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1.
Eur Rev Med Pharmacol Sci ; 27(22): 11143-11155, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38039046

RESUMEN

OBJECTIVE: This retrospective study employed a competing-risks analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database to identify precise prognostic factors associated with ovarian serous cystadenocarcinoma (OSCC) in patients. PATIENTS AND METHODS: Patients with OSCC during 2004-2015 were identified in the SEER database, and their clinicopathological, demographic, and survival data were examined. Univariate analysis using Gray's test and the cumulative incidence function was used to evaluate the prognoses of events of interest. The multivariate analysis involved several models, including the Cox proportional hazards, Fine-Gray, and cause-specific (CS) hazard function models, to estimate the hazard functions of competing risks. Hazard ratios were analyzed to identify the reliability of the prognostic factors. RESULTS: Among the 10,400 individuals diagnosed with OSCC, 5,713 died from the illness, and 1,125 died from other causes. The cumulative incidence rate of events of interest was found to be significant for ethnicity, age at diagnosis, histological grade, American Joint Committee on Cancer (AJCC) stage, chemotherapy and surgery status, tumor size, marital status, and local lymph node metastases (p<0.05). The multivariate analysis revealed that ethnicity, histological grade, surgery and chemotherapy status, age at diagnosis, AJCC stage, marital status, and distant metastases were independent prognostic factors in the Cox model (p<0.05). Finally, the Fine-Gray and CS models demonstrated that ethnicity, histological grade, surgery and chemotherapy status, age at diagnosis, AJCC stage, tumor size, marital status, and combination summary stage were all identified as independent prognostic factors (p<0.05). CONCLUSIONS: This study determined the risk factors for OSCC using a competing risk analysis model established by the SEER database. The findings can help clinicians understand OSCC better and provide more accurate medical support to affected patients.


Asunto(s)
Cistadenocarcinoma Seroso , Neoplasias Ováricas , Femenino , Humanos , Pronóstico , Causas de Muerte , Estudios Retrospectivos , Reproducibilidad de los Resultados , Carcinoma Epitelial de Ovario , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/patología
2.
medRxiv ; 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37162985

RESUMEN

Background: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide. Methods/Findings: In our ongoing USA feasibility/efficacy clinical trial, data collated with other ongoing and earlier published results proved high performance of an Immunochromatographic-test(ICT) that enables accurate, rapid diagnosis/treatment, establishing new paradigms for care. Overall results from patient blood and/or serum samples tested with ICT compared with gold-standard-predicate-test results found ICT performance for 4606 sera/1876 blood, 99.3%/97.5% sensitive and 98.9%/99.7% specific. However, in the clinical trial the FDA-cleared-predicate test initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon's Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO ASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening. Conclusions/Significance: This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories. Author's Summary: Toxoplasmosis is a major health burden for developed and developing countries, causing damage to eyes and brain, loss of life and substantial societal costs. Prompt diagnosis in gestational screening programs enables treatment, thereby relieving suffering, and leading to > 14-fold cost savings for care. Herein, we demonstrate that using an ICT that meets WHO ASSURED-criteria identifying persons with/without antibody to Toxoplasma gondii in sera and whole blood with high sensitivity and specificity, is feasible to use in USA clinical practice. We find this new approach can help to obviate the problem of detection of false positive anti- T.gondii IgM results for those without IgG antibodies to T.gondii when this occurs in present, standard of care, predicate USA FDA cleared available assays. Thus, this accurate test facilitates gestational screening programs and a global initiative to diagnose and thereby prevent and treat T.gondii infection. This minimizes likelihood of false positives (IgG and/or IgM) while maintaining maximum sensitivity. When isolated IgM antibodies are detected, it is necessary to confirm and when indicated continue follow up testing in ∼2 weeks to establish seroconversion. Presence of a positive ICT makes it likely that IgM is truly positive and a negative ICT makes it likely that IgM will be a false positive without infection. These results create a new, enthusiastically-accepted, precise paradigm for rapid diagnosis and validation of results with a second-line test. This helps eliminate alarm and anxiety about false-positive results, while expediting needed treatment for true positive results and providing back up distinguishing false positive tests.

3.
Haemophilia ; 22(6): e527-e536, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27704689

RESUMEN

INTRODUCTION: Joint haemorrhage is the principal clinical manifestation of haemophilia frequently leading to advanced arthropathy and arthrofibrosis, resulting in severe disability. The degree and prevalence of arthrofibrosis in hemophilic arthropathy is more severe than in other forms of arthropathy. Expression of connective tissue growth factor (CTGF) has been linked to many fibrotic diseases, but has not been studied in the context of haemophilic arthropathy. AIM: We aim to compare synovial tissues histologically from haemophilia and osteoarthritis patients with advanced arthropathy in order to compare expression of proteins that are possibly aetiologic in the development of arthrofibrosis. METHODS: Human synovial tissues were obtained from 10 haemophilia and 10 osteoarthritis patients undergoing joint surgery and processed for histology and immunohistochemistry. RESULTS: All samples from haemophilia patients had synovitis with hypertrophy and hyperplasia of synovial villi. Histologically, synovial tissues contained hyperplastic villi with increased cellularity and abundant haemosiderin- and ferritin-pigmented macrophage-like cells (HMCs), with a perivascular localization in the sub-surface layer. CTGF staining was observed in the surface layer and sub-surface layer in all haemophilia patients, exclusively co-localizing with HMCs. Quantification showed that the extent of CTGF-positive areas was correlated with the degree of detection of HMCs. CTGF was not observed in any of the samples from osteoarthritis patients. CONCLUSION: Using histological analysis, we showed that CTGF expression is elevated in haemophilia patients with arthrofibrosis and absent in patients with osteoarthritis. Additionally, we found that CTGF is always associated with haemosiderin-pigmented macrophage-like cells, which suggests that CTGF is produced by synovial A cells following the uptake of blood breakdown products.


Asunto(s)
Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Hemartrosis/metabolismo , Hemofilia A/metabolismo , Artropatías/metabolismo , Adulto , Femenino , Hemartrosis/complicaciones , Hemofilia A/complicaciones , Humanos , Artropatías/etiología , Masculino , Persona de Mediana Edad , Adulto Joven
4.
J Periodontal Res ; 46(6): 730-41, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21848615

RESUMEN

BACKGROUND AND OBJECTIVE: Adaptive properties of the bone-periodontal ligament-tooth complex have been identified by changing the magnitude of functional loads using small-scale animal models, such as rodents. Reported adaptive responses as a result of lower loads due to softer diet include decreased muscle development, change in structure-function relationship of the cranium, narrowed periodontal ligament space, and changes in the mineral level of the cortical bone and alveolar jaw bone and in the glycosaminoglycans of the alveolar bone. However, the adaptive role of the dynamic bone-periodontal ligament-cementum complex to prolonged reduced loads has not been fully explained to date, especially with regard to concurrent adaptations of bone, periodontal ligament and cementum. Therefore, in the present study, using a rat model, the temporal effect of reduced functional loads on physical characteristics, such as morphology and mechanical properties and the mineral profiles of the bone-periodontal ligament-cementum complex was investigated. MATERIAL AND METHODS: Two groups of 6-wk-old male Sprague-Dawley rats were fed nutritionally identical food with a stiffness range of 127-158 N/mm for hard pellet or 0.3-0.5 N/mm for soft powder forms. Spatio-temporal adaptation of the bone-periodontal ligament-cementum complex was identified by mapping changes in the following: (i) periodontal ligament collagen orientation and birefringence using polarized light microscopy, bone and cementum adaptation using histochemistry, and bone and cementum morphology using micro-X-ray computed tomography; (ii) mineral profiles of the periodontal ligament-cementum and periodontal ligament-bone interfaces by X-ray attenuation; and (iii) microhardness of bone and cementum by microindentation of specimens at ages 6, 8, 12 and 15 wk. RESULTS: Reduced functional loads over prolonged time resulted in the following adaptations: (i) altered periodontal ligament orientation and decreased periodontal ligament collagen birefringence, indicating decreased periodontal ligament turnover rate and decreased apical cementum resorption; (ii) a gradual increase in X-ray attenuation, owing to mineral differences, at the periodontal ligament-bone and periodontal ligament-cementum interfaces, without significant differences in the gradients for either group; (iii) significantly (p < 0.05) lower microhardness of alveolar bone (0.93 ± 0.16 GPa) and secondary cementum (0.803 ± 0.13 GPa) compared with the higher load group insert bone = (1.10 ± 0.17 and cementum = 0.940 ± 0.15 GPa, respectively) at 15 wk, indicating a temporal effect of loads on the local mineralization of bone and cementum. CONCLUSION: Based on the results from this study, the effect of reduced functional loads for a prolonged time could differentially affect morphology, mechanical properties and mineral variations of the local load-bearing sites in the bone-periodontal ligament-cementum complex. These observed local changes in turn could help to explain the overall biomechanical function and adaptations of the tooth-bone joint. From a clinical translation perspective, our study provides an insight into modulation of load on the complex for improved tooth function during periodontal disease and/or orthodontic and prosthodontic treatments.


Asunto(s)
Adaptación Fisiológica , Proceso Alveolar/fisiología , Cemento Dental/fisiología , Análisis del Estrés Dental , Ligamento Periodontal/fisiología , Proceso Alveolar/anatomía & histología , Proceso Alveolar/química , Proceso Alveolar/diagnóstico por imagen , Animales , Birrefringencia , Densidad Ósea , Colágeno/ultraestructura , Fuerza Compresiva , Cemento Dental/anatomía & histología , Cemento Dental/química , Cemento Dental/diagnóstico por imagen , Alimentos , Dureza , Pruebas de Dureza , Masculino , Ligamento Periodontal/anatomía & histología , Ligamento Periodontal/química , Ligamento Periodontal/diagnóstico por imagen , Ratas , Ratas Sprague-Dawley , Soporte de Peso , Microtomografía por Rayos X
5.
Osteoarthritis Cartilage ; 16(1): 70-82, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17644010

RESUMEN

OBJECTIVE: Articular cartilage is separated from subchondral bone by the tidemark and a calcified cartilage zone. Advancement of the calcified region and tidemark duplication are both hallmarks of osteoarthritis (OA). Currently the mechanisms controlling post-natal articular cartilage mineralization are poorly understood. The objective of this study is to test the hypothesis that cellular communication between different cartilage layers regulates articular chondrocyte mineralization. DESIGN: Co-culture models were established to evaluate the interaction of chondrocytes derived from the surface, middle and deep zones of articular cartilage. The cultures were stimulated with triiodothyronine (T3) to promote chondrocyte hypertrophy. The effects of zonal chondrocyte interactions on chondrocyte mineralization were examined over time. RESULTS: Co-culture of deep zone chondrocytes (DZCs) with surface zone chondrocytes (SZCs) suppressed the T3-induced increase in alkaline phosphatase (ALP) activity and related mineralization. Moreover, SZC-DZC co-culture was associated with a significantly higher parathyroid hormone-related peptide (PTHrP) expression when compared to controls. When PTHrP(1-40) was added to the DZC-only culture, it suppressed DZC ALP activity similar to the inhibition observed in co-culture with SZC. In addition, treatment with PTHrP reversed the effect of T3 stimulation on the expression of hypertrophic markers (Indian hedgehog, ALP, matrix metalloproteinases-13, Type X collagen) in the DZC cultures. Moreover, blocking the action of PTHrP significantly increased ALP activity in SZC+DZC co-culture. CONCLUSION: Our findings demonstrate the role of zonal chondrocyte interactions in regulating cell mineralization and provide a plausible mechanism for the post-natal regulation of articular cartilage matrix organization. These findings also have significant implications in understanding the pathology of articular cartilage as well as devising strategies for functional cartilage repair.


Asunto(s)
Fosfatasa Alcalina/metabolismo , Cartílago Articular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Proteína Relacionada con la Hormona Paratiroidea/farmacología , Triyodotironina/farmacología , Animales , Cartílago Articular/metabolismo , Bovinos , Condrocitos/metabolismo , Técnicas de Cocultivo , Colágeno Tipo X/metabolismo , Proteínas Hedgehog/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Proteína Relacionada con la Hormona Paratiroidea/metabolismo
6.
Singapore Med J ; 41(3): 111-3, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11063193

RESUMEN

UNLABELLED: Genital Chlamydia trachomatis infection has long been recognised as the major cause of pelvic disease and subsequently infertility. The diagnosis of this infection has traditionally relied on tissue culture. The availability of DNA amplification methods like ligase chain reaction promises faster and more sensitive results. This study was conducted to evaluate the prevalence of chlamydial infection in a subfertile population subgroup. AIM: A case control longitudinal study of 100 subfertile women in a tertiary teaching hospital were analyzed for the prevalence of genital Chlamydia trachomatis infection using ligase chain reaction test kit. RESULTS: A prevalence rate of 8% was detected, the majority being 25 years old or less (33.3%), p = 0.007. All patients gave no prior history of abnormal PAP smears, hospitalisation for pelvic inflammatory disease or abnormal vaginal discharge at the time of investigation. CONCLUSION: Our infertile group of patients has a relatively high incidence of silent genital Chlamydia trachomatis infection. This being highest in the below 25 years old age group. This finding indicates that screening for chlamydia may be necessary for the subfertile couple presenting to clinic. This is especially so if the patient is of the younger age group.


Asunto(s)
Infecciones por Chlamydia/diagnóstico , Chlamydia trachomatis/aislamiento & purificación , Enfermedades de los Genitales Femeninos/diagnóstico , Infertilidad Femenina/complicaciones , Adulto , Infecciones por Chlamydia/complicaciones , Femenino , Enfermedades de los Genitales Femeninos/complicaciones , Humanos , Reacción en Cadena de la Ligasa , Embarazo
7.
Singapore Med J ; 41(1): 29-31, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10783677

RESUMEN

AIM OF STUDY: The aim was to analyse the pregnancy outcome among girls, aged 17 and below, at KK Hospital. METHODOLOGY: This is a retrospective study. A total of 108 adolescent pregnancies were analysed with regards to pregnancy order, antenatal complications, mode of delivery and pregnancy outcome. RESULTS: The 2 most common antenatal complications were anaemia and preterm labour. The repeat pregnancy rate was 15.7%. Vaginal delivery was achieved in 7.2%; 21.2% of babies born weighed less than 2.5 kg. CONCLUSIONS: Adolescent pregnancies accounted for only a small proportion of all deliveries in our hospital. Late or non-existent antenatal care was a feature in most pregnancies. The incidence of repeat pregnancies reflects the need for a more effective counselling on contraception.


Asunto(s)
Resultado del Embarazo , Embarazo en Adolescencia/estadística & datos numéricos , Adolescente , Peso al Nacer , Femenino , Humanos , Embarazo , Complicaciones del Embarazo/epidemiología , Estudios Retrospectivos , Singapur/epidemiología
8.
Ann Acad Med Singap ; 28(2): 260-5, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10497679

RESUMEN

Embryo cryopreservation is a vital part of any assisted conception programme. We analysed our experience with respect to various clinical factors which may influence success and help modify our own practice. Factors studied were endometrial preparation, number of embryos transferred, woman's age at embryo freezing and endometrial thickness. The 212 cycles analysed represented all our frozen embryo-transfers from 1994 to 1996. Four cycles were excluded because of incomplete data. Statistical analysis was done with Student's t-test, Fisher's exact test and chi-square test for trend. The clinical pregnancy rate rose yearly and it was 12.3% per transfer in 1996. The most important clinical factor appeared to be the type of endometrial preparation. Natural cycles resulted in a pregnancy rate of 17.7%, almost twice hormone-replacement cycles. When transfer was on days 14 to 16 of the natural cycle, the pregnancy rate reached 33%. Other factors that were suggestive of success were younger age at embryo freezing, transferring at least 2 embryos and endometrium thickness > or = 11 mm. The natural cycle gave the best pregnancy rate in our hands and is our method of choice for ovulatory women with normal cycle lengths. For all other women, hormonal preparation is needed but our protocols need refinement. Our initial performance is encouraging and embryo cryopreservation has certainly enhanced our overall success rate.


Asunto(s)
Criopreservación , Embrión de Mamíferos , Técnicas Reproductivas , Adulto , Factores de Edad , Distribución de Chi-Cuadrado , Transferencia de Embrión , Endometrio/anatomía & histología , Endometrio/efectos de los fármacos , Estradiol/análogos & derivados , Estradiol/uso terapéutico , Terapia de Reemplazo de Estrógeno , Estrógenos Conjugados (USP)/uso terapéutico , Femenino , Humanos , Fase Luteínica/efectos de los fármacos , Ciclo Menstrual/efectos de los fármacos , Ovulación , Inducción de la Ovulación , Embarazo , Progesterona/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
9.
Singapore Med J ; 40(12): 752-5, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10709427

RESUMEN

AIM OF STUDY: The aim of this prospective clinical trial was to determine if intranasal nafarelin acetate (NA) is as effective as leuprolide (LA), our standard GnRHa, in IVF cycles. In addition, we believe that this may be the first report of such a trial in an Asian IVF population. METHOD: Midluteal GnRHa administration (LA = 0.5 mg/d; NA = 800 micrograms/d) was used with a standardised hMG ovarian stimulation protocol for all 88 consecutive cycles, randomised at recruitment. RESULTS: There were no significant differences between LA and NA in terms of the mean duration of agonist to reach pituitary suppression, total hMG dosage, number of embryos produced or frozen and the clinical pregnancy rate (LA = 21.4% and NA = 16.3% per cycle). CONCLUSION: Intranasal nafarelin acetate was as effective as leuprolide acetate in our series of IVF patients of Asian origin, and may be offered as an alternative choice for pituitary suppression.


Asunto(s)
Fertilización In Vitro , Hormonas/farmacología , Nafarelina/farmacología , Hipófisis/efectos de los fármacos , Administración Intranasal , Adulto , Femenino , Fármacos para la Fertilidad Femenina/uso terapéutico , Hormonas/uso terapéutico , Humanos , Leuprolida/uso terapéutico , Nafarelina/uso terapéutico , Ovulación , Hipófisis/fisiología , Embarazo , Índice de Embarazo , Estudios Prospectivos , Singapur
10.
Singapore Med J ; 37(1): 66-8, 1996 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8783917

RESUMEN

The next step in the treatment of infertility after ovulation induction is usually in vitro fertilization (IVF) or some other sophisticated and expensive assisted reproductive technique. This study looks at the method of superovulation-intrauterine insemination (SO-IUI) as an alternative before IVF in the treatment of infertility. The first 7 months of this programme were reviewed. There was a clinical pregnancy rate of 20.5% per patient. Ninety-six percent of the pregnancies occurred in the first two cycles. The cycle-cancellation rate was 5.1%. The highest success was in couples with ovulatory disorders, endometriosis and cervical factor infertility. The study suggested that SO-IUI is a cheaper and effective additional tool in the treatment of some infertility disorders before proceeding to IVF or other sophisticated techniques.


Asunto(s)
Infertilidad/terapia , Inseminación Artificial , Superovulación , Adulto , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Embarazo , Resultado del Embarazo , Estudios Retrospectivos
11.
Surgery ; 118(2): 212-9, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7638736

RESUMEN

BACKGROUND: The induction of specific tolerance could prevent acute and chronic rejection, as well as immunosuppressive complications, in recipients of vascularized organ allografts. Mixed hematopoietic chimerism is one approach to allogeneic tolerance. In these studies we examined whether mixed chimerism can confer tolerance to heart allografts across major and minor histocompatiblity barriers. We also examined the transcription of cytokine genes within the allografts of tolerance animals and in cell culture. METHODS: Adult Lewis rats were lethally irradiated and reconstituted with a mixture of 50 x 10(6) T-cell depleted bone marrow cells. Chimeric animals received heterotopic donor strain and third-party heart allografts and were assessed daily for rejection. Another set of chimeras received heart allografts that were examined at varying time points for transcription of cytokine genes by reverse-transcriptase polymerase chain reaction. RESULTS: Median graft survival in control animals was 6 days. Graft survival in 11 mixed chimeras ranged from more than 165 to more than 274 days (p < 0.001), and no episode of rejection or graft-versus-host disease was observed. Examination of cytokine transcriptions revealed dramatic alterations in interleukin-4 transcription in vivo and in vitro. CONCLUSIONS: Alterations in cytokine gene transcription are descriptive of tolerance in this model. Mixed chimerism confers long-term unresponsiveness to heart allografts across major and minor histocompatibility barriers with desirable features for clinical application.


Asunto(s)
Quimera , Hematopoyesis , Tolerancia Inmunológica , Interleucina-4/metabolismo , Animales , Trasplante de Médula Ósea , Citocinas/genética , Supervivencia de Injerto , Interleucina-4/genética , Masculino , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Ratas Sprague-Dawley , Transcripción Genética
12.
Singapore Med J ; 36(1): 63-7, 1995 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7570139

RESUMEN

OBJECTIVE: The purpose of this study was to determine the incidence, presentation, management and outcome of uterine perforation during elective first trimester abortions. METHODS: We conducted a retrospective study of 40 patients, including 2 transferred patients, who sustained uterine perforation during elective abortions from January 1980 to December 1992. RESULTS: The incidence of uterine perforation was 0.8 per 1,000 procedures (0.08%). There were 8 (20%) nulliparae and 3 (7.5%) grand multigravidae. 82.5% of the cases occurred when the abortion was performed by medical officers or junior registrars under training. The commonest perforating instrument was the suction cannula (25%) followed by the uterine sound (22.5%) and the dilator (20%). Three (7.5%) cases were treated conservatively, 33 (82.5%) cases underwent emergency operation, 2 (5%) cases were discovered during subsequent sterilisation, and 2 (5%) cases suffered undiagnosed perforation and were re-admitted for emergency surgery. Morbidity included post operative fever (12.5%), bowel injury (7.5%), retained conceptus (5%) and wound breakdown (2.5%). There was no mortality. CONCLUSION: A careful assessment of the uterine size and position, vigilance in the use of uterine sound and dilators, greater care in the use of suction cannula, and experience in vacuum aspiration will decrease the incidence of uterine perforation during elective abortions. A high degree of suspicion, early diagnosis and treatment will prevent the potential complications that may arise from uterine perforation.


Asunto(s)
Aborto Inducido/efectos adversos , Perforación Uterina/etiología , Aborto Inducido/métodos , Adulto , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Morbilidad , Embarazo , Primer Trimestre del Embarazo , Estudios Retrospectivos , Singapur/epidemiología , Perforación Uterina/epidemiología , Perforación Uterina/terapia
13.
Transplantation ; 59(2): 282-8, 1995 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-7839452

RESUMEN

Chronic rejection is a major cause of graft failure in solid organ transplants after the first year. A characteristic lesion in a variety of chronically rejecting organs is a fibrointimal proliferative arteriosclerosis. It has been speculated that approaches to tolerance induction may be effective in obviating not only acute, but also chronic, rejection. A picture of chronic rejection develops naturally in heart grafts transplanted from the Lewis-to-F-344 strain of rat. We examined whether tolerance induction by bone marrow transplantation and development of hematopoietic chimerism or tolerance induction by intrathymic inoculation of alloantigen could effectively prevent chronic rejection in an established model of chronic rejection. Bone marrow chimeras were developed in F-344 hosts by transplantation of T cell-depleted allogeneic marrow (TCD A BMT). Another set of F-344 hosts was inoculated with intrathymic allogeneic bone marrow cells. Heart grafts in these animals demonstrated tolerance for 120 days after transplantation. Control F-344 animals treated with a short course of cyclosporine consistently developed chronic rejection by 120 days following heart transplantation. Strikingly absent from the tolerant animals was any sign of graft arteriosclerosis, which was demonstrated in the vast majority of control animals. Analysis of cytokine mRNA profiles at 30 days following heart transplantation demonstrated differences between control and tolerant animals. These results suggest that tolerance induction can effectively prevent chronic rejection.


Asunto(s)
Arteriosclerosis/prevención & control , Rechazo de Injerto/prevención & control , Quimera por Trasplante/inmunología , Animales , Arteriosclerosis/etiología , Trasplante de Médula Ósea/inmunología , Enfermedad Crónica , Vasos Coronarios/fisiología , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Rechazo de Injerto/complicaciones , Rechazo de Injerto/inmunología , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/inmunología , Tolerancia Inmunológica , Isoantígenos/inmunología , Masculino , Miocardio/patología , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas Lew , Ratas Sprague-Dawley , Linfocitos T/inmunología
14.
Surgery ; 116(2): 222-8, 1994 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8047988

RESUMEN

BACKGROUND: The induction of specific tolerance would greatly improve survival and functional state of organ transplant recipients. One approach that has recently received attention is the creation of mixed hematopoietic chimerism through the transplantation of allogeneic and syngeneic T-cell-depleted (TCD) bone marrows. In these studies we examined whether tolerance to highly immunogenic small-bowel transplants could be induced by mixed allogeneic chimerism. Tolerance induction depends on the sharing of antigens between bone marrow cells and small-bowel tissue. METHODS: Adult Lewis rats were lethally irradiated and reconstituted with a mixture of 50 x 10(6) TCD bone marrow cells. Thirty days after reconstitution, animals were tested for chimerism by fluorescence-activated cell sorter analysis. Chimeric animals then received ACI heterotopic small-bowel allografts and were assessed daily for rejection. Small-bowel allograft survival was compared to three control groups: (1) untreated Lewis recipients, (2) irradiated TCD syngeneically reconstituted Lewis recipients, and (3) Lewis bone marrow recipients that did not develop chimerism. RESULTS: Median graft survival in control groups was 8 days. Graft survival in eight mixed chimeras ranged from more than 135 to more than 304 days (p < 0.0001), and no episode of rejection or graft-versus-host disease was observed. Mixed lymphocyte reactivity of chimeric lymphocytes confirmed in vivo observation of tolerance. CONCLUSIONS: Bone marrow cells share tissue-specific antigens with small-bowel cells to permit induction of tolerance.


Asunto(s)
Tolerancia Inmunológica , Intestino Delgado/trasplante , Animales , Quimera , Enfermedad Injerto contra Huésped/etiología , Intestino Delgado/patología , Depleción Linfocítica , Masculino , Ratas , Ratas Endogámicas ACI , Ratas Endogámicas BN , Ratas Sprague-Dawley , Trasplante Homólogo
15.
Bone Marrow Transplant ; 14(1): 137-45, 1994 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-7951101

RESUMEN

We describe the recipient of a marrow graft from an HLA-serologically identical unrelated donor from whom highly potent host-reactive CTL of donor origin were isolated in association with acute GVHD. Extensive sequence and biochemical analysis of the HLA complex of this donor and recipient revealed several disparities in class I and class II HLA with the potential to be recognized by T cells from the donor or the host. The donor-derived CTL exclusively recognized a class I HLA difference associated with HLA-B44. Nucleotide sequencing of donor and recipient cells revealed that the patient possessed the HLA-B*4402 allele recognized by IEF as B44.2 while the donor possessed HLA-B*4403 (IEF variant B44.1). These alleles differ at one amino acid residue located at position 156 in the alpha 2 domain. The donor-derived CTL were shown to be specific for B44.2 by blocking studies and by the lysis of five different B44.2+ unrelated cell lines, two of which were confirmed by sequencing to be homozygous for B*4402. A host-specific difference involving a HLA-DRB1 allele was not recognized by the CTL, neither did HLA differences unique to the donor HLA-B*4403 and HLA-DQ8 elicit a host response. These data show that certain HLA disparities may be tolerated at the same time that other disparities elicit a potent immunologic response. The chemical nature of the difference, its structural impact, as well as the conditions of transplant appear to influence the type of response which occurs.


Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Antígenos HLA-B , Linfocitos T Citotóxicos/inmunología , Enfermedad Aguda , Adulto , Alelos , Secuencia de Bases , Trasplante de Médula Ósea/inmunología , Pruebas Inmunológicas de Citotoxicidad , Cartilla de ADN/genética , Enfermedad Injerto contra Huésped/inmunología , Antígenos HLA-B/genética , Antígeno HLA-B44 , Prueba de Histocompatibilidad , Humanos , Leucemia Mieloide de Fase Acelerada/genética , Leucemia Mieloide de Fase Acelerada/inmunología , Leucemia Mieloide de Fase Acelerada/terapia , Masculino , Datos de Secuencia Molecular , Donantes de Tejidos , Trasplante Homólogo
17.
Bone Marrow Transplant ; 12(3): 289-95, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8241989

RESUMEN

The mechanism by which GVHD augments the graft-versus-leukemia (GVL) effect of marrow transplants has not been ascertained. One possibility involves the secondary activation of natural killer (NK) cells by cytokines released during the GVHD process. To evaluate this possibility we have compared NK activity and lymphokine-activated killer cell precursor (LAKp) frequencies in serially sampled PBMC from recipients of unmanipulated autologous or allogeneic marrow with and without active GVHD. NK activity recovered rapidly after BMT and was elevated during episodes of acute GVHD. However, NK activity did not differ between recipients of autologous or allogeneic marrow without GVHD nor was NK activity increased in association with chronic GVHD. Endogenously-activated NK cells were detected only in recipients of allogeneic marrow but this did not correlate with GVHD status. In contrast to NK activity, LAKp frequencies fell below the control range during the first 8 weeks after BMT. By 9-14 weeks the median LAKp frequency was normal and did not differ between the three groups then or later after transplant. We conclude that acute GVHD may serve to increase the lytic activity of NK cells but does not result in increased LAKp. LAKp frequencies are below normal during the first two months after BMT, a finding not previously recognized from bulk culture LAK studies. The role of LAK effectors in GVL may involve more the degree of cellular activation rather than the number of cells activated.


Asunto(s)
Trasplante de Médula Ósea/inmunología , Enfermedad Injerto contra Huésped/inmunología , Células Asesinas Activadas por Linfocinas/inmunología , Células Asesinas Naturales/inmunología , Enfermedad Aguda , Anemia Aplásica/inmunología , Anemia Aplásica/cirugía , Trasplante de Médula Ósea/efectos adversos , Humanos , Leucemia/inmunología , Leucemia/cirugía , Linfoma/inmunología , Linfoma/cirugía , Mieloma Múltiple/inmunología , Mieloma Múltiple/cirugía , Recurrencia
19.
J Singapore Paediatr Soc ; 31(1-2): 90-2, 1989.
Artículo en Inglés | MEDLINE | ID: mdl-2528027

RESUMEN

Hydrops fetalis is an unusual manifestation of Down's syndrome and diagnosis of Down's syndrome in the hydropic newborn can be difficult as the clinical signs are masked by severe oedema. The baby may also be seriously ill and die soon after birth, before any investigative procedures could be done. Down's syndrome should be considered in foetuses or babies presented with pleural effusion and/or ascites.


Asunto(s)
Quilotórax/complicaciones , Síndrome de Down/complicaciones , Hidropesía Fetal/complicaciones , Femenino , Humanos , Recién Nacido , Derrame Pleural/etiología , Embarazo
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