Positive panel reactive antibody titers in patients bridged to transplantation with a mechanical assist device: risk factors and treatment

Patients who are bridged-to-transplantation with mechanical support have a high incidence of pretransplant sensitization defined by panel reactive antibody (PRA) titers greater than 10. Risk factors for positive PRA in patients with assist devices were investigated. From 1993 to 1997, 17 patients underwent implant surgery with CardioWest C-70 total artificial hearts (TAHs; CardioWest Technologies, Inc., Tucson, AZ), and 13 with Novacor left ventricular assist systems (LVASs; Baxter Healthcare, Novacor Division, Oakland, CA) for bridge-to-transplantation at this institution. Two patients died during implantation of the assist devices. Of the remaining 28 patients, four (14%) were women (3 with TAHs and 1 with an LVAS). All four women (100%) had a positive PRA, whereas only two of the 24 men (8%) had positive PRA (p < 0.0001). The transfusion histories of these patients were reviewed. Using chi-squared analysis (alpha = 0.05), the PRA levels were independent of transfusion of packed red blood cells and fresh frozen plasma. There was an association, however, between platelet transfusions and PRA levels. The times on device awaiting cardiac transplantation were also compared between the PRA positive and PRA negative groups. The average time to transplantation for PRA positive patients was 116 days, whereas the average waiting time for the PRA negative patients was 55 days (p = 0.05). Based on these data, a female patient with consistently positive PRA (93%) after TAH implantation underwent a transplant on post implant day 25 despite a positive lymphocytotoxic crossmatch with the donor. She was treated with plasmapheresis during cardiopulmonary bypass at the time of transplantation, and with four further treatments post transplant. As of this writing, she is alive and well on our standard triple immunotherapy. Therefore, women who are bridged-to-transplantation with assist devices are at risk for positive PRA. It is recommended that patients who are bridged-to-transplantation with assist devices and have high PRA levels be treated with perioperative plasmapheresis. With this aggressive approach, it may no longer be necessary to keep patients on mechanical support for prolonged periods, but possible to perform transplants as soon as suitable donors become available.     

Stereotactic radiosurgery with linear accelerator

Stereotactic radiosurgery is a method that applies a radiation dose to a limited and well-defined volume while the irradiation of adjacent healthy tissues is minimized. It is most commonly used in the treatment of intracranial lesions because the skull hardness assures the stable location of its contents. Treatment of the rest of the body has recently been proposed and carried out, using original immobilization systems. Stereotactic radiosurgery was first described in 1951 by the Swedish neurosurgeon Lars Leksell who originally used X-rays and then high-energy protons as a source of radiation. In the '80s photons from linear accelerators were used as radiation source, with various stereotactic systems and computerized treatment planning. The method used with all radiosurgical systems, regardless of the source of irradiation, is similar. The lesion is detected with common diagnostic imaging and adequate location frames. At present, to prevent errors in location, MRI and CT data are matched using an Image Fusion computer program. The objective of stereotactic radiosurgery is to destroy tumor cells or to induce changes in tissues that, as in brain arteriovenous malformations lead to the occlusion of their abnormal vessels. Stereotactic radiosurgery is increasingly used today in the treatment of a variety of intracranial lesions to the patients' benefit.     

Vapor-liquid equilibria for the ternary system N2 + CO2 +n-C4H10 at 250 and 270 K1

The system studied was nitrogen + carbon dioxide +n-butane at 250 and 270 K and at pressures from 1.5 to 14 MPa. The Peng-Robinson equation was used to model the results, since it is the most widely accepted equation of state in the gas processing industry. In general, the predictions are most accurate at low and moderate pressures and poorest at high pressures, especially near the critical region.     

Radiation-induced changes in transforming growth factor beta and collagen expression in the murine bladder wall and its correlation with bladder function

Late radiation-induced changes in transforming growth factor beta (TGF-beta), collagen I and collagen III content of the bladder wall, as well as morphological alterations of the uroepithelium, were analyzed quantitatively in an immunohistochemical study. An interlaboratory, i.e. interstrain, comparison of two mouse strains (Amsterdam C3H/Hen Af-nu+ and Munich C3H Neu) with different dose-effect relationships for late bladder damage was made, choosing radiation doses producing equivalent functional alterations in both strains (ED80 of 25 Gy and 19 Gy, respectively, 40 weeks after irradiation). In one strain of mouse, cystometry was also performed in the same animals at different times after irradiation. The TGF-beta staining intensity showed a progressive increase between 90 and 360 days after irradiation. This increase was similar in both strains of mouse treated with functionally equivalent doses (ED80) and was less pronounced after a lower, ED40, dose in the Munich mice. In both strains, there was a radiation-induced increase in both collagen subtypes from 180 days after irradiation with the ED80. The ratio of collagen type I/III, however, decreased in the Amsterdam mice and increased in the Munich mice. The relative radioresistance of the Amsterdam mice may therefore be partly due to a greater contribution of the elastic collagen type III, affording greater bladder compliance after irradiation. The extent of radiation-induced uroepithelial denudations or papillomatous outgrowths, the TGF-beta staining intensity and collagen I/III ratio were each correlated to bladder function determined by cystometry for the Munich mice. This correlation was statistically significant for all three parameters for group mean responses and, with the exception of the collagen I/III ratio, also for individual mice. These experiments indicate that chronic radiation-induced alterations in TGF-beta expression and connective tissue metabolism in the bladder wall are possibly important factors determining reduced bladder function after irradiation.     

Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1.     

Segmented genome and nucleocapsid of La Crosse virus

La Crosse (LAC) virions purified by velocity and equilibrium gradient centrifugation contained three single-stranded RNA species. The three segments had sedimentation coefficients of 31S, 25S, and 12S by sodium dodecyl sulfate-sucrose gradient centrifugation. By comparison with other viral and cellular RNA species, the LAC viral RNAs had molecular weights of 2.9 x 10(6), 1.8 x 10(6), and 0.4 x 10(6). Phenol-sodium dodecyl sulfate-extracted LAC virion RNA was not infectious for BHK-21 cell cultures under conditions in which Sindbis viral RNA was infectious. Treatment of LAC virus with the nonionic detergent Triton X-100 and salt released three nucleocapsid structures, each containing one species of virion RNA. The nucleocapsids had sedimenation coefficients of 115S, 90S, and 65S. Negative-contrast electron microscopy of the nucleocapsids indicated that they were convoluted, supercoiled, and apparently circular. They had a mean diameter of 10 to 12 nm and modal lengths of 200, 510, and 700 nm (some were even longer). By chemical and enzymatic analysis of purified viral RNA, one type of 5' nucleotide (pppAp) present in the proportion of one per RNA segment was identified. After periodate oxidation, each virion RNA species was labeled by reduction with [3H]sodium borohydride. Taken together, these results suggest that although the nucleocapsids appear as closed loops, the viral RNA has free 5' and 3' ends and is, therefore, not circular.     

Malignant lymphoma obscured by concomitant extensive epithelioid granulomas: report of three cases with similar clinicopathologic features

Three similar cases are described of an unusual combination of malignant lymphoma and extensive non-necrotic granulomas. The three patients presented with prominent splenomegaly without peripheral lymphadenopathy. They had normal or moderately elevated lymphocyte counts, abnormal lymphoid cells in the peripheral blood and bone marrow, and abnormalities of serum immunoglobulins. The lymphoid tumor was difficult to recognize but it was best identified in abdominal lymph nodes, it was composed of small atypical lymphocytes proliferating in a vaguely nodular pattern. The presence of multiple epithelioid granulomas obscured the neoplastic proliferation in the spleens and misled or delayed the final interpretation of the malignant disease. Abdominal lymph nodes and liver also contained granulomas although to a lesser extent. Studies of the lymphocyte surface characteristics in one patient suggested that the neoplasm derived from a monoclonal proliferation of B cells. The relationship between the exuberant epithelioid granulomas and the underlying neoplastic lymphoid proliferation is not clear. Regardless of whether it represents a distinct clinicopathological entity, recognition of this remarkable association has important practical implications since the lesions may be erroneously interpreted by the pathologist.     

Attitudes to female roles, aspects of menstruation and complaining of menstrual symptoms

Mofidied limb electrode positions are often used in studies which require the recording of rest and exercise ECGs, whereby the arm electrodes are placed at the infraclavicular fossae and the left lef electrode on the left lower abdomen. The effect of the modified limb electrode positions on electrocardiographic waveforms was investigated in 68 supine adult male subjects at rest. The modification produced profound amplitude and waveform changes in the frontal plane ECG leads. The QRS axis shifted on the average by 16 degrees towards a more vertical position with considerable individual variation. Concomitant with the QRS axis shift, the R wave amplitude decreased in leads I and a VL and increased in leads II, III, and aVF. The S wave amplitude increased in leads III and aVF and decreased in lead III. The P and T wave amplitude changes were in a direction similar to those observed for the R waves: a reduction of the amplitude in aVL and an increase in II, III and aFV. Of importance to exercise ECG interpretation are the ST segment waveform changes: The ST slope decreased in aVL and increased in leads II, III and aVF. Waveform changes in the chest leads caused by the modification were less important although statistically significant. These systematic changes in recorded ECG waveforms arise from changes directions and strength of the lead vectors of the six frontal plane leads. Large inter-individual variations in the magnitude of the changes produced by modification of the limb electrode positions prevent effective systematic correction of the distortions by means of a universal lead transformation.