Successful Liver-Kidney Transplantation in Two Children With aHUS Caused by a Mutation in Complement Factor H

A 12-month-old boy and his 16-year-old aunt became acutely ill 6 months apart and were diagnosed to have atypical hemolytic uremic syndrome (aHUS). Genetic analysis revealed heterozygous R1215Q mutation in complement factor H (CFH) in both patients. The same mutation was found in five healthy adult relatives indicating incomplete penetrance of the disease. The patients developed terminal renal failure and experienced reversible neurological symptoms in spite of plasma exchange (PE) therapy. In both cases, liver-kidney transplantation was successfully performed 6 months after the onset of the disease. To minimize complement activation and prevent thrombotic microangiopathy or overt thrombotic events due to the malfunctioning CFH, extensive PE with fresh frozen plasma was performed pre- and perioperatively and anticoagulation was started a few hours after the operation. No circulatory complications appeared and all four grafts started to function immediately. Also, no recurrence or other major clinical setbacks have appeared during the postoperative follow-up (15 and 9 months) and the grafts show excellent function. While more experience is needed, it seems that liver-kidney transplantation combined with pre- and perioperative PE is a rational option in the management of patients with aHUS caused by CFH mutation.     

Experimental sports drinks with minimal dental erosion effect

The effects of new experimental sports drinks on dental enamel were studied in vitro using bovine tooth specimens. Profilometric analysis was used to measure the loss of tooth material after immersion of the specimens in the drinks. Thereafter the specimens' surface hardness was measured and scanning electron microphotographs were taken. In addition, 13 commercial sports drinks and experimental drinks containing either citric acid or malic acid were tested for their capacity to dissolve hydroxyapatite in vitro. The erosive effect increased markedly with decreasing pH. The citric acid containing drinks were more erosive than malic acid containing drinks. No erosion was observed with the malic acid containing drink (pH 5.90) but the drink of similar composition containing citric acid caused an erosion 1.3 +/- 1.1 microns deep and a commercial citric acid containing drink caused a lesion 12.3 +/- 4.5 microns deep after 120 min immersion. Softening of enamel was greater in specimens immersed in citric acid than in those immersed in malic acid containing drink. The in vitro hydroxyapatite dissolving effect of the commercial sports drink samples studied (all having a pH under 4.22) was markedly greater (0.48-4.38 mmol/l) than that of the malic acid containing experimental drink (pH 5.50, Ca++ concentration in the supernatant 0.19 mmol/l) and of the similar citric acid containing drink (0.35 mmol/l). The hydroxyapatite dissolving effect of both drinks started to be marked at a pH level of about 5.0 but increased thereafter exponentially with decreasing pH. At pH levels above 4.0 the hydroxyapatite dissolving effect of citric acid containing drinks was greater than that of malic acid containing drinks.     

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     

Prospective follow-up of primary CMV infections after 6 months of valganciclovir prophylaxis in renal transplant recipients

Background. The occurrence and clinical course of late primaryCMV infections developing after valganciclovir prophylaxis inhigh-risk renal transplant recipients are poorly described. Methods. Helsinki University Hospital district kidney allograftrecipients between January 2004 and March 2007 (N = 175) wereprospectively investigated. Patients with D+/R– CMV serostatusand 1-year follow-up were included (N = 25). After 6 monthsof oral valganciclovir prophylaxis, the patients were monitoredfor CMV-DNAemia with real-time quantitative plasma PCR at 2–6weeks interval and if CMV infection was suspected. Infectionswere treated with i.v. ganciclovir or high-dose valganciclovir,followed by 1–3 months of secondary valganciclovir prophylaxis. Results. CMV infection developed in 12/25 patients a mean of107 days (range 26–330 days) after prophylaxis ended.Two were asymptomatic. In 10 patients symptoms included fever(N = 7), gastrointestinal (N = 5), upper respiratory tract (N= 3) and hepatopathy (N = 2). One patient with infection hadprophylaxis terminated after 5 months (leukopenia). The meanviral load at diagnosis was 49 517 (range 490–325 300),and peak viral load was 84 654 (range 1250–527 400)copies/ml. Five infections were treated with valganciclovirand six with i.v. ganciclovir resulting with negative PCR results.One mild infection with low viral load was treated successfullywith minimization of immunosuppression. Infection relapse developedin three patients a mean of 31 (range 15–61) days afterthe end of the therapy. Relapses were treated with valganciclovir. Conclusions. CMV primary infections were common after 6 monthsof valganciclovir prophylaxis and mostly symptomatic. Relapsescommonly occurred. Primary infections seem to be delayed, butwere not efficiently prevented by 6 months of prophylaxis.     

生理模型同时预报普鲁卡因胺及其代谢物乙酰普鲁卡因胺在大鼠体内处置动力学

用生理模型同时对iv普鲁卡因胺(PA)后,PA及其代谢产物乙酰普鲁卡因胺(NAPA)在大鼠体内处置动力学进行预报。测定了所需的有关PA参数.结果PA在大鼠血液、肝和肾脏清除率分别为47.28,13.56和33.71 ml·kg^-1·min^-1。估算的组织/血液药物浓度比表明,心、肝、肾、肌肉和小畅对PA的亲和力大于血液成分。对大鼠iv PA后,PA及其NAPA在组织中浓度进行预报,并与实验结果比较。结果大多数组织中浓度预报值与观察值基本—致。同时对PA及其NAPA在人血浆中浓度进行了预报。     

Computerized rotometer apparatus for recording circling behavior

A computerized rotometer for recording rotational behavior in rats is described. The digital pulses derived from the infrared photocell detector induced by animal rotations were input directly to a 20-megabyte microcomputer for on-line recording and were processed further to the Digital Equipment Corporation's VAX computer with the SAS software system for statistical and graphical analysis. The typical results obtained with drugs (apomorphine and amphetamine) eliciting contralateral and ipsilateral rotation in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the nigrostriatal dopamine pathway were presented. The effect of catechol-O-methyltransferase (COMT) inhibitor, OR-611, on the potentiation of L-dopa-induced contralateral rotation in 6-OHDA-lesioned rats was also studied. The automation of rotometer apparatus and the speed of data analysis facilitate screening novel antiparkinsonian drugs in rats with unilateral lesions of 6-OHDA.     

Simultaneous confirmation and differentiation of human T-lymphotropic virus types I and II infection by modified western blot containing recombinant envelope glycoproteins

A modified Western blot (WB) that includes both shared (r21e) and unique recombinant envelope proteins from human T-lymphotropic virus (HTLV) type I (rgp46I) and type II (rgp46II) was compared to conventional HTLV serologic tests in 379 United States blood donors and individuals residing in diverse geographic regions, and the specimens were categorized as positive (n = 158), indeterminate (n = 158), or negative (n = 63) for HTLV infection. Of the 158 HTLV-I/II-positive specimens (66 requiring radioimmunoprecipitation assay [RIPA] for confirmation), 156 reacted concordantly with r21e, gag, and either rgp46I or rgp46II, thus eliminating the need for RIPA in all but two specimens and yielding a test sensitivity of 98.7 percent. Of the 158 indeterminate and 63 negative specimens, none reacted with r21e and rgp46I or rgp46II, yielding a test specificity of 100 percent. Furthermore, analysis of an additional 184 consecutive specimens from a retrovirology reference laboratory demonstrated that the modified WB correctly identified 27 of 28 HTLV-I specimens and all 13 HTLV-II specimens, with a test sensitivity of 97.6 percent. None of specimens that were indeterminate or nonreactive in conventional WB and/or RIPA and none of the screening enzyme immunoassay-negative specimens reacted with r21e and either rgp46I or rgp46II, for a test specificity of 100 percent. Thus, the modified WB appears to be highly sensitive and specific for simultaneous detection and discrimination of HTLV-I from HTLV-II and has the advantage of being a one-step assay that is easily performed in all types of laboratory settings and allows rapid, reliable, and standardized testing for HTLV-I/II infection.     

Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study.

OBJECTIVE--To determine coronary heart disease (CHD) incidence among dyslipidemic subjects with non-insulin-dependent diabetes mellitus (NIDDM) and to assess the effect of lipid-modifying treatment on serum and lipoprotein lipids and the CHD incidence in these patients. RESEARCH DESIGN AND METHODS--Of the 4081 men participating in the Helsinki Heart Study, a coronary primary prevention trial with gemfibrozil in middle-aged men with high non-high-density lipoprotein (HDL) cholesterol (greater than 5.2 mM; 200 mg/dL), 135 had NIDDM at entry. The incidence of definite myocardial infarction and cardiac death and changes in serum and lipoprotein lipids were determined during the 5-yr trial in the NIDDM patients and compared with those observed in nondiabetic trial participants. RESULTS--Compared with nondiabetic subjects, NIDDM patients had lower HDL cholesterol (P less than 0.001), higher triglyceride concentration (P less than 0.0001), and greater body mass index (P less than 0.001), there were more hypertensive patients (P less than 0.001) among them. The incidence of myocardial infarction and cardiac death was significantly higher among diabetic than nondiabetic participants (7.4 vs. 3.3%, respectively, P less than 0.02). CHD incidence in the gemfibrozil-treated diabetic men (n = 59) was 3.4% compared with 10.5% in the placebo group (NS). In multivariate analysis, diabetes (P less than 0.05), age (P less than 0.0001), smoking (P less than 0.0001), low HDL cholesterol (P less than 0.05), and high low-density lipoprotein cholesterol (P less than 0.005) were independently related to CHD incidence. Gemfibrozil-induced serum and lipoprotein lipid changes in diabetic patients were similar to those observed in nondiabetic subjects. CONCLUSIONS--Compared with similarly dyslipidemic nondiabetic subjects, patients with NIDDM are at markedly increased risk of CHD. This elevated risk can be somewhat reduced by gemfibrozil.