[5-Year-Follow-up of the MEmbeR Multicenter Study on Medical-Occupational Rehabilitation]. / 5-Jahres-Follow-Up der multizentrischen Evaluationsstudie zur medizinisch-beruflichen Rehabilitation (MEmbeR).

In Germany, medical-occupational rehabilitation represents an essential link between rehabilitation programs focusing either on medical or occupational rehabilitation. Its main objective is return to work. The current study presents the vocational integration 5 years after medical-occupational rehabilitation and determines possible prognostic factors for long-term occupational integration. To evaluate the effectiveness of medical-occupational rehabilitation, a 5-year-follow-up interview was conducted with participants (n=105) of the multicenter study on medical-occupational rehabilitation (MEmbeR). As a main result, 76% of the participants were still employed 5 years after medical-occupational rehabilitation and the return to work rate was 57%. Prognostic factors for long-term occupational integration could not be identified. However, a low degree of disability, an unrestricted capacity for teamwork as well as an unrestricted ability to judge might be beneficial factors for a successful reintegration. The high amount of participants who returned to work 5 years after medical-occupational rehabilitation, supports the concept of medical-occupational rehabilitation. However, more studies are needed to identify further factors influencing the outcome.

[The MEmbeR Multicenter Study on medical-occupational rehabilitation]. / Multizentrische Evaluationsstudie zur medizinisch-beruflichen Rehabilitation (MEmbeR).

INTRODUCTION: MEmbeR is a prospective multi-center study on medical-occupational rehabilitation in Germany. METHODS: 196 neurological, psychiatric, orthopaedic, and internal medicine patients from 21 rehabilitation centres all across Germany have been enrolled and followed-up for 2 years after discharge. Primary outcome parameter was defined as return to work. Further, the SF-12 and a Mini-ICF-Rating have been used. RESULTS: Mean age was 34.1 (9.9) years, length of stay 150.0 (223.5) days. Prior to occupational rehabilitation, 69.9% were unable to work, 2 years after discharge only 5.6%. Rate of participants seeking a job was reduced from 19.7% to 3.1%. In summary, 78.1% returned to work. Employed participants were younger (32.8 [9.7] vs. 38.5 [9.4] years, p=0.001) and less disabled (Degree of Disablement [GdB]: 20.0 [31.2] vs. 36.1 [33.7], p<0.05). CONCLUSION: The multicenter cohort study MEmbeR provides further knowledge about the outcome of medical-occupational rehabilitation in Germany.

Cerebellar atrophy decreases the threshold of carbamazepine toxicity in patients with chronic focal epilepsy.

BACKGROUND: Cerebellar atrophy (CA) is a frequent finding in patients with chronic epilepsy. Since gaze-evoked nystagmus, dizziness, and ataxia are some of the typical adverse effects (AEs) of the dose-dependent toxicity of carbamazepine, preexisting CA could possible explain in part the interindividual variation in the tolerance of high serum concentrations of carbamazepine. OBJECTIVE: To determine whether CA reduces the threshold for overdose symptoms with carbamazepine in patients with chronic focal epilepsy in a prospective study. DESIGN: Cohort study. SETTING: A fourth-level epilepsy center to which patients were referred. PATIENTS: Twenty-six consecutive patients with chronic focal epilepsy were prospectively studied while they were receiving high-dose monotherapy with carbamazepine. Patients were slowly titrated to doses at which the first toxic AEs of carbamazepine occurred. The determination of multiple serum levels was carried out, together with an evaluation of toxicity that comprised a standardized neurologic examination, a questionnaire for AEs, and posturography. MAIN OUTCOME MEASURES: Serum concentrations of carbamazepine at the occurrence of the first dose-dependent AEs were related to the presence or absence of CA in magnetic resonance imaging studies as rated by 2 independent and blinded neuroradiologists. RESULTS: In 9 patients (35%), magnetic resonance imaging scans revealed moderate (n = 7) or severe (n = 2) CA. In these patients, gaze-evoked nystagmus (P = .001, log rank test), dizziness (P = .008), and ataxia of stance as measured by posturography (P = .02) occurred at significantly lower serum concentrations of carbamazepine compared with patients without CA. This was also found for the first individually observed AE (P = .03). CONCLUSION: Cerebellar atrophy occurs in a considerable percentage of patients with chronic focal epilepsy and obviously increases the susceptibility for cerebellar AEs of carbamazepine.

Establishment of human Ig producing heterohybridomas by fusion of mouse myeloma cells with human lymphocytes derived from peripheral blood, bone marrow, spleen, lymph node, and synovial fluid. Effect of polyclonal prestimulation and cryopreservation.

50 fusion experiments were carried out to analyse heterohybridization efficiencies on mouse myeloma cells of the P3 X63 Ag8/653 line with human lymphocytes derived from peripheral blood, bone marrow, lymph node, spleen or synovial fluid. We found higher yields of growing and human Ig-producing hybridoma lines when lymphocytes from spleen or lymph node were fused. Although primary hybridomas could be established from fusions with bone marrow-derived cells, only in nine out of 1616 initially seeded wells was Ig production registered. Four fusions using immune cells from synovial fluid were made without success. Independently of the source of lymphocytes pokeweed mitogen (PWM) prestimulation had no enhancing effect on the percentage of wells with cell growth and this did not alter the IgM:IgG ratio in primary hybridomas (9:1), although cells from all compartments used here (with the exception of bone marrow cells) could be stimulated with PWM to produce both IgG and IgM in cultures. Cryopreserved lymphocytes from different sources could be used for fusions with comparable results registered for the fresh material.

Pharmacokinetic interactions of the new antiepileptic drugs.

Therapy with traditional antiepileptic drugs is associated with a wide range of pharmacokinetic drug-drug interactions. In particular, enzyme induction, enzyme inhibition and displacement from protein binding may result in important changes in serum concentrations of antiepileptics. Relevant interactions have also been described for some new antiepileptics. Felbamate increases serum concentrations of phenytoin, phenobarbital and valproic acid (sodium valproate). On the other hand, it reduces concentrations of carbamazepine and increases concentrations of its metabolite carbamazepine-10,11-epoxide. Concentrations of felbamate itself are reduced by phenytoin and carbamazepine. Concentrations of lamotrigine are considerably increased by valproic acid and decreased by phenytoin, carbamazepine and phenobarbital (phenobarbitone). Vigabatrin reduces serum concentrations of phenytoin by approximately 20%. On the other hand, some new antiepileptics have the important advantage of not interfering with the metabolism of other antiepileptics; this is the case for gabapentin, lamotrigine and oxcarbazepine. Furthermore, the pharmacokinetics of gabapentin, oxcarbazepine and vigabatrin are independent of concomitant drugs. These aspects are especially important as, until now, new antiepileptics have been most often utilised as add-on therapy.

Immune restoration in children after partial splenectomy.

Splenectomy (SE) is recognized to be a therapeutical approach in treating children with severe autoimmune diseases (chronic idiopathic thrombocytopenia; hemolytic anemia) or hypersplenism because of portal hypertension. Nevertheless, removal of a main immune organ results in elevated infection risk for these patients. Partial splenectomy (PSE) was developed as a therapeutical compromise to retain immunologically active spleen tissue. Here, we document the analysis of immune parameters obtained from children after both partial and total splenectomy, which have been followed up for a period of more than 6 years: (i) Lymphocytes from both groups of patients failed to produce IgG in response to pokeweed mitogen in vitro. This was observed in 11/20 splenectomized patients even 10 years after operation, whereas in PSE patients a restoration of this parameter after 1-2 years was seen. (ii) In patients after PSE, but not in splenectomized persons, an elevated number of HLA-class II positive cells had been detected suggesting a different situation of immune regulation following this operation. However, in parallel with an improvement of B cell in vitro activity this parameter was found to achieve normal values. Our findings indicate that partial splenectomy may be a therapeutical alternative, if the therapeutic goal can be achieved by this procedure.

Expression of early genes in light-induced chloroplast differentiation of cultured plant cells.

The objective of this study was to identify genes, preferentially of the plastid, which are rapidly expressed during the initial phase of blue-light-induced chloroplast development in suspension-cultured cells (Chenopodium rubrum L.) and to analyse the encoded proteins. A cDNA library (lambda gt 10) was constructed using total RNA from plastid preparations of dark-grown cells exposed to blue light for 3, 6 and 12 h. By differential screening, at least three clones were identified which correspond to rapidly light-induced plastid genes. For these and a number of nuclear genes represented by other clones, a temporary accumulation of the specific mRNA was observed between 12 and 48 h of blue-light exposure. With regard to their nucleotide sequence and derived amino-acid sequence they seem to represent a novel group of genes distinctive in structure and encoded product.

[Compliance with antiepileptic drugs]. / Medikamenten-Compliance bei Epilepsie.

Inadequate adherence to a prescribed medication regimen, so-called noncompliance (NC), occurs in 30-50% of patients with epilepsy and is thought to be a major cause of insufficient seizure control. This article gives an overview on how NC can be diagnosed, its causes, which patient groups are at risk, and which interventions are suitable to improve or maintain compliance.

Engineering high-temperature stable nanocomposite materials.

The low thermal stability of nanoparticles typically restricts their use in catalytic and other applications to low- to moderate-temperature conditions. We present a novel approach to the stabilization of nanosized noble metal particles by embedding them in a high-temperature stabilized hexa-aluminate matrix. The simple 'one-pot' approach is based on a microemulsion-templated sol-gel synthesis and yields mesoporous nanocomposite materials with pure textural porosity and excellent high-temperature stability up to about 1200 °C. To our knowledge, this is the first time that metal nanoparticles have been stabilized to such high temperatures. We furthermore find that the microemulsion templating allows a tailoring of the ceramic matrix without influencing the size of the embedded Pt particle. This opens up the possibility of a true multiscale engineering of nanocomposite materials. We see these novel materials therefore not only as very promising candidates for a broad range of high-temperature catalytic applications, but generally view this versatile synthesis route as a first step towards expanding the parameter range for nanoparticle applications.

[Ultrastructural-morphometric studies on the rat liver in the postnatal period. 1. Changes in the extrahepatocyte volume, the hepatocyte nuclei the cytoplasm and and the nucleus-cytoplasm ratio]. / Ultrastrukturell-morphometrische Untersuchungen der Rattenleber in der Postnatalperiode 1. Die Veränderungen des Extrahepatocytärvolumens, der Hepatocytennuclei, des Cytoplasmas und der Kern-Plasma-Relation.

Quantitative changes in the volume densities of extrahepatocyte spaces, nuclei of hepatocytes, cytoplasm and of the nucleus-cytoplasm-ratio were studied in male Wistar-rats aged 0 (birth), 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 days and 2, 3, 4, 5 and 6 months. The ratio of hepatocyte/nonhepatocyte fractions is 40.3 : 59.7 at birth and it increases to 86.6 : 13.4 by the 6th month. We observed 2 phases of proliferations of hepatocytes in the first 4 days, while the single volume of hepatocytes reaches lower levels. After the 4th day the single volume of hepatocytes increases because of the augmentation of volume density of cytoplasm. According to these changes the nucleus-cytoplasm-ratio will be reduced to 0.077 by the 5th month.

Discontinuation of clonazepam after long-term treatment.

Frequent unwanted side effects and development of tolerance are the main disadvantages of clonazepam (CZP) in long-term treatment of epileptic patients. A review of the literature shows that CZP tolerance more often appears in severe forms of childhood epilepsy (West and Lennox-Gastaut syndromes) than in other epileptic syndromes. We prospectively studied the consequences of CZP discontinuation in 40 consecutive children with difficult-to-treat epilepsies and multiple-drug therapy. The CZP was reduced stepwise in a variable daily reduction rate (0.003-0.16 mg/kg), while serum levels of the comedication were kept unchanged. In only three children (7.5%), CZP was believed to have had some antiepileptic effect; in 30 (75%) it had been ineffective, whereas in six (15%), a decrease in seizure frequency after CZP discontinuation even suggested a negative therapeutic effect. Discontinuation symptoms, mostly in the form of a transitory exacerbation of seizure frequency, occurred in 19 children (47.5%). These children had a significantly higher CZP dose and longer duration of treatment than did children without discontinuation symptoms, but there was no difference between the two groups related to the rate of CZP discontinuance.

[Prenatally diagnosed mesenchymal hamartoma of the liver]. / Pränatal diagnostiziertes mesenchymales Hamartom der Leber.

Reported in this paper is the case of a female newborn with mesenchymal hamartoma of the liver. High-accuracy ultrasonography diagnostics were applied to the mother admitted for examination for suspicion of fetal hydronephrosis in the 31st week of pregnancy. A 7 x 4 cm compartmental process was delineable in the abdominal region of the foetus and was variably viewed in ultrasonography in cystic or solid form. A girl, 2,650 g in body weight and 47 cm in body length, was delivered by caesarean section in the 35th week of pregnancy. Postnatal nutritional disorders were accompanied with recurrent vomiting. Sonography, computed tomography and scintigraphy were performed, and the prenatally diagnosed process was identified as a cystic growth in the right liver lobe with enclosure of the V. cava inferior. A typical hepatolobectomy was performed on the newborn on her 15th day of age, with the V. cava enclosing part being left unextirpated. Mesenchymal hamartoma of the liver was the histological diagnosis. Only one prenatally diagnosed case of this kind had been known from literature before.

[Experiences with the use of cerium nitrate silver sulfadiazine in the local treatment of thermal injuries in childhood]. / Erfahrungen mit der Anwendung von Cerium-Nitrat-Silbersulfadiazin bei der Lokalbehandlung thermischer Verletzungen im Kindesalter.

Ointment containing cerium nitrate and silver sulphadiazine (Flammacerium) was applied to 47 children with second-degree to third-degree thermal injuries, with something between five and 60 per cent of the body surface being affected, as had been reported in a one-year prospective study. This ointment proved to be superior to several alternative approaches with regard to local properties, antimicrobial effectiveness, and applicability to several degree of burns. The process of treatment can be optimised due to unproblematic applicability in open and closed variants under both hospitalised and outpatient conditions. This assessment has been underlined by good to very good therapeutic results.

[Production of human monoclonal antibodies by heterohybridization of human B lymphocytes of the spleen with mouse myeloma cells]. / Herstellung humaner monoklonaler Antikörper durch Heterohybridisierung von humanen B-Lymphozyten der Milz mit Maus-Myelomzellen.

Human lymphocytes were derived from the spleen of a 15-year-old female patient after partial splenectomy. High cell yield and percentage of human B-lymphocytes (over 30%) gave useful conditions for their fusion to mouse myeloma cells (P3 X63/Ag8/653). Fusion efficiency (cultures with growth) was 96%. From 288 initially seeded cultures 176 showed IgM and only one IgG production as determined by enzyme immunoassays. Twenty primary cell lines were cloned with differing results and 17 heterohybridoma cell clones with high IgM production rates could be established for more than 6 months in vitro. The present results show the possibility to produce human monoclonal antibodies in heterohybrids derived from human spleen lymphocytes.

[Fetal teratoma--diagnosis and management]. / Fetale Teratome--Diagnostik und Management.

Fetal and neonatal teratoma is rare, but it is the most common tumor of the fetus and meonate. We report seven cases with fetal sacrococcygeal teratoma and two cases with craniocervical teratoma. The diagnosis, further management of pregnancy and birth are described and compared with recent literature. While craniocervical teratoma is associated with very poor prognosis, there are sacrococcygeal teratoma with good survival rate and postoperative good functional results. Very important is prolongation of pregnancy near to term.

Postictal serum levels of antiepileptic drugs for detection of noncompliance.

Medication noncompliance (NC) is thought to be a major cause of insufficient seizure control. In an explorative study we investigated whether postictal serum levels (PISLs) of antiepileptic drugs (AEDs) are a reliable indicator of NC. Young adults with epilepsy on a stable AED regimen were asked to contact medical service as soon as possible when a seizure occurred to obtain serum levels of their AEDs. PISLs were compared with the mean value of two routine serum levels of the same medication. PISLs lower than 50% of the individual reference value were regarded as an indicator of NC. PISL samples in 61 seizures of 52 patients treated mainly with carbamazepine, valproic acid, or lamotrigine were evaluated. A drop in serum levels >50% indicating NC was noted in 44.3% of the seizures. Determination of PISLs seems to be a simple and useful method for detecting or ruling out irregular intake patterns as a cause of "breakthrough" seizures.

Partial splenectomy for treatment of chronic idiopathic thrombocytopenia in childhood.

The aim of this paper was to demonstrate the efficiency of partial splenic resection in treatment of chronic idiopathic thrombocytepenie purpura (Werlhof-Disease). In all but one case remissions of thrombocyte counts over 100 Gpt/l could be achieved. Immunological studies demonstrate the existence of a suppressor-state after this operation, which could be responsible for success of this procedure. In contrast to general considerations the partial-splenectomized child must be considered as an immunological deficient organism for about 6 to 12 months. Restoration of immunological-means whole splenic functions-parameters is to expect always after this time.

MOSES: an educational program for patients with epilepsy and their relatives.

The knowledge of patients with epilepsy about their own condition is poor, and thus the need for educational programs for people with epilepsy has long been recognized. However, no such programs have been established in their routine care. The Modular Service Package Epilepsy (MOSES) now tries to fill this gap for patients in German-speaking countries. The program was developed by a multidisciplinary group (neurologists, nonmedical professional helpers, and representatives of national epilepsy associations) for people with epilepsy older than 16 years, independent of the kind and severity of their epilepsy. MOSES is designed for group education and can be used in inpatient and outpatient settings in epilepsy centers, in clinics, and by neurologists in private practice. The program aims to help patients achieve a better understanding of their disease, to gain more self-confidence, and to take over responsibility, thus supporting patients to become experts in managing their own illness. Being modular in structure, MOSES includes nine units: living with epilepsy, epidemiology, basic knowledge, diagnostics, therapy, self-control, prognosis, psychosocial aspects, and network epilepsy. MOSES consists of a workout manual for patients and a trainer manual. For potential trainers, special "train-the-trainer seminars" are offered and considered mandatory. About 400 patients have participated in a MOSES training program in Germany, Switzerland, and Austria. The efficacy of the program is currently been evaluated.

Cerebellar atrophy does not increase susceptibility to carbamazepine toxicity.

Cerebellar atrophy (CA) is a frequent finding in patients with chronic epilepsy. To find out whether the existence of CA has an influence on the tolerance of high-dose monotherapy with carbamazepine, we compared the lowest individual toxic serum levels in patients with complex focal seizures, with CA (n = 27) and without CA (n = 20) in computerized tomography (CT). There was no statistical difference between the groups, even after separating patients with mild CA (n = 20) from those with more severe damage (n = 7). In addition, other clinical, EEG and CT data also seemed to have no influence on the individual toxic threshold serum levels of carbamazepine.

Cerebellar atrophy and prognosis after temporal lobe resection.

OBJECTIVE: Experimental data indicate inhibitory effects of the cerebellum on seizure activity. Structural damage such as cerebellar atrophy, which is a common finding in patients with chronic epilepsy, may reduce these effects. METHODS: Outcome after temporal lobectomy was studied in 78 consecutive patients, with or without cerebellar atrophy diagnosed by MRI. RESULTS: Thirty five patients (45%) showed cerebellar atrophy. At a mean follow up of 14.6 (range, 6-40) months, 50 patients (64%) had no postoperative seizures. In these patients, the frequency of cerebellar atrophy was significantly lower (34%) than in patients who relapsed (64%, p < 0.01). Occurrence of generalised tonic-clonic seizures (GTCS) within two years before surgery, occurrence of GTCS at any time preoperatively, long duration of epilepsy, and older age at surgery were also associated with recurrence of seizures. Multiple logistic regression analysis suggested occurrence of GTCS within two years before surgery and cerebellar atrophy as the main predictive indicators. When both factors were present, the percentage of patients remaining seizure free since surgery fell to 30%, compared with 60% when only GTCS were present, 78.6% when only cerebellar atrophy was present, and 87.5% when both factors were absent. CONCLUSIONS: Cerebellar atrophy shown by MRI was a frequent finding in surgically treated patients with temporal lobe epilepsy. The presence of cerebellar atrophy seems to worsen the prognosis after temporal lobe resection.