Reduction of embryonic intracellular pH: a potential mechanism of acetazolamide-induced limb malformations

The effects of acetazolamide on the developing rodent limb bud were postulated to result from a reduction of intracellular pH (pHi). Embryonic intracellular pH was calculated from transplacental distribution of the weak acid, 5,5'-dimethyloxazolidine-2,4-dione, in teratogenically sensitive (C57BL/6) and resistant (SWV) inbred mice. pHi was reduced by acetazolamide treatment in C57 embryos and limb buds but not in SWV samples. Acetazolamide teratogenesis can be exacerbated by coadministration of amiloride, presumably through inhibition of Na+/H+ exchange attributable to the latter agent. pHi reduction after such treatment was more profound than after acetazolamide alone, providing further support for the central hypothesis. pH was also reduced in other embryonic (embryo plasma) and extraembryonic compartments (exocoelomic fluid, amniotic fluid). pH changes in these compartments could also lead or contribute to abnormal development.     

Cup containment and orientation in cemented total hip arthroplasties

We reviewed the radiographs of 864 Charnley and STH (Zimmer) cemented total hip arthroplasties with a mean follow-up of seven years (maximum 16 years). Survivorship analysis was used to assess the correlation between radiographic performance and the bony containment or the coronal orientation of the acetabular cup. The cup orientation and containment were interrelated; all vertically oriented cups were completely contained, whereas 25% of more horizontal cups were only partially contained. Completely contained cups had significantly lower incidences of complete cement-bone radiolucency (p = 0.02) and of wear (p = 0.09). Vertically oriented cups had a lower incidence of continuous radiolucency than neutrally oriented cups, but this was not statistically significant (p = 0.25). Our results confirm the importance of complete bony containment, and also indicate that it is better to accept vertical orientation and obtain full bony coverage than to have a more horizontal orientation with partial containment.     

Serum bone-gla protein after fracture

Serum bone Gamma-carboxyglutamic acid (bone-gla) protein (BGP), a marker of bone formation, was measured in serial blood samples drawn from 14 patients who had fractured at least one of their tibial or femoral diaphyses and from two other patients who had sustained major trauma without fracture but who had been immobilized. A total of 85 samples were taken and analyzed during the first three months after the fractures occurred. Serum BGP significantly increased and positively correlated with the time that had elapsed after the fracture, with an average twofold increase after two months. The fracture site and the duration of immobilization had no influence on the serum BGP levels. Serum BGP levels from the two non-fractured cases increased in the first two weeks with no subsequent consistent trend. These data suggest that serum BGP increases one to two months after a major fracture, possibly as a manifestation of bone repair. Further studies are required to determine the potential clinical value of serum BGP in the management of such patients.     

No excess of DR*3/4 in Ashkenazi Jewish or Hispanic IDDM patients

The gene frequencies, haplotype relative risks, and zygotic assortments of HLA-DR in three ethnically defined samples of insulin-dependent diabetes mellitus (IDDM) patients were determined in a prospective family study. Although DR3 and DR4 were positively associated with IDDM in the probands of 123 northern European, 94 Ashkenazi Jewish, and 49 New York Hispanic families, significant excess of DR*3/4 heterozygotes was observed only among the probands from families of northern European ancestry. There was also a significant decrease in the frequency of Bw62,DR4 haplotypes derived by northern European patients from their mothers compared with their fathers. This difference, together with data reported in the literature, suggests that the expressivity of the susceptible genotype(s) in IDDM patients may be modified by protective maternal effects associated with Bw62,DR4 and probably other DR4 haplotypes. Samples of IDDM patients from populations with high frequencies of these modifiers should have different DR-gene frequencies contributed by fathers and mothers, capable of accounting for the observed Hardy-Weinberg disequilibrium. We postulate that, because the mechanism of action of these modifiers is distinct from that of the susceptibility gene, the difference must be considered in devising strategies for elucidation of the mode of inheritance of the disease and for understanding the molecular nature of the susceptibility.     

Diagnosis of ligament rupture of the ankle joint: Physical examination, arthrography, stress radiography and sonography compared in 160 patients after inversion trauma

We prospectively enrolled 160 consecutive patients with inversion trauma of the ankle in a diagnostic protocol that included physical examination within 2 days and at 5 days after trauma, arthrography, stress radiography, and ultrasonography. 135 patients had pathological lateral ligament laxity on the later physical examination or lateral ligament rupture diagnosed on arthrography and they were operated on. 122 of these patients had ligament ruptures.

At clinical follow-up after a minimum of half a year, all of the patients who were not operated on had stable joints without signs of previous ligament ruptures.

Delayed physical examination at 5 days after the injury led to the highest overall sensitivity (96%) and specificity (84%) for the detection of a ligament rupture. Additional diagnostic procedures, at a considerable cost, yielded little additional information.     

New peritoneal dialysis solutions

Summary: Current peritoneal dialysis solutions are not biocompatible, particularly in respect to low pH, high osmolality and use of lactate. In addition, glucose is not an ideal osmotic agent. Recent advances in the formulation of peritoneal dialysis fluids aim to provide a more physiological environment to preserve membrane integrity. the effects of pH and lactate have been overcome by the use of bicarbonate based solutions whilst icodextrin (glucose polymers) often prolonged ultrafiltration in spite of being isomotic to uraemic plasma. Future formulations will see a combination of osmotic agents (including amino acids) and bicarbonate to achieve a more biocompatible solution whilst still meeting the ultrafiltration needs of the patients. Additives (glycosaminoglycans, procysteine) may protect the peritoneum from free radical injury.     

Food choice in response to computer-generated nutrition information provided about meal selections in workplace restaurants

Aim : The study was designed to determine the effect of computerized nutrition information on consumer food choice in two workplace restaurants, one in which customers had to pay for their lunch and the other providing a free lunch. Methods : Customers entering the restaurants were asked to make selections from the menu on a computer screen. The energy, saturated fatty acids, non-milk extrinsic sugars and non-starch polysaccharide content of the meal selected was displayed graphically in proportion to the dietary reference values. They were given the opportunity to change their selected meal and the composition of all meals was recorded. Results : The nutritional composition of the first meal provoked 16% of customers to make a second selection. The proportion of energy in the first selection had been 31% higher for saturated fatty acids and 23% higher for non-milk extrinsic sugars than the first selection made by people who were satisfied with their first choice. In their second attempt they succeeded in reducing both nutrients to levels similar to those present in the meals selected by people who had been satisfied with their first selection. Customers>> selections for non-starch polysaccharide and energy did not differ between the groups. The main changes made by customers to achieve improved second choices were to omit dishes (44%), add dishes (19%), make changes within a menu category (46%), and make changes from one menu category to another (26%). Conclusion : It was concluded that provision of graphical nutrition information on a computer screen could be used by a subset of the users of both restaurants to enable them to improve their menu selections to a similar composition to that selected by the other people who used the computer system.