The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission

Factors involved in the stability of trinucleotide repeats during transmission were studied in 139 families in which a full mutation, premutation or intermediate allele at either FRAXA or FRAXE was segregating. The transmission of alleles at FRAXA, FRAXE and four microsatellite loci were recorded for all individuals. Instability within the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for FRAXE) was extremely rare; only one example was observed, an increased in size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were unstably transmitted. Instability was more frequent for FRAXA intermediate alleles that had a tract of pure CGG greater than 37 although instability only occurred in two of 13 such transmissions: the changes observed were limited to only one or two repeats. Premutation FRAXA alleles over 100 repeats expanded to a full mutation during female transmission in 100% of cases, in agreement with other published series. There was no clear correlation between haplotype and probability of expansion of FRAXA premutations. Instability at FRAXA or FRAXE was more often observed in conjunction with a second instability at an independent locus suggesting genomic instability as a possible mechanism by which at least some FRAXA and FRAXE mutations arise.      

Determination of gallium concentration in "blood-free" tissues using a radiolabeled blood marker

Radioiodinated serum albumin has been used as a blood marker to define and quantitate physiological volumes for 12 organs and tissue types. The concentration of gallium-67 in "blood-free" tissues of rats was also determined at various times after intravenous administration. Tissues were divided into two kinetically distinguishable types based on reported nonuniform distribution of the blood marker and the gallium distribution observed in the present study. Gallium distribution into the liver and spleen was observed to be slow, with a discernable accumulation phase followed by monoexponential elimination. In contrast, gallium accumulation into the stomach, small and large intestines, heart, lung, skin/adipose tissue, and muscle was rapid and elimination was monophasic.     

Lipoma of the temporal region: a rare case series

Lipomas are common benign tumours that can occur in most parts of the body. Lipomas arising from the deep temporal fat pad, found between the two layers of the deep temporal fascia, are rare, however; there has been only one documented case report to our knowledge. We describe a second case arising from the temporal fat pad in a patient treated at our unit, having previously reported the first one, and discuss the relevant anatomy and management.     

Evaluating and Strengthening the Evidence for Nutritional Bone Research: Ready to Break New Ground?

A healthy diet is essential to attain genetically determined peak bone mass and maintain optimal skeletal health across the adult lifespan. Despite the importance of nutrition for bone health, many of the nutritional requirements of the skeleton across the lifespan remain underexplored, poorly understood, or controversial. With increasingly aging populations, combined with rapidly changing diets and lifestyles globally, one anticipates large increases in the prevalence of osteoporosis and incidence of osteoporotic fractures. Robust, transparent, and reproducible nutrition research is a cornerstone for developing reliable public health recommendations to prevent osteoporosis and osteoporotic fractures. However, nutrition research is often criticized or ignored by healthcare professionals due to the overemphasis of weak science, conflicting, confusing or implausible findings, industry interests, common misconceptions, and strong opinions. Conversely, spurious research findings are often overemphasized or misconstrued by the media or prominent figures especially via social media, potentially leading to confusion and a lack of trust by the general public. Recently, reforms of the broader discipline of nutrition science have been suggested and promoted, leading to new tools and recommendations to attempt to address these issues. In this perspective, we provide a brief overview of what has been achieved in the field on nutrition and bone health, focusing on osteoporosis and osteoporotic fractures. We discuss what we view as some of the challenges, including inherent difficulties in assessing diet and its change, disentangling complex interactions between dietary components and between diet and other factors, selection of bone-related outcomes for nutrition studies, obtaining evidence with more unbiased designs, and perhaps most importantly, ensuring the trust of the public and healthcare professionals. This perspective also provides specific recommendations and highlights new developments and future opportunities for scientists studying nutrition and bone health. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Gastrointestinal absorption of phenytoin from an oil-in-water microemulsion

The absorption profile of phenytoin Na emulsion were examined compared to that of phenytoin suspension after oral administration in the rat. The corn oil-in-water emulsion, particle size of 184±57.8 nm, was prepared using a microfludizer, and phenytoin Na added by shaft homogenizer. The phenytoin emulsion or suspension, 100 mg/kg, were intubated intragastrically using oral dosing needle and blood samples were withdrawn via an indwelling cannula from the conscious rat. Plasma concentrations of phenytoin were measured with HPLC using phenacetin as an internal standard. The plasma concentration versus time data were fitted to a one compartment open model and the pharmacokinetic parameters were calculated using the computer program, Boomer. The phenytoin plasma concentrations from the emulsion at each observed time were about 1.5–2 times higher than those from the suspension, significantly at time of 5, 6 and 7 hr after administration. The absorption (k_a) and elimination rate constant (k_e) were not altered significantly, however the AUC increased from 65.6 to 106.7 μg·hr/ml after phenytoin suspension or emulsion oral administration, respectively. From an equilibrium dialysis study, the diffusion rate constant (k_IE) was considerably higher from the phenytoin Na emulsion (0.0439 hr⁻¹) than phenytoin suspension (0.0014 hr⁻¹).     

Fractures of the patella after total knee replacement

Pateller fractures in association with total knee replacement are uncommon, but potentially a cause of an unsatisfactory clinical outcome. Patient, implant, and technical factors are important predisposing causes of these patellar fractures. Prevention is the best treatment. Important outcome criteria include the integrity of the extensor mechanism, patellar implant fixation, and anatomic location. Patients requiring operative intervention often have an unsatisfactory outcome.     

Sudden death in early infancy due to delayed cardiac tamponade complicating central venous line insertion and cardiac catheterization.

Cardiac tamponade is an unusual cause of sudden death in the first weeks of life. We present two cases of cardiac tamponade in the neonatal period that caused death 5 to 6 days following the insertion of intracardiac lines, to draw attention to the possibility of a "delay phenomenon" between the time of the initial procedure and the occurrence of sudden and unexpected death. The presence of blood or clear fluid within the pericardial sac should prompt careful examination of the myocardium for small foci of traumatic damage, particularly when the fluid is under pressure or of large volume. Although the development of circulatory impairment or shock in the days following central line insertion or catheterization raises the possibility of tamponade, it should be noted that sudden death may occur in the absence of any significant antemortem symptoms or signs.