Perioperative donor bone marrow infusion augments chimerism in heart and lung transplant recipients

Background.: We and others have demonstrated that a low level of donor cell chimerism was present for years after transplantation in tissues and peripheral blood of heart and lung recipients; it was associated, in the latter, with a lower incidence of chronic rejection. To augment this phenomenon, we initiated a trial combining simultaneous infusion of donor bone marrow with heart or lung allotransplantation. Methods.: Between September 1993 and January 1995, 15 nonconditioned patients received either heart (n = 10) or lung (n = 5) allografts concurrently with an infusion of unmodified donor bone marrow (3.0 × 108 cells/kg), and were maintained on an immunosuppressive regimen consisting of tacrolimus and steroids. Results.: There was no complication associated with the infusion of donor bone marrow. Chimerism was detectable in 73% of bone marrow-augmented patients up to the last sample tested. Of the 5 control recipients who did not receive bone marrow infusion, only 1 had detectable chimerism by flow on postoperative day 15, which dwindled to an undetectable level by postoperative day 36. None of the patients had evidence of donor-specific immune modulation by mixed lymphocyte reaction. Conclusions.: The combined infusion of donor bone marrow and heart or lung transplantation, without preconditioning of the recipient, is safe and is associated with an augmentation of donor cell chimerism. © 1995 The Society of Thoracic Surgeons

Effects of donor bone marrow infusion in clinical lung transplantation

Background. We have demonstrated that donor cell chimerism is associated with a lower incidence of obliterative bronchiolitis (OB) in lung recipients, and that donor chimerism is augmented by the infusion of donor bone marrow (BM). We herein report the intermediate results of a trial combining the infusion of donor BM and lung transplantation. Methods. Clinical and in vitro data of 26 lung recipients receiving concurrent infusion of donor bone marrow (3.0 to 6.0 x 108 cells/kg) were compared with those of 13 patients receiving lung transplant alone. Results. Patient survival and freedom from acute rejection were similar between groups. Of the patients whose graft survived greater than 4 months, 5% (1 of 22) of BM and 33% (4 of 12) of control patients, developed histologic evidence of OB (p = 0.04). A higher proportion (but not statistically significant) of BM recipients (7 of 10, 70%) exhibited donor-specific hyporeactivity by mixed lymphocyte reaction assays as compared with the controls (2 of 7, 28%). Conclusions. Infusion of donor BM at the time of lung transplantation is safe, and is associated with recipients' immune modulation and a lower rate of obliterative bronchiolitis. (C) 2000 by The Society of Thoracic Surgeons

Current Mathematical Methods Used in QSAR/QSPR Studies

This paper gives an overview of the mathematical methods currently used in quantitative structure-activity/property relationship (QASR/QSPR) studies. Recently, the mathematical methods applied to the regression of QASR/QSPR models are developing very fast, and new methods, such as Gene Expression Programming (GEP), Project Pursuit Regression (PPR) and Local Lazy Regression (LLR) have appeared on the QASR/QSPR stage. At the same time, the earlier methods, including Multiple Linear Regression (MLR), Partial Least Squares (PLS), Neural Networks (NN), Support Vector Machine (SVM) and so on, are being upgraded to improve their performance in QASR/QSPR studies. These new and upgraded methods and algorithms are described in detail, and their advantages and disadvantages are evaluated and discussed, to show their application potential in QASR/QSPR studies in the future

Validity of Verbal Autopsy Procedures for Determining Malaria Deaths in Different Epidemiological Settings in Uganda

BACKGROUND: Verbal autopsy (VA) procedures can be used to estimate cause of death in settings with inadequate vital registries. However, the sensitivity of VA for determining malaria-specific mortality may be low, and may vary with transmission intensity. We assessed the diagnostic accuracy of VA procedures as compared to hospital medical records for determining cause of death in children under five in three different malaria transmission settings in Uganda, including Tororo (high), Kampala (medium), and Kisoro (low). METHODS AND FINDINGS: Caretakers of children who died in participating hospitals were interviewed using a standardized World Health Organization questionnaire. Medical records from the child's hospitalization were also reviewed. Causes of death based on the VA questionnaires and the medical records were assigned independently by physician reviewers and then compared. A total of 719 cases were included in the final analysis, 67 in Tororo, 600 in Kampala, and 52 in Kisoro. Malaria was classified as the underlying or contributory cause of death by review of medical records in 33 deaths in Tororo, 60 in Kampala, and 0 in Kisoro. The sensitivity of VA procedures for determining malaria deaths in Tororo was 61% (95% CI 44-78%) and 50% in Kampala (95% CI 37-63%). Specificity for determining malaria deaths in Tororo and Kampala was high (>88%), but positive predictive value varied widely, from 83% in Tororo to 34% in Kampala (difference 49%, 95% CI 31-67, p<0.001). The difference between the cause-specific mortality fraction for malaria as determined by VA procedures and medical records was -11% in Tororo, +5% in Kampala, and +14% in Kisoro. CONCLUSIONS: Our results suggest that these VA methods have an acceptable level of diagnostic accuracy for determining malaria deaths at the population level in high and medium transmission areas, but not in low transmission areas

Associations between APOE Variants and Metabolic Traits and the Impact of Psychological Stress

In a previous study, we observed that associations between APOE rs439401 and metabolic traits were moderated by chronic stress. Thus, in a population of stressed and non-stressed Danish men, we examined whether associations between APOE rs439401 and a panel of metabolic quantitative traits, all metabolic traits which may lead to T2D and CVD were moderated by psychological stress.Obese young men (n = 475, BMI ≥ 31.0 kg/m(2)) and a randomly selected control group (n = 709) identified from a population of 141,800 men were re-examined in two surveys (S-46: mean age 46, S-49: mean age 49 years) where anthropometric and biochemical measures were available. Psychological stress factors were assessed by a self-administered 7-item questionnaire. Each item had the possible response categories "yes" and "no" and assessed familial problems and conflicts. Summing positive responses constituted a stress item score, which was then dichotomized into stressed and non-stressed. Logistic regression analysis, applying a recessive genetic model, was used to assess odds ratios (OR) of the associations between APOE rs439401 genotypes and adverse levels of metabolic traits.The APOE rs439401 TT-genotype associated positively with BMI (OR = 1.09 [1.01; 1.17]), waist circumference (OR = 1.09 [1.02; 1.17]) in stressed men at S-46. Positive associations were observed for fasting plasma glucose (OR = 1.42 [1.07; 1.87]), serum triglycerides (OR = 1.41 [1.05; 1.91]) and with fasting plasma insulin (OR = 1.48 [1.05; 2.08]) in stressed men at S-49. Rs439401 TT-genotype also associated positively with surrogate measures of insulin resistance (HOMA-IR; OR = 1.21 [1.03; 1.41]) and inversely with insulin sensitivity (Stumvoll index; OR = 0.90 [0.82; 0.99], BIGTT-S(I); OR = 0.60 [0.43; 0.85]) in stressed men. No significant associations were observed in non-stressed men, albeit the estimates showed similar but weaker trends as in stressed men.The present results suggest that the APOE rs439401 TT-genotype is associated with an adverse metabolic profile in a population of psychologically stressed Danish men

Preventing the Reintroduction of Malaria in Mauritius: A Programmatic and Financial Assessment

Sustaining elimination of malaria in areas with high receptivity and vulnerability will require effective strategies to prevent reestablishment of local transmission, yet there is a dearth of evidence about this phase. Mauritius offers a uniquely informative history, with elimination of local transmission in 1969, re-emergence in 1975, and second elimination in 1998. Towards this end, Mauritius's elimination and prevention of reintroduction (POR) programs were analyzed via a comprehensive review of literature and government documents, supplemented by program observation and interviews with policy makers and program personnel. The impact of the country's most costly intervention, a passenger screening program, was assessed quantitatively using simulation modeling

Acetylsalicylic acid as an adjuvant therapy for schizophrenia

BACKGROUND: Findings from both epidemiological and basic research point to the possibility that NSAIDS impede the deterioration in schizophrenia. METHODS: To study the efficacy of acetylsalicylic acid we will perform a randomized placebo controlled double-blind add-on trial of 80 inpatients and outpatients with schizophrenia, schizophreniform or schizoaffective disorder. Patients will be 1:1 randomized to either 3 months 1000 mg acetylsalicylic acid per day or 3 months placebo, in addition to their regular antipsychotic treatment. All patients will receive pantoprazole treatment for gastroprotection. The outcomes of this study are 3-month change in psychotic and negative symptom severity, cognitive function, and several immunological parameters. This trial may (1) yield a new (adjuvant) therapy for schizophrenia and (2) add to the knowledge on the pathogenesis of this major psychiatric disorder

A Re-conceptualization of Access for 21st Century Healthcare

Many e-health technologies are available to promote virtual patient–provider communication outside the context of face-to-face clinical encounters. Current digital communication modalities include cell phones, smartphones, interactive voice response, text messages, e-mails, clinic-based interactive video, home-based web-cams, mobile smartphone two-way cameras, personal monitoring devices, kiosks, dashboards, personal health records, web-based portals, social networking sites, secure chat rooms, and on-line forums. Improvements in digital access could drastically diminish the geographical, temporal, and cultural access problems faced by many patients. Conversely, a growing digital divide could create greater access disparities for some populations. As the paradigm of healthcare delivery evolves towards greater reliance on non-encounter-based digital communications between patients and their care teams, it is critical that our theoretical conceptualization of access undergoes a concurrent paradigm shift to make it more relevant for the digital age. The traditional conceptualizations and indicators of access are not well adapted to measure access to health services that are delivered digitally outside the context of face-to-face encounters with providers. This paper provides an overview of digital “encounterless” utilization, discusses the weaknesses of traditional conceptual frameworks of access, presents a new access framework, provides recommendations for how to measure access in the new framework, and discusses future directions for research on access

A mathematical model of brain glucose homeostasis

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Blood Flow and Glucose Metabolism in Stage IV Breast Cancer: Heterogeneity of Response During Chemotherapy

Objective: The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy. Methods: Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone were scanned before treatment and after the first course of chemotherapy. BF, distribution volume of water (Vd), MRglu/BF ratio, MRgluand its corresponding rate constants K1and k3were compared per tumor lesion before and during therapy. Results: At baseline, mean BF and MRgluvaried among different tumor lesions, but mean Vdwas comparable in all lesions. After one course of chemotherapy, mean MRgludecreased in all lesions. Mean BF decreased in breast and node lesions and increased in bone lesions. Vddecreased in breast and nodes, but did not change in bone lesions. The MRglu/BF ratio decreased in breast and bone lesions and increased in node lesions. In patients with multiple tumor lesions BF and MRgluresponse could be very heterogeneous, even within similar types of metastases. BF and MRgluincreased in lesions of patients who experienced early disease progression or showed no response during clinical follow-up. Conclusion: BF and MRgluchanges separately give unique information on different aspects of tumor response to chemotherapy. Changes in BF and MRgluparameters can be remarkably heterogeneous in patients with multiple lesions