Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses.

PURPOSE: To measure the CD8+ T-cell response to a melanoma peptide vaccine and to compare an every-2-weeks with an every-3-weeks vaccination schedule. PATIENTS AND METHODS: Thirty HLA-A2-positive patients with resected stage I to III melanoma were randomly assigned to receive vaccinations every 2 weeks (13 vaccines) or every 3 weeks (nine vaccines) for 6 months. The synthetic, modified gp100 peptide, g209-2M, and a control peptide, HPV16 E7, were mixed in incomplete Freund's adjuvant and injected subcutaneously. Peripheral blood mononuclear cells obtained before and after vaccination by leukapheresis were analyzed using a fluorescence-based HLA/peptide-tetramer binding assay and cytokine flow cytometry. RESULTS: Vaccination induced an increase in peptide-specific T cells in 28 of 29 patients. The median frequency of CD8+ T cells specific for the g209-2M peptide increased markedly from 0.02% before to 0.34% after vaccination (P <.0001). Eight patients (28%) exhibited peptide-specific CD8+ T-cell frequencies greater than 1%, including two patients with frequencies of 4.96% and 8.86%, respectively. Interferon alfa-2b-treated patients also had significant increases in tetramer-binding cells (P <.0001). No difference was observed between the every-2-weeks and the every-3-weeks vaccination schedules (P =.59). CONCLUSION: Flow cytometric analysis of HLA/peptide-tetramer binding cells was a reliable means of quantifying the CD8+ T-cell response to peptide immunization. This assay may be suitable for use in future trials to optimize different vaccination strategies. Concurrent interferon treatment did not inhibit the development of a peptide-specific immune response and vaccination every 2 weeks, and every 3 weeks produced similar results.     

Preoperative low molecular weight heparin as venous thromboembolism prophylaxis in patients at risk for prosthetic infection after knee arthroplasty.

OBJECTIVE: To investigate the effect of preoperative initiation of low molecular weight heparin as prophylaxis for deep venous thrombosis in patients at risk of developing surgical-site infections after knee arthroplasty. DESIGN: Case-control study nested in a cohort. The incidence of surgical-site infection in the cohort was calculated. With the use of data extracted from medical histories and after adjustment for other risk factors, the effect of preoperative heparinization on the risk of incisional and prosthetic infection among case-patients and control-patients (1:3 ratio) was assessed. SETTING: Orthopedic department in a tertiary-care referral hospital. PATIENTS: A cohort of 160 consecutive patients who had received prosthetic knee implants between October 1, 2001, and November 30, 2003. RESULTS: Eighteen patients with surgical-site infections were identified, yielding an incidence of incisional and prosthetic infection of 6.9 (95% confidence interval [CI95], 3.5 to 12.0) and 4.4 (CI95, 1.8 to 8.8) cases per 100 patients undergoing surgery, respectively. Surgical-site infection was associated with preoperative use of low molecular weight heparin (odds ratio [OR], 6.2 after adjustment for medical and surgical factors; CI95 1.5 to 23). Prosthetic infection was strongly associated with preoperative use of prophylaxis (OR, undetermined [100% exposure in case-patients vs 35% exposure in control-patients]; P = .002), but incisional surgical-site infection was not. CONCLUSION: The use of low molecular weight heparins immediately before knee arthroplasty as prophylaxis for deep venous thrombosis should be questioned because of probable increased risk of prosthetic infection.     

Changes in the Household Calorie Supply during the 1994 Economic Crisis in Mexico and Its Implications on the Obesity Epidemic

To characterize the effects of the 1994 economic crisis on calorie sources of Mexican households, five nutrition surveys done every leap year (1992–2000) in national representative samples (> 10,000 households) were analyzed. Each household was visited during 7 days to collect data on foods purchased, exchanged or home-grown and their monetary value. We selected 88 food items to calculate kilocalories/ person/day and cost in pesos/megacalorie (CPMC) for rural-urban strata (localities <2500, ≥2500). The food items were classified in 8 groups and the summation of kilocalories and CPMCs of items in each group were our units of analysis. Linear regressions for 1992–2000 were performed, and slopes and intercepts were used to characterize changes. Available calories showed very little change at the height of the economic crisis. Expensive calories (meat in ur-bans, eggs and milk in rurals, and industrialized meat and soft drinks in both) tended to increase, whereas the most inexpensive staples (cereals, legumes, sugars) decreased their share in both strata. An increase in obesigenic calories was seen, notably in soft drinks, despite a cost increase second only to meat. Main conclusions were: (1) the economic crisis did not affect total calories availability in Mexican households; (2) the 1992–2000 trends in calorie sources were contrary to any crisis effect in rurals and urbans (i.e., expensive foods increased and inexpensive staples decreased); (3) there were sizable rural-urban differences in number, source, and cost of calories; and (4) obesigenic calories increased and soft drinks emerged as a food with its own dynamic.     

Attention deficit disorders: Are we barking up the wrong tree?

Attention deficit disorder (AAD) and attention deficit/hyperactivity disorder (ADHD) are very frequent and protean developmental disorders without a definite biologic marker. This review proposes a framework to understand the enlarged spectrum of its manifestations based on current knowledge of the mechanisms underlying arousal and attention variations during sleep/wake cycle. The neuro-modulation's pivotal role in this process as well as in the fine tuning of synaptic architecture during development must be taken into account when trying to understand the marked fuzziness of the symptoms and the very high prevalence of reported co-morbidities. The series of related interactions includes a cyclic deactivation of the dorso-lateral portion of the prefrontal cortex (DLPFC) during sleep, suspending executive functions, co-occurring with rhythmic periods of decreased noradrenergic tonus. A protracted unbalance in modulation, with catecholaminergic relative deficiency, could explain less-than-optimum waking DLPFC activation and the most important manifestations of ADD. Beside the well documented dopaminergic effects of stimulant medication used in ADD and ADHD, a more important role must be assigned to noradrenaline (NA). At this light hyperactivity and impulsivity are less important dimensions. Rather, an attention deficit spectrum disorder should probably be regarded as a complication of a core defect in prefrontal cortex dependent inhibitory control, underlying inattention.     

Psychosocial effect of mastectomy versus conservative surgery in patients with early breast cancer

Purpose To compare the quality-of-life (QoL) and psycho-social changes in a group of patients with early breast cancer who underwent conservative surgery (BCS) or modified radical mastectomy (MRM). Methods Self-administered questionnaire assessing body image perception, social habits, sexual attraction and self-consciousness with relatives/friends, was randomly assigned to 125 patients (61 BCS, 64 MRM; aged 53±8 and 50±9 years, respectively, p=NS). Results MRM patients reported a significantly higher frequency of changes in body image perception and other related social behaviour such as avoiding going to the beach or using low-cut clothes, and reticence with friends. Conversely, no differences were found regarding sexuality, denial of the disease by the husband/partner, or concealing the disease from family members. Also, no significant differences were found between patients above and below the age of 50 years, for all variables studied after adjustment for surgical procedure. Conclusions Modified radical mastectomy has a negative effect on body image perception and in social behaviour patterns of patients and with a concomitant decrease in QoL. The sexuality of the patient is not significantly affected.     

TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival

Background  

Ovarian carcinomas from 30 BRCA1 germ-line carriers of two distinct high penetrant founder mutations, 20 carrying the 1675delA and 10 the 1135insA, and 100 sporadic cases were characterized for somatic mutations in the TP53 gene. We analyzed differences in relation to BRCA1 germline status, TP53 status, survival and age at diagnosis, as previous studies have not been conclusive.     

Effect of reminder cards on compliance with antihypertensive medication

Objective Poor compliance to antihypertensive medications has been identified as a primary cause of uncontrolled blood pressure (BP), with consequent increases in hypertension‐related morbidity and mortality. Therefore, any measure known to improve compliance should be encouraged. This study assessed the impact of reminder cards on compliance to antihypertensive therapy. Method A field trial was undertaken in pharmacies located in the districts of Lisbon and Porto. Eligible participants comprised those aged 30–74 years, prescribed an angiotensin‐converting enzyme inhibitor (ACEI) in monotherapy, and taken on a once‐daily regimen. Patients were allocated to control group (CG) or intervention group (IG), the latter being provided with a reminder card, an alarm‐type device due to remind the patient of the time to take his medication. Patients were monitored monthly during 3 months for compliance and blood pressure control. Key findings Seventy‐one patients participated in the study (intervention: 35; control group: 36). Compliance was similar between the groups in the first 2 months of follow‐up (97.1% IG vs 94.9% CG at first follow‐up and 97.5% IG vs 94.2% CG at second follow‐up) and higher in the intervention group at the end of the study (97.3% IG vs 87.3% CG; P = 0.011). There were no mean blood pressure differences between compliant and non‐compliant subjects at the end of the study (P value for differences in systolic BP (P_syst) = 0.580; and P value for differences in diastolic BP (P_dlast) = 0.175). Conclusion This small‐scale study indicates a possible positive impact on patients' compliance resulting from the use of reminder cards. However, this needs confirming in larger scale studies with longer monitoring periods.     

Significance of High Density Lipoprotein-Cholesterol in Cardiovascular Risk Prevention

In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the 'low HDL syndrome' with the metabolic syndrome. These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels. We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome.     

Efficacy of a single dose of urapidil for preventing arterial hypertension during the pre-bypass period in coronary surgery

OBJECTIVES: To assess the effect of a single prophylactic dose of urapidil for arterial hypertension during the period before start of extracorporeal circulation. PATIENTS AND METHODS: Forty-four patients with good ventricular function (ejection fraction < 40%) scheduled for coronary surgery were enrolled for prospective study. The patients were randomly assigned to receive 0.5 mg/kg of urapidil (group U, n = 22) or nothing (group N, n = 22) 3 min before skin incision. If hypertension developed sodium nitroprusside was administered, starting with a dose of 0.5 microgram/kg/min. Monitoring of arterial pressure, heart rate and ST segment (DII and V5) was continuous. The study ended with cannulation of the aorta. RESULTS: The demographic features, cardiovascular history, medication and duration of surgery were comparable in the two groups. Six patients in group U (27%) and 19 in group N (86%) developed arterial hypertension (p < 0.001), the duration of which was 2.23 +/- 4.49 min in group U and 9.64 +/- 9.7 min in group N (p < 0.05). Arterial hypotension was observed in 13 group U patients and 7 group N patients (NS). No significant differences in duration of tachycardia, bradycardia or myocardial ischemia were found. CONCLUSIONS: The administration of a single dose of urapidil prevents arterial hypertension during the phase before extracorporeal circulation for coronary surgery and reduces the need for nitroprusside. No clinically relevant side effects are evident.     

Calidad de vida relacionada con la salud informada por los padres en preescolares españoles: propiedades psicométricas del Kiddy-KINDL-R

IntroductionAlthough several tools have been developed to assess general HRQoL in children, parental reports are required to supplement this information, especially in very young children. The parents version of the Kiddy-KINDL-R was developed to assess HRQoL in children aged 3 to 7 years through the reports of their parents or legal guardians.ObjectiveThe aim of this study was to validate the parents version of the Kiddy-KINDL-R questionnaire and assess its psychometric properties in a sample of Spanish preschool-aged children.MethodCross-sectional study in 283 parents or legal guardians of children aged 3 to 6 years that completed the Kiddy-KINDL-R questionnaire and an additional scale to assess anxiety problems. We performed confirmatory factor analysis to assess whether the original Kiddy-KINDL-R version fit the Spanish data; we assessed internal consistency by means of the ordinal alpha and the discriminant validity by means of the Preschool Anxiety Scale.ResultsAlthough the original six-factor model showed a good fit, we propose a model consisting of 22 items and the same 6 factors for the Spanish version. The reliability was excellent, and the internal consistency values were adequate. Our results showed significant negative correlations between the Kiddy-KINDL-R and the external anxiety measure, which was evidence of discriminant validity.ConclusionWe demonstrated that the Spanish version of the Kiddy-KINDL-R had good psychometric properties and that this questionnaire is an adequate assessment tool that could be useful in clinical practice.