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1.
Am J Transplant ; 15(2): 445-52, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25612497

ABSTRACT

Pediatric kidney transplant recipients experience a high-risk age window of increased graft loss during late adolescence and early adulthood that has been attributed primarily to sociobehavioral mechanisms such as nonadherence. An examination of how this age window affects recipients of other organs may inform the extent to which sociobehavioral mechanisms are to blame or whether kidney-specific biologic mechanisms may also exist. Graft loss risk across current recipient age was compared between pediatric kidney (n = 17,446), liver (n = 12,161) and simultaneous liver-kidney (n = 224) transplants using piecewise-constant hazard rate models. Kidney graft loss during late adolescence and early adulthood (ages 17-24 years) was significantly greater than during ages <17 (aHR = 1.79, 95%CI = 1.69-1.90, p < 0.001) and ages >24 (aHR = 1.11, 95%CI = 1.03-1.20, p = 0.005). In contrast, liver graft loss during ages 17-24 was no different than during ages <17 (aHR = 1.03, 95%CI = 0.92-1.16, p = 0.6) or ages >24 (aHR = 1.18, 95%CI = 0.98-1.42, p = 0.1). In simultaneous liver-kidney recipients, a trend towards increased kidney compared to liver graft loss was observed during ages 17-24 years. Late adolescence and early adulthood are less detrimental to pediatric liver grafts compared to kidney grafts, suggesting that sociobehavioral mechanisms alone may be insufficient to create the high-risk age window and that additional biologic mechanisms may also be required.


Subject(s)
Graft Rejection/epidemiology , Kidney Transplantation/statistics & numerical data , Liver Transplantation/statistics & numerical data , Transplant Recipients , Adolescent , Age Factors , Child , Child, Preschool , Female , Humans , Incidence , Infant , Male , Outcome Assessment, Health Care , Registries , Retrospective Studies , Risk Assessment , Young Adult
2.
Euro Surveill ; 18(42)2013 Oct 17.
Article in English | MEDLINE | ID: mdl-24176581

ABSTRACT

Multidrug-resistant tuberculosis (MDR-TB; resistance to at least rifampicin and isoniazid) is a global public health concern. In 2010­2011, Uzbekistan, in central Asia, conducted its first countrywide survey to determine the prevalence of MDR-TB among TB patients. The proportion of MDR-TB among new and previously treated TB patients throughout the country was measured and risk factors for MDR-TB explored. A total of 1,037 patients were included. MDR-TB was detected in 165 treatment-naïve (23.2%; 95% confidence interval (CI) 17.8%­29.5%) and 207 previously treated (62.0%; 95% CI: 52.5%­70.7%) patients. In 5.3% (95% CI: 3.1%­8.4%) of MDR-TB cases, resistance to fluoroquinolones and second-line injectable drugs (extensively drug resistant TB; XDR-TB) was detected. MDR-TB was significantly associated with age under 45 years (adjusted odds ratio: 2.24; 95% CI: 1.45­3.45), imprisonment (1.93; 95% CI: 1.01­3.70), previous treatment (4.45; 95% CI: 2.66­7.43), and not owning a home (1.79; 95% CI: 1.01­3.16). MDR-TB estimates for Uzbekistan are among the highest reported in former Soviet Union countries. Efforts to diagnose, treat and prevent spread of MDR-TB need scaling up.


Subject(s)
Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Health Surveys , Humans , Incidence , Male , Microbial Sensitivity Tests , Middle Aged , Mycobacterium tuberculosis/genetics , Population Surveillance , Prevalence , Risk Factors , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/microbiology , Uzbekistan/epidemiology , Young Adult
3.
Pediatr Transplant ; 16(5): 486-95, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22672018

ABSTRACT

Little data concerning hospital charges and long-term outcomes of LDLT in North American children according to transplant indications have been published. To compare outcomes of patient and graft survival and healthcare charges for LDLT for those with BA vs. other diagnoses (non-BA). A retrospective review of 52 children receiving 53 LDLT (38 BA and 14 non-BA) from 1992 to 2010 at our institution was performed. One-, five-, and 10-yr patient and graft survival data were comparable to national figures reported to UNOS. Average one-yr charges for recipients and donors were $242 849 for BA patients and $183 614 for non-BA (p = 0.074). BA patients were 1.23 ± 1.20 yr of age vs. 4.25 ± 5.02 for non-BA, p = 0.045. Examination of the total population of patients who were alive in 2010 in five chronological groupings showed that the crude five-yr survival rates were 1992-1995: 9/11 (82%); 1995-1997: 6/10 (60%); 1997-1999: 8/10 (80%); 1999-2001: 9/10 (90%); and 2001-2003: 7/7 (100%). Thus, examination of the clinical and financial data together over the entire period of the transplant program suggests that the dramatic improvement in patient survival was accomplished without a dramatic increase in indexed charges. All 53 donors survived, and only 10% had complications requiring hospitalization. LDLT in children results in excellent outcomes for patients and donors. Ways to lower costs and maximize graft outcome should be investigated.


Subject(s)
Biliary Atresia/complications , End Stage Liver Disease/surgery , Liver Transplantation , Living Donors , Adolescent , Biliary Atresia/economics , Biliary Atresia/mortality , Biliary Atresia/surgery , Child , Child, Preschool , End Stage Liver Disease/economics , End Stage Liver Disease/etiology , End Stage Liver Disease/mortality , Female , Follow-Up Studies , Graft Survival , Hospital Charges/statistics & numerical data , Humans , Infant , Kaplan-Meier Estimate , Liver Transplantation/economics , Liver Transplantation/mortality , Male , Maryland , Retrospective Studies , Survival Rate , Treatment Outcome , Young Adult
4.
J Cell Biol ; 102(1): 145-50, 1986 Jan.
Article in English | MEDLINE | ID: mdl-3484481

ABSTRACT

Cyclosporine A is a noncytotoxic, natural, 11 amino acid cyclic peptide used clinically as an immunosuppressant to prevent organ rejection after transplantation. Cyclosporine A is an in vitro calmodulin antagonist. At the low concentrations required to inhibit calmodulin-dependent phosphodiesterase in vitro, cyclosporine A causes a dramatic alteration in the nuclear morphology of 23% of human peripheral blood mononuclear leukocytes in vitro without loss of viability. The shape of the nucleus changes from ovoid to a distinctive, radially splayed lobulated structure. The changes occur in a dose-dependent manner in 60 min at 37 degrees C. Specific monoclonal antibodies to human leukocytes identify the cells susceptible to nuclear lobulation by cyclosporine A as OKT4 antigen-positive T cell lymphocytes and monocytes. The lobulated nuclei are 2N as determined by flow cytometric measurement of ethidium bromide fluorescence of DNA. The cyclosporine A-induced lobulation of T cell nuclei requires both physiologic temperature and metabolic energy. Although structurally different than cyclosporine A, the calmodulin antagonists R24571 and W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide] also produce T cell nuclear lobulations that are indistinguishable from the nuclear lobulations caused by cyclosporine A. These data indicate that nonmitotic structural elements that govern normal nuclear morphology in a subset of mononuclear leukocytes appear to require a calmodulin-mediated process. Cyclosporine A may be a useful noncytotoxic inhibitor of calmodulin-dependent systems that influence nuclear structure and function.


Subject(s)
Calmodulin/antagonists & inhibitors , Cell Nucleus/drug effects , Cyclosporins/pharmacology , Monocytes/drug effects , T-Lymphocytes/drug effects , Antigens, Surface/analysis , Cell Survival/drug effects , Dose-Response Relationship, Drug , Energy Metabolism/drug effects , Humans , Imidazoles/pharmacology , Monocytes/immunology , RNA Processing, Post-Transcriptional/drug effects , T-Lymphocytes/immunology , Temperature , Transcription, Genetic/drug effects
5.
Science ; 228(4697): 337-9, 1985 Apr 19.
Article in English | MEDLINE | ID: mdl-3885394

ABSTRACT

Cyclosporin A, a potent immunosuppressive agent, has been widely used to treat patients with solid organ transplants. Although its precise mechanism of action is unknown, it appears to inhibit subsets of T lymphocytes at an early stage in cell activation. Fluorescent, fully active derivatives of cyclosporin A and calmodulin, a protein that binds calcium and is therefore essential to normal cell function, were utilized to demonstrate that cyclosporin A binds to calmodulin. Flow cytometry showed that the calmodulin inhibitors R24571 and W-7 competitively inhibited binding of cyclosporin A to cloned T lymphocytes. Cyclosporin A inhibited the calmodulin-dependent activation of phosphodiesterase in a dose-dependent manner. Binding of cyclosporin A to calmodulin may prevent the latter's role in the activation of the second messengers and enzymes required for effective cell proliferation and function in the immune response.


Subject(s)
Calmodulin/metabolism , Cyclosporins/metabolism , T-Lymphocytes/metabolism , Binding, Competitive , Carrier Proteins/metabolism , Cyclosporins/pharmacology , Dose-Response Relationship, Drug , Flow Cytometry , Imidazoles/pharmacology , Lymphocyte Activation/drug effects , Peptidylprolyl Isomerase , Sulfonamides/pharmacology , T-Lymphocytes/drug effects
6.
Int J Tuberc Lung Dis ; 22(2): 197-205, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29506617

ABSTRACT

SETTING: The true prevalence of multidrug-resistant tuberculosis (MDR-TB) in Ukraine is not known. Available data are a decade old and limited to only one province. OBJECTIVE: To determine the prevalence of MDR-TB among new and previously treated TB cases in Ukraine and explore the risk factors associated with drug resistance. METHODS: A total of 1550 sputum smear-positive pulmonary TB patients were recruited from 40 clusters throughout Ukraine. Sputum specimens were examined using culture, drug susceptibility testing and pncA gene sequencing. RESULTS: The proportion of MDR-TB among new and previously treated TB cases was respectively 24.1% (95%CI 20.7-27.6) and 58.1% (95%CI 52.1-64.1). More than one third (38.0%) of MDR-TB or rifampicin (RMP) resistant cases showed resistance to either a fluoroquinolone (FQ) or a second-line injectable agent or both. Resistance to pyrazinamide and FQs was low in patients with RMP-susceptible TB. Among new TB cases, the odds of MDR-TB were higher among patients who were younger, female and living in south-eastern provinces, as well as among human immunodeficiency virus-positive patients who belonged to a low socio-economic group. CONCLUSIONS: Our study showed that the burden of MDR-TB in Ukraine was much greater than previously assumed. Urgent actions are needed to prevent further spread of drug-resistant TB in Ukraine.


Subject(s)
Tuberculosis, Multidrug-Resistant/epidemiology , Adult , Aged , Antitubercular Agents/pharmacology , Female , HIV Infections , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Prevalence , Risk Factors , Sex Factors , Socioeconomic Factors , Sputum/microbiology , Surveys and Questionnaires , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/prevention & control , Ukraine/epidemiology , Young Adult
7.
Eur J Clin Nutr ; 61(1): 19-24, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16835599

ABSTRACT

OBJECTIVE: To determine the glycemic index (GI) dependence on the training state of healthy adult males. SUBJECTS AND DESIGN: Young, adult males of normal body mass index and normal glucose tolerance were tested twice with a 50 g reference glucose solution and twice with a breakfast cereal containing 50 g of available carbohydrates in a randomized order. Ten subjects were sedentary (SE), 12 were moderately trained (MT) and 12 were endurance trained (ET). Blood glucose, insulin and glucagon were measured. RESULTS: The GI differed significantly between SE and ET subjects (P=0.02, mean difference: 23 GI units, 95% CI=3-42 GI units). The GI of the MT subjects was intermediary, but did not differ significantly from the SE or ET subjects. The insulin index did not differ significantly between the groups (P=0.65). CONCLUSION: The GI of the commercially available breakfast cereal depended on the training state of the healthy males. The training state is the first reported factor influencing the GI that is subject specific rather than food specific.


Subject(s)
Blood Glucose/metabolism , Dietary Carbohydrates/metabolism , Glucagon/metabolism , Glycemic Index , Insulin/blood , Physical Fitness/physiology , Adolescent , Adult , Anthropometry , Area Under Curve , Cross-Over Studies , Dietary Carbohydrates/administration & dosage , Edible Grain/metabolism , Glucose Tolerance Test , Humans , Male , Oxygen Consumption
8.
J Perinatol ; 27(1): 50-5, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17036030

ABSTRACT

OBJECTIVE: Gastroschisis is a rare congenital abdominal wall defect through which intraabdominal organs herniate and it requires surgical management soon after birth. The objectives of this study were to profile patient characteristics of this anomaly utilizing data from two large national databases and to validate previous risk stratification categories of infants born with this condition. METHODS: An analysis was performed using 13 years of the National Inpatient Sample database (1988-1996, 1998, 1999, 2001, 2002) and 3 years of the Kids' Inpatient Database (1997, 2000, 2003). These combined databases contain information from nearly 93 million discharges in the United States. Infants with gastroschisis were identified by International Classification of Disease-9 procedure code 54.71 (repair of gastroschisis) and an age at admission of <8 days. Variables of gender, race, geographic region, co-existing diagnoses, length of stay, hospital charges adjusted to 2005 dollars, complications and inpatient mortality were collected from the databases. Infants were divided into simple and complex categories based on the absence or presence of intestinal atresia, stenosis, perforation, necrosis or volvulus. Comparisons between groups were performed using Pearson's chi (2) for categorical outcomes and the Kruskal-Wallis test for non-normally distributed continuous variables. RESULTS: A total of 4344 infants with gastroschisis were identified. These were comprised of 44.0% female infants (n=1910), 46.4% male infants (n=2017) whereas 9.6% were not reported (n=415). Racial analysis showed the largest subset being white in 40.9% of infants (n=1775) with Hispanic infants being the next highest group reported at 17.2% (n=745). Co-existing intestinal anomalies were the most common, affecting 9.9% (n=429) infants, whereas certain cardiac (6.8%, n=294) and pulmonary (1.7%, n=72) conditions were also identified. Simple gastroschisis represented 89.1% (n=3870) of the group whereas 10.9% (n=474) were complex in nature. Simple and complex patients differed in median length of stay (28 vs 67 days, P<0.01), inpatient mortality (2.9 vs 8.7%, P<0.01) and median inflation-adjusted hospital charges (90,788 dollars vs 197,871 dollars, P<0.01). CONCLUSIONS: These data represent a national analysis of the largest group of infants with gastroschisis to date which further aids the characterization and understanding of this serious congenital condition.


Subject(s)
Gastroschisis/epidemiology , Female , Gastroschisis/complications , Gastroschisis/pathology , Humans , Infant, Newborn , Male , Risk Assessment , United States/epidemiology
9.
J Clin Oncol ; 10(12): 1857-64, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1453200

ABSTRACT

PURPOSE: The purpose of this study was to determine the toxicities of and responses to high-dose busulfan and cyclophosphamide with autologous bone marrow transplant (ABMT) in patients with recurrent or refractory pediatric solid tumors. PATIENTS AND METHODS: We treated 18 patients (ages, 2 to 38 years; median, 14) who had tumors that were resistant to conventional chemotherapy and radiotherapy with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg. Seventeen patients received bone marrow purged with 4-hydroperoxycyclophosphamide; one received unpurged marrow. RESULTS: Despite extensive prior treatment, including radiotherapy in 16 patients, toxicity generally was acceptable. For seven patients with measurable disease, there were three partial responses of 2, 10, and 20 months' duration, three patients with stable disease (SD), and one early, toxic death. Of the 11 patients with no measurable disease at the time of transplantation, one patient with osteosarcoma continues in remission at 57+ months and one third of the patients survived for at least 16 months. Mucositis was the predominant nonhematopoietic toxicity. CONCLUSION: Although the high-dose busulfan and cyclophosphamide combination showed modest activity, changes in the preparative regimen should be considered to improve the response rate in refractory tumors.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Transplantation , Neoplasms/therapy , Adolescent , Adult , Bone Marrow Purging , Busulfan/administration & dosage , Child , Child, Preschool , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Humans , Recurrence , Survival Analysis , Transplantation, Autologous
10.
Crit Rev Immunol ; 6(2): 123-49, 1986.
Article in English | MEDLINE | ID: mdl-2942335

ABSTRACT

Cyclosporine (CsA) is a novel immunosuppressive agent currently used clinically, to prevent rejection of solid organ allografts and to prevent graft-vs.-host disease. Early studies in a variety of animal models exhibited transplantation tolerance after limited treatment with this unique agent. The apparent specific immunological unresponsiveness induced by CsA is thought to be maintained by antigen-specific suppressor T lymphocytes. Studies attempting to dissect the mechanism of action of this unique agent suggested that CsA selectively affected different T lymphocyte populations. Cyclosporine was very effective at inhibiting the production of interleukin-2 (IL-2), a soluble lymphokine known to amplify cytotoxic T cell responses and was also capable of preventing IL-2 receptor expression on the precursor cytotoxic T lymphocyte. In contrast, to the effect on T helper cells and on the precursor cytotoxic T lymphocyte, studies in vitro and in vivo demonstrated that CsA had a sparing effect on suppressor T cell induction. More recent studies have indicated that CsA allows for the amplification of suppressor T lymphocytes independent of interleukin-2 indicating that other cellular and/or soluble factors are important for potentiation of suppressor T lymphocyte activity. However, the molecular action of CsA at the cellular level still remains unresolved. Thus, CsA is not only a useful drug in clinical transplantation but it has become increasingly important as an immunologic probe allowing the dissection of complex cellular interactions involved in the immune response.


Subject(s)
Cyclosporins/pharmacology , Lymphocyte Activation/drug effects , Lymphocytes/immunology , Animals , Histocompatibility Antigens/immunology , Humans , Lymphocytes/drug effects , Lymphokines/immunology , Macrophages/drug effects , Macrophages/immunology , Models, Biological , Subcellular Fractions/immunology , T-Lymphocytes/classification , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Regulatory/immunology
11.
Public Health Action ; 5(3): 194-201, 2015 Sep 21.
Article in English | MEDLINE | ID: mdl-26399291

ABSTRACT

SETTING: National tuberculosis programmes (NTPs) of the 53 Member States of the World Health Organization (WHO) European Region. OBJECTIVES: To identify the social determinants and underlying risk factors for tuberculosis (TB) as routinely monitored by NTPs and to identify those feasible and appropriate to be included in the annual reporting to the joint European Centre for Disease Prevention and Control (ECDC) WHO reporting platform. DESIGN: A semi-structured questionnaire sent to 53 national TB surveillance correspondents. RESULTS: A total of 47 countries submitted questionnaires; most of the countries collect a number of social determinants and risk factors that are not requested for reporting to the Joint ECDC-WHO Reporting Platform. Occupation/employment, homelessness, diabetes mellitus and use of alcohol are collected by the majority of countries, but without standardised definitions. CONCLUSIONS: Four social determinants/risk factors are already included in the national TB surveillance systems of the majority of countries and could be incorporated in the annual reporting to the Joint ECDC/WHO Reporting Platform. Standardised epidemiological case definitions need to be adopted.


Contexte : Programmes nationaux contre la tuberculose (PNT) des 53 états membres de la région Europe de l'Organisation Mondiale de la Santé (OMS).Objectifs: Identifier les déterminants sociaux et les facteurs de risque sous-jacents de la tuberculose (TB) tels qu'ils sont suivis en routine par les PNT et identifier ceux qui sont faciles à recueillir et appropriés pour les inclure dans le rapport annuel à la plate-forme conjointe du Centre européen de prévention et contrôle des maladies (CEPCM) et l'OMS.Schéma : Un questionnaire semi-structuré a été envoyé à 53 correspondants des programmes nationaux de surveillance de la TB.Résultats : Au total, 47 pays ont soumis leurs questionnaires ; la plupart des pays recueillent un certain nombre de déterminants sociaux et de facteurs de risque qui ne sont pas exigés dans les rapports destinés à la plate-forme conjointe CEPCM-OMS. Profession, absence de domicile fixe, diabète et consommation d'alcool sont recueillis par la majorité des pays, mais sans définitions standardisées.Conclusions : Quatre déterminants sociaux/facteurs de risque sont déjà inclus dans le système national de surveillance de la TB dans la majorité des pays et pourraient être incorporés dans le rapport annuel à la plate-forme conjointe CEPCM/OMS. Mais il faut adopter des définitions de cas épidémiologiques standardisées.


Marco de referencia: Los programas nacionales contra la tuberculosis (PNT) de los 53 Estados Miembros de la Región Europea de la Organización Mundial de la Salud (OMS)Objetivos: Encontrar los determinantes sociales y los factores de riesgo subyacentes de contraer la tuberculosis (TB), como se recogen de manera sistemática en la vigilancia de los PNT y escoger los determinantes cuya recogida es factible y es apropiado incluirlos en el informe anual que se presenta a la plataforma de notificación conjunta del Centro Europeo para la Prevención y el Control de las Enfermedades (CEPCE) y la OMS.Métodos: Se envió un cuestionario semiestructurado a 53 corresponsales nacionales de la vigilancia de la TB.Resultados: Se recibieron cuestionarios de 47 países; la mayoría de países recoge una serie de determinantes sociales y factores de riesgo cuya notificación no se exige en el informe a la plataforma conjunta de notificación del CEPCE y la OMS. La mayor parte de los países obtiene información sobre los siguientes determinantes: ocupación o empleo, falta de vivienda, diabetes y consumo de alcohol, sin definiciones normalizadas.Conclusión: El sistema de vigilancia de la TB de la mayoría de los países incluye ya cuatro determinantes sociales o factores de riesgo de padecer la enfermedad que se podrían incorporar a la plataforma de notificación conjunta del CEPCE y la OMS. Es preciso adoptar definiciones de caso epidemiológicas normalizadas.

12.
Transplantation ; 46(2 Suppl): 61S-67S, 1988 Aug.
Article in English | MEDLINE | ID: mdl-2970140

ABSTRACT

The primary effects of CsA on human lymphocyte responses in vitro appear to be the inhibition of IL-2 production and the inhibition of cytotoxic T cell activation. Induction of suppressor T cell activity is resistant to the effects of CsA. These data imply two distinct subsets of lymphocytes: CsA-resistant and CsA-sensitive. The current studies used a bioactive, dansylated derivative of CsA (dans-CsA), which is fluorescent, to assess binding of CsA at the single-cell level by flow cytometry. The results demonstrate that two populations of cells can be distinguished based on differential staining with dans CsA--a weakly staining subset and a population that binds intensely. Both subsets consist of CD4 (helper) and CD8 (cytotoxic/suppressor) T lymphocytes. Functional analysis revealed that the weakly staining subset consists of IL-2-producing T cells and precursor cytotoxic T lymphocytes. On the other hand, the intensely staining subset includes T cells that suppress in an antigen-specific manner after activation with alloantigen. Further studies showed that the weakly staining subset is markedly sensitive to the immunosuppressive effects of CsA in a PHA stimulation assay, while the intensely binding population is markedly resistant, requiring 10- to 100-fold more CsA to inhibit the PHA response. These studies suggest that sensitivity and resistance to CsA is inversely correlated with binding.


Subject(s)
Cyclosporins/metabolism , Lymphocytes/metabolism , Antigens, Differentiation/analysis , Cytotoxicity, Immunologic , Drug Resistance , Flow Cytometry , Humans , In Vitro Techniques , Interleukin-2/biosynthesis , Kinetics , Lymphocytes/classification , Lymphocytes/physiology , T-Lymphocytes, Regulatory/physiology , Temperature
13.
Transplantation ; 60(2): 115-22, 1995 Jul 27.
Article in English | MEDLINE | ID: mdl-7624952

ABSTRACT

Cyclosporine (CsA) has profound but paradoxical effects on the immune system. CsA can facilitate the induction of transplantation tolerance in some animal systems but it inhibits the clonal deletion of MHC class II autoreactive T cells. The present studies evaluated whether the autoreactive T cells participate in the induction of facilitated graft acceptance after CsA treatment by recognizing and eliminating activated allograft responsive T cells that express MHC class II determinants. Transfer of autoreactive T cells into naive Lewis rats pretreated with cyclophosphamide significantly prolonged the survival of heterotopic cardiac allografts from MHC-disparate BN strain donors. Following transfer of the autoreactive T cells, there was a marked reduction in the frequency of alloreactive T lymphocytes responsive to donor alloantigens. The role of MHC class II autoreactive CD8+ V beta 8.5+ T cells in facilitated graft acceptance was also supported by the findings that (1) treatment with anti-MHC class II antibody abrogated prolonged allograft survival after CsA therapy and (2) V beta 8.5+ lymphocytes infiltrate the allograft during CsA therapy but are absent in the graft in non-CsA-treated control animals. Although these data are consistent with the hypothesis that autoreactive T cells prolong cardiac allograft survival after CsA treatment, the autoaggressive cells failed to inhibit the development of chronic rejection of both heart and skin allografts. These data suggest either that the autoreactive T cells do not inhibit immune mechanisms responsible for chronic graft rejection or that the autoaggressive lymphocytes may participate in and exacerbate chronic rejection of allografts. Taken together, the induction of MHC class II autoreactive T cells may provide a common fundamental mechanism explaining the paradoxical effects of CsA.


Subject(s)
Cyclosporine/pharmacology , Graft Rejection , Graft Survival , T-Lymphocytes/drug effects , Animals , Female , Graft vs Host Disease/etiology , Heart Transplantation/immunology , Histocompatibility Antigens Class II/physiology , Immunotherapy, Adoptive , Rats , Rats, Inbred BN , Rats, Inbred Lew , Receptors, Antigen, T-Cell, alpha-beta/analysis , T-Lymphocytes/physiology , Transplantation, Homologous
14.
Transplantation ; 67(11): 1487-9, 1999 Jun 15.
Article in English | MEDLINE | ID: mdl-10385092

ABSTRACT

BACKGROUND: B cell lymphoproliferative disorders (LPD) and liver rejection are major lethal complications after hepatic transplantation. Reduction in immunosuppression is the treatment for the former, but is a risk factor for the latter. METHODS: Here, we report three consecutive children with monoclonal LPD complicating orthotopic liver transplantation. All of them were treated with brief (<4 months) but intensive chemotherapy. RESULTS: These three patients have remained in complete remission for LPD for 18 months to more than 3 years. Aggressive antimicrobial prophylaxis was successful in preventing life-threatening infections. The patient who received the highest cumulative doses of chemotherapy may have also developed relative immune tolerance to the allograft. CONCLUSIONS: High-dose-intensity chemotherapy may be effective in the treatment of monoclonal LPD, as well as in the induction of immune tolerance for the prevention of allograft rejection and LPD recurrence.


Subject(s)
Immune Tolerance/drug effects , Liver Transplantation/adverse effects , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/etiology , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Female , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Infant , Liver Transplantation/immunology , Male , Remission Induction , Tacrolimus/therapeutic use , Time Factors
15.
Transplantation ; 63(5): 669-74, 1997 Mar 15.
Article in English | MEDLINE | ID: mdl-9075836

ABSTRACT

In 1995, changes to the United Network for Organ Sharing renal allocation system eliminated points for certain HLA matches, increased points for waiting time and for pediatric patients, and extended the mandatory share rule to include the zero-antigen mismatch. We analyzed data, from the period December 1993 to August 1996, on 393 donors, 348 kidney-only cadaveric transplants, and 615 patients ranked first or second on the allocation lists generated for each donor, to assess the effect of the changes in the point system. There was an appreciable (46%) but not significant increase in the frequency of transplants occurring under the mandatory share rule, with a greater relative increase seen in African-Americans than in Caucasians. Recipients of transplants not falling under the mandatory share rule had an increased average waiting time but no increase in sensitization or HLA mismatch, whereas patients ranked at the top of the allocation list had higher levels of sensitization but no increase in waiting time. There was an appreciable increase in the percentage of transplants occurring in African-Americans. Of the various changes we observed, only those involving the mandatory share rule could be attributed to changes in the allocation system, whereas others paralleled changes in the composition of our local waiting list.


Subject(s)
Health Care Rationing , Kidney Transplantation , Black People , Histocompatibility Testing , Humans , Kidney Transplantation/statistics & numerical data , Phenotype , Time Factors , Tissue and Organ Procurement , Waiting Lists , White People
16.
Transplantation ; 69(11): 2319-23, 2000 Jun 15.
Article in English | MEDLINE | ID: mdl-10868632

ABSTRACT

BACKGROUND: Laparoscopic live donor nephrectomy offers advantages to the donor in terms of decreased pain and shorter recuperation. Heretofore no detailed analysis of the recipient of laparoscopically procured kidneys has been performed. The purpose of this study was to determine whether laparoscopic donor nephrectomy had any deleterious effect on the recipient. METHODS: A retrospective review was conducted of all live donor renal transplantations performed from January 1995 through April 1998. The control group received kidneys procured via a standard flank approach (Open). Rejection was diagnosed histologically. Creatinine clearance was calculated using the Cockroft-Gault formula. RESULTS: A total of 110 patients received kidneys from laparoscopic (Lap) and 48 from open donors. One-year recipient (100% vs. 97.0%) and graft (93.5% vs. 91.1%) survival rates were similar for the Open and Lap groups, respectively. A similar incidence of vascular thrombosis (3.4% vs. 2.1%, P=NS) and ureteral complications (9.1% vs. 6.3%, P=NS) were seen in the Lap and Open groups, respectively. The incidence of acute rejection for the first month was 30.1% for the Lap group and 31.9% for the Open group (P=NS). The rate of decline of serum creatinine level in the early posttransplantation period was initially greater in the Open group, but by postoperative day 4 no significant difference existed. No difference was observed in allograft function long-term. The median length of hospital stay was 7.0 days for both groups. CONCLUSIONS: Laparoscopic live donor nephrectomy does not adversely effect recipient outcome. The previously demonstrated benefits to the donor, and the increased willingness of individuals to undergo live kidney donation, coupled with the acceptable outcomes experienced by recipients of laparoscopically procured kidneys justifies the continued development and adoption of this operation.


Subject(s)
Laparoscopy , Living Donors , Nephrectomy , Acute Disease , Adult , Creatinine/blood , Female , Graft Rejection/epidemiology , Graft Survival , Humans , Incidence , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Survival Analysis , Thrombosis/epidemiology
17.
J Heart Lung Transplant ; 20(6): 692-5, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11404176

ABSTRACT

An unusual case of peribronchial eosinophilic infiltrates associated with peripheral blood eosinophilia in a lung transplant patient is described. The role that eosinophils play in lung allograft rejection is reviewed. Tissue eosinophils have been associated with acute pulmonary allograft rejection. Although, eosinophils in bronchoalveolar lavage fluid (BAL) have been observed in allograft rejection, this relationship is less well defined. The role of eosinophils in the pathophysiology of allograft rejection is unclear.


Subject(s)
Eosinophilia/blood , Eosinophils/metabolism , Graft Rejection/blood , Lung Transplantation/pathology , Cadaver , Child , Cystic Fibrosis/surgery , Eosinophilia/pathology , Female , Graft Rejection/pathology , Humans
18.
Surgery ; 107(3): 342-5, 1990 Mar.
Article in English | MEDLINE | ID: mdl-2309151

ABSTRACT

An alternative solution to the problem of liver transplantation in the patient with an occluded portal vein is described. It uses a bridge graft of donor iliac vein from the superior mesenteric vein at the base of the colonic mesentery. The graft is tunnelled over the pancreas and under the stomach to the region of the liver hilum to provide portal inflow. This procedure was employed successfully in four patients, with patency for more than 2 years in the patient with the longest follow-up. By this approach it is routinely possible to perform a transplant procedure in a recipient with an occluded portal vein.


Subject(s)
Liver Transplantation/methods , Mesenteric Veins/transplantation , Portal Vein/surgery , Adult , Female , Humans , Male , Middle Aged
19.
Science ; 233(4767): 988-9, 1986 Aug 29.
Article in English | MEDLINE | ID: mdl-17732041
20.
Ann Thorac Surg ; 53(4): 597-602; discussion 602-3, 1992 Apr.
Article in English | MEDLINE | ID: mdl-1554267

ABSTRACT

Between 1968 and 1990, we operatively treated 39 patients (19 boys, 20 girls) with congenital aortic arch anomalies. Median age was 7 months (range, 1.5 months to 23 years). Thirty-seven patients (95%) had respiratory symptoms. Barium swallow was diagnostic in 95%. Right arch with aberrant left subclavian artery and double aortic arch were the most common types (11 each). Treatment of an aortic diverticulum was documented in 19 patients; the aortic diverticulum was excised (9), managed by aortopexy (7), or left in situ (3). Postoperative recovery was rapid, with a median intensive care unit stay of 2 days, time to oral feeding of 1 day, and postoperative time to discharge of 7 days. Two deaths occurred: 1 infant had undergone emergent operation for control of hemorrhage from an aortotracheal fistula due to tracheostomy tube erosion, and the other had multiple associated congenital heart defects. Postoperative complications included bleeding (1), pneumonia (5), and chylothorax (4). One boy had persistent severe symptoms due to an untreated aortic diverticulum and underwent subsequent excision of the aortic diverticulum with complete relief of symptoms. Median length of follow-up was 12.5 months, with at least 97% of survivors completely or nearly completely free of symptoms from the vascular ring. These results suggest that early repair of congenital aortic vascular rings, including fixating or excising an associated serious aortic diverticulum, is safe and effective and allows for normal tracheal growth.


Subject(s)
Aorta, Thoracic/abnormalities , Adolescent , Adult , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Aortic Diseases/surgery , Brachiocephalic Trunk/abnormalities , Brachiocephalic Trunk/surgery , Child , Child, Preschool , Deglutition Disorders/etiology , Diverticulum/surgery , Esophagus/diagnostic imaging , Female , Follow-Up Studies , Humans , Infant , Magnetic Resonance Imaging , Male , Radiography , Respiratory Sounds/etiology , Subclavian Artery/abnormalities , Subclavian Artery/surgery , Survival Rate , Treatment Outcome
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