Idiopathic slow-transit constipation is not associated with mutations of theRET proto-oncogene or GDNF

PURPOSE: Idiopathic slow-transit constipation is a severe disorder of unknown cause. The onset in early childhood and history of constipation or Hirschsprung's disease in close family relatives suggest that slow-transit constipation could have a genetic basis. Several germline mutations have been described in Hirschsprung's disease, including mutations of RET and the gene encoding its ligand glial cell-derived neurotrophic factor. The aim of this study was to screen a panel of 16 cases of familial idiopathic slow-transit constipation, including 4 families in which there were relatives with Hirschsprung's disease, for RET and glial cell-derived neurotrophic factor mutations previously identified in Hirschsprung's disease. METHODS: Genomic DNA from 16 patients with slow-transit constipation and four relatives with Hirschsprung's disease was analyzed using single strand and heteroduplex conformation polymorphism analysis at two conditions and by direct DNA sequencing using the fluorescent dideoxy terminator method. RESULTS: Although common sequence polymorphisms were demonstrated with a frequency comparable with published data, no published or new mutation was seen in any of the exons of RET or glial cell-derived neurotrophic factor. CONCLUSIONS: Mutation of RET or glial cell-derived neurotrophic factor is not a frequent cause of idiopathic slow-transit constipation.     

Sleep disorders in the elderly

Problems with sleep, including acute and chronic conditions, increase with age. Expertise in dealing with sleep problems using pragmatic management strategies is an essential component of comprehensive geriatric patient care. This article provides a succinct review of the physiology, diagnosis, and treatment of sleep disorders in the elderly.     

Screening for breast cancer

Screening for breast cancer using the combination of physical examination of the breasts and mammography was effective in women age 50 or more in the HIP study. However, major questions remain, especially the benefit of screening women age 40-49, and the independent effect of mammography. Such questions can only be answered by large-scale randomized controlled trials, and trials to answer these questions are now underway in Canada (the NBSS) and Sweden. Only the NBSS, however, is attempting to replicate the HIP study in women age 40-49, and to evaluate the additional contribution of mammography to annual physical examination in women age 50-59. The Swedish studies are evaluating the effectiveness of mammography alone, while studies in Britain will help to evaluate breast self-examination (BSE) and biannual mammography with annual physical examination. Because much of the benefit in HIP could have derived from the physical examination, it is necessary to complete the present trials before population-based screening for breast cancer using mammography can be advocated. Trials are justifiable because the risk of mammographic screening seems likely to be negligible, and the use of the combination of annual mammography and physical examination to be cost-effective. In the meantime, there seems no immediate substitute on a population basis for efficient physical examination of the breasts by primary care physicians coupled with breast self-examination by the woman. Techniques such as ultrasound and diaphanography seem unlikely to supplant mammography in screening, and in any case, have to be evaluated in comparison with mammography.     

The experimental induction of parathyroid hyperplasia in rats,and the use of toluidine blue O forin vivo identification of parathyroid tissue

An experiment was designed to compare the degree of parathyroid hyperplasia induced in rats by subtotal nephrectomy and by oral phosphate administration singly or in combination. The greatest degree of parathyroid hyperplasia was×4.49 and was seen in the rats with both subtotal nephrectomy and oral phosphate administration. Over the 77-day period of the experiment, subtotal nephrectomy alone did not produce a significant increase in the size of the glands, whereas phosphate fed to otherwise normal rats did produce a significant increase.Toluidine blue was given intravenously before killing the rats and was found to stain the hyperplastic glands in the same way that it stains normal and adenomatous glands. Staining was found to be satisfactory for identification purposes in both the normal and in the hyperplastic glands with 5 mg/kg body weight. A greater depth of staining was given by 10 mg/kg body weight.

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Zusammenfassung Es wurde ein Experiment an Ratten durchgeführt, um den Grad der Parathyreoidea-Hyperplasie anhand folgender Punkte zu vergleichen: subtotale Nephrektomie, orale Phosphatverabreichung oder eine Kombination von beiden. Die maximale Parathyreoidea-Hyperplasie war 4,49mal größer als bei den Kontrollen und wurde bei Ratten mit subtotaler Nephrektomie und mit oraler Phosphatverabreichung festgestellt.Während der 77 Tage des Experimentes erzeugte subtotale Nephrektomie allein keine bedeutende Zunahme der Drüsengröße; Phosphat hingegen, welches im übrigen normalen Ratten verfüttert wurde, bewirkte eine bedeutende Zunahme.Toluidinblau wurde den Ratten intravenös injiziert, bevor sie getötet wurden; es färbte die hyperplastischen Drüsen ebenso befriedigend wie normale und adenomatöse Drüsen. Die Färbung war mit 5 mg/kg Körpergewicht befriedigend zur Identifizierung der normalen wie der hyperplastischen Drüsen. Eine tiefere Färbung wurde mit 10 mg/kg Körpergewicht erreicht.

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Résumé Le degré d'hyperplasie parathyroidïenne a été étudié chez le Rat après néphrectomie subtotale, après administration buccale de phosphate ou par combinaison des deux. Le degré le plus élevé d'hyperplasie parathyroidïenne est de ×4.49 et a été observé chez le rat après néphrectomie sub-totale et administration buccale de phosphate.Au cours des77 jours d'expérience, la néphrectomie sub-totale ne produit pas une augmentation significative de la taille des glandes, alors que le phosphate, mélangé à l'alimentation de rats normaux, produit une augmentation significative.Le bleu de toluidine, administré par voie intra-veineuse avant le sacrifice des rats, colore les glandes hyperplasiques de la même façon qu'il colore les glandes normales et adénomateuses. La coloration s'avère intéressante pour l'identification des glandes normales et hyperplasiques à la concentration de 5 mg/kg de poids corporel. Une coloration plus intense est obtenue avec 10 mg/kg de poids corporel.