rapid-eye movement latency and slow-wave sleep were not altered. The results demonstrate that SDZ ENA 713 is centrally active in man at well-tolerated doses.

Adolescent↗

[Ionomer cement in cochlear implant surgery].

Ionomer-based cement is a new bone replacement material. After promising results have been obtained with this material in middle ear and skull base surgery as well as in plastic reconstructive surgery, this material can be used to fix a cochlear implant system (internal receiver as well as the electrode) to the temporal bone. This material is formed via a reaction of a glass powder with a polycarboxylic acid. The cement has a manipulation period of about 5 minutes. After setting, the cement is well tolerated by tissue and has the additional advantage of being biocompatible and permanently stable in a biological environment. The cement and the acid are commercially available as a two-component capsulated system. In cochlear implant surgery this material is used to achieve a stable attachment of the internal receiver to the temporal bone. Displacement and damaging of the internal receiver and the electrode are prevented.

Cochlear Implants↗

Interindividual differences in the pituitary-thyroid axis influence the interpretation of thyroid function tests.

OBJECTIVE: We investigated interindividual differences in the shape, slope and setpoint of the pituitary-thyroid axis (PTA) in normal persons. Based on these physiological data we propose a novel bivariate concept for the interpretation of thyroid function tests which is less biased by interindividual differences in the PTA than the currently used univariate approach. DESIGN: In two separate trials (A and B), healthy volunteers were given small, increasing doses of T3 (7.5-45 micrograms/day orally) over 5 days. The regulation characteristics of the individual PTAs and the effects of age and gender were assessed by general linear regression models. In addition, serum samples were collected from normal persons to establish the proposed bivariate approach for the interpretation of thyroid function tests. SUBJECTS: The regulatory characteristics of the PTA were determined in a total of 21 normal volunteers (eight females, 13 males; age 24-49 years). Single blood samples were collected from 257 normal volunteers. The participants had no history of pituitary or thyroid disease. MEASUREMENTS: Free and total thyroid hormone and TSH concentrations were determined in the serum. All samples from one person were analysed in the same assay in duplicate. RESULTS: A log-linear relationship between T3 and TSH was found to describe best the individual PTA (multiple r = 0.96). However, significant differences in the setpoint (P < 0.001) and to a lesser degree in the slope (P < or = 0.05) of the PTA were detected; this variability was not dependent on age or gender. Since these findings invalidate the assumptions on which the current univariate interpretation of thyroid function tests is based, we propose a novel model for the evaluation of thyroid function tests derived from the experimentally determined shape and average slope of the PTA. CONCLUSIONS: The presence of significant age and gender-independent interindividual variations in the setpoint of the pituitary-thyroid axis raises conceptual problems with the current approach for interpreting thyroid function tests. An easy to use graphical bivariate representation of the normal ranges for thyroid function tests is presented and exemplified by the thyroid hormone and TSH measurements in a large reference population. This concept should improve the diagnostic accuracy in the borderline-normal, and particularly subclinical hypothyroid region of these hormone measurements.

Adult↗

Immunohistochemical markers of carcinoma in situ of the testis also expressed in normal infantile germ cells.

Carcinoma in situ of the testis is an intratubular, pre-invasive lesion preceding germ cell tumour. In adult men, carcinoma in situ cells differ in several aspects from normal germ cells. For example, placental-like alkaline phosphatase and/or the epitopes for the monoclonal antibodies M2A, 43-9F and TRA-1-60 are not seen in normal germ cells, whereas their presence is considered a specific sign of carcinoma in situ. As it is known that placental-like alkaline phosphatase and the epitope for TRA-1-60 are expressed in normal fetal germ cells it is possible that the markers could appear in normal infantile germ cells in a period after birth before they lose their expression. In children, carcinoma in situ cells may be difficult to identify morphologically and the use of the markers could be of great value. However, little information is available on the expression of the markers of adult carcinoma in situ in normal infantile germ cells. We investigated gonads from 66 boys less than 15 years old who died suddenly. Their deaths were unrelated to testicular disease. Immunohistochemical staining with anti-placental-like alkaline phosphatase antibody and monoclonal antibodies TRA-1-60 and 43-9F were performed. We found that these markers were expressed in some normal infantile germ cells until the age of 1 year. Therefore, these markers are not suitable for diagnosis of carcinoma in situ during the early postnatal period of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus.

The importance of the vpr gene for simian immunodeficiency virus (SIV) replication, persistence, and disease progression was examined by using the infectious pathogenic molecular clone called SIVmac239. The ATG start codon of the vpr gene was converted to TTG by site-specific mutagenesis. The constructed Vpr- mutant virus is identical with the parental SIVmac239/nef-stop virus with the exception of this one nucleotide. These viruses replicated with similar kinetics and to similar extents in rhesus monkey lymphocyte cultures and in the human CEMX174 cell line. Five rhesus monkeys were inoculated with the Vpr- variant of SIVmac239/nef-stop, and two monkeys received SIVmac239/nef-stop as controls. Both controls showed reversion of the TAA stop signal in nef by 2 weeks postinfection, as has been observed previously. Reversion of the TAA stop codon in nef also occurred in the five monkeys that received the Vpr- variant, but reversion was delayed on average to about 4 weeks. Thus, the mutation in vpr appeared to delay the rapidity with which reversion occurred in the nef gene. Reversion of the TTG sequence in vpr to ATG was observed in three of the five test animals. Reversion in vpr was first observed in these three animals 4 to 8 weeks postinfection. No vpr revertants were found over the entire 66 weeks of observation in the other two test animals that received the vpr mutant. Antibodies to vpr developed in those three animals in which reversion of vpr was documented, but antibodies to vpr were not observed in the two animals in which reversion of vpr was not detected. Antibody responses to gag and to whole virus antigens were of similar strength in all seven animals. Both control animals and two of the test animals in which vpr reverted maintained high virus loads and developed progressive disease. Low virus burden and no disease have been observed in the two animals in which vpr did not revert and in the one animal in which vpr reversion was first detected only at 8 weeks. The reversion of vpr in three of the five test animals indicates that there is significant selective pressure for functional forms of vpr in vivo. Furthermore, the results suggest that both vpr and nef are important for maximal SIV replication and persistence in vivo and for disease progression.

Amino Acid Sequence↗

Spermaturia and puberty.

The pattern of spermaturia in boys at different stages of puberty was investigated. Fractionated 24 hour urine was collected for nine consecutive days from eight boys aged 13-14 years and 10 boys aged 15-17 years. Spermatozoa were detected by microscopic examination of the sediment. Sex characteristics were recorded. Fifty five per cent of all urine samples were positive for sperm and all boys showed spermaturia. A large variation in spermaturia was found between and within boys at the same stage of puberty. Spermaturia was a more common and regular event during early and mid-puberty than in more mature subjects. This indicates that the mechanism of spermaturia in early and late puberty could be different. It is suggested that spermaturia in non-virilised boys could be a result of a spontaneous, continuous flow of spermatozoa to the urethra in contrast with the peristaltic flow during ejaculation occurring at a later stage of puberty.

Adolescent↗

Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate.

Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s-PIIINP changed significantly with age and pubertal development stages. For s-PIIINP, a peak was seen at 12 yr for girls and 13 yr for boys; no peak could be discerned for s-PICP. The prepubertal (Tanner stage 1) s-PICP value (mean +/- SD) for girls was 374 +/- 132 micrograms/L, the midpubertal value (stage 3) was 442 +/- 135 micrograms/L, and the postpubertal value (stage 5) was 203 +/- 103 micrograms/L. The mean s-PIIINP levels for girls were 9.1 +/- 2.4, 15.0 +/- 4.3, and 6.8 +/- 3.1 micrograms/L, respectively. For boys, levels were 362 +/- 119, 544 +/- 138, and 359 +/- 256 micrograms/L for s-PICP and 8.5 +/- 2.2, 14.5 +/- 5.0, and 8.6 +/- 3.8 micrograms/L for s-PIIINP (P < 0.001 for both propeptides in both boys and girls). There was, however, a large variation in normal values for both propeptides within the age groups and pubertal stages. There was a significant correlation of s-PICP and s-PIIINP levels to height velocity in girls (r = 0.35; P < 0.001 and r = 0.33; P < 0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P < 0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s-PICP were normal (PICP SDS, 0.39). Levels of both propeptides decreased within 2 months after initiation of therapy and remained below initial values (P < 0.01). The decrease in s-PIIINP after 2 months of therapy showed a significant correlation with the fall in height velocity SDS for chronological age after 6 months of therapy (r = 0.64; P < 0.01). We conclude that s-PIIINP and, to a lesser degree, s-PICP reflect growth in normal children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children.

Adolescent↗

[A mathematical description of the relative dosage distributions of stereotactic collimator tubes in 6-MV photon radiation].

The relative dose distributions of small circular fields for 6 MV photons may be calculated using a simple mathematical model. This model has been developed for stereotactic collimators with cylindrical cross section and diameters between 5 mm and 30 mm. The model consists of the description of depth dose curves and off-axis dose distributions. The function for off-axis dose distributions is calculated by convolution of a simple profile function with a constant function. The width of the constant function is defined by beam geometry. In the result of integration only the width of the profile function is unknown, but it can be iteratively calculated. The agreement between measured and calculated dose distributions was tested at 5 cm and 20 cm depth in water and 100 cm source-to-surface distance using thermoluminescent dosimetry (TLD) and films, giving a resolution of 1 mm. The depth dose curve is described using the inverse square law and two exponential functions. The first of these functions contains the effective attenuation coefficient in the argument, the second describes the build-up. The increase of irradiated volume with increase of field diameter is accounted for using scatter-air ratios. The calculations were compared with TLD and ion-chamber measurements.

Electrons↗

Endothelial dysfunction in human atherosclerotic coronary arteries.

Human coronary arteries were taken from heart transplant patients. Arteriosclerotic arteries were more depolarized and constricted over the whole PO2 range between 535 and 0 mmHg. During oxygen deficiency, control preparations showed a maximal hyperpolarization of delta V = 10.9 mV and a maximal relaxation of delta T = 0.466 g. Arteriosclerotic arteries, however, became hyperpolarized by merely delta V = 7.1 mV and relaxed by delta T = 0.258 g. In normal coronary arteries, indomethacin reduced the hypoxic hyperpolarization and dilatation at 30 mmHg PO2 by about 51%. The reduction was 27% in arteriosclerotic vessels. The complete removal of the endothelium caused a 49% (73% in arteriosclerotic coronaries) restriction of dilatory vascular reactivity. The relationship was quite similar for a carbogen Krebs solution. The hyperpolarizing and dilatory contribution of prostacyclin was 32% in normal and 12% in arteriosclerotic coronary arteries. The remainder could be attributed to the basal release of endothelium-derived hyperpolarizing factor (EDHF). Thus, it may be concluded that in arteriosclerotic blood vessels, prostacyclin (PGI2) synthesis and release are predominantly diminished. Finally, we found that the ratio PGI2/EDHF in the voltage and tension changes strongly shifted to the PGI2 side with a declining oxygen concentration. This is true for normal and arteriosclerotic vessels. In addition, a disturbed transmembrane cation distribution in the arteriosclerotic coronary vessels may be an additional explanation for the depolarized membrane potential and increased muscle tone. [Na+]i of normal arteries amounted to 16.6, of arteriosclerotic arteries to 60.9 mmol.l-1; [K+]i values were 134.6 in normal and 95.0 mmol.l-1 in arteriosclerotic coronaries, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Disease↗

[Characteristics of fungus carriers as a source of infection].

1. The great majority of Central Europeans is colonized by a commensal yeast flora, mostly Candida species. These colonized humans permanently liberate yeasts mainly via the faeces. 2. The commensal yeast flora in an individual is qualitatively and quantitatively stable for long periods. 3. The commensal yeast flora is not dangerous for the immunocompetent human and should not be drug-treated without indication. An eradication of the commensal yeast flora by non-resorbable polyene antimycotics is not possible. 4. Infectious complications of the intestinal tract are etiologically rarely caused by fungi. The diagnosis of an intestinal mycosis requires the exclusion of other more frequent etiological factors. The rate of Candida excretion in a human with Candida enteritis or Candida enterocolitis is higher than in healthy carriers. 5. The immunocompromised neutropenic risk patient is highly dangered by candidosis originating from the commensal yeast reservoir of the patient's own gastrointestinal tract or from the environment. 6. The faecal and, to a minor extent, the aerogenic excretion of commensal yeasts may cause anal-oral or oral-oral infections. Due to a relatively minor environmental resistance of the yeasts these infection chains are not stable and limited relating to space and time. Immunocompromised risk patients, however, being present in the vicinity of carriers are dangered. Prominent examples are the colonization of the gastrointestinal tract of newborns as well as the colonization of catheters in the intensive care wards. A preventive monitoring to interrupt infection chains may be necessary in this domain.

Candida↗

Characterisation of the central nervous depressant activity of a commercially available valerian root extract.

The evaluation of a commercially available valerian root extract (Valdispert) revealed pronounced sedative properties in the mouse with respect to a reduction in motility and an increase in the thiopental sleeping-time. A direct comparison with diazepam and chlorpromazine revealed a moderate sedative activity for the tested extract. The extract showed only weak anticonvulsive properties.

Animals↗

[Pharmacokinetics and relative bioavailability of iron and folic acid in healthy volunteers].

The pharmacokinetics and the relative bioavailability of iron and of folic acid was investigated in a randomized, balanced 2-way cross-over study with 14 healthy male participants. The drugs were given in a combined preparation dragée (Ferro-Folsan) containing 100 mg of ferrous-II-sulfate x 1.5 H2O (CAS 13463-43-9) and 0.85 mg of folic acid (CAS 59-30-3). Other established preparations were used as reference drugs. All subjects had a normal iron body level and were brought to a saturated folic acid level prior to the investigation. After administration of 2 dragées of the test medication and determination of serum iron level until 9 h p.a., a relative bioavailability of 64%, compared to an equal dose of a ferrous-II-sulfate-ascorbic acid reference solution, was calculated. From the serum folate AUC (0-9 h) the relative bioavailability was evaluated with 97% for the oral formulation compared to the i.m. administration. The ratio of the cumulative renal folate excretion in the 0-9 h interval amounted to 76% for the oral compared to the i.m. administration. However, in order to understand this differing result it should be kept in mind that during the first hours following parenteral administration a greater amount of the unchanged compound is renally excreted than after oral dosing. This is presumably based upon the different rate of absorption following both administrations with a steeper absorption phase following the parenteral dose.

Administration, Oral↗

[Bioavailability of folic acid following intramuscular and intravenous administration to healthy volunteers].

Bioavailability of Folic Acid Following Intramuscular and Intravenous Administration to Healthy Volunteers 2 mg folic acid (Folsan 2, CAS 59-30-3) were either i.m. or i.v. administered as injection solution to 15 male healthy subjects within an open balanced two-way crossover study. The concentration-time profile of folic acid was determined up to 12 h p.a. in serum and urine using a radioassay. Each change-over phase included a 9 days lasting saturation phase with once-per-day oral administration of a tablet containing 5 mg folic acid. Saturation was performed in order to guarantee filled-up endogenous folate storage compartments in the body of the subjects. After a four-day wash-out phase the subjects were confined and the basic serum level and basic renal 0-12 h folate excretion determined. On the following morning the respective dose of 2 mg folic acid was either i.m. or i.v. applied to the subjects (treatment day 14). 11 (i.m.) and 15 (i.v.) venous blood specimens were drawn up to 12 h p.a. and urine collected following the same schedule as the day before in 4 different fractions. The mean predose level of folic acid in serum was 13.2 +/- 4.85 ng/ml before the i.m. administration and 13.3 +/- 5.59 ng/ml before i.v. administration. The serum concentration data following the respective single administrations were corrected by subtraction of the individual predose values. After 0.50 +/- 0.19 h (mean tmax) the folate serum level increased by 101 +/- 27.2 ng/ml after the i.m. dose. Serum concentration decreased in the following 6-8 h approximately to the predose values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[The solitary pulmonary histoplasmoma].

A 63-year-old man who grows orchids as a hobby, fell ill with weakness and pain in his hips and legs 2 months after his latest trip to South America (Ecuador). The WBC count was 9900/microliters with unremarkable differential count while blood sedimentation rate was raised to 60/100 mm. The chest X-ray demonstrated in the right upper lobe a well-circumscribed coin lesion (3 cm diameter) of soft-tissue density, uncalcified and without cavitation. Computed tomography in addition revealed an enlarged lymph-node at the lower hilar pole, but no mediastinal lymphoma. Bronchoscopy demonstrated narrowing of a subsegmental ostium of the 6th segment on the right. An attempt at transbronchial biopsy failed. As a peripheral bronchial carcinoma was suspected, a posterolateral thoracotomy was performed (4 months after the trip to Ecuador). Rapid histological examination was negative for tumour and the lesion was therefore enucleated. Histologically (Grocott silver staining) a histoplasmoma was diagnosed. Several serum samples were positive for precipitating (M-band) and complement-binding antibodies (titre 12 days preoperatively was 1:16). The postoperative course was without complication. No anti-histoplasma antibodies were demonstrable 1 year postoperatively.

Antibodies, Fungal↗

Synthesis and degradation of polyphosphate in the fission yeast Schizosaccharomyces pombe: mutations in phosphatase genes do not affect polyphosphate metabolism.

The fission yeast Schizosaccharomyces pombe was found to accumulate large amounts of polyphosphate, particularly when grown on arginine as the nitrogen source. Upon transfer to a medium without phosphate, polyphosphate was degraded and served as an endogenous phosphate reserve. When phosphate was added again after a prolonged period of phosphate starvation, fission yeast cells synthesized more polyphosphate than they had contained before starvation, a phenomenon known as over-compensation. Strains carrying mutated structural genes for three different phosphatases, pho1, pho2 or pho3, degraded polyphosphate at the same rate as the wild-type strain during phosphate starvation and showed the same type of over-compensation when phosphate was added again.

Genes, Fungal↗