Immune Cells and Immunosenescence.

Aging is associated with progressive loss of physiological integrity, leading to impaired physical and mental functions as well as increased morbidity and mortality. With advancing age, the immune system is no longer able to adequately control autoimmunity, infections, or cancer. The abilities of the elderly to slow down undesirable effects of aging may depend on the genetic background, lifestyle, geographic region, and other presently unknown factors. Although most aspects of the immunity are constantly declining in relation to age, some features are retained, while e.g. the ability to produce high levels of cytokines, response to pathogens by increased inflammation, and imbalanced proteolytic activity are found in the elderly, and might eventually cause harm. In this context, it is important to differentiate between the effect of immunosenescence that is contributing to this decline and adaptations of the immune system that can be quickly reversed if necessary.

Use of photoacoustic excitation and laser vibrometry to remotely detect trace explosives.

In this paper, we examine a laser-based approach to remotely initiate, measure, and differentiate acoustic and vibrational emissions from trace quantities of explosive materials against their environment. Using a pulsed ultraviolet laser (266 nm), we induce a significant (>100 Pa) photoacoustic response from small quantities of military-grade explosives. The photoacoustic signal, with frequencies predominantly between 100 and 500 kHz, is detected remotely via a wideband laser Doppler vibrometer. This two-laser system can be used to rapidly detect and discriminate explosives from ordinary background materials, which have significantly weaker photoacoustic response. A 100 ng/cm2 limit of detection is estimated. Photoablation is proposed as the dominant mechanism for the large photoacoustic signals generated by explosives.

Histopathological grading systems analysis of oral squamous cell carcinomas of young patients.

BACKGROUND: To analyze the clinicopathological profile of young patients (≤ 40 years) with oral SCC and correlate with a control group (≥ 50 years) by means of histopathological grading systems. MATERIAL AND METHODS: 14 young patients and 14 control patients were selected with similar clinical stage and tumor location. Demographic and clinical data were obtained from patient records and histological sections were evaluated according to four histopathological grading systems. Associations between categories of demographic and clinical data were performed through Chi-square test and Exact Fisher test. The survival analyzes were performed according to the Kaplan-Meier method. RESULTS: The comparison between groups showed a greater association of treatment modalities in younger patients (p=0.022), they had a higher incidence of local recurrence and regional metastasis (p=0.018) and lower disease-free survival in 5 years (p=0.069). There was no difference in 5-year overall survival among the studied groups. There was no difference in histological grading between studied groups according to the four used systems. CONCLUSIONS: This study showed that, despite tumors had similar histological grade and more therapeutic modalities were used in the young group, tumors in young patients had a higher incidence of recurrence/metastasis, showing tendency to a more aggressive behavior.

The prognostic value of histopathological grading systems in oral squamous cell carcinomas.

OBJECTIVE: This study evaluated the association of four histopathological grading systems (WHO grading system, malignancy grading of the deep invasive margins (MG), histological risk (HR) model, and tumor budding and depth of invasion (BD) model) with clinicopathological parameters and outcome of 113 oral squamous cell carcinomas to identify their roles in prognosis. METHODS: Demographic and clinical features were obtained from patients' records. Sections from all paraffin-embedded blocks were evaluated according to the four grading systems. Demographic and clinical associations were analyzed using chi-square test, and correlations between the grading systems were established with the Spearman's rank correlation test. Survival curves were performed with Kaplan-Meier method, and multivariate analysis based on Cox proportional hazard model was calculated. RESULTS: Significant associations with survival were observed for WHO grading system and BD model in the univariate analysis, but only the BD model was significantly associated with disease outcome as an independent prognostic marker. Age, tumor size, and presence of regional metastasis were also independent markers of reduced survival. CONCLUSION: A significant association between the BD model and outcome of OSCC patients was observed, indicating this new histopathological grading system as a possible prognostic tool.

Trace aerosol detection and identification by dynamic photoacoustic spectroscopy.

Dynamic photoacoustic spectroscopy (DPAS) is a high sensitivity technique for standoff detection of trace vapors. A field-portable DPAS system has potential as an early warning provider for gaseous-based chemical threats. For the first time, we utilize DPAS to successfully detect the presence of trace aerosols. Aerosol identification via long-wavelength infrared (LWIR) spectra is demonstrated. We estimate the sensitivity of our DPAS system to aerosols comprised of silica particles is comparable to that of SF(6) gas based on a signal level per absorbance unit metric for the two materials. The implications of these measurements are discussed.

Noncontact optical detection of explosive particles via photodissociation followed by laser-induced fluorescence.

High-sensitivity (ng/cm²) optical detection of the explosive 2,4,6-trinitrotoluene (TNT) is demonstrated using photodissociation followed by laser-induced fluorescence (PD-LIF). Detection occurs rapidly, within 6 laser pulses (~7 ns each) at a range of 15 cm. Dropcasting is used to create calibrated samples covering a wide range of TNT concentrations; and a correspondence between fractional area covered by TNT and PD-LIF signal strength is observed. Dropcast data are compared to that of an actual fingerprint. These results demonstrate that PD-LIF could be a viable means of rapidly and remotely scanning surfaces for trace explosive residues.

Noncontact detection of homemade explosive constituents via photodissociation followed by laser-induced fluorescence.

Noncontact detection of the homemade explosive constituents urea nitrate, nitromethane and ammonium nitrate is achieved using photodissociation followed by laser-induced fluorescence (PD-LIF). Our technique utilizes a single ultraviolet laser pulse (approximately 7 ns) to vaporize and photodissociate the condensed-phase materials, and then to detect the resulting vibrationally-excited NO fragments via laser-induced fluorescence. PD-LIF excitation and emission spectra indicate the creation of NO in vibrationally-excited states with significant rotational energy, useful for low-background detection of the parent compound. The results for homemade explosives are compared to one another and 2,6-dinitrotoluene, a component present in many military explosives.

Donor-derived aspergillosis from use of a solid organ recipient as a multiorgan donor.

The growing need for organs and the scarcity of donors has resulted in an increased use of extended criteria donors. We report a case where a recipient of a cardiac graft was used as an organ donor. Death of the recipient occurred 9 days after transplantation and was attributed to presumed cerebral hemorrhage, which post mortem was diagnosed as invasive aspergillosis of the brain. One recipient of a kidney transplant lost the graft due to infection with Aspergillus fumigatus, whereas prompt initiation of therapy successfully prevented disseminated aspergillosis in the other recipients. Despite the pressure to extend the use of organs by lowering the acceptance criteria, organs should only be accepted if the cause of death of the donors is unequivocally explained.

[Benefit assessment of PET in malignant lymphomas. The IQWiG point of view]. / Nutzenbewertung der PET bei malignen Lymphomen - Standpunkt des IQWiG.

The call by the Institute for Quality and Efficiency in Health Care (IQWiG) for randomised controlled trials (RCTs) to prove the patient-relevant benefit of positron emission tomography (PET) is currently a controversial topic in Germany. From a methodological point of view there is essentially no difference between diagnostic procedures and therapeutic (drug or non-drug) interventions in proving their causal benefit. A broad consensus has been reached since the 1960s (e.g. FDA regulations) that RCTs are the methodological gold standard for therapeutic interventions. Nevertheless, the same arguments that were cited against RCTs in assessing the benefit of therapeutic interventions are now used against RCTs in evaluating diagnostic tests (e.g. ethical problems, feasibility, etc.). This paper summarizes the central methodological arguments of the discussion on the benefit assessment of PET in malignant lymphomas from the perspective of IQWiG and its external experts.

Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults.

BACKGROUND: Postoperative adynamic bowel atony interferes with recovery following abdominal surgery. Prokinetic pharmacologic drugs are widely used to accelerate postoperative recovery. OBJECTIVES: To evaluate the benefits and harms of systemic acting prokinetic drugs to treat postoperative adynamic ileus in patients undergoing abdominal surgery. SEARCH STRATEGY: Trials were identified by computerised searches of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the Cochrane Colorectal Cancer Group specialised register. The reference lists of included trials and review articles were tracked and authors contacted. SELECTION CRITERIA: Randomised controlled parallel-group trials (RCT) comparing the effect of systemically acting prokinetic drugs against placebo or no intervention. DATA COLLECTION AND ANALYSIS: Four reviewers independently extracted the data and assessed trial quality. Trial authors were contacted for additional information if needed. MAIN RESULTS: Thirty-nine RCTs met the inclusion criteria contributing a total of 4615 participants. Most trials enrolled a small number of patients and showed moderate to poor (reporting of) methodological quality, in particular regarding allocation concealment and intention-to-treat analysis. Fifteen systemic acting prokinetic drugs were investigated and ten comparisons could be summarized. Six RCTs support the effect of Alvimopan, a novel peripheral mu receptor antagonist. However, the trials do not meet reporting guidelines and the drug is still in an investigational stage. Erythromycin showed homogenous and consistent absence of effect across all included trials and outcomes. The evidence is insufficient to recommend the use of cholecystokinin-like drugs, cisapride, dopamine-antagonists, propranolol or vasopressin. Effects are either inconsistent across outcomes, or trials are too small and often of poor methodological quality. Cisapride has been withdrawn from the market due to adverse cardiac events in many countries. Intravenous lidocaine and neostigmine might show a potential effect, but more evidence on clinically relevant outcomes is needed. Heterogeneity among included trials was seen in 10 comparisons. No major adverse drug effects were evident. AUTHORS' CONCLUSIONS: Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect.

Detection of condensed-phase explosives via laser-induced vaporization, photodissociation, and resonant excitation.

We investigate the remote detection of explosives via a technique that vaporizes and photodissociates the condensed-phase material and detects the resulting vibrationally excited NO fragments via laser-induced fluorescence. The technique utilizes a single 7 ns pulse of a tunable laser near 236.2 nm to perform these multiple processes. The resulting blue-shifted fluorescence (226 nm) is detected using a photomultiplier and narrowband filter that strongly block the scatter of the pump laser off the solid media while passing the shorter wavelength photons. Various nitro-bearing compounds, including 2,6-dinitrotoluene (DNT), 2,4,6-trinitrotoluene (TNT), pentaerythritol tetranitrate (PETN), and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) were detected with a signal-to-noise of 25 dB. The effects of laser fluence, wavelength, and sample morphology were examined.

Randomisation to protect against selection bias in healthcare trials.

BACKGROUND: Randomised trials use the play of chance to assign participants to comparison groups. The unpredictability of the process, if not subverted, should prevent systematic differences between comparison groups (selection bias), provided that a sufficient number of people are randomised. OBJECTIVES: To assess the effects of randomisation and concealment of allocation on the results of healthcare trials. SEARCH STRATEGY: We searched the Cochrane Methodology Register, MEDLINE, SciSearch, reference lists up to August 2000 and used personal communication. SELECTION CRITERIA: Cohorts of trials, systematic reviews or meta-analyses of healthcare interventions that compared outcomes or prognostic factors for one of the following comparisons: randomised versus non-randomised trials, randomised trials with adequately versus inadequately concealed allocation, or high versus low quality trials where selection bias could not be separated from other sources of bias. DATA COLLECTION AND ANALYSIS: One of us went through all of the citations in the Cochrane Methodology Register and accumulated reference lists. Studies that appeared to meet the inclusion criteria were retrieved and assessed independently by two of the reviewers. The methodological quality of included studies was appraised and information extracted by one of us and checked by a second. Tabular summaries of the results were prepared for each comparison and the results across studies were assessed qualitatively to identify common trends or discrepancies. MAIN RESULTS: We identified 32 studies including over 3000 trials. Twenty-two studies compared randomised versus non-randomised trials, three compared adequately versus inadequately concealed allocation, and nine compared high versus low quality trials (some studies included more than one comparison). Five studies were of high methodological quality. In 15 of the 22 studies that compared randomised and non-randomised trials of the same intervention, important differences were found in the estimates of effect. Some of these differences were due to a poorer prognosis in the control groups in the non-randomised trials. The results of the other seven studies that compared randomised and non-randomised trials across different interventions are less clear. Comparisons of adequately and inadequately concealed allocation in randomised trials of the same intervention provided high quality evidence that concealment can be crucial in achieving similar treatment groups and, therefore, unbiased estimates of treatment effects. Studies with inadequate concealment tended to overestimate treatment effects. Comparisons of high and low quality trials of the same intervention have found important differences in estimates of effect, but it is not possible to determine the extent to which these differences can be attributed to randomisation or concealment of allocation. Omitting comparisons between randomised trials and non-randomised trials using historical controls did not substantially alter the results or conclusions of our review. AUTHORS' CONCLUSIONS: On average, non-randomised trials and randomised trials with inadequate concealment of allocation tend to result in larger estimates of effect than randomised trials with adequately concealed allocation. However, it is not generally possible to predict the magnitude, or even the direction, of possible selection biases and consequent distortions of treatment effects.

Chemical restraint of coatis by the association of Detomidine, Tiletamine and Zolazepam, in allometrically scaled dosages / [Contenção farmacológica de quatis pela associação de detomidina, tiletamina e zolazepam, em doses calculadas por extrapolação alométrica]

Ten free-living adult coatis (two males and eight females) were chemically restrained with "ZAD-50", a concentrated formulation prepared with the dehydrated content of a Zoletil/50® vial diluted with 0.25mL of 1% atropine, 0.265mL of Dormiun-V®, and 2.2mL of distilled water, being exactly 3.0mL. The formula was administered to each animal previously captured and physically contained with a net. The loss of righting reflex (RR) occurred at 2.3±0.8 minutes post-injection (MPI), with anesthesia beginning at 4.4±2.7 MPI. Myorelaxant and analgesia were considered excellent at all moments of the evaluation. Conscious reactions were observed at 78.7±22.2 MPI, the return of the RR occurred at 101 ± 18 MPI, and normal ambulation was acquired at 137.0±31.0 MPI. The mean values ​​of physiological parameters measured every 10 minutes between 10 and 50 MPI were 152.2 heartbeats per minute for heart rate, 66.4 respiratory movements per minute for respiratory rate, 39.2oC for rectal temperature, 86.2% for SpO2 and 14.6 mmHg for systolic blood pressure. In the same times, the EEG registered sinus rhythm. No adverse reactions were observed, and the assessed vital parameters remained compatible with the state of chemical restraint.(AU)

Dez quatis adultos de vida livre (dois machos e oito fêmeas) foram contidos empregando-se a formulação denominada "ZAD-50". A fórmula foi preparada a partir do conteúdo desidratado de um frasco de Zoletil/50® diluído em 0,25mL de atropina a 1%, 0,265mL de Dormiun-V® e 2,2mL de água destilada, obtendo-se volume final de 3,0mL. A associação foi administrada, por via intramuscular, a cada animal capturado e contido fisicamente com puçá, em dose calculada por meio de extrapolação alométrica interespecífica. A perda da reação postural de endireitamento (RPE) ocorreu aos 2,3±0,8 minutos pós-injeção (MPI), observando-se início da anestesia aos 4,4±2,7 MPI. Miorrelaxamento e analgesia foram considerados excelentes em todos os momentos da avaliação. Reações conscientes foram observadas aos 78,7±22,2 MPI, o retorno da RPE ocorreu aos 101±18 MPI, e os animais voltaram à ambulação normal aos 137,0±31,0 MPI. Os valores médios dos parâmetros fisiológicos mensurados a cada 10 minutos entre 10 e 50 MPI foram 152,2 batimentos por minuto para frequência cardíaca, 66,4 movimentos por minuto para frequência respiratória, 39,2oC para temperatura retal, 86,2% para saturação parcial de oxigênio e 14,6mmHg para pressão arterial sistólica. Nesses tempos, observou-se ritmo sinusal no eletrocardiograma, e não foram observadas reações adversas.(AU)

[Contribution of early systole to total antegrade flow volume in breath-hold phase-contrast flow measurements]. / Anteil des frühen systolischen Flussanstiegs am antegrad fliessenden Gesamtvolumen bei Phasenkontrast-Flussmessungen in Atemanhaltetechnik.

PURPOSE: To evaluate the contribution of early systole for the assessment of antegrade aortic flow volume by breath-hold velocity-encoded magnetic resonance (MR) flow measurements. MATERIALS AND METHODS: Expiratory breath-hold fast low-angle shot (FLASH) phase-contrast flow measurements (temporal resolution tRes 61 msec, shared phases) perpendicular to the proximal ascending aorta and short axis true fast imaging with steady-state precession (TrueFISP) cine MR ventriculometry (tRes 34.5 msec) were performed in ten healthy male volunteers on a 1.5 T MR system (Sonata, Siemens Medical Solutions). Antegrade aortic flow volume (AFV) and left ventricular stroke volume (LV-SV) were evaluated using Argus Ventricular Function and Argus Flow Software, version MR 2002B (Siemens Medical Solutions). A beta release of Argus Flow MR 2004A allowed interpolation of the flow up-slope during early systole to the preceding R-wave trigger. The respective intraindividual median differences between the AFV of each flow evaluation and LV-SV as well as between both AFV measurements were calculated and compared using the sign test for paired samples. RESULTS: Non-interpolated AFV significantly deviated from LV-SV (p = 0.006), underestimating the latter by 13.1 mL (13 %). Interpolating aortic flow during early systole significantly increased AFV by 10.8 mL (13 %) compared to the flow evaluation which did not take early systole into account (p = 0.006). AFV with interpolation of early systolic flow agreed well with LV-SV (median difference - 3.0 mL or - 3 %, respectively), and no significant difference between these measurements was found (p = 1.0). CONCLUSION: Flow during early systole contributes substantially to total forward flow volume in the ascending aorta. Interpolation of the early systolic up-slope is therefore recommended for the evaluation of breath-hold phase-contrast flow measurements.

[Systematic analysis of the geometry of a defined contrast medium bolus--implications for contrast enhanced 3D MR-angiography of thoracic vessels]. / Systematische Analyse der Geometrie eines definierten Kontrastmittelbolus -- Implikationen für die kontrastmittelverstärkte 3D-MR-Angiographie thorakaler Gefässe.

PURPOSE: Little is known about the dispersion of a defined contrast bolus during its passage through the heart and pulmonary vasculature. The purpose of this study was to analyze factors influencing a defined contrast bolus for ce-MRA of thoracic vessels. MATERIALS AND METHODS: For analysis of bolus geometry, an ECG-gated saturation-recovery Turbo-Flash sequence with a TI of 20 msec was used. It was acquired axially at the level of the pulmonary trunc, so that with one data acquisition a curve analysis was possible in the ascending and descending aorta, and in the pulmonary trunc. Twenty-nine patients received 3 ml of Gd-DTPA diluted with saline to a total of 20 ml. Contrast injection was done using a MR compatible power injector with injection rates varying between 1, 2 and 4 ml/sec. Each injection was followed by a saline flush of 20 ml with the same injection rate and mode. Cardiac function was assessed by cine imaging, and phase contrast measurements. After normalization to baseline signal intensity (SI), bolus curves were fitted using a gamma-variate fit and peak signal intensity (peak SI), time-to-peak (TP), upslope, mean transit time (MTT) and dispersion of the contrast bolus were calculated. Furthermore, T (1) and [Gd] in the experimental setting were calculated as follows: T (1) = T (1 o)/ ln [SI/SI (0)], and [Gd] (exp) = [1/T (1) - 1/T (1 o)]/ R (1.) They were then extrapolated [Gd] to clinical conditions by [Gd] (clin) = [Gd] (exp) . 10/1.5, and minimal blood T (1) by T (1)(clin) = 1 / [1/T (1 o) + R (1) [Gd] (clin)]. RESULTS: With increasing injection rate, there was a significant decrease (p < 0.001) of MTT in all target vessels. However, this decrease was not linear: a 4-fold increase in injection rate lead to a 2-fold decrease in MTT e. g. in the ascending aorta. MTT was significantly shorter in the pulmonary trunc compared with that in the ascending and descending aorta (p < 0.001), regardless of injection rate (p < 0.001). Vice versa, dispersion of the contrast bolus was significantly lower in the pulmonary trunc, and increased with higher injection rates. There was no clinically relevant difference in minimal blood T (1) between the different target vessels, for clinical conditions extrapolated values ranged between 20 und 79 msec. Heart function parameters only had a minor influence of bolus curve parameters. CONCLUSION: Analysis of bolus geometry enables determination of transit times of a defined contrast bolus through a defined target vessel in the thoracic cavity. Bolus geometry is mainly determined by injection parameters, cardiac function is of minor importance. Dispersion of contrast bolus and MTT increase from the pulmonary trunc to the ascending aorta. The knowledge of these facts may help optimizing of injection parameters and the total amount of contrast agent for contrast-enhanced MRA of thoracic vessels.

Association between the angiotensinogen 235T-variant and essential hypertension in whites: a systematic review and methodological appraisal.

Recently, an allelic variant of the angiotensinogen gene (AGT 235T) has been associated with increased risk of hypertension. However, this finding has not been confirmed by all investigators. A meta-analysis was performed to examine the association between the AGT 235T-allele and hypertension in whites and to identify potential reasons for the controversial results. All relevant articles published between 1992 and 1996 were identified through multiple sources. The studies were methodologically appraised, and the frequency of the AGT 235T-allele was extracted. The 235T-allele frequency was pooled using the common odds ratio (OR) estimator by Mantel-Haenszel. Homogeneity was assessed using the Breslow-Day test. Together these studies present data on 5493 patients. The AGT 235T-allele was significantly associated with hypertension (OR: 1.20; 95% [CI]: 1.11 to 1.29; P<.0001). This association increased in studies with positive family history (OR: 1.42; 95% CI: 1.25 to 1.61, P<.0001), recruitment of cases from referral centers (OR: 1.39; 95% CI: 1.20 to 1.62, P<.0001), and more severe hypertension (OR: 1.34; 95% CI: 1.22 to 1.47, P<.0001). However, the presence of methodological problems in all studies gives rise to serious concerns regarding bias and confounding. Despite a statistically significant, albeit weak, association between the AGT 235T variant and hypertension that has been confirmed through sensitivity analysis, this finding has to be interpreted with caution, as the methodological weaknesses of the individual studies are likely to have biased the outcome of the meta-analysis. Clearly, more rigorous methods need to be applied in association studies on the genetics of human hypertension.

Genetic variants of the renin-angiotensin system and ambulatory blood pressure in essential hypertension.

OBJECTIVE: To examine whether the angiotensinogen M235T and angiotensin converting enzyme insertion/deletion (I/D) variants are related to the severity of hypertension in patients with established essential hypertension. DESIGN: A cross-sectional study. SETTING: The hypertension clinic of the Benjamin Franklin University Hospital, Free University of Berlin. PARTICIPANTS: Three hundred and forty-three consecutive Caucasian patients who presented with treated or untreated (n = 115) hypertension were enrolled into the study. Twenty-two patients were excluded from analysis because they had secondary hypertension. MAIN OUTCOME MEASURES: Angiotensinogen M235T and angiotensin-converting enzyme I/D genotypes, 24 h ambulatory blood pressure values, the number of antihypertensive medications administered and left ventricular dimensions assessed by two-dimensional echocardiography. RESULTS: Neither the angiotensinogen nor the angiotensin converting enzyme genotype was related significantly to the average ambulatory blood pressure and left ventricular dimensions in hypertensives. Furthermore, neither the number of antihypertensive medications administered to treated patients nor blood pressure levels in untreated patients (n = 115) differed significantly between the genotypic groups. CONCLUSIONS: These results do not support the hypothesis that the studied molecular variants of the renin-angiotensin system may represent clinically useful markers of the severity of hypertension in Caucasians with established essential hypertension.

Maintenance therapy with triple versus double immunosuppressive regimen in renal transplantation: a meta-analysis.

BACKGROUND: The purpose of this study was to compare the effect of triple immunosuppressive maintenance therapy (cyclosporine, azathioprine, and prednisolone) with that of double therapy (cyclosporine and prednisolone) in renal transplant patients using graft failure, mortality, and acute rejection episodes as outcome measures. METHODS: A systematic overview of articles published between 1984 and 1995 was done. MEDLINE, Science Citation Index, reference lists, and expert files were searched. Of 449 originally identified studies, five controlled trials were finally selected. Information was retrieved on the topics of methodological quality, baseline characteristics, interventions, and outcomes. The Mantel-Haenszel fixed effect method was used to combine results from different studies. RESULTS: Pooled analysis did not show a statistically significant difference between triple-drug therapy and double-drug therapy in the main outcome of graft failure (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.61-1.16), survival (OR, 0.83; 95% CI, 0.57-1.21), or the occurrence of acute graft rejection (OR, 1.02; 95% CI, 0.76-1.36). There was a nonsignificant trend for better graft survival under triple therapy. A lower withdrawal rate suggests a more stable immunosuppressive effect on triple therapy. CONCLUSIONS: There is no statistically significant difference in the long-term management of renal transplant recipients between the two treatment regimens.

Practice variations in the evaluation of adult candidates for cadaveric kidney transplantation: a survey of the European Transplant Centers.

BACKGROUND: This survey was conducted to investigate similarities and differences in the diagnostic evaluation of adult candidates for cadaveric renal transplantation and the criteria for acceptance to the cadaveric renal transplant waiting-list in the European transplant centers. METHODS: A questionnaire listing 45 diagnostic procedures (consultations of 9 specialties, 18 imaging techniques and 18 laboratory investigations), 45 medical conditions constituting possible reasons for exclusion from renal transplantation, and 10 properties characterizing the responding transplant center was sent to 214 European transplant centers. RESULTS: A completed questionnaire was returned by 154 of 214 centers (72%). Significant disagreement (P<0.001) exists about the necessity of 28 of the 45 surveyed diagnostic procedures and about the acceptability of transplant candidates for 15 of the 45 surveyed medical conditions. The influence of center characteristics on the observed practice variations was examined by multinomial logistic regression (factors: Center size, waiting-list pressure, responsibility for organizing the diagnostic work-up, status of transplant center, responsibility for decision about acceptance of candidates and geographic location of center): In 13 of 28 controversial diagnostic procedures, geographic location of the centers turned out to be the only significant determining factor (P<0.001), whereas the dissent about medical conditions is not influenced significantly by the analyzed factors. CONCLUSION: The detected significant practice variations in the evaluation of renal transplant candidates may either indicate where scientific evidence is missing and more clinical research is needed or where the existing evidence has not been adequately disseminated and convincing guidelines should be established.

Influence of cold ischemia time, pretransplant anti-porcine antibodies, and donor/recipient size matching on hyperacute graft rejection after discordant porcine to cynomolgus kidney transplantation.

Organs transplanted between phylogenetically disparate species, such as from the pig into the primate, are subject to hyperacute rejection (HAR). This form of xenograft rejection is mediated by preformed natural antibodies and is believed to occur invariably in discordant xenografts thus leading to rapid destruction and complete thrombosis of the graft. Recent data, however, have shown that in the porcine to cynomolgus monkey setting, HAR is not inevitably seen after porcine kidney transplantation. The influence of preoperative antiporcine antibody levels in the recipient, cold ischemia time, and donor organ weight on the onset of HAR was investigated by using unmodified large white pigs (aged 3-12 weeks) as organ donors and adult cynomolgus monkeys (aged 1.5-3.5 years) as recipients. Porcine kidney xenotransplantation was performed in either a non-life-supporting model (n=7) or in a life-supporting model (n=8). In both models, no correlation was found between cold ischemia time and HAR. When preoperative anti-porcine antibody levels were investigated, a significant increase in incidence of HAR was observed in animals with elevated anti-porcine IgM (P<0.05) but not IgG levels (P=NS). Interestingly, although 5 of 12 grafts with an organ weight of less than 50 g underwent HAR, none of three grafts with a donor organ weight of more than 70 g showed signs of HAR. In addition, all three larger grafts showed intraoperative and postoperative urine production, although only in 1 (48 g) of the 12 grafts weighing less than 50 g primary graft function was observed. In one animal, a second porcine kidney (23 g) was successfully transplanted (without HAR) immediately after HAR and subsequent removal of a first porcine kidney (20 g). These results indicate that in the porcine to cynomolgus monkey setting anti-porcine IgM rather than IgG anti-porcine antibody levels seem to be of predominant importance for the induction of HAR. By increasing the donor organ size and weight the frequency of the onset of HAR can be at least reduced. This is most likely due to immunoabsorption of the recipients preformed antibodies in the porcine kidney without lethal damage for the graft.