Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy

BACKGROUND: Mutations in the gene for cardiac myosin-binding protein C account for approximately 15 percent of cases of familial hypertrophic cardiomyopathy. The spectrum of disease-causing mutations and the associated clinical features of these gene defects are unknown. METHODS: DNA sequences encoding cardiac myosin-binding protein C were determined in unrelated patients with familial hypertrophic cardiomyopathy. Mutations were found in 16 probands, who had 574 family members at risk of inheriting these defects. The genotypes of these family members were determined, and the clinical status of 212 family members with mutations in the gene for cardiac myosin-binding protein C was assessed. RESULTS: Twelve novel mutations were identified in probands from 16 families. Four were missense mutations; eight defects (insertions, deletions, and splice mutations) were predicted to truncate cardiac myosin-binding protein C. The clinical expression of either missense or truncation mutations was similar to that observed for other genetic causes of hypertrophic cardiomyopathy, but the age at onset of the disease differed markedly. Only 58 percent of adults under the age of 50 years who had a mutation in the cardiac myosin-binding protein C gene (68 of 117 patients) had cardiac hypertrophy; disease penetrance remained incomplete through the age of 60 years. Survival was generally better than that observed among patients with hypertrophic cardiomyopathy caused by other mutations in the genes for sarcomere proteins. Most deaths due to cardiac causes in these families occurred suddenly. CONCLUSIONS: The clinical expression of mutations in the gene for cardiac myosin-binding protein C is often delayed until middle age or old age. Delayed expression of cardiac hypertrophy and a favorable clinical course may hinder recognition of the heritable nature of mutations in the cardiac myosin-binding protein C gene. Clinical screening in adult life may be warranted for members of families characterized by hypertrophic cardiomyopathy.     

Water impurity in low-loss silica fibre

Water contamination in silica based optical fibre waveguides has been studied. The height of the 950nm water peak was found to vary with fibre pulling speed and reduced sharply from 64 dB/km to 20.5 dB/km as the speed was increased from 0.12 m/sec to 1.47 m/sec. The results have been fitted to a diffusion curve indicating that the water diffuses into the core region from the support tubes used in preform manufacture. Deposition inside a water free Spectrosil tube gave a water peak of only 4 dB/km. A B₂O₃ doped cladding layer was used to provide a barrier to OH migration and the 950nm water peak was reduced from 24 dB/km to 3 dB/km by increasing the B₂O₃ content in the layer from 2 to 4 mole per cent.     

Oligoribonucleotides containing 8-oxo-7,8-dihydroguanosine and 8-oxo-7,8-dihydro-2''-O-methylguanosine: synthesis and base pairing properties

OBJECTIVE: To test whether a rigid or a flexible ankle orthosis affects postural sway in single-limb stance as quantified by stabilometry. DESIGN: Crossover trial. SETTING: University laboratory. PARTICIPANTS: Twenty-two athletes with functional ankle instability (consecutive sample of patients with recurrent ankle sprains but without mechanical instability) and 22 healthy athletes (control group of volunteers matched to age, height, weight, physical activity). INTERVENTIONS: Stabilometry in single-limb stance on a force platform. Participants were tested on each leg with and without a rigid or a flexible ankle orthosis. The order of test conditions was randomized. MAIN OUTCOME MEASURES: Sway velocities, sway pattern, and sway area as calculated from center of pressure movements. The two groups were compared by Mann-Whitney test, and the different orthoses within each group were compared by Wilcoxon test, paired samples (type I error 5%, Bonferroni adjustment). RESULTS: In athletes with functional ankle instability, both a rigid and a flexible ankle orthosis significantly reduced mediolateral sway velocity. A flexible ankle orthosis also changed sway pattern significantly, by reducing the percentage of linear movements of less than 5 degrees per .01 sec. CONCLUSIONS: In athletes with functional ankle instability, ankle orthoses reduce mediolateral sway velocity, possibly because of improved mediolateral proprioception.     

Elecroencephalographic charactistics of Creutzfeldt-Jakob disease and its differential diagnosis

Although clinical electroencephalography is no longer as important as it used to be in differential diagnosis of a fair number of neurological and psychiatric diseases ever since imaging techniques have been making enormous strides, EEG is still an important diagnostic tool in dementias where specific morphological lesions are not immediately or not at all apparent which would otherwise be visible by imaging. Sporadic Creutzfeldt-Jakob disease is an important case in point. Although this is associated with some unspecific EEG findings, typical periodical sharp wave complexes (PSWC) become conspicuous in the course of the disease. If these are meticulously studied and particular attention is paid to their periodicity, a sensitivity of 67% and a specificity of 86% are attained. With the exception of one familial variant of Creutzfeldt-Jakob disease PSWC ar usually absent all other human prion diseases. Hence, it is not likely that they are linked to the aetiology of sporadic Creutzfeldt-Jakob disease. We present a patho-physiological hypothesis on the development of PSWC basing on the assumption that the specific periodicity of PSWC results from a still functionally active but greatly impaired subcortical-cortical circuit of neuronal excitability. This specific pattern of neuronal degeneration may obviously arise--albeit very rarely--also in other diseases independent of their aetiology, so that the EEG patterns appear identical. For this reason it is imperative to make complementary use of EEG and of recent clinical and laboratory data of Creutzfeldt-Jakob disease before PSWC and be considered a relevant diagnostic criterion. Conversely, clinical diagnosis of Creutzfeldt-Jakob disease should be reconsidered if repeated EEG recordings fail to reveal PSWC even under technically adequate conditions.     

Myocardial infarction and percent arteriographic stenosis of culprit lesion: report from the Program on the Surgical Control of the Hyperlipidemias (POSCH)

Domestic violence is a significant public health issue affecting women. Numerous medical organizations have recommended that routine screening of women be conducted to assist in the prevention, identification, and care for victims of violence. This article examines the scope of domestic violence in women, reviews ways to recognize abuse, examines the potential impact of abuse upon health and discusses the management of victims.     

Induction of pulmonary edema and emphysema in goats by intraruminal administration of 3-methylindole

An elementary school in Broward County, Florida, reported an outbreak of scabies in January and February 1975. Investigation identified 23 cases of scabies in schoolchildren, with at least two cases in each grade. The first case had appeared as early as July 1974, but most occurred after December. There was little contact between students in different grades; most transmission was found to have taken place within families and in the community. An additional 28 cases were found in families and contacts; altogether, 51 cases in 24 families were identified on clinical or historical grounds. Infestation was more frequent in children who exchanged clothes with friends or relatives and in those who, on occasion, spent the night with other children.     

Idiosyncratic cardiovascular response of human neonates to acoustic stimuli

The heart rate response of acoustic stimuli was assssed for 15 newborns between the ages of 24 and 48 hr. Results of the analyses of covariance demonstrated that although the subjects responded to the stimuli, their responses were idiosyncratic in magnitude, direction, and pattern of rate change. Although spectrum and duration of the stimuli were varied, they were found not to be significant sources of response variation.