Lessons from Cuba: mass campaign administration of trivalent oral poliovirus vaccine and seroprevalence of poliovirus neutralizing antibodies.

The immunogenicity of trivalent oral poliovirus vaccine (TOPV), which is less effective in tropical than in temperate areas, may potentially be improved in several ways, including increasing the number of doses. Little information is available on TOPV when more than 6 doses are given. The situation in Cuba provides a unique opportunity to relate the seroprevalence of neutralizing antibodies to the dose of TOPV because Cuba has not reported culture-confirmed poliomyelitis since 1973 and TOPV is only administered in twice yearly 1-week mass immunization campaigns. Sera from 2000 children nationwide were studied for neutralizing antibody among children who received 0, 2, 4, 6 and 8 doses of TOPV. These doses were administered in the period 1989-91, when TOPV (from the USSR) was being used with 500,000, 200,000, and 300,000 median tissue-culture-infecting doses (TCID50) for types 1, 2 and 3, respectively--the 5:2:3 formulation. Seroprevalence of neutralizing antibody after two TOPV doses was 91.5% for type 1, 90.8% for type 2, and 45.9% for type 3. Seroprevalence of type-3 neutralizing antibody after 6 doses remained low (73.4%), but increased to 83.5% after 8 doses (P < 0.05). Although 16.5% of the children remained unprotected for type-3 infection even after 8 doses, mass campaign immunization strategies were sufficient to eradicate the transmission of wild poliovirus in Cuba. Because the seroprevalence of type-1 neutralizing antibody was high (91.5%) after two campaign doses, additional studies using different formulations are needed to determine whether simultaneous improvement in the type-3 response to two campaign doses can be achieved.     

The heat stability of Plasmodium lactate dehydrogenase-based and histidine-rich protein 2-based malaria rapid diagnostic tests

Malaria rapid diagnostic tests (RDTs) have performed well in a variety of studies, but recent reports have described sensitivity for Plasmodium falciparum as significantly lower than that required for operational deployment. Exposure to high temperature has been suggested as an explanation. This study assessed the temperature stability of two different Plasmodium lactate dehydrogenase (pLDH)- and three histidine-rich protein 2 (HRP2)-detecting RDTs. One HRP2 test proved insufficiently sensitive for assessment. After incubation at 35, 45 and 60 degrees C, two RDTs detecting pLDH showed a substantial fall in percentage test line positivity over time, which was not seen with the remaining two HRP-2-based RDTs. For the particular products studied, variability was high, with the pLDH-based RDTs being less sensitive than HRP2-based RDTs against the sample of P. falciparum used and more susceptible to heat-induced damage, but the reasons for this are unclear. The performance of malaria RDTs can be adversely affected at the temperatures to which they will be exposed when transported to, and used in, the rural tropics.     

Mitigating the health effects of disasters for medically underserved populations: electronic health records, telemedicine, research, screening, and surveillance

The Regional Coordinating Center for Hurricane Response (RCC) collaborated with the EXPORT Centers (Centers of Excellence in Partnerships for Community Outreach, Research on Health Disparities and Training) to rebuild, revitalize, and improve the health care infrastructure in the Gulf Coast states damaged by Hurricanes Katrina and Rita. This initiative aims to enhance the provision of health care by installing Electronic Health Records and Telepsychiatry systems throughout the Gulf Coast. Through the EXPORT Centers, the RCC plans to perform screening and surveillance projects within the communities and develop research projects focused on eliminating health disparities affecting underserved populations in the region. Another goal is to establish partnerships with EXPORT Centers, Community Health Centers, and other essential primary care practices in hurricane-ravaged communities. Through these partnerships, the overarching goal is to create a balanced health care system model that academic institutions can integrate into preventive care for emergency planning and research.     

The Anti-HIV potency of cyclotriazadisulfonamide analogs is directly correlated with their ability to down-modulate the CD4 receptor

9-Benzyl-3-methylene-1,5-di-p-toluenesulfonyl-1,5,9-triazacyclododecane (CADA) has been identified as a novel antiviral lead compound with significant anti-human immunodeficiency virus and anti-human herpesvirus 7 activity. Surprisingly, this compound selectively decreased the expression of the CD4 glycoprotein, the primary receptor needed for the entry of both viruses. Herein, we describe the CD4 down-modulating and antiviral potencies of more than 25 CADA derivatives. Flow cytometric evaluation of cellular CD4 receptor expression in T cells demonstrated the specific CD4 down-modulating capacity of the CADA derivatives, with IC(50) values similar to those obtained in the antiviral assays. The close correlation observed between the CD4 down-regulating and anti-HIV potencies of the CADA derivatives further points to CD4 receptor down-modulation as the primary mode of antiviral action for this group of compounds.     

Permanent hair dyes and bladder cancer: risk modification by cytochrome P4501A2 and N-acetyltransferases 1 and 2

We have previously reported permanent hair dye use to be a significant risk factor for bladder cancer in US women. We also have examined N-acetyltransferase-2 (NAT2) phenotype in relation to the hair dye-bladder cancer relationship, and found that the association is principally confined to NAT2 slow acetylators. In the present study, we assessed the possible modifying effects of a series of potential arylamine-metabolizing genotypes/phenotypes (GSTM1, GSTT1, GSTP1, NAT1, NAT2, CYP1A2) on the permanent hair dye-bladder cancer association, among female participants (159 cases, 164 controls) of the Los Angeles Bladder Cancer Study. Among NAT2 slow acetylators, exclusive permanent hair dye use was associated with a 2.9-fold increased risk of bladder cancer (95% CI = 1.2-7.5). The corresponding relative risk in NAT2 rapid acetylators was 1.3 (95% CI = 0.6-2.8). Frequency- and duration-related dose-response relationships confined to NAT2 slow acetylators were all positive and statistically significant. No such associations were noted among NAT2 rapid acetylators. Among CYP1A2 'slow' individuals, exclusive permanent hair dye use was associated with a 2.5-fold increased risk of bladder cancer (95% CI = 1.04-6.1). The corresponding risk in CYP1A2 'rapid' individuals was 1.3 (95% CI = 0.6-2.7). Frequency- and duration-related dose-response relationships confined to CYP1A2 'slow' individuals were all positive and statistically significant. No such associations were noted among CYP1A2 'rapid' individuals. Among lifelong non-smoking women, individuals exhibiting the non-NAT1*10 genotype showed a statistically significant increase in bladder cancer risk associated with exclusive permanent hair dye use (OR = 6.8, 95% CI = 1.7-27.4). The comparable OR in individuals with the NAT1*10 genotype was 1.0 (95%CI = 0.2-4.3). Similarly, all frequency- and duration-related dose-response relationships confined to individuals possessing the non-NAT1*10 genotype were positive and statistically significant. On the other hand, individuals of NAT1*10 genotype exhibited no such associations.     

Squamous cell carcinoma of the oral cavity in patients aged 45 years and under: a descriptive analysis of 116 cases diagnosed in the South East of England from 1990 to 1997

BACKGROUND: there is, currently, much anecdotal and some epidemiological evidence for a rise in oral cancer rates amongst younger individuals, many of whom have had no exposure to traditional risk factors such as tobacco and heavy alcohol use, or at least not the exposure over decades usually associated with this disease. The probity of this assertion and the presence or absence of traditional risk factors needs further evidence. OBJECTIVES: this paper describes the demography and the exposure to potential risk factors amongst a cohort aged 45 years and younger, diagnosed with squamous cell carcinoma of the oral cavity between 1990 and 1997 from the South East of England. MATERIALS AND METHODS: eligible patients registered with a cancer registry were included in this retrospective study. Information was accessed from the database and by a postal questionnaire survey. The self-completed questionnaire contained items about exposure to the following risk factors: tobacco; alcohol; diet; frequency of dental visits and familial cancer. RESULTS AND CONCLUSIONS: this is the largest UK epidemiological study so far to be undertaken on young subjects diagnosed with oral cancer. One-hundred and sixteen cases were recruited representing a response rate of 59%. Slightly over 90% of this cohort were classified as white European. A large proportion of cases (40%) were from social classes I & II suggesting either a true social class difference in young cases versus older oral cancer cases or a possible bias in responders or survivors. Risk factors of tobacco use and excessive alcohol consumption were present in the majority (75%) of patients. Significant differences in the pattern of alcohol consumption were found in female subjects, who were less likely to consume over the recommended amounts of alcohol compared with male subjects. Daily regular fresh fruit and vegetable consumption during the ten year period before cancer diagnosis was recorded to be low. There was a distinct subgroup of cases, 26% of the group, that showed little, if any, exposure to any major risk factors.     

The five amino acid-deleted isoform of hepatocyte growth factor promotes carcinogenesis in transgenic mice

Hepatocyte growth factor (HGF) is a polypeptide with mitogenic, motogenic, and morphogenic effects on different cell types including hepatocytes. HGF is expressed as two biologically active isotypes resulting from alternative RNA splicing. The roles of each HGF isoform in development, liver regeneration and tumorigenesis have not yet been well characterized. We report the generation and analysis of transgenic mice overexpressing the five amino acid-deleted variant of HGF (dHGF) in the liver by virtue of an albumin expression vector. These ALB-dHGF transgenic mice develop normally, have an enhanced rate of liver regeneration after partial hepatectomy, and exhibit a threefold higher incidence of hepatocellular carcinoma (HCC) beyond 17 months of age. Moreover, overexpression of dHGF dramatically accelerates diethyl-nitrosamine induced HCC tumorigenesis. These tumors arise faster, are significantly larger, more numerous and more invasive than those appearing in non-transgenic littermates. Approximately 90% of female dHGF-transgenic mice had multiple macroscopic HCCs 40 weeks after injection of DEN; whereas the non-transgenic counterparts had only microscopic nodules. Liver tumors and cultured tumor cell lines from dHGF transgenics showed high levels of HGF and c-Met mRNA and protein. Together, these results reveal that in vivo dHGF plays an active role in liver regeneration and HCC tumorigenesis.     

Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer.

Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin alpha in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4-6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin alpha 150 IU kg(-1) subcutaneously (s.c.) three times a week (n = 42) or 300 IU kg(-1) s.c. three times a week (n = 44). Reductions in epoetin alpha dosage were made during the study if Hb level increased to >15 g dl(-1). The mean weekly dosage was 335 and 612 IU kg(-1), respectively, in the two active treatment groups. Significantly fewer (P < 0.05) epoetin alpha-treated patients experienced anaemia (Hb < 10 g dl(-1)) during the course of chemotherapy (300 IU kg(-1), 39%; 150 IU kg(-1), 48%; untreated, 66%). This was reflected in the significantly lower number of treated patients transfused [300 IU kg(-1), 20% (P< 0.001); 150 IU kg(-1), 45% (P< 0.05); untreated, 59%]. Epoetin alpha was well-tolerated, and there was no evidence of sustained, clinically significant, hypertension. In summary, epoetin alpha is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC.