Cobalamin F deficiency in a girl with severe skin hyperpigmentation and a homozygous LMBRD1 variant.

Cobalamin (vitamin B12) is important in gastrulation, nervous system development and haemoglobin formation. Mutations of the ABCD4 or LMBRD1 genes can lead to cobalamin-related disorders. We report a patient with disseminated skin hyperpigmentation caused by a homozygous LMBRD1 variant. Genetic disorders of cobalamin metabolism caused by variants in the ABCD4 or LMBRD1 genes should be considered in patients presenting with cutaneous hyperpigmentation. Click https://www.wileyhealthlearning.com/#/online-courses/a6ef1275-8325-4834-89d2-aa18fa31e63f for the corresponding questions to this CME article.

Beclin 1 and autophagy are required for the tumorigenicity of breast cancer stem-like/progenitor cells.

Malignant breast tissue contains a rare population of multi-potent cells with the capacity to self-renew; these cells are known as cancer stem-like cells (CSCs) or tumor-initiating cells. Primitive mammary CSCs/progenitor cells can be propagated in culture as floating spherical colonies termed 'mammospheres'. We show here that the expression of the autophagy protein Beclin 1 is higher in mammospheres established from human breast cancers or breast cancer cell lines (MCF-7 and BT474) than in the parental adherent cells. As a result, autophagic flux is more robust in mammospheres. We observed that basal and starvation-induced autophagy flux is also higher in aldehyde dehydrogenase 1-positive (ALDH1(+)) population derived from mammospheres than in the bulk population. Beclin 1 is critical for CSC maintenance and tumor development in nude mice, whereas its expression limits the development of tumors not enriched with breast CSCs/progenitor cells. We found that decreased survival in autophagy-deficient cells (MCF-7 Atg7 knockdown cells) during detachment does not contribute to an ultimate deficiency in mammosphere formation. This study demonstrates that a prosurvival autophagic pathway is critical for CSC maintenance, and that Beclin 1 plays a dual role in tumor development.

[The methods of using the echocardiogram in outpatients. The role of the cardiologist for more appropriate use of the procedure. The Ligurian Group of the Italian Society of Cardiovascular Echocardiography]. / Modalità di utilizzazione dell'ecocardiogramma in pazienti ambulatoriali. Ruolo del cardiologo per l'appropriatezza della prescrizione. Gruppo Ligure della Società Italiana di Ecografia Cardiovascolare.

Concerns about the increasing medical care costs are causing the medical community to focus its attention on the appropriate of diagnostic tests such as echocardiography. Prerequisite to a better utilization of the limited economic resources assigned to our health care system is an analysis of how, why, and with which results diagnostic tests with a widespread use and relevant cost, like echocardiography, are requested. During the last 2 weeks of September 1994, a transversal, observational study was carried out at 13 hospital echocardiographic laboratories. Ordering physician characteristics, reasons for ordering the test, cardiological diagnostic tests previously performed and their relationship with the test results, were evaluated with a questionnaire completed by the physician who performed the test, in all the out-patients undergoing echocardiogram in that fortnight. Five hundred and sixteen consecutive questionnaires were successfully completed. Fourty-five percent of the echocardiograms were ordered by cardiologists, 35% by general practitioners, 10% by internists, and 10% by other specialists. Hypertension (16.4%) and ischemic heart disease (14.8%) were the most common indications for the test, followed by palpitations or arrhythmias (7.5%), mitral valve prolapse or mitral valve disease (7.3%), chest pain or angina pectoris (6.3%), cardiac murmur (5.5%), dyspnea or heart failure (5.2%), aortic valve disease (5%), prosthetic heart valve evaluation (4.6%), others (27%). Before undergoing the echocardiogram, 433 (84%) patients underwent an electrocardiogram, 242 (47%) a cardiological clinical evaluation, 196 (38%) a chest X-ray, and 191 (37%) had had a previous echocardiogram. The most common echocardiographic diagnosis was normal (29.2%) followed by hypertensive heart disease (16.2%), mitral valve disease (12.3%), aortic valve disease (10.5%), ischemic heart disease (9.3%), cardiomyopathy (4.9%) normal prosthetic heart valve function (4.5%), pericardial effusion (3.8%), others (11.3%). Among the echocardiograms ordered by cardiologists, 21.8% were normal in comparison with 35.4% of those ordered by general practitioners (p < 0.004), 35.3% of those ordered by internists (p = 0.04), 35.3% of those ordered by other specialists (p = 0.04). Among the 284 patients whose echocardiograms were not requested by a cardiologist, only 215 (76%) had undergone an electrocardiogram and only 68 (24%) a clinical evaluation by a cardiologist. In these patients, the frequency of normal echocardiograms was not influenced by having undergone a previous electrocardiogram or a chest X-ray. Conversely, patients in whom the echocardiogram was ordered after a cardiology consult showed a significant lower frequency of normal results compared to patients not evaluated by a cardiologist (23% vs 39%; p < 0.05). More than 50% of the echocardiograms performed in out-patients are ordered by physicians who are not cardiologists. Among these echocardiograms, about 1 out of 3 results normal. This finding suggests an improper use of echocardiogram as a screening tool by non-cardiologists in out-patients. A preceding clinical evaluation by a cardiologist, but not an electrocardiogram or a chest X-ray alone, may determine a more appropriate use of the test being associated with a reduced frequency of normal results.

The influence of age on the flash visual evoked potentials.

The effect of age on flash visual evoked potentials was investigate in 148 normal subjects aged 6 yo 84 years. The occurrence of the P1 wave progressively increased with age, while the P2 wave was recordable in all the subjects. There were significant effects of age on the P2 latency (p < or = 0.01). The latency of the N1 and N2 waves significantly changed with age. In particular, the N2 wave that occurred in the absence of the P1 wave had a latency similar to that of the N1 wave was present. We suggest that the cases apparently without the P1 wave could be explained with a merging of this was with the P2 wave in a major single deflection.

A Detailed Monte Carlo Study of Multiple Scattering Contamination in Compton Tomography at 90 degrees.

A low dose technique has been recently proposed for tomographic studies of the lung, which makes use of a gamma camera to detect 90 degrees Compton-scattered photons from external planar gamma source. In this paper, we present a detailed Monte Carlo study of this technique. A 20 x 20 x 20 cm3 water phantom was simulated as a target and a large gamma camera equipped with an imaging collimator as a detector. The multiple scattering contamination of the single scattered signal was studied as a function of the source-detector geometry and of the incident energy in the range 100-500 keV. The multiple to single scatter ratio has an approximate 1/E0.7 dependence and increases almost linearly with the phantom depth and the transversal thickness at 90 degrees . Simulation has been also performed with a 16 x 16 x 10 cm3 sawdust phantom of 0.3 g/cm3 density; the Monte Carlo results agree to within a few percent with experimental data.

Reproductive toxicology of fenbufen.

The reproductive toxicology of gamma-oxo[1,1-biphenyl]-4-butanoic acid (fenbufen), a new non-steroidal antiinflammatory, analgesic and antipyretic agent was investigated in rats, rabbits and mice after oral administration. This drug showed no evidence of teratogenic or other embryotoxic effects in these three species when administered during organogenesis at dosages as high as 40 mg/kg/day. In male rats no effects on fertility and general reproductive performance were noted except those related to the ulcerogenic effect of this compound. In female rats there were no apparent effects on gonadal function, estrus cycle, mating behavior or fertility. Maternal dystocia and increased mortality of offspring (stillbirths) were observed in rats at doses of 20 mg/kg/d and greater. Increased duration of gestation and prolonged parturition were seen also in rats. Prostaglandin inhibition has been produced in vitro and in vivo by fenbufen and/or its metabolite, biphenyl acetic acid. This suggests that fenbufen shares with other non steroidal antiinflammatory agents the potential for inhibiting prostaglandin-mediated reproductive processes in the human.