Stored blood - an effective immunosuppressive method for transplantation of kidneys from unrelated donors: An 11-year follow-up

Thirty-seven patients were submitted to kidney transplantation after transfusion at 2-week intervals with 4-week stored blood from their potential donors. All patients and donors were typed for HLA-A-B and DR antigens. The patients were also tested for cytotoxic antibodies against donor antigens before each transfusion. The percentage of panel reactive antibodies (PRA) was determined against a selected panel of 30 cell donors before and after the transfusions. The patients were immunosuppressed with azathioprine and prednisone. Rejection crises were treated with methylprednisolone. The control group consisted of 23 patients who received grafts from an unrelated donor but who did not receive donor-specific pretransplant blood transfusion. The incidence and reversibility of rejection episodes, allograft loss caused by rejection, and patient and graft survival rates were determined for both groups. Non-parametric methods (chi-square and Fisher tests) were used for statistical analysis, with the level of significance set at P<0.05. The incidence and reversibility of rejection crises during the first 60 post-transplant days did not differ significantly between groups. The actuarial graft and patient survival rates at five years were 56% and 77%, respectively, for the treated group and 39.8% and 57.5% for the control group. Graft loss due to rejection was significantly higher in the untreated group (P = 0.0026) which also required more intense immunosuppression (P = 0.0001). We conclude that tranfusions using stored blood have the immunosuppressive effect of fresh blood transfusions without the risk of provoking a widespread formation of antibodies. In addition, this method permits a reduction of the immunosuppressive drugs during the process without impairing the adequate functioning of the renal graft

Application of various antioxidants in the treatment of influenza

We determined the effect of the antioxidants superoxide dismutase, desferrioxamine and allopurinol on the survival of male CBA mice infected intranasally with 2-5 LD50 lung influenza virus A/Aichi/2/68. Survival for at least 20 days was observed for 45% of the mice that received 1000 U/day superoxide dismutase prepared from red blood cells on days 5, 6, 7 and 8 after infection, and 75% survival was observed for mice that received the same dose on days 4, 5, 6, 7 and 8. Desferrioxamine, 25 mg/kg per day and 100 mg/kg per day injected subcutaneously, resulted in survival rates of 5 and 0%, respectively, compared to 10% survival observed for saline-injected controls. Allopurinol at doses of 5 to 50 mg/kg per day had no effect on mouse survival. These data demonstrate the efficacy of superoxide dismutase for the protection of mice against hemorrhagic lung edema. The ineffectiveness of allopurinol suggests that the xanthine oxidase system does not play a major role in hemorrhage or lung edema and that caution is necessary when desferrioxamine is administered during an acute inflammatory process accompanied by erythrocyte lysis

Dialysis, time and death: comparisons of two consecutive decades among patients treated at the same Brazilian dialysis center

The survival of hemodialysis patients is likely to be influenced not only by well-known risk factors like age and comorbidity, but also by changes in dialysis technology and practices accumulated along time. We compared the survival curves, dialysis routines and some risk factors of two groups of patients admitted to a Brazilian maintenance hemodialysis program during two consecutive decades: March 1977 to December 1986 (group 1, N = 162) and January 1987 to June 1997 (group 2, N = 237). The median treatment time was 22 months (range 1-198). Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank method. The Cox proportional hazard regression model was used to investigate the more important variables associated with outcome. The most important changes in dialysis routine and in patient care during the total period of observation were the progressive increase in the dose of dialysis delivered, the prohibition of potassium-free dialysate, the use of bicarbonate as a buffer and the upgrading of the dialysis equipment. There were no significant differences between the survival curves of the two groups. Survival rates at 1, 5 and 10 years were 84, 53 and 29%, respectively, for group 1 and 77, 42 and 21% for group 2. Patients in group 1 were younger (45.5 ± 15.2 vs 55.2 ± 15.9 years, P<0.001) and had a lower prevalence of diabetes (11.1 vs 27.4%, P<0.001) and of cardiovascular disease (9.3 vs 20.7%, P<0.001). According to the Cox multivariate model, only age (hazard ratio (HR) 1.04, confidence interval (CI) 1.03-1.05, P<0.001) and diabetes (HR 2.55, CI 1.82-3.58, P<0.001) were independent predictors of mortality for the whole group. Patients of group 2 had a lower prevalence of sudden death (19.1 vs 9.7%, P<0.001). After adjusting for age, diabetes and other mortality risk factors, the risk of death was 17% lower in group 2, although this difference was not statistically significant. We conclude that the negative effects of advanced age and of higher frequency of comorbidity on the survival of group 2 patients were probably offset by improvements in patient care and in the quality and dose of dialysis delivered, so that the survival curves did not undergo significant changes along time.

Irinotecan and oxaliplatin: an overview of the novel chemotherapeutic options for the treatment of advanced colorectal cancer

Colorectal cancer is one of the most frequent malignancies in humans and an important cause of cancer death. Metastatic colorectal cancer remains incurable with available systemic therapeutic options. The most active cytotoxic drug against this malignancy, the antimetabolite 5-fluorouracil, was developed more than forty years ago, and as a single agent produces responses in only 10 to 15% of patients which in general last less than one year. Efforts to ameliorate these poor results resulted in the 5-fluorouracil/leucovorin combination, which enhances response rates about two-fold, without, however, significantly improving survival rates. The recent emergence of a handful of new 5-fluorouracil analogues and folate antagonists, as well as the topoisomerase I inhibitor irinotecan, and the third-generation platinum compound oxaliplatin, is likely to alter this gloomy scenario. These agents are at least as effective as 5-fluorouracil in patients with advanced colorectal carcinoma, both untreated and previously treated with 5-fluorouracil-based regimens. This has led to the approval of irinotecan as second-line treatment for 5-fluorouracil-refractory disease, while the use of oxaliplatin has been suggested for patients having a defective 5-fluorouracil catabolism. Recently, FDA approved the combination of irinotecan with 5-fluorouracil and leucovorin for first-line treatment of advanced colon cancer. Based on the synergistic preclinical antitumor effects of some of these agents, their meaningful single-agent activity, distinct mechanisms of cytotoxicity and resistance, and only partially overlapping toxicity profiles, effective combination regimens are now being developed, which are likely to lead to a new, more hopeful era for patients suffering from advanced colorectal carcinoma.

The availability of full match sibling donors and feasibility of allogeneic bone marrow transplantation in Brazil

The feasibility of allogeneic bone marrow transplantation (alloBMT) in a developing country has not yet been demonstrated. Many adverse factors including social and economic limitations may reduce the overall results of this complex and expensive procedure. Our objective was to characterize the most important clinical, social and economic features of candidates for transplantation and their potential donors as well as the influence of these factors on overall survival in a retrospective and exploratory analysis at a university hospital. From July 1993 to July 2001, candidates for BMT were referred to the Bone Marrow Transplantation Unit by Hematology and Oncology Centers from several regions of Brazil. A total of 1138 patients were referred to us as candidates for alloBMT. Median age was 25 years (range: 2 months-60 years), 684 (60.1%) were males and 454 (39.9%) were females. The clinical indications were severe aplastic anemia and hematological malignancies. From the total of 1138 patients, 923 had HLA-typing; 497/923 (53.8%) candidates had full match donors; 352/1138 (30.8%) were eligible for alloBMT. Only 235 of 352 (66.7%) were transplanted. Schooling was 1st to 8th grade for 123/235 (52.3%); monthly family income ranged from US$60 (7%) to more than US$400 (36%). Overall survival for patients with chronic myeloid leukemia, severe aplastic anemia and acute myeloid leukemia was 58, 60 and 30%, respectively. Thus, overall survival rates for the most frequent hematological diseases were similar to those reported in the International Registry, except for acute myeloid leukemia. This descriptive and exploratory analysis suggests the feasibility of alloBMT in a developing country like Brazil.

Prognosis of colorectal cancer with liver metastasis: value of a prognostic index

The objective of the present study was to explore the factors related to the prognosis of colorectal cancer (CRC) and to establish a prognostic model for the selection of patients who might benefit from hepatic resection for metastatic CRC. A total of 293 patients undergoing liver resection for metastatic CRC (172 males and 80 females ranging in age from 26 to 80 years) were selected and clinical, pathological and outcome data were examined in this retrospective study. The prognostic index (PI) of the patients was calculated on the basis of results of multivariate analysis. Patients were stratified into different groups, with survival curves projected according to PI. The 1-, 3-, and 5-year overall survival rates were 58.3, 26.4, and 11.3%, respectively. Univariate analysis indicated that degree of primary tumor differentiation, resection margin, preoperative carcinoembryonic antigen (CEA) level, number of liver metastases, and resection of liver metastases were associated with prognosis (P < 0.05). In multivariate analysis, the last three factors were found to be independent prognostic factors. The resection of liver metastases was a favorable factor. Patients were classified into three groups according to PI, which differed significantly in survival rate (P < 0.05). The individual survival rate was evaluated based on PI. Resection of hepatic colorectal metastases may produce long-term survival and cure. The proposed PI was easy to use, was highly predictive of patient outcome, and permitted categorization of patients into treatment groups.

Outcomes and organ dysfunctions of critically ill patients with systemic lupus erythematosus and other systemic rheumatic diseases

Our objective was to compare the pattern of organ dysfunctions and outcomes of critically ill patients with systemic lupus erythematosus (SLE) with patients with other systemic rheumatic diseases (SRD). We studied 116 critically ill SRD patients, 59 SLE and 57 other-SRD patients. The SLE group was younger and included more women. Respiratory failure (61%) and shock (39%) were the most common causes of ICU admission for other-SRD and SLE groups, respectively. ICU length-of-stay was similar for the two groups. The 60-day survival adjusted for the groups’ baseline imbalances was not different (P = 0.792). Total SOFA scores were equal for the two groups at admission and during ICU stay, although respiratory function was worse in the other-SRD group at admission and renal and hematological functions were worse in the SLE group at admission. The incidence of severe respiratory dysfunction (respiratory SOFA >2) at admission was higher in the other-SRD group, whereas severe hematological dysfunction (hematological SOFA >2) during ICU stay was higher in the SLE group. SLE patients were younger and displayed a decreased incidence of respiratory failure compared to patients with other-SRDs. However, the incidences of renal and hematological failure and the presence of shock at admission were higher in the SLE group. The 60-day survival rates were similar.

Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.

Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis

The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI) with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males) diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m2), normal weight (18.5≤BMI<25.0 kg/m2), overweight (25.0≤BMI<30.0 kg/m2), and obese (BMI≥30.0 kg/m2). Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m2. The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ2=35.16, P<0.001). The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis.

Low-intensity red and infrared laser effects at high fluences on Escherichia coli cultures

Semiconductor laser devices are readily available and practical radiation sources providing wavelength tenability and high monochromaticity. Low-intensity red and near-infrared lasers are considered safe for use in clinical applications. However, adverse effects can occur via free radical generation, and the biological effects of these lasers from unusually high fluences or high doses have not yet been evaluated. Here, we evaluated the survival, filamentation induction and morphology of Escherichia coli cells deficient in repair of oxidative DNA lesions when exposed to low-intensity red and infrared lasers at unusually high fluences. Cultures of wild-type (AB1157), endonuclease III-deficient (JW1625-1), and endonuclease IV-deficient (JW2146-1) E. coli, in exponential and stationary growth phases, were exposed to red and infrared lasers (0, 250, 500, and 1000 J/cm2) to evaluate their survival rates, filamentation phenotype induction and cell morphologies. The results showed that low-intensity red and infrared lasers at high fluences are lethal, induce a filamentation phenotype, and alter the morphology of the E. coli cells. Low-intensity red and infrared lasers have potential to induce adverse effects on cells, whether used at unusually high fluences, or at high doses. Hence, there is a need to reinforce the importance of accurate dosimetry in therapeutic protocols.

Correlation of cadherin-17 protein expression with clinicopathological features and prognosis of patients with sporadic gastric cancer

This study aimed to explore the correlations between cadherin-17 (CDH17) protein expression and the clinicopathological features and prognosis of patients with sporadic gastric cancer (GC). Nine relevant studies of 1,960 patients were identified using electronic database searches supplemented with a manual search in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted using STATA 12.0 statistical software. Relative risks and 95% confidence intervals were determined, and Z test was used to measure the significance of the overall effect size. A total of nine eligible cohort studies were included in this meta-analysis. The expression of CDH17 in patients with diffuse GC was significantly higher than in those with intestinal-type GC. Moreover, the tumor depth of invasion differed significantly between patients with positive CDH17 (CDH17+) and negative CDH17 (CDH17-) GC. However, there were no significant differences between CDH17+ and CDH17- GC patients with respect to tumor node metastasis clinical stages, histological grades, or lymph node metastasis. Despite the differences in invasive depth, there was no significant difference in 5-year survival rates between CDH17+ and CDH17- GC patients. Our meta-analysis provides evidence that CDH17 protein expression may be associated with the development of GC, suggesting that CDH17 is an important biomarker that could be useful for the early diagnosis of GC. However, CDH17 levels do not appear to impact overall survival.

Cardiovascular health and fitness after childhood acute lymphoblastic leukaemia

The last few decades have turned childhood acute lymphoblastic leukaemia (ALL) from a virtually incurable disease to a disease with 80–90% survival rates. However, this has not come without a cost. Various late effects of the treatment are nowadays well acknowledged, and the survivors have increased cardiovascular (CV) morbidity and mortality. While the treatment of ALL may have direct toxic effects on various organ systems, lifestyle factors affect the CV risk of the survivors as well. Data on CV health and fitness after treatment with common Nordic protocols since 1986 has been scarce. This thesis aimed to study CV health and fitness and the effects of a 3-month exercise intervention in 16–30-year-old long-term survivors of childhood ALL. Fitness was poor especially in female survivors. One third reported ≤1h of moderate physical activity (PA) weekly. While the levels of other CV risk factors were similar in survivors and controls, attenuations in vascular endothelium and cardiac function were found when using advanced echocardiographic methods. The exercise programme improved fitness, insulin resistance, endothelial function as well as measures of cardiac function. While the results do not allow definite conclusions on whether the subclinical signs of cardiac and vascular endothelial dysfunction are due to the treatment of ALL or sedentary lifestyle/poor fitness after treatment, the results are interesting and emphasize the effects of PA in this population. The results indicate beneficial effects of PA on the heart health in ALL survivors and suggest that they should be encouraged to physically active lifestyle.

A retrospective study of cholinesterase inhibitors for Alzheimer's disease : the effect of cerebrovascular disease on patient outcomes and the impact of biases on the results.

Introduction: La démence peut être causée par la maladie d’Alzheimer (MA), la maladie cérébrovasculaire (MCEREV), ou une combinaison des deux. Lorsque la maladie cérébrovasculaire est associée à la démence, les chances de survie sont considérées réduites. Il reste à démontrer si le traitement avec des inhibiteurs de la cholinestérase (ChEIs), qui améliore les symptômes cognitifs et la fonction globale chez les patients atteints de la MA, agit aussi sur les formes vasculaires de démence. Objectifs: La présente étude a été conçue pour déterminer si la coexistence d’une MCEREV était associée avec les chances de survie ou la durée de la période jusqu’au placement en hebergement chez les patients atteints de la MA et traités avec des ChEIs. Des études montrant de moins bons résultats chez les patients souffrant de MCEREV que chez ceux n’en souffrant pas pourrait militer contre l’utilisation des ChEIs chez les patients atteints à la fois de la MA et la MCEREV. L'objectif d'une seconde analyse était d'évaluer pour la première fois chez les patients atteints de la MA l'impact potentiel du biais de « temps-immortel » (et de suivi) sur ces résultats (mort ou placement en hebergement). Méthodes: Une étude de cohorte rétrospective a été conduite en utilisant les bases de données de la Régie de l’Assurance Maladie du Québec (RAMQ) pour examiner la durée de la période jusqu’au placement en hebergement ou jusqu’au v décès des patients atteints de la MA, âgés de 66 ans et plus, avec ou sans MCEREV, et traités avec des ChEIs entre le 1er Juillet 2000 et le 30 Juin 2003. Puisque les ChEIs sont uniquement indiquées pour la MA au Canada, chaque prescription de ChEIs a été considérée comme un diagnostic de la MA. La MCEREV concomitante a été identifié sur la base d'un diagnostic à vie d’un accident vasculaire cérébral (AVC) ou d’une endartériectomie, ou d’un diagnostic d'un accident ischémique transitoire au cours des six mois précédant la date d’entrée. Des analyses séparées ont été conduites pour les patients utilisant les ChEIs de façon persistante et pour ceux ayant interrompu la thérapie. Sept modèles de régression à risque proportionnel de Cox qui ont varié par rapport à la définition de la date d’entrée (début du suivi) et à la durée du suivi ont été utilisés pour évaluer l'impact du biais de temps-immortel. Résultats: 4,428 patients ont répondu aux critères d’inclusion pour la MA avec MCEREV; le groupe de patients souffrant seulement de la MA comptait 13,512 individus. Pour le critère d’évaluation composite considérant la durée de la période jusqu’au placement en hebergement ou jusqu’au décès, les taux de survie à 1,000 jours étaient plus faibles parmi les patients atteints de la MA avec MCEREV que parmi ceux atteints seulement de la MA (p<0.01), mais les différences absolues étaient très faibles (84% vs. 86% pour l’utilisation continue de ChEIs ; 77% vs. 78% pour la thérapie avec ChEIs interrompue). Pour les critères d’évaluation secondaires, la période jusqu’au décès était plus courte chez les patients avec la MCEREV que sans la MCEREV, mais la période jusqu’au vi placement en hebergement n’était pas différente entre les deux groupes. Dans l'analyse primaire (non-biaisée), aucune association a été trouvée entre le type de ChEI et la mort ou le placement en maison d'hébergement. Cependant, après l'introduction du biais de temps-immortel, on a observé un fort effet différentiel. Limitations: Les résultats peuvent avoir été affectés par le biais de sélection (classification impropre), par les différences entre les groupes en termes de consommation de tabac et d’indice de masse corporelle (ces informations n’étaient pas disponibles dans les bases de données de la RAMQ) et de durée de la thérapie avec les ChEIs. Conclusions: Les associations entre la coexistence d’une MCEREV et la durée de la période jusqu’au placement en hebergement ou au décès apparaissent peu pertinentes cliniquement parmi les patients atteints de la MA traités avec des ChEIs. L’absence de différence entre les patients atteints de la MA souffrant ou non de la MCEREV suggère que la coexistence d’une MCEREV ne devrait pas être une raison de refuser aux patients atteints de la MA l’accès au traitement avec des ChEIs. Le calcul des « personne-temps » non exposés dans l'analyse élimine les estimations biaisées de l'efficacité des médicaments.

Étude de l’impact de la température et de l’humidité sur la survie et la dynamique de la ponte de la mouche du chou (Delia radicum L.)

Réalisé en cotutellle avec Gaétan Bourgeois et avec la participation de Guy Boivin, d'Agriculture et Agroalimentaire Canada, du Centre de Recherche et Développement en Horticulture à Saint-Jean-sur-Richelieu, QC J3B 3E6, Canada

Étude de cohorte rétrospective analytique et descriptive des résultats échocardiographiques et cliniques de la chirurgie valvulaire tricuspidienne

Résumé - Les données concernant la prise en charge chirurgicale de la maladie tricuspidienne reposent sur des études de cohortes à petite échelle et peu d’entre elles se sont intéressées aux résultats échocardiographiques et aux facteurs de risque de mortalité et de morbidité. Une étude de cohorte rétrospective descriptive et analytique fut effectuée pour analyser l’expérience de l’Institut de Cardiologie de Montréal concernant la chirurgie de la VT. Les données ont été récoltées à l’aide des dossiers médicaux. Durant la période 1977-2008, 792 PVT et 134 RVT furent effectués (âge médian : 62 ans). La mortalité opératoire était de 13,8%. Les taux de survie actuarielle à 5, à 10 et à 15 ans étaient respectivement de 67±2%, de 47±2% et de 29±2%. Au dernier suivi, de l’IT ≥3/4 était présente chez 31% des patients du groupe PVT et chez 12% des patients du groupe RVT (p<0,001). La classe fonctionnelle NYHA s’est améliorée significativement au dernier suivi par rapport à la période pré-opératoire (p<0,001). L’analyse de propension montre que par rapport à une PVT, un RVT est associé significativement à des taux de mortalité opératoire et tardive accrus, mais à moins d’IT ≥2/4 ou ≥3/4 lors du suivi. Cette étude montre que malgré le risque chirurgical substantiel associé à la chirurgie de la VT, les patients bénéficient d’une amélioration fonctionnelle significative. Les facteurs de risque de mortalité et de morbidité sont décrits et des études de sous-groupes sur la chirurgie tri-valvulaire et la chirurgie isolée de la VT sont exposées.