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1.
Theriogenology ; 222: 31-44, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38615434

ABSTRACT

There is still no consensus regarding the role of lipid modulators during in vitro embryo production. Thus, we investigated how lipid reducers during the in vitro maturation of oocytes (IVM) or in vitro culture (IVC) of embryos impact their cryotolerance. A literature search was performed using three databases, recovering 43 articles for the systematic review, comprising 75 experiments (13 performed in IVM, 62 in IVC) and testing 13 substances. In 39 % of the experiments, an increase in oocyte and/or embryo survival after cryopreservation was reported, in contrast to 48 % exhibiting no effect, 5 % causing negative effects, and 8 % influencing in a dose-dependent manner. Of the 75 experiments extracted during IVM and IVC, 41 quantified the lipid content. Of those that reduced lipid content (n = 26), 50 % increased cryotolerance, 34 % had no effect, 8 % harmed oocyte/embryo survival, and 8 % had different results depending on the concentration used. Moreover, 28 out of the 43 studies were analyzed under a meta-analytical approach at the IVC stage in cattle. There was an improvement in the cryotolerance of bovine embryos when the lipid content was reduced. Forskolin, l-carnitine, and phenazine ethosulfate positively affected cryotolerance, while conjugated linoleic acid had no effect and impaired embryonic development. Moreover, fetal bovine serum has a positive impact on cryotolerance. SOF and CR1aa IVC media improved cryotolerance, while mSOF showed no effect. In conclusion, lipid modulators did not unanimously improve cryotolerance, especially when used in IVM, but presented positive effects on cryotolerance during IVC when reaching lipid reduction.


Subject(s)
Cryopreservation , Embryo Culture Techniques , Animals , Cryopreservation/veterinary , Cryopreservation/methods , Embryo Culture Techniques/veterinary , Lipids/chemistry , In Vitro Oocyte Maturation Techniques/veterinary , In Vitro Oocyte Maturation Techniques/methods , Fertilization in Vitro/veterinary , Cattle/embryology , Lipid Metabolism , Embryo, Mammalian/physiology
2.
BJS Open ; 5(2)2021 03 05.
Article in English | MEDLINE | ID: mdl-33839747

ABSTRACT

BACKGROUND: Recipient selection for liver transplantation in hepatocellular carcinoma (HCC) is based primarily on criteria affecting the chance of long-term success. Here, the relationship between pretransplant bridging therapy and long-term survival was investigated in a subgroup analysis of the SiLVER Study. METHODS: Response to bridging, as defined by comparison of imaging at the time of listing and post-transplant pathology report, was categorized into controlled versus progressive disease (more than 20 per cent tumour growth or development of new lesions). RESULTS: Of 525 patients with HCC who had liver transplantation, 350 recipients underwent pretransplant bridging therapy. Tumour progression despite bridging was an independent risk factor affecting overall survival (hazard ratio 1.80; P = 0.005). For patients within the Milan criteria (MC) at listing, mean overall survival was longer for those with controlled versus progressive disease (6.8 versus 5.8 years; P < 0.001). Importantly, patients with HCCs outside the MC that were downsized to within the MC before liver transplantation had poor outcomes compared with patients who never exceeded the MC (mean overall survival 6.2 versus 6.6 years respectively; P = 0.030). CONCLUSION: Patients with HCCs within the MC that did not show tumour progression under locoregional therapy had the best outcomes after liver transplantation. Downstaging into the limits of the MC did not improve the probability of survival.Prognostic factors determining the long-term success of liver transplantation in patients with hepatocellular carcinoma are still under discussion. A subgroup analysis of the SiLVER trial showed that disease control under bridging therapy is strongly associated with improved prognosis in terms of overall survival. However, in tumours exceeding the limits of the Milan criteria, downstaging did not restore the probability of survival compared with that of patients within the Milan criteria.


Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Liver Transplantation/statistics & numerical data , Neoplasm Recurrence, Local/prevention & control , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Disease Progression , Female , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Prognosis , Risk Factors , Survival Analysis , Time Factors , Treatment Outcome , Waiting Lists
3.
World J Urol ; 37(11): 2355-2363, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30707304

ABSTRACT

PURPOSE: To analyze outcomes and complication rates in an unselected cohort of men with unfavorable (NCCN intermediate and high-risk) PCa receiving combined-modality radiation treatment (CRT). METHODS: Patients received androgen deprivation therapy for 1 year and combined-modality radiation treatment (CRT) consisting of external-beam radiotherapy (EBRT, 59.4 Gy, 33 fractions) and 125J seed-brachytherapy (S-BT, 100 Gy). Subgroups, including WHO group 3-5, and initial PSA (iPSA) < 20 and > 20 ng/ml were identified. Biochemical recurrence-free (BRFS), metastasis-free (MFS), cancer-specific (CSS) and overall survival (OS) were calculated at 5 and 10 years using the Kaplan-Meier method. Subgroups were compared using log-rank test and Cox proportional hazards regression. Urogenital and gastrointestinal side-effects were reported according to the CTCAE classification. RESULTS: After a median of 6.9 years (range 2-13) calculated 5- and 10-year rates for the whole cohort of 425 men were 92.8% and 82.5% for BRFS, 95.1%, and 88.8% for MFS, 98.2%, and 95.1 for CSS, and 95.4%, and 80.1% for OS, respectively. Univariate (UVA) and multivariate analysis (MV) identified a group with unfavorable outcome with iPSA > 20 ng/ml, comprising 24% of all patients, in which 55% of recurrences, 54% of metastases and 71% of cancer-specific deaths occurred. Side-effects were limited, with < 5% of patients complaining of genitourinary and 0.5% of gastrointestinal AEs after 5 years. CONCLUSION: CRT is an excellent treatment option for men with unfavorable PCa. In a subgroup of patients with iPSA > 20 ng/ml further, possibly systemic, treatment options should be identified.


Subject(s)
Androgen Antagonists/therapeutic use , Brachytherapy/methods , Iodine Radioisotopes/therapeutic use , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Androgen Antagonists/adverse effects , Brachytherapy/adverse effects , Cohort Studies , Combined Modality Therapy , Humans , Male , Middle Aged , Radiotherapy/adverse effects , Radiotherapy/methods , Retrospective Studies , Risk Assessment , Treatment Outcome
4.
Eur Radiol ; 27(11): 4544-4551, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28608164

ABSTRACT

OBJECTIVES: To evaluate the impact of CT scans on diagnosis or change of therapy in patients with systemic inflammatory response syndrome (SIRS) or sepsis and obscure clinical infection. METHODS: CT records of patients with obscure clinical infection and SIRS or sepsis were retrospectively evaluated. Both confirmation of and changes in the diagnosis or therapy based on CT findings were analysed by means of the hospital information system and radiological information system. A sub-group analysis included differences with regard to anatomical region, medical history and referring department. RESULTS: Of 525 consecutive patients evaluated, 59% had been referred from internal medicine and 41% from surgery. CT examination had confirmed the suspected diagnosis in 26% and had resulted in a different diagnosis in 33% and a change of therapy in 32%. Abdominal scans yielded a significantly higher (p=0.013) change of therapy rate (42%) than thoracic scans (22%). Therapy was changed significantly more often (p=0.016) in surgical patients (38%) than in patients referred from internal medicine (28%). CONCLUSIONS: CT examination for detecting an unknown infection focus in patients with SIRS or sepsis is highly beneficial and should be conducted in patients with obscure clinical infection. KEY POINTS: • Evaluation of patients with obscure clinical infection is a challenging task. • CT examination of patients with SIRS or sepsis seems to be beneficial. • CT examination confirmed suspected diagnosis in 26% of patients. • CT examination yielded a new infection focus in 33% of patients. • CT examination changed therapy in up to 32% of patients.


Subject(s)
Multidetector Computed Tomography/methods , Sepsis/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , Sepsis/therapy , Systemic Inflammatory Response Syndrome/therapy , Young Adult
5.
Ann Surg Oncol ; 23(12): 3972-3977, 2016 11.
Article in English | MEDLINE | ID: mdl-27313067

ABSTRACT

PURPOSE: Peritoneal carcinomatosis (PC) is a dismal feature of gastric cancer that most often is treated by systemic palliative chemotherapy. In this retrospective matched pairs-analysis, we sought to establish whether specific patient subgroups alternatively should be offered a multimodal therapy concept, including cytoreductive surgery (CRS) and intraoperative hyperthermic chemotherapy (HIPEC). METHODS: Clinical outcomes of 38 consecutive patients treated with gastrectomy, CRS and HIPEC for advanced gastric cancer with PC were compared to patients treated by palliative management (with and without gastrectomy) and to patients with advanced gastric cancer with no evidence of PC. Kaplan-Meier survival curves and multivariate Cox regression models were applied. RESULTS: Median survival time after gastrectomy was similar between patients receiving CRS-HIPEC and matched control patients operated for advanced gastric cancer without PC [18.1 months, confidence interval (CI) 10.1-26.0 vs. 21.8 months, CI 8.0-35.5 months], resulting in comparable 5-year survival (11.9 vs. 12.1 %). The median survival time after first diagnosis of PC for gastric cancer was 17.2 months (CI 10.1-24.2 months) in the CRS-HIPEC group compared with 11.0 months (CI 7.4-14.6 months) for those treated by gastrectomy and chemotherapy alone, resulting in a twofold increase of 2-year survival (35.8 vs. 16.9 %). CONCLUSIONS: We provide retrospective evidence that multimodal treatment with gastrectomy, CRS, and HIPEC is associated with improved survival for patients with PC of advanced gastric cancer compared with gastrectomy and palliative chemotherapy alone. We also show that patients treated with CRS-HIPEC have comparable survival to matched control patients without PC. However, regardless of treatment scheme, all patients subsequently recur and die of disease.


Subject(s)
Cytoreduction Surgical Procedures , Hyperthermia, Induced , Peritoneal Neoplasms/therapy , Stomach Neoplasms/pathology , Antineoplastic Agents/administration & dosage , Gastrectomy , Humans , Kaplan-Meier Estimate , Middle Aged , Palliative Care , Peritoneal Neoplasms/secondary , Proportional Hazards Models , Retrospective Studies , Stomach Neoplasms/surgery , Survival Rate
6.
Am J Transplant ; 16(4): 1139-47, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26855194

ABSTRACT

Transplant recipients face an increased risk of cancer compared with the healthy population. Although several studies have examined the direct effects of immunosuppressive drugs on cancer cells, little is known about the interactions between pharmacological immunosuppression and cancer immunosurveillance. We investigated the different effects of rapamycin (Rapa) versus cyclosporine A (CsA) on tumor-reactive CD8(+) T cells. After adoptive transfer of CD8(+) T cell receptor-transgenic OTI T cells, recipient mice received either skin grafts expressing ovalbumin (OVA) or OVA-expressing B16F10 melanoma cells. Animals were treated daily with Rapa or CsA. Skin graft rejection and tumor growth as well as molecular and cellular analyses of skin- and tumor-infiltrating lymphocytes were performed. Both Rapa and CsA were equally efficient in prolonging skin graft survival when applied at clinically relevant doses. In contrast to Rapa-treated animals, CsA led to accelerated tumor growth in the presence of adoptively transferred tumor-reactive CD8(+) OTI T cells. Further analyses showed that T-bet was downregulated by CsA (but not Rapa) in CD8(+) T cells and that cancer cytotoxicity was profoundly inhibited in the absence of T-bet. CsA reduces T-bet-dependent cancer immunosurveillance by CD8(+) T cells. This may contribute to the increased cancer risk in transplant recipients receiving calcineurin inhibitors.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Cyclosporine/pharmacology , Graft Rejection/immunology , Immune Tolerance/immunology , Melanoma, Experimental/immunology , Skin Transplantation , T-Box Domain Proteins/physiology , Animals , Female , Graft Rejection/drug therapy , Graft Survival/drug effects , Graft Survival/immunology , Immune Tolerance/drug effects , Immunosuppressive Agents/pharmacology , Male , Melanoma, Experimental/drug therapy , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Sirolimus/pharmacology
7.
Crit Rev Toxicol ; 43(1): 45-72, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23190036

ABSTRACT

Endocrine disruption is considered a highly relevant hazard for environmental risk assessment of chemicals, plant protection products, biocides and pharmaceuticals. Therefore, screening tests with a focus on interference with estrogen, androgen, and thyroid hormone pathways in fish and amphibians have been developed. However, they use a large number of animals and short-term alternatives to animal tests would be advantageous. Therefore, the status of alternative assays for endocrine disruption in fish and frogs was assessed by a detailed literature analysis. The aim was to (i) determine the strengths and limitations of alternative assays and (ii) present conclusions regarding chemical specificity, sensitivity, and correlation with in vivo data. Data from 1995 to present were collected related to the detection/testing of estrogen-, androgen-, and thyroid-active chemicals in the following test systems: cell lines, primary cells, fish/frog embryos, yeast and cell-free systems. The review shows that the majority of alternative assays measure effects directly mediated by receptor binding or resulting from interference with hormone synthesis. Other mechanisms were rarely analysed. A database was established and used for a quantitative and comparative analysis. For example, a high correlation was observed between cell-free ligand binding and cell-based reporter cell assays, between fish and frog estrogenic data and between fish embryo tests and in vivo reproductive effects. It was concluded that there is a need for a more systematic study of the predictive capacity of alternative tests and ways to reduce inter- and intra-assay variability.


Subject(s)
Androgens/toxicity , Animal Testing Alternatives/methods , Endocrine Disruptors/toxicity , Estrogens/toxicity , Thyroid Hormones/toxicity , Amphibians , Androgens/analysis , Animals , Biological Assay/methods , Biological Assay/veterinary , Cell Line , Cell-Free System , Endocrine Disruptors/analysis , Estrogens/analysis , Fishes , Reproduction/drug effects , Risk Assessment , Thyroid Hormones/analysis , Toxicogenetics
8.
Transpl Immunol ; 24(3): 157-63, 2011 Apr 15.
Article in English | MEDLINE | ID: mdl-21194567

ABSTRACT

Donor-derived mesenchymal stem cells (MSC) can induce long-term acceptance in a rat heart transplantation model when injected prior to transplantation in combination with mycophenolate mofetil (MMF). In contrast, MSC alone cause accelerated graft rejection. To better understand these conflicting data we studied the effects of MSC and MMF on lymphocyte populations in heart allografts and secondary lymphatic organs. Allogeneic MSC injected prior to transplantation are immunogenic in this model because activated CD4+ and CD8+ cells emerged earlier in secondary lymphatic organs of MSC- and MSC/MMF-treated animals, compared to animals not treated with MSC. Consequently T cells infiltrated the grafts of MSC-only treated animals promptly causing accelerated graft rejection. However, few T cells or antigen-presenting cells (APC) infiltrated the grafts of animals treated with MSC and MMF. Consistent with this finding, intercellular adhesion molecule 1 (ICAM-1) and E-selectin was down-regulated exclusively in MSC/MMF-treated grafts, indicating that MSC together with MMF interfere with endothelial activation. Additionally, the presence of interferon-gamma (IFN-γ) enhanced MSC capabilities to suppress T cell proliferation in vitro. Interestingly, MMF did not influence serum IFN-γ levels in vivo. Together, our data indicate that MSC pre-activate T cells, but co-treatment with MMF eliminates these T cells, decreases intragraft APC and T cell trafficking by inhibiting endothelial activation, and allows IFN-γ stimulation of suppressive MSC.


Subject(s)
E-Selectin/metabolism , Graft Rejection/prevention & control , Heart Transplantation/immunology , Intercellular Adhesion Molecule-1/metabolism , Mesenchymal Stem Cells , Mycophenolic Acid/analogs & derivatives , Animals , Antigen-Presenting Cells/drug effects , Antigen-Presenting Cells/immunology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , E-Selectin/immunology , Endothelium, Lymphatic/drug effects , Endothelium, Lymphatic/metabolism , Graft Rejection/immunology , Immunosuppression Therapy/methods , Immunosuppressive Agents/immunology , Immunosuppressive Agents/pharmacology , Intercellular Adhesion Molecule-1/immunology , Interferon-gamma/blood , Interferon-gamma/immunology , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/immunology , Mycophenolic Acid/immunology , Mycophenolic Acid/pharmacology , Rats , Rats, Inbred ACI , Rats, Inbred Lew
9.
Transpl Immunol ; 22(3-4): 144-9, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19840851

ABSTRACT

The immunomodulatory properties of CD8 T cells with regulatory phenotype have become evident. It remains unclear whether the immunomodulatory function of CD8(+)CD28(-) T cells requires antigen-specific TCR interaction with major histocompatibility complex class I (MHC I). We have isolated naïve CD8(+)CD28(-) T suppressor cells (Tsup) from H2-Kk Des-TCR mice that express a transgenic, MHC class I-restricted, clonotypic TCR against an allogeneic MHC class I molecule (H2-Kb) plus self-peptide. These cells were compared to B10.BR wild type (w/t) CD8(+)CD28(-) T cells and to naïve CD4(+)CD25(+) regulatory T cells (Treg) of the same strains. Des CD8 effector T cells proliferated more readily when stimulated by H2-Kb splenocytes than w/t controls, whereas Des CD4 T cells showed the same alloresponse as w/t cells. Activation and proliferation of B10.BR CD4 T cells stimulated by H2-Kb APC were suppressed more effectively by Des CD8(+)CD28(-) T cells than by w/t CD8(+)CD28(-) T cells. On the contrary, Des CD4(+)CD25(+) T cells inhibited T cell proliferation less effectively than w/t CD4(+)CD25(+) T cells. In conclusion, we demonstrate that the function of naive Tsup is strongly enhanced by antigen recognition. Therefore we expect that Tsup are possible candidates for antigen-specific immunosuppressive therapy.


Subject(s)
Immunosuppression Therapy , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes, Regulatory/metabolism , Animals , Antigens, CD/biosynthesis , Autoantigens/immunology , Autoantigens/metabolism , Cell Proliferation , Cells, Cultured , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class I/metabolism , Isoantigens/immunology , Isoantigens/metabolism , Lymphocyte Activation/immunology , Mice , Mice, Inbred Strains , Mice, Transgenic , Receptors, Antigen, T-Cell/immunology , T-Cell Antigen Receptor Specificity/immunology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/pathology
10.
Transplant Proc ; 41(6): 2607-11, 2009.
Article in English | MEDLINE | ID: mdl-19715984

ABSTRACT

Mesenchymal stem cells (MSC) have emerged to be one of the most promising candidates for cellular immunotherapy in solid organ transplantation because the reduction of conventional immunosuppression is highly desirable. However, little is known about the details of MSC-mediated immunomodulation and their clinical relevance. To address conflicting studies about the ability of MSC to suppress or augment T-cell proliferation, we introduce a transplantation-related rat model that allows studying the influence of MSC on alloproliferation. Hearts transplanted in a fully allogeneic transplantation model (LEW to ACI) were rejected earlier when recipients were pretreated with donor MSC, indicating activation of T cells in vivo. In additional co-culture experiments, T cells were differently affected by allogeneic MSC depending on the extent of previous activation: When conditions were rendered proinflammatory by adding high concanavalin A (ConA) concentrations or proinflammatory cytokines (interferon-gamma, interleukin-2, or tumor necrosis factor-alpha), MSC inhibited proliferation. Application of low doses of ConA or anti-inflammatory cytokines like IL-10 abrogated the suppressive effect of MSC. For application of MSC in solid organ transplantation, it will be important to further describe this switch effect of MSC function.


Subject(s)
Heart Transplantation/immunology , Immunosuppression Therapy/methods , Mesenchymal Stem Cell Transplantation/methods , Animals , Antibodies, Monoclonal/immunology , Cell Culture Techniques , Flow Cytometry , Lymphocyte Activation , Models, Animal , Rats , Rats, Inbred ACI , Rats, Inbred Lew , Spleen/cytology , T-Lymphocytes/immunology , Transplantation, Heterotopic , Transplantation, Homologous
11.
Rev. Méd. Clín. Condes ; 19(5): 462-465, nov. 2008. tab
Article in Spanish | LILACS | ID: lil-511234

ABSTRACT

En los últimos 10 años el estudio de la Esclerosis Múltiple (EM) ha presentado numerosos avances clínicos y terapéuticos, que han permitido un manejo más racional de la enfermedad, con significativo beneficio para los pacientes. De ser una enfermedad crónica sin tratamientos específicos, actualmente existen al menos seis fármacos con demostrada actividad sobre la enfermedad, y herramientas útiles para establecer pronósticos y controlar la evolución. En el presente trabajo (dividido en dos partes) se analizaran algunos aspectos de los avances observados en EM, especialmente aquellos que han incidido directa o indirectamente en un beneficio para los pacientes, y que apuntan a un tratamiento precoz de la enfermedad.


New data gathered for the past 5-10 years suggest that it is possible to define the rísk of clinically definite MS, as well as long term disability. This is specially significant in patients presenting with a Clinically Isolated Syndrome (OS), based on clinical presentation and MRI imaging. Longitudinal studies of patients with OS have permitted the realization of clinical trials of early treatment with Interferon Beta (1 a, 1 b) and Glatiramer acetate on these patients. These trials have shown significant benefit with all these treatments, and it is expected a better prognosis for patients with Multiple Sclerosis at early stages.


Subject(s)
Humans , Multiple Sclerosis/drug therapy , Immunologic Factors/pharmacology , Adjuvants, Immunologic/pharmacology , Multiple Sclerosis/diagnosis , Interferon-beta/pharmacology
12.
Rev. Méd. Clín. Condes ; 19(5): 490-497, nov. 2008. tab
Article in Spanish | LILACS | ID: lil-511250

ABSTRACT

La cefalea es una de las causas más frecuentes de consulta en los servicios de urgencia, en la atención primaria y por supuesto en la consulta del neurólogo. Es una patología que afecta a la calidad de vida de las personas que la padecen y es una importante causa de ausentismo laboral. Dado lo transversal de esta patología, es que médicos de todas las especialidades nos vemos en la obligación de satisfacer la demanda de nuestros pacientes por un alivio. Este artículo no pretende hacer una revisión extensa sobre el tema, sino que en particular nos enfocaremos sobre algunos aspectos que han sido objeto debate, tales como "migraña y hormonas", "migraña y accidente cerebrovascular" y sobre aquellos aspectos que han tenido importantes avances en el último tiempo, tales como el conocimiento de la fisiopatología de la migraña, así como también el reconocimiento, diagnóstico y manejo de la cefalea crónica diaria.


Migraine is one of the most important reasons that explain emergency calls, general medicine and neurological office consultations. Migraine affects the patients quality of daily life and is a cause of working absenteeism. Therefore, many physicians may be in volved in the management of these patients and all of them must be updated about this prevalent condition.The aim of this review is not to make a thorough analysis of migraine; we will mainly focus on important issues such as migraine and hormones, migraine and stroke, a, advances in the understandig of migraine pathophysiology Finally, we address the appropriate diagno management of the prevalent chronic daily headache.


Subject(s)
Humans , Male , Female , Migraine Disorders/complications , Migraine Disorders/physiopathology , Chronic Disease , Headache Disorders, Secondary/complications , Sex Factors , Migraine Disorders/etiology , Migraine Disorders/therapy
13.
Transpl Immunol ; 20(1-2): 55-60, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18762258

ABSTRACT

The induction of tolerance towards allogeneic solid organ grafts is one of the major goals in transplantation medicine. Mesenchymal stem cells (MSC) inhibit the immune response in vitro, and thus are promising candidate cells to promote acceptance of transplanted organs in vivo. Such novel approaches of tolerance induction are needed since, to date, graft acceptance can only be maintained through life-long treatment with unspecific immunosuppressants that are associated with toxic injury, opportunistic infections and malignancies. We demonstrate that donor-derived MSC induce long-term allograft acceptance in a rat heart transplantation model, when concurrently applied with a short course of low-dose mycophenolate. This tolerogenic effect of MSC is at least partially mediated by the expression of indoleamine 2,3-dioxygenase (IDO), demonstrated by the fact that blocking of IDO with 1-methyl tryptophan (1-MT) abrogates graft acceptance. Moreover we hypothesize that MSC interact with dendritic cells (DC) in vivo, because allogeneic MSC are rejected in the long-term but DC acquire a tolerogenic phenotype after applying MSC. In summary, we demonstrate that MSC constitute a promising tool for induction of non-responsiveness in solid organ transplantation that warrants further investigation in clinical trials.


Subject(s)
Graft Rejection/prevention & control , Graft Survival/immunology , Heart Transplantation , Immunosuppression Therapy/methods , Immunosuppressive Agents/administration & dosage , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/immunology , Mycophenolic Acid/analogs & derivatives , Animals , Dendritic Cells/immunology , Graft Survival/drug effects , Heart Transplantation/pathology , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Mesenchymal Stem Cells/drug effects , Mycophenolic Acid/administration & dosage , Rats , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Tryptophan/analogs & derivatives , Tryptophan/pharmacology
14.
Dig Surg ; 25(3): 213-9, 2008.
Article in English | MEDLINE | ID: mdl-18577867

ABSTRACT

BACKGROUND: Intestinal ischemia is the prime vascular emergency for the visceral surgeon. However, the diagnosis of mesenteric ischemia is difficult, the surgical options are often limited and the overall outcome is generally poor. METHODS: We report on a single center series of 83 patients undergoing surgery for mesenteric ischemia during a 3-year period. Risk factors, clinical presentation, type and timing of imaging studies and their implications for surgical therapy and outcome are analyzed. RESULTS: Hypertension and diabetes were the most common risk factors (68/64% of all patients). Abdominal pain was the most general symptom upon presentation to the surgical unit (73%). Two-phase, contrast-enhanced computed tomography was applied as the standard preoperative imaging modality (correct diagnosis in 69%). Bowel resections were necessary in most patients; approaches to restore blood flow by vascular surgery interventions were applied in 17 patients (20%). The overall morbidity and mortality rate in our study cohort was expectedly high (59% 1 month mortality). CONCLUSION: The diagnosis and surgical treatment of mesenteric ischemia remains a major difficulty. We recommend preoperative CT analysis followed by an aggressive indication for early surgical exploration and bowel resection. An attempt of revascularization is justified for selected patients with limited macrovascular disease.


Subject(s)
Ischemia , Mesentery/blood supply , Postoperative Complications/etiology , Aged , Female , Humans , Ischemia/diagnosis , Ischemia/etiology , Ischemia/surgery , Male , Retrospective Studies , Risk Factors , Survival Analysis , Treatment Outcome
15.
Article in German | MEDLINE | ID: mdl-17334893

ABSTRACT

The new drinking water ordinance (TrinkwV 2001) entered into force in 2003. In this paper we report about experiences with monitoring microbiological quality of drinking water. Special problems, for instance requirements concerning the quality of raw water, new and "old" microbiological parameters, microbiological methods, assessment of parametric values, especially in the case of values higher than the imperative value, are also described. Possible developments in this field are discussed. The paper should support microbiological laboratories, public health officers and other public authorities in monitoring and assessment of drinking water quality.


Subject(s)
Water Microbiology/standards , Water Supply/standards , Colony Count, Microbial , Germany , Guidelines as Topic/standards , Humans , Water Purification/legislation & jurisprudence , Water Purification/standards , Water Supply/legislation & jurisprudence
16.
Chemistry ; 7(12): 2563-80, 2001 Jun 18.
Article in English | MEDLINE | ID: mdl-11465448

ABSTRACT

A comprehensive study into the coordination chemistry of two C3-chiral tripodal amido ligands has been carried out. The amido ligands contain a trisilylmethane backbone and chiral peripheral substituents. The amine precursors. HC(SiMe2NH[(S)-1-phenylethyl]]3 (1) and HC[SiMe2NH[(R)-1-indanyl]]3 (2) were found to be in equilibrium in solution with the cyclic diamines HC[SiMe2N[(S)-1-phenylethyl]2](SiMe2NH-[(S)-1-phenylethyl]] (3) and HC[SiMe2NH[(R)-1-indanyl]][SiMe2NH[(R)-1-indanyl]) (4), which are generated upon ejection of one molecule of the chiral primary amine. Reaction of these equilibrium mixtures with three molar equivalents of butyllithium instantaneously gave the trilithium triamides HC[SiMe2N(Li)[(S)-1-phenylethyl]]3 (5) and HC[SiMe2N(Li)[(R)-1-indanyl]]3 (6), both of which were characterised by an X-ray diffraction study. Both lithium compounds possess a central heteroadamantane core, in which the two-coordinate Li atoms are additionally weakly solvated by the three aryl groups of the chiral peripheral substituents, the Li-C contacts being in the range of 2.65-2.73 A. Reaction of 5 and 6 with [TiCl4(thf)2] and ZrCl4 gave the corresponding amido complexes [TiCl-[HC[SiMe2N[(S)-1-phenylethyl]]3]] (7), [TiCl(HC[SiMe2N[(R)-1-indanyl]]3]] (8), [ZrCl[HC[SiMe2N[(S)-1-phenylethyl]]3]] (9) and [ZrCl[HC[SiMe2N[(R)-1-indanyl]]3]] (10), respectively. Of these, compound 7 was structurally characterised by X-ray structure analysis and was shown to possess a C3-symmetrical arrangement of the tripod ligand. The chiral anionic dinuclear complex [Li-(OEt2)4][Zr2Cl3[HC[SiMe2N[(S)-1-phenylethyl]]3]2] (11) was isolated from reaction mixtures leading to 9. An X-ray diffraction study established its dimeric structure, in which the chiral amido ligands cap the two metal centres, which are linked through three symmetrically arranged, bridging chloro ligands. Reaction of 9 and 10 with a series of alkyl Grignard and alkyllithium reagents yielded the corresponding alkylzirconium complexes. X-ray structure analyses of [Zr(CH3)[HC[SiMe2N[(S)-1-phenylethyl]]3]] (12) and [Zr(CH3)-[HC[SiMe2N)[(R)-1-indanyl]]3]] (20) established their detailed molecular arrangements. While the reaction of 12 with the aryl ketones PhC(O)R (R = CH = CHPh, iPr, Et) gave the corresponding C-O insertion products, which contain an additional chiral centre in the alkoxy group, with low stereoselectivity (0-40% de). The corresponding conversions with several aryl aldehydes yielded the alkoxo complexes with high stereoselectivity. Upon hydrolysis, the chiral alcohols were isolated and shown to have enantiomeric excesses between 68 and 82%. High stereodiscrimination was also observed in the insertion reactions of several chiral ketones and aldehydes. However, this was shown to originate primarily from the chirality of the substrate. In analogous experiments with carbonyl compounds, the ethyl- and butyl-zirconium analogues of 12 did not undergo CO insertion into the metal-alkyl bond. Instead, beta-elimination and formal insertion into the metal-hydride bond occurred. It was found that the elimination of the alkene was induced by

17.
J Clin Child Psychol ; 29(4): 479-92, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11126628

ABSTRACT

Provides a critical review of performance-based assessment measures in autism. Currently, performance-based measures of autism are being explored in two domains: structured play sessions and cognitive-neuropsychological assessments. Structured play sessions are designed to elicit the behavioral symptoms associated with autism to provide a consistent and valid means of early detection and diagnosis of autism across different evaluators and settings. These structured play sessions provide a supplement to diagnostic instruments based on parental report. Cognitive-neuropsychological tasks have been used to identify possible underlying cognitive impairments in autism including executive function, theory of mind, selective attention, and abstraction. Currently, cognitive tasks are useful in treatment planning but are inappropriate for diagnostic purposes. Important goals for the future will be to integrate parent-report diagnostic interviews and structured play observations and to identify a profile of cognitive impairments that are specific to pervasive developmental disorders that can be incorporated into diagnostic protocols.


Subject(s)
Autistic Disorder/diagnosis , Cognition , Autistic Disorder/classification , Child , Humans , Neuropsychological Tests , Play and Playthings , Psychometrics , Task Performance and Analysis
18.
J Autism Dev Disord ; 30(1): 3-14, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10819116

ABSTRACT

Medial temporal lobe amnesic disorder is characterized by an impairment in explicit memory (e.g., remembering a shopping list) and intact implicit memory (e.g., a woman seems familiar although you cannot remember having met her before). This study examined whether children with high-functioning autism have this same dissociation between explicit and implicit memory abilities. Children with autism and normal development participated in three memory tasks: one implicit task (perceptual identification) and two explicit tasks (recognition and recall). Children with autism showed intact implicit and explicit memory abilities. However, they did not show the typical pattern of recalling more items from both the beginning and end of a list and instead only recalled items from the end of the list. These results do not support the theory that high-functioning autism is a type of medial temporal lobe amnesia. However, these findings suggest that persons with autism use different organizational strategies during encoding or retrieval of items from memory.


Subject(s)
Amnesia/diagnosis , Autistic Disorder/diagnosis , Adolescent , Child , Female , Humans , Male , Mental Recall/physiology , Neuropsychological Tests , Psychiatric Status Rating Scales
19.
Zentralbl Hyg Umweltmed ; 202(1): 41-50, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10418099

ABSTRACT

Within the framework of the standardisation efforts on disinfectant testing on the European level the test germ Enterococcus hirae ATCC 10541 has been included for some time in the test requirements whereas the test strain Enterococcus faecium, which has frequently been used up to now, has been largely ignored. We compared the thermal and the chemical resistance of both test germ species. In the quantitative suspension test with active ingredients from the group of aldehydes, phenols, quaternaries and oxidizing agents with the exception of peracetic acid, no significant differences were determined between the two strains. In the case of the studies on thermal resistance at 65 degrees C and 68 degrees C, Enterococcus faecium ATCC 6057, by contrast, proved to be far more resistant than Enterococcus hirae ATCC 10541. According to these results, priority should be given to Enterococcus faecium over Enterococcus hirae as the test germ for chemical and also chemothermal disinfection.


Subject(s)
Disinfectants/pharmacology , Disinfection/methods , Enterococcus faecium/growth & development , Enterococcus/growth & development , Hot Temperature , Benzalkonium Compounds/pharmacology , Chloramines/pharmacology , Colony Count, Microbial , Cresols/pharmacology , Disinfectants/standards , Disinfection/standards , Drug Resistance, Microbial , Enterococcus/drug effects , Enterococcus faecium/drug effects , European Union , Formaldehyde/pharmacology , Glutaral/pharmacology , Peracetic Acid/pharmacology , Tosyl Compounds/pharmacology
20.
Zentralbl Hyg Umweltmed ; 200(5-6): 479-90, 1998 Feb.
Article in German | MEDLINE | ID: mdl-9531721

ABSTRACT

Testing the ability of commercial compounds to provide an effective disinfection of instruments requires test conditions that are close to reality which includes the proper selection of the material used to contaminate the test objects. The adhesion of the material must be strong enough to keep it attached to the test object during and after insertion into the disinfectant solution. Its characteristics should come as close as possible to those of the contaminations encountered in practice. The guideline for instrument disinfectants published by the Robert Koch-Institute recommends the use of coagulated blood. Accordingly, heparinized sheep blood is mixed with the test germs, and protamin is added to initiate coagulation. In the present investigation we compared this contamination procedure with a second one, in which coagulation was achieved by adding a CaCl2 solution to citrate blood. We also included agarose as an almost inert contaminant in our experiments. The results showed that protamine is able to increase the microbicidal efficacy of formaldehyde on staphylococci significantly. When these test germs were embedded either in citrat blood or in agarose, it took about twice the disinfectant concentrations to achieve the same microbicidal effects as with protamine blood (Fig. 1). Remarkably, the results obtained with citrate blood were the same as those with agarose, regardless of the differences in material between the two contaminants. It should also be noted that the microbicidal effect of the formaldehyde proved to be almost independent from the amount of contaminant per test area, hence, from the thickness of the layer. When M. terrae was employed as test germ, the results obtained with protamine blood and citrate blood, respectively, as contaminants were identical (Fig. 2). The same was true for the other test germs investigated, except for E. faecium (Fig. 3). The addition of even very small amounts of protamine to the embedding compound, agarose led to a substantially increased efficacy of the formaldehyde against staphylococci (Fig. 4). This effect was especially distinct in suspension (Fig. 5). Whenever the efficacy of formaldehyde-containing disinfectants is to be tested and evaluated, one should be aware of this synergism between protamine and formaldehyde. In these cases, it is advised to employ other contaminating agents, such as coagulated blood prepared by addition of CaCl2 to citrate blood.


Subject(s)
Disinfectants/pharmacology , Disinfection/methods , Equipment and Supplies , Formaldehyde/pharmacology , Protamines/pharmacology , Animals , Blood , Humans , Sheep
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