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Biomedical subjects

M Ludwig

Publications and source records attributed to M Ludwig.

297 records · Page 17Linked to original sources
PubMedDate not supplied

CYP2D6 polymorphism and tardive dyskinesia in schizophrenic patients.

Antipsychotic drug-induced tardive dyskinesia (TD) is a serious problem during psychopharmacologic treatment of schizophrenic patients. In search of genetic factors contributing to TD, there is a lack of consensus regarding the role of the polymorphic isozyme cytochrome P450 CYP2D6, which is involved in the oxidative metabolism of antipsychotic drugs. In the present case-control study, we tested the putative influence of the CYP2D6 genotype on the development of TD. Out of 157 patients, 109 were retrospectively selected meeting DSM IV criteria for schizophrenia or schizoaffective disorder, and 50 of them persistently presenting with TD. Genotyping detected the functional allele CYP2D6 *1, the known major defective alleles CYP2D6 *3, *4, *5, *6, and gene duplication. According to their number of functional CYP2D6 alleles, subjects were divided into carriers of none, one, or at least two functional CYP2D6 alleles. The proportions of these categories did not differ between patients and an ethnically homogenous control population (n = 195, p = 0.99) or between patients with and without TD (p = 0.818). Schizophrenic patients were carriers of gene duplication more often than healthy probands, without revealing statistical significance (p = 0.10). Out of seven patients with gene duplication, three developed persistent TD. Furthermore, patients with and without TD were comparable according to age, age of onset, gender, and duration of illness, but subjects with TD had taken more lifetime chlorpromazine equivalents (CPZ) than had patients without TD (chi 2-test, Student's t-test). Forward as well as backward logistic regression analyses confirmed that the presence of TD was influenced by lifetime CPZ but not by age, age of onset, gender, duration of illness, or CYP2D6 genotype. In contrast to the relevance of lifetime CPZ, the lifetime dose of antipsychotic drugs known to be metabolized by CYP2D6 did not significantly influence the presence of TD. In conclusion, our results provide no evidence for the contribution of CYP2D6 genotype to the development of TD in schizophrenic patients receiving long-term antipsychotic medication.

Adult↗
PubMedDate not supplied

Relevance of male accessory gland infection for subsequent fertility with special focus on prostatitis.

Infections of the male genitourinary tract may contribute to infertility to a various extent depending on the site of inflammation. Especially in prostatitis, the exact classification of the infection contributes to its impact on changes in the ejaculate. Similarly, in urethritis, epididymitis and orchitis, only a clear clinical diagnosis allows a rational approach to altered sperm parameters. Several inflammatory and reactive alterations of sperm quality seem to be proven; nevertheless, the impact of these findings on male fertility remains in many cases unclear. Even therapeutic trials do not provide more insights into the association of male genital infections and impaired fertility, although the efficacy of antibiotic trials seems to be proven. For the future, it may be decisive to evaluate inflammatory changes in the ejaculate not only on the basis of standard but also on functional parameters, thus providing new definitions of the interactions between male urogenital tract infection and disturbances of male fertility.

Anti-Bacterial Agents↗
PubMedDate not supplied

Is intracytoplasmic sperm injection itself an indication to perform preimplantation genetic diagnosis (PGD)? About PGD, invasive prenatal diagnosis and genetic sonography.

Intracytoplasmic sperm injection (ICSI) provides the only sufficient treatment to overcome severe forms of male infertility. However, male infertility is linked to several genetic problems as an increased number of chromosomal aberrations, cystic fibrosis transmembrane conductance regulator gene mutations, Y-chromosome microdeletions, and androgen receptor mutations. Therefore, these couples are at a higher risk of transmitting genetic problems to their offspring compared to the general population. A proposed increased number of gonosomal aberrations in the offspring possibly results from the ICSI technique itself. This led in general to a worldwide agreement to counsel those couples to undergo invasive prenatal diagnosis in order to exclude chromosome abnormalities, especially gonosomal aberrations. In this paper the genetic risks of these couples and the possible implications of ICSI itself are discussed. Preimplantation genetic diagnosis may be considered a procedure of choice in these cases, but substantial ethical problems arise when such a screening is sought. An alternative procedure of prenatal diagnosis in these couples seems to be 'genetic sonography', i.e. high-resolution ultrasound with measurement of nuchal translucency at the end of the first trimester, and detailed fetal evaluation at 18-22 weeks of gestation.

Chromosome Aberrations↗
PubMedDate not supplied

Female pseudohermaphroditism associated with a novel homozygous G-to-A (V370-to-M) substitution in the P-450 aromatase gene.

The conversion of C19 androgens to their corresponding C18 estrogens is catalyzed by an enzyme complex known as aromatase. P-450 aromatase is expressed in a tissue-specific manner and placental deficiency abolishes its function in protecting the female fetus from masculinization and the mother from prepartum virilization due to an excess of androgens. Here we report a novel homozygous aromatase mutation (Val370-to-Met) found in a girl with pseudohermaphroditism (Prader V). Sequence analysis showed the parents to be heterozygous for this amino acid substitution. Since P-450arom deficiency is a rare autosomally recessive transmitted disease, consanguinity in this kindred seemed to be obvious. With the characterization of four intragenic polymorphisms and subsequent haplotype analysis this assumption turned out to be most likely.

Aromatase↗
PubMedDate not supplied

Selenium deficiency and fatal cardiomyopathy in a patient receiving long-term home parenteral nutrition.

Fatal cardiomyopathy in a patient who received home parenteral nutrition (HPN) for eight years is reported, and the relationship of selenium deficiency to cardiomyopathy and other adverse effects is discussed. A 42-year-old white man with Crohn's disease who was receiving HPN was admitted to the hospital with severe chest pain and dyspnea. During the three days following admission, his symptoms of congestive heart failure and compensated metabolic acidosis persisted despite treatment. On hospital day 6, the patient developed increased ventricular irritability and refractory ventricular fibrillation and died. At autopsy, the heart weighted 500 g, all chambers were dilated, and the myocardium was grossly flabby. Extremely low concentrations of selenium (5-12% of normal) were found in plasma, heart, liver, and kidney tissue samples. The pathological findings in this patient were similar to those in two previously reported cases and strongly suggest that the fatal cardiomyopathy was secondary to selenium deficiency. Selenium is an integral part of the enzyme glutathione peroxidase, which plays an important role in the metabolism of tissues and organs. For metabolically stable patients receiving total parenteral nutrition, the suggested selenious acid dosage is 25-60 micrograms/day for adults and 1.4-30 micrograms/kg/day for pediatric patients. In selenium-depleted adults, a dosage of 100 micrograms/day administered intravenously for 21-31 days has been recommended to reverse symptoms. All HPN patients and hospitalized patients receiving extended parenteral nutrition should be monitored for selenium deficiency and given supplements if necessary.

Adult↗