Renal Allograft Biopsies with Borderline Changes: Predictive Factors of Clinical Outcome

The clinical outcome and appropriate management for patients showing 'borderline changes' on allograft biopsy after renal transplantation is still controversial. In an attempt to identify predictive factors of clinical outcome of patients with such lesions, we reviewed the clinical course of 91 patients with borderline changes. Multivariate analysis revealed significant and independent effects of histological stage (i + t < or = or > 2) and time to borderline changes (< or = or > 3 months after transplant) on serum creatinine levels at 1 year from borderline changes episodes (respectively, p = 0.04 and p = 0.02) and only a significant effect of time to borderline changes on serum creatinine levels at 2 years (p = 0.005). Renal function at 1 year and 2 years as 5- and 8-year graft survival were not significantly different in the group of patients treated with antirejection therapy (T group, n = 49) compared with the untreated group (UT group, n = 42). This study strongly suggests that borderline changes with histological score (i + t) > 2 and late episodes of borderline changes should be considered to be of poor prognosis.     

Th‐17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney Transplants Using Extended Criteria Donors During Acute T Cell–Mediated Rejection

Although renal transplantation using expanded criteria donors has become a common practice, immune responses related to immunosenescence in those kidney allografts have not been studied yet in humans. We performed a retrospective molecular analysis of the T cell immune response in 43 kidney biopsies from patients with acute T cell–mediated rejection including 25 from recipients engrafted with a kidney from expanded criteria donor and 18 from recipients grafted with optimal kidney allograft. The clinical, transplant and acute T cell–mediated rejection characteristics of both groups were similar at baseline. The expression of RORγt, Il‐17 and T‐bet mRNA was significantly higher in the elderly than in the optimal group (p = 0.02, p = 0.036, and p = 0.01, respectively). Foxp3 mRNA levels were significantly higher in elderly patients experiencing successful acute T cell–mediated rejection reversal (p = 0.03). The presence of IL‐17 mRNA was strongly associated with nonsuccessful reversal in elderly patients (p = 0.008). Patients with mRNA IL17 expression detection and low mRNA Foxp3 expression experienced significantly more treatment failure (87.5%) than patients with no mRNA IL17 expression and/or high mRNA Foxp3 expression (26.7%; p = 0.017). Our study suggests that the Th17 pathway is involved in pathogenesis and prognosis of acute T cell–mediated rejection in recipients of expanded criteria allograft.     

Myocardial perfusion imaging with technetium-99m sestamibi SPECT in the evaluation of coronary artery disease

Technetium-99m hexakis-2-methoxy-isobutyl-isonitrile(^99mTc sestamibi) has been used for myocardial perfusion imaging in the evaluation of coronary artery disease (CAD) since 1990. The experience of its use in an Asian population with and without previous myocardial infarction (Ml), diabetes mellitus (DM), hypertension (HPT) and collateral circulation (COL) is reported. One hundred and thirty-nine patients who underwent treadmill exercise testing with ^99mTc sestamibi single photon emission computed tomography (SPECT) and coronary angiogram were studied. The overall sensitivity for the detection of CAD was 91.0% and specificity was 64.7%. For patients without previous myocardial infarction, the sensitivity was 83.8% and specificity was 83.3%. Patients with COL had a higher sensitivity while those with HPT had a lower specificity. Sensitivity was higher in patients with multi-vessel disease (MVD) than single vessel disease (SVD). The overall detection for individual artery stenosis was 74.1% with a specificity of 73.1 %. Amongst the three major coronary arteries, sensitivity was highest for the right coronary artery and specificity was highest for the left circumflex artery. Specificity was higher in patients without MI or COL. We found that the agreement between ^99mTc sestamibi SPECT and coronary angiogram for the extent of CAD was only 52.5%. The concordance rate was higher for patients with MVD than SVD. It is concluded that ^99mTc sestamibi SPECT is a sensitive and specific test for the detection of CAD and localization of disease to individual coronary arteries in our patients with some differences in the subgroups. Agreement between coronary angiogram and ^99mTc sestamibi for the extent of coronary artery disease was also satisfactory.     

Analgesia for shock wave lithotripsy

PURPOSE: We evaluated the effectiveness of and patient preference for analgesia used during shock wave lithotripsy by comparing diclofenac alone with a combination of diclofenac and patient controlled analgesia, that is alfentanil. MATERIALS AND METHODS: A total of 64 patients were treated using a Lithotriptor S (Dornier Medical Systems, Marietta, Georgia) and randomized to receive diclofenac alone or combined with an alfentanil patient controlled analgesia pump. If treated twice, they crossed over to the alternative form of analgesia. A record was maintained of the site and size of the stone, maximum power achieved, number of shocks, amount of alfentanil used and need for additional analgesia. After treatment patients scored on a visual analog scale the maximum level of pain and satisfaction with analgesia. RESULTS: There was no difference in the mean size of the stone treated (8.6 and 7.5 mm.), energy level (71% and 71% or approximately 17 kV.) or number of shocks (3,000 and 2,900, respectively) in the groups. Only 2 patients in the diclofenac group required additional analgesia and there were no significant side effects from either treatment. The mean pain scores were not significantly different in the diclofenac and patient controlled analgesia groups (3.54 and 2.93, respectively, (p = 0.34), although those on patient controlled analgesia were more satisfied (7.72 versus 9.14, p = 0.04). Of the 38 patients who presented twice 58% preferred diclofenac alone. CONCLUSIONS: This study suggests that there is no significant difference in the level of pain experienced with diclofenac alone or when combined with an alfentanil patient controlled analgesia pump during shock wave lithotripsy. However, patients are more satisfied with treatment when a patient controlled analgesia pump is available.     

Long-term kidney graft survival across a positive historic but negative current sensitized cross-match

BACKGROUND: The sensitive cross-match (XM) techniques that have been introduced for clinical transplantation can detect anti-donor immune reactivity despite a negative standard National Institute of Health (NIH) cross-match. One of them uses anti-kappa human light chain globulins (AHG). But there is some discussion about the clinical consequences of a positive AHG-XM in the historical sera that became negative in the sera collected just before the transplantation (pretransplant sera). This study was intended to assess the risk of kidney graft failure associated with a positive historic but negative pretransplant AHG-XM in allosensitized patients having a negative historic NIH-XM. METHODS: This retrospective study includes 90 consecutive renal transplants in immunized patients performed at one center between 1985 and 1991. All of the patients had negative historical and pretransplant standard NIH lymphocytotoxic cross-matches and received the same immunosuppressive regimen. The AHG-XMs were done retrospectively using peak historic and sera collected on the day of the transplantation. RESULTS: The AHG cross-match (AHG-XM) was positive in 17 patients, although the standard NIH cross-match was negative. Fourteen of them had a positive historical but negative pretransplant AHG-XM. The actuarial graft survival in this group of 14 patients was 100% at 1 year and 78% at 9 years compared with 90 and 67%, respectively, in patients with negative historical AHG-XM. In addition, the number of rejection episodes per patient as well as renal function at 1, 2, and 5 years were similar in the two groups. IgG anti-donor HLA class I accounted for the XM positivity in 12 of the 14 patients; most rapidly lost all antibody reactivity by NIH technique in an average time of 8 months before the transplantation. In conclusion, this study suggests that transplant patients having a negative historic NIH-XM but a positive historic AHG-XM may not be at high risk of graft failure especially if there is a well-documented sera history showing a marked decrease in PRA level before transplantation and a negative pretransplant AHG-XM.     

Prevention of preeclampsia

THE CURRENT SITUATION: Preeclampsia is associated with increased risk of adverse maternal (abruptio placentae, HELLP syndrome, eclampsia.) and perinatal death. Its prevention, therefore, is of particular importance. The latter must be determined together with the group of women who would benefit from it. THE INTEREST OF ASPIRIN: The best studied preventive treatment is low dose aspirin. The various studies on low-dose aspirin have confirmed its safety in pregnant women. These studies, in small cohorts of selected patients at risk or in large series of women with moderate risk, show that the use of aspirin is associated with a 15% reduction in the risk of preeclampsia. OTHER THAN ASPIRIN: Other preventive treatments, such as calcium have not demonstrated their efficacy, or their effect requires confirmation, such as with anti-oxidants or low molecular weight heparin. IN PRACTICE: The prevention of preeclampsia currently relies on low-dose aspirin started at the beginning of pregnancy. The moderate benefit of such prevention justifies its administration in patients at high risk, selected on their obstetrical past history.     

Protein and allergen analysis of latex mattresses.

BACKGROUND: Latex allergy is a well-recognized health problem. The wide use of latex in daily life raised the question whether latex articles could be a source of allergens. The present study was carried out to analyse various latex mattresses for protein and allergen characterization. METHODS: Five latex foam mattresses were reduced to powder and proteins were extracted using either water or urea. The protein content of the extracts was analyzed by SDS-PAGE, IEF, 2-D gel electrophoresis and amino acid sequence analysis. The presence of specific IgE, directed toward mattress proteins found in human sera of latex-allergic patients, was tested using ELISA and immunoprints. RESULTS: The results showed that no protein or allergen could be extracted from synthetic foam. However, depending on the type of mattress and extraction procedure, various quantities of proteins could be extracted from mattresses containing natural latex. The ELISA levels of various latex-allergic patients were always more significant against urea extracts than against water extracts, except for one mattress. The protein and allergen patterns were qualitatively similar for all mattresses containing natural latex. Hev b 1 was identified by N-terminal amino acid sequence analysis. CONCLUSION: Because the natural rubber of the mattresses contains latex allergens, these allergens are a potential source of sensitization and could constitute a risk, at least to allergic individuals.     

The impact of a quadrivalent human papillomavirus (types 6, 11, 16, 18) virus-like particle vaccine in European women aged 16 to 24

Background  Quadrivalent human papillomavirus (HPV types 6/11/16/18) L1 VLP vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and external genital disease. Herein, we evaluated the impact of the quadrivalent HPV 6/11/16/18 L1 VLP vaccine on prevention of HPV-associated cervico-genital lesions in a broad population of sexually active European women.
Methods  Female subjects ( N = 9265) aged 16–24 with four or fewer lifetime sexual partners were enrolled and randomized to quadrivalent HPV vaccine or placebo. Subjects underwent cervicovaginal sampling for HPV DNA detection. Papanicolaou testing and anti-HPV 6/11/16/18 serology testing was also performed.
Results  Vaccine efficacy against lesions representing immediate cervical cancer precursors (cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ ) related to HPV 6/11/16/18 in the per-protocol population was 100.0%[95% confidence interval (95% CI), 89.8–100.0]. Efficacy against external genital lesions (vulvar or vaginal intraepithelial neoplasia, condyloma, vulvar or vaginal cancer) related to vaccine HPV types in the per-protocol European population was 99.0% (95% CI, 94.4–100.0).
Conclusion  These data demonstrate that quadrivalent HPV 6/11/16/18 vaccination programs in 16- to 24-year-old European women can be beneficial.
NCT0009252, NCT00092534, NCT00092495