Complex Genetic Disease: Can Genetic Strategies in Alzheimer's Disease and New Genetic Mechanisms Be Applied to Epilepsy?

Summary: Strategies used in molecular genetics have changed modern neurology. The gene or genes responsible for several major neurologic diseases have now been identified using "reverse" or positional genetics. Unexpected new genetic mechanisms have been discovered in human neurologic diseases, including (a) identical mutations of the prion protein gene in Creutzfeldt-Jakob disease and fatal familial insomnia with the phenotypic expression directed by an accompanying polymorphism; (b) stable duplications of chromosome 17 in Charcot-Marie-Tooth disease (type 1 A) that involve many genes, only one of which appears to cause neuropathy; and (c) highly variable, dynamic mutations in myotonic dystrophy, fragile X syndrome, and Kennedy's syndrome that modulate variable expressivity in multiple tissues. There is growing recognition that neurologic diseases are often complex genetic diseases with multifactorial rather than simple modes of inheritance. For example, genetic association/linkage strategies have interacted with biochemistry and immunopathology studies to produce new insights into the disease mechanism of late-onset Alzheimer's disease. The role of apolipoprotein E in late-onset Alzheimer's disease is an example of how new analytical techniques of genetic disease can be applied to dissect multiple genes. Similar research strategies are suggested for the study of epilepsy as a complex disease.     

Alexithymia in Holocaust Survivors with and Without PTSD

Alexithymia was measured in non-treatment seeking, community-dwelling Holocaust survivors using the Toronto Alexithymia Scale—Twenty Item Version (TAS-20). Scores of survivors with (n = 30) and without (n = 26) posttraumatic stress disorder (PTSD) were compared, and associations among alexithymia, severity of trauma, and severity of PTSD symptoms were determined. Survivors with PTSD had significantly higher scores on the TAS-20 compared to survivors without PTSD. TAS-20 scores were significantly associated with severity of PTSD symptoms, but not with severity of trauma. This study adds to our knowledge of the relationship between alexithymia and trauma by demonstrating that this characteristic is related to the presence of posttraumatic symptoms and not simply exposure to trauma.     

Evaluation of the float sign for determining adequacy of specimens obtained with transbronchial biopsy.

This study prospectively evaluated the alveolar content of transbronchial biopsy specimens based on whether or not they floated in formalin. One hundred biopsy specimens were obtained from 18 patients. Specimens with any alveoli were significantly more likely to float (45 of 61, 74%) than those with no alveolar tissue (15 of 39, 39%; p less than 0.001). The majority of diagnostic specimens were obtained in eight patients with sarcoidosis, where 47 biopsies were obtained. Fourteen of 19 specimens (74%) with noncaseating granulomas floated, whereas only 11 of 28 (39%; p less than 0.05) nondiagnostic specimens floated. The results of this study suggest that this simple bedside observation may serve to determine the adequacy of transbronchial biopsy specimens, particularly in sarcoidosis.     

Galanin- and CGRP-like immunoreactivity coexist in rat spinal motoneurons.

We can report, that by the use of indirect immunofluorescence techniques, that rat spinal motoneurons contain galanin-like immunoreactivity (LI). Furthermore, that galanin and calcitonin gene-related peptide (CGRP)-LI coexist in a number of spinal motoneurons. Co-localization could be demonstrated as thoracic, lumbar as well as sacral spinal cord levels in individual neurons by studying adjacent sections each stained by one of the two antisera, as well as by double labelling experiments. Small neurons, within the gamma-motoneuron and interneuron size-range, were also positive for galanin-LI.     

A meta-analysis of randomized trials of fish oil in prevention of restenosis following coronary angioplasty.

The efficacy of fish oil in decreasing restenosis following percutaneous transluminal coronary angioplasty (PTCA) remains controversial despite seven published reports of randomized trials involving 951 patients. We performed a meta-analysis to determine whether these trials, viewed in aggregate, demonstrate a significant benefit. We evaluated rates of restenosis two to 12 months after PTCA and calculated an estimate of the overall effect and 95% confidence interval (CI). The typical odds ratio (treatment versus control) was 0.71 (95% CI 0.54, 0.94), P = 0.016 (two-tailed). The data show a strong and highly significant (P less than .0001) relationship between daily fish oil dose and gastrointestinal side effects. While compatible with a small to moderate benefit of fish oil on rates of restenosis, these results require confirmation in a randomized clinical trial large enough to distinguish reliably between a clinically meaningful benefit and a null result.     

Psychiatric morbidity among people aged 85+ in 1987. A follow-up study at two and a half years: Associations with changes in psychiatric morbidity

This article reports findings from a longitudinal survey of very elderly people living at home in London. The research aimed to identify social, psychological and physical characteristics associated with positive ageing and successful survival in the community in later life and its converse—negative ageing—as well as the associated policy implications. Associations with psychiatric morbidity, measured using the General Health Questionnaire, among sample members without cognitive impairment between the baseline interviews in 1987 and at follow-up, two and a half years later in 1990, are reported. Twenty-five per cent of survivors scored over the threshold of the GHQ in 1987 and 30% scored over the threshold in 1990. Half of those with a score over the threshold in 1990 also scored over the threshold in 1987. Hierarchical regression (using residualized change analysis) was used to estimate the effects of the independent variables on changes in psychiatric morbidity. The most significant predictor of psychiatric morbidity (GHQ score) in 1990 was baseline GHQ score, followed by health and functional status scores. Health and functional status were also the strongest predictors of baseline (1987) GHQ scores. The uniqueness of the study lies in the collection of follow-up data on a sample of very elderly people, given that most surveys are corss-sectional and contain too few people aged 85+ to merit separate analysis. It contributes to the small body of literature on outcome of depression. The lack of consistent associations with recovery from psychiatric morbidity in the literature enhances the importance of studies aiming to identify factors associated with different outcomes.     

An inexpensive, self-assembly pressure algometer

We have developed a simple instrument for pressure algometry. It can be made easily using components found in most anaesthetic rooms. Ten students were able to make the device using written instructions. All the resulting algometers performed within 10% accuracy limits for values up to 4 kgcm⁻².