Bone disease in primary biliary cirrhosis: Lack of association with distal renal tubular acidosis

Background and Aims: Primary biliary cirrhosis (PBC) might be complicated by osteoporosis, whose etiology remains unknown but seems to be multifactorial. Prevalence rates of 30% to 60% for distal renal tubular acidosis (DRTA) have been reported in PBC patients, generally as incomplete DRTA. Although it is undisputed that a reduced bone mineral density (BMD) is the expected outcome among patients who have been suffering from longstanding chronic metabolic acidosis, it is unclear if incomplete DRTA is also associated with metabolic bone disease in PBC patients. The present study was undertaken to compare the BMD of PBC patients with and without DRTA.
Methods: The BMD of 23 PBC patients (11 with DRTA and 12 without), all with normal clearance of creatinine, was assessed by dual energy radiograph absorptiometry. The diagnosis of DRTA was made if the urine pH was above 5.4 in all samples after the oral acid overload, showing tubular inability to acidify urine in the presence of test-induced systemic metabolic acidosis.
Results: Densitometric signs of osteoporosis were found in 82% of DRTA cases and in 83% of patients without DRTA (difference not significant). There were no significant differences in BMD measurement, T and Z scores of patients with and without DRTA.
Conclusions: The present study could not support a correlation between the presence of DRTA and the bone loss observed in PBC patients.     

Paramyosin is the Schistosoma mansoni (Trematoda) homologue of antigen B from Taenia solium (Cestoda)

Antigen B, a major antigen of the cestode parasite Taenia solium, has been purified and a portion of amino acid sequence obtained. Paramyosin of the trematode parasite Schistosoma mansoni, an immunogenic protein that has shown promise as a vaccine candidate, has several biochemical and immunological properties in common with antigen B. A full-length cDNA clone of S. mansoni paramyosin has been obtained and the predicted translation product contains a sequence that is highly homologous to the sequence obtained for antigen B. The predicted amino acid composition and isolectric point of paramyosin are nearly identical to those established for antigen B. Recombinant S. mansoni paramyosin, expressed in Escherichia coli as a fusion protein with beta-galactosidase, was recognized by antisera against T. solium antigen B. We conclude from these results that S. mansoni paramyosin and T. solium antigen B are homologous proteins. Since S. mansoni paramyosin is thought to be a muscle protein and T. solium antigen B a secreted glycoprotein with anti-complement activity, this conclusion raises some interesting questions regarding the role of this class of proteins in the host-parasite relationship.     

Pneumothorax and other lung diseases: effect of altered resolution and edge enhancement on diagnosis with digitized radiographs

Prior studies have shown that pneumothorax is one of the more difficult entities to diagnose with digitized radiography. This study was designed to test whether increasing resolution from 1.25 to 2.5 line pairs per millimeter (lp/mm) and image processing (edge enhancement from unsharp masking) would increase accuracy and confidence in the diagnosis of pneumothorax, as well as normal cases and other forms of lung disease. Conventional radiographs were digitized with use of a laser reader and then reformatted as film hard copy. Eleven observers read 35 cases reformatted in three different ways (1.25 lp/mm, 2.5 lp/mm, 1.25 lp/mm unsharp mask). The images with finer resolution (2.5 lp/mm) and unsharp mask images were superior to those with coarser resolution (1.25 lp/mm) for the diagnosis of pneumothorax. There was no difference in diagnostic accuracy for normal patients. For abnormalities other than pneumothorax, the unsharp mask images were significantly worse. Confidence in the diagnosis of pneumothorax and other abnormalities was highest with the finest resolution (2.5 lp/mm).     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.     

Biphasic materials for bone grafting and hyperthermia treatment of cancer

Three biphasic materials have been synthesized from a magnetic glass-ceramic (Si-Ca-Fe) and a bioactive sol-gel glass (Si-P-Ca). The ratios of glass-ceramic:sol-gel glass used in this work were 1:1, 2:1, and 5:1. These materials show bioactive and magnetic properties and can be used as thermoseeds for hyperthermia treatment of bone tumors. The sol-gel glass content affects the textural properties of the glass-ceramic, giving rise to porosity, which plays a fundamental role in the formation of an apatite-like layer on the surface. On the other hand, as the sol-gel glass content increases, the magnetic properties change due to the diffusion of Fe ions to the glassy phases of the biphasic materials. The biphasic nature of these materials allows the changing of both properties, depending on the requirements of the patient.     

Human leukocyte antigen matching and fetal loss: results of a 10 year prospective study

The role that maternal and fetal human leukocyte antigen (HLA) genes play in pregnancy is unknown, but it has been suggested that fetuses whose HLA alleles do not differ from maternal alleles (i.e. histocompatible fetuses) are more likely to be aborted than fetuses with HLA alleles that differ from maternal alleles (i.e. histoincompatible fetuses). To elucidate the role of HLA compatibility in pregnancy, we tested the hypothesis that couples who match for HLA alleles or haplotypes would have reduced fertility because only these couples could produce histocompatible fetuses. We conducted a 10 year prospective study of HLA matching and pregnancy outcome in 111 Hutterite couples, providing information on 251 pregnancies. A logistic regression analysis was performed to determine the effects of HLA matching at HLA regions and loci on pregnancy outcome (fetal loss versus delivery). Significantly increased fetal loss rates were observed among couples matching for the entire 16-locus haplotype (P = 0.002). Among the individual loci, loss rates were increased among couples matching for HLA-B (P = 0.019), HLA-C (P = 0.033) and the complement component, C4 (P = 0.043). We interpret these results as evidence that matching for the entire 16-locus haplotype and/or alleles at an HLA-B-linked locus confers significant risk for fetal loss.      

Attitudes about genetic risk of couples undergoing in-vitro fertilization

Many couples undergoing in-vitro fertilization (IVF) are at a higher risk of having a child with a genetic abnormality. In a sample of 55 consecutive couples starting IVF, only 33% had no genetic risk factor. The most common genetic risks were advanced maternal age and possible abnormalities associated with severe male infertility. Despite education on these risks, 71% of couples had no interest in receiving formal genetic counselling. Only 14% of couples at risk would consider using a gamete donor to avoid transmitting a genetic disorder to a child. The triple test to screen for fetal abnormalities was acceptable to 82% of couples, but only 47% planned to have amniocentesis or chorionic villi sampling. Couples were significantly more likely to opt for prenatal testing if they would consider terminating a pregnancy should the fetus have a severe genetic abnormality (P < 0.01). Roman Catholic couples tended to have more conservative attitudes about pregnancy termination. Socio-economic status and whether the infertility factor was male or female were not predictors of a couple's attitudes.