Characterization of silicon pore optics for the NewAthena X-ray observatory in the PTB laboratory at BESSY II.

The New Advanced Telescope for High ENergy Astrophysics (NewAthena) will be the largest space-based X-ray observatory ever built. It will have an effective area above 1.1 m2 at 1 keV, which corresponds to a polished mirror surface of about 300 m2 due to the grazing incidence. As such a mirror area is not achievable with an acceptable mass even with nested shells, silicon pore optics (SPO) technology will be utilized. In the PTB laboratory at BESSY II, two dedicated beamlines are in use for their characterization with monochromatic radiation at 1 keV and a low divergence well below 2 arcsec: the X-ray Pencil Beam Facility (XPBF 1) and the X-ray Parallel Beam Facility (XPBF 2.0), where beam sizes up to 8 mm × 8 mm are available while maintaining low beam divergence. This beamline is used for characterizing mirror stacks and controlling the focusing properties of mirror modules (MMs) - consisting of four mirror stacks - during their assembly at the beamline. A movable CCD based camera system 12 m from the MM registers the direct and the reflected beams. The positioning of the detector is verified by a laser tracker. The energy-dependent reflectance in double reflection through the pores of an MM with an Ir coating was measured at the PTB four-crystal monochromator beamline in the photon energy range 1.75 keV to 10 keV, revealing the effects of the Ir M edges. The measured reflectance properties are in agreement with the design values to achieve the envisaged effective area.

Cytotoxic and apoptotic effects of recombinant subtilase cytotoxin variants of shiga toxin-producing Escherichia coli.

In this study, the cytotoxicity of the recently described subtilase variant SubAB2-2 of Shiga toxin-producing Escherichia coli was determined and compared to the plasmid-encoded SubAB1 and the chromosome-encoded SubAB2-1 variant. The genes for the respective enzymatic active (A) subunits and binding (B) subunits of the subtilase toxins were amplified and cloned. The recombinant toxin subunits were expressed and purified. Their cytotoxicity on Vero cells was measured for the single A and B subunits, as well as for mixtures of both, to analyze whether hybrids with toxic activity can be identified. The results demonstrated that all three SubAB variants are toxic for Vero cells. However, the values for the 50% cytotoxic dose (CD50) differ for the individual variants. Highest cytotoxicity was shown for SubAB1. Moreover, hybrids of subunits from different subtilase toxins can be obtained which cause substantial cytotoxicity to Vero cells after mixing the A and B subunits prior to application to the cells, which is characteristic for binary toxins. Furthermore, higher concentrations of the enzymatic subunit SubA1 exhibited cytotoxic effects in the absence of the respective B1 subunit. A more detailed investigation in the human HeLa cell line revealed that SubA1 alone induced apoptosis, while the B1 subunit alone did not induce cell death.

Deinococcus as new chassis for industrial biotechnology: biology, physiology and tools.

Deinococcus spp are among the most radiation-resistant micro-organisms that have been discovered. They show remarkable resistance to a range of damage caused by ionizing radiation, desiccation, UV radiation and oxidizing agents. Traditionally, Escherichia coli and Saccharomyces cerevisiae have been the two platforms of choice for engineering micro-organisms for biotechnological applications, because they are well understood and easy to work with. However, in recent years, researchers have begun using Deinococcus spp in biotechnologies and bioremediation due to their specific ability to grow and express novel engineered functions. More recently, the sequencing of several Deinococcus spp and comparative genomic analysis have provided new insight into the potential of this genus. Features such as the accumulation of genes encoding cell cleaning systems that eliminate organic and inorganic cell toxic components are widespread among Deinococcus spp. Other features such as the ability to degrade and metabolize sugars and polymeric sugars make Deinococcus spp. an attractive alternative for use in industrial biotechnology.

Characterizing Deficit Accumulation Among Gulf War Era Veterans.

BACKGROUND: Veterans of the first Gulf War (1990-1991) are reaching middle and older adulthood in differing degrees of health and biological age. Many Gulf War veterans report myriad negative symptoms classified as Gulf War illness (GWI), a chronic multi-symptom illness. OBJECTIVES: To describe and analyze deficit accumulation, among veterans with Severe GWI (SGWI+) and those without Severe GWI (SGWI-), to assess the association between a medically unexplained illness and aging. DESIGN: This study uses a retrospective cohort design with quasi-longitudinal data. SETTING: The recruitment sample included 10,042 Gulf War era veterans across all four US Census regions. PARTICIPANTS: The analytic sample included 1,054 participants of the GWECB for whom SGWI case status could be determined and who had valid responses for at least 90% of the deficits included in the deficit accumulation index. MEASUREMENTS: Chronic health conditions were retroactively reported, including year of diagnosis, enabling us to create a longitudinal measure of deficit accumulation. This deficit accumulation index (DAI) ranged from 0-1 for each respondent in each year between 1991-2013. We compare veterans with SGWI+ to those with SGWI- using the CDC case definition. RESULTS: Most veterans in our sample could expect to spend more years with moderate or substantial deficits than without deficits. SGWI+ was associated with spending more years with substantial deficits than those with SGWI-. Veterans in middle age (age 35-65) experienced more years with substantial deficits than younger veterans. Individuals with SGWI+ had 13 times the hazard of accumulating substantial deficits than those without. CONCLUSIONS: This study demonstrated that veterans with SGWI+, even those in midlife, experienced aging as measured by accumulating deficits. Practitioners should consider patients with multi-symptom illnesses as at risk of accelerated aging, tailoring treatments to address patients' holistic needs.

Self-reported gastrointestinal disorders among veterans with gulf war illness with and without posttraumatic stress disorder.

BACKGROUND: Gulf War Illness (GWI) is a chronic, multi-symptom disorder affecting 25%-32% of Gulf War veterans. Veterans with GWI disproportionately suffer from gastrointestinal (GI) disorders. Given the increasing evidence supporting a gut-brain axis, we explore the relationship between post-traumatic stress disorder (PTSD), GWI, and self-reported GI disorders among GW veterans. METHODS: Veterans from the Gulf War Era Cohort and Biorepository responded to a mail-based survey (N = 1058). They were stratified by GWI (Centers for Disease Control definition) and PTSD status. This yielded three groups: GWI-, GWI+/PTSD-, and GWI+/PTSD+. Multivariable logistic regression adjusting for demographic and military characteristics examined associations between GWI/PTSD groups and GI disorders. Results were expressed as adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). KEY RESULTS: The most frequently reported GI disorders were irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and colon polyps (CP). The GWI+/PTSD+ group had a higher odds of these disorders than the GWI+/PTSD- group (aORIBS  = 3.12, 95% CI: 1.93-5.05; aORGERD  = 2.04, 95% CI: 1.44-2.90; aORCP  = 1.85, 95% CI: 1.23-2.80), which had a higher odds of these disorders than the GWI- group (aORIBS  = 4.38, 95% CI: 1.55-12.36; aORGERD  = 2.51 95% CI: 1.63-3.87; aORCP  = 2.57, 95% CI: 1.53-4.32). CONCLUSIONS & INFERENCES: GW veterans with GWI and PTSD have significantly higher odds of specific self-reported GI disorders than the other groups. Given the known bidirectional influences of the gut and brain, these veterans may benefit from a holistic healthcare approach that considers biopsychosocial contributors to the assessment and management of disease.

Different mutations in the oafA gene lead to loss of O5-antigen expression in Salmonella enterica serovar Typhimurium.

AIMS: To analyse genetic changes in the oafA gene explaining the loss of O5-antigen expression in Salmonella Typhimurium and Salm. 4,[5],12:i:-. METHODS AND RESULTS: The oafA gene in 52 O5-antigen-negative and 77 O5-antigen-positive Salm. Typhimurium (N = 47) and Salm. 4,[5],12:i:- (monophasic Salm. Typhimurium strains, N = 82) was investigated by a combination of PCR screening and DNA sequencing to identify mutations leading to the suppression of the O5-antigen. Various DNA sequence changes within the open reading frame (ORF) of oafA in O5-antigen-negative strains could be identified. In 77% of the O5-antigen-negative strains, a 7-bp deletion of a duplicated sequence within the functional oafA gene led to a frameshift in the ORF. In four strains, an IS4 element and in two, an IS1 element was inserted at different positions. Four other strains carried at different positions single base pair substitutions causing a premature stop codon. Finally, in two strains, a deletion of the oafA 3'end of undetermined size was responsible for the lack of O5-antigen expression. In none of the strains investigated, the complete ORF of oafA was deleted. Primers were designed and used to detect the most prominent variants. CONCLUSIONS: O5-antigen-negative Salm. Typhimurium and Salm. 4,[5],12:i:- strains carry an oafA pseudogene caused by different genetic events indicating that there is a selection for oafA mutations leading to the loss of O5-antigen expression. SIGNIFICANCE AND IMPACT OF THE STUDY: The loss of O5-antigen expression may be an example of a common evolutionary mechanism to escape host defence or to adapt to environmental changes. The data are the basis for the development of diagnostic PCR assays for the differentiation of O5-antigen-positive and O5-antigen-negative Salm. Typhimurium and its monophasic (Salm. 4,[5],12:i-) strains.

A large sample of finnish diabetic sib-pairs reveals no evidence for a non-insulin-dependent diabetes mellitus susceptibility locus at 2qter.

In the first reported positive result from a genome scan for non-insulin-dependent diabetes mellitus (NIDDM), Hanis et al. found significant evidence of linkage for NIDDM on chromosome 2q37 and named the putative disease locus NIDDM1 (Hanis et al. 1996. Nat. Genet. 13:161-166). Their total sample was comprised of 440 Mexican-American affected sib-pairs from 246 sibships. The strongest evidence for linkage was at marker D2S125 and best estimates of lambdas (risk to siblings of probands/population prevalence) using this marker were 1.37 under an additive model and 1.36 under a multiplicative model. We examined this chromosomal region using linkage analysis in a Finnish sample comprised of 709 affected sib-pairs from 472 sibships. We excluded this region in our sample (multipoint logarithm of odds score /= 1.37. We discuss possible reasons why linkage to 2q37 was not found and conclude that this region is unlikely to be playing a major role in NIDDM susceptibility in the Finnish Caucasian population.

Potential for expanded power in linkage studies using the ALLEGRO and MERLIN software programs.

Multipoint linkage analysis in complex diseases requires the use of fast algorithms that can handle many markers and a large number of moderately sized pedigrees with unknown mode of inheritance. This need has led to the development of several competitive software programs. We recently completed a genomic screen of neural tube defects using GENEHUNTER-PLUS and the more recent ALLEGRO. The ALLEGRO software was found to offer expanded power for linkage studies, particularly for childhood onset diseases like neural tube defects, though the results must be treated with caution.

Glycation of albumin, not glomerular basement membrane, alters permeability in an in vitro model.

The effects of glycation of either albumin, a plasma protein, or GBM were examined in an in vitro model of GBM permeability. Albumin was incubated with glucose in vitro, and nonglycated and glycated albumin were separated by affinity chromatography. Rat GBM was glycated either in vivo after the induction of diabetes or in vitro after incubation with 25 mM glucose. 150 micrograms of GBM was consolidated in an ultrafiltration cell, and albumin permeability across the GBM filter was assessed at an applied pressure (50 mmHg) selected to approximate glomerular capillary pressure in vivo. The sieving coefficient of glycated albumin was greater than the sieving coefficient of nonglycated albumin (0.25 +/- 0.03 vs. 0.10 +/- 0.02; P < 0.05). GBM glycated in vivo in diabetic rats exhibited native albumin and water permeability that was indistinguishable from that for GBM from control rats. Similarly, GBM glycated in vitro by incubation with 25 mM glucose exhibited water and albumin permeability identical to that for GBM incubated in buffer. Thus, the glycation of albumin, but not of GBM, leads to enhanced permeability in an in vitro GBM filtration system. Increased permeability of glycated albumin may contribute to albuminuria and/or renal injury in states of increased circulating glycated albumin such as diabetes and experimental galactosemia.

Brainstem auditory evoked potentials and visually evoked potentials in young patients with IDDM.

OBJECTIVE: To investigate whether young IDDM patients develop central nervous dysfunction and to establish a possible relationship with various disease parameters. RESEARCH DESIGN AND METHODS: Thirty-two patients, aged 13.5 +/- 2 years, with disease duration of 6 +/- 2.6 years and age of onset of 7.7 +/- 3.2 years (group 1), and 21 patients with short-term disease, age 9.7 +/- 3.5 years, duration of disease < 2 years and age of onset of 9.4 +/- 3.3 years (group 2) were compared with age- and sex-matched control subjects. Exclusion criteria were clinical signs of neuropathy, retinopathy, nephropathy, or hearing impairment. Neurophysiological studies included auditory and visually evoked potentials (EPs). RESULTS: Patients in group 1 revealed increased P100 latencies of visually EPs (103.4 +/- 4.5 vs. 96.8 +/- 3.7 ms) and interpeak latencies I-V of auditory EPs (4.16 +/- 0.10 vs. 3.99 +/- 0.09 ms) and had abnormal latencies (values outside 2.5 SD) in 37%. However, short-term patients (group 2) had results within normal limits compared with control subjects. In group 1, longer disease duration and younger age at onset correlated with an increase of P100 latency (P < 0.001) and IPL I-V (P < 0.001). Patients with a history of severe hypoglycemic episodes had increased latencies compared with patients without hypoglycemia (P < 0.05). Furthermore, metabolic control during the last 2 years was related to P100 latencies (P < 0.05). CONCLUSIONS: EPs noninvasively detect subclinical central nervous system involvement in children and adolescents with IDDM. Most important risk factors are duration of disease and frequency of severe hypoglycemia.

Mapping genes for NIDDM. Design of the Finland-United States Investigation of NIDDM Genetics (FUSION) Study.

OBJECTIVE: To map and identify susceptibility genes for NIDDM and for the intermediate quantitative traits associated with NIDDM. RESEARCH DESIGN AND METHODS: We describe the methodology and sample of the Finland-United States Investigation of NIDDM Genetics (FUSION) study. The whole genome search approach is being applied in studies of several different ethnic groups to locate susceptibility genes for NIDDM. Detailed description of the study materials and designs of such studies are important, particularly when comparing the findings in these studies and when combining different data sets. RESULTS: Using a careful selection strategy, we have ascertained 495 families with confirmed NIDDM in at least two siblings and no history of IDDM among the first-degree relatives. These families were chosen from more than 22,000 NIDDM patients, representative of patients with NIDDM in the Finnish population. In a subset of families, a spouse and offspring were sampled, and they participated in a frequently sampled intravenous glucose tolerance test (FSIGT) analyzed with the Minimal Model. An FSIGT was completed successfully for at least two nondiabetic offspring in 156 families with a confirmed nondiabetic spouse and no history of IDDM in first-degree relatives. CONCLUSIONS: Our work demonstrates the feasibility of collecting a large number of affected sib-pair families with NIDDM to provide data that will enable a whole genome search approach, including linkage analysis.

Genetic analysis of eight breast-ovarian cancer families with suspected BRCA1 mutations.

BRCA1 is a breast cancer-related tumor suppressor gene located on human chromosome 17q21. Inherited mutations in BRCA1 are thought to be responsible for approximately half of all inherited breast cancer and to confer increased risk for ovarian, colon, or prostate cancer. Studies of affected families and population-based studies have provided some information on the prevalence of BRCA1 mutations in Caucasian U.S. and European populations as well as on the penetrance of these mutations. We review the available data on the epidemiology of breast cancer with specific reference to BRCA1. In addition, we describe the genetic analysis of one large family with multiple affected individuals now known to harbor a BRCA1 germline mutation but initially identified by genetic linkage analysis. This family is presented as a model of the challenges that can be encountered in genetic analysis of familial forms of cancer. To this end, we compare the outcome of analysis before and after the identification of a mutation that predisposes family members to early-onset breast and ovarian cancers. We describe seven additional families with evidence of linkage between breast cancer and genetic markers in the BRCA1 region. Each of these families generated a 2-point LOD (i.e., logarithm of the odds) score greater than 1.18 for at least one polymorphic marker flanking BRCA1. These families have formed the basis of our efforts to characterize BRCA1 mutations. First-pass mutation analysis using the single-strand conformation polymorphism approach failed to identify any mutations in the seven families. We consider the possible reasons for the apparent low mutation-detection efficiency.

Synthesis of crossed [2 + 2] photocycloadducts: a novel approach to the synthesis of bridged bicyclic alkenes.

[reaction: see text] A solution to the synthesis of "crossed" intramolecular [2 + 2] photocycloadducts has been achieved. Through the use of a temporary heteroatom linker, the equivalent of a crossed photocycloadduct can be accessed at the expensive of the normal "straight" adduct. Selectivity as high as 94:6 for the "crossed" adduct has been observed.

Auditory evoked potentials in young patients with Down syndrome. Event-related potentials (P3) and histaminergic system.

Subjects with Down syndrome exhibit various types of cognitive impairment. Besides abnormalities in a number of neurotransmitter systems (e.g. cholinergic), histaminergic deficits have recently been identified. Brainstem auditory evoked potentials (BAEPs) and auditory event-related potentials (ERPs), were recorded from 10 children (aged 11-20 years) with Down syndrome and from 10 age- and sex-matched healthy control subjects. In Down subjects, BAEPs revealed shortened latencies for peaks III and V with shortened interpeak latencies I-III and I-V. ERPs showed a delay of components N1, P2, N2 and P3. In addition, subjects with Down syndrome failed to show P3 amplitude reduction during repeated stimulation. To evaluate the cognitive effects of histaminergic dysfunction, ERPs were recorded from 12 healthy adults (aged 20-28 years) before and after antihistaminergic intervention (pheniramine) compared to placebo. Whereas components N1, P2, N2 remained unchanged after H1-receptor antagonism, P3 latency increased and P3 amplitude showed no habituation in response to repeated stimulation. The results suggest that the characteristic neurofunctional abnormalities present in children with Down syndrome must be the consequence of a combination of structural and neurochemical aberrations. The second finding was that antihistaminergic treatment affects information processing tested by ERPs similar to that seen with anticholinergic treatment.

Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats.

We have previously demonstrated that susceptibility of Lewis (LEW/N) rats to inflammatory disease, compared to relatively resistant Fischer (F344/N) rats, is related to deficient glucocorticoid counter-regulation of the immune response resulting from deficient corticotropin-releasing hormone (CRH) responsiveness to inflammatory and other stress mediators. The GABA/benzodiazepine receptor complex is an important negative modulator of CRH secretion and responsiveness to excitatory stimuli. In this study, we have examined in vitro binding of [3H]flunitrazepam to hypothalamic membrane preparations from LEW/N and F344/N rats. LEW/N rats had significantly more hypothalamic benzodiazepine binding sites (Bmax) than F344/N rats, but there were no differences in benzodiazepine binding affinities (Kd) between these two strains. The differences in benzodiazepine receptor number were consistent with the respective plasma corticosterone levels in the two strains, and with previous work indicating a negative correlation between corticosterone levels and benzodiazepine binding site number. Adrenalectomy of F344/N rats increased benzodiazepine binding to levels comparable to LEW/N animals and treatment of adrenalectomized F344/N rats with DEX resulted in lowering of benzodiazepine Bmax to levels that did not differ significantly from those of intact F344/N rats. There was no significant change in receptor number in either adrenalectomized or DEX-treated LEW/N rats. These findings suggest that basal benzodiazepine receptor differences between these strains may be partially related to strain differences in corticosterone levels, however that additional factors may contribute to maintenance of these differences in LEW/N rats. Since benzodiazepines attenuate hypothalamic CRH secretion through GABAergic inhibition, we suggest that strain differences in receptor number could also augment strain differences in hypothalamic-pituitary-adrenal axis function through differential sensitivity to GABA-mediated feedback.

Spectrum of cognitive, behavioural and emotional problems in children and young adults with Down syndrome.

In comparison to most other groups with intellectual disability individuals with Down syndrome are at lower risk for significant psychopathology, although relative to their typically developing peers they have higher rates of behavioural and emotional problems. A total of 43 Down syndrome patients (21 females and 22 males), who ranged in age from 5.33 to 30.58 years, were examined for the presence of age-related changes in the spectrum of externalizing and internalizing problems. Intelligence tests included Hamburg-Wechsler-Intelligenz Test für Kinder III (HAWIK-III), Hamburg-Wechsler-Intelligenz Test für Erwachsene (HAWIE-R) and Kaufman-Assessment-Battery for Children, German Version (K-ABC). Behavioural and emotional problems were assessed by the the Strengths and Difficulties Questionnaire for Parents, German Version (SDQ) and the Clinical Assessment Scale for Child and Adolescent Psychopathology (CASCAP). IQ was significantly inversly related to the age of patients. Externalizing behaviours (dominant, opposing/refusing, impulsiveness, inattention and increased motor activity) were significantly higher in the 5-10 years old group, whereas internalizing behaviours (shy/insecure, low self confidence, decreased motor activity) where more prevalent in adolescents and adults (10-30 years). Possible relationships between this age-related changes and increased risks of later-onset psychopathology (depression and dementia) are discussed.

Overexpression of DNAse I in brain of patients with Down syndrome.

Human DNAse I (EC 3.1.21.1) is an enzyme most probably involved in apoptotic processes. Splicing of the DNAse I primary transcript in normal and apoptotic cells into up to 20 splicing forms and the recent description of a different family of caspase-activated DNAses, hampered studies on the role of DNAse I in apoptosis research. Performing gene hunting in fetal brain of patients with DS we found a sequence with 100% homology to DNAse I and this formed the Rationale for studies in adult DS brain. It was therefore the aim of the study to evaluate DNAse I-mRNA steady state levels in DS brain using adult brain without brain pathologies and Alzheimer's Disease (AD) brain as control, in order to rule out that DNAse I--overexpression may not be specific for DS but rather reflecting apoptosis per se, a hallmark of both disorders. Determination of DNAse I-mRNA steady state levels was carried out by a blotting method in frontal, parietal, temporal occipital lobe and cerebellum. We found significantly increased DNAse I transcripts in brain of DS and AD both, when normalized versus the house-keeping gene beta actin or total RNA. We demonstrate the significant increase of DNAse I--transcript in the pathogenesis of DS and AD suggesting a role for this enzyme in the apoptotic process known to occur in both disorders. We are now going to carry out protein and enzyme activity levels in our laboratory to confirm our findings at the transcriptional level.

Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice.

It is commonly accepted, that regenerative capacity of striated muscle is confined to skeletal muscle by activation of satellite cells that normally reside quiescent between the plasmalemma and the basement membrane of muscle fibers. Muscular dystrophies are characterized by repetitive cycles of de- and regeneration of skeletal muscle fibers and by the frequent involvement of the cardiac muscle. Since during the longstanding course of muscular dystrophies there is a permanent demand of myogenic progenitors we hypothesized that this may necessitate a recruitment of additional myogenic precursors from an undifferentiated, permanently renewed cell pool, such as bone marrow (BM) cells. To this end normal and dystrophic (mdx) female mice received bone marrow transplantation (BMT) from normal congenic male donor mice. After 70 days, histological sections of skeletal and cardiac muscle from BMT mice were probed for the donor-derived Y chromosomes. In normal BMT recipients, no Y chromosome-containing myonuclei were detected, either in skeletal or in cardiac muscle. However, in all samples from dystrophic mdx skeletal muscles Y chromosome-specific signals were detected within muscle fiber nuclei, which additionally were found to express the myoregulatory proteins myogenin and myf-5. Moreover, in the hearts of BMT-mdx mice single cardiomyocytes with donor derived nuclei were identified, indicating, that even cardiac muscle cells are able to regenerate by recruitment of circulating BM-derived progenitors. Our findings suggest that further characterization and identification of the BM cells capable of undergoing myogenic differentiation may have an outstanding impact on therapeutic strategies for diseases of skeletal and cardiac muscle.

Prognosis of childhood epilepsy in newly referred patients.

The aim of this study was to investigate the prognosis of childhood epilepsy and to analyze prognostic factors in addition to remission rate in a follow-up of newly referred patients. Two hundred eighty-one patients were followed for a mean period of 5.3 years. Overall, 253 patients (90%) achieved 1-year remission. The beginning of a 1-year seizure-free period was achieved in 77.9% by 1 year, in 84% by 2 years and in 88.6% by 3 years after onset of treatment. Early onset of seizures, symptomatic etiology, and neurologic handicap predicted a worse prognosis. In 44 of 253 children with complete suppression of seizures for 1 year, relapses occurred within the follow-up period. In one child with a relapse, remission could not be achieved in the 2nd year thereafter. In conclusion, our study shows a good prognosis for most children with epilepsy, especially in patients with idiopathic epilepsy and late onset of seizures and without neurologic dysfunction. Moreover, our data strongly suggest that the long-term pattern of seizure control is largely established during the first 2 years of treatment.

Familial idiopathic West syndrome.

Two families, each with occurrence of West syndrome in two siblings, are presented. Monozygotic twins in family 1 developed infantile spasms at the age of 4 months. Two female siblings in family 2 started to have seizures at the age of 6 months, but 2 years apart. The family history; development prior to West syndrome; clinical, electroencephalographic, and neuroradiologic findings; diagnostic work-up; and treatment are described. The outcome in family 1 (follow-up after 2 years) showed no conspicuous findings on physical and neurologic examination, and psychomotor development appropriate to cognitive, motor, and language developmental age in both twins. In family 2 (follow-up after 3 and 5 years), the older sister only was one standard deviation below mean in intellectual developmental age. Simultaneous occurrence of infantile spasms in both siblings from these two families but with variable clinical expression suggests there is a genetic susceptibility and variable phenotypic expression. Long-term follow-up will demonstrate whether these cases may be classified as "familial idiopathic West syndrome."