G6PD Hillbrow: A New Variant of Glucose-6-Phosphate Dehydrogenase Associated with Drug-induced Haemolytic Anaemia

A new genetic variant of the red cell enzyme glucose-6-phosphate dehydrogenase is described. It was observed in a patient presenting with severe haemolytic anaemia and renal failure following ingestion of an overdose of Beserol (paracetamol and chlormezanone). The enzyme in the red cell had 12% of the activity of a normal B+ control, but only slightly lower activity in the kidney compared with a normal control. The red cell enzyme showed normal electrophoretic mobility and thermostability, a biphasic pH optimum curve, higher than normal utilization of the substrate analogues 2-deoxy-glucose-6-phosphate and deamino-NADP, and lower than normal Michaelis constants for both substrates, glucose-6-phosphate and NADP. The enzyme was strongly inhibited in vitro by high concentrations of paracetamol and chlormezanone. The extent of inhibition was similar to that for the enzyme from a normal B+ individual.     

Evaluation of the Pharmacokinetic Interaction between Repeated Doses of Rifapentine or Rifampin and a Single Dose of Bedaquiline in Healthy Adult Subjects

This study assessed the effects of rifapentine or rifampin on the pharmacokinetics of a single dose of bedaquiline and its M2 metabolite in healthy subjects using a two-period single-sequence design. In period 1, subjects received a single dose of bedaquiline (400 mg), followed by a 28-day washout. In period 2, subjects received either rifapentine (600 mg) or rifampin (600 mg) from day 20 to day 41, as well as a single bedaquiline dose (400 mg) on day 29. The pharmacokinetic profiles of bedaquiline and M2 were compared over 336 h after the administration of bedaquiline alone and in combination with steady-state rifapentine or rifampin. Coadministration of bedaquiline with rifapentine or rifampin resulted in lower bedaquiline exposures. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the maximum observed concentration (C_max), area under the concentration-time curve to the last available concentration time point (AUC_0–t), and AUC extrapolated to infinity (AUC_0–inf) of bedaquiline were 62.19% (53.37 to 72.47), 42.79% (37.77 to 48.49), and 44.52% (40.12 to 49.39), respectively, when coadministered with rifapentine. Similarly, the GMRs and 90% CIs for the C_max, AUC_0–t, and AUC_0–inf of bedaquiline were 60.24% (51.96 to 69.84), 41.36% (37.70 to 45.36), and 47.32% (41.49 to 53.97), respectively, when coadministered with rifampin. The C_max, AUC_0–t, and AUC_0–inf of M2 were also altered when bedaquiline was coadministered with rifapentine or rifampin. Single doses of bedaquiline, administered alone or with multiple doses of rifapentine or rifampin, were well tolerated, with no safety concerns related to coadministration. Daily administration of rifapentine to patients with tuberculosis presents the same drug interaction challenges as rifampin and other rifamycins. Strong inducers of the cytochrome P450 isoenzyme CYP3A4 should be avoided when considering the use of bedaquiline. (This study is registered at clinicaltrials.gov under identifier {"type":"clinical-trial","attrs":{"text":"NCT02216331","term_id":"NCT02216331"}}NCT02216331.)     

Intestinal ischemia due to vascular elastosis caused by metastasizing carcinoid tumor of Meckel's diverticulum

A case of a carcinoid tumor arising in a Meckel's diverticulum is reported. By the time of detection, the tumor had spread to the mesentery causing ischemia of the small intestine due to the associated vascular elastosis.     

Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndrome

AIM: To study the different endocrine cell types in the oxyntic mucosa of patients with irritable bowel syndrome (IBS).METHODS: Seventy-six patients with IBS were included in the study (62 females and 14 males; mean age 32 years, range 18-55 years), of which 40 also fulfilled the Rome III criteria for functional dyspepsia (FDP). Of the entire IBS cohort, 26 had diarrhea as the predominant symptom (IBS-D), 21 had a mixture of diarrhea and constipation (IBS-M), and 29 had constipation as the predominant symptom (IBS-C). Forty-three age and sex-matched healthy volunteers without any gastrointestinal complaints served as controls. The patients were asked to complete the Birmingham IBS symptom questionnaire. Both the patients and controls underwent a standard gastroscopy, during which three biopsy samples were taken from the corpus. Sections from these biopsy samples were immunostained using the avidin-biotin complex (ABC) method, for ghrelin, serotonin, somatostatin and histamine. The densities of these cell types and immunoreactivity intensities were quantified using computerized image analysis with Olympus cellSens imaging software (version 1.7).RESULTS: The densities of the ghrelin cells in the control, IBS-total, IBS-D, IBS-M and IBS-C groups were 389 (320, 771), 359 (130, 966), 966 (529, 1154), 358 (120, 966) and 126 (0, 262) cells/mm², respectively. There was a significant difference between the tested groups (P < 0.0001). Dunn’s multiple comparison test showed that the ghrelin cell density was significantly higher in IBS-D and lower in IBS-C than in the controls (P = 0.03 and 0.0008, respectively). The ghrelin cell density in patients with both IBS and FDP was 489 (130, 966), and in those with IBS only 490 (130, 956). There was no statistical significant difference between these 2 groups of patients (P = 0.9). The immunoreactivity intensity did not differ between any of the groups (P = 0.6). The diarrhea score of the Birmingham IBS symptom questionnaire was significantly positively correlated with ghrelin cell density (r = 0.65; P < 0.0001) and significantly inversely correlated with that of constipation (r = 90.69; P < 0.0001). The densities of the serotonin cells were 63 (51, 82), 51 (25, 115), 120 (69, 128), 74 (46, 123) and 40 (0, 46) cells/mm² in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively. A statistically significant difference was found between the tested groups (P < 0.0001). Posttest revealed that serotonin cell density was significantly higher in IBS-D and lower in IBS-C than in controls (P = 0.02 and 0.004, respectively), but did not differ in the IBS-total and IBS-M groups from that in controls (P = 0.5 and 0.4, respectively). The serotonin cell density in patients with both IBS and FDP was 62 (25, 115) and in those with IBS only 65 (25, 123). There was no statistically significant difference between these 2 groups of patients (P = 1). The immunoreactivity intensity of serotonin did not differ significantly between any of the groups (P = 0.0.9). The serotonin cell density was significantly positively correlated with the diarrhea score of the Birmingham IBS symptom questionnaire (r = 0.56; P < 0.0001) and significantly inversely correlated with that of constipation (r = 0.51; P < 0.0001). The densities of the somatostatin cells were 97 (72, 126), 72 (0, 206), 29 (0, 80), 46 (0, 103) and 206 (194, 314) cells/mm² in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively (Figures 7 and 8). There was a statistically significant difference between the controls and the IBS subgroups (P < 0.0001). The density of somatostatin cells was significantly lower in the IBS-D and IBS-M groups but higher in IBS-C patients than in the controls (P < 0.01, P = 0.02, and P = 0.0008, respectively). The somatostatin cell density in patients with both IBS and FDP was 86 (0-194), and in those with IBS only 110 (0-206). There was no statistically significant difference between these 2 groups of patients (P = 0.6). There was no significant difference in somatostatin immunoreactivity intensity between the controls. The diarrhea score of the Birmingham IBS symptom questionnaire was inversely correlated with somatostatin cell density (r = 0.38; P = 0.0007) and was positively correlated with that of constipation (r = 0.64; P < 0.0001).CONCLUSION: The finding of abnormal endocrine cells in the oxyntic mucosa shows that the endocrine cell disturbances in IBS are not restricted to the intestine. Furthermore, it appears that ghrelin, serotonin and somatostatin in the oxyntic mucosa of the stomach may play an important role in the changing stool habits in IBS through their effects on intestinal motility.     

A randomized controlled trial of stage-matched intervention for smoking cessation in cardiac out-patients

Aim To examine the effectiveness of a stage‐matched smoking cessation counselling intervention for smokers who had cardiac diseases. Methods A total of 1860 Chinese cardiac patients who smoked at least one cigarette in the past 7 days and aged 18 years or above recruited from cardiac out‐patient clinics in Hong Kong hospitals were allocated randomly to an intervention group or control group. The intervention group (n = 938) received counselling matched with their stage of readiness to quit by trained counsellors at baseline, 1 week and 1 month. The control group (n = 922) received brief counselling on healthy diet at baseline. The primary outcomes were self‐reported 7‐day and 30‐day point prevalence (PP) of tobacco abstinence at 12 months after baseline. The secondary outcome measures included biochemically validated abstinence at 12‐month follow‐up, self‐reported 7‐day and 30‐day PP abstinence and reduction of cigarette consumption by 50% at 3 and 6 months. Results By intention‐to‐treat analysis, the intervention and control groups showed no significant difference in self‐reported 7‐day PP abstinence (intervention: 26.5% versus control: 25.5%; P = 0.60) and 30‐day PP (intervention: 25.4% versus control: 24.2%; P = 0.55), biochemically validated abstinence (intervention: 6.6% versus control: 4.9%; P = 0.14) and overall quit attempts of least 24 hours (intervention: 40.3% versus control: 34.3%; P = 0.007) at the 12‐month follow‐up, adjusted for the baseline stage of readiness to quit smoking. Conclusions An intervention, based on the Stages of Change model, to promote smoking cessation in cardiac patients in China failed to find any long‐term benefit.     

Impact of a prior medical degree on students' dental school performance in Innsbruck, Austria

The purpose of this study was to identify the performance differences between two groups of Austrian dental students (one with a prior medical degree and one without a medical degree) during their dental school training and final dental licensure examination. A specific aim was to determine if having a medical degree is a predictive factor for dental students' scores on the Austrian Dental Admission Test (Austrian DAT), performance in the dental clinic, and scores on final exam. The study consisted of a retrospective analysis of 122 students (thirty-nine with a medical degree and eighty-three without a medical degree) who were enrolled in the Dental Clinic at Innsbruck Medical University, Innsbruck, Austria, between 2001 and 2006. Three performance categories were considered: Austrian DAT results, clinical performance after the first clinical year in dental school, and performance on the final dental licensure examination. Information on students' age, gender, and previous medical degree was collected from official records. Analyses with student's t-test and Pearson's chi-square test revealed that the students with a medical degree had significantly higher Austrian DAT total test scores, grade point averages after the first clinical year, and scores on the final exam. Additionally, those students had significantly better performance on the final exam in prosthodontics and oral and maxillofacial surgery. The linear regression analysis showed that a medical degree had an independent effect on average scores on the final exam, age, and Austrian DAT test scores, while gender showed no statistically significant effect. Overall, the study found that dental students with a prior medical degree had significantly higher Austrian DAT total test scores and performed significantly better in the first clinical year and on the final exam than those without a prior medical degree.