The impact of hepatitis B virus (HBV) infection on clinical outcomes of patients with diffuse large B-cell lymphoma.

We performed a retrospective study to analyse the characteristics and clinical outcomes of diffuse large B-cell lymphoma (DLBCL) patients with hepatitis B virus (HBV) infection and compare with those without HBV infection. The occurrence of hepatitis after withdrawal of prophylactic antiviral treatment on completion of chemotherapy was also assessed. The HBsAg-positive patients were given prophylactic antiviral treatment until 6 months after finishing chemotherapy. A total of 81 patients were recruited with 16 in the HBsAg-positive group and 65 in the HBsAg-negative group. The clinical characteristics were similar in both groups of patients. There was no significant difference in complete remission rate between the two groups (63% in HBsAg-positive group vs. 54% in HBsAg-negative group, P = 0.59). There was also no statistically significant difference in overall survival between the two groups (P = 0.23). Four of the 16 HBsAg-positive patients (25%) had hepatitis after cessation of chemotherapy and prophylactic lamivudine. The mean time of onset of hepatitis was 3 months after stopping lamivudine. In conclusion, HBV infection did not appear to affect the prognosis of DLBCL patients given antiviral prophylaxis. It is reasonable to consider prophylactic antiviral therapy to extend to at least one year on completion of chemotherapy.

Health impact assessment of marine emissions in Pearl River Delta region.

Global marine vessels emissions are adversely affecting human health particularly in southeast Asia. But health burdens from both ocean- and river-going vessels in Pearl River Delta (PRD) regions are not quantified. We estimated the potential health impacts using pooled relative risks of mortality and hospital admissions in China, and the model derived concentrations of sulfur dioxide (SO2), particulate matter (PM10), nitrogen dioxide (NO2) and ozone (O3) due to vessels emissions. SO2 concentrations due to marine emissions in Hong Kong were 13.6 µg m⁻³ compared with 0.7 µg m⁻³ in PRD regions that were far from the marine vessels. In PRD regions, the estimated annual numbers (per million people) of excess deaths from all natural causes and hospital admissions from cardiorespiratory causes attributable to SO2, NO2, O3 and PM10 combined from marine emissions were 45 and 265 respectively. Marine emission control measures could contribute a large reduction in mortality and hospital admissions in PRD regions especially in Hong Kong.

Effect of influenza on cardiorespiratory and all-cause mortality in Hong Kong, Singapore and Guangzhou.

1. Using a common modelling approach, mortality attributable to influenza was higher in the two subtropical cities Guangzhou and Hong Kong than in the tropical city Singapore. 2. The virus activity appeared more synchronised in subtropical cities, whereas seasonality of influenza tended to be less marked in the tropical city. 3. High temperature was associated with increased mortality after influenza infection in Hong Kong, whereas relative humidity was an effect modifier for influenza in Guangzhou. No effect modification was found for Singapore. 4. Seasonal and environmental factors probably play a more important role than socioeconomic factors in regulating seasonality and disease burden of influenza. Further studies are needed in identifying the mechanism behind the regulatory role of environmental factors.

Use of radiosynovectomy in recurrent warfarin-related haemarthrosis in degenerative arthritis.

Radiosynovectomy is a local and minimally invasive radiotherapy for treating various chronic inflammatory arthritis such as rheumatoid arthritis, osteoarthritis and haemophilic arthropathy. In haemophilic arthropathy, it reduces the frequency of haemarthrosis and delays the development of severe joint destruction, which ultimately requires surgical intervention. Its role in warfarin-related haemarthrosis is less clear. Haemarthrosis is an uncommon complication of warfarin use, and anticoagulation may need to be discontinued. We describe yttrium-90 radiosynovectomy use in a 74-year-old man with underlying ischaemic heart disease, atrial fibrillation, previous embolic stroke and recurrent haemarthrosis of an osteoarthritic right knee. Anticoagulation was vital and could not be permanently stopped. Due to continuing anticoagulation, he had multiple hospitalisations with recurrent right knee haemarthrosis. Intraarticular right knee yttrium-90 citrate colloid injection led to a cessation of haemarthrosis for eight months. We examined the available literature for the role of radiosynovectomy in such circumstances.

A review of effects of particulate matter-associated nickel and vanadium species on cardiovascular and respiratory systems.

Many epidemiological investigations indicate that excess risks of mortality and morbidity may vary among specific PM(2.5) components. Nickel (Ni) and vanadium (V) particulate metal species may potentially be related to increasing respiratory and cardiovascular mortality and morbidity. This review focuses on exposure concentrations of these two species in various settings, their health effects based on epidemiological and toxicological studies and the underlying mechanisms. The evidence shows that environmental exposure concentrations of Ni and V in general setting are lower than the World Health Organization standard (V, 1 microg/m(3)/day) in 2000, or the European Environment Agency standard (Ni, 1 microg/m(3)/day) in 2003, but their associations with cardiopulmonary diseases can still be found. The toxicological mechanism can be explained by laboratory-based studies. Updated safe guidelines on environmental and human exposure of Ni and V are necessary in order to clarify the associations between them and cardiopulmonary diseases and provide environmental intervention policies.

Interaction of retinoic acid and interferon in renal cancer cell lines.

Retinoic acid (RA) can potentiate the antitumor effect of interferons (IFN) in a variety of tumor types, including renal cell carcinoma (RCC). The mechanisms by which RA and IFN increase the antitumor effects in RCC are unknown. We used growth assays and mobility shift assays to examine the effects of combining 13-cis-retinoic acid (CRA) and IFN-alpha (plus IFN-gamma) on proliferation and on the expression of the IFN-specific transcription factor IFN-stimulated gene factor 3 (ISGF3) in RCC cell lines. Combining CRA and IFN-alpha resulted in a significant increase in growth inhibition in four cell lines compared with IFN-alpha or CRA alone. Binding of nuclear extracts from RCC cells to an IFN-stimulated response element (ISRE) oligonucleotide probe following incubation with IFN-alpha was not increased by CRA but was significantly increased by pretreatment by IFN-gamma in a time-dependent fashion. Proliferation assays showed that sequential addition of IFN-gamma and IFN-alpha significantly increased growth inhibition. IFN-alpha but not IFN-gamma or CRA increased the cellular levels Stat2 and p48 but not Statl. IFN-gamma pretreatment enhanced the upregulation of p48 levels by IFN-alpha. Combining RA and IFN results in additive growth inhibition on RCC cell lines. This increase in growth inhibition is not mediated by increased ISGF3 expression.

The promyelocytic leukemia (PML) protein suppresses cyclin D1 protein production by altering the nuclear cytoplasmic distribution of cyclin D1 mRNA.

The majority of the promyelocytic leukemia (PML) protein is present in nuclear bodies which are altered in several pathogenic conditions including acute promyelocytic leukemia. PML nuclear bodies are found in nearly all cells yet their function remains unknown. Here, we demonstrate that PML and the eukaryotic initiation factor 4E (elF-4E) co-localize and co-immunopurify. eIF-4E is involved in nucleocytoplasmic transport of specific mRNAs including cyclin D1. eIF-4E overexpression leads to increased cyclin D1 protein levels; whereas, overexpression of PML leads to decreased cyclin D1 levels. Neither PML nor eIF-4E cause significant changes in cyclin D1 mRNA levels. The association with eIF-4E led us to investigate if PML could alter mRNA distribution as a possible post-transcriptional mechanism for suppressing cyclin D1 production. We show that overexpression of PML results in nuclear retention of cyclin D1 mRNA and that intact PML nuclear bodies are required. Addition of eIF-4E overcomes PML induced retention and alters the morphology of PML bodies suggesting a mechanism by which eIF-4E can modulate PML function. These results raise the possibility that PML nuclear bodies may participate in the regulation of nucleocytoplasmic transport of specific mRNAs.

Expression of the kidney-associated differentiation glycoprotein gp160 and resistance to the antitumor effects of interferon alpha in renal cell carcinomas.

BACKGROUND: Alpha interferon (IFN-alpha) is commonly used to treat patients with advanced renal cell carcinoma (RCC). We previously reported that resistance of RCCs to IFN-alpha in vitro correlated with the expression of a cell-surface glycoprotein of 160,00 kD molecular weight (gp160) which we subsequently identified as aminopeptidase A. MATERIALS AND METHODS: To directly test the role of gp160/APA in IFN-resistance, we stably introduced the gp160/APA cDNA into IFN-sensitive SK-RC-49 cells resulting in the expression of an enzymatically active gp160/APA protein. In addition, to determine if gp160/APA expression could function as a marker of IFN-resistance in vivo, we assessed gp160/APA protein levels in autologous normal kidney and primary renal cancer specimens from 29 patients half of which were randomized to receive adjuvant IFN-alpha therapy following nephrectomy. RESULTS: Four clones which possessed varying amounts of gp160/APA specific enzyme activity were assayed for sensitivity to the antiproliferative effects of IFN-alpha. All four clones exhibited sensitivity to IFN-alpha similar to that observed with parental SK-RC-49 cells. The analysis of tumor tissue detected no significant difference between the mean level of gp160/APA in tissue from control and IFN-alpha treated patients (1.33 A.U. versus 0.9981 A.U., p = 0.23); however, the mean gp160/APA level was significantly less in tumor tissue (mean = 1.15 A.U.) compared to normal tissue (mean = 2.15 A.U.; p < 0.00001). Within the IFN-alpha treated group, tumor gp160/APA levels did not correlate with the development of metastases or survival (p = 0.469). CONCLUSIONS: These data indicate that gp160/APA does not directly convey IFN-resistance to RCC cells and suggest that expression of gp160/APA in primary RCCs does not predict the benefit of IFN-alpha therapy.