The effects of intraduodenal bile acid administration on biliary secretion of ionized calcium and carbonate in man

The importance of calcium in gallstone formation is increasingly recognized. Calcium carbonate is an important constituent of gallbladder stones and may be present in the nidus of cholesterol stones. Secondary deposition of calcium carbonate on the surface of cholesterol gallstones is an important reason for failure of oral bile acid dissolution therapy. We sought to determine the effects of bile acids on the crystallization conditions of calcium carbonate in bile. We studied 18 patients with choledocholithiasis with a percutaneous or endoscopically placed catheter high in the biliary tree. Samples of bile in the basal state and following replacement of the bile acid pool with cholic acid, chenodeoxycholic acid and ursodeoxycholic acid were analyzed for total calcium, ionized calcium, bicarbonate and carbonate, and the saturation index for calcium carbonate was calculated. Hepatic bile in the basal state was supersaturated with calcium carbonate. Total calcium concentrations rose linearly with rising bile acid concentrations but ionized calcium was maintained in a relatively narrow range. These data are consistent with an important role for bile acids in binding calcium. Extrapolation of the linear regressions between bile acid concentration and calcium concentrations suggested that in the absence of bile acids, biliary calcium concentrations are in passive equilibrium with plasma. Chenodeoxycholic acid and ursodeoxycholic acid caused a bicarbonate-rich choleresis and significantly augmented the saturation index for calcium carbonate, whereas cholic acid caused no change. In contrast with animal models, the apparent choleretic activity of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid was similar, and no hyper-choleresis was observed with ursodeoxycholic acid. Chenodeoxycholic acid and ursodeoxycholic acid therefore increase the thermodynamic possibility for calcium carbonate precipitation.     

Endoscopic modified Lothrop procedure after failure of primary endoscopic sinus surgery: a meta‐analysis

Background

The endoscopic modified Lothrop procedure (EMLP) has been used as a salvage technique for frontal sinusitis following failed endoscopic sinus surgery (ESS). We aim to examine the safety and efficacy of the EMLP following failure of primary ESS.

Methods

All English‐language publications from 2000 to 2016 reporting the use of EMLP after primary ESS were identified using the PubMed database and evaluated per Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Random effects summaries of patient demographics, comorbidities, and surgical outcomes were obtained through meta‐analysis.

Results

Eleven studies constituting 778 patients were included and 86.5% had chronic rhinosinusitis (CRS). Mean follow‐up duration was 28.4 months. The mean number of surgeries prior to EMLP was 3.5. Symptom improvement was reported in 82.3%. Subgroup analysis of 7 studies in which all 357 patients had CRS revealed a mean follow‐up of 31.5 months. Symptom improvement occurred in 75.9% of cases and 23.1% experienced polyp recurrence. The cerebrospinal fluid leak rate was 2.5%. Restenosis of the neo‐ostium occurred in 17.1% with complete closure occurring in 3.9% of cases. The reoperation rate after EMLP was 9.0%. Aspirin sensitivity was associated with an increased risk of cerebrospinal fluid (CSF) leak (p = 0.0339) and a reduced incidence of neo‐ostium closure (p = 0.0001). Aspirin sensitivity and asthma were associated with a reduced incidence of reoperation (p ≤ 0.001) and increased symptom improvement (p < 0.005). Restenosis or closure of the frontal neo‐ostium was associated with less symptom improvement (p < 0.04) but not with reoperation.

Conclusion

The EMLP is an effective salvage procedure for refractory frontal sinusitis based on data from higher‐volume centers.

     

Deficit in implicit motor sequence learning among children and adolescents with spastic Cerebral Palsy

Skill learning (SL) is learning as a result of repeated exposure and practice, which encompasses independent explicit (response to instructions) and implicit (response to hidden regularities) processes. Little is known about the effects of developmental disorders, such as Cerebral Palsy (CP), on the ability to acquire new skills. We compared performance of CP and typically developing (TD) children and adolescents in completing the serial reaction time (SRT) task, which is a motor sequence learning task, and examined the impact of various factors on this performance as indicative of the ability to acquire motor skills. While both groups improved in performance, participants with CP were significantly slower than TD controls and did not learn the implicit sequence. Our results indicate that SL in children and adolescents with CP is qualitatively and quantitatively different than that of their peers. Understanding the unique aspects of SL in children and adolescents with CP might help plan appropriate and efficient interventions.     

Physicians' perspectives on the uncertainties and implications of chromosomal microarray testing of children and families

Chromosomal microarray analysis (CMA) has improved the diagnostic rate of genomic disorders in pediatric populations, but can produce uncertain and unexpected findings. This article explores clinicians' perspectives and identifies challenges in effectively interpreting results and communicating with families about CMA. Responses to an online survey were obtained from 40 clinicians who had ordered CMA. Content included practice characteristics and perceptions, and queries about a hypothetical case involving uncertain and incidental findings. Data were analyzed using nonparametric statistical tests. Clinicians' comfort levels differed significantly for explaining uncertain, abnormal, and normal CMA results, with lowest levels for uncertain results. Despite clinical guidelines recommending informed consent, many clinicians did not consider it pertinent to discuss the potential for CMA to reveal information concerning biological parentage or predisposition to late‐onset disease, in a hypothetical case. Many non‐genetics professionals ordering CMA did not feel equipped to interpret the results for patients, and articulated needs for education and access to genetics professionals. This exploratory study highlights key challenges in the practice of genomic medicine, and identifies needs for education, disseminated practice guidelines, and access to genetics professionals, especially when dealing with uncertain or unexpected findings.     

Knowledge,attitudes & barriers to condom use among female sex workers and truck drivers in Uganda: a mixed-methods study

Background

There is limited documentation on knowledge, attitudes and barriers to condom use among female sex workers (FSWs) and truck drivers (truckers).

Objective

To explore knowledge, attitudes and barriers to condom use among FSWs and truckers operating along major transport corridors in Uganda

Methods

Structured questionnaires were administered to explore FSWs'' and truckers'' knowledge of and attitudes towards condom use among 259 FSWs and 261 truckers. Qualitative data were collected on barriers to condom use using focus group discussions. Quantitative data were analyzed using SPSS while qualitative data were audio-recorded, transcribed and thematically analyzed.

Results

Condom knowledge was high with 97% of FSWs and 95% of truckers agreeing with the statement, “using condoms properly and consistently reduces risk of HIV infection”. Attitudes towards condom use were generally favorable with 91% of FSWs and 82% of truckers agreeing with the statement, “condom use is the best method of HIV prevention”. Qualitative findings show that poverty, refusal to use condoms by male partners, alcohol use before sex and beliefs that condoms ‘kill the mood for sex’ remain key barriers to consistent condom use.

Conclusions

Consistent condom use among FSWs and truckers is still hampered by economic and relationship factors.     

Negative computer‐imaged ThinPrep Pap test and positive hybrid capture2 HPV co‐testing results: A quality assurance review

Women ≥30 years of age with negative (?) Pap tests and positive (+) HPV co‐test results have a higher prevalence and cumulative risk of developing high‐grade cervical intraepithelial neoplasia (CIN 2+). Thus, the current management in these women is to repeat co‐test in 12 months or immediate reflex genotyping for HPV16 or HPV 16/18. If genotyping is not an option, timely quality assurance (QA) rescreen of such Pap tests may be a valuable alternative. All ThinPrep Pap tests (TPPT) interpreted as negative for intra epithelial lesion (NILM) or NILM with reactive cellular changes (NILM/RCC) and a (+) high‐risk HPV [Hybrid Capture 2 (HC2), Qiagen, Hilden, Germany] co‐test result over a 45‐month period (10/2009‐06/2013) underwent monthly QA review. The TPPT were screened by the TP Imaging System [TIS, Hologic Inc., Bedford, MA]. Twenty five thousand six hundred and seventy five (18%) NILM and NILM/RCC TPPT of a total of 141,548 TPPT underwent HPV co‐test. HPV test was (+) in 2,300 (8.9%) TPPT cases. HPV (+) cases by age group were <30 years, 486 (21%), and ≥30 years, 1,814 (79%). Upon QA review, 10 cases (0.4%) were reclassified, with significant findings in three cases in ≥30 years. Two cases showed high‐grade squamous intraepithelial lesion (HSIL) on repeat Pap, and one case showed endocervical adenocarcinoma in situ (AIS) on biopsy. Timely QA review of HPV (+) Pap (?) co‐tests is a valuable monitor. Ninety percentage of reclassified cases were in ≥30 age group and 70% were originally signed out by using TIS 22 Field of View (FOV) only. Three reclassified cases had significant findings on follow up (F/U). Diagn. Cytopathol. 2015;43:763–769. © 2015 Wiley Periodicals, Inc.