Human gammadelta T cells: a nonredundant system in the immune-surveillance against cancer.

Down-regulation of expression of MHC alleles, as well as tumor-specific antigens, is observed frequently during tumor progression, resulting in an impairment of MHC-restricted, alphabeta-T-cell-mediated, tumor-specific immunity. Given the unique set of antigens recognized and the lack of requirement for classical antigen-presenting molecules, gammadelta T cells might, therefore, represent a nonredundant system in anticancer surveillance, as proposed for the immune response against pathogens. Evidence that gammadelta and alphabeta T cells make distinct contributions to anticancer surveillance has been provided recently in mice. Here, we discuss the potential role played by resident Vdelta1(+) and circulating Vdelta2(+) T cells in the defense against solid tumors and hematological malignancies.     

Costs of Immunization Programs for 10 Vaccines in 94 Low- and Middle-Income Countries From 2011 to 2030

ObjectivesUnderstanding the level of investment needed for the 2021-2030 decade is important as the global community faces the next strategic period for vaccines and immunization programs. To assist with this goal, we estimated the aggregate costs of immunization programs for ten vaccines in 94 low- and middle-income countries from 2011 to 2030.MethodWe calculated vaccine, immunization delivery and stockpile costs for 94 low- and middle-income countries leveraging the latest available data sources. We conducted scenario analyses to vary assumptions about the relationship between delivery cost and coverage as well as vaccine prices for fully self-financing countries.ResultsThe total aggregate cost of immunization programs in 94 countries for 10 vaccines from 2011 to 2030 is $70.8 billion (confidence interval: $56.6-$93.3) under the base case scenario and $84.1 billion ($72.8-$102.7) under an incremental delivery cost scenario, with an increasing trend over two decades. The relative proportion of vaccine and delivery costs for pneumococcal conjugate, human papillomavirus, and rotavirus vaccines increase as more countries introduce these vaccines. Nine countries in accelerated transition phase bear the highest burden of the costs in the next decade, and uncertainty with vaccine prices for the 17 fully self-financing countries could lead to total costs that are 1.3-13.1 times higher than the base case scenario.ConclusionResource mobilization efforts at the global and country levels will be needed to reach the level of investment needed for the coming decade. Global-level initiatives and targeted strategies for transitioning countries will help ensure the sustainability of immunization programs.     

Docetaxel, 5-fluorouracil, and leucovorin as treatment for advanced gastric cancer: results of a phase II study

Background: Previous studies have shown that the taxane, docetaxel, is effective in treating gastric cancer. The aim of this study was to assess the efficacy and safety of docetaxel in combination with 5-fluorouracil (5-FU) and leucovorin (LV). Methods: Thirty patients with histologically proven locally advanced and/or metastatic gastric cancer with WHO performance status 0–2 were enrolled and received either 75 or 100 mg/m² docetaxel as a 1-h intravenous infusion on day 1 every 28 days. All patients also received 5-FU (1800 mg/m²) plus LV (500 mg/m²), by continuous intravenous infusion over 24 h on days 1, 8, and 15 every 28 days. Chemotherapy was given for at least two cycles. Results: Of the 25 evaluable patients, 3 showed a complete response, 4 showed a partial response, and 11 patients had stable disease. The overall response rate was 28.0% (95% confidence interval [CI], 10.4, 45.6). The median time to progression was 5.9 months (95% CI, 5.4, 6.5), and the median overall survival was 7.7 months (95% CI, 7.2, 8.3) for the intent-to-treat population. The most frequent grade III and IV hematological toxicities were neutropenia and anemia. Febrile neutropenia was observed in 10% of patients and 2.4% of cycles. The prophylactic use of granulocyte colony-stimulating factor (G-CSF) in 3 patients reduced the incidence and severity of neutropenia. Other hematological toxicities were rare. Conclusion: Docetaxel in combination with weekly 5-FU and LV is effective in treating patients with advanced/metastatic gastric cancer. This new docetaxel-containing combination shows promise as a third-generation treatment option for gastric cancer. Received: December 25, 2001 / Accepted: April 22, 2002 Offprint requests to: M. Constenla     

A retrospective analysis of the outcome of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck refractory to a platinum-based chemotherapy

AimsRecurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) develops in around 72 000 people in Europe every year. Treatment options are limited, mainly consisting of platinum-based palliative chemotherapy, with median overall survival times of only 6–8 months. No standard second-line treatment after progression on platinum-based chemotherapy is available. Few data have reported the efficacy of these treatments and the outcome of the patients. In an effort to generate such data, this retrospective study analysed clinical records from 151 patients with SCCHN refractory to platinum-based chemotherapy treated between 1990 and 2000 at seven different centres around Europe.Materials and methodsMost patients (45%) received only best supportive care (BSC), and had a median survival of 56 days. A total of 28.5% of the patients received second-line chemotherapies: 16.6% radiotherapy and 9.9% chemoradiotherapy.ResultsNo objective response was observed with the various second-line chemotherapies. The overall median survival was 103 days (95% confidence interval [CI]: 77–126 days) for the whole cohort. The overall objective response rate (ORR) to second-line treatment in this population was calculated to be 2.6%.ConclusionThese results highlight the need for additional treatment options for this disease. Similar, if not superior, response rates have already been observed in initial clinical studies of novel, targeted anti-cancer agents.     

Spondylodiskitis caused by Candida albicans. Report of two new cases

Recently, candidiasis infection is on the increase and several factors have been associated, such us immunodepression, catheters, weakening diseases, prolonged antibiotherapy, HIV infection and IDU. Spondylodiskitis due to Candida sp. is a rare entity. Two cases of spondylodiskitis due to Candida albicans were diagnosed: a 29 year old man and a 35 year old woman. Both were IDUs with a previous history of HIV infection. The most prominent clinical features in both cases were pain, fever and constitutional syndrome. We describe the clinical, diagnostic, and therapeutic features of both cases.     

Cryptic 1p36.3/6q25.2 translocation in three generations ascertained through a foetus with IUGR and cerebral malformations

Here we describe a foetus with intrauterine growth retardation (IUGR), cerebral malformations and a 46,XY,der(1),t(1;6)(p36.3;q25.2) karyotype owing to a familial cryptic translocation segregating in three generations. A balanced translocation was present in the mother, the maternal uncle, the aunt and the grandmother. A female first cousin with dysmorphisms, hydrocephalus and mental retardation was a carrier of a partial trisomy 1p and a partial monosomy 6q. Multiple miscarriages were present in the family pedigree. Parents of the foetus had three other pregnancies: a male with a balanced translocation, and two foetuses with 1p36.3-pter monosomy and 6q25.2-qter trisomy.     

Potential cost-effectiveness of vaccination for rotavirus gastroenteritis in eight Latin American and Caribbean countries.

OBJECTIVES: To estimate the costs, benefits and cost-effectiveness of vaccination for rotavirus gastroenteritis in eight Latin American and Caribbean countries: Argentina, Brazil, Chile, the Dominican Republic, Honduras, Mexico, Panama, and Venezuela. METHODS: An economic model was constructed to estimate the cost-effectiveness of vaccination from the health care system perspective, using national administrative and published epidemiological evidence, country-specific cost estimates, and vaccine efficacy data. The model was applied to the first five years of life for the 2003 birth cohort in each country. The main health outcome was the disability-adjusted life year (DALY), and the main summary measure was the incremental cost per DALY averted. A 3% discount rate was used for all predicted costs and benefits. Sensitivity analyses evaluated the impact of uncertainty regarding key variables on cost-effectiveness estimates. RESULTS: According to the estimates obtained with the economic model, vaccination would prevent more than 65% of the medical visits, deaths, and treatment costs associated with rotavirus gastroenteritis in the eight countries analyzed here. At a cost of US$ 24 per course (for a two-dose vaccine), the incremental cost-effectiveness ratio ranged from 269 US dollars/DALY in Honduras to 10,656 US dollars/DALY in Chile. Cost-effectiveness ratios were sensitive to assumptions about vaccine price, mortality, and vaccine efficacy. CONCLUSIONS: Vaccination would effectively reduce the disease burden and health care costs of rotavirus gastroenteritis in the Latin American and Caribbean countries analyzed here. From the health care system perspective, universal vaccination of infants is predicted to be cost-effective, based on current standards.