Infant hearing screening with an automated auditory brainstem response screener and the auditory brainstem response

From 1653 babies hospitalized in the Veterans General Hospital—Taipei from 1993 to 1995, 260 infants at risk of hearing impairment were selected. The risk criteria of hearing impairment for neonates were based on the recommendation of the US Joint Committee on Infant Hearing, 1990 Position Statement. All these infants were screened with the Algo-1 Plus, an automated auditory brainstem response (ABR) screener at a mean postconceptional age of 40.7 ± 4.5 weeks. Thirty-nine cases (39/260, 15%) involving 57 ears (57/520, 11%), failed the screening. Except for one infant who died, the babies had an ABR test for both air- and bone-conducted stimuli and an otological examination. The case-specific incidence of conductive hearing deficit at the initial ABR test was 5.4%. The prevalence of sensorineural hearing deficits was between 2.3% confirmed and 3.1% including infants who did not have follow-up tests. The n-value that indicated agreement between the Algo-1 and ABR results was 0.64, and the overall efficiency of using Algo-1 to correctly identify pass or failure of the ABR was 83%.     

The Efficacy of Lamotrigine in Children and Adolescents with Refractory Generalized Epilepsy: A Randomized, Double-Blind, Crossover Study

Summary: Purpose: We report a double-blind, placebo-controlled crossover study of lamotrigine (LTG) as add-on treatment in therapy-resistant, generalized epilepsy in children and adolescents (n = 30).
Methods: Twenty patients had Lennox-Gastaut syndrome. Each patient acted as his or her own control. LTG and placebo were randomly added to existing antiepileptic medication (AEDs). The LTG dosage was individualized in an open phase preceding the placebo/treatment phase. Patients who responded to LTG in the open phase went on to the double-blind phase. "Responders" were defined as patients with a >50% seizure reduction or less severe seizures or both, or improved behavior or improved motor skills or both. "Nonresponders" were defined as children who showed no positive effects of LTG with plasma levels of 10 μg/ml or children who had adverse events during the open phase.
Results: There was a clear statistically significant reduction of seizure frequency in LTG compared with placebo treatment. None of the children studied showed abnormal biochemical or hematologic findings, or changes in plasma levels of concomitantly administered AEDs.
Conclusions: LTG is a well-tolerated and effective treatment in children with intractable generalized epilepsies, including those with Lennox-Gastaut syndrome. The study design allowed a double-blind placebo-controlled assessment of LTG although the participating children used 19 different AED combinations at entry.     

Evaluation of the safety and bioactivity of purified and semi-purified glucoraphanin.

The anti-carcinogenic effects of broccoli have been attributed to sulforaphane, the hydrolysis product of glucoraphanin (GRP). Here we determined if purified GRP, in the absence of the plant-derived hydrolyzing enzyme myrosinase, could affect pulmonary and hepatic ethoxyresorufin O-deethylase (EROD) and/or NAD(P)H-quinone oxidoreductase 1 (NQO1) activity. Male F344 rats were administered semi-synthetic, semi-purified or purified GRP (240 mg/kg: 550 micromol/kg rat daily for 4 days) by gavage. Hepatic and pulmonary NQO1 activity increased ( approximately 20%), but not EROD. Varying doses of semi-purified GRP (30, 60, or 120 mg/kg rat daily for 4 days) again caused no change in EROD activity, although a dose-dependent increase in NQO1 was seen. Urinary excretion of mercapturic acids showed no difference between preparations, and recovery increased with decreasing dose. Histopathologic examination revealed no abnormal tissues other than cecum, where inflammation was dose dependent; mild at 120 mg/kg and severe at 240 mg/kg, a greatly supra-physiological dose. We conclude that GRP 30-60 mg/kg p.o. is safe and effectively enhances NQO1 in all tissues evaluated.     

Ten candidate ADAMTS13 mutations in six French families with congenital thrombotic thrombocytopenic purpura (Upshaw–Schulman syndrome)

Summary.  ADAMTS13, the specific von Willebrand factor (VWF)-cleaving metalloprotease, prevents the spontaneous formation of platelet thrombi in the microcirculation by degrading the highly adhesive ultralarge VWF multimers into smaller forms. ADAMTS13 severe enzymatic deficiency and mutations have been described in the congenital thrombotic thrombocytopenic purpura (TTP or Upshaw–Schulman syndrome), a rare and severe disease related to multivisceral microvascular thrombosis. We investigated six French families with congenital TTP for ADAMTS13 enzymatic activity and gene mutations. Six probands with congenital TTP and their family were tested for ADAMTS13 activity in plasma using a two-site immunoradiometric assay and for ADAMTS13 gene mutations using polymerase chain reaction and sequencing. ADAMTS13 activity was severely deficient (< 5%) in the six probands and one mildly symptomatic sibling but normal (> 50%) in all the parents and the asymptomatic siblings. Ten novel candidate ADAMTS13 mutations were identified in all families, showing either a compound heterozygous or a homozygous status in all probands plus the previous sibling and a heterozygous status in the parents. The mutations were spread all over the gene, involving the metalloprotease domain (I79M, S203P, R268P), the disintegrin domain (29 bp deletion in intron/exon 8), the cystein-rich domain (acceptor splice exon 12, R507Q), the spacer domain (A596V), the 3rd TSP1 repeat (C758R), the 5th TSP1 repeat (C908S) and the 8th TSP1 repeat (R1096stop). This study emphasizes the role of ADAMTS13 mutations in the pathogenesis of congenital TTP and suggests that several structural domains of this metalloprotease are involved in both its biogenesis and its substrate recognition process.     

Antiphospholipid antibodies in HELLP syndrome: clinical and biological study in 68 women

PURPOSE: Pregnancy complicated by the HELLP syndrome and antiphospholipid syndrome have rarely been reported. We report a study on anticardiolipin antibodies in HELLP syndrome. METHODS: Between March 1996 and September 1999, anticardiolipin antibodies were checked in all women with HELLP syndrome hospitalised in a maternity of the North of France. The women with positive anticardiolipin antibodies were seen month later in a internal medicine department. RESULTS: In the period 68 women with HELLP syndrome were checked for anticardiolipin antibodies. Apl were present in 9 patients (Incidence 42.8/1000 HELLP Year). They persisted after the accident only in 3 patients. Antiphospholipid syndrome was diagnosed in 2 patients, prevalence between the HELLP syndrome for the 42 month period was 0.03. CONCLUSIONS: HELLP syndrome may be a manifestation linked to the antiphospholipid syndrome and may revealed it.     

What is the most relevant definition of orthostatic hypotension: systolic blood pressure drop, diastolic blood pressure drop, or both?

The agreed definition of orthostatic hypotension (OH) is a drop of 20 mmHg systolic and/or 10 mmHg diastolic blood pressure (BP) within the first 3 min of erect posture. For elderly people, a question can be raised about diastolic BP relevance in OH's definition. OBJECTIVE: To determinate HO's prevalence and risks factors considering systolic blood pressure (SBP)'s drop, or diastolic blood pressure (DBP)'s drop, or either. METHODS: We assessed OH for 554 consecutive, ambulatory, elderly subjects, attending a geriatric outpatient clinic. OH was defined as a SBP drop>20mmHg (SBP-OH), or a DBP drop>10 mmHg (DBP-OH), or a drop in either (SBP. DBP-OH). OH's prevalence and risks factors were determined. RESULTS: In this population, 76 +/- 6 years of age, (70% hypertension), SBP-OH's prevalence was 17%, DBP-OH's prevalence was 12% and SBP. DBP-OH's prevalence was 25%. OH's risks factors varied considering OH's definition. After adjusting for significant determinants, SBP-OH's risk factors were: Antihypertensive therapy (OR=2.95; IC 95%: 1.21-4.04), age>75years (OR=2.11; IC 95%: 1.22-3.66), anti-hypertensive poly therapy (OR=2.01; IC 95%: 1.39-2.92) and SBP level (OR=1.16; IC 95%: 1.01-1.33). Considering DBP-OH, the only significant risk factor was DBP's level (OR=2.64; IC 95%: 1.89-3.68). SBP. DBP-OH was only determined by anti-hypertensive poly therapy (OR=1.61; IC 95%: 1.13-2.29) and DPB level (OR=1.32; IC 95%: 1.08-1.60). CONCLUSION: For elderly people, OH's prevalence and risks factors vary considering OH's definition. SBP's drop seems to be more relevant than DBP's drop. A long term follow up is necessary to determine if SBP-OH is correlated with HO' s side effects and to establish the dangerous level of SBP' s drop.     

A contactin-receptor-like protein tyrosine phosphatase beta complex mediates adhesive communication between astroglial cells and gonadotrophin-releasing hormone neurones

Although it is well established that gonadotrophin-releasing hormone (GnRH) neurones and astrocytes maintain an intimate contact throughout development and adult life, the cell-surface molecules that may contribute to this adhesiveness remain largely unknown. In the peripheral nervous system, the glycosylphosphatidyl inositol (GPI)-anchored protein contactin is a cell-surface neuronal protein required for axonal-glial adhesiveness. A glial transmembrane protein recognised by neuronal contactin is receptor-like protein tyrosine phosphatase β (RPTPβ), a phosphatase with structural similarities to cell adhesion molecules. In the present study, we show that contactin, and its preferred in cis partner Caspr1, are expressed in GnRH neurones. We also show that the RPTPβ mRNA predominantly expressed in hypothalamic astrocytes encodes an RPTPβ isoform (short RPTPβ) that uses its carbonic anhydrase (CAH) extracellular subdomain to interact with neuronal contactin. Immunoreactive contactin is most abundant in GnRH nerve terminals projecting to both the organum vasculosum of the lamina terminalis and median eminence, implying GnRH axons as an important site of contactin-dependent cell adhesiveness. GT1-7 immortalised GnRH neurones adhere to the CAH domain of RPTPβ, and this adhesiveness is blocked when contactin GPI anchoring is disrupted or contactin binding capacity is immunoneutralised, suggesting that astrocytic RPTPβ interacts with neuronal contactin to mediate glial–GnRH neurone adhesiveness. Because the abundance of short RPTPβ mRNA increases in the female mouse hypothalamus (but not in the cerebral cortex) before puberty, it appears that an increased interaction between GnRH axons and astrocytes mediated by RPTPβ–contactin is a dynamic mechanism of neurone–glia communication during female sexual development.