Induction of antibodies to methadone during methadone maintenance treatment of heroin addicts and its possible clinical implications

By means of two different types of enzyme-linked immunosorbent assay (ELISA) techniques, antibodies to methadone were detected in blood plasma of heroin addicts on methadone maintenance treatment. In 11-15% of cases immunoglobulin (Ig) M antibodies were detected, while IgG antibodies were observed in 33-40%. At least two types of antibodies to methadone were induced-antibodies with high affinity to methadone and low-affinity antibodies more specific for morphine than for methadone. The methadone antibody-positive group of patients had a significantly higher plasma methadone concentration--440 ng/ml, than the antibody-negative group--250 ng/ml (P < 0.005) despite almost the same mean therapeutic doses of methadone. Of patients with all types of antibodies to methadone 52% were human immunodeficiency virus (HIV)-positive, whereas in the group without antibodies, HIV-positive reactions were observed in 10.5% only (P < 0.002). Alternatively, 87.5% of HIV-positive patients had antibodies to methadone, a fact which should be taken into consideration during methadone dose adjustment.     

High-performance liquid-chromatographic-atmospheric-pressure chemical-ionization ion-trap mass-spectrometric identification of isomeric C6-hydroxy and C20-hydroxy metabolites of methylprednisolone in the urine of patients receiving high-dose pulse therapy

Fourteen metabolites of methylprednisolone have been analysed by gradient-elution high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The compounds were separated on a Cp Spherisorb 5 microm ODS column connected to a guard column packed with pellicular reversed phase. The mobile phase was an acetonitrile- 1.0% aqueous acetic acid gradient at a flow rate of 1.5 mL min(-1) The analysis gave a complete picture of parent drug, prodrugs and metabolites, and the alpha/beta stereochemistry was resolved. The short (1-2 h) elimination half-life of methylprednisolone is explained by extensive metabolism. The overall picture of the metabolic pathways of methylprednisolone is apparently simple-reduction of the C20 carbonyl group and further oxidation of the C20,C21 side chain (into C21COOH and C20COOH), in competition with or in addition to oxidation at the C6 position.     

Distribution of genotypes and response to alpha-interferon in patients with hepatitis C virus infection in Germany

To determine the distribution of hepatitis C virus (HCV) genotypes in German isolates, nucleotide sequences of the viral nonstructural 5 (NS5) genome domains were analyzed in isolates from 107 chronically HCV-infected patients. Of these 107 patients, 46 (43.0% were infected with subtype 1a and 47 (43.9%) with subtype 1 b. Six patients (5.6%) with a history of intravenous drug abuse were infected with subtype 3a. Eight patients (7.5%) who had acquired their HCV infection in Egypt carried subtype 4a. Forty-three of the 107 patients were treated with -interferon. Of these 43 patients, 16 (37.2%) were infected with subtype 1a and 27 patients (62.8%) with subtype 1b. Three patients infected with HCV-subtype 1a (18.7%) and four patients infected with subtype 1b (14.8%) showed a sustained complete response after interferon therapy. The HCV genotype 1 with its subtypes 1a and 1 b was the most common source of HCV infection in this group of patients. There was no significant difference in response to -interferon treatment of HCV infection with the subtypes 1a or 1b.     

Information video about oral hygiene. Short term effects on knowledge, attitude and behavior of 1st and 2nd graders of LBO and MAVO

The short term effects of a dental health educational video on adolescents' knowledge, attitude and future behaviour were assessed. Results showed a large effect on knowledge and a small effect on five attitudinal aspects. No effects were found on future behaviour.     

Correlation of freeze-fracture and scanning electron microscopy of epiphyseal chondrocytes

Summary Chondrocytes in epiphyseal cartilage were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) using freeze-fracture techniques. Freeze-fracture replicas showed large numbers of fingerlike, 0.11–0.15 m diameter, projections from the chondrocyte surface, with numerous 95–180 Å diameter intramembranous particles associated with both the cell membrane surface and these projections. With SEM, these cytoplasmic projections were also obvious, but appeared collapsed into clusters of globular-shaped projections on the surface of the chondrocytes. With freeze-fracture techniques, in which shrinkage artifacts were essentially eliminated, the cytoplasmic projections were often seen in intimate contact with the extracapsular matrix. However, with chondrocytes prepared by both SEM and conventional TEM, there was evidence of shrinkage, the cytoplasmic projections having little contact with the extracapsular matrix. These findings show that the cytoplasmic processes are not artifacts of tissue processing and provide morphological evidence in support of the hypothesis that matrix vesicles are of cellular origin.Correlation of Freeze-Fracture and Scanning Electron Microscopy of Epiphyseal Chondrocytes     

Magnetic resonance imaging in the clinical diagnosis of Creutzfeldt-Jakob disease

OBJECTIVE: To evaluate the diagnostic usefulness of magnetic resonance imaging (MRI) in the clinical diagnosis of Creutzfeldt-Jakob disease (CJD). BACKGROUND: Creutzfeldt-Jakob disease is a rare neurodegenerative disease that belongs to the group of human spongiform encephalopathies and usually affects elderly people. It is clinically characterized by rapidly progressive dementia and development of neurological symptoms, such as myoclonus or ataxia. Until now, neuroradiologic investigations have only played a minor role in establishing the clinical diagnosis of CJD, and they are often performed to exclude differential diagnoses. SETTING: A university hospital, base of the German National Creutzfeldt-Jakob Disease Surveillance Study. METHODS AND PATIENTS: In this study, MRIs from suspected cases of CJD were examined by one investigator blinded to the diagnosis. Patients were classified according to the established clinical and neuropathological criteria. RESULTS: Bilateral symmetric, high signal intensities on T2-weighted MRIs were present in the basal ganglia of 109 (67%) of 162 patients with CJD. In the control group, which consisted of non-CJD dementia patients, these abnormalities on T2-weighted MRIs were found in 4 (7%) of 58 patients. This corresponds to a high specificity in the differential diagnosis of CJD. CONCLUSION: These results indicate that MRI is a useful and valuable tool with reasonable sensitivity (67%) and high specificity (93%) and should be considered as an additional cornerstone in the clinical diagnosis of CJD.     

Neuromuscular and psychomotor abnormalities in patients with schizophrenia and their first-degree relatives

In previous studies of schizophrenic patients, neuromuscular (histopathological and electrophysiological) and psychomotor (finger tapping) abnormalities were found. The present study was designed to investigate relationships between these abnormalities and a family history of psychosis in 14 schizophrenic patients and 25 unaffected first-degree relatives compared to 14 healthy controls. Muscle biopsies were performed in either m. tibialis anterior or m. lateralis. Macro EMG recordings were made from m. tibialis anterior. A finger tapping test was used to investigate psychomotor performance. Neuromuscular abnormalities (muscle biopsies and/or macro EMG) and/or aberrant psychomotor performance (finger tapping test) were found in 13 (93%) patients, 14 (56%) first-degree relatives and in three (21%) controls. A statistically significant relationship for the psychomotor, but not neuromuscular changes to a family history of psychosis was found using a logistic regression method. The percentage of patients, relatives and healthy controls exhibiting were 36/40/7% in the muscle biopsy, 50/20/0% in the macro EMG, and 71/82/14% in the finger tapping investigations. A higher frequency of neuromuscular and psychomotor abnormalities was found in patients with schizophrenia and their first-degree relatives compared to healthy controls. The relationship between psychomotor findings and a family history of psychosis indicate that central aspects of motor aberrations are associated with a hereditary disposition of psychosis. The neuromuscular as well as psychomotor changes indicate that schizophrenia may be a systemic disease involving the central nervous system as well as peripheral organs. An altered cell membrane is suggested to be an underlying factor based on the type of neuromuscular findings.     

Carotid artery stiffness in patients with end-stage renal disease: no effect of long-term homocysteine-lowering therapy

BACKGROUND: The excess of cardiovascular disease in end-stage renal disease (ESRD) patients is unexplained, but could relate to altered intrinsic vascular wall properties, such as increased arterial stiffness, which could be mediated by hyperhomocysteinemia. We investigated potential determinants of carotid artery stiffness in ESRD patients and the effect of long-term homocysteine-lowering treatment. PATIENTS AND METHODS: Fifty-four patients on maintenance dialysis treatment were studied at baseline. Fourty-one patients completed the treatment protocol, which consisted of a 12-week treatment with folic acid 5 mg daily with or without betaine 4 g per day, and of 1 or 5 mg of folic acid thereafter for 40 weeks. Both phases were randomized. Compliance and distensibility coefficients (CC and DC) and the stiffness index (beta) of the common carotid artery were determined at baseline and after 52 weeks of treatment using a non-invasive vessel wall movement detector system. RESULTS: At baseline, plasma total homocysteine was elevated (44.1+/-33.7 micromol/l), but showed no relationship with CC, DC or beta. Age and mean arterial pressure (MAP) were the only independent determinants of CC and DC, whereas beta was associated with age only. Plasma homocysteine showed a sustained decrease after therapy (20.7+/-9.0 micromol/l at week 52). No significant changes occurred in CC (from 0.59+/-0.21 to 0.60+/-0.22 mm2/kPa; p = 0.47), in DC (from 14.9+/-6.1 to 15.3+/-6.2 10(-3)/kPa; p = 0.55), or in beta (from 10.9+/-4.7 to 11.2+/-4.4; p = 0.64). No independent determinants were detected for the change in CC, whereas the change in DC was inversely related to the change in MAP (stand. r = -0.58; p<0.0002). The decrease in MAP after therapy was significant (p = 0.003) and was related to the dialysis mode (p = 0.003) and smoking status (p = 0.02). CONCLUSION: Folic acid treatment of hyperhomocysteinemia has no major effect on carotid artery stiffness in chronic dialysis patients. The results do, however, emphasize the importance of tight blood pressure control in these patients.