Molecular typing shows a high level of HLA class I incompatibility in serologically well matched donor/patient pairs: implications for unrelated bone marrow donor selection

In comparison with HLA-matched sibling bone marrow transplants, unrelated donor transplants are associated with increased graft-versus-host disease and graft failure. This is likely in part due to HLA incompatibilities not identified by current matching strategies. High resolution DNA-based typing methods for HLA class II loci have improved donor selection and treatment outcome in unrelated donor bone marrow transplantation. By using DNA-based typing methods for HLA-A and -B on a cohort of 100 potential bone marrow donor/patient pairs, we find that serological typing for HLA class I is limited in its ability to identify incompatibilities in unrelated pairs. Furthermore, the incompatibilities identified are associated with the presence at high frequency of alloreactive cytotoxic T-lymphocyte precursors. DNA typing also indicates that HLA-C mismatches are common in HLA-A and -B serologically matched pairs. Such mismatches appear to be significantly less immunogenic with respect to cytotoxic T-lymphocyte recognition, but are expected to influence natural killer cell activity. Thus, improved resolution of HLA class I shows many previously undisclosed mismatches that appear to be immunologically functional. Use of high resolution typing methods in routine matching is expected to improve unrelated donor selection and transplant outcome.     

Quantitative analysis of microvascular changes in diffuse astrocytic neoplasms with increasing grade of malignancy

BACKGROUND: Despite concerns about its prevalence and ramifications, harassment has not been well quantified among physicians. Previous published studies have been small, have surveyed only 1 site or a convenience sample, and have suffered from selection bias. METHODS: Our database is the Women Physicians' Health Study, a large (4501 respondents; response rate, 59%), nationally distributed questionnaire study. We analyzed responses concerning gender-based and sexual harassment. RESULTS: Overall, 47.7% of women physicians reported ever experiencing gender-based harassment, and 36.9% reported sexual harassment. Harassment was more common while in medical school (31% of gender-based and 20% for sexual harassment) or during internship, residency, or fellowship (29% for gender-based and 19% for sexual harassment) than in practice (25% for gender-based and 11% for sexual harassment). Respondents more likely to report gender-based harassment were physicians who were now divorced or separated and those specializing in historically male specialties, whereas those of Asian and other (nonwhite, nonblack, non-Asian, non-Hispanic) ethnicity, those living in the East, and those self-characterized as politically very conservative were less likely to report gender-based harassment. Being younger, born in the United States, or divorced or separated were correlated with reporting ever experiencing sexual harassment; those who were Asian or who were currently working in group or government settings were less likely to report it. Those who felt in control of their work environments, were satisfied with their careers, and would choose again to become physicians reported lower prevalences of ever experiencing harassment. Those with histories of depression or suicide attempts were more likely to report ever having been harassed. CONCLUSIONS: Women physicians commonly perceive that they have been harassed. Experiences of and sensitivity to harassment differ among individuals, and there may be substantial professional and personal consequences of harassment. Since reported rates of sexual harassment are higher among younger physicians, the situation may not be improving.     

Tuberculin reactivity in the elderly. Comparison of PPD-RT23 and PPD-CT68

BACKGROUND: Tuberculin reactivity varies on the basis of the PPD lot and the population studied. AIMS: To compare tuberculin reactivity in the elderly following successive applications of PPD from 2 different lots. POPULATION: Elderly nursing-home residents, from the province of Guadalajara, Spain. METHODS: The elderly were randomly selected and administered with a first Mantoux intradermoreaction of 2 UT of PPD-RT23 or 2 UT of PPD-CT68. The study was performed in a scaled basis, eliminating the reactors (transversal induration > or = 5 mm at 72 h). The non reactors were restudied with a second and third test in alternative arms at a 7-day interval with the same lot and initial dosis of PPD. At one year the scaled study was repeated with 2 UT of PPD-CT68. RESULTS: Eight hundred and thirty elderly persons (79 +/- 9 years) were studied, with 410 receiving PPD-RT23 and 420 receiving PPD-CT68. No differences were observed in the percentage of initial reactors (31% vs 29%; p = 0.26) or in the booster reactors (23% vs 20%; p = 0.16). The PPD-RT23 was found to trigger more intensive reactions than the PPD-CT68 leading to a greater frequency of indurations > 14 mm. After one year, the percentage of stable reactions was similar in both groups (50.5% vs 49.5%; NS). CONCLUSIONS: 1) In elderly nursing-home residents 2 UT of PPD-RT23 and 2 UT of PPD-CT68 showed similar results in regard to the number of reactors and the frequency of booster reactions. 2) The proportion of intense reactions was greater with 2 UT of PPD-RT23 than with 2 UT of PPD-CT68. 3) The stability of the reactions at one year was independent of the lot used in the first phase.     

Human vaginal mucosal immune system: characterization and function

The analysis of 49 fatal cases of venous thromboembolism--VTE (15% of total ambulatory patients number during long observation was performed. The advanced age of patients, multiple risk factors, underlying circulatory and respiratory tract diseases, malignancies, previous episodes of VTE especially with secondary pulmonary hypertension were the most important factors determining fatal prognoses in those patients.     

In vitro 2,3,7,8-tetrachlorodibenzo-p-dioxin interference with the anterior pituitary hormone adrenocorticortropin

Pharmacological effects of acute treatment with venlafaxine (VEN), a clinically active antidepressant [a noradrenaline (NA) and 5-hydroxytryptamine (5-HT) reuptake inhibitor without any affinity for neurotransmitter receptors] were studied in mice and rats. VEN inhibited the reserpine- or apomorphine-induced hypothermia and enhanced the L-5-HTP-induced head twitches in mice. It reduced the immobility time in Porsolt's test in mice and rats, but either did not change the locomotor activity (mice) or decreased it (rats). VEN reduced the locomotor hyperactivity induced by amphetamine (AMP), apomorphine (APO) and quinpirole (QUI), as well as the APO-induced stereotypy; the stereotypy induced by AMP in rats was prolonged. VEN neither changed the clonidine-induced aggressiveness in mice nor the behavioral syndrome induced by oxotremorine in rats. The obtained results indicate that VEN, given acutely, shows a pharmacological profile similar to that of tricyclic NA and 5-HT reuptake inhibitors. In contrast to the antidepressants mentioned above, VEN does not exhibit an alpha 1-adrenolytic or a cholinolytic activity (in vivo tests).