Prevalence of cryoglobulinaemia in hepatitis C virus‐ and hepatitis C virus/human immunodeficiency virus‐infected individuals: implications for renal function

Background and aims: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) demonstrate an affinity towards lymphocytes B, stimulating the production of cryoglobulins. Deposits of cryoprecipitates contribute to glomerulonephritis and renal failure. The presence of cryoglobulins was investigated in the sera of HCV‐monoinfected and HCV/HIV‐coinfected individuals. Associations between types of cryoglobulins and HCV genotypes, viral load and renal function tests were also evaluated. Patients and methods: Seventy‐seven patients were enrolled in this study. Forty‐four were HCV infected and 33 were HCV/HIV coinfected. Cryoglobulins were detected in the sera by electrophoresis and immunofixation. Serum urea and creatinine concentration, glomerular filtration rate (GFR) and serum cystatin C concentration (CC) were analysed to evaluate renal function. The control group included 16 healthy individuals. Results: The occurrence of cryoglobulinaemia in HCV‐monoinfected patients was 55%, whereas in HCV/HIV‐coinfected patients it was 64%. Mixed cryoglobulinaemia type II was determined in 34%, whereas type III in 25%. The prevalence of cryoglobulinaemia was significantly higher in infection with HCV genotype 1 vs. genotype 3 (65 vs. 50%; P<0.01). The most frequently occurring heavy chains were γ‐type (96%). Light chains, the κ‐type, were detected in all patients. The CC concentration was significantly higher in HCV/HIV‐coinfected patients compared with controls (718 vs. 392 ng/ml; P<0.005) or HCV‐monoinfected patients (508 ng/ml; P<0.007). There was correlation between the serum CC concentration and the incidence of cryoglobulinaemia (R=0.44; P<0.00015), which was particularly evident in HCV monoinfection (R=0.43; P<0.0034). Conclusions: Genotype‐1 infection is an important risk factor for cryoglobulinaemia. Standard renal function tests are not sufficient for the prediction of renal failure in HCV‐infected patients. Serum CC concentration allows to establish an early diagnosis of renal insufficiency related to cryoglobulinaemia.     

Baseline psychosocial predictors of survival in localized melanoma

OBJECTIVE: There is no certainty about the contributing factors or the psychological processes involved in cancer progression. Many studies have suffered from poor theoretical basis, methodological flaws, and only one or few psychosocial factors investigated at a time. We examined the simultaneous contribution of several theory-based psychosocial elements to survival time in melanoma. METHODS: A consecutive sample of patients with localized (Clarke II-IV) melanoma (N=59) were evaluated with validated questionnaires on coping with cancer, anger expression, perceived social support, noncancer life stresses, and domains of quality of life (QOL) 3-4 months after diagnosis. Cox regression analyses were used to determine the predictors of survival time from the date of diagnosis to the date of death or the last follow-up. RESULTS: After controlling for age, gender, and Breslow depth for the tumor, the baseline psychological variables related to the cancer-prone Type C response pattern, namely, anger nonexpression (repression), hopelessness, and better single-item self-reported QOL predicted shorter survival. Before hopelessness was added to the model, the amount of depressive symptoms and heavy perceived impact of diagnosis were also predictive. In addition, longer survival was strongly predicted by Cognitive Escape-Avoidance coping, which included items close to the concept of denial/minimizing. CONCLUSION: Anger nonexpression, hopelessness, and overpositive reporting of QOL--all proposed to include in the Type C response style or reflect emotional nonexpression--seem to comprise a set of factors that reduce survival, whereas denial/minimizing response to the diagnosis as such predicts longer survival.     

Pinching off syndrome in free-ranging white-tailed sea eagles (Haliaeetus albicilla) in Europe: frequency and geographic distribution of a generalized feather abnormality

Generalized feather abnormalities are rarely documented in free-living birds. Pinching off syndrome (POS) is a feather abnormality in which all remiges and retrices become malformed and are lost during the nestling stage, rendering the bird unable to fly. To determine the frequency of occurrence and geographic distribution of this syndrome in white-tailed sea eagles (Haliaeetus albicilla) in Europe, we sent questionnaires to ornithologists in 19 countries within the European range of this species. We also searched for reported cases of sea eagles with feather abnormalities that met the criteria of POS. Overall, 32 nestlings or fledglings with POS were identified between 1975 and 2006. The geographic distribution of cases was primarily restricted to 4 European countries: Germany (17 cases), Poland (11 cases), the Czech Republic (3 cases), and Great Britain (1 case). Eleven eagles from Germany and 2 eagles from the Czech Republic were examined clinically. In 15 birds in which sex was determined, 8 were female and 7 were male. From 2000 to 2005, the 5-year incidence of POS in white-tailed sea eagles in Germany was 3.5 cases per 1000 birds. Although the etiology of this syndrome in wild sea eagles is unknown, our results support a possible genetic cause.     

Cytostatic and Antiviral Activity Evaluations of Hydroxamic Derivatives of Some Non‐steroidal Anti‐inflammatory Drugs

Non‐steroidal anti‐inflammatory drugs (NSAID) pharmacophores are interesting in designing potential anticancer drugs. Indeed, numerous experimental, epidemiologic and clinical studies suggest that NSAIDs are promising anticancer drugs. Herein, NSAID hydroxamic acids 3a‐i were prepared by a new synthetic procedure and evaluated for their antiviral and cytostatic activity against malignant tumor cell lines and normal human fibroblasts (WI38). Antiviral activity evaluation results indicated that 3f had only a minor activity against the influenza virus A/H1N1 subtype with a selectivity index of 7–10. On the other hand, the results of the in vitro cytostatic activity evaluations revealed that the majority of NSAID hydroxamic acid derivatives 3a – i exhibited a strong non‐specific antiproliferative effect at the highest concentration (100 μm ) on the tested cell line panel. Only compounds 3b , 3e and 3i exerted a differential dose‐dependent inhibitory activity against the growth of HeLa cells (p < 0.05) at concentration 10 μm . Among those three compounds, only compound 3b showed a selective cytostatic effect on HeLa in comparison with normal fibroblasts.     

Primary central nervous system vasculitis imitating a brain tumour--a case report

Primary central nervous system vasculitis (PCNSV) is a rare disease with an annual incidence rate of 2.4 cases per 1,000,000 person-years. PCNSV causes various neurological symptoms dominated by headache as well as consciousness and mental disturbances. The disease sometimes imitates a brain tumour on CT and rarely presents as stroke. The diagnosis of PCNSV is difficult and frequently requires a brain biopsy in which transmural vascular inflammation involving leptomeningeal or parenchymal vessels is typically found. Angiographic changes indicating an irregular course of vessels with characteristic segmental narrowing can be observed but sometimes the angiogram is normal. The authors present a 57-year-old man in whom PCNSV was diagnosed in brain biopsy. The patient was treated with corticosteroid pulses for 18 months with good effect lasting for 2.5 years. After one year of ending glucocorticoid therapy the symptoms had occurred again and in spite of combined therapy of glucocorticoids with cyclophosphamide the patient died.     

Occurrence of the alpha-glucosidase inhibitor 1,4-Dideoxy-1,4-imino-D-arabinitol and related iminopentitols in marine sponges

The alpha-glucosidase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (1) was isolated from two marine sponges collected in Western Australia and shown by LC-MS to be responsible for the alpha-glycosidase inhibitory activity in different sponge extracts collected over a wide geographic area. The configuration of 1 was determined by application of Marfey's method. The two most inhibitory extracts contained only 1, while the less inhibitory extracts contained 1,4-dideoxy-1,4-imino-D-xylitol (2) or the putative diastereomeric imino pentitols 3 and 4. The least active or inactive extracts showed no detectable imino pentitols. While both 1 and 2 are known from plants, this is the first report on the isolation and detection of 1 and 2 in marine invertebrates.     

A deletion in CHEK2 of 5,395 bp predisposes to breast cancer in Poland

Abstract To investigate the contribution of a founder deletion in the CHEK2 gene to the burden of breast cancer in Poland we studied 4,454 women with breast cancer and 5,496 population controls. Cases and controls were genotyped for the presence of a 5,395 bp founder deletion that removes exons 9 and 10 of the CHEK2 gene. This deletion has recently been described in a Czech and Slovak population. The cases and controls had previously been tested for two protein-truncating (IVS2 + 1G > A and 1100delC) and one missense CHEK2 mutation (I157T) which are characteristic for the population. The exons 9 and 10 deletion was present in 0.4% of the controls, in 1.0% (19 of 1,978) of unselected breast cancer cases (OR=2.2; 95% CI: 1.2–4.0; p = 0.01) and in 0.9% (28 of 3,228) of the early-onset cases (OR=2.0; 95% CI: 1.3–1.8; p = 0.02). One of the three truncating CHEK2 mutations (del5395; 1100delC or IVS2 + 1G > A) was seen in 101 of 4,454 (2.3%) cases and in 58 of 5,496 controls (1.1%) (OR=2.2; 95% CI: 1.6–3.0 p < 0.0001). A 5,395 bp founder deletion contributes to the burden of breast cancer in Poland. The deletion was present in 0.9% of the women with breast cancer diagnosed under the age of 51 and in 0.9% of women with breast cancer over the age of 50. This is one of the most common protein-truncating CHEK2 variants in Poland. Overall, 2% of all breast cancers in Poland can be attributed to one of three protein-truncating mutatiosns in CHEK2.     

Recent progress in the management of chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a clonal disease characterized by proliferation and accumulation of small CD5-positive B cells. More than 50% of patients are asymptomatic at diagnosis and usually require no treatment. However, treatment is needed in the advanced and progressive disease. Chlorambucil with or without steroids has been the drug of choice for many years in previously untreated patients with CLL. The purine nucleoside analogs (PNAs), fludarabine (FA), cladribine (2-CdA-chlorodeoxyadenosine) and pentostatin (DCF, 2'-deoxycoformycin) also have been introduced for treatment of CLL. Significantly higher overall response (OR) and complete response (CR) and longer progression free survival (PFS) in patients with CLL treated with FA or 2-CdA have been confirmed in randomized, multicenter trials and more recently in meta-analysis. However, the median survival time did not differ between patients treated with PNA and alkylating agents. Combination therapies with PNAs and cyclophosphamide and especially with cyclophosphamide and rituximab are more active than monotherapy in terms of OR, CR and PFS. Several reports have shown significant activity of alemtuzumab in previously untreated and pretreated patients even when refractory to FA. Alemtuzumab also can be used in CLL as a preparative regimen before stem cell transplantation (SCT) and to eliminate minimal residual disease (MRD). Recently, several new agents have shown promise in treating CLL, including new monoclonal antibodies, agents targeting bcl-2 family of proteins, antisense oligonucleotides and other agents. Moreover, autologous and allogenic hematopoietic cell transplantations are increasingly considered for treatment of patients with CLL. In this review current therapeutic strategies in CLL are presented.