Autoreactive, cytotoxic T lymphocytes specific for peptides derived from normal B-cell differentiation antigens in healthy individuals and patients with B-cell malignancies.

PURPOSE: To investigate potential immunotherapeutic strategies in B lymphocytic malignancies we looked for CTLs recognizing CD19 and CD20 epitopes. EXPERIMENTAL DESIGN: Three CD19 and CD20 peptides binding to HLA-A*0201 were identified and used to detect peptide specific CTLs by a quantitative real-time PCR to measure IFN-gamma mRNA expression in 23 healthy individuals and 28 patients (18 chronic lymphocytic leukemia (CLL), 7 follicular lymphoma, 2 acute lymphocytic leukemia, and 1 large cell lymphoma). Peptide-specific CTLs were expanded in culture with CD40-activated B cells to test lytic activity in three patients. RESULTS: In healthy individuals, CD8+ T-cell responses were detected in one to CD19(74-82), in three to CD20(127-135), and three to CD20(188-196). Seven of 27 patients (6 with CLL) had CD8+ T cells recognizing CD19(74-82). Seven patients responded to CD20(127-135) and three to CD20(188-196). All were CLL patients. CD19(74-82)-specific CTLs from three patients were expanded over 4 weeks. These cells were HLA-A*0201 specific and lytic for peptide-loaded antigen-presenting cells but not to malignant or unpulsed B cells. CONCLUSIONS: CTLs that recognize CD19 and CD20 epitopes exist in healthy individuals and may be increased in CLL patients. They are of low avidity and require high doses of peptide for activation. Strategies to increase T-cell avidity would be necessary for T-cell immunotherapeutic approaches using the peptides studied.     

Efficacy and Safety of Orally Administered Intravenous Midazolam Versus a Commercially Prepared Syrup

Background:

Among different categories of sedative agents, benzodiazepines have been prescribed for more than three decades to patients of all ages. The effective and predictable sedative and amnestic effects of benzodiazepines support their use in pediatric patients. Midazolam is one of the most extensively used benzodiazepines in this age group. Oral form of drug is the best accepted route of administration in children.

Objectives:

The purpose of this study was to compare the efficacy and safety of a commercially midazolam syrup versus orally administered IV midazolam in uncooperative dental patients. Second objective was to determine whether differences concerning sedation success can be explained by child‘s behavioral problems and dental fear.

Patients and Methods:

Eighty eight uncooperative dental patients (Frankl Scales 1,2) aged 3 to 6 years, and ASA I participated in this double blind, parallel randomized, controlled clinical trial. Midazolam was administered in a dose of 0.5 mg/kg for children under the age 5 and 0.2 mg/kg in patients over 5 years of age. Physiologic parameters including heart rate, respiratory rate, oxygen saturation and blood pressure were recorded. Behavior assessment was conducted throughout the course of treatment using Houpt Sedation Rating Scale and at critical moments of treatment (injection and cavity preparation) by North Carolina Scale. Dental fear and behavioral problems were evaluated using Child Fear Schedule Survey-Dental Subscale (CFSS-DS), and Strength and Difficulties Questionnaire (SDQ). Independent t-test, Chi-Square, and Pearson correlation were used for statistical analysis.

Results:

Acceptable overall sedation ratings were observed in 90% and 86% of syrup and IV/Oral group respectively; Chi-Square P = 0.5. Other domains of Houpt Scale including: sleep, crying and movement were also not significantly different between groups. Physiological parameters remained in normal limits during study without significant difference between groups.

Conclusions:

“Orally administered IV midazolam” preparation can be used as an alternative for commercially midazolam syrup.     

Isfahan Healthy Heart Programme: a comprehensive integrated community-based programme for cardiovascular disease prevention and control. Design,methods and initial experience

The Isfahan Healthy Heart Programme (IHHP) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases (CVD) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population. IHHP started late in 1999 and will be finished in 2005-2006. A primary survey was done to collect baseline data from interventional (Isfahan and Najaf-Abad) and reference (Arak) communities. In a two-stage sampling method, we randomly selected 5 to 10 percent of households from randomly selected clusters. Then individuals aged > or = 19 years were selected for the survey. This way, data from 12,600 individuals (6300 in interventional counties and 6300 in the reference county) was collected and stratified according to living area (urban vs. rural) and different age and sex groups. The samples underwent a 30-minute interview to complete validated questionnaires containing questions on demography, socioeconomic status, smoking behaviour, physical activity, nutritional habits and other behaviour regarding CVD. Blood pressure and body mass index (BMI) measurements were done and fasting blood samples were taken for two hours post load plasma glucose (2 hpp), serum (total, HDL and LDL) cholesterol and triglyceride levels. A twelve-lead electrocardiogram was recorded in all persons above 35 years of age. Community-wide surveillance of deaths, hospital discharges, myocardial infarction and stroke registry was carried out in the intervention and control areas. Four to five years of interventions based on different categories such as mass media, community partnerships, health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention. Considering the results of the baseline surveys, (assessments needed, the objectives, existing resources and the possibility of national implementation) the interventions were planned. They were set based on specific target groups like school children, women, work-site, health personnel, high-risk persons, and community leaders were actively engaged as decision makers. A series of teams was arranged for planning and implementation of the intervention strategies. Monitoring will be done on small samples to assess the effect of different interventions in the intervention area. While four periodic surveys will be conducted on independent samples to assess health behaviours related to CVD risk factors in the intervention and reference areas, the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death, fatal and nonfatal MI and stroke. The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study.     

Randomized controlled trial of aripiprazole versus risperidone for the treatment of amphetamine-induced psychosis

Background: Lifetime prevalence of amphetamine-induced psychotic disorder is reported as being up to 23% for methamphetamine (MA) abusers. Approximately 25% of those with a baseline DSM-IV diagnosis of substance-induced psychosis are diagnosed with primary psychosis at one-year follow-up. Evidence on the treatment of amphetamine psychosis is very limited. Objectives: To investigate the efficacy of risperidone versus aripiprazole in treatment of amphetamine-induced psychotic symptoms. Methods: In a double-blind study, 45 participants were randomly allocated to either aripiprazole 15?mg or risperidone 4?mg daily over a six-week trial. Positive and negative symptoms of psychosis were assessed using the Scale for Assessment of Negative Symptoms (SANS) and the Scale for Assessment of Positive Symptoms (SAPS) at baseline and completion of the trial. Results: SANS and SAPS scores decreased significantly in both groups. Mean SAPS score reduction in risperidone and aripiprazole group was 16.20 and 10.80, respectively, after trial course (p?p?=?0.08). Conclusions: Both aripiprazole and risperidone were effective for patients diagnosed with amphetamine-induced psychotic disorder. However, risperidone had the greater effect on positive psychotic symptoms while patients with negative symptoms may respond better to aripiprazole. There is a case for further studies evaluating the efficacy of atypical antipsychotics in this disorder.     

Percutaneous vertebroplasty in symptomatic hemangioma versus osteoporotic compression fracture

Background:

Percutaneous vertebroplasty (PVP) is more commonly used for osteoporotic compression fractures (OCFs) and osteolytic vertebral body tumors. This study aimed to study the differences between OCFs and vertebral hemangiomas (VHs) treated with PVP.

Materials and Methods:

Between September 2007 and January 2010, we prospectively treated 28 consecutive patients of OCFs (43 recently symptomatic OCFs) and 24 cases of VHs (26 VHs). We used visual analogue scale (VAS) pain and Oswestry Disability Index (ODI) to evaluate the patients. The followup period in group 1 and 2 were 25.1 months (range 12 - 31 months) and 21.3 months (range 14 - 28 months), respectively. Comparison of means was carried out with the Chi Square Tests, t-test, and N Par-Test for multiple comparisons, whenever appropriate. The level of statistical significance was set at P < 0.05.

Results:

Following PVP the VAS score decreased to 4.57 and 4.17 in group 1 and 2, respectively. The ODI scores were 32.5% and 30%, respectively. This decrease in ODI scores lasted throughout the followup period.

Conclusions:

Although the preoperative scores were significantly different between group 1 and 2, there was no significant difference between two groups following the PVP.