Cytomegalovirus infection in patients with haematological diseases and after autologous stem cell transplantation as consolidation: a single-centre study

Because of the widespread use of immunosuppressive drugs, CMV infection is one of the most important causes of morbidity and mortality in patients with haematological malignancies worldwide. The aim of the study was to retrospectively analyse the epidemiology of CMV infection in haematological patients. Between 2008 and 2014, 1238 quantitative CMV DNA detections from plasma specimens were performed. These specimens were collected from 271 patients with haematological malignancy. Patients were grouped on the basis of underlying diseases (lymphoid and myeloid malignancies and other haematological diseases). In the lymphoid and myeloid groups, we distinguished ASCT and non-ASCT groups. During the studied period, the majority of examined patients (82.6 %) were treated with lymphoproliferative disease. A total of 126 (46.5 %) patients underwent ASCT, while 145 (53.5 %) did not have stem cell transplantation. A total of 118 (9.5 %) of 1238 plasma specimens proved to be positive for CMV DNA; these specimens were collected from 66 (24.4 %) patients. Twenty-four (16.6 %) of 145 non-ASCT patients had CMV PCR positive specimens. Among non-ASCT patients with positive CMV PCR results, 10 patients were asymptomatic, 14 had symptomatic reactivation, while 2 had CMV disease. In the ASCT group, 42 (33.3 %) patients had CMV PCR positive samples. CMV reactivation was asymptomatic in 34 (81 %) cases, and 8 (19 %) patients had symptomatic reactivation. In the non-ASCT group, the rate of CMV infection is low. In the ASCT group, the prevalence of CMV infection was higher than in the non-ASCT group, but the majority of CMV infection was asymptomatic and only small number of patients had symptomatic reactivation. Thus, our results also showed that the use of routine CMV DNA monitoring is not necessary in patients with haematological malignancies not receiving fludarabine-containing regimen or alemtuzumab, in spite of this to decrease the mortality we have to consider the use of molecular tests in case of suspected infectious conditions.     

Positive modulation of δ-subunit containing GABA(A) receptors in mouse neurons

δ-subunit containing extrasynaptic GABA_A receptors are potential targets for modifying neuronal activity in a range of brain disorders. With the aim of gaining more insight in synaptic and extrasynaptic inhibition, we used a new positive modulator, AA29504, of δ-subunit containing GABA_A receptors in mouse neurons in vitro and in vivo. Whole-cell patch-clamp recordings were carried out in the dentate gyrus in mouse brain slices. In granule cells, AA29504 (1 μM) caused a 4.2-fold potentiation of a tonic current induced by THIP (1 μM), while interneurons showed a potentiation of 2.6-fold. Moreover, AA29504 (1 μM) increased the amplitude and prolonged the decay of miniature inhibitory postsynaptic currents (mIPSCs) in granule cells, and this effect was abolished by Zn²⁺ (15 μM). AA29504 (1 μM) also induced a small tonic current (12.7 ± 3.2 pA) per se, and when evaluated in a nominally GABA-free environment using Ca²⁺ imaging in cultured neurons, AA29504 showed GABA_A receptor agonism in the absence of agonist. Finally, AA29504 exerted dose-dependent stress-reducing and anxiolytic effects in mice in vivo. We propose that AA29504 potentiates δ-containing GABA_A receptors to enhance tonic inhibition, and possibly recruits perisynaptic δ-containing receptors to participate in synaptic phasic inhibition in dentate gyrus.     

Refractory sprue--precursor lesion of enteropathy type T-cell lymphoma--a clinicopathological case report

INTRODUCTION: Refractory sprue is characterised by distinctive morphologic alterations and the emergence of clonal intraepithelial lymphocytes. Aim: In this case report the authors emphasize the importance of histopathology in the diagnosis of refractory sprue. METHODS: The sequential biopsies from this patient have been investigated with routine histology, immunohistochemistry and molecular genetics for T-cell clonality analysis. RESULTS: The severely cachectic patient presenting with malabsorption syndrome has been diagnosed with celiac disease through a duodenal biopsy, and the CD8 negativity of the intraepithelial lymphocytes suggested the possible diagnosis of refractory sprue. Azathioprine and glucocorticoid therapy was administered due to the failed jejunal feeding and gluten-free diet, resulting in clinically complete, morphologically partial remission. Intestinal T-cell lymphoma developed in the ileocecal region within two years after the first clinical presentation. DISCUSSION: Refractory sprue and the enteropathy-type T-cell lymphoma constitute a disease spectrum. The reported case shows how a simple method can provide crucial information in the diagnosis of refractory sprue.     

Predictors of caesarean section – a cross-sectional study in Hungary

Purpose: The aim of this study was to analyse the factors associated with caesarean section (CS) at the Department of Obstetrics and Gynaecology, University of Szeged, Hungary.

Study design: Data collection was based on self-administered questionnaire and medical records related to the deliveries in the year of 2014. Maternal age, education level, marital status, pre-gestational body mass index (BMI), infertility treatment, previous CS, gestational diabetes mellitus (GDM), pre-pregnancy hypertension and pregnancy-induced hypertension (HT/PIH) were examined. The participation rate was 67.3%, multiple pregnancies and questionnaires with missing data were excluded (n?=?1493). Univariate and multivariate comparisons were performed.

Results: There were 1125 (45.4%) CSs out of 2479 deliveries. CS rate: 40.0%. Underweight 109 (7.1%), normal 921 (60.2%), overweight 320 (20.9%) obese 181 (11.8%). HT/PIH: 7.6% (n?=?117), GDM: 10.1% (n?=?155). The odds of CS were significantly higher among obese mothers (OR: 1.81) compared with the normal weight group. Increasing maternal age (OR: 0.97) and being underweight (OR: 0.59) significantly decreased, previous CS (OR: 12.19), infertility treatment (OR: 1.91) and HT/PIH (OR: 1.87) significantly increased the probability of CS.

Conclusions: Pre-gestational obesity, infertility treatment, previous CS and HT/PIH had significant effect on the mode of delivery.     

Protease inhibitors partially overcome the interferon nonresponse phenotype in patients with chronic hepatitis C

The outcome of triple therapy with protease inhibitors (PI) depends on the intrinsic response to interferon. Interferon‐stimulated gene (ISG) expression differs by cell type in the liver and is a strong predictor of interferon responsiveness. Patients who respond well to interferon have low/absent ISG expression in hepatocytes but significant ISG expression in macrophages. Nonresponders (NRs) show the opposite pattern. We aimed to determine the association between cell‐type‐specific ISG staining and treatment outcome with PI‐based triple therapy. Liver biopsy tissue from consecutive patients treated with boceprevir or telaprevir with peginterferon and ribavirin was stained for myxovirus A (MxA). Staining was scored 0–3 in macrophages (M‐MxA) and hepatocytes (H‐MxA), and IL28B genotyping was performed. Of 56 patients included 41 achieved SVR (73%) (sustained virological response), 2 (4%) relapsed, 10 (18%) were NRs, and 3 (5%) were lost to follow‐up. Median M‐MxA staining was stronger and H‐MxA staining was weaker in patients who achieved SVR. MxA staining correlated with IL28B genotype and with the HCV RNA decline during lead‐in phase. However, unlike with dual therapy, the negative predictive value (NPV) of absent or weak M‐MxA staining was poor (42%), while the positive predictive value improved (93%). Although by multivariable logistic regression M‐MxA staining was significantly associated with SVR (OR 4.35, 1.32–14.28, P = 0.012), the predictive ability was inadequate to withhold therapy. The interaction between macrophages and hepatocytes plays a critical role in interferon responsiveness; however, the addition of a PI at least partially overcomes the interferon nonresponse phenotype making the predictive ability of ISG staining less clinically useful.     

G-protein coupled receptor kinase-like immunoreactivity in the snail, Helix pomatia, neurons

GPRCs are regulated via phosphorylation by different protein kinases including GRKs and PKA and PKC. The purpose of this study was to determine the presence and physiological role of GRKs in the tissues of the snail, Helix pomatia. Here we report that immunoblotting of brain homogenate with anti-GRK2/3 antibody prepared from mammalian tissue can be detected in snail GRK-like immunoreactivity. The GRK2/3 immunoreactivity was found at approximately 80 kDa in a variety of cells, including salivary duct, salivary gland and eye. Intracellular injection of the anti-GRK2/3 prevented the neuron from desensitization and agonist-induced activation augmented the phosphorylated GRKs in the membrane fraction suggesting that GRKs may have a functional role in the neuropeptide receptor desensitization in snail.