A phase III study of high-dose intensification without hematopoietic progenitor cells support for patients with high-risk primary breast carcinoma

Patients with more than nine ipsilateral lymph node involvement or inflammatory breast cancer have a 5-year survival rate of approximately 50%. We studied the efficacy of high-dose intensification, comparing it with the standard dose chemotherapy for patients with high-risk primary breast cancer. Patients with inflammatory breast cancer or more than nine ipsilateral lymph node involvement without evidence of distant metastasis were randomized to receive either standard dose 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for nine courses (control) or six courses of FAC followed by two courses of cyclophosphamide (5.25 g/m2), etoposide (1,500 mg/m2), and cisplatin (165 mg/m2) (HDCVP). The study was terminated in 1998 because of slow accrual of patients. Forty-six patients were entered in the study. At 4 years, the overall survival was 72.8% (SE 11.9%) and 61.7% (SE 12.4%), and disease-free survival were 45.5% (SE 12.3%) and 33.7% (SE 11.9%) for the control and HDCVP groups, respectively (p = 0.757 and 0.720). With the small number of patients in our study, a small overall survival benefit of high-dose intensification compared with the standard therapy cannot be excluded. However, any substantial benefit is unlikely.     

Ubiquitin and ubiquitin conjugates in human lens.

Ubiquitin, an 8.5 kDa polypeptide found almost universally in plants and animals, is a normal component in the lens. The best documented function for ubiquitin involves its conjugation to proteins as a signal to initiate degradation. Conjugates for ubiquitin-dependent degradation tend to be of very high molecular mass and are rapidly degraded. Another role of ubiquitin conjugation may be as a stabilizer during stress for protection of constituent proteins, resulting in ubiquitin conjugates that are long-lived. Examination of clear and cataractous human lenses of < 1 to > 50 years revealed the dramatic accumulation of ubiquitin and ubiquitin conjugates with age, beginning at approximately 10 years. Epithelial tissue contained predominantly conjugates of > 250 kDa, although ubiquitin conjugates were found at 98 and 40-60 kDa in tissues from older donors. The water-soluble, urea-soluble and urea-insoluble fractions of lens cortex and core also contain ubiquitin conjugates that accrue with age. High molecular mass conjugates (> 250 kDa) are particularly prominent in older lens tissue. Cataractous lenses, as compared with normal lenses of the same age, show more of these high molecular mass conjugates in the urea-soluble and urea-insoluble fractions of cortex and core. Heterogeneous conjugates in the 20-85 kDa range accumulate in an age-related fashion in all lens cortex and core fractions. While levels of free ubiquitin are significant in the epithelium and the water-soluble cortex and core for all ages, there is no detectable free ubiquitin in the urea-soluble and urea-insoluble fraction under conditions used in this study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ocular findings in systemic cutaneous basophil hypersensitivity.

SCBH was induced by immunizing guinea pigs with a protein antigen and challenging 1 week later with a large intraperitoneal dose of the same antigen. Animals developed a delayed-onset, erythematous skin rash and dermal infiltration by basophils and eosinophils. The uveal tracts of these animals were infiltrated by eosinophils, as were several other internal organs. The eye is affected in SCBH, and as in other forms of ocular cell-mediated hypersensitivity, the eosinophil is a prominent cellular component of these reactions.     

Occupational risks for uveal melanoma results from a case-control study in nine European countries

Objective Uveal melanoma is a rare disease with poor prognosis and largely unknown etiology. We studied potential occupational risk factors.Methods A population based case-control study was undertaken during 1995–1997 in nine European countries using population and colon cancer controls with personal interviews. Occupational exposure to sunlight and artificial UV radiation was assessed with a job exposure matrix. In total, 320 uveal melanoma cases were eligible at pathology review, and 292 cases were interviewed, participation 91%. Out of 3357 population controls, 2062 were interviewed, 61%, and out of 1272 cancer controls 1094 were interviewed, 86%.Results Using population controls, occupational exposure to sunlight was not associated with an increased risk (RR=1.24, 95% CI=0.88−1.74), while an excess risk found with use of colon cancer controls was attributed to confounding factors. An excess risk in welders was restricted to the French part of the data. Cooks, RR=2.40; cleaners, RR 2.15; and laundry workers, RR=3.14, were at increased risk of uveal melanoma.Conclusion Our study does overall not support an association between occupational sunlight exposure and risk of uveal melanoma. The finding of an excess risk of eye melanoma in cooks in several European countries is intriguing.     

Seat-belt injuries in children involved in motor vehicle crashes.

BACKGROUND: The efficacy of seat belts in reducing deaths from motor vehicle crashes is well documented. A unique association of injuries has emerged in adults and children with the use of seat belts. The "seat-belt syndrome" refers to the spectrum of injuries associated with lap-belt restraints, particularly flexion-distraction injuries to the spine (Chance fractures). METHODS: We describe the injuries sustained by 8 children, including 2 sets of twins, in 3 different motor vehicle crashes. RESULTS: All children were rear seat passengers wearing lap or 3-point restraints. All had abdominal lap-belt ecchymosis and multiple abdominal injuries due to the common mechanism of seat-belt compression with hyperflexion and distraction during deceleration. Five of the children had lumbar spine fractures and 4 remained permanently paraplegic. CONCLUSIONS: These incidents illustrate the need for acute awareness of the complete spectrum of intra-abdominal and spinal injuries in restrained pediatric passengers in motor vehicle crashes and for rear seat restraints that include shoulder belts with the ability to adjust them to fit smaller passengers, including older children.     

A novel intranasal Protollin-based measles vaccine induces mucosal and systemic neutralizing antibody responses and cell-mediated immunity in mice

Protollin-MV is a vaccine produced by mixing split measles virus (MV) antigen with the novel adjuvant Protollin (Neisseria meningitidis outer membrane proteins non-covalently complexed with Shigella flexneri 2a lipopolysaccharide). Intranasal immunization of mice with two or three doses of Protollin-MV induces both serum IgG and mucosal IgA with strong neutralizing activity. There is a dose-dependent shift towards lower IgG1:IgG2a ratios and MV-specific IFNgamma production in splenocytes. Intranasal Protollin-MV can therefore induce systemic and mucosal neutralizing antibody responses as well as elicit a balanced TH1/TH2-type response.     

Treatment of field water with sodium hypochlorite for surgical irrigation

BACKGROUND: Early irrigation and surgical debridement of high-energy wounds and open fractures effectively prevents infection. Rapid wound care has been maximized by the United States military's "forward surgical teams." However, the volume of sterile irrigant required to treat multiple patients with multiple wounds presents a significant logistical burden. Using ground-derived field water could eliminate this burden. METHODS: We collected 100 water samples from five sources. An initial bacterial count (CFU/mL) was determined before treatment. 5% sodium hypochlorite was then added to each sample to derive a concentration of 0.025%. After treatment, a final bacterial colony count was performed. RESULTS: We found no bacterial growth in 99/100 samples. One post-treatment sample grew a single colony of a Bacillus species not present in the pretreatment culture and was determined to be an air contaminant. CONCLUSIONS: Our field-expedient modification of Dakin's solution could substitute for sterile irrigation fluid when it is neither available nor logistically feasible.