Juvenile myoclonic epilepsy

CONCLUSION: We conclude that despite inevitable variability the clinical picture of JME is characteristic. It is easy to diagnose JME if one thinks of it while the history should be thoroughly analyzed. An EEG recording during sleep confirms the diagnosis. An early diagnosis of JME permits adequate prognosis of the subsequent course of epilepsy, and adequate therapy brings remission in most of the patients. If treatment starts following the large number of severe GTC seizures, the response to therapy is incomplete. The persistency of the illness throughout the life, the need for continuous medication and therapeutic unresponsiveness in cases with late diagnosis, do not justify the increasing misconception that JME is of benign nature. Diagnosis of JME is rare because of insufficient familiarily of physicians with the illness. BACKGROUND: Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epileptic syndrome characterized with the combination of myoclonic, generalized tonic-clonic (GTC) and absence seizures that are readily provoked by sleep deprivation. PATIENTS: Forty-three patients, aged from 14 to 51 years, participated in a 5-year follow-up study. Diagnosis was made according to the criteria (Table 1) for diagnosis of JME set by Panayiotopoulos et al. (1994). Nineteen patients made their first contact with a neurologist at the Institute of Neurology and were diagnosed as JME, while the remaining 24 were referred to from other medical institutions with a diagnosis of therapy resistant to focal epilepsy. All patients underwent a somatic and neurological examination, "mini mental test," EEG in waking and CT scan of the brain. Some patients had EEG performed during sleep and some had MRI of the head. RESULTS: JME began between 9 and 26 (average 17) years. All patients had myoclonic seizures, 98% had GTC and 23% absence seizures. The first myoclonic seizure occurred between 9 and 24 years while the frst GTC seizure occurred between 10 and 32 years. Myoclonic seizures (83% of patients) and GTC seizures (70% of patients) occurred most often immediately after awaking. The most frequent provocative factors were insufficient sleep, alcohol abuse and tiredness. Epilepsy in the family was present in 39%, focal neurological deficiency in 9% and pathological findings on of CT and MRI in 7% of patients. Waking EEG was pathological in 77% of patients; it included generalized spike-wave discharges in 73%, multiple spike-wave complexes in 33% and focal discharges in 12% of patients, respectively. In all 26 patients tested, sleep EEG was pathological most often with multiple spike-wave complexes in 85% and 3-4 Hz spike-wave complexes in 57% of patients. The correct diagnosis of JME following a comprehensive examination was made in 24 (56%) patients after a delay of 1 to 35 years. In 24 patients with delayed diagnosis of JME the replacement of earlier medication with valproic acid (VPA) induced remission in 18 patients (75%) while 1 patient (4%) experienced a reduction in the number of seizures. Five patients (21%) did not respond to VPA medication: 2 due to a weak compliance, another 2 due to inefficient medication and 1 because of the preexistent malabsorption syndrome. In 19 patients (44%) with initial diagnosis of JME, VPA was introduced immediately upon diagnosis. Of them, 15 (79%) had excellent response to VPA, 1 refused therapy and for 3 patients there is no information. In 2 patients VPA was substituted due to side effects (hepatotoxicity and alopetia) with lamotrigine (low doses), which brought about decrease in frequency and mitigation in myoclonic seizures.     

Insulin-like growth factor I-dependent regulation of prolidase activity in cultured human skin fibroblasts

In metastatic breast cancer the goal to reach must be the best possible palliation with minimum discomfort for the patient. We reviewed our experience with radiotherapy (20 or 30 Gy), systemic therapy and brace. Among 2200 breast cancer patients, we extracted 28 potential candidates for resection. All of them developed new metastases outside the treated field within one year. Local control was achieved in 68%, and 80% of them had stable or better performance status at 3 months. From our analysis, even patients with a so called "solitary lesion" do not seem to have a better prognosis than others. We conclude that radiotherapy (with systemic therapy and a brace) is still first-choice treatment for vertebral metastases; CT-guided percutaneous biopsy can avoid worthless major operations. The role of surgery should be limited to neurological compression, severe mechanical instability and to salvage the failures of conservative treatment.     

Cardiovascular function and brain metabolites in normal weight and intrauterine growth restricted newborn piglets--effect of mild hypoxia

In order to clarify the influence of intrauterine growth restriction on systemic hemodynamics, catecholamine response, and regional distribution of brain energy metabolites per se and during mild hypoxic episodes a study was performed in thirty newborns with a well-characterized state of intrauterine and intra-natal development. Thirty animals were divided into fifteen normal weight piglets (NW) and fifteen intrauterine growth restricted (IUGR) piglets according to their birth weight. Category "NW" covered animals with a birth weight of > 40th percentile; IUGR category covered animals with a birth weight of > 5th and < 10th percentiles. Animals were anesthetized with halothane in 70% nitrous oxide and 30% oxygen and after immobilization artificially ventilated. The acid-base balance and blood gas values at baseline conditions were similar within the different groups investigated and consistent with other data obtained from anesthetized and artificially ventilated newborn piglets. Mild hypoxic hypoxia which was induced by lowering the FiO2 from 0.35 to 0.15 resulted in reduced arterial pO2 (NW: from 115 +/- 37 mmHg to 39 +/- 7 mmHg; IUGR: from 117 +/- 23 mmHg to 39 +/- 3 mmHg; p < 0.05), but arterial pH and pCO2 remained unchanged. Under baseline conditions arterial blood pressure, cardiac output, and myocardial contractility, expressed as dp/dt(max) and plasma catecholamine values were similar in all groups studied. Heart rate was slightly increased in IUGR (p < 0.05). Mild hypoxia led to a strong increase of myocardial contractility in NW as well as IUGR piglets to 2.4 and 2.7 fold and remained increased during recovery (p < 0.05). Moreover, total peripheral resistance was enhanced at the end of recovery period in IUGR animals (p < 0.05). There was a significant increase of epinephrine (E) in NW animals in comparison to sham-operated animals (p < 0.05). Interestingly, during reoxygenation the further increase in E and norepinephrine (NE) levels were enhanced in the animals which suffered from mild hypoxia (p < 0.05). Regional distribution of brain tissue metabolites was partly affected by intrauterine growth restriction. In particular, brain tissue glucose content was strongly reduced by 65 to 72 per cent in all brain regions investigated. Mild hypoxia led to an increase of about 30 percent in NW animals (p < 0.05). In IUGR piglets the percentage increase of brain glucose content was on an average more pronounced but with considerably higher variance. Also, a strong increase of brain lactate content appeared here (p < 0.05). In contrast, brain tissue ATP was quite similar in all groups studied, but brain creatine phosphate was significantly reduced in some forebrain structures of IUGR piglets after mild hypoxia (figure 2, p < 0.05). In summary, this investigation provides information on cardiovascular functions and brain metabolites of normal weight and naturally occurring growth restricted newborn piglets. Mild hypoxemia was well-tolerated from both animal groups. It is suggested that lactate may play a significant role as a source for brain energy production in the newborn IUGR piglets.     

Dietary factors influence the recovery rates of Helicobacter pylori in a BALB/cA mouse model

We have identified a number of type I and type II keratins in the zebrafish Danio rerio by two-dimensional polyacrylamide gel electrophoresis, complementary keratin blot-binding assay and immunoblotting. These keratins range from 56 kDa to 46 kDa in molecular mass and from pH 6.6 to pH 5.2 in isoelectric point. Type II zebrafish keratins exhibit significantly higher molecular masses (56-52 kDa) compared with the type I keratins (50-48 kDa), but the isoelectric points show no significant difference between the two keratin subclasses (type II: pH 6.0-5.5; type I: pH 6.1-5.2). According to their occurrence in various zebrafish tissues, the identified keratins can be classified into "E" (epidermal) and "S" (simple epithelial) proteins. A panel of monoclonal anti-keratin antibodies has been used for immunoblotting of zebrafish cytoskeletal preparations and immunofluorescence microscopy of frozen tissue sections. These antibodies have revealed differential cytoplasmic expression of keratins; this not only includes epithelia, but also a variety of mesenchymally derived cells and tissues. Thus, previously detected fundamental differences in keratin expression patterns between higher vertebrates and a salmonid, the rainbow trout Oncorhynchus mykiss, also apply between vertebrates and the zebrafish, a cyprinid. However, in spite of notable similarities, trout and zebrafish keratins differ from each other in many details. The present data provide a firm basis from which the application of keratins as cell differentiation markers in the well-established genetic model organism, the zebrafish, can be developed.     

Monitored high-dose azathioprine treatment reduces acute rejection episodes after renal transplantation

A novel complex mutation consisting of a small deletion/insertion (3958del5ins4) was found in the breast cancer-1 gene (BRCA-1) in three unrelated French breast and/or ovarian cancer families. These mutations occurred at the same nucleotide position of the 3' end of exon 11. The wild-type sequence, CTCAG, was deleted and replaced by AGGC in the three families. The consequence is the generation of a stop codon, TAG, resulting in a truncated protein. We propose two different mechanisms to explain the generation of this complex mutation: (i) the simultaneous occurrence of a deletion and an insertion in a stem-loop structure and (ii) the abortive integration of a human transposable element (Tigger 1) that deleted 5 nucleotides and inserted a 4-nucleotide "scar", corresponding to the 5' extremity of the transposon.     

Chloroquine treatment for uncomplicated childhood malaria in an area with drug resistance: early treatment failure aggravates anaemia

Using the polymerase chain reaction (PCR) and two primers for conserved regions of the small subunit ribosomal RNA (SSU-rRNA) of Microsporidia, a DNA segment about 1,195 base pairs long was amplified from a DNA template prepared from purified spores of the microsporidian species Pleistophora anguillarum. These spores had been isolated from adult eels (Anguilla japonica) with "Beko Disease." A comparison of sequence data from other microsporidian species showed P. anguillarum SSU-rRNA to be most similar to Vavraia oncoperae. When juvenile eels were artificially infected with P. anguillarum, enzyme-linked immunosorbent assay could detect a positive infection only 12 days post-infection. However, when suitable PCR primers were used, a DNA fragment of about 0.8 kb was detected from these juvenile eels after only 3 days post infection. No PCR product was obtained with templates prepared from clinically healthy control animals.     

Pulmonary infiltrates in neutropenic patients with acute leukemia during chemotherapy: outcome and prognostic factors

STUDY OBJECTIVE: To determine predictors of mortality from pulmonary infiltrates in neutropenic patients with acute leukemia during chemotherapy, and the significance of those factors related to the underlying malignancy and its therapy as well as of those related to the severity of the illness associated with pulmonary infiltrates. DESIGN: A historical cohort study. SETTING: A university teaching hospital and tertiary referral center. PATIENTS AND METHODS: Overall, 53 patients with neutropenia during chemotherapy and with first episodes of pulmonary infiltrates during a 4-year period were studied. Prognostic analysis included 38 variables. Multivariate analyses were performed by logistic regression. RESULTS: The survival rate from pneumonia was 57% (30/53). The following eight parameters were significantly associated with death in univariate analysis: comorbidity present; development of "late" pulmonary infiltrates (> or = 14 days after hospital admission); heart rate > or = 100 beats/min; a ratio heart rate/systolic blood pressure (HR/SBP) > or = 1.2; urea nitrogen > 7 mmol/L; radiographic score > or = 3; neutropenia < 1.0x10(9)/L at the treatment end point; and failed complete remission. In a multivariate model including only parameters available at diagnosis of pulmonary infiltrates, the presence of a ratio HR/SBP > or = 1.2 and of a radiographic score > or = 3 remained independently associated with death. In a second model also including the evolutionary parameter neutropenia < or = 1.0x10(9)/L at the treatment end point, both parameters remained significant together with neutropenia <1.0x 10(9)/L at the treatment end point. The presence of a ratio HR/SBP > or = 1.2 was a strong marker of early death. CONCLUSION: Both therapy- and malignancy-associated neutropenia as well as the severity of illness associated with pulmonary infiltrates are independent prognostic factors. Patients with a ratio HR/SBP > or = 1.2 at diagnosis of pulmonary infiltrates suffer from potentially reversible acute illness, are at risk for early death and, therefore, may be appropriate candidates for treatment in an ICU.     

Biosynthesis of progesterone derived neurosteroids by developing avian CNS: in vitro effects on the GABAA receptor complex

Although enthusiasm for measuring health-related quality of life (HRQL) in clinical trials exists, information is limited on the meaning of scores. We examined the relation between scores from the 34-item Medical Outcomes Study HIV Health Survey (MOS-HIV) and the more detailed HIV Overview of Problems-Evaluation System (HOPES) using the responses of 318 HIV-infected outpatients being treated in Los Angeles and Baltimore. With the HOPES problem statements as independent variables, statistically significant predictors of the variation in MOS-HIV scores for the Physical Function, Mental Health, and Energy/Fatigue scales were identified using stepwise regression. Approximately 60% to 70% of the variation in each of the scores was explained by five to seven different HOPES problem statements, with a single item explaining 47% to 59% of the variation. We created illustrative profiles for each of the three MOS-HIV scales using the HOPES items identified in the regressions. Independent of the scale, persons scoring in the top MOS-HIV quartile tended to report few if any problems, whereas a decline in score to the next quartile was characterized by functional difficulties (e.g., "HIV interferes with work"). The onset of specific problems might trigger further evaluation and potential intervention from health care providers to help maintain patient functioning.     

Genetic effects of 1,3-butadiene and associated risk for heritable damage

A summary of the results of the studies conducted in the EU Project "Multi-endpoint analysis of genetic damage induced by 1,3-butadiene and its major metabolites in somatic and germ cells of mice, rats and man" is presented. Results of the project are summarized on the detection of DNA and hemoglobin adducts, on the cytotoxic and clastogenic effects in somatic and germinal cells of mice and rats, on the induction of somatic mutations at the hprt locus of experimental rodents and occupationally exposed workers, on the induction of dominant lethal mutations in mice and rats, and on heritable translocations induced in mice, after exposure to butadiene (BD) or its major metabolites, butadiene monoepoxide (BMO), diepoxybutane (DEB) and butadiene diolepoxide (BDE). The primary goal of this project was to collect experimental data on the genetic effects of BD in order to estimate the germ cell genetic risk to humans of exposure to BD. To achieve this, the butadiene exposure are based on data for heritable translocations and bone marrow micronuclei induced in mice and chromosome aberrations observed in lymphocytes of exposed workers. A doubling dose for heritable translocations in human germ cells of 4900 ppm/h is estimated, which, assuming cumulative BD exposure over the sensitive period of spermatogenesis, corresponds to 5-6 weeks of continuous exposure at the workplace to 20-25 ppm. Alternatively, the rate of heritable translocation induction per ppm/h of BD exposure is estimated to be approximately 0.8 per million live born, compared to a spontaneous incidence of balanced translocations in humans of approximately 800 per million live born. These estimates have large confidence intervals and are only intended to indicate orders of magnitude of human genetic risk. These risk estimates are based on data from germ cells of BD-exposed male mice. The demonstration that clastogenic damage was induced by DEB in preovulatory oocytes at doses which were not ovotoxic implies that additional studies on the response of mammalian female germ cells to BD and its metabolites are needed. The basic assumption of the above genetic risk estimates is that experimental mouse data obtained after BD exposure can be extrapolated to humans. Several points exist in the present report and in the literature which contradict this assumption: (1) the level of BMO-hemoglobin adducts was significantly elevated in BD-exposed workers; however, it was considerably lower than would have been predicted from comparable rat and mouse exposures; (2) the concentrations of the metabolites DEB and BMO were significantly higher in mouse than in rat blood after BD exposure. Thus, while metabolism of BD is qualitatively similar in the two species, it is quantitatively different; (3) no increase of HPRT mutations was shown in 19 workers exposed on average to 1.8 ppm of BD, while in a different population of workers from a US plant exposed on average to 3.5 ppm of BD, a significant increase of HPRT variants was detected; and (4) data from cancer bioassays and cancer epidemiology suggest that rat is a more appropriate model than mouse for human cancer risk from BD exposure. However, the dominant lethal study in rats gave a negative result. At present, we do not know which BD metabolite(s) may be responsible for the genetic effects even though the bifunctional alkylating agent DEB is the most likely candidate for the induction of clastogenic events. Unfortunately, methods to measure DEB adducts in hemoglobin or DNA are only presently being developed. Despite these several uncertainties the use of the mouse genetic data is regarded as a justifiable and conservative approach to human genetic risk estimation given the considerable heterogeneity observed in the biotransformation of BD in humans.