Catecholaminergic polymorphic ventricular tachycardia in a child: an often unrecognized diagnosis]

Catecholaminergic polymorphic ventricular tachycardia is important to be diagnosed as an underlying disease in children with syncope and normal heart, because of its poor prognosis. CASE REPORT: A 3-year-old boy was referred for stress and emotion induced syncope. Primary ventricular arrhythmia, consisting of salvos of bidirectional ventricular tachycardia, was reproducibly induced by physical exertion. The syncopal events and severe arrhythmia disappeared with beta-blocking therapy. CONCLUSION: Despite its rare occurrence, catecholaminergic polymorphic ventricular tachycardia is an important cause of stress and emotion induced syncope and sudden death in children.     

Gold: an old drug still working in refractory pemphigus

BACKGROUND: The mainstay of treatment for pemphigus is systemic corticosteroids. Different adjuvants have been used to reduce side-effects of long-term corticotherapy. Gold is an anti-inflammatory drug used in autoimmune diseases, whose use has waned with the advent of new immunosuppressive agents. OBJECTIVE: To study the outcome of the use of intramuscular gold treatment of pemphigus vulgaris refractory to previous therapies. METHODS: Thirteen patients with pemphigus vulgaris who had failed to respond to several prior therapies were treated with aurothiomalate, as a steroid-sparing agent. Patients were monitored to assess disease activity and gold toxicity. RESULTS: Seven patients achieved complete remission. Four patients were able to taper prednisone doses, although pemphigus flared when prednisone was discontinued or reduced. Toxicity was observed in the other two patients. CONCLUSIONS: In 53.4% of the patients, the use of chrysotherapy resulted in the complete clearing of the disease, discontinuation of all systemic therapies and induced a long-term clinical remission. Prednisone doses were able to be reduced in the remaining 46.6%. Any side-effects were reversible with drug discontinuation. Gold therapy showed efficacy as a secondary line treatment in refractory pemphigus vulgaris.     

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean ± SD of total stool output (g kg⁻¹) was 532 ± 476 vs 479 ± 354 and the duration (h) of diarrhoea was 108 ± 68 vs 103 ± 53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.     

Cardiac arrhythmia observed in 400 workers without obvious heart disease by Holter monitoring

To obtain information on the cardiac rhythm characteristics of subjects without heart disease during their daily work, we examined the continuous 24-hour electrocardiographic recordings of 400 workers from 4 factories in Eastern France presenting with criteria of cardiac normality. Sex, age and socio-professional category were taken into account. Supraventricular extrasystoles were extremely common, being observed in 52 p. 100 of men and 39 p. 100 of women. In men, the frequency of these extrasystoles increased with age (p less than 0.001), and their number was less than 20 per 24 hours in 90 p. 100 of the cases. Ventricular extrasystoles were detected in 40 p. 100 of men and 32 p. 100 of women. They too were age-related, though not significantly. Their number was less than 10 per 24 hours in 68 p. 100 of the cases and 10 to 50 per 24 hours in 28 p. 100. These ventricular extrasystoles usually were monomorphous, regularly coupled (92 p. 100) and isolated. However, 2 attacks of tachycardia were discovered. Episodes of bradyarrhythmia (RR superior or equal to 1500 ms) were present in 25 p. 100 of men and 19 p. 100 of women. They occurred more frequently before the age of 35 than later (p less than 0.001) and the recordings confirmed that they were predominantly nocturnal. Recordings without "disorders of rhythm" were relatively rare (20 p. 100 of men, 28.5 p. 100 of women). Finally, there was no clear-cut correlation between the prevalence or characteristics of these various "rhythmic abnormalities" and the type of professional activity.     

Respiratory hazards in hard metal workers: a cross sectional study

A cross sectional study was conducted on 513 employees at three hard metal plants: 425 exposed workers (351 men, 74 women) and 88 controls (69 men, 19 women). Cough and sputum were more frequent in workers engaged in "soft powder" and presintering workshops compared with controls (12.5% and 16.5% v 3.5%). Spirometric abnormalities were more frequent among women in sintering and finishing workshops compared with control women (56.8% v 23.8%) and abnormalities of carbon monoxide test were more frequent in exposed groups than in controls; this difference was more pronounced in women (31.4% v 5.6%) than in men (18.5% v 13%). No significant correlation was observed between duration of exposure and age adjusted lung function tests. Slight abnormalities of chest radiographs (0/1, 1/1 according to ILO classification) were more frequent in exposed men than controls (12.8% v 1.9%) and mostly in soft powder workers. In subjects with abnormal chest radiographs FVC, FEV1 and carbon monoxide indices (fractional uptake of CO or CO transfer index or both) were lower compared with those with normal chest radiographs. Although relatively mild, the clinical, radiological, and functional abnormalities uncovered call for a regular supervision of workers exposed to hard metal dust.     

Progression and regression of cervical lesions: Review of smears from women followed without initial biopsy or treatment

Cervical smears were reviewed from patients in whom a cytological abnormality was followed, after an interval without interference, either by regression to `negative' or else by progression to invasive carcinoma. Twenty-eight cases were from a previously analysed series with positive smears and an interval of at least two years before investigation, resulting from refusal or failure to trace. Slides were also reviewed from 25 cases in which `positive' smears had regressed to negative without escaping from surveillance, and from 10 patients subsequently developing invasive carcinoma whose previous slides, taken several years earlier, showed abnormalities on review. None of these 63 patients had any biopsy or other surgical procedure to the cervix between the initial smear and the outcome.

Slides showing `superficial cell dyskaryosis' and/or well-differentiated `parabasal cell dyskaryosis' were found only among the groups with subsequent regression. Those showing dissociated poorly differentiated dyskaryotic parabasal cells regressed to negative in two cases and progressed to invasion in nine. This suggests that many examples of spontaneous regression correspond to mild dysplasias which are not precancerous, and overdiagnosis must often have resulted in unnecessary surgical procedures in the past.

`Regressing' and `progressing' groups both included cases in which the spatula had removed coherent pieces of undifferentiated epithelium. These are difficult to interpret cytologically. In nine of them (including four which regressed) the cytological picture was that of carcinoma in situ. The remainder (14 cases) were probably examples of reserve cell hyperplasia, and it is noteworthy that, of the 21 cases subsequently progressing to invasive carcinoma, five were preceded by appearances of this type. It is concluded that cell aggregates suggesting an unusual degree of reserve cell hyperplasia are a danger signal and require careful surveillance.

     

The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis

Tuberous sclerosis is an autosomal dominant trait in which the dysregulation of cellular proliferation and differentiation results in the development of hamartomatous growths in many organs. The TSC2 gene is one of two genes determining tuberous sclerosis. Inactivating germline mutations of TSC2 in patients with tuberous sclerosis and somatic loss of heterozygosity at the TSC2 locus in the associated hamartomas indicate that TSC2 functions as a tumour suppressor gene and that loss of function is critical to expression of the tuberous sclerosis phenotype. The TSC2 product, tuberin, has a region of homology with the GTPase activating protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in vitro. Here we show that the region of homology between tuberin and human rap1GAP and the murine GAP mSpa1 is more extensive than previously reported and spans approximately 160 amino acid residues encoded within exons 34-38 of the TSC2 gene. Single strand conformation polymorphism analysis of these exons in 173 unrelated patients with tuberous sclerosis and direct sequencing of variant conformers together with study of additional family members enabled characterisation of disease associated mutations in 14 cases. Missense mutations, which occurred in exons 36, 37 and 38 were identified in eight cases, four of whom shared the same recurrent change P1675L. Each of the five different missense mutations identified was shown to occur de novo in at least one sporadic case of tuberous sclerosis. The high proportion of missense mutations detected in the region of the TSC2 gene encoding the GAP-related domain supports its key role in the regulation of cellular growth.      

Formaldehyde in cryoprotectant propanediol and effect on mouse zygotes

Cryopreservation of human zygotes and embryos has been routinely performed by in-vitro fertilization clinics for many years. Karran and Legge (1996) first reported that formaldehyde (FA) present in the cryoprotective solutions can have a deleterious effect on mouse oocytes. FA is a cytotoxic, carcinogenic and mutagenic chemical. The effect of FA on mouse zygotes was investigated. In addition, the concentrations of FA in propanediol (PROH) obtained from various sources were determined. Pooled 1-cell embryos were dispensed into droplets of modified Ham's F10 or human tubal fluid containing various concentrations of FA. Since bovine serum albumin (BSA) may minimize toxicity additional trials were done as above in the absence of BSA. FA concentration in the standard 1.5 M PROH, from different sources in water, was measured in the same assay using a standard curve of 0-100 microM FA. FA in a complex medium had a significant deleterious effect on embryo development and hatching but only at 1 mM concentration (P < 0.000001; see Tables I-III). There was no significant effect of FA at 100 microM. However, in a simple medium even 50 microM FA decreased embryo hatching. FA was present in 1.5 M PROH from different sources (range 1.0-35.3 microM concentration). It appears that FA concentrations do not increase with storage because FA concentrations were low even after opening and storage for 3 years on the shelf. This suggests that FA is a contaminant during the manufacturing process and may vary from manufacturer to manufacturer and batch to batch. Until further studies are done to confirm the lack of toxicity to embryos during cryopreservation (with or without FA scavengers) it may be prudent to screen all batches of cryoprotectants for FA as part of quality control.