A case-control study of the effectiveness of BCG vaccine for preventing leprosy in Yangon, Myanmar

BACKGROUND: Five randomized trials, a follow-up study, and six case-control investigations of BCG vaccine's effectiveness (VE) for preventing leprosy have been conducted internationally, with widely varying estimates of VE. Because of the difficulty of generalizing from disparate results, local estimates of VE are needed for health planning purposes and are currently particularly relevant, given the World Health Organization's (WHO) goal to eliminate leprosy by the year 2000. METHODS: We conducted a case-control study in Yangon, Myanmar. Residents of Yangon between the ages of 6 years and 24 years who were listed in the National Leprosy Registry as being on active treatment for leprosy between December 1992 and April 1993 were eligible to participate in the study as cases. Control subjects were matched to the cases on age, sex, and neighbourhood. RESULTS: One or more doses of BCG were associated with a VE of 66%. The results show a significant trend of increasing VE with increasing number of BCG doses (one dose, VE = 55%; two doses, VE = 68%; three doses, VE = 87%). One dose of BCG vaccine appeared to provide protection substantially higher than that found in an earlier vaccine trial in Myanmar, but consistent with results from case-control studies in other countries. CONCLUSIONS: These data suggest that BCG reduces the risk of leprosy in Myanmar, and that BCG vaccination of infants, along with early case-finding and treatment, should be considered an important part of the leprosy intervention strategy.     

Comparison of the safety and immunogenicity of the lyophilized Mérieux seed and the World Health Organization working reference BCG vaccines in school-aged children in Senegal

In order to validate two new lots of Mérieux BCG vaccine (Mérieux seed derived from strain 1072), a calibration study was performed to compare their safety and immunogenicity to a full dose of the WHO-reference BCG vaccine (Tokyo strain 172) as well as the WHO-reference vaccine given at 1/10 of its normal concentration, in an open, randomized, four-arm, multicenter study in Senegal. A total of 1041 healthy Senegalese children aged 8-10 years were screened for participation in this study, of whom 548 had a negative Mantoux test and complied with inclusion and exclusion criteria. These children were randomly allocated a single dose of one of the following vaccines: full-dose Mérieux BCG vaccine (lot E0650); full-dose Mérieux BCG vaccine (lot E0624); full-dose WHO-reference vaccine (Tokyo strain 172); or 1/10 dose WHO-reference vaccine. A follow-up examination, including a tuberculin test, was performed 10-12 weeks after BCG vaccination for 465 (85%) children: 236 Mérieux BCG vaccine (117 lot E0650; 119 lot E0624); 115 full-dose WHO; 114 1/10 dose WHO. The percentage of subjects with a positive tuberculin test after vaccination was significantly lower (P < 0.001) in the 1/10 dose group (81.5%) compared to the other three groups (> 96%). The mean induration diameter was significantly smaller in subjects who received the low-dose of WHO vaccine compared to the others, according to analyses considering all subjects vaccinated, as well as only those subjects with a positive tuberculin test after vaccination. More children in the low-dose group did not have a vaccination scar, and the mean diameter of scars was smaller in this group. The rate of tuberculin reactions, the classification of reactions (Palmer and Edwards), and the characteristics of the vaccinal lesion were similar for the Mérieux BCG vaccines and the full-dose WHO-reference vaccine. All vaccines were safe, as evidenced by the absence of adenitis or suppurative adenitis during the course of the study. Results from this trial show that the two lots of Mérieux BCG vaccine behave equally as well as the full-dose WHO-reference BCG vaccine. The WHO-reference vaccine, given at 1/10 of its normal concentration was significantly less immunogenic, according to all parameters evaluated.     

Anterior-inferior capsular length insufficiency in the painful shoulder

BACKGROUND: Haemophilus influenzae type b (Hib) conjugate vaccines have demonstrated an impressive impact in diminishing Hib disease in industrialized countries. However, their high cost prompts nonindustrialized countries to corroborate their effectiveness under local conditions before considering their programmatic implementation. Such a postlicensure evaluation of vaccine effectiveness was undertaken in Chile. METHODS: After its licensure in Chile polyribosylribitol phosphate-tetanus toxoid protein conjugate vaccine (PRP-T), combined with diphtheria-tetanus-pertussis vaccine, was introduced into the Expanded Program on Immunization schedules in 36 health centers throughout metropolitan Santiago for 12 months, whereas 35 similar health centers administered only diphtheria-tetanus toxoid-pertussis vaccine. Bacteriologic surveillance data for invasive Hib cases collected over the ensuing 30 months were analyzed. RESULTS: In an intent-to-vaccinate (effectiveness) analysis, PRP-T provided 90.2% protection (95% confidence interval, 74.5 to 100%) against invasive Hib disease (40 vs. 4 cases, P < 0.001). Vaccine effectiveness was 91.3% against meningitis (22 vs. 2 cases) and 80% against pneumonia and empyema (10 vs. 2 cases, P = 0.039). Vaccine efficacy among infants who received all three doses of PRP-T was 91.7% (95% confidence interval, 64.8 to 100%). CONCLUSIONS: Programmatic use of Hib conjugate vaccine administered in combination with diphtheria-tetanus-pertussis vaccine constitutes a highly effective and practical intervention in Chile, a newly industrializing country.     

Perceived value of providing peer reviewers with abstracts and preprints of related published and unpublished papers

Owing to the civil war, the inhabitants of Kabul in Afghanistan are suffering a major epidemic of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica. Surveys conducted among children in 2 high-rise apartment blocks in the city revealed that the prevalence of active lesions was much lower on upper stories: 84% lower in one block (chi 2 = 7.13, d.f. = 1, P = 0.008) and 54% lower in the other (chi 2 = 6.17, d.f. = 1, P = 0.01). Similar trends were apparent with regard to scars from old lesions. These results suggest that in Kabul most transmission of ACL takes place in the home. In addition, the results imply that there must be limited vertical movement of the vector within apartment blocks. Together, these findings suggest that indoor spraying should be an effective means of control and that insecticidal applications could probably be restricted to lower stories.     

Sexual segregation in infant mice: behavioural and neuroendocrine responses to d-amphetamine administration

An epidemiologic survey (n = 466) was conducted in an area of subtropical rainforest in north-west Ecuador with the following objectives: (1) to determine the prevalence of cutaneous leishmaniasis (CL), (2) to identify the Leishmania species causing human disease, (3) to investigate the major clinical manifestations of leishmaniasis, (4) to study cellular and humoral immune response indicators associated with disease status and (5) to identify risk factors for CL. Fourteen percent of subjects had parasitologically confirmed CL; 33% had evidence of prior disease. However, 17.2% of subjects with a negative CL clinical history presented with a positive Montenegro skin test (MST), indicating the possibility of subclinical infection. The species isolated from subject lesions were L. guyanensis (63%), L. panamensis (33%), and L. brazilensis (4%). Mean specific anti-Leishmania IgG and IgM OD serum levels were highest in subjects diagnosed with current CL, followed by those with prior CL, and were lowest in healthy subjects, respectively (0.56 +/- 0.27 vs 0.33 +/- 0.2 vs 0.22 +/- 0.14; F-ratio = 74; P < 0.00001) and (665 +/- 270 vs 481 +/- 220 vs 301 +/- 128.5; F-ratio = 37; P < 0.00001). Likewise, subjects with present CL had measurably higher MST reactions (13 +/- 6.7 mm) than those with prior CL (10.9 +/- 7.8 mm) or healthy individuals (2.4 +/- 2.5 mm; F-ratio = 106; P < 0.00001). Serum concentrations of IgG were predicted by lesion number (t = 2.5; P = 0.018), size (t = 3.7; P = 0.0006), and duration (t = 3.5; P = 0.0013). Furthermore, the MST induration size increased as a function of lesion number (t = 3.0; P = 0.005) and size (t = 3.4; P = 0.022). Subject age and sex did not predict serum IgG or IgM concentrations or MST reactions in the 3 disease groups. Although no sex differences were found with respect to clinical characteristics, children < or = 12 years of age were almost 3 times more likely to have CL lesions or scars located on the face and head area compared to adults (OR = 2.75; 95% CI = 1.4-5.6, P = 0.004). The risk factors associated with disease included age under 5 years (AOR = 1.5; 95% CI = 0.48-2.35), male gender in adults (AOR = 2.8; 95% CI = 1.1-7.8), and wood and/or cane exterior house walls (AOR = 1.8; 95% CI = 1.4-2.5). In contrast, electric home lighting was associated with decreased risk (AOR = 0.7; 95% CI = 0.4-2.3). The results suggest that it may be possible to modify a portion of the risk of CL by making changes in the housing environment which may help to reduce the amount of human-vector contact.     

Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo

PURPOSE: To investigate the efficacy and safety of oral ondansetron in the control of cisplatin-induced delayed emesis in patients who do not require rescue antiemetic therapy for acute emesis. PATIENTS AND METHODS: Five hundred thirty-eight chemotherapy-naive patients who received cisplatin chemotherapy (> or = 70 mg/m2), and who were not rescued for acute emesis, were eligible to be randomized to receive one of the three oral regimens to control delayed emesis. Group I received placebo on days 2 to 6; group II received ondansetron 8 mg twice daily on days 2 and 3 and placebo on days 4 to 6; group III received ondansetron 8 mg twice daily on days 2 to 6. All patients received intravenous ondansetron (0.15 mg/kg every 4 hours for three doses) for the control of acute emesis on day 1. The number of emetic episodes on days 2 and 3 combined (days 2/3, when incidence and severity of delayed emesis were expected to be greatest) was considered the primary measure of efficacy. RESULTS: Patients who received odansetron had significantly fewer emetic episodes on days 2/3, 4, and 5 than those who received placebo (P < or = .002 on each day). Additionally, significantly more patients who received ondansetron had a complete plus major response (C+MR; < or = two two emetic episodes) than those who received placebo on days 2/3 (56% v 37%, P = .001), 4 (94% v 85%, P = .005), and 5 (98% v 88%, P = .006). Patients who received ondansetron had significantly less nausea on day 2/3 when day-1 nausea was used as the baseline score (P = .025). Patients who received ondansetron also had significantly less nausea on day 4 (P = .042) and the results approached significance on day 5 (P = .066). CONCLUSION: Oral ondansetron had a significant effect in the control of cisplatin-induced delayed emesis and nausea in patients who had not required rescue antiemetics during the acute emesis period. The control of delayed nausea and vomiting was most notable in the immediate 2 days following cisplatin administration, with the clinical difference narrowing between the two treatment arms on subsequent days.     

Hepatitis A vaccination

The safety and immunogenicity of an inactivated hepatitis A virus vaccine were assessed in 101 healthy adults. Seronegative persons with normal serum aminotransferase levels were grouped according to age: Group 1 (n = 24) and group 3 (n = 22) were between 18 and 40 years of age, and group 2 (n = 25) and group 4 (n = 30) were older than 40 years. Groups 1 and 2 received vaccine on a 0-, 1-, and 2-month schedule (schedule A), and groups 3 and 4 received the vaccine on a 0-, 1-, and 12-month schedule (schedule B). Of the 101 vaccinated subjects, 98 (97%) seroconverted with antibody titers to hepatitis A virus of > or = 20 IU per liter after the first dose, and all subjects seroconverted after the second dose. The geometric mean titers a month after the third vaccine dose were significantly greater (P < .03) on both schedules for younger subjects (schedule A, 1,743 IU per liter, and schedule B, 7,882 IU per liter) than for older subjects (schedule A, 826 IU per liter, and schedule B, 4,279 IU per liter). Also, the differences in geometric mean titers a month after the third dose were significantly greater (P < .001) for subjects in both age groups on schedule B (group 3, 7,882 IU per liter, and group 4, 4,279 IU per liter) than for those on schedule A (group 1, 1,743 IU per liter, and group 2, 826 IU per liter). The hepatitis A virus was well tolerated, with mild discomfort at the injection site being the main side effect. This vaccine is both safe and highly immunogenic.     

Treatment of major depression in HIV-seropositive men. HIV Neurobehavioral Research Center Group

BACKGROUND: The purpose of this randomized double-blind, placebo-controlled study was to compare the efficacy and safety of fluoxetine plus group psychotherapy versus group psychotherapy alone in HIV-seropositive men (based on 1986 CDC classes II, III, and IV.C.2) who had been diagnosed with major depressive disorder (DSM-III-R). METHOD: During a 7-week trial, patients were treated with fluoxetine 20-60 mg or placebo 1-3 capsules per day and were seen in weekly supportive group psychotherapy. In addition, subjects were rated on the 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinical Global Impressions scales for Improvement (CGI-I) and Severity of Illness (CGI-S), and the short version of the Beck Depression Inventory (BDI-13). Of the 47 patients enrolled in the study, 25 were administered fluoxetine and 22 were given placebo. RESULTS: Subjects who received fluoxetine began to show significantly more improvement than patients who received placebo on both self- and observer-rated scales by the end of the first week of treatment. By endpoint, patients treated with fluoxetine experienced greater mean changes from baseline compared with placebo-treated patients on the HAM-D-17 (12.1 vs. 6.6; F = 6.53, df = 1,45; p < .05) and BDI-13 (5.9 vs. 1.2; F = 5.73, df = 1,45; p < .05), and a greater percentage of fluoxetine-treated patients experienced a > or = 50% in HAM-D-17 scores (64% vs. 23%; chi2= 8.60, df = 1, p < .01). Differences were particularly apparent in subjects whose initial depressive episodes were rated as severe (i.e., HAM-D-17 score > or = 24). Severely depressed patients treated with fluoxetine had an endpoint CGI-I of 1.4 compared with an endpoint CGI-I of 2.7 for patients treated with placebo (F = 6.02, df = 1,11; p < .05). Further, side effects were generally mild and transient. The most frequently noted effects reported by subjects treated with fluoxetine were nausea, dry mouth, headache, and diarrhea, in decreasing order of frequency. CONCLUSION: This study supports the efficacy and safety of fluoxetine over and above group psychotherapy for the treatment of HIV-associated major depression.     

Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside

PURPOSE: To perform a double-blind randomized trial with American Joint Commission on Cancer (AJCC) stage III melanoma patients for the following reasons: (1) to confirm our previous finding that patients with antibodies against the melanoma differentiation antigen GM2 have an improved prognosis, and (2) to demonstrate clinical benefit from GM2 antibody induction. PATIENTS AND METHODS: One hundred twenty-two patients with AJCC stage III melanoma who were free of disease after surgery were randomized: 58 to receive treatment with the GM2/BCG vaccine, and 64 to receive treatment with bacille Calmette-Guèrin (BCG) alone. All patients were pretreated with low-dose cyclophosphamide (Cy). RESULTS: GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. With a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval (P = .004) and a 17% increase in overall survival (P = .02) in these 57 antibody-positive patients, confirming our earlier experience. Exclusion of all patients with preexisting GM2 antibodies (one in the GM2/BCG group and five in the BCG group) from statistical analysis resulted in a 23% increase in disease-free interval (P = .02) and a 14% increase in overall survival (P = .15) at 51 months for patients treated with the GM2/BCG vaccine. However, when all patients in the two treatment groups were compared as randomized, these increases were 18% for disease-free interval and 11% for survival in the GM2/BCG treatment group, with neither result showing statistical significance. CONCLUSION: (1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.     

Comparative study of the efficacy of two types of BCG vaccines administered in different doses

BACKGROUND: In 1993, WHO and UNICEF recommended the administration of 0.05 ml doses of BCG, instead of 0.1 ml, to newborns. This recommendation was adopted by the Chilean Ministry of Health, using the Mérieux vaccine. Subsequently, different Health Services detected a high percentage of children without BCG scar at the time of their growth and development control. AIM: To assess the efficacy of BCG vaccination in a double blind randomized fashion, using two vaccine types and different doses. PATIENTS AND METHODS: Newborns of two public hospitals of Santiago were randomly assigned to receive the Tokio or Mérieux BCG strains in doses of 0.05 or 0.1 ml. Ninety five to 125 days after vaccination, vaccine scar was measured and inmunogenicity was assessed using the tuberculin test. RESULTS: Six hundred newborns (150 in each group) were included in the protocol and results were assessed in 408. The percentage of children with a PPD reaction of 0 mm was 9.3, 3.7, 7.8 and 0% with the Mérieux vaccine in doses of 0.1 ml, Tokio vaccines in doses of 0.1 ml, Mérieux vaccine in doses of 0.05 ml and Tokio vaccine in doses of 0.05 ml, respectively. In the same groups the scar diameters were 6.4 +/- 3.4, 7.3 +/- 2.7, 5.6 +/- 2.8 and 7.3 +/- 2.9 mm. The observed differences for each group are significant, depending on the type of strain and dose, but favoring the Tokio type of vaccine. CONCLUSIONS: The BCG scar diameters obtained in this study are similar to those obtained in previous works in 1984 and 1986. This scar is the evidence of vaccination that nurses detect in health controls. Therefore the use of 0.1 doses for vaccination, that result in better scars and PPD response, is recommended.     

Results of the BCG vaccination in Hungary since 1929: evaluation of preventive and immunotherapeutic effectiveness

BACKGROUND: The BCG (Bacille Calmette-Guérin), a living attenuated bacterial vaccine with a characteristic residual virulence, has been used to prevent tuberculosis since 1921 (in Hungary non-systematically since 1929) and applied for immunostimulation in neoplasia since the 1960s. MEASURES: Considering the grave tuberculosis epidemiological situation in Hungary, the BCG revaccination became compulsory up to 20 years old tuberculin negatives since 1959. The Pasteur P1173P2 BCG strain has been used for vaccine manufacturing with improved quality control methods according to the requirements of the WHO. With in systematic BCG primo and revaccination policy 8.1 million BCG vaccination from 1959 to 1983 then further 3.1 million between 1984 and 1996 have been performed. RESULTS: Linear regression analysis demonstrates that the decrease of the TB incidence in children was 3-5 times more rapid (annual average decrease was 25.5%) than in adult since 1959. Multiple regression analysis indicates that the BCG is the strongest explanatory variable decreasing children TB incidence among other antituberculosis measures. The BCG vaccination efficacy ins demonstrated by 2 x 2 table analysis. The systematic BCG vaccination, the living and persisting BCG in the macrophages, confers acquired resistance against virulent TB infections. The immunostimulation in neoplasia has been applied with concentrated BCG developed in Hungary since 1979. The adverse reactions are at accepted frequency. The number of BCG vaccinated subjects was estimated at 1.5 billion from 1948 to 1974 in the world. The yearly number of BCG vaccination in the WHOI-EPI System is estimated 50-100 million. CONCLUSION: The efficacy of the BCG vaccination can only be ensured if the vaccine is manufactured and controlled with standardized methods, and applied in a systematic vaccination programme. The effectiveness has to be evaluated in statistically valid biostatistical models.     

Lack of correlation between the reduction of sevoflurane MAC and the cerebellar cyclic GMP concentrations in mice treated with 7-nitroindazole

The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. In humans, production of IFN-gamma is associated with the control of infection in children infected by Leishmania chagasi. In visceral leishmaniasis, an impairment in IFN-gamma production and high IL-4 and IL-10 levels (Th2 cytokines) are observed in antigen-stimulated peripheral blood mononuclear cells (PBMC). Moreover, IL-12 restores IFN-gamma production and enhances the cytotoxic response. IL-10 is the cytokine involved in down-regulation of IFN-gamma production, since anti-IL-10 monoclonal antibody (mAb) restores in vitro IFN-gamma production and lymphoproliferative responses, and IL-10 abrogates the effect of IL-12. In cutaneous and mucosal leishmaniasis, high levels of IFN-gamma are found in L. amazonensis-stimulated PBMC. However, low or absent IFN-gamma levels were observed in antigen-stimulated PBMC from 50% of subjects with less than 60 days of disease (24 +/- 26 pg/ml). This response was restored by IL-12 (308 +/- 342 pg/ml) and anti-IL-10 mAb (380 +/- 245 pg/ml) (P < 0.05). Later during the disease, high levels of IFN-gamma and TNF-alpha are produced both in cutaneous and mucosal leishmaniasis. After treatment there is a decrease in TNF-alpha levels (366 +/- 224 pg/ml before treatment vs 142 +/- 107 pg/ml after treatment, P = 0.02). Although production of IFN-gamma and TNF-alpha might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involved in the tissue damage seen in tegumentary leishmaniasis.     

鸦胆子、丝裂霉素和卡介苗膀胱灌注预防浅表性膀胱癌术后复发的前瞻性临床研究

Objective: The aim of this study was to evaluate the effects and safety of brucea javanica oil, mitomycin and BCG for preventing postoperative relapse of superficial bladder cancer through perfusion. Methods: From July 2000 to May 2006, 178 patients with primary superficial bladder cancer (Ta-1, G1-2) were divided into three groups after operation in random: 57 pa-tients in group A received perfusion of 60 mL 10% brucea javanica oil, and 66 patients in group B received perfusion of 20 mg mitomycin while 55 patients in group C received perfusion of 120 mg BCG. Eighteen perfusions per patient were carried out regularly a week after operation. Patients were followed up for clinical, analytical and cystoscopic evaluations every 3 months for 2 years. The tumor relapse rates and side effects after treatment were evaluated. Results: The relapse rate was 14.04% (8/57), 34.85% (23/66) and 18.18% (10/55) in group A, B and C respectively. The relapse rate in group A was obviously lower than that in group B (χ2 = 6.17, P < 0.05). Disease free interval in group A was significantly different from that in group B (F = 7.03, P < 0.05). Side effect in group A (12.28%) was observably lower than that in group B (43.94%) and group C (83.64%) (χ2AB = 15.72, P < 0.01; χ2AC = 55.34, P < 0.01). Conclusion: Perfusion of 10% brucea javanica oil after operation is safer and more effective in preventing superficial bladder tumour relapse and worth for popularizing.     

Effect of prednisone on response to influenza virus vaccine in asthmatic children

OBJECTIVE: To evaluate the immunogenicity of the influenza virus vaccine in children receiving short-course (a burst) prednisone therapy for acute asthmatic exacerbations. DESIGN: Prospective cohort study. SETTING: Outpatient pediatric clinic of a military medical center. PATIENTS: Children aged 6 months to 18 years requiring the 1996 influenza virus vaccine were eligible for the study. A total of 58 children were enrolled initially. The control group included 37 asthmatic children requiring less than 900 microg/d of inhaled prednisone and their siblings. The prednisone group included 21 children vaccinated at the beginning of a course of prednisone prescribed to treat an asthma exacerbation. Thirty-one control subjects (84%) and 19 patients in the prednisone group (90%) completed the study. Dropout was due to failure to come in for the postvaccination serum sampling. INTERVENTIONS: All study patients underwent immunization with the 1996-1997 trivalent subvirion influenza virus vaccine (FluShield; Wyeth Laboratories Inc, Marietta, Pa) containing 15-microg hemagglutinin antigens each of A/Texas/36/91 (H1N1) (A/H1), A/Wuhan/359/95 (H3N2)(A/H3), and B/Beijing/184/93 (B). The prednisone cohort received a burst of oral prednisone therapy (2 mg/kg per day for 5 days). MAIN OUTCOME MEASURES: To assess the immunogenicity of the vaccine between both groups, at least a 4-fold rise in titer and end titers of at least 1:40 to each of the 3 antigens were compared. Mean changes in geometric titers to the 3 antigens were also compared. RESULTS: Proportion of patients in each group with at least a 4-fold rise in titer to each of the influenza antigens was as follows: for A/H3N3 antigen, 15 patients (79%) in the prednisone group vs 22 controls (71%) (P = .74); for A/ H1N1 antigen, 16 patients in the prednisone group (84%) vs 20 controls (64%) (P = .20); and for B antigen, 7 patients in the prednisone group (37%) vs 8 controls (26%) (P = .53). Proportion of patients in each group with an end titer of at least 1:40 to each of the antigens was as follows: for A/ H3N2 antigen, 18 patients in the prednisone group (95%) vs 28 controls (90%) (P = .69); for A/H1N1 antigen, 17 patients in the prednisone group (89%) vs 26 controls (84%) (P = .99); and for B antigen, 7 patients in the prednisone group (37%) vs 13 controls (42%) (P = .99). There were also no significant differences between groups in the mean changes in geometric titers to any of the 3 antigens. CONCLUSIONS: Prednisone bursts did not diminish the response of asthmatic children to the 1996 influenza virus vaccine, compared with controls. Children can be effectively vaccinated against influenza virus while they are receiving prednisone therapy bursts for asthmatic exacerbations.     

Serum antibodies against Helicobacter pylori proteins VacA and CagA are associated with increased risk for gastric adenocarcinoma

Infection with Helicobacter pylori is associated with the development of gastric cancer. To study whether the infection with H. pylori strains expressing the vacuolating cytotoxin (VacA) and/or the cytotoxin-associated protein (CagA) is associated with an increased risk of developing gastric adenocarcinoma, sera of 90 patients with gastric cancer and 90 matched controls with cardiovascular diseases were investigated for the presence of antibodies to VacA and CagA by immunoblot. Although no significant difference in the overall H. pylori seropositivity was found between cancer patients and controls, antibodies against VacA or CagA were significantly more frequent in cancer patients than in control subjects. Seventy-five (97.4%) of 77 H. pylori-positive patients in the cancer group, but only 60 (84.5%) of 71 H pylori-positive control patients had antibodies against either VacA or CagA (chi 2 = 6.63; relative risk, 2.00; 95% confidence interval, 1.18-3.39; P = 0.01). The presence of antibodies against VacA or CagA alone was also associated with an increased cancer risk (92.2% vs 80.3%; chi 2 = 5.30; relative risk, 1.74; 95% confidence interval, 1.08-2.78; P = 0.021, for VacA; and 87.0% vs 74.6%; chi 2 = 4.90; relative risk, 1.61; 95% confidence interval, 1.06-2.45; P = 0.037, for CagA). The relative risk for gastric cancer was mainly elevated in patients under 65 years, but not in patients at or over 65 years. There is evidence that infection with VacA- or CagA-producing H. pylori strains increases the risk of developing gastric cancer, especially in younger patients.     

The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children

BACKGROUND: Influenzavirus vaccine is used infrequently in healthy children, even though the rates of influenza in this group are high. We conducted a multicenter, double-blind, placebo-controlled trial of a live attenuated, cold-adapted, trivalent influenzavirus vaccine in children 15 to 71 months old. METHODS: Two hundred eighty-eight children were assigned to receive one dose of vaccine or placebo given by intranasal spray, and 1314 were assigned to receive two doses approximately 60 days apart. The strains included in the vaccine were antigenically equivalent to those in the inactivated influenzavirus vaccine in use at the time. The subjects were monitored with viral cultures for influenza during the subsequent influenza season. A case of influenza was defined as an illness associated with the isolation of wild-type influenzavirus from respiratory secretions. RESULTS: The intranasal vaccine was accepted and well tolerated. Among children who were initially seronegative, antibody titers increased by a factor of four in 61 to 96 percent, depending on the influenza strain. Culture-positive influenza was significantly less common in the vaccine group (14 cases among 1070 subjects) than the placebo group (95 cases among 532 subjects). The vaccine efficacy was 93 percent (95 percent confidence interval, 88 to 96 percent) against culture-confirmed influenza. Both the one-dose regimen (89 percent efficacy) and the two-dose regimen (94 percent efficacy) were efficacious, and the vaccine was efficacious against both strains of influenza circulating in 1996-1997, A(H3N2) and B. The vaccinated children had significantly fewer febrile illnesses, including 30 percent fewer episodes of febrile otitis media (95 percent confidence interval, 18 to 45 percent; P<0.001). CONCLUSIONS: A live attenuated, cold-adapted influenzavirus vaccine was safe, immunogenic, and effective against influenza A(H3N2) and B in healthy children.     

Glimepiride, a new once-daily sulfonylurea. A double-blind placebo-controlled study of NIDDM patients. Glimepiride Study Group

OBJECTIVE: To compare the efficacy and safety of two daily doses of the new sulfonylurea, glimepiride (Amaryl), each as a once-daily dose or in two divided doses, in patients with NIDDM. RESEARCH DESIGN AND METHODS: Of the previously treated NIDDM patients, 416 entered this multicenter randomized double-blind placebo-controlled fixed-dose study. After a 3-week placebo washout, patients received a 14-week course of placebo or glimepiride 8 mg q.d., 4 mg b.i.d., 16 mg q.d., or 8 mg b.i.d. RESULTS: Fasting plasma glucose (FPG) and HbA1c values were similar at baseline in all treatment groups. The placebo group's FPG value increased from 13.0 mmol/l at baseline to 14.5 mmol/l at the last evaluation endpoint (P < or = 0.001). In contrast, FPG values in the four glimepiride groups decreased from a range of 12.4-12.9 mmol/l at baseline to a range of 8.6-9.8 mmol/l at endpoint (P < or = 0.001, within-group change from baseline; P < or = 0.001, between-group change [vs. placebo] from baseline). Two-hour postprandial plasma glucose (PPG) findings were consistent with FPG findings. In the placebo group, the HbA1c value increased from 7.7% at baseline to 9.7% at endpoint (P < or = 0.001), whereas HbA1c values for the glimepiride groups were 7.9-8.1% at baseline and 7.4-7.6% at endpoint (P < or = 0.001, within-group change from baseline; P < or = 0.001, between-group change from baseline). There were no meaningful differences in glycemic variables between daily doses of 8 and 16 mg or between once- and twice-daily dosing. Adverse events and laboratory data demonstrate that glimepiride has a favorable safety profile. CONCLUSIONS: Glimepiride is an effective and well-tolerated oral glucose-lowering agent. The results of this study demonstrate maximum effectiveness can be achieved with 8 mg q.d. of glimepiride in NIDDM subjects.     

Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and diabetic retinopathy in subjects with IDDM and NIDDM

Angiotensin 1 converting enzyme (ACE) catalyses the step which generates angiotensin II, and also inactivates bradykinin, peptides which play a key role in modulating vascular tone. Plasma ACE levels are under genetic control and up to 50% of the variation is due to an insertion/deletion (I/D) polymorphism of ACE gene with highest levels found in DD homozygotes. Studies have shown an association of diabetic nephropathy and ischaemic heart disease with angiotensin converting enzyme gene polymorphism in subjects with diabetes. We examined the association between diabetic retinopathy and ACE gene insertion/deletion polymorphism in 363 subjects with NIDDM (aged 68.3 +/- 10.7 years; 201 male, 162 female), 186 subjects with IDDM (aged 42.4 +/- 15.0 years; 100 male, 86 female) and 98 controls. These subjects were characterized for ACE I/D polymorphism employing standard primers. Diabetic retinopathy was diagnosed by ophthalmoscopy through dilated pupils by an ophthalmologist and classified as non-proliferative or proliferative retinopathy. As expected, diabetic retinopathy was strongly associated with duration of diabetes (p < 0.001) in both IDDM and NIDDM. Any retinopathy was present in 51% subjects with IDDM and 49% of subjects with NIDDM, while 22% of IDDM subjects and 5% of subjects with NIDDM had proliferative retinopathy. The frequency of I allele was 0.477 vs 0.482 vs 0.510 and D allele was 0.523 vs 0.518 vs 0.490, among subjects with IDDM, NIDDM and controls, respectively. The frequency of ACE I/D genotype was similar in subjects with IDDM, NIDDM, and controls (chi 2 = 0.46, df = 4, p = ns). Presence or absence of retinopathy was not significantly associated with ACE genotype in subjects with IDDM (chi 2 = 3.42, df = 2, p = ns) or NIDDM (chi 2 = 0.51, df = 2, p = ns). Among subjects with retinopathy, there was no significant association between ACE genotype and type of retinopathy. Controlled for duration of diabetes, the frequency of I/D genotype was not significantly different in 271 subjects with retinopathy (IDDM and NIDDM combined) when compared with 86 subjects without retinopathy at 15 years or more after diagnosis of diabetes (chi 2 = 1.29, df = 2, p = ns). These findings indicate that I/D polymorphism of ACE gene is not a useful marker and is unlikely to play a major role in determining genetic susceptibility to diabetic retinopathy or the severity of diabetic retinopathy.     

MST-16, a novel derivative of bis(2,6-dioxopiperazine), synergistically enhances the antitumor effects of anthracyclines

OBJECTIVE: The aim of this study was to evaluate whether toluene, like many other organic solvents and solvent mixtures, could impair color vision. SUBJECTS AND METHODS: We investigated color vision impairment in three groups of workers, two groups occupationally exposed to toluene and a nonexposed group. The first exposed group, group E1, comprised 41 workers (median value of toluene in air 35.00 ppm, range 11.3-49.3 ppm) and the second exposed group, group E2, comprised 32 subjects (median value of toluene in air 156.00 ppm, range 66.0-250.0 ppm). The nonexposed group, group NE, comprised 83 subjects. Color vision was evaluated by the Lanthony D-15 desaturated test according to Verriest's classification: type I, loss in the red-green range; type II, loss in the blue-yellow and red-green ranges, and type III, loss in the blue-yellow range. Subjects were classified as dyschromates if specific acquired loss was determined in at least one eye. In both exposed groups, exposure was evaluated by measurement of the concentration of toluene in the ambient air and in the blood. In group E2, level of hippuric acid and orthocresol in urine after the work shift were also determined. The Mann-Whitney U-test, t-test, chi 2-test, and Spearman's rank correlation and multiple regression analysis were used for statistical analysis. RESULTS: Type III dyschromatopsia was detected in all groups examined: 26.6% of the workers in group NE, 31.7% of those in group E1, and 50% of those in group E2. As many as 15.6% of the workers in group E2, 4.8% of those in group E1, and only 1.2% of those in group NE had type II dyschromatopsia. A statistically significant difference in the prevalence of total dyschromatopsia (type III + type II) was established among the three examined groups together (chi 2 = 14.13; df = 2; P < 0.01), between group E2 and group E1 (chi 2 = 4.96; P < 0.05), and between group E2 and group NE (chi 2 = 12.50; P < 0.005), whereas no significant difference was found between groups E1 and NE. Type III dyschromatopsia was significantly correlated with age in group NE (P < 0.01) and in group E1 (P < 0.005). In group E2, both type II (P < 0.05) and type III dyschromatopsia correlated with toluene in ambient air and with the duration of exposure to toluene (both P < 0.005). In group E2, total dyschromatopsia correlated significantly with toluene in ambient air and in blood (both P < 0.05) as well as with hippuric acid in urine after the work shift (P < 0.001). CONCLUSION: This study suggests that toluene can impair color vision.     

Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis

BACKGROUND: Rotavirus is the most common cause of acute childhood gastroenteritis. Vaccination with live oral heterologous rotavirus vaccines may prevent rotavirus gastroenteritis. We assessed the efficacy of rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) against severe rotavirus gastroenteritis in Finnish children in a randomised placebo-controlled double-blind trial. METHODS: Placebo or RRV-TV (titre 4x10(5) plaque-forming units) was given to infants at ages 2, 3, and 5 months. The children were followed up for one or two rotavirus epidemic seasons. The main outcome measure was protection against severe rotavirus gastroenteritis (score > or =11 on a 20-point severity scale). 2398 children were enrolled and received at least one dose of RRV-TV (n=1191) or placebo (n=1207). The primary efficacy analysis was based on children who received three doses of RRV-TV (n=1128) or placebo (n=1145). FINDINGS: 256 episodes of rotavirus gastroenteritis occurred at any time during the study; 65 were among 1191 RRV-TV recipients, and 191 among 1207 placebo recipients (vaccine efficacy 66% [95% CI 55-74]; intention-to-treat analysis). 226 episodes were included in the primary efficacy analysis of fully vaccinated children (54 among 1128 RRV-TV recipients, 172 among 1145 placebo recipients; vaccine efficacy 68% [57-76]). 100 episodes were severe, eight in RRV-TV recipients and 92 in placebo recipients (vaccine efficacy 91% [82-96]). INTERPRETATION: RRV-TV vaccine was highly effective against severe rotavirus gastroenteritis in young children. Incorporation of this vaccine into routine immunisation schedules of infants could reduce severe rotavirus gastroenteritis by 90% and severe gastroenteritis of all causes in young children by 60%.