Detection of novel gammaherpesviruses in wild animals of South Africa.

Herpesviral DNA was detected in 24/261 DNA samples that were extracted from whole blood of 13 wild animal species in South Africa. Herpesviral DNA was shown in 22 impalas (Aepyceros melampus) and 2 springboks (Antidorcas marsupialis). All of DNA sequences detected in impalas were identical, whereas two DNA sequences detected in springboks were different each other. These three sequences showed 44 to 72% homology to the corresponding gene of the Gammaherpesvirinae, indicating that these three viruses should be unrecognized novel gammaherpesviruses. The putative novel herpesviruses were tentatively designated as Aepyceros melampus (impala) herpesvirus 1 (ImHV-1), Antidorcas marsupialis (springbok) herpesviruses 1 (SpHV-1) and 2 (SpHV-2). ImHV-1 seems to be a relatively independent virus. SpHV-1 belongs to a group of ruminant lymphotropic herpesviruses and SpHV-2 is closer to a malignant catarrhal fever virus group. Potential threat of these herpesviruses to domestic animals should be considered.

Natural recombinant between equine herpesviruses 1 and 4 in the ICP4 gene.

Equine herpesvirus 1 (EHV-1) is a pathogen causing rhinopneumonia in young horses, abortion in mares, and myeloencephalitis in adult horses. Two types, EHV-1 P and EHV-1 B, have recently been dominant among 16 electropherotypes. EHV-1 P and EHV-1 B viruses were compared by long and accurate polymerase chain reaction (LA-PCR) and restriction fragment length polymorphism (RFLP) analysis. Differences in restriction sites were found to be focused in ORF64, which encodes the infected cell protein 4 (ICP4), and downstream of the ICP4 gene. The 3 ' -end and downstream of ICP4 gene of EHV-1 B were found to be replaced by the corresponding region of EHV-4, indicating that EHV-1 B is a naturally occurring recombinant virus between progenitors of EHV-1 P and EHV-4. This is the first report showing a natural interspecies recombinant in alphaherpesviruses.

[Evidence-based management of neutropenia and fever].

Neutropenia and related fever are the most frequently observed toxicities associated with chemotherapy use. In this review, the current approaches based on various Japanese and American medical societies' guidelines in managing these toxicities are examined. First, the therapeutic and prophylactic use of G-CSF is explored. Clinical efficacy of G-CSF as exemplified by the results of a randomized comparative trial conducted based on the latest guidelines of the American as well as Japan Societies of Clinical Oncology is demonstrated. In addition, the difference in clinical efficacy of the therapeutic use of G-CSF with the presence or absence of fever is assessed. Lastly, the current approaches based on the latest guidelines of the American Society of Infectious Diseases and National Comprehensive Cancer Network (NCCN) to manage patients with febrile neutropenia are also reviewed. Specifically, infection work-ups, antibiotics selection, proper methods of usage, and follow-up methods from these guidelines are delineated. It is hoped that this report will provide readers with the most up-to-date information in managing patients with these toxicities.

[Chemotherapy for advanced or metastatic pancreatic cancer: analysis of 43 randomized trials in 3 decades (1974-2002)].

Pancreatic cancer represents a major challenge to oncologists because of its high chemoresistant nature and dismal outcomes, especially in advanced diseases. Clinical trials on the effects of systemic chemotherapy for patients with advanced pancreatic cancer have not been shown to have consistent benefits. A systematic review and meta-analysis was therefore conducted to examine this issue. All randomized trials on chemotherapy treatment for advanced pancreatic cancer published since the 1970's were identified by means of Medline and other major oncology databases. Systematic review of all trials was carefully conducted and data from trials with similar designs and regimens were pooled and grouped together in the benefit outcome analyses. Data for 5,365 patients from 43 randomized controlled trials were identified. Survival benefit over best supportive care was demonstrated in 5-FU-based chemotherapy in 9 randomized trials. However, trials that comparing 5-FU or other cytotoxic agent alone versus 5-FU-based combinations did not show any statistical differences, nor were various 5-FU-combinations comparing among themselves. On the other hand, gemcitabine was shown to improve survival and clinical benefit responses better than 5-FU and other new agents. Overall, these results were encouraging and future research to explore means to optimize drug treatment (especially gemcitabine-based regimens) for advanced pancreatic cancer is warranted.

Long-term follow-up of patients with aplastic anemia and refractory anemia responding to combination therapy with recombinant human granulocyte colony-stimulating factor and erythropoietin.

In our previous study, approximately 60% of aplastic anemia (AA) and refractory anemia (RA) patients treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human erythropoietin (rhEpo) showed a multilineage response. In this study, we analyzed the long-term follow-up of the multilineage responders (multi-R). In the follow-up analysis of 11 multi-R (6 AA and 5 RA), 10 patients (5 AA and 5 RA) were evaluable. The range of time from the start of treatment to the final contact was 50 to 125 months. Analysis of survival times revealed a significant difference between multi-R and non-multi-R among AA patients given this treatment (P = .016). One AA and 1 RA patient among the multi-R developed acute leukemia. Of 7 living multi-R, 3 AA and 2 RA patients did not need transfusion at final contact. Four of them maintained the target hemoglobin concentration of more than 11 g/dL for quality-of-life benefit. The findings suggested that this result is an important advantage of this treatment.

[Gemcitabine-based chemotherapy for non-small cell lung cancer (NSCLC)--a review of 30 randomized trials].

Non-small cell lung cancer (NSCLC) represents a major challenge to oncologists because of its dismal outcomes. Conventional cytotoxic therapies for advanced disease have been unsatisfactory with modest efficacy and high toxicities. The last decade witnessed the introduction of many novel agents with enhanced efficacy and more manageable safety profile than conventional therapies. Gemcitabine is one of these novel agents which was introduced in the mid 1990's in the US/Europe and has been available in Japan since 1999. Due to its unique profile of great efficacy, mild toxicities and combinability with other agents, gemcitabine and its combination have been widely accepted as one of the standard regimens for the treatment of advanced NSCLC. There were multiple clinical trials demonstrated the superiority of gemcitabine or its combination over conventional therapies, especially in terms of increased response, prolonged survival, and quality of life enhancement for these patients. The current review presents an overview of all the randomized clinical trials of gemcitabine and its combination for advanced NSCLC published over the last decade.

What's new in pancreatic cancer treatment?

Pancreatic cancer represents a major challenge to oncologists because of its high chemoresistant nature and dismal outcomes. Conventional therapy for advanced disease relied for a long time on palliative 5-fluorouracil (5-FU)-based chemotherapy, but with unsatisfactory results. The introduction of the novel antimetabolite gemcitabine provides new optimism for patients with advanced pancreatic cancer, as multiple clinical trials have demonstrated the superiority of gemcitabine over 5-FU and other agents for these patients. The benefits of gemcitabine over conventional therapies include improved response rate and enhanced survival, as well as improvement in disease-related symptoms and quality of life in these patients. With these data, gemcitabine is widely accepted worldwide as the therapy of choice by many oncologists for advanced pancreatic cancer. The current review presents an overview of the clinical studies of gemcitabine over the past decade for the treatment of patients with advanced pancreatic cancer. Other investigational regimens or uses (e.g., fixed dose-rate infusion, intraarterial infusion, adjuvant use, chemo-radiation, etc) are also reviewed.

[Systemic capillary leak syndrome presenting remarkable erythrocytosis].

Systemic capillary leak syndrome (SCLS) is a disorder characterized by hypotension, edema, and an increased hematocrit (Ht) due to sudden leakage of plasma into the extravascular space through some unknown mechanism, in which monoclonal gammopathy is observed. A 30-year-old man visited our emergency department because of abdominal pain, and was admitted to our hematology department because of a markedly increased hemoglobin concentration reaching 26.2 g/dl. The polycythemia was thought to be pseudo-polycythemia due to hemoconcentration, and we diagnosed the patient as having SCLS based on the triad of increased hematocrit, whole-body edema which was especially marked in the lower extremities, and monoclonal gammopathy. The patient recovered after administration of extracellular fluids and albumin, but the attacks recurred. Prophylaxis with terbutaline sulfate, theophylline and corticosteroid reduced the frequency of severe attacks. Because there is possibility that patients with SCLS may be admitted to hematology departments due to severe erythrocytosis, we report this case to increase the awareness of hematologists that SCLS is one of the important differential diagnoses of erythrocytosis.

Efficacy of carboplatin with an MEP (mitoxantrone, etoposide and prednisone) regimen for relapsed and CHOP-resistant diffuse large B-cell lymphomas.

Mitoxantrone, etoposide and prednisone (MEP)-based regimens using granulocyte colony-stimulating factor (G-CSF) were designed for relapsed and CHOP-resistant diffuse large B-cell lymphomas in a single institution, and the therapeutic effects and adverse reactions were studied. In a total of 49 patients, the MEP regimen had a 41% (9/22) overall response rate compared with 48% (13/27) for the MEP plus carboplatin (C-MEP) regimen (Chi-squared test, P=0.602). Among 38 CHOP-resistant patients, however, the overall response rate to C-MEP [42% (10/24)] was significantly superior compared with MEP [7% (1/14)] (P=0.023), and the overall survival to C-MEP was superior compared with MEP (P=0.088). Taken together, our results, although non-randomized, suggest that a combination of MEP with carboplatin is better than MEP alone in CHOP-resistant diffuse large B-cell lymphomas.