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- In utero meconium exposure increases spinal cord necrosis in a rat model of myelomeningocelePublication . Correia-Pinto, J.; Reis, J.; Hutchins, G.; Baptista, M.; Estevão-Costa, J.; Flake, A.; Leite-Moreira, A.Abstract BACKGROUND/PURPOSE: The rationale for in utero repair of myelomeningocele has been supported experimentally by the observation of preserved neural function after prenatal closure of surgically created defects compared with nonrepaired controls. The mechanism of injury to the exposed neural elements is unknown. Postulated mechanisms include trauma to the herniated neural elements or progressive injury from amniotic fluid exposure as gestation proceeds. A component of amniotic fluid that may contribute to neural injury is meconium. In the current study the effect of human meconium on the exposed spinal cord in a fetal rat model of myelomeningocele was examined. METHODS: Twenty time-dated pregnant rats underwent laparotomy at 181/2 days of gestation. The exposed uterus was bathed in ritrodrine for tocolysis. The amniotic cavity was opened over the dorsal midline of the fetal rat, and, under a dissecting microscope (x25), a 2- to 3-level laminectomy was performed. Under magnification (x40), the translucent dura was opened using a 25-gauge needle as a knife. Two fetuses per dam were operated on. In the control group, the amniotic fluid was restored with saline solution, whereas in the experimental group a solution of Human meconium diluted (10%) in saline was used to restore the amniotic fluid. Fetuses were harvested by cesarean section at 211/2 days' gestational age. The liveborn pups were then killed and fixed in 10% formaline. Sections 10 micrometer thick were stained with H&E and studied by light microscopy for evidence of spinal cord injury. RESULTS: Seven of 20 (35%) experimental rat pups and 6 of 20 (30%) control rat pups were liveborn. All liveborn pups had severe paralysis of the hindlimbs and tail, so that functional differences between the 2 groups could not be detected. Histologic examination of 13 spinal cords at the site of surgical exposure showed that necrosis of neural tissue in 5 of 7 meconium-exposed rat pups was increased when compared with that observed in the 6 fetuses exposed to amniotic fluid without meconium. In general, inflammation was greater and repair processes appeared delayed in meconium-exposed rat pups. CONCLUSIONS: Exposure of the spinal cord of fetal rats to amniotic fluid by surgically created myelomeningocele leads to severe functional impairment. Histologically recognizable necrosis of neural elements was increased in those animals that were exposed to diluted human meconium in the amniotic fluid. The results support the hypothesis that meconium may contribute to the pathophysiology of spinal cord injury observed in myelomeningocele.
- Early gastric cancer: ten years of experiencePublication . NOGUEIRA, C.; SILVA, A.S.; SANTOS, J.N.; SILVA, A.G.; FERREIRA, J.; MATOS, E.; VILACA, H.World J Surg. 2002 Mar;26(3):330-4. Epub 2001 Dec 21. Early gastric cancer: ten years of experience. Nogueira C, Silva AS, Santos JN, Silva AG, Ferreira J, Matos E, Vilaça H. Surgery Department, Surgery 1, Hospital Geral de Santo António, Largo Prof. Abel Salazar, 4000 Oporto, Portugal. carlosnog2001@yahoo.com Abstract Gastric cancer is a disease in which the main treatment is surgical extirpation. The modifications introduced in the surgical treatment over the last decades were accompanied by a clear increase of survival, which reaches global values of 61% at 5 years in Japan. One of the reasons that contribute to this improvement is early diagnosis of the lesions. In the period between January 1, 1990 and December 31, 1999 662 patients with gastric adenocarcinoma were treated in the Service of Surgery 1 of our hospital; 110 were refused surgical treatment. Of the resected patients, 91 (21.4%) were classified as early gastric cancer according to the definition of the Japanese Society of Digestive Endoscopy. There were 30 women and 61 men, with a median age of 60.2 +/- 15 years; 3 patients had a preoperative diagnosis of gastric ulcer; 2 others were operated without recent histology; and 1 patient was urgently resected for a bleeding ulcer. In all the remaining patients biopsy confirmed the presence of cancer (89%) or serious dysplasia (4.6%). The lesions had been distributed essentially in the medium 1/3 (48.3%) and distal 1/3 of the stomach. Subtotal gastrectomy was accomplished in 48 patients, total gastrectomy in 40, total desgastrogastrectomy in 3, and in 9 patients the surgery involved the spleen (8 patients) and the spleen and tail of the pancreas in 1 patient. Lymphadenectomy was not performed in 5 patients, lymph nodes by the first lymph node barrier were removed in 25 patients and by the second barrier in 61 patients (67%). Median tumor size was 26 +/- 1.8 mm. The lesion reached the mucosa in 46 patients and the mucosa and submucosa in 45. In 6 patients the removed lymph nodes were microscopically invaded (6.7%). Five patients died (5.7%). The median follow-up of the patients is 41 +/- 26 months; 7 patients died (8.1%) during this period; 4 died unequivocally of disease progression. The median survival of patients was 85% at 5 years and 80% at 10 years. In our series, survival was affected by the presence of invaded lymph nodes, not by the penetration in depth of the lesion or the size of the tumor. PMID: 11865370 [PubMed - indexed for MEDLINE]
- Philadelphia‐positive T‐cell acute lymphoblastic leukemia with polymyositis, migratory polyarthritis and hypercalcemia following a chronic myeloid leukemiaPublication . LIMA, M.; COUTINHO, J.; BERNARDO, L.; DOS ANJOS TEIXEIRA, M.; CASAIS, C.; CANELHAS, A.; QUEIROS, L.; ORFAO, A.; JUSTICA, B.Ann Hematol. 2002 Mar;81(3):174-7. Epub 2002 Jan 31. Philadelphia-positive T-cell acute lymphoblastic leukemia with polymyositis, migratory polyarthritis and hypercalcemia following a chronic myeloid leukemia. Lima M, Coutinho J, Bernardo L, dos Anjos Teixeira M, Casais C, Canelhas A, Queirós L, Orfão A, Justiça B. Department of Clinical Hematology, Hospital Geral de Santo António, Rua D Manuel II, s/n, 4099-001 Porto, Portugal. mmc.lima@clix.pt Abstract Transformation of chronic myeloid leukemia (CML) often results in acute myeloblastic or, less frequently, in precursor B-cell acute lymphoblastic leukemia (ALL). T-cell blast crisis is rare. Hypercalcemia has also been described as a rare complication of CML, but this usually occurs as a terminal event. Here we report a case of a 35-year-old woman who developed a CD4(+)/CD8(+) T-cell ALL 2 years after the diagnosis of a typical Ph(+) CML. Polymyositis and polyarthritis preceded by 4 months, and symptomatic hypercalcemia occurred just before blastic transformation, probably representing paraneoplastic manifestations of the disease. PMID: 11904747 [PubMed - indexed for MEDLINE]
- Compared to mycophenolate mofetil, rapamycin induces significant changes on growth factors and growth factor receptors in the early days post‐kidney transplantationPublication . OLIVEIRA, J.G.; XAVIER, P.; SAMPAIO, S.M.; HENRIQUES, C.; TAVARES, I.; MENDES, A.A.; PESTANA, M.We found 1 article: Transplantation. 2002 Mar 27;73(6):915-20. Compared to mycophenolate mofetil, rapamycin induces significant changes on growth factors and growth factor receptors in the early days post-kidney transplantation. Oliveira JG, Xavier P, Sampaio SM, Henriques C, Tavares I, Mendes AA, Pestana M. Renal Department, Hospital S. João, Porto, Portugal. Abstract BACKGROUND: The new immunosuppressive drug Rapamycin (Rapa) is endowed with a mechanism of action that is distinct from that of calcineurin inhibitors. It has been claimed that Rapa does not significantly modulate either the cytokine expression or the transcription of several growth factors in mitogen-activated T cells. Previously, we reported that fine-needle aspiration biopsy (FNAB) sample cultures synthesize a large array of cytokines, and some of them may be powerful predictors of acute rejection in renal transplants. We hypothesized that Rapa may induce significant changes on cytokine production by FNAB sample cultures and on serum cytokine receptors when compared to other immunosuppressive drugs. METHODS: Kidney transplants treated with CsA-Rapa-Pred (Rapa group) were compared with transplants treated with CsA-mycophenolate mofetil-Pred (MMF group). They were studied on day 7 posttransplantation, and they remained rejection free for at least the first 6 months. FNAB samples were cultured and the supernatants were collected at 48 hr of incubation and analyzed by ELISA for interleukin 1 receptor antagonist (IL-1ra), IL-2, IL-6, IL-10, IL-18, monocyte chemotactic protein 1 (MCP-1), soluble tumor necrosis factor I, and transforming growth factor (TGF)-beta(1). The soluble receptors for IL-1, IL-2, IL-6, and tumor necrosis factor alpha, together with IL-2 and IL-18 were also measured in serum. RESULTS: Significant differences were observed when comparing Rapa with the MMF group. IL-18 and TGF-beta(1) synthesis were up-regulated, whereas IL-6 and MCP-1 were down-regulated in FNAB sample cultures. The Rapa group showed a significant down-regulation of each cytokine receptor and of IL-2 in serum. CONCLUSIONS: Rapa was associated with a decreased synthesis of primarily monocyte-derived cytokines and enhanced production of TGF-beta(1), which in an appropriate cytokine milieu may promote allograft tolerance. The down-regulation of cytokine receptors and IL-2 may be associated with a depressed immune response towards the kidney allograft. PMID: 11923692 [PubMed - indexed for MEDLINE]
- The "ex vivo" patterns of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA‐DR expression identify acute/early and chronic/late NK‐cell activation states.Publication . LIMA, M.; ALMEIDA, J.; DOS ANJOS TEIXEIRA, M.; QUEIROS, M.L.; JUSTICA, B.; ORFAO, A.Blood Cells Mol Dis. 2002 Mar-Apr;28(2):181-90. The "ex vivo" patterns of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR expression identify acute/early and chronic/late NK-cell activation states. Lima M, Almeida J, dos Anjos Teixeira M, Queirós ML, Justiça B, Orfão A. Service of Clinical Hematology, Hospital Geral de Santo António, Porto, Portugal. mmc.lima@clix.pt Abstract To define a dynamic sequence of phenotypic changes related to early and late phases of NK-cell activation, we have analyzed by four-color flow cytometry the immunophenotype of normal blood NK-cells from 12 healthy individuals and compared it with those from 15 patients with acute viral infections and 15 patients with either chronic infections or tumors. Although a great interindividual variability was found, nonstimulated CD56(+) NK-cells, present in normal blood samples, usually were CD2(-/+lo), CD7(+hi), HLA-DR(-), CD11b(+), CD38(+), CD11a(+hi), CD45RA(+hi), and CD45RO(-), the expression of CD11c and CD57 being heterogeneous and variable. Recently activated NK-cells, herein corresponding to NK-cells from patients with acute viral infections, displayed a pattern of expression of CD2/CD7 similar to that referred to above, but they typically showed higher levels of CD11a, CD38, and HLA-DR, as well as downregulation of CD11b and CD45RA, accompanied in some cases by coexpression of CD45RO; in addition, these NK-cells were CD11c(+) and CD57(-/+lo). Late-activated NK-cells, represented by NK-cells present in patients with chronic infections and tumors, converted into a CD2(+hi)/CD7(-/+lo) immunophenotype and expressed heterogeneously low levels of CD38 and CD11b; moreover, they were CD57(+) and CD11c(-/+). At this stage, most NK-cells had already reverted into their original CD45RA(+)/CD45RO(-)/HLA-DR(-) phenotype. In summary, we show that the patterns of expression of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR may help us to define the immunophenotypic profiles associated with early and late NK-cell activation phases in 'in vivo' models. PMID: 12064914 [PubMed - indexed for MEDLINE]