Systematic screening for fragile X syndrome in a cohort of 574 mentally retarded children

The Sense of Coherence Scale is used frequently world-wide and is thought to be appropriate to any population. The purpose of this study was to highlight some of the potential limitations of the scale. Fifteen members of the Pentecostal Movement described several difficulties in completing the scale, especially items measuring manageability and comprehensibility. The following three statements indicate the nature of their interpretation of the items and the ambiguity of their answers as they argued that: (1) the concept of 'I' was interpreted as 'I and God', (2) it is not necessary to understand everything in life, because it is enough that God understands, and (3) life is meaningful in itself because of the salvation. According to this interpretation of the items, every proposed answer could be suitable and consequently, the scores can readily be misconstrued. Many of the respondents proposed additions or changes in the wording to make the scale more suitable. The strong ego-centred items seem to be inappropriate for the participants in this study and other populations might also be confronted with similar difficulties.     

Thrombotic thrombocytopenic purpura in 13 Dutch centres: treatment and longterm follow-up

OBJECTIVE: Analysis of the incidence, treatment modalities and disease course of thrombotic thrombocytopenic purpura (TTP) in the Netherlands. DESIGN: Retrospective follow-up study. SETTING: 13 centres in the Netherlands. METHODS: Regarding all patients admitted between 1-1-1979 and 1-1-1992 to one of 13 Dutch haematological centres, in whom the diagnosis of TTP was made for the first time, information was gathered from the medical records and from the patients own physicians on patient characteristics at presentation and the occurrence of relapse or death. The follow-up period tended on 1-4-1995. RESULTS: A total of 65 patients with newly diagnosed TTP were identified: 0.34 per 1,000,000 persons a year (95% confidence interval (95%-CI): 0.26-0.45), increasing to 0.83 in the last year of the study. Forty-six (95%) patients were treated with fresh frozen plasma: 18 (28%) by plasma infusion and 44 (68%) by plasma exchange; 48 (74%) (additionally) received corticosteroids. All 52 patients (80%) who survived the first four weeks after admission reached complete remission. Twelve patients with relapsing TTP underwent splenectomy in remission. The 5-year survival rate was 77% (95% CI: 66-87) and the 5-year relapse-free survival rate 38% (95% CI: 25-52). Cardiac symptoms, severe thrombocytopenia and a high serum LDH were risk factors for acute mortality, but no risk factors for relapse or late-occurring death could be identified. CONCLUSION: TTP is a rare disease which is increasingly being recognized. Plasma exchange and corticosteroids are the most frequently used therapies. The disease has a high mortality rate in the acute phase of the disease.     

Selective modification of insulin action in adipose tissue by hyperthyroidism

Adipose-tissue lipolysis (assessed from glycerol release) and glucose uptake were examined in parametrial and mesenteric adipocytes prepared from control or hyperthyroid rats in relation to changes in insulin sensitivity. Basal rates of lipolysis did not differ significantly between adipose-tissue depots. Lipolysis was maximally stimulated by noradrenaline at 1 microM, half-maximal anti-lipolytic effects of insulin were observed at approximately 11 microU/ ml insulin, and half-maximal stimulation of glucose uptake was observed at approximately 16 microU/ml insulin in adipocytes from both depots. Wortmannin caused a dose-dependent inhibition of the anti-lipolytic effect of insulin (150 microU/ml) on noradrenaline-stimulated lipolysis. Half-maximal effects of wortmannin were observed at 20-40 nM. The p70S6K inhibitor rapamycin and the mitogen-activated protein kinase kinase inhibitor PD098059 had no effects on noradrenaline-stimulated lipolysis. Hyperthyroidism increased basal rates of lipolysis and the maximal response of lipolysis to noradrenaline stimulation (3.1-fold, P < 0.001 and 2.1-fold, P < 0.05 respectively) in parametrial adipocytes. Hyperthyroidism markedly blunted the sensitivity of noradrenaline-stimulated lipolysis to half-maximal suppression by insulin in both parametrial and mesenteric adipocyte depots, and noradrenaline-stimulated lipolysis at a maximal insulin concentration remained significantly higher in adipocytes prepared from hyperthyroid rats compared with controls. Hyperthyroidism had no effect on basal and little effect on insulin-stimulated glucose uptake. Tri-iodothyronine administered at a low dose selectively influenced the anti-lipolytic action of insulin in parametrial adipocytes, and led to significantly less marked elevation in plasma non-esterified fatty acid concentrations in vivo. The results demonstrate a selective effect of hyperthyroidism to impair insulin's anti-lipolytic action, and are consistent with the operation of different downstream signalling mechanisms for the effects of insulin on adipocyte glucose transport and lipolysis.     

Hostility, cigarette smoking and alcohol consumption in the general population

Hostility has been associated with coronary heart disease, and hostility may affect coronary risk through its influence on risk factors such as cigarette smoking and alcohol consumption. The objective of this study was to determine relationships between hostile personality, cigarette smoking and alcohol consumption in the general population. The Edinburgh Artery Study comprises a cross-sectional survey of 1592 men and women aged 55-74 years sampled from age-sex registers of 10 general practices throughout the city. The Bedford-Foulds Personality Deviance Questionnaire was used to elicit extrapunitiveness (including hostile thoughts), dominance (including hostile acts) and intropunitiveness. Social class, age and deprivation score were controlled for in multivariate analyses. The hostile thoughts scale emerged as a significant independent predictor of alcohol consumption in men and women (P < or = 0.01), and the models accounted for 4-9% of the variance in alcohol consumption. Hostile acts were independently predictive of smoking in men (P < or = 0.001), with the model accounting for 5% of the variance in smoking. Hostile thoughts were independently predictive of smoking in women (P < or = 0.001), and the model accounted for 4% of the variance in their smoking. We conclude that hostility may affect coronary risk through its influence on lifestyle-related coronary risk factors, although in future further elucidation of hostility type and standard measurement of hostility are necessary.     

Clincal, immunologic, and genetic features of an autoimmune lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis

To examine the effect of elastic loading on variational activity of breathing, we studied 11 healthy subjects breathing at rest and with inspiratory elastic loads of 9 and 18 cm H2O/L, applied randomly for 1 h each. Compared with rest, a load of 18 cm H2O/L decreased gross variability, quantitated as standard deviation, of tidal volume (VT) and expiratory time (TE) (p < 0.01 in both instances) but increased that of inspiratory time (TI) (p < 0.03). The autocorrelation coefficients at a lag of 1 breath for each breath component were not altered by elastic loading, although the number of breath lags with significant serial correlations for TE tended to increase with a load of 18 cm H2O/L (p = 0.08). A load of 18 cm H2O/L decreased only the fraction of variational activity of VT and TE due to uncorrelated, random behavior (white noise), while it increased that fraction for TI (p < 0.05 in each instance); the correlated and oscillatory fractions did not change. Uncorrelated random behavior constituted > 87% of the variance of each breath component, correlated behavior represented 3 to 11%, and oscillatory behavior represented < 1.5% during both rest and loaded breathing. Elastic loading changed the gross variability of each primary breath component by altering the random fraction of variational activity; it had no significant effect on the structured, correlated fraction. We speculate that the observed changes in variational activity may reflect an attempt by the controller to compensate for the increased load while simultaneously minimizing load-induced dyspnea.     

Oculocerebral dysgenesis in the linear nevus sebaceous syndrome

PURPOSE: The authors document the association of peripapillary staphyloma and an atypical variant of hemimegalencephaly with the linear nevus sebaceous syndrome. BACKGROUND: Linear nevus sebaceous syndrome is an uncommon neurocutaneous disorder that has a propensity to involve the eyes. METHODS: Clinical, histopathologic, and neuroimaging findings are examined in a child with linear nevus sebaceous syndrome. RESULTS: In addition to bilateral peripapillary staphylomas, ophthalmologic abnormalities included a corneal dermoid, a complex conjunctival choristoma, macular hypoplasia, and optic nerve hypoplasia with contralateral optic atrophy. Magnetic resonance imaging disclosed a rare form of hemimegalencephaly characterized by hypoplasia of an optic radiation within the enlarged, dysgenetic cerebral hemisphere. CONCLUSION: The spectrum of oculocerebral dysgenesis in the linear nevus sebaceous syndrome can be expanded to include peripapillary staphyloma and atypical hemimegalencephaly with hypoplasia of an optic radiation.     

Conditioning-related protection from acoustic injury: effects of chronic deefferentation and sham surgery

The inner ear can be made less vulnerable to acoustic injury by a "conditioning" treatment involving exposure to a moderate-level acoustic stimulus before the acoustic overexposure. The present study was designed to explore the role of the olivocochlear (OC) system in this "protection." Guinea pigs were divided into a number of groups: some (trauma-only) were exposed to a traumatic noise for 4 h at 109 dB SPL; others (condition/trauma) were conditioned by daily exposure to the same noise at 85 dB SPL before the traumatic exposure. In OC-intact animals, the condition/trauma group showed significantly less permanent threshold shift (PTS) than the trauma-only group as measured via compound action potentials and distortion-product otoacoustic emissions (DPOAEs). Other animals with identical noise-exposure regimens underwent deefferentation surgery before the start of conditioning: the OC bundle (OCB) was cut in the brain stem, either at the midline (cutting the crossed OCB to both ears) or at the sulcus limitans (cutting all OC fibers to 1 side). Lesion success was quantified by measuring OC fascicles to the outer hair cell region in each ear. The results from the surgical groups showed that total loss of the OCB significantly increased the noise-induced PTS, whereas loss of the COCB only did not; that the conditioning exposure in deefferented animals increased, rather than decreased, the PTS from the traumatic exposure; and that animals undergoing sham surgery (brain stem cuts that failed to transect the OCB) appeared protected whether or not they received the conditioning noise exposure. The latter result suggests that conditioning-related protection may arise from a generalized stress response, which can be elicited by noise exposure, brain surgery, or a variety of other means. The former results make an OC role in the conditioning process, per se, difficult to assess, given the large effects of OC activity on general acoustic vulnerability.     

Late functional outcome after reconstruction of the upper aerodigestive tract with free transplanted microvascular anastomosed jejunum

Since 1983, 90 autologous jejunal transplantations for reconstruction of the upper digestive tract have been performed in 89 patients (9 females, 80 males, average age 56.3 years). 73 patients were operated primarily, in 16 patients a recurrent tumor had been treated. One patient received a second jejunal graft after necrosis. In these heterogenous patients, the primary tumor was located in the hypopharynx 48 times, in the larynx 21 times, in the oropharynx 19 times and twice in the oral cavity. There was nearly always tumor stage III or IV without distant metastases. Following locoregional tumor resection, speech restoration was achieved 35 times by a siphon-like tube, and the upper digestive tract was reconstructed using a patch 18 times and by a tube 28 times. A combination of tube or patch with a siphon-like tube was employed 9 times. In only two of 16 patients with recurrent tumor, speech reconstruction was performed, in the other 14, the upper digestive tract was reconstructed. In those patients, in whom speech reconstruction (by siphon tube or by combination with tube/patch) was intended, this was achieved in 81.5%. Successful functional reconstruction of the upper digestive tract (by patch, tube, combination) could be achieved in about 60% of these patients.     

Evaluation of mental retardation: recommendations of a Consensus Conference: American College of Medical Genetics

A Consensus Conference utilizing available literature and expert opinion sponsored by the American College of Medical Genetics in October 1995 evaluated the rational approach to the individual with mental retardation. Although no uniform protocol replaces individual clinician judgement, the consensus recommendations were as follows: 1. The individual with mental retardation, the family, and medical care providers benefit from a focused clinical and laboratory evaluation aimed at establishing causation and in providing counseling, prognosis, recurrence risks, and guidelines for management. 2. Essential elements of the evaluation include a three-generation pedigree: pre-, peri-, and post-natal history, complete physical examination focused on the presence of minor anomalies, neurologic examination, and assessment of the behavioral phenotype. 3. Selective laboratory testing should, in most patients, include a banded karyotype. Fragile X testing should be strongly considered in both males and females with unexplained mental retardation, especially in the presence of a positive family history, a consistent physical and behavioral phenotype and absence of major structural abnormalities. Metabolic testing should be initialed in the presence of suggestive clinical and physical findings. Neuroimaging should be considered in patients without a known diagnosis especially in the presence of neurologic symptoms, cranial contour abnormalities, microcephaly, or macrocephaly. In most situations MRI is the testing modality of choice. 4. Sequential evaluation of the patient, occasionally over several years, is often necessary for diagnosis, allowing for delineation of the physical and behavioral phenotype, a logical approach to ancillary testing and appropriate prognostic and reproductive counseling.