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BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic cardiomyopathy is a rare inherited disease with incomplete penetrance and an environmental component. Although a rare disease, ARVC is a common cause of sudden cardiac death in young adults. Data on the different stages of ARVC remains scarce. The purpose of this study is to describe the initial presentation and cardiac phenotype of definite and non-definite ARVC for patients seen at a tertiary service. METHODS: This is a single centre, observational cohort study of patients with definite and non-definite ARVC seen at the Inherited Cardiac Conditions services at University Hospital Birmingham (UHB) in the period 2010-2021. Patients were identified by interrogation of digital health records, medical history, imaging and by examining 12-lead electrocardiograms (ECG). RESULT: The records of 1451 patients were reviewed; of those, 165 patients were at risk of ARVC (mean age 41 ± 17 years, 56% male). 60 patients fulfilled task force criteria for definite ARVC diagnosis (n = 40, 67% males), and 38 (72%) of them carried a known pathogenic variant. The remaining 105 patients (50% males) were non-definite, and of these 45 (62%) carried a known pathogenic variant. Patients in the definite group were more symptomatic, with palpitations (57% vs. 17%), syncope (35% vs. 6%) and shortness of breath (28% vs. 5%, p < 0.001). T-wave inversion in V1-V3 and epsilon waves were observed only in the definite group. Both PR interval and QRS duration were longer in the definite (170 ± 34 ms and 100 ± 19 ms, p < 0.001) compared to (149 ± 25 and 91 ± 14 ms, p = 0.005). Patients with definite ARVC had significantly larger RV end diastolic areas and significantly reduced biventricular function (RVEDA = 27 ± 10 cm2, RVFAC = 37 ± 11% and EF = 56 ± 12%) compared to the non-definite group (RVEDA = 18 ± 4 cm2, RVFAC 49 ± 6% and LVEF 64 ± 7%, p < 0.001). Sustained ventricular tachycardia (VT) occurred more frequently in the definite group compared to the non-definite group (27% vs. 2%, p < 0.001). Ventricular fibrillation was observed in the definite group only (8 of 60 patients, 13%). CONCLUSION: Our study showed differences between definite and non-definite ARVC patients in terms of clinical, electrophysiological and imaging features. Major adverse cardiac events occurred more commonly in the definite group, but also were observed in non-definite ARVC. This single centre observational cohort study forms a basis for further prospective multicentre interventional studies.

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OBJECTIVE: To review the major indications for cesareans performed by Médecins Sans Frontières (MSF) personnel from the Operational Center Brussels. METHODS: A retrospective study was undertaken of all singleton cesarean deliveries from 2008-2012 for which indications were recorded. Location of project, age of patient, type of anesthesia, and duration of operation were also recorded. RESULTS: A total of 14 151 singleton cesarean deliveries were identified from 17 countries. Among the 15 905 indications recorded, the most common was failure to progress or cephalopelvic disproportion (4822 [30.3%]), followed by previous uterine scar (2504 [15.7%]), non-reassuring fetal status (2306 [14.5%]), and fetal malpresentation (1746 [11.0%]). Other indications were placenta or vasa previa (794 [5.0%]), uterine rupture (676 [4.3%]), hypertensive disorders (659 [4.1%]), placental abruption (520 [3.3%]), pre-rupture (450 [2.8%]), and cord prolapse (365 [2.3%]). CONCLUSION: Indications for cesareans in MSF settings differ from those in higher-income countries. Further investigation is needed for adequate emergency obstetric care coverage.

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Histoplasmosis is a progressive granulomatous disease caused by the intracellular dimorphic fungus Histoplasma capsulatum. We report a rare case of esophageal histoplasmosis in a renal allograft recipient. A 55-year-old male who received a live, unrelated renal allograft 20 years ago presented with complaints of recurrent fever for ten to 12 months, weight loss over six months, progressive dysphagia more for solids for five to six months and joint pain and swelling involving the bilateral metacarpo-phalangeal and proximal interphalangeal joints. Biopsy from the esophageal ulcers revealed dense inflammation infiltrated with lymphocytes and macrophages with clusters of strongly positive intracellular fungal spores with a clear area or "halo-like" zone suggestive of Histoplasma capsulatum invasion. The patient was treated with intravenous liposomal amphotericin B for ten days and later switched over to oral itraconazole. Repeated endoscopy revealed significant improvement of the lesions.

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BACKGROUND: Pancreatic exocrine insufficiency (PEI) results in maldigestion, leading to abdominal pain, steatorrhoea, malnutrition and weight loss. AIM: To assess the efficacy and safety of pancreatin (Creon 40000 MMS) in treating PEI due to chronic pancreatitis (CP). METHODS: This was a 1-week, double-blind, randomised, placebo-controlled, parallel-group, multicentre study in India. Men and women ≥18 years of age with proven CP and PEI [defined as a coefficient of fat absorption (CFA) ≤80% during run-in phase] were randomised 1:1 to pancreatin or placebo (two capsules orally per main meal, one with snacks). The primary outcome measure was change in CFA from baseline to end of double-blind treatment (analysis of covariance). RESULTS: Of 62 patients randomised (34 pancreatin, 28 placebo), 61 completed treatment; one patient in the placebo arm withdrew consent before completion. Patient characteristics were similar in both groups except for the proportion of men (pancreatin 82% vs. placebo 68%). Patients receiving pancreatin had a statistically significant greater improvement in fat absorption from baseline to the end of double-blind treatment compared with those receiving placebo, with a least squares mean change (95% CI) in CFA of 18.5% (15.8-21.2) vs. 4.1% (1.0-7.2), respectively. This resulted in a treatment difference of 14.4% (10.3-18.5); P = 0.001. Patients receiving pancreatin also had a statistically significant greater improvement in nitrogen absorption and greater reductions in mean stool fat, stool frequency and stool weight compared with those receiving placebo. Treatment-emergent adverse events occurred in 12 patients on pancreatin and in seven on placebo; none led to study discontinuation. CONCLUSIONS: The results provide evidence for the efficacy of pancreatin (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis, and confirm that this formulation is well tolerated, with a good safety profile, at the dose administered.

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Ras association domain family protein 1A (RASSF1A) is one of the more heavily methylated genes in human cancers. In addition to promoter-specific methylation, RASSF1A polymorphisms have been identified in cancer patients. RASSF1A is a tumor suppressor protein involved in death receptor-dependent apoptosis and it is localized to microtubules. Currently, the biological importance of RASSF1A microtubule localization and the functional consequences of RASSF1A polymorphisms is not understood. In this study, we have investigated both RASSF1A microtubule association and polymorphisms. Loss of RASSF1A microtubule association resulted in the nuclear appearance of RASSF1A and the loss of association with α-, γ- and ß-tubulin. Moreover, the loss of microtubule localization of RASSF1A resulted in enhanced tumor-promoting potential, as determined by a xenograft transplantation model in nude mice. It is surprising that, several RASSF1A polymorphisms also lost the ability to associate with α-, γ- and ß-tubulin and lost the ability to prevent tumor formation in a xenograft nude mouse model when compared with wild-type RASSF1A. Our results demonstrate a role for RASSF1A microtubule localization in eliciting its tumor suppressor function. In addition, some RASSF1A polymorphisms lack the tumor suppressor function of RASSF1A and, if present in patients, may be tumorigenic.

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Soluble adhesion molecules namely soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sELAM-1) were assayed in hydatid patients with or without complications. It was found that sICAM-1 was significantly increased in patients with hydatid cysts as compared to the control group. In lymphoedemic filariasis cases both sICAM-1 and sELAM-1 showed highly significant increase more than the control group. However, non of both soluble adhesion molecules were significantly elevated in patients with ascariasis, hymenolepiasis, heterophyiasis and strongyloidiasis as compared to controls. The results indicated that SICAM-1 & S ELAM-1 are useful markers for hydatidosis and filariasis, but not for ascariasis, hymenolepiasis, heterophyiasis and strongyloidiasis

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Two groups of patients were studied. First one included 50 schistosomiasis mansoni patients, 30 with simple infection, 10 with splenomegaly and with ascites. Second group included 111 patients of whom 20 with pure S. mansoni, 27 with pure HCV infection, 54 with mixed infection of schistosomiasis and HCV and 10 with schistosomiasis, HCV and typhoid fever. Serum transaminases and anti-HCV antibodies performed, showed anti-HCV raised levels in 10% of simple schistosomiasis, 60% in splenomegalic patients, 80% in ascites patients, and 7.1% in controls. Liver function tests in first group were within normal range except in those with ascites. In second group, liver function tests was norma in pure schistosomiasis patients, in pure HCV patients serum bilirubin was normal in 22.2%, AST, ALT and alkaline phosphatase were higher. In mixed infection, serum bilirubin was normal in 18.5%, serum transaminases were higher and alkaline phosphatase was normal among 77.7%. Patients with typhoid fever, HCV and schistosomiasis (12.6%) showed significant increase of liver function as compared with each of pure HCV or HCV and schistosomasis. Results were discussed.

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A total of 47 patients with toxoplasmosis (21 cases) with amoebic liver abscess (14 cases) and with giardiasis (12 cases) as well as 14 healthy control were subjected to thorough history taking, clinical examination, stool & urine analysis, complete blood picture, ESR, C-reactive protein, ASO, widal test, blood cultures, liver function tests, serum creatinine, hepatitis viral markers, rheumatoid factor, auto-antibodies, stool culture, rectal snip, chest X-ray, abdominal sonar, level of serum adhesion molecules (sICAM-1, sELAM-1), ELISA detection of Toxoplasma antibodies in serum, liver biopsy, detection and counting of Giardia cysts. In toxoplasmosis group, highly significant increase in serum levels of sICAM-1 (P<0.01) and significant increase in serum levels of sELAM-1 (P<0.05) in comparison to control. However, only sICAM-1 levels were significantly increased in IgM cases more than in IgG cases. In amoebic liver abscess group, both sICAM-1 and sELAM-1 significantly increased when compared with control. In giardiasis group, highly significant increase of serum levels of sELAM-1 was noticed than in control group (P<0.01), while sICAM-1 showed no significant difference (P>0.05). There was no correlation between sELAM-1 and number of cysts in the stool (intensity of infection). Soluble forms of adhesion molecules especially sICAM-1 have the potentiality as good markers of endothelial damage, severity of disease and to less extend load of infection.

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Two adeno-associated virus (AAV) elements are necessary for the integration of the AAV genome: Rep78/68 proteins and inverted terminal repeats (ITRs). To study the contribution of the Rep proteins and the ITRs in the process of integration, we have compared the integration efficiencies of three different plasmids containing a green fluorescent protein (GFP) expression cassette. In one plasmid, no viral sequences were present; a second plasmid contained AAV ITRs flanking the reporter gene (integration cassette), and a third plasmid consisted of an integration cassette plus a Rep78 expression cassette. One day after transfection of 293 cells, fluorescent cells were sorted by flow cytometry and plated at 1 cell per well. Two weeks after sorting, colonies were monitored for stable expression of GFP. Transfection with the GFP plasmid containing no viral sequences resulted in no stable fluorescent colonies. Transfection with the plasmid containing the integration cassette alone (GFP flanked by ITRs) produced stable fluorescent colonies at a frequency of 5.3% +/- 1.0% whereas transfection with the plasmid containing both the integration cassette and Rep78 expression cassette produced stable fluorescent colonies at a frequency of 47% +/- 7.5%. Southern blot analysis indicated that in the presence of Rep78, integration is targeted to the AAVSI site in more than 50% of the clones analyzed. Some clones also showed tandem arrays of the integrated GFP cassette. Both head-to-head and head-to-tail orientations were detected. These findings indicate that the presence of AAV ITRs and the Rep78 protein enhance the integration of DNA sequences into the cellular genome and that the integration cassette is targeted to AAVS1 in the presence of Rep78.

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In 15 asthmatic children and 3 healthy adult volunteers the pharmacokinetics and pharmacodynamics of proxyphylline under oral treatment, and the pharmacokinetics after intravenous administration were determined. The concentration-time-courses after intravenous application could best be fitted to an open 2-compartment model whereas the pharmacokinetics after oral treatment followed an open 1-compartment model. Under oral administration great inter- and intraindividual variances of the serum levels occurred. These differences which showed no age-dependency were suggested to be due to variations of the absorption velocity and the elimination half-lifes. In order to evaluate the curative efficacy of proxyphylline on lung function parameters all children had to undergo a whole body-plethysmography. No significant antiobstructive effects on the relevant baseline ventilation parameters could be observed. The protective efficacy of proxyphylline was determined in asthmatic children who developed an exercise induced asthma after a 7 minutes run. Only in 3 of 11 children a significant reduction of the enhanced airway resistance occurred. No correlation between serum levels and the protective effects was found. The present results show that there is no positive association between pharmacokinetics and pharmacodynamics of proxyphylline in asthmatic children. A safe antiobstructive therapy appears to be impossible within the dose range recommended so far.

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