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.     

A method for evaluating systems of epidemiological surveillance

Epidemiological surveillance is the systematic collection, analysis and dissemination of health data for the planning, implementation and evaluation of public health programmes. Established surveillance systems should be regularly reviewed on the basis of explicit criteria of usefulness, cost and quality; systems should be modified as a result of such review. Attributes of quality include: (i) sensitivity, (ii) specificity, (iii) representativeness, (iv) timeliness, (v) simplicity, (vi) flexibility and (vii) acceptability. To date, evaluation of surveillance systems has been limited in scope and content. The evaluation method proposed in this article offers an organized approach to the evaluation of epidemiological surveillance systems. The usefulness of a surveillance system is measured by whether it leads to prevention or control or a better understanding of adverse health events. The measure can be qualitative, in terms of the subjective views of those using the system, or quantitative in terms of the impact of surveillance data on policies, interventions or the occurrence of a health event. The cost of a system includes indirect as well as direct costs, and should be measured in relation to the benefits obtained, such as reduction of medical-care expenses and of time lost from work. All elements of the system should be included in the cost: data collection, analysis and dissemination. The sensitivity of a surveillance system is its ability to detect health events (completeness of reporting). Its specificity is inversely proportional to the number of false positives it reports. Reports of a disease that do not meet the case definition are false positives, and may result in resources being wasted in investigating them.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Considerations in the choice of sutures for wound closure of the genitourinary tract

The ideal suture for use within the urinary tract should maintain its tensile strength until wound repair is satisfactory and then it should undergo rapid total absorption without promoting stone formation. The bladder has a great potential for repair, attaining 100 per cent of the strength of the unwounded tissue in 14 to 21 days. Braided synthetic absorbable sutures appear to be suited ideally for closure of incised wounds of a urinary conduit. They maintain their tensile strength for approximately 21 days, during which time the healing tissues regain strength rapidly. Because sutures are foreign bodies and have access to urine, they may serve as a nidus for stone formation. Several factors that have been identified as important determinants of foreign body urolithiasis include the presence of urine, urine volume and pH, infection, physical and chemical configuration of the foreign body, and animal species. The incidence of suture urolithiasis is related directly to the duration in which the sutures are present in the urinary tract. Consequently, absorbable sutures are preferred over nonabsorbable sutures for closure of wounds of the urinary conduit. In the absence of infection braided synthetic absorbable sutures have distinct advantages over gut sutures for closure of urinary tract wounds. They are absorbed by nonenzymatic hydrolysis in a predictable manner with limited inflammatory response. In contrast, gut sutures have an unpredictable absorption rate by enzymatic degradation and elicit an exaggerated inflammatory response. Because infected urine, especially Proteus species, accelerates the degradation of absorbable synthetic sutures to a greater degree than gut sutures, wound closure in the presence of infection should be accomplished with the absorbable natural fiber suture. Nonabsorbable sutures or staples should not be used in the urinary tract because they predictably promote urolithiasis.     

Costello syndrome: Clinical phenotype,genotype, and management guidelines

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence‐based guidelines due to the lack of data for this rare condition.     

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.