Co-inheritance of the Hb Sun Prairie mutation with a point mutation at 5'-UTR in the eastern Indian population

Haemoglobin (Hb) Sun Prairie (alpha2-globin cd130, GCT-->CCT, Ala-->Pro) is detected in three unrelated chromosomes, in association with a C-->T transition in the 5'-untranslated region (UTR), two bases upstream from the translation start site. Reported inversion of alpha/beta-mRNA ratio observed in Hb Sun Prairie mutants might stem from the second mutation and should be investigated. Molecular modelling studies indicate that the 130th residue of alpha-globin faces primarily the central cavity of the molecule and is not in contact with any beta-chain residue; further, no significant disruption of the Hb structure because of the Sun Prairie mutation is discernible. Depression of translation because of the second mutation of a conserved base in the 5'-UTR might explain the observed clinical severity.     

Cartilage MR imaging at 3.0 versus that at 1.5 T: preliminary results in a porcine model

PURPOSE: To compare 1.5- and 3.0-T magnetic resonance (MR) images of porcine knee specimens containing artificial cartilage lesions in terms of accuracy of lesion depiction, image quality, and signal-to-noise ratio (SNR). MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act-compliant study had institutional review board approval, and informed consent was obtained from the human volunteers. Two fat-saturated cartilage MR imaging sequences (an intermediate-weighted fast spin-echo [SE] sequence and a spoiled gradient-echo [GRE] sequence) were optimized for imaging at 3.0 T in two human volunteers and then used to image 10 porcine knees in which 29 artificial cartilage lesions had been created. Corresponding sequences were used at 1.5 T for all specimens. Images were assessed by two radiologists in consensus, and diagnostic performance in lesion depiction was determined by using macroscopic findings in specimen slices as a reference standard. SNRs were also calculated. For statistical analysis, the McNemar test of discordant pairs was used with a level of significance of P < .05. RESULTS: The best diagnostic performance for both the intermediate-weighted fast SE and the spoiled GRE sequences was achieved at 3.0 T. With use of corresponding fat-saturated intermediate-weighted fast SE sequences with an identical acquisition time (9 minutes 44 seconds), 26 (90%) of 29 lesions were detected at 3.0 T, while 18 (62%) were detected at 1.5 T. With use of fat-saturated spoiled GRE sequences, 24 (83%) of 29 lesions were detected at 3.0 T (acquisition time, 8 minutes 48 seconds), and 23 (79%) lesions were detected at 1.5 T (acquisition time, 11 minutes 14 seconds). The rate of correct lesion grade assessment was 65% (17 of 26 lesions) at 3.0 T and 61% (11 of 18 lesions) at 1.5 T with the intermediate-weighted fast SE sequences and 83% (20 of 24 lesions) at 3.0 T and 70% (16 of 23 lesions) at 1.5 T with the spoiled GRE sequences. Both subjective evaluation of image quality and SNR values were significantly higher at 3.0 T (P < .05). CONCLUSION: In this animal model, MR imaging at 3.0 T increased the accuracy of cartilage lesion assessment when compared with imaging at 1.5 T. Image quality and SNR were highest at 3.0 T.     

Controlled trial of interventions to increase testing and treatment for Helicobacter pylori and reduce medication use in patients with chronic acid-related symptoms

BACKGROUND: Many symptomatic patients take proton pump inhibitors or histamine-2 blockers for years and those without gastro-oesophageal reflux disease might benefit from Helicobacter pylori eradication. AIM: To increase testing and treatment of H. pylori and reduce chronic use of proton pump inhibitors and histamine-2 blockers. METHODS: We conducted a three-armed controlled trial in 14 managed care practices. We included adults who used proton pump inhibitors or histamine-2 blockers for >1 year and excluded those with gastro-oesophageal reflux disease or previous endoscopy. We compared usual care (n = 312 patients from 6 practices) to low-intensity (n = 147 from 3 practices) and high-intensity (n = 122 from 5 practices) interventions. Low-intensity intervention consisted of guidelines, patient-lists, and a "toolkit"; high-intensity intervention added academic group detailing by a gastroenterologist with reinforcement by pharmacists. RESULTS: Compared with usual care, the high-intensity intervention increased H. pylori test-ordering (29% versus 9% at 12 months, P = 0.02). About half (23 of 58) of patients tested positive and 22 received eradication treatments. The high-intensity intervention decreased proton pump inhibitor use by 9% per year (P = 0.028), but did not alter histamine-2 blocker use. The low intensity intervention was ineffective. CONCLUSIONS: Providing guidelines, patient-lists, and toolkits was no better than usual care. Adding group detailing and pharmacist reinforcements led to improvements in H. pylori management and decreases in proton pump inhibitor use.     

Effect of impaired renal function and haemodialysis on the pharmacokinetics of aprepitant

BACKGROUND: The neurokinin NK(1)-receptor antagonist aprepitant has demonstrated efficacy in preventing highly emetogenic chemotherapy-induced nausea and vomiting. OBJECTIVE: The objective of the present study was to investigate the effects of impaired renal function on the pharmacokinetics and safety of aprepitant. SUBJECTS AND METHODS: A total of 32 patients and healthy subjects were evaluated in this open-label, two-part study. Pharmacokinetic parameters after a single oral dose of aprepitant 240 mg were measured in eight patients with end-stage renal disease (ESRD) requiring haemodialysis, eight patients with severe renal insufficiency (SRI [24-hour creatinine clearance <30 mL/min/1.73 m(2)]) and 16 healthy and age-, sex- and weight-matched subjects (controls). RESULTS: In ESRD patients, the area under the plasma concentration-time curve (AUC) from 0 to 48 hours (AUC(48)) for aprepitant was on average approximately 36% lower than that observed in control subjects (ratio [ESRD patients/healthy controls] of geometric means = 0.64), but the 90% confidence interval 0.52, 0.78 for the ratio of true mean AUC(48) fell within the predefined target interval of 0.5, 2.0. Also in ESRD patients, there was no statistically or clinically significant difference in unbound aprepitant AUC (which may be more clinically relevant than total aprepitant AUC) when compared with healthy control subjects. Aprepitant pharmacokinetic parameters in ESRD patients were clinically similar when haemodialysis was initiated at 4 hours or 48 hours after aprepitant administration. In SRI patients, the ratio (SRI patients/healthy controls) of aprepitant AUC from zero to infinity (AUC(infinity)) geometric mean value was 0.79 with a 90% confidence interval of 0.56, 1.10. On average, in SRI patients the principal aprepitant pharmacokinetic parameters (AUC(infinity), initial maximum plasma concentration [C(max)], time to initial C(max), and apparent elimination half-life) were not statistically different from those obtained in healthy control subjects. Aprepitant was generally well tolerated in both ESRD and SRI patients. CONCLUSION: The results of this study demonstrate that ESRD, haemodialysis and SRI have no clinically meaningful effect on aprepitant pharmacokinetics. Therefore, no dosage adjustment of aprepitant is warranted in SRI or ESRD patients.     

Effect of aprepitant on the pharmacokinetics and pharmacodynamics of warfarin

Objective To examine the effect of aprepitant on the pharmacokinetics and pharmacodynamics of warfarin. Aprepitant is a neurokinin-1 (NK₁)-receptor antagonist developed as an antiemetic for chemotherapy-induced nausea and vomiting.Methods This was a double-blind, placebo-controlled, randomized, two-period, parallel-group study. During period 1, warfarin was individually titrated to a stable prothrombin time (expressed as international normalized ratio, INR) from 1.3 to 1.8. Subsequently, the daily warfarin dose remained fixed for 10–12 days. During period 2, the warfarin dose was continued for 8 days, and on days 1–3 administered concomitantly with aprepitant (125 mg on day 1, and 80 mg on days 2 and 3) or placebo. At baseline (day –1 of period 2) and on day 3, warfarin pharmacokinetics was investigated. INR was monitored daily. During period 2, warfarin trough concentrations were determined daily.Results The study was completed by 22 healthy volunteers (20 men, 2 women). On day 3, steady-state pharmacokinetics of warfarin enantiomers after aprepitant did not change, as assessed by warfarin AUC_0-24h and C_max. However, compared with placebo, trough S(–) warfarin concentrations decreased on days 5–8 (maximum decrease 34% on day 8, P<0.01). The INR decreased after aprepitant with a mean maximum decrease on day 8 of 11% versus placebo (P=0.011).Conclusion These data are consistent with a significant induction of CYP2C9 metabolism of S(–) warfarin by aprepitant. Subsequently, in patients on chronic warfarin therapy, the clotting status should be monitored closely during the 2-week period, particularly at 7–10 days, following initiation of the 3-day regimen of aprepitant with each chemotherapy cycle.     

New nematodes from birds. Part II

Summary Two new Ascarids are described. Amplicaecum ixobrychusi n. sp. is characterised by the possession of two intestinal caeca and no dentigerous ridges on the lips. Duplicaecum ibisi gen. et sp. nov. bears oesophageal ventriculus, two ventricular appendices and an intestinal caecum.With 6 Figures in the Text