RESUMEN

There is still a need for a better and affordable seasonal influenza vaccine and the use of an adjuvant could solve both issues. Therefore, immunogenicity of a combination of low dose of 1/5TH (3 µg of HA) a licensed seasonal flu vaccine with the novel carbohydrate fatty acid monosulfate ester (CMS)-based adjuvant was investigated in ferrets and safety in rabbits. Without CMS, hemagglutination inhibition (HI) antibody titers ranged from ≤5 to 26 three weeks post immunization 1 (PV-1) and from 7 to 134 post-immunization 2 (PV-2) in ferrets. Virus neutralizing (VN) antibody titers ranged from 20 to 37 PV-1 and from 21 to 148 PV-2. CMS caused 10 to 111- fold increase in HI titers and 3 to 58- fold increase in VN titers PV-1 and PV-2, depending on influenza strain and dose of adjuvant. Eight mg of CMS generated significantly higher antibody titers than 1 or 4 mg, while 1 and 4 mg induced similar responses. Three µg of HA plus 4 mg of CMS was considered the highest human dose and safety of two-fold this dose was determined in acute and repeated-dose toxicity studies in rabbits conducted according to OECD GLP guidelines. The test item did not elicit any clinical signs, local reactions, effect on body weight, effect on urine parameters, effect on blood biochemistry, or gross pathological changes. In blood, increased numbers of neutrophils, lymphocytes and/or monocytes were noted and in iliac lymph nodes, increased cellularity of macrophages of minimal to mild degree were observed. In both ferrets and rabbits, body temperature increased with increasing dose of CMS to a maximum of 1 ˚C during the first day post-immunization, which returned to normal values during the second day. In the local tolerance study, histopathology of the site of injection at 7 days PV-1 revealed minimal, mild or moderate inflammation in 5, 8 and 5 animals, respectively. In the repeated-dose study and 21 days PV-3, minimal, mild or moderate inflammation was observed in 15, 18 and 3 animals, respectively. We concluded that the data show CMS is a potent and safe adjuvant ready for further clinical development of a seasonal influenza vaccine and combines high immunogenicity with possible antigen-sparing capacity.

Asunto(s)

Vacunas contra la Influenza , Gripe Humana , Animales , Humanos , Conejos , Hurones , Estaciones del Año , Anticuerpos Antivirales , Gripe Humana/prevención & control , Adyuvantes Inmunológicos , Pruebas de Inhibición de Hemaglutinación , Carbohidratos , Ácidos Grasos , Anticuerpos Bloqueadores , Ésteres , Inflamación

RESUMEN

PURPOSE: The purpose of the study was to evaluate the feasibility and efficacy of an accelerated radiotherapy schedule using weekend boost in terms of tumor response, compliance, and acute toxicities for head and neck squamous cell carcinoma, and to report long-term clinical outcomes. MATERIALS AND METHODS: Twenty-six patients with stages III-IV head and neck squamous cell carcinoma receiving radical chemoradiotherapy were accrued prospectively into the study. External beam radiation therapy to a total dose of 66-70 Gy in 33-35 fractions, 1.8-2.0 Gy per fraction along with concurrent weekly cisplatin was planned. Radiation regimen included delivery of six fractions per week, with boost field delivered as the sixth fraction on the weekend. The compliance, tumor response, and toxicities were recorded. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Twenty-one of 26 patients (81%) completed treatment as planned and five patients died during the course of treatment. Sixteen patients (62%) completed treatment in less than 44 days and, at the end of 3 months' follow-up, 18 patients (69%) showed complete response and two patients (8%) showed partial response. The 2- and 5-year actuarial disease-free survival were 90% and 65%, respectively, and 2- and 5-year actuarial overall survival were 60% and 38%, respectively. CONCLUSION: Accelerated fractionation using weekend boost, along with concurrent weekly concurrent cisplatin, is an effective and promising approach with favorable impact on initial tumor response, comparable results, and acceptable toxicities.

RESUMEN

Following reports of heparin use in burn treatment, an ethics-committee-approved prospective randomized study with controls compared results obtained using traditional usual burn treatment without heparin with results in similar patients similarly treated with heparin added topically. The subjects were 100 consecutive burn patients (age, 15-35 yr) with second-degree superficial and deep burns of 5-45% TBSA size. Two largely similar cohort groups, i.e. a control group (C) and a heparin group (H) with 50 subjects per group, were randomly treated, the main difference between the groups being that 13 C patients had burns of 35-45% extent vs. only one such patient in H (p < 0.01). The 50 C patients received traditional routine treatment, including topical antimicrobial cream, debridement, and, when needed, skin grafts in the early post-burn period. The 50 H patients, without topical cream, were additionally treated, starting on day 1 post-burn, with 200 IU/ml sodium aqueous heparin solution USP (heparin) dripped on the burn surfaces and inserted into the blisters 2-4 times a day for 1-2 days, and then only on burn surfaces for a total of 5-7 days, prior to skin grafting, when needed. Thereafter, C and H treatment was similar. It was found that the H patients complained of less pain and received less pain medicine than the C patients. H needed fewer dressings and oral antibiotics than C. Significantly less intravenous fluid was infused in H: 33.5 litres in 39 H patients vs. 65 litres in 41 C patients, i.e. nearly 50% less (p < 0.04). The 50 H patients had four skin graftings (8%), while the 50 C patients had 10 (20%). Five 5 C patients died (mortality, 10%). No H patients died. The number of days in hospital for H vs. C was significantly less (overall, p < 0.0001): 58% of H were discharged within 10 days vs. 6% of C; 82% of H were out in 20 days vs. 14% of C; 98% of H vs. 44% of C were out in 30 days; and while 100% of H were discharged by day 40, 56% of C required up to another 10 days. The burns in H patients healed on average in 15 days (maximum period 37 days) vs. an average of 25 days (maximum > 48 days) in C (p < 0.0006). Procedures and costs in H were much reduced compared with C. Photographs of the differences between H and C are presented for the sake of comparison. It is concluded that heparin applied topically for 5-7 days improved burn treatment: it reduced pain, pain medicine, dressings, and use of antibiotics; it significantly reduced IV fluids (p < 0.04), days in hospital (p < 0.0001), and healing time (p < 0.0006); and it reduced skin grafts, mortality, and costs.