Is Magnetic Resonance Imaging the 'Reference Standard' for Cardiac Functional Assessment? Factors Influencing Measurement of Left Ventricular Mass and Volumes

Purpose MRI is considered reference standard for the assessment of left ventricular (LV) volume and mass measurements. There are few accepted guidelines for uniform assessment of cardiac function with MRI. We sought to investigate different confounding factors influencing LV measurement results. Material and Methods In 60 diabetic type-II patients (group A) we compared intra-/inter-reader variability of MRI for cardiac function measured twice at a 3 month interval by one MRI trained reader and one untrained. In 20 patients (group B) two different techniques were compared for determining the epicardial and endocardial LV-borders. Results Bland Altman analysis showed excellent intra-observer measurement agreement for the trained reader 1 for EDM (mean=–2.3 (–23.6–19)), EDV (2.9(–9.2–15.0)), ESV (3.3(–5.8–12.4)) and EF (1.2(–3.3–5.7)). Untrained reader 2 measurement agreement was considerably less appropriate for EDM (mean=–8.2 (–25.8–9.5)), EDV (7.8(–5.1–20.7)), ESV (5.3(–8.0–18.6)). Only for EF (0.8 (–6.5–8.1)) results were comparable to reader 1. Inter-observer measurement in the beginning was poor for EDM (–13.5(–55.6–28.6)) and EDV (7.3(–61.9–76.6)), whereas agreement for ESV (2.1(–29.9–34.2)) and EF (–0.9(–11.6–9.9)) was good. After 3 months, measurement agreement for EDM (–5.3 (–46.4–35.8)) was considerably improved, for EDV (0.4(–67.0–66.2)) was excellent, whereas agreement for ESV (3.1(–34.4–28.1)) and EF (–1.7(–13.0–9.6)) was similar. Using different techniques for determining the epicardial and endocardial borders, only end-diastolic volume was unchanged whereas all other parameters were significantly different using the two methods (p ≤ 0.03). Conclusion Intra- and inter-reader variability, analyst experience as well as different techniques for determining the boundaries of the left ventricle significantly affect MRI parameters for cardiac function. These results suggest a need for developing commonly accepted standards for cardiac MRI evaluation.     

Is the hepatitis C virus epidemic over in Egypt? Incidence and risk factors of new hepatitis C virus infections

Objectives: To estimate hepatitis C virus (HCV) incidence rates and identify risk factors for current HCV transmission with emphasis on the role of living with infected household family members in rural Egypt. Methods: A 4‐year population‐based, cohort study of seronegative villagers was conducted to identify incident HCV seroconversion cases. A risk factor questionnaire and blood samples for anti‐HCV EIA‐3 and HCV RNA polymerase chain reaction testing were collected at two rounds of follow‐up. Incidence rates, relative risks and 95% confidence interval (CI) were calculated based on a Poisson distribution. A matched case–control analysis to explore specific behavioural predictors of infection was conducted and odds ratios were obtained by conditional logistic regression. Results: Twenty‐five participants (11 females) seroconverted in 10 578 person years of follow‐up (PY), (incidence rate of 2.4/1000 PY; 95% CI: 1.6–3.5). The median age at seroconversion was 26 years [interquartile range (IQR) 19–35] among males and 20 years (IQR 13–24) among females. The only significant risk factor identified for these cases was receiving injections [adjusted odds ratio (OR_adj)=3.3; 95% CI: 1.1–9.8]. Two of the 17 viraemic seroconvertors were infected with the same strain as at least one of their family members. Conclusion: This study identified the important role of injections in spreading HCV infection in this rural community. National healthcare awareness and infection control programmes should be strengthened to prevent further transmission. Screening of families of infected HCV subjects should be an essential part of case management for early detection and management.     

MEFV mutations in Egyptian patients suffering from familial Mediterranean fever: analysis of 12 gene mutations

The objective of the study is to screen 12 MEFV gene mutations in Egyptian patients with familial Mediterranean fever (FMF) and to study the initial hypothesis that the phenotypic expression of the disease may be attributable to the existence of a particular mutation. We enrolled 136 Egyptian patients (74 males, and 62 females) with a clinical diagnosis of FMF. DNA was amplified by PCR and subjected to reverse hybridization for the detection of 12 MEFV gene mutations. The phenotypic expression of the disease was compared in two subgroups according to the presence of homozygote E148Q and M694V gene mutations. The most frequent gene mutations in the studied group were V726A, M694V, M680I, E148Q and M694I in 41.2, 32.4, 29.4, 25 and 20.6%, respectively. At least one of these main five founder mutations was present in 132 patients (97.1%). Thirty-two patients (23.5%) were homozygote for one of the main five founder mutations. The most common homozygote gene mutations were E148Q and M694V, each in 12 patients (8.8%). Significant increase in abdominal pain and arthritis was found in patients with homozygote M694V mutation compared to those with E148Q mutation. All patients with amyloidosis had M694V gene mutation. The increased frequency of V726A gene mutation and the rarity of amyloidosis in this study suggest that Egyptian patients may have a milder form of FMF compared to other populations. The five main founder mutations account for the vast majority of cases of FMF. M694V gene mutation may be associated with increased frequency of abdominal pain, arthritis and the presence of amyloidosis.     

Comparison of in vitro and in vivo performance of a colonic delivery system

The aim of this work is to compare in vitro to in vivo performance of a colonic drug delivery system, made of small pectin-ethylcellulose coated drug beads. The delivery system was evaluated in vitro by conducting drug release studies in different dissolution media to mimic transit times and pH conditions in the stomach, small intestine and colon and in vivo by using gamma-scintigraphic studies in dogs and absorption studies in human volunteers under fed and fasted conditions. In vitro release studies indicated that drug release rate depended on the ratio of the pectin to ethylcellulose in the coat and the thickness of the coat. In vivo release studies obtained by deconvolution of biostudy data did not correlate with in vitro results obtained from most coat formulations. Beads showing ideal release profiles in vitro showed very poor performance in vivo and only those beads showing colonic premature drug release in vitro might be able to deliver the drug to the colon. Scintigraphic studies of a selected formulation showed that the labeled beads had an estimated gastric emptying time of 3 h, an estimated small intestine transit time of 2 h and an estimated colonic transit time of 36 h. Average in vivo lag times of the selected formulation from absorption studies in humans were found to be 6.1 h and 4.8 h under fed and fasted conditions, respectively. The C(max) was also observed at 6.8 h and 5.5 h on average, under fed and fasted conditions, respectively, which might indicate that release of drug from the beads, resulted from degradation of pectin in the coat by enzymatic action in the colon rather than by simple diffusion. Deconvolution of biostudy data showed that drug absorption continued on average for at least 12 h under both fed and fasted conditions.