Role of passenger leukocytes in allograft rejection: effect of depletion of donor alveolar macrophages on the local production of TNF-alpha, T helper 1/T helper 2 cytokines, IgG subclasses, and pathology in a rat model of lung transplantation

Acute lung allograft rejection is believed to be initiated by passenger leukocytes, such as alveolar macrophages (AM), in the donor organ, which release TNF-alpha, and present alloantigens to host lymphocytes, to up-regulated Th1 cellular and humoral immunity. However, the role of donor AM in local TNF-alpha synthesis, and their ability to induce local Th1 cellular and humoral immunity have not been evaluated. By depleting Brown Norway (BN, RT1n) rat lung allografts of AM before transplantation into Lewis rat (LEW, RT1(1)) recipients, the current study determined the role of donor AM in including the production of TNF-alpha, IFN-gamma (Th1 cytokine), IL-4 (Th2 cytokine), IgG subtypes, and rejection pathology in the allograft. The data show that compared with untreated BN allografts, pretransplant depletion of donor lung AM resulted in significantly less TNF-alpha, and IFN-gamma production in allograft bronchoalveolar lavage fluid with variable effects on local IL-4 production. Depletion of AM in the donor lung before transplantation affected the local production of several IgG subclasses. However, pretransplant depletion of donor AM had no effect on the development of the pathology of severe acute rejection. These data show that donor AM have a central role in the local synthesis of TNF-alpha and induce the production of IFN-gamma and IgG subtypes, locally, during acute lung allograft rejection. However, depletion of AM before transplantation does not prevent the development of severe acute rejection in BN rat lungs, transplanted into LEW recipients.     

Degeneration at the insertion weakens the tensile strength of the supraspinatus tendon: a comparative mechanical and histologic study of the bone-tendon complex

The purpose of this investigation was to determine the relationship between the degree of degeneration at the supraspinatus insertion, the tensile strength, and the site of failure of this tendon. Thirty-three fresh cadaveric shoulders (average age: 62 years; range: 39-83 years) were examined. A tensile load to failure was applied at a constant crosshead speed of 25.4 mm/min to a 10 mm wide strip of the supraspinatus tendon that remained attached to the bone. Preexisting degenerative changes at the insertion were assessed and scored histologically and compared with the ultimate tensile stress. Twenty tendons failed at the insertion (the insertion group), and 11 failed in the midsubstance (the midsubstance group). The histologic score of degeneration for the insertion group was significantly higher than that for the midsubstance group (p = 0.0026). There was a negative correlation between the ultimate tensile stress at the insertion and the degeneration score for the insertion group (r = -0.60; p = 0.013). Histologic observations revealed that disruptions of tendon fibers were located mostly in the articular half of the tendon and that they enlarged during mechanical testing in 90% of the specimens of the insertion group. It seems that degenerative changes at the supraspinatus insertion reduce the tensile strength of the tendon and constitute a primary pathogenetic factor of rotator cuff tear.     

A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey

The associations between serum concentrations of oestradiol, testosterone and sex hormone-binding globulin (SHBG) and risk of breast cancer in post-menopausal women were investigated in a prospective study on the island of Guernsey. Sixty-one women who developed breast cancer an average of 7.8 years after blood collection were matched for age, year of blood collection and number of years post-menopausal with 179 control subjects. Women using exogenous hormones at the time of blood collection were excluded from the study. Women who subsequently developed breast cancer had a 29% higher geometric mean oestradiol concentration than control women (P = 0.004). The odds ratio for breast cancer in the top third compared with the lowest third of the oestradiol concentration distribution was 5.03 (95% confidence interval 2.02-12.49, P for trend < 0.001). Adjusting for testosterone and SHBG concentrations did not substantially alter the odds ratio for oestradiol. Although testosterone and SHBG concentrations were associated with breast cancer risk, the concentrations of these hormones were correlated with those of oestradiol; the associations were not statistically significant after adjusting for oestradiol concentration. These data provide evidence that serum oestradiol concentrations in post-menopausal women may have a substantial effect on breast cancer risk.     

Tumour seeding following percutaneous endoscopic gastrostomy placement in head and neck cancer

We report the case of a patient with advanced squamous carcinoma of the supraglottic larynx and hypopharynx who developed metastatic gastric deposits occurring at the site of a percutaneous endoscopic gastrostomy tube, inserted 10 months previously by the pull technique. We review seven previous reports of tumour deposits occurring at the site of placement of a percutaneous endoscopic gastrostomy in patients with head and neck cancer, and consider alternative methods of enteral feeding in such patients.     

Assessment of the Massachusetts Medicaid managed Behavioral Health Program: year three

This evaluation of the third year of the Massachusetts Medicaid managed Mental Health/Substance Abuse Program showed that overall utilization increased slightly and expenditures were nearly the same in FY1994 compared to FY1993; however, they were lower for disabled members. Providers believed that access to care, utilization, and quality of care were the same or better than a year earlier and that the clinical review process was improved. Client severity was higher. Aftercare planning improved but gaps in services persisted. Integration of care improved. Administrative and management problems continued. Lessons for similar, more recent initiatives are discussed.