Specificity of the passive antibody-induced suppression of the humoral immune response of mice to surface antigens on human cells

The effect of passively administered antibody on the humoral immune response of BALB/c mice to antigenic determinants on human cells has been examined. Antiserum raised by immunizing mice with the human leukaemic cell line K562, which lacks HLA-A,B,C antigens, was administered to mice, together with the HLA-A,B,C-positive cell line, BALM-1. The antibody response to the unique antigen was assessed by measuring the ability of the resultant antiserum to inhibit the binding to BALM-1 cells of a labelled monoclonal antibody, 7B6, which is specific for a monomorphic HLA-A,B,C determinant. As an indication of the immune response to antigens common to K562 and BALM-1, the ability of the same antiserum to inhibit the binding of monoclonal antibody 6B1, which detects an epitope common to both cell lines, was measured. Passive antibody to K562 blocked the immune response of mice to the common antigen on BALM-1 cells. However, the response to the antigen not recognized by the passive antibody was unaffected, even though the two antigens were present on the same immunizing cell. Thus, the effect of passive antibody was 'determinant specific'. Similar results were obtained, irrespective of whether the i.v. or i.p. route of immunization was used, and whether the passive antibody was adsorbed onto the immunizing cells prior to injection, or administered separately. The blocking of the immune response did not depend on simple masking of the antigenic determinants by the passive antibody, since non-saturating amounts of antibody were effective. In addition, blocking activity was dependent on antibody class and on an intact Fc region. The latter considerations also imply that the outcome of passive antibody administration in this system was determined by factors other than the ability of the antigen-antibody complexes to interact directly with B cells, and indicate the importance of antigen processing and/or a mechanism such as antigen-reactive cell opsonization.     

Personality profiles of pilots

Samples of Air Force fighter pilots, trainee commercial pilots, and males drawn from the general community completed the Edwards Personality Preference Schedule (EPPS). Four significant effects were found for individual sub-scales; three (Achievement, Affiliation, and Nurturance) identifying air force fighter pilots. Commercial pilot trainees scored significantly less than the community sample on Succorance and Nurturance. The data suggest that the EPPS consists of several related personality dimensions. One of these, "sociability," discriminated fighter pilots from the general community.     

Tirapazamine, Cisplatin, and Radiation versus Fluorouracil, Cisplatin, and Radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02).

PURPOSE: To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost). RESULTS: Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms. CONCLUSION: Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.     

Osteonecrosis of the jaws associated with use of risedronate: report of 2 new cases.

Use of various bisphosphonates has been associated with the development of osteonecrosis of the jaws (ONJ). At least 865 cases of ONJ attributed to these agents have been reported in the English-language literature. Approximately 96% of these published cases were seen with administration of the intravenous agents pamidronate and zoledronate, whereas only 26 cases have been associated with oral bisphosphonates, 25 of them with alendronate. Only a single case of ONJ associated with the oral bisphosphonate risedronate has been previously cited. We report 2 cases of ONJ attributed to risedronate administration. The patients developed osteonecrosis 15 and 24 months after treatment for osteopenia. A regimen of antibiotics and chlorhexidine mouthrinse resolved the osseous defect in the mandible caused by complete exfoliation of a lingual torus in 1 patient. The other patient required sequestrectomy, repeated courses of antibiotics, surgical debridement, and steroids to promote closure of an oroantral fistula and management of sinusitis after bone grafting and implant placement in the posterior maxilla. A demographic profile of reported oral bisphosphonate users affected by ONJ is also provided. With the millions of patients receiving various oral bisphosphonates for osteopenia and osteoporosis, health care practitioners should be aware of the potential for the onset of osteonecrosis and familiar with its management.     

Single UK centre experience on the treatment of PD peritonitis--antibiotic levels and outcomes.

BACKGROUND: There are few studies of the pharmacokinetics of vancomycin and gentamicin in peritoneal dialysis (PD) patients and the influence of antibiotic concentrations on treatment outcome. Concerns about resistance to ceftazidime and potential of aminoglycoside toxicity make the choice of empiric antibiotic difficult. METHODS: We retrospectively collected data from 613 patients on PD between 1 June 2002 and 31 December 2005. During this time, we adopted a protocol that minimized aminoglycoside exposure to patients with residual renal function and carefully monitored serum antibiotic concentrations. RESULTS: There were no statistical differences in mean day-5 vancomycin concentrations for continuous ambulatory peritoneal dialysis (CAPD) vs automated peritoneal dialysis (APD) and for anuric vs not-anuric patients. However, low levels (<12 mg/l) were recorded for 12.8% CAPD and 15% APD patients. These remained low at day 10 in 16% patients (25% if not anuric) despite incremental dosing. Vancomycin concentration did not predict cure or relapse of Gram-positive or culture-negative peritonitis. Gentamicin concentration (>2 mg/l in >50% patients) did not predict outcome of Gram-negative and culture-negative peritonitis. Moreover, cure rates were the same irrespective of whether gentamicin was continued for 14 days or was switched to ceftazidime after 5 days. CONCLUSION: We have confirmed that the International Society for Peritoneal Dialysis (ISPD) dosing guideline for vancomycin in CAPD and APD patients produces adequate serum concentrations of the antibiotics in the vast majority. However, large incremental dosing of vancomycin is needed if day-5 levels are low; especially for not-anuric patients. Whilst evidence of gentamicin toxicity in PD remains controversial, ISPD dosing regimen resulted in high levels for >50% patients. High gentamicin concentrations did not correlate with treatment success, but switching gentamicin to ceftazidime at day 5 appeared safe and limited aminoglycoside exposure. Increasing vancomycin and gentamicin concentrations do not appear to improve cure rates and alternative strategies (such as combination treatment) should be considered for future research.     

MR patterns of involvement of humeral head osteonecrosis

PURPOSE: To characterize osteonecrosis of the humeral head on coronal and axial MR images. METHODS: We retrospectively reviewed MR examinations in patients with humeral head osteonecrosis. The angle of the entire affected articular surface at three levels was measured and an angle subtended by the margins of osteonecrosis was also measured. RESULTS: The appearance of osteonecrosis is identical to that in the femoral head with signal abnormality (13/13), double-line sign (7/13), and subchondral fractures (3/13). The superior aspect of the humeral head was the most common location of osteonecrosis. The MR staging resulted as follows: stage II (6/13), stage IIIA (1/13), stage IIIB (1/13), and stage IV (5/13). The maximum percentage of involvement of the articular surface demonstrated the following distribution: 0% to 25%, 0/11; 25% to 50%, 1/13; 50% to 75%, 5/13; and 75% to 100%, 7/13. CONCLUSIONS: Quantitative analysis of the percentage of involvement of the humeral head was performed and indicates that in most cases, 75% to 100% of the articular surface at the levels measured was involved.     

Effect of test position on pelvic floor muscle assessment

The aims of this study were to analyse the effect of different body positions on pelvic floor muscle (PFM) assessment using digital muscle testing, manometry and transabdominal ultrasound. In addition, subject acceptance of each testing position was recorded. Subjects were 20 women's health physiotherapists. The testing protocol included the best of three maximum voluntary contractions tested in each of four positions (crook lying, supine, sitting and standing). Significant differences in muscle strength and subject acceptance between positions were found with each tool, most often between lying and upright positions. Digital muscle testing and vaginal squeeze-pressure scores were highest in the lying position, and vaginal resting pressure and transabdominal ultrasound scores were highest in the standing position. Subjects preferred the lying positions for internal examinations. The clinical significance of these differences and the reasons for these variations require further investigation.     

Extracranial radiosurgery—applications in the management of benign intradural spinal neoplasms

Stereotactic radiosurgery has enabled the delivery of higher doses of radiation and decreased fractionation due to improved accuracy. Spinal radiosurgery has been increasingly utilized for the management of metastatic extradural spinal disease. However, surgical resection remains the primary treatment strategy for intradural spinal tumors. Preliminary evidence suggests that radiosurgical ablation with stereotactic radiation for intradural spinal lesions may be efficacious in certain clinical scenarios. Local tumor control, pain relief, and improvement in neurologic function with minimal morbidity have been reported in short-term follow-up. However, long-term efficacy of radiosurgery in the management of intradural spinal neoplasms necessitates further validation. As extracranial radiosurgery is a newly evolving modality, a continuative review of the current literature is appropriate. Until a standardized therapeutic window of safety and efficacy can be determined, the recommendation of radiosurgical applications for benign spinal tumors should be reserved for carefully selected cases.