Immunogenicity of a Salmonella typhi CVD 908 candidate vaccine strain expressing the major surface protein gp63 of Leishmania mexicana mexicana

Attenuated Salmonella typhi are attractive for use as live vector vaccines to express protozoal antigens and deliver them to the human immune system. The gene encoding the mature form of Leishmania mexicana mexicana gp63 under control of tac promoter was integrated into the delta aroC locus of the chromosome of attenuated delta aroC, delta aroD S. typhi strain CVD 908. After oral immunization of BALB/c mice with two 1 x 10(9) colony forming unit doses given 21 days apart, CVD 908 omega (delta aroC::Ptac-gp63) elicited a broad T cell-mediated immune response against L. m. mexicana gp63 as demonstrated by: (1) lymphoproliferative response to fixed whole L. m. mexicana promastigotes; (2) activation of IL-2 (but not IL-4)-producing lymphocytes; (3) appearance of cytotoxic T cells against mouse mastocytoma cells expressing gp63. This T-cell mediated immune response was associated with significant protection in F1 (BALB/cXC57Bl/6) mice challenged in their footpads with a wild type strain of L. m. mexicana.     

Economic evaluation of cancer treatments: methodological and practical issues

Economic evaluation is a comparative analysis of alternatives in terms of both their costs and consequences. Therefore, the basic task of economic evaluation is to identify, measure, value and compare the costs and effects of the alternatives being considered. In this paper, the methodology of economic evaluation in general and in cancer in particular is reviewed and practical issues are illuminated. In the treatment of cancer patients not only survival and disease-free survival are important outcome parameters, but also quality of years alive. Hence, specific attention is given to the measurement and valuation of quality of life. Economic evaluation is intended to support health policy at different levels of decision making. In cancer treatment, health policy concerns both preventive, curative and palliative strategies, and decisions are often made at the micro and macro level. Economic evaluation can provide essential information on the costs and benefits of each option, and consequently on the optimal policy mix, and thus support decisions on the adoption and utilization of new treatments. Such information may assist policy makers in formulating regulatory policies and legislation, industry in developing products, health professionals in treating and serving patients, and consumers in making personal health decisions.     

Compliance with primary prevention in private practice: creating a tobacco-free environment

A sample of private orthodontic practices (n = 40) from a controlled trial for clinician-initiated tobacco-use prevention was used to test the effectiveness of preventive medicine representative (PMR) visits in creating and maintaining an anti-tobacco office environment. Clinical staff of 20 offices, randomly assigned to the experimental group, were trained by a PMR on the use of anti-tobacco materials (no-smoking signs, posters, and print materials). Twenty control-group offices did not receive any training or special treatment. Subsequently, experimental-group offices were visited by a PMR once every three months and were telephoned six weeks after each visit over a 12-month period. During visits and phone calls, PMRs prompted offices to order anti-tobacco materials. Visits served to introduce offices to new materials and to encourage their continued use. Data from direct observations and self-report measures showed significant differences between experimental and control offices for display of anti-tobacco materials at 1.5 months and 12 months (P < .001). Results suggest that PMR visits may serve as an effective method of introducing and maintaining preventive medicine procedures in clinical environments.     

Chronic lithium treatment decreases brain phospholipase A2 activity

BACKGROUND/AIMS: The hepatitis C virus (HCV) genome consists of quasispecies populations of heterogeneous variants, especially in the hypervariable region. To assess the profiles of viral quasispecies in HCV-related hepatocellular carcinoma, we studied the viral population patterns in serum and liver tissues of 13 HCV-positive patients with hepatocellular carcinoma developed on cirrhotic and non-cirrhotic livers (5 and 8 cases, respectively). METHODS: HCV genome heterogeneity was analyzed by polymerase chain reaction-mediated single-strand conformation polymorphism analysis, which showed multiple DNA bands representing different hypervariable region sequences. RESULTS: The HCV populations were different between tumorous and nontumorous tissues in 3/5 hepatocellular carcinomas with cirrhosis and in 6/8 without cirrhosis. At least one or more than one common band was detected in both compartments in all but one case. No significant differences in the complexity of HCV quasispecies were found in hepatocellular carcinoma with or without underlying cirrhosis. Comparison of the HCV quasispecies profiles in serum and liver tissues showed a different distribution of HCV variants between these two compartments in 6/7 patients. In four cases, both common and compartmentalized sequences were detected, whereas in two cases, both without cirrhosis, the HCV population in serum was completely different from that found in the liver. CONCLUSIONS: These results suggest that the complexity of HCV populations is influenced by the presence of hepatocellular carcinoma rather than by the severity of the underlying chronic liver disease. The different quasispecies patterns found in serum and liver may reflect different biological properties of circulating and intrahepatic HCV particles or the existence of extrahepatic sites of replication.     

Clinical comparison of radiolocalization of two monoclonal antibodies (mAbs) against the TAG-72 antigen

Ten patients with colorectal cancer metastases received 125I-B72.3 and 131I-CC49 prior to laparotomy (five patients received 1 mg, and five 20 mg of each mAb). Tumor:serum ratios of 131I-CC49 were better than those of 125I-B72.3 (P < 0.01 at 1 mg; P = 0.05 at 20 mg; P < 0.01 at both doses). All known lesions > or = 1 cm in diameter were visualized at the 20 mg dose. There was no difference in absolute tumor uptake of 125I-B72.3 or 131I-CC49. We conclude that mAb CC49 has better relative uptake in colorectal cancers than mAb B72.3.     

Analogues of the thrombin receptor tethered-ligand enhance mesangial cell proliferation

Thrombin stimulates cytosolic calcium mobilization and tritiated thymidine incorporation in rat glomerular mesangial cells. This effect may be mediated by a thrombin receptor similar to the receptor found in human platelets. In order to test this possibility, a series of analogues of the thrombin receptor peptide, SFLL-RNPNDKYEPF, was evaluated for their effects on mesangial cells. Analogues of the thrombin receptor peptide containing five, six, seven and 14 amino acids were as efficacious as thrombin with respect to calcium mobilization and thymidine incorporation, although they were significantly less potent. The dissimilarity in potency between thrombin and the thrombin receptor peptides is consistent with the kinetics of the proposed mechanism of action of the enzyme, since the cleavage by thrombin of its receptor results in a tethered ligand which is at a relatively high concentration compared to the free peptides in solution. Those thrombin receptor peptide analogues which showed decreased activity in platelets were tested in mesangial cells. Removal of serine at position one, N-acetylation, or replacement of the phenylalanine at position two with alanine resulted in analogues which were inactive in stimulating mesangial cell proliferation or calcium mobilization. In addition, those analogues which had no stimulatory effects in mesangial cells were not antagonists of SFLLRN-mediated calcium mobilization and thymidine incorporation in mesangial cells.     

Impact of a children's health insurance program on newly enrolled children

CONTEXT: Although there is considerable interest in decreasing the number of US children who do not have health insurance, there is little information on the effect that health insurance has on children and their families. OBJECTIVE: To determine the impact of children's health insurance programs on access to health care and on other aspects of the lives of the children and their families. DESIGN: A before-after design with a control group. The families of newly enrolled children were interviewed by telephone using an identical survey instrument at baseline, at 6 months, and at 12 months after enrollment into the program. A second group of families of newly enrolled children were interviewed 12 months after the initial interviews to form a comparison sample. SETTING: The 29 counties of western Pennsylvania, an area with a population of 4.1 million people. SUBJECTS: A total of 887 families of newly enrolled children were randomly selected to be interviewed; 88.3% agreed to participate. Of these, 659 (84%) responded to all 3 interviews. The study population consists of 1031 newly enrolled children. The children were further classified into those who were continuously enrolled in the programs. The 330 comparison families had 460 newly enrolled children. MAIN OUTCOME MEASURES: The following access measures were examined: whether the child had a usual source of medical or dental care; the number of physician visits, emergency department visits, and dentist visits; and whether the child had experienced unmet need, delayed care, or both for 6 types of care. Other indicators were restrictions on the child's usual activities and the impact of being insured or uninsured on the families. RESULTS: Access to health care services after enrollment in the program improved: at 12 months after enrollment, 99% of the children had a regular source of medical care, and 85% had a regular dentist, up from 89% and 60%, respectively, at baseline. The proportion of children reporting any unmet need or delayed care in the past 6 months decreased from 57% at baseline to 16% at 12 months. The proportion of children seeing a physician increased from 59% to 64%, while the proportion visiting an emergency department decreased from 22% to 17%. Since the comparison children were similar to the newly enrolled children at enrollment into the insurance programs, these findings can be attributed to the program. Restrictions on childhood activities because of lack of health insurance were eliminated. Parents reported that having health insurance reduced the amount of family stress, enabled children to get the care they needed, and eased family burdens. CONCLUSIONS: Extending health insurance to uninsured children had a major positive impact on children and their families. In western Pennsylvania, health insurance did not lead to excessive utilization but to more appropriate utilization.     

The regulation of drugs and medicines in horse racing in the United States. The Association of Racing Commissioners International Uniform Classification of Foreign Substances Guidelines

It is proposed that both polar and radical reactions should be considered when discussing radical ion reactivity. The fact that only the polar reactivity has dominated previous discussions is pointed out. It is argued that if the configuration mixing model is applicable for the estimation of radical cation-nucleophile (or cation-nucleophile) combination reaction barriers, the theory should also explain the reactivity of the proton toward anionic nucleophiles. The model severely overestimates reaction barriers for the latter reactions. The discussion is centered around the following hypothesis: In the absence of severe steric effects, the reactivity of radical ions, especially evident in the reactions with radicals (for example very few radical cations react with dioxygen at measurable rates), is dominated by the degree of coupling between charge and radical centers. Evidence from the literature supporting the hypothesis is presented for a number of different classes of radical ion reactions. Further work to test the validity of the hypothesis is proposed for many of the reaction types. Triarylmethyl radicals and carbenium ions are suggested as models to which the radical and polar reactivities of 9,10-diarylanthracene radical cations may be compared. It is concluded that the radical cation/carbenium ion comparison (for the reaction with acetate ion) would show similar reactivities while the radical cation/free radical comparison (for the reaction with dioxygen) would fail, since no reaction at all would be observed with the radical cation while the free radical reacts rapidly.