Childhood absence epilepsy and febrile seizures: A family with a GABAA receptor mutation

Although several genes for idiopathic epilepsies from families with simple Mendelian inheritance have been found, genes for the common idiopathic generalized epilepsies, where inheritance is complex, presently are elusive. We studied a large family with epilepsy where the two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS), which offered a special opportunity to identify epilepsy genes. A total of 35 family members had seizures over four generations. The phenotypes comprised typical CAE (eight individuals); FS alone (15), febrile seizures plus (FS+) (three); myoclonic astatic epilepsy (two); generalized epilepsy with tonic-clonic seizures alone (one); partial epilepsy (one); and unclassified epilepsy despite evaluation (two). In three remaining individuals, no information was available. FS were inherited in an autosomal dominant fashion with 75% penetrance. The inheritance of CAE in this family was not simple Mendelian, but suggestive of complex inheritance with the involvement of at least two genes. A GABA(A) receptor gamma2 subunit gene mutation on chromosome 5 segregated with FS, FS+ and CAE, and also occurred in individuals with the other phenotypes. The clinical and molecular data suggest that the GABA(A) receptor subunit mutation alone can account for the FS phenotype. An interaction of this gene with another gene or genes is required for the CAE phenotype in this family. Linkage analysis for a putative second gene contributing to the CAE phenotype suggested possible loci on chromosomes 10, 13, 14 and 15. Examination of these loci in other absence pedigrees is warranted.

John Waldridge, The Leaven of the Ancients: Suhrawardi and the Heritage of the Greeks, SUNY Series in Islam (Albany: State University of New York Press, 1999). Pp. 323

In the Leaven of the Ancients, John Walbridge studies the appropriation of non–Peripatetic philosophical ideas by an anti–Aristotelian Islamic philosopher, Shihab al-Din al-Suhrawardi (d. 1191). He proposes a comprehensive explanation of the origin of Suhrawardi's philosophical system, a revival of the “wisdom of the Ancients” and its philosophical affiliations “grounded” in Greek philosophy (p. xiii). Walbridge attempts to uncover the reasons for Suhrawardi's rejection of the prevailing neo–Aristotelian synthesis in Islamic philosophy, Suhrawardi's knowledge and understanding of non–Aristotelian Greek philosophy, the ancient philosophers Suhrawardi was attempting to follow, the relationship between Suhrawardi's specific philosophical teachings (logic, ontology, physics, and metaphysics), and his understanding of non–Aristotelian ancient philosophy and the relationship between Suhrawardi's system and the major Greek philosophers, schools, and traditions—in particular the Presocratics, Plato, and the Stoics (p. 8). Copyright © 2003 Cambridge University Press

Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation

We have identified truncating mutations in the human DLG3 ( neuroendocrine dlg) gene in 4 of 329 families with moderate to severe X-linked mental retardation. DLG3 encodes synapse-associated protein 102 (SAP102), a member of the membrane-associated guanylate kinase protein family. Neuronal SAP102 is expressed during early brain development and is localized to the postsynaptic density of excitatory synapses. It is composed of three amino-terminal PDZ domains, an src homology domain, and a carboxyl-terminal guanylate kinase domain. The PDZ domains interact directly with the NR2 subunits of the NMDA glutamate receptor and with other proteins responsible for NMDA receptor localization, immobilization, and signaling. The mutations identified in this study all introduce premature stop codons within or before the third PDZ domain, and it is likely that this impairs the ability of SAP102 to interact with the NMDA receptor and/or other proteins involved in downstream NMDA receptor signaling pathways. NMDA receptors have been implicated in the induction of certain forms of synaptic plasticity, such as long-term potentiation and long-term depression, and these changes in synaptic efficacy have been proposed as neural mechanisms underlying memory and learning. The disruption of NMDA receptor targeting or signaling, as a result of the loss of SAP102, may lead to altered synaptic plasticity and may explain the intellectual impairment observed in individuals with DLG3 mutations.

Assessing cost-effectiveness in mental health: family interventions for schizophrenia and related conditions

Objective: Existing evidence suggests that family interventions can be effective in reducing relapse rates in schizophrenia and related conditions. Despite this, such interventions are not routinely delivered in Australian mental health services. The objective of the current study is to investigate the incremental cost-effectiveness ratios (ICERs) of introducing three types of family interventions, namely: behavioural family management (BFM); behavioural intervention for families (BIF); and multiple family groups (MFG) into current mental health services in Australia. Method: The ICER of each of the family interventions is assessed from a health sector perspective, including the government, persons with schizophrenia and their families/carers using a standardized methodology. A two-stage approach is taken to the assessment of benefit. The first stage involves a quantitative analysis based on disability-adjusted life years (DALYs) averted. The second stage involves application of 'second filter' criteria (including equity, strength of evidence, feasibility and acceptability to stakeholders) to results. The robustness of results is tested using multivariate probabilistic sensitivity analysis. Results: The most cost-effective intervention, in order of magnitude, is BIF (A$8000 per DALY averted), followed by MFG (A$21 000 per DALY averted) and lastly BFM (A$28 000 per DALY averted). The inclusion of time costs makes BFM more cost-effective than MFG. Variation of discount rate has no effect on conclusions. Conclusions: All three interventions are considered 'value-for-money' within an Australian context. This conclusion needs to be tempered against the methodological challenge of converting clinical outcomes into a generic economic outcome measure (DALY). Issues surrounding the feasibility of routinely implementing such interventions need to be addressed.

A family of perfect hashing methods

Minimal perfect hash functions are used for memory efficient storage and fast retrieval of items from static sets. We present an infinite family of efficient and practical algorithms for generating order preserving minimal perfect hash functions. We show that almost all members of the family construct space and time optimal order preserving minimal perfect hash functions, and we identify the one with minimum constants. Members of the family generate a hash function in two steps. First a special kind of function into an r-graph is computed probabilistically. Then this function is refined deterministically to a minimal perfect hash function. We give strong theoretical evidence that the first step uses linear random time. The second step runs in linear deterministic time. The family not only has theoretical importance, but also offers the fastest known method for generating perfect hash functions.

Family advocacy roles and highly dependent residents in nursing homes

A developing critique has questioned the practical utility of user rights policy initiatives for highly dependent residents of nursing homes. This paper seeks to extend this critique to the advocacy roles that families have been accorded within the policy initiatives, The discussion is based on a qualitative research study of family participation in six aged care units, The paper argues that the capacity of families to act as advocates for highly dependent nursing home residents is is limited by the their weak position within the organisations and the complexity of their relations with staff It questions both the applicability and the appropriateness of rights models which do not take sufficient account of the structure and meaning of care.

Cell-wall polysaccharides from Australian red algae of the family Solieriaceae (Gigartinales, Rhodophyta): Novel, highly pyruvated carrageenans from the genus Callophycus

Cell-wall polysaccharides from six species of red algae of the genus Callophycus were mainly galactans comprised predominantly of galactose (Gal) and 3,6-anhydrogalactose (AnGal), and were rich in pyruvate and sulfate. The Fourier Transform Infrared (FTIR) spectra of the polysaccharides superficially resembled that of alpha-carrageenan (composed of the repeating disaccharide carrabiose 2-sulfate), with major bands of absorption indicative of if-linked AnGal, axial 2-sulfate on 4-linked AnGal, and unsulfated, 3-linked Gal. The FTIR spectra of solutions of Callophycus polysaccharides in D2O-phosphate buffer displayed absorption, corresponding to the carboxylate anion of the pyruvate acetal substituent. Methylation analysis showed that 3,4,6-linked Galp (interpreted as 4,6-pyruvated, 3-linked Galp) and 2,4-linked AnGalp (interpreted as 4-linked AnGalp 2-sulfate) were the dominant links, together with significant quantities of 3-linked Galp. Proton-decoupled C-13 nuclear magnetic resonance (NMR) spectroscopy showed the polysaccharides to be composed predominantly of pyruvated carrageenans. The C-13 NMR spectra were completely assigned by a J-modulated spin-echo pulse sequence and 2D experiments employing gradient Heteronuclear Multiple Bond Correlation (HMBC), C-13/H-1 Heteronuclear Multiple Quantum Coherence (HMQC), and HMQC Total Correlation Spectroscopy (HMQC-TOCSY). The Callophycus galactans thus consist predominantly of the novel repeating disaccharide 4',6'-O-(1-carboxyethylidene)carrabiose 2-sulfate and minor amounts of the alpha-carrageenan repeating unit (carrabiose 2-sulfate), and other structural variations. (C) 1997 Elsevier Science Ltd.