BSHI/BTS guidance on crossmatching before deceased donor kidney transplantation.

All UK H&I laboratories and transplant units operate under a single national kidney offering policy, but there have been variations in approach regarding when to undertake the pre-transplant crossmatch test. In order to minimize cold ischaemia times for deceased donor kidney transplantation we sought to find ways to be able to report a crossmatch result as early as possible in the donation process. A panel of experts in transplant surgery, nephrology, specialist nursing in organ donation and H&I (all relevant UK laboratories represented) assessed evidence and opinion concerning five factors that relate to the effectiveness of the crossmatch process, as follows: when the result should be ready for reporting; what level of donor HLA typing is needed; crossmatch sample type and availability; fairness and equity; risks and patient safety. Guidelines aimed at improving practice based on these issues are presented, and we expect that following these will allow H&I laboratories to contribute to reducing CIT in deceased donor kidney transplantation.

Seeded optical parametric generation in CdSiP2 pumped by a Raman fiber amplifier at 1.24 µm.

We report a seeded optical parametric generator (OPG) producing tunable radiation from 4.2-4.6 µm. The seeded OPG employs a 13 mm long CdSiP2 (CSP) crystal cut for non-critical phase-matching, pumped by a nanosecond-pulsed, MHz repetition rate Raman fiber amplifier system at 1.24 µm. A filtered, continuous-wave fiber supercontinuum source at 1.72 µm is used as the seed. The source generates up to 0.25 W of mid-infrared (MIR) idler power with a total pump conversion of 42% (combined signal and idler).

Identification of risk epitope mismatches associated with de novo donor-specific HLA antibody development in cardiothoracic transplantation.

The development of de novo donor-specific HLA antibodies (dnDSA) after transplantation is associated with graft failure, mortality, and cost. There is no effective therapeutic intervention to prevent dnDSA or ameliorate associated injury. The aims of this study were to identify specific HLA factors associated with dnDSA development and to propose primary prevention strategies that could reduce the incidence of dnDSA without prohibitively limiting access to transplant. The investigation cohort included heart transplant recipients from 2008 to 2015 (n = 265). HLA typing was performed and HLA antibody testing was undertaken before and after transplantation. HLAMatchmaker analysis was performed for persistent dnDSA to identify potentially more immunogenic eplet differences. Validation was performed in recipients of lung transplants from 2008 to 2013 (n = 433). The majority of recipients with dnDSA had antibodies to identical eplet positions on DQ2 and DQ7. A high-risk epitope mismatch (found in DQA1*05 +  DQB1*02/DQB1*03:01(7)) was associated with a 4.2- and 4.9-fold increased risk of dnDSA in heart and lung recipients respectively. HLA electrostatic potential modeling provided a plausible explanation for this observed immunogenicity. A theoretical allocation algorithm avoiding high-risk epitope mismatches was generated and predicted to reduce dnDSA by up to 72% without additional testing, eplet analysis, or cost.

Allosensitization Following Bone Graft.

It is recognized that patients may become sensitized to donor-specific HLA antigens as a result of previous antigenic exposures, classically through previous transplantation, pregnancy, or blood transfusion. We present an unusual case of a patient who unexpectedly developed a range of anti-HLA antibodies following orthopedic surgery where a bone graft was deployed intraoperatively. We describe the case of a 52-year-old man awaiting a renal transplantation, undergoing elective orthopedic surgery requiring a small-volume bone graft. His postoperative antibody profile was found to be substantially changed compared to his previous negative samples, with the presence of HLA-DR, DQ, and DP specificities, at levels that would be likely to give a positive flow cytometry crossmatch and therefore according to local procedures required listing as unacceptable antigens for organ allocation. We perform a literature review of all previous cases of allosensitization following bone graft. This case is the first to demonstrate allosensitization following minor surgery with ;low-volume bone graft. Previous evidence is very limited and pertains only to massive osteochondral surgery for trauma or malignancy, and is confounded by potential concomitant blood transfusion. Clinicians should be aware of the risk of allosensitization where bone grafts are used.

'Smoking': use of cigarettes, cigars and blunts among Southeast Asian American youth and young adults.

Increased use of cigars has been noted among youth, as well as use of blunts (hollowed-out cigars filled with marijuana). Three types of relationships have been previously hypothesized between use of tobacco and marijuana in substance use progression. We aimed to assess these relationships for Southeast Asian American youth and adults in an urban population. We conducted in-person interviews with 164 Southeast Asians, smokers and non-smokers, in two low-income urban communities in Northern California, collecting both quantitative and qualitative data. Analysis of the quantitative data indicated distinct use patterns for blunts, cigars and other forms of marijuana in terms of associations with generation in the United States. The use of these items was also found to be related: ever having smoked cigarettes or blunts increased the risk of ever having smoked the other three items. Qualitative data found indications of all three hypothesized relationships between tobacco and marijuana for youths but not for older adults. For youths in the study, 'smoking' was found to constitute a social construct within which use of cigarettes, cigars and blunts were somewhat interchangeable. Youths in similar settings may initiate into and progress through smoking as an activity domain rather than any one of these items.

Optical spectroscopy of PPV-based block copolymers of nanostructured supramolecular organic semiconductor.

The third-order nonlinearity of a PPV-based nanostructured supramolecular organic semiconductor (DBAB), with an electron donor (D) connected to an electron acceptor (A) via nonconjugated and flexible bridge (B) units, was investigated in this work at both near-resonant (532 nm) and nonresonant (1064 nm) wavelength by using degenerate four-wave mixing. The second hyperpolarizabilities of D, A, and DBAB at 532 nm were found to be approximately 2.42 x 10(-43) m2/V2, 7.75 x 10(-44) m2/V2, and 1.80 x 10(-43) m2/V2 in copolarization geometry, and approximately 1.59 x 10(-43) m2/V2, 2.59 x 10(-44) m2/V2, and 1.18 x 10(-43) m2/V2 in orthogonal polarization geometry, respectively. The second hyperpolarizabilities of DBAB at 1064 nm were approximately 1.66 x 10(-46) m2/V2 and approximately 8.77 x 10(-47) m2/V2 for parallel and orthogonal polarization cases.

Quantitative analysis of human leucocyte antigen expression during culture of Epstein-Barr virus-transformed cell lines using the dako QIFIKIT.

Pre-existing donor-specific human leucocyte antigen (HLA) antibodies in renal allograft recipients result in hyperacute and accelerated graft failure. These antibodies can be detected in flow cytometric assay systems using HLA-characterised Epstein-Barr virus (EBV)-transformed B-lymphocyte cell lines. Confident assay performance is predicated by the expression of HLAs on the EBV-transformed B-cell line surface. Surface HLA expression of three EBV-transformed B-cell lines that had previously been used as part of a potential organ recipient serum screening panel at St James' University Hospital, Leeds, are assessed for changes in the level of HLA expression over the nominal culture duration of eight days using the QIFIKIT (Dako, Denmark), a quantitative flow cytometry kit for assessing cell surface antigens. A comparison of the mean fluorescence intensity (MFI) of the known antigen levels of the beads via a calibration graph permits determination of the antibody binding capacity of the cell lines. Results showed that HLA expression is not consistent throughout the cell culture, with optimal expression occurring during day 2 of culture. Inconsistent HLA expression demonstrated during the cell culture means that no assumption of the level of HLA expression can be made, and that cell lines used as part of a screening panel should have their HLA expression in cell culture determined.

Hemodynamic characteristics of congenital aortic stenosis: a quantitative stress echocardiography study.

BACKGROUND: Several investigators have studied the effects of exercise on pressure gradients and valve area measurements in patients with senile calcific aortic stenosis. However, there are limited data on young patients with congenital aortic stenosis. The current study was conducted to assess the dynamic effect of exercise on aortic valve area and to determine whether pressure gradients or valve area determinations correlate with duration of exercise in these patients. METHODS AND RESULTS: Twenty-five young patients with congenital aortic stenosis and 10 normal control patients performed symptom-limited bicycle exercise stress tests with quantitative 2-dimensional and Doppler analysis. Compared with normal patients, there were no significant differences in the directional changes in blood pressure, left ventricular volumes, and ejection fraction. There was no correlation between either peak instantaneous or mean transaortic pressure gradient and exercise duration. A small but statistically significant correlation was detected between the continuity equation aortic valve area and duration of exercise (r = 0.49, P =.013). Aortic valve area did not change with exercise in the patient cohort (1.5 +/- 0.6 vs 1.5 +/- 0.6; P = not significant). CONCLUSIONS: Aortic valve area does not change significantly with exercise in asymptomatic patients with congenital aortic stenosis. Consistent with prior studies, there was no correlation between the duration of exercise and the mean resting aortic valve gradient. A modest but statistically significant correlation was detected between exercise duration and aortic valve area. Further studies are required to determine whether aortic valve area measurements would provide useful adjunctive data on which to base recommendations for participation in competitive sports.

Are African American women worried about getting AIDS? A qualitative analysis.

The aims of this study were to explore and describe AIDS-related worry among African American women and determine whether AIDS risk behaviors were associated with women's AIDS-related worry status. Of 142 women interviewed, 36% (n = 51) expressed some worry about getting AIDS, compared to 64% (n = 91) who did not express worry. In general, both worried and nonworried women were equally likely to report risk behaviors such as no condom use or having risky sexual partners and no significant relationships were found between worry status and self-reported HIV/AIDS risk behaviors. Women gave several reasons for why they did or did not feel worried about getting AIDS. For example, 23% of worried women responded that they were worried about getting AIDS because of the uncertainty of their sex partners' risk behaviors. This contrasted strongly with the nonworried women, 10% of whom reported trusting their partners and 64% of whom reported engaging in some type of protective behavior. Results indicate that regardless of worry status, women were not protecting themselves by using condoms or using careful partner selection. Therefore we recommend that future HIV/AIDS educational intervention programs appeal to and encourage participation for all women whether or not they express concern about contracting the disease. In addition, programs must carefully address the issue of denial, and provide skills for assessing and modifying risky behaviors.

HIV risk among low-income African American mothers of elementary school children.

Data from 119 African American low-income mothers of school aged children in Oakland, California show that 38% engaged in behavior that might place them at risk of exposure to the human immunodeficiency virus (HIV). Risk behaviors that were investigated included having multiple partners and having a partner with an incarceration history. Of women studied, 23% were at risk because of multiple partners, while 15% were at risk as a result of having had an incarcerated partner. Women who were < or = 35 years of age were three times more likely to report having had an incarcerated partner compared to women > or = 36 years of age (22% vs. 6%) mean 2 = 5.59, P < or = .01). Single women were also more likely to report having had a partner who had been incarcerated, 21% compared to 9% of married women (mean 2 = 3.73, P < or = .05). Although no significant relationships were found with respect to condom use, a larger proportion of women with an incarcerated partner reported never using condoms (71%) compared to women without an incarcerated partner (63%); whereas, fewer women with multiple partners reported never using condoms (56%) compared to women without multiple partners (67%). Findings suggest that low-income African American women outside of traditional high-risk groups (i.e., generally studied in high-risk settings such as drug treatment centers, sexually transmitted disease [STD] clinics, hospitals or from the sex industry) may be at risk and should be targeted in HIV risk prevention programs. These women may not consider themselves to be at risk and are not generally targeted in HIV risk prevention programs because they are mothers, housewives, and working women.

Prevalence of pulmonary hypertension in limited and diffuse scleroderma.

STUDY OBJECTIVES: To characterize the prevalence of undiagnosed pulmonary hypertension in patients with limited and diffuse scleroderma. DESIGN: Prospective cross-sectional study. SETTING: University-based outpatient clinic. PATIENTS: Thirty-four consecutive patients with limited (n = 29) or diffuse (n = 5) scleroderma but without the clinical diagnosis of pulmonary hypertension. MEASUREMENTS AND RESULTS: All patients had 12-lead ECGs and two-dimensional and Doppler echocardiograms. The pulmonary artery systolic pressure (PAs) was calculated as the sum of the Doppler transtricuspid pressure gradient and the right atrial pressure as estimated by the caval respiratory index. Thirty-three patients (97%) had adequate spectral signals of tricuspid regurgitation. The velocity of tricuspid regurgitation ranged from 1.6 to 4.5 m/s. The calculated PAs ranged from 15 to 95 (mean +/- SD = 30 +/- 14 mm Hg). Twelve patients (35% of the total cohort) had pulmonary hypertension defined as PAs of 30 mm Hg or greater. CONCLUSIONS: Undiagnosed elevation of PAs is common in patients with scleroderma. Noninvasive assessment of PAs can be performed accurately in most patients independent of clinical signs of pulmonary hypertension. If successful treatment strategies are identified, it may be possible to identify patients early in the development of pulmonary hypertension and intervene before significant end-organ damage occurs.

Evaluation of kinesthetic deficits indicative of balance control in gymnasts with unilateral chronic ankle sprains.

If ankle proprioception can be determined to be impaired, then treatment can be more specifically directed toward correcting the proprioceptive deficit, thereby improving functional ability. The purpose of this study was to determine if collegiate level gymnasts with unilateral, multiple ankle sprains (ie., chronic ankle sprains) had decreased ability to detect passive plantar flexion of the ankle (ie., decreased ankle proprioception) and to determine if balance deficits existed during one-legged stance. Eleven gymnasts participated in 30 passive movement trials (15 movement and 15 nonmovement) presented randomly on both the injured and noninjured sides. The nonmovement trials consisted of either no movement of the ankle or passive movement of the ankle into 5 degrees of plantar flexion. Luce's choice theory determined that subjects were not biased in responding to a "yes" in perceiving movement or no movement during the movement/nonmovement trials of passive plantar flexion. Subjects were better able to detect movement during movement trials with their uninjured ankles than their injured ankles. Subjects also performed single 30-second trials of one-legged standing on each leg, with eyes open and with eyes closed. Subjects reported better balance when standing on the uninjured ankle during the one-legged stance conditions. Although our results cannot be extrapolated to balance abilities during complex gymnastic routines, they do suggest that physical therapy assessment includes passive detection of joint position as well as single-legged stance tests, and that perhaps rehabilitation programs incorporate sports-specific balance activities for such injuries.

HIV testing among low-income African-American mothers.

HIV testing patterns were examined among low-income African Americans who were mothers of young school-age children. In-person interviews were conducted to determine whether African-American women had been tested for HIV; their sexual behaviors, including the number of sexual partners and condom use; and health care access and utilization. Forty-one percent of the women had been tested for HIV; 18 percent tested more than once. Levels of education, source of primary health care, and type of insurance were not associated with HIV testing. The total number of sexual partners for their current lifetime and within the past five years was significantly associated with their HIV testing status (chi 2 = 39.97; DF = 3; p < .01 and chi 2 = 66.68; DF = 3; p < .01 respectively). Women who have used condoms during their last intercourse (20%) were less likely to have been tested than women who did not use a condom (50%) (p < .01). Results suggest that low-income African-American women get tested for HIV. This suggests that these women understand the concept of risk and how certain behaviors may place them at risk. However, these women still confront conditions that place them at risk, such as having sex with multiple partners and/or partners with a history of incarceration, in addition to drug use. HIV testing may not serve as the most effective intervention for this sub-population of women. Educational and preventive measures should extend to women outside traditional high-risk populations by incorporating methods to promote protective behavioral changes which will empower women with self-esteem and confidence.

Effects of exercise on left ventricular performance determined by echocardiography in chronic, severe mitral regurgitation secondary to mitral valve prolapse.

Data on the effects of exercise on left ventricular (LV) volumes and ejection performance in patients with severe mitral regurgitation (MR) are limited. With use of a matched-pairs design, 10 asymptomatic patients with chronic, severe MR and normal LV systolic function who were not receiving vasodilator therapy (group 1) and 10 matched normal control subjects with no structural heart disease (group 2) performed symptom-limited upright bicycle ergometry with quantitative echocardiographic analysis. An additional 8 patients with severe, chronic MR and normal LV systolic function who were receiving vasodilator therapy at the time of testing (group 3) were studied for comparison. The 3 cohorts exercised for similar periods of time. Group 1 and 3 patients had similar end-diastolic volumes at rest, both of which were significantly greater than those of normal controls. Although resting LV end-systolic volume was greater in groups 1 and 3 than in normal controls, the 3 groups had similar relative percent reductions in end-systolic volume during exercise (30 +/- 12%, 32 +/- 13%, and 30 +/- 24%; p = NS). A similar percent increase in LV ejection fraction was also observed in all 3 cohorts (18 +/- 9%, 15 +/- 9%, and 14 +/- 6%; p = NS). Forward stroke volume increased significantly in group 1 (59 +/- 21 and 71 +/- 18 ml; p <0.001) and in group 3 (59 +/- 17 and 68 +/- 13 ml; p < 0.05). Thus, in asymptomatic patients with chronic, severe MR and normal LV ejection fraction at rest, there is an improvement in LV ejection fraction and an increase in forward stroke volume during exercise. These effects are comparable to those observed in normal controls. Directional differences in the cohort receiving no activity therapy were indistinguishable from either patients receiving vasodilator therapy or normal control subjects.