Long-term course of epilepsy in a large cohort of intellectually disabled patients.

This study was designed to describe the course of epilepsy (in terms of seizure frequency) and to assess the variables (antiepileptic therapy regimens and others) correlated to improvement. Seizure frequency (categories: seizure free, more than one seizure/year, monthly seizures, weekly seizures and daily seizures) and antiepileptic medication were retrospectively compared between 1992 and 2002 in a large cohort of 550 inpatients with chronic epilepsy and different degrees of intellectual disability or multiple handicaps. RESULTS: Seizure frequency decreased significantly (p<0.001). 218 of the 394 patients (55.3%) not seizure free in 1992 improved (changed into a better frequency category). The improvement rate was marginally higher in patients who had undergone a medication change (p=0.08). A high seizure frequency in 1992 (p=0.016) and older age (p=0.006), but not epilepsy syndrome or degree of intellectual disability, were predictors for improvement (stepwise logistic regression analysis). 56.4% of the improved patients were on combinations of two AEDs (17.4%, monotherapy; 20.2%, triple therapy). The most frequent therapy regimens in the improved patients were lamotrigine/valproate (48 patients), carbamazepine/phenobarbital (21) and carbamazepine only (19). Lamotrigine/valproate was effective in all kinds of epileptic syndromes. Most patients on lamotrigine had serum concentrations above 10microg/ml, approximately one half had dosages above 200mg/day. The rate of seizure freedom increased from 28.4 to 37.6%. The 84% of the patients seizure free in 1992 remained seizure free. Predictors for seizure freedom in 2002 were higher age (stepwise logistic regression, p<0.0005) and seizure freedom in 1992 (p<0.0005). CONCLUSIONS: Substantial improvement can be achieved even in intellectually disabled patients with chronic epilepsy. Although the rate of seizure freedom is reduced in comparison with a non-ID population, once seizure freedom has been achieved it is most likely to continue. For a majority of this patient population, monotherapy may not be sufficient. Lamotrigine/valproate appears to be a major therapeutic innovation.     

Body Mass Index and Glomerular Hyperfiltration in Renal Transplant Recipients: Cross-Sectional Analysis and Long-Term Impact

Obesity is a risk factor for renal graft loss. Higher body mass index (BMI) in native kidneys is associated with glomerular hyperfiltration. Whether higher BMI in renal transplants is associated with hyperfiltration is unknown. We investigated the impact of BMI on renal hemodynamics 1 year post-transplant. We analyzed glomerular filtration rate (GFR, (125)I-iothalamate) and effective renal plasma flow (ERPF, (131)I-hippurate) in 838 kidney transplants. Data were analyzed for all patients and for the subpopulation without diabetes. Long-term impact of BMI and renal hemodynamics were explored by Cox-regression. With higher BMI GFR and filtration fraction (FF) increased significantly. Multivariate analysis supported impact of BMI on GFR (adjusted r(2) of the model 0.275) and FF (adjusted r(2) of the model 0.158). This association was not explained by diabetes mellitus. On Cox-regression analysis, lower GFR and higher FF were independent determinants of overall graft loss and graft loss by patient mortality. Lower GFR and higher BMI were determinants of death-censored graft loss, with borderline contribution of higher FF. In renal transplants higher BMI is independently associated with higher GFR and FF one year posttransplant, suggesting glomerular hyperfiltration with altered afferent-efferent balance. Mechanisms underlying the long-term prognostic impact of hyperfiltration deserve further exploration.     

Plant growth substances produced by microorganisms of the rhizosphere and the soil

Microorganisms isolated from the soil and the rhizosphere of wheat plants produce growth regulating substances with effects similar to gibberellins when grown in submerse cultures. Bioassays and thin layer chromatography were used for characterization. Different plant growth regulating substances and variations in their quantity were observed among microorganisms. The amounts of gibberellin-like substances found in culture filtrates varied, in a range from 0.01 to 1.0 mg GA₃ equivalents per liter.     

Measurement of functional ability and health status in the arthritic patient

Chronic arthritis may have great impact on the patient but also on his or her family, relatives and friends. The assessment of the consequences of chronic arthritis and the effect of therapy not only in terms of physical, but also psychological and social dimensions deserves more attention. Functional ability and health status can be measured using a questionnaire or ‘instrument’, high-lighting important aspects not quantified with more traditional measurements. In this paper, arguments to apply such instruments more frequently are given. Health status instruments can be used not only to assess beneficial but also deleterious (side-)effects of therapeutic interventions. The properties are summarized of the most frequently used instruments assessing functional ability and health status. Many of these instruments have been evaluated sufficiently for validity and reliability; their sensitivity to detect change seems to be satisfactory. Therefore it is advisable to choose an internationally accepted, frequently used instrument, reflecting the area of interest.     

Immunocytochemical analysis of cellular responses to BCG.

The study reported here was performed to find out whether changes in the number of mycobacteria in various organs of BCG-infected mice can be related to changes in the phenotype of monocytes, macrophages and lymphocytes in the blood, various tissues, and peritoneal cavity and to the formation of granulomas in the spleen, liver and lungs. The relative amounts of various antigens on the leukocytes were assessed semi-quantitatively after immunocytochemical detection of the binding of monoclonal antibodies. Granuloma formation was determined after immunocytochemical staining of cells in sections of liver and lung tissue with a monoclonal antibody against the common leukocyte antigen and in sections of the spleen with a monoclonal antibody against the Mac-2 antigen. The results showed that during the first week of infection the number of BCG in spleen, liver and lungs declined considerably. Multiplication of mycobacteria during the second week of infection was associated with decreased expression of antigen F4/80 and increased expression of Ia antigen and Mac-2 antigen by blood monocytes and macrophages. Reduction of the numbers of BCG in the spleen and liver during the third week after i.v. injection of BCG and in lungs during the fourth week of the infection was found to be correlated with the degree of granuloma formation in these organs. After intravenous injection of killed BCG no changes were observed in the phenotype of monocytes and the macrophages in spleen, liver, lungs and peritoneal cavity. These mice showed considerably less granuloma formation than BCG-infected mice. The present results indicate that live but not killed mycobacteria induce macrophage activation.     

Membranes of the adrenal medulla: A comparison of membranes of chromaffin granules with those of the endoplasmic reticulum

The protein and lipid composition of the membrane of the chromaffin granule has been compared with that of an endoplasmic reticulum fraction isolated from bovine adrenal medulla. The endoplasmic reticulum was purified by centrifugation of a microsomal fraction in sucrose and Ficoll density gradients. Only insignificant amounts of chromomembrin B, dopamine β-hydroxylase and cytochrome b₅₅₉, which are characteristic protein components of the chromaffin granule membrane, were present in the endoplasmic reticulum fraction; whereas glucose-6-phosphatase and galactosyltransferase, marker enzymes of membranes of endoplasmic reticulum and Golgi complex respectively, were absent from the membranes of chromaffin granules. The lipid composition of the two types of membranes varies in the relative amounts of lysolecithin, lecithin and sphingomyelin and in the molar ratio of cholesterol to phospholipid. Lysolecithin, which is a major phospholipid of the chromaffin granule membrane, is virtually absent from membranes of the endoplasmic reticulum. Different protein patterns were obtained when these two membrane fractions were solubilized with detergent and subjected to polyacrylamide gel electrophoresis.It is concluded that membranes of the endoplasmic reticulum and those of the chromaffin granules are basically different and therefore that the transport of secretory proteins from their site of synthesis to their site of storage occurs, in the chromaffin cell, by a mechanism that does not involve a mixing of the participating membranes.     

Energy dependence of contraction band formation in perfused hearts and isolated adult myocytes.

Aggregation of sarcomeres into contraction bands is a prominent feature of the oxygen paradox, the calcium paradox, and caffeine injury to calcium-free perfused hearts. For investigation of the mechanism of contraction banding, it was necessary to devise a method of evaluating the degree of sarcomere contraction and to define objectively a contraction band. Hearts with mechanical detachment of cells caused by hypocalcemic perfusion and isolated myocytes both allow unrestrained contracture of cells and permit direct optical measurements to quantitate the degree of cell contracture. With the use of the calcium paradox as a model of contraction band necrosis, it was found that cells with lengths of less than 37.3 mu could be considered as containing contraction bands. It was found that the mitochondrial inhibitors cyanide and amytal, as well as the uncoupler 2,4-dinitrophenol, allowed cell contracture but inhibited hypercontracture of sarcomeres into contraction bands during both the calcium paradox and caffeine injury to perfused hearts. However, when 2mM adenosine triphosphate (ATP) was included in the perfusion media, contraction band formation occurred despite the continued presence of cyanide or amytal. In isolated myocyte preparations the addition of the glycolytic inhibitor iodoacetate (IAA, 5 mM) and the mitochondrial inhibitor amytal (3 mM) caused relaxed rod-shaped cells (length/width ratio greater than 3:1) to contract into a stable population of square-shaped forms (length/width ratio less than 3:1), indicating an abrupt and severe decline in cellular ATP levels. Removal of amytal from the incubation medium in the presence of IAA produced a significant conversion of square-shaped cells into round-shaped cells containing contraction bands. Either IAA alone or amytal alone resulted in a mixed population of square and round cells. The results indicate that ATP is required for the formation of contraction bands in intact hearts and for the rounding of isolated myocytes. Formation of contraction bands appears to be an energy-dependent process requiring ATP.     

Increased sharing of maternal HLA haplotypes among children exposed to diphenylhydantoin during pregnancy.

During investigation of HLA types among children exposed to diphenylhydantoin (DPH) in utero, we found no evidence of a distortion in haplotype sharing among affected sib pairs. Unexpectedly, however, we found a marked increase in the proportion of all sib pairs (not just affected ones) sharing maternal haplotypes. Among 14 two child families, 12 shared the maternal haplotype (expected would be seven); among families with more than two children the distortion was also pronounced. This finding, if verified in future studies, could indicate that something in the mothers, whether DPH use during pregnancy, or some genetic factor associated with seizures, or some effect of the seizures themselves, may be leading to non-random segregation of HLA haplotypes in their offspring.