Search PubMed⌕ Search

Biomedical subjects

S Todo

Publications and source records attributed to S Todo.

At least 109 records · Page 6Linked to original sources
PubMed1998

Anatomic variability of rejection in intestinal allografts after pediatric intestinal transplantation.

BACKGROUND: Rejection of the allograft is a major contributor to morbidity and mortality in children who undergo a small intestinal transplant. Operational definitions for histologic rejection have been established, but little is known about the anatomic variability of the histologic abnormalities. STUDY DESIGN: Biopsy reports were reviewed retrospectively from more than 1200 endoscopies performed on the 41 children who received intestinal transplantation between 1990 and 1995. RESULTS: Biopsies were performed in the proximal jejunum and distal ileum allograft simultaneously on 248 occasions. In 168 biopsies, neither site was histologically abnormal; in 80, rejection was found. In 42, both regions were abnormal; however, in 17 only the jejunum was involved and in 21 the rejection exclusively involved the ileum. Among children whose allograft included colon, rejection was absent in colon and ileum in 34 biopsies, involved both in 6, involved ileum but not colon in another 6 and involved colon but not ileum in only one. When the allograft included stomach, rejection was absent in the stomach and jejunum 39 times, involved both sites 8 times, involved jejunum and not the stomach 10 times, but involved the stomach and not jejunum only once. Endoscopic appearance correctly predicted histologic rejection 63% of the time. CONCLUSION: Anatomic variability may exist in the rejection process. Sampling the jejunum and ileum seems to have similar sensitivity in detecting rejection, whereas sampling stomach and the colon is less sensitive. When allograft rejection is suspected on clinical grounds, sampling more than one area of the graft may be necessary for histologic confirmation.

Adolescent↗
PubMed1998

Endoscopies in pediatric small intestinal transplant recipients: five years experience.

OBJECTIVE: Intestinal transplantation has become an option as a treatment for permanent intestinal failure. Endoscopy is an essential tool in assessing the intestinal allograft after intestinal transplantation. The aim of this study was to analyze our experience using endoscopy in intestinal transplant recipients. METHODS: This was a retrospective review of endoscopic and histological reports in 41 children who received an intestinal transplant between 1990 and 1995 at Children's Hospital of Pittsburgh. RESULTS: A total of 1273 endoscopies was performed of which 760 were ileoscopies via allograft ileostomy, 273 were upper endoscopies, and 240 were colonoscopies. One hundred four rejection episodes were documented histologically in 32 patients, 6 days to >4 yr after transplantation. Most episodes were mild and easily treated with increased immunosuppression; however, severe rejection with mucosal exfoliation was seen in nine patients. Rejection sometimes involved only part of the allograft. Endoscopic appearance alone without biopsies was sensitive enough to diagnose only 63% of the rejection episodes. Epstein-Barr and cytomegalovirus infections occurred in 11 and eight patients, respectively, and involved both native bowel and allograft in some. Complications of endoscopy were few: one perforation, three episodes of bleeding, and three episodes of transient respiratory compromise. CONCLUSIONS: Endoscopy is an essential tool in the postoperative assessment of intestinal transplant recipients. Frequent surveillance ileoscopies with biopsies should be performed after transplantation. If patients clinically deteriorate with fever, diarrhea, bacteremia, or gastrointestinal bleeding and a clear cause is not elucidated by ileoscopy, an upper endoscopy with biopsies is indicated.

Adolescent↗
PubMed1998

Extrinsic intestinal reinnervation after canine small bowel autotransplantation.

BACKGROUND: The process of extrinsic reinnervation after small bowel transplantation is poorly understood. METHODS: Jejunal and ileal specimens, obtained from the dogs that underwent intestinal autotransplantation by an end-to end (E-E) or end-to-side arterial reconstruction, were analyzed at 1 (n = 7), 3 (n = 6), 6 (n = 6), 12 (n = 6), or 24 (n = 2) months and compared with control specimens (n = 7). Tissue catecholamine levels and indirect immunohistochemistry results for extrinsic neuropeptides, calcitonin gene-related peptide, neuropeptide Y, substance P, and tyrosine hydroxylase (TH) were examined. RESULTS: Catecholamine levels in the grafts were undetectable until 6 months but increased significantly after 12 months, particularly in the E-E group. Immunohistochemistry results showed no significant indication of extrinsic reinnervation until 12 months, when TH fibers were observed in five of six dogs. The E-E group revealed some TH fibers extending across the arterial anastomosis toward the graft mesentery. Examination of the intestinal anastomosis at 12 months showed abundant peptidergic and TH extrinsic fibers in the host side, whereas there were few or none on the graft side. CONCLUSIONS: These results suggest that extrinsic reinnervation of the graft intestinal wall does occur but requires a prolonged period, and the major route of extrinsic reinnervation is along the arterial axis of the intestinal graft, not beyond the enteric anastomosis.

Animals↗
PubMed1998

[TNM classification--pediatric tumors].

The clinical and postsurgical TNM classifications (cTNM and pTNM) for neuroblastoma (NB), nephroblastoma (WT) and soft tissue sarcomas were presented in 1982 by the TNM Committee in UICC in collaboration with SIOP. The Japanese TNM Committee proposed new pTNM systems (J-pTNM) for NB and WT, and new cTNM and pTNM system for primary liver carcinoma in infants and children (HT). These pTNMs were based on the staging systems developed by the Malignant Tumor Committee of the Japanese Society of Pediatric Surgeons. The proposal of subdivision of M category in NB was presented for testing the new telescopic ramifications of TNM. The TNM for HT was added as a new classification recommended for testing. The effectiveness of these TNM systems was assessed using NB, WT and hepatoblastoma (HB) cases which were registered in collaborating institutes. The analyses suggested that pTNM, especially the J-pTNM system in NB, WT and HT were effective for the assessment of prognoses, although cTNM systems were not enough to assess the extent of the disease.

Child↗
PubMed1998

[Post-transplant EBV-associated lymphoproliferative disorders--report of two cases].

We report two cases of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) after allogenic bone marrow transplantation which were conditioned with regimens including antithymocyte globulin (ATG). The first case was a 31 year-old man which severe aplastic anemia who was transplanted from HLA-matched unrelated donor conditioned with total lymphoid irradiation (TLI)/ cyclophosphamide/ATG and prophylactic administration of ganciclovir Grade I acute GVHD improved in response to cyclosporine (CsA). LPD as a polyclonal epipharyngeal mass developed at day +53 and spontaneously regressed along with the withdrawal of CsA. Second case was a 11 year-old boy with acute myelomonocytic leukemia (FAB:M4E). He was transplanted from HLA B locus mismatched mother conditioned with total body irradiation (TBI)/busulfan/L-PAM/ATG. He showed grade IV acute GVHD, which was controlled by steroids and FK-506. LPD as a monoclonal intestinal lymphoma was diagnosed at day +82, and he was unsuccessfully treated with ganciclovir, acyclovir, chemotherapy and transfusions of EBV-specific cytotoxic lymphocytes in addition to discontinuation of immunosuppressants, and died at day +18 due to sepsis and multiple cerebral infarction. Early detection and introduction of appropriate treatment for post bone marrow transplantation LPD is necessary.

Adult↗
PubMed1998

Mutational analysis of the p73 gene localized at chromosome 1p36.3 in colorectal carcinomas.

Genetic alteration of p53, which monitors DNA damage and operates cellular checkpoints, is a major factor in the development of human colorectal carcinoma (CRC). Recently, p73, a novel family member of p53, has been identified and found, like p53, to activate p21Waf1/Cip1 and to induce apoptosis. The p73 gene was mapped at chromosome 1p36.3 which is a region frequently deleted in CRCs and other cancers including neuroblastoma. To assess whether or not p73 is a tumor suppressor gene of CRC, we performed mutational analysis of p73 in 82 colorectal tumor tissues paired with constitutional DNA. Using a microsatellite marker for p73, the loss of heterozygosity (LOH) study was performed and allelic loss of p73 was found in 17% of the CRCs. RT-PCR single strand conformation polymorphism analysis showed no mutation except three polymorphisms in the p73 coding region. In addition, p73 was expressed at higher levels in the CRC tissues than in the normal mucosa or neuroblastoma tissues, though the transcripts were detectable only by the RT-PCR method. Our results suggest that, in CRCs, p73 may not play a role as a tumor suppressor, at least not in a classic Knudson manner.

Adolescent↗
PubMed1998

[Comparison of crossing-over between 30-minute drip infusion vs 30-second injection of granisetron for nausea and vomitting with cisplatin].

Recently, Granisetron (KYT) was proved to have a strong effect for cisplatin (CDDP)-induced emesis. We compared the effect of KYT for CDDP-induced emesis between two different administration schedules. Forty micrograms/kg of KYT was administered either by 30-minute drip infusion with 100 ml of saline (Group A) or 30-second injection with 10 ml of saline (Group B). We investigated the therapeutic effect of KYT in both group A and Group B by the crossing-over method. After the patients who had a malignant tumor and were going to receive CDDP (over 50 mg/m2) in two courses were selected, KYT was administered by the method of Group A or Group B in a double-blind comparison. The clinical efficacy was at least "effective" in 70% (7/10) of Group A and Group B. The study treatment was considered "useful" in 80% (8/10) of Group A, 90% (9/10) of Group B, and "safe" in 100% of Group A and B. There was no difference between two groups in this respect. The results showed that the slow intravenous injection of KYT also has an excellent antiemetic effect on CDDP-induced emesis and a high degree of safety.

Adult↗
PubMed1998

Involvement of macrophage migration inhibitory factor (MIF) in the mechanism of tumor cell growth.

BACKGROUND: Macrophage migration inhibitory factor (MIF) was recently rediscovered as a cytokine, pituitary hormone, and glucocorticoid-induced immunomodulator. MIF is constitutively expressed in various cells and enhances production of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1, and interferon gamma. Recently, it was reported that MIF mRNA was overexpressed in prostatic tumors, which suggests that MIF is a protein involved in tumor cell growth beyond inflammatory and immune responses. MATERIALS AND METHODS: We examined the expression of MIF in the murine colon carcinoma cell line colon 26 by Western and Northern blot analyses and immunohistochemistry. Next, we investigated the effects of transforming growth factor (TGF) beta, basic fibroblast growth factor (b-FGF), and platelet-derived growth factor (PDGF) on the expression of MIF mRNA. Furthermore, we examined whether MIF is involved in tumor cell proliferation, using an MIF anti-sense plasmid transfection technique. RESULTS: We demonstrated that MIF protein and its mRNA were highly expressed in colon 26 cells, using Western and Northern blot analyses, respectively. By immunohistochemical analysis, we found that MIF was localized largely in the cytoplasm of the tumor cells. In response to TGF-beta, b-FGF, and PDGF, MIF mRNA expression was significantly up-regulated. Following this, we transfected the cells with an anti-sense MIF plasmid, which revealed that this treatment induced significant suppression of cell proliferation. CONCLUSION: Although MIF plays multifunctional roles in a broad spectrum of pathophysiological states, little has been done to investigate the role of this protein in association with tumor growth. The current results suggest the possibility that MIF induces tumor cell growth in concert with other growth factors, which encouraged us to investigate a novel approach for tumor therapy using an anti-MIF antibody and an MIF anti-sense plasmid transfection technique.

Animals↗
PubMed1997

The effect of small bowel transplantation on the morphology and physiology of intestinal muscle: a comparison of autografts versus allografts in dogs.

The effects of acute (AR) and chronic rejection (CR) on intestinal smooth muscle that are responsible for the dysmotility following small bowel transplantation (SBTX) are incompletely understood. Jejunal and ileal specimens from normal control dogs (n=7), and autotransplanted dogs were examined at 7 days (n=6) and 1 (n=7), 3 (n=6), 6 (n=6), and 12 months (n=6). Allotransplanted dogs that developed AR (n=8) and CR (n=5) were examined for gross and microscopic morphology (muscle thickness, the number and size of myocytes, and inflammatory infiltrate), and for contractile and intracellular electrical function in vitro. Auto-SBTX did not alter morphology at any period, but contractile function was impaired at 7 days (73.6%) compared with normal intestine. Acute rejection did not influence myocyte number or size, but was associated with a prominent infiltrate of neutrophils and lymphocytes, and severely impaired contractile function (20.6%) compared with auto-SBTX controls. Acute rejection also significantly inhibited the amplitude of slow waves and of inhibitory junction potentials. Chronic rejection caused thickening of muscularis propria by both hyperplasia (175.5%) and hypertrophy (202.6%) accompanied by moderate inflammatory cell infiltrate compared with auto-SBTX controls. We conclude that the marked inflammatory infiltrate into the muscularis propria indicates that the graft muscle is injured by both acute and chronic rejection; impaired function of intestinal smooth muscle following SBTX results from both rejection and the injury associated with transplantation, and chronic rejection following SBTX is associated with both hyperplasia and hypertrophy of the muscularis propria.

Analysis of Variance↗
PubMed1997

Comparison of various lazaroid compounds for protection against ischemic liver injury.

Lazaroids are a group of 21-aminosteroids that lack steroid action but have a potent cytoprotective effect by inhibiting iron-dependent lipid peroxidation. However, there have been conflicting reports on the effectiveness and potency of the various lazaroid compounds. In this study, we compared the effectiveness of three major lazaroids on warm liver ischemia in dogs using a 2-hr hepatic vascular exclusion model. The agents were given to the animals intravenously for 30 min before ischemia. The animals were divided into 5 groups: Control (n=10), no treatment; Group F (n=6), U-74006F (10 mg/kg); Group G (n=6), U-74389G (10 mg/kg); Group A1 (n=6), U-74500A (10 mg/kg); Group A2 (n=6), U-74500A (5 mg/kg). The effect of treatment was evaluated by two-week animal survival, hepatic tissue blood flow, liver function tests, blood and tissue biochemistry, and histological analyses. Animal survival in all treated groups was significantly improved compared with the control (83-100% versus 30%). Elevation of liver enzymes after reperfusion was markedly attenuated in treated groups, except for an early significant increase in Group G. Postreperfusion hepatic tissue blood flow was much higher in all treated animals (50% of the preischemic level vs. 25% in the control). Lazaroids, particularly U-74500A at 5 mg/kg (Group A2), suppressed adenine nucleotide degradation during ischemia and enhanced the resynthesis of high-energy phosphates after reperfusion. Although structural abnormalities in postreperfusion liver tissues were markedly ameliorated in all treated groups, Group A2 showed significantly less neutrophil infiltration. Liver injury from warm ischemia and reperfusion was attenuated with all lazaroid compounds, of which U-74500A at 5 mg/kg exhibited the most significant protective activity.

Animals↗
PubMed1997

Attenuation of ischemic liver injury by augmentation of endogenous adenosine.

Hepatic grafts from non-heartbeating donors may alleviate the organ shortage, but they inherently suffer from warm ischemia. In the present study, we tested our hypothesis that augmentation of endogenous adenosine by inhibition of nucleoside transport with R75231 attenuates ischemic liver injury. Adult female beagle dogs underwent 2-hr hepatic vascular exclusion with venovenous bypass. R75231 was given to the animals by continuous intravenous infusion for 30 min before ischemia at a dose of 0.1 mg/kg (Group 2, n=6), 0.05 mg/kg (Group 3, n=6), or 0.025 mg/kg (Group 4, n=6). Nontreated animals were used as the control (Group 1, n= 10). Animal survival, hepatic tissue blood flow, liver function, and histopathology were analyzed. Two-week animal survival was 30% in Group 1, 83% in Group 2, 100% in Group 3, and 100% in Group 4. Postreperfusion hepatic tissue blood flow was markedly improved by the treatment. Treatment significantly attenuated liver enzyme release, lipid peroxidation, and changes in adenine nucleotides and purine catabolites. Structural abnormality of the liver after reperfusion was markedly improved by R75231 treatment, showing better architecture and less neutrophil infiltration. Preischemic administration of a nucleoside transport inhibitor ameliorated ischemic liver injury due to the positive effects of augmented endogenous adenosine, and is applicable clinically when the liver is procured from a controlled non-heartbeating donor.

Adenosine↗
PubMed1997

Treatment of fibrolamellar hepatoma with subtotal hepatectomy or transplantation.

Fibrolamellar hepatoma (FL-HCC) is an uncommon variant of hepatocellular carcinoma (HCC), distinguished by histopathological features suggesting greater differentiation than conventional HCC. However, the optimal treatment and the prognosis of FL-HCC have been controversial. Follow-up studies are available from 1 year to 27 years, after 41 patients with FL-HCC were treated with partial hepatectomy (PHx) (28 patients) or liver transplantation (13 patients). In this retrospective study, the effect on outcome was determined for the pTNM stage and other prognostic factors routinely recorded at the time of surgery. Cumulative survival at 1, 3, 5, and 10 years was 97.6%, 72.3%, 66.2%, and 47.4%. Tumor-free survival at these times was 80.3%, 49.4%, 33%, and 29.3%. The TNM stage was significantly associated with tumor-free survival. Patients with positive nodes had a shorter tumor-free survival than those with negative nodes (P < .015). Patient survival was most adversely affected by the presence of vascular invasion (P < .05). FL-HCC is an indolently growing tumor of the liver, which usually was diagnosed in our patients at a stage too advanced for effective surgical treatment of most conventional HCC. Nevertheless, long-term survival frequently was achieved with aggressive surgical treatment. When a subtotal hepatectomy could not be performed, total hepatectomy (THx) with liver transplantation was a valuable option.

Adolescent↗
PubMed1997

Internal hernia and volvulus of the small bowel following liver transplantation.

Internal herniation with volvulus of the small intestine is an uncommon, but potentially fatal, complication after liver transplantation. We present here four cases in which the herniation occurred around the Roux-en-Y loop used for the biliary reconstruction. One patient died due to intestinal and liver allograft necrosis; another lost almost the entire small intestine and has since undergone successful intestinal transplantation. Two patients survived following surgery that involved reduction of the hernia and closure of the mesenteric defect. Clinical diagnostic implications emphasize early diagnosis and appropriate operative intervention.

Adolescent↗
PubMed1997

Use of DNA amplification for diagnosis of cytomegalovirus enteritis after intestinal transplantation.

BACKGROUND & AIMS: Intestinal transplantation is a feasible therapy for patients with short-bowel syndrome. However, cytomegalovirus (CMV) enteritis can cause complications. The aim of this study was to investigate the value of polymerase chain reaction (PCR)-based detection methods for CMV in the management of patients with small bowel transplants. METHODS: Comparative evaluation of PCR with histopathology, shell-vial assay, and tube culture of intestinal biopsy specimens was used for the diagnosis of CMV enteritis in 21 patients. RESULTS: Ten patients experienced 21 episodes of CMV enteritis, diagnosed by histopathology, virology, or both. PCR had a sensitivity and specificity of 96% and 69%, respectively, compared with traditional methods, whereas the positive and negative predictive values were 35% and 99%, respectively. Three+ and 4+ signals corresponded to a specificity of 91% and positive predictive value of 59%, respectively. CMV was detected by PCR a median of 11 days (range, 0-32) earlier than other methods and lasted a median of 40 days (range, 21-80) in the 13 episodes, which became PCR-negative and in those patients who developed asymptomatic infection. In 8 episodes, CMV by PCR never became negative and was associated with a relapse of disease confirmed by other methods. CONCLUSIONS: PCR is a sensitive method for the early detection of CMV in intestinal biopsy specimens and can be used for preemptive therapy after intestinal transplantation.

Adult↗
PubMed1997

Hemophagocytic lymphohistiocytosis in infancy and childhood.

OBJECTIVE: The current status of hemophagocytic lymphohistiocytosis (HLH) in infants and children has been studied. STUDY DESIGN: Eighty-two cases of pediatric HLH, for which there was no confirmed familial inheritance, were comparatively studied between 36 patients less than 2 years of age and 46 patients more than 2 years of age. RESULTS: In all cases, persistent fever, cytopenia, liver dysfunction, and hepatosplenomegaly were the most frequently noted symptoms. Hyperferritinemia (> 1000 micrograms/L) and elevated blood levels of lactate dehydrogenase (> 1000 IU/L) were observed in 90% and 89.7%, respectively. These figures were considerably higher than for either hypertriglyceridemia (> 2 mmol/L) (50%) or hypofibrinogenemia (< 1.5 gm/L) (57.4%), indicating that increased serum ferritin and lactate dehydrogenase concentrations might be good diagnostic parameters for HLH. These parameters are nonspecific but are of follow-up and prognostic value in these HLH cases. No differences were found in clinical signs and symptoms or other laboratory findings for the two age groups. Immunochemotherapy was administered in the similar regimens to patients in both groups. Of the 82 patients, 13 (15.9%) succumbed to a fatal course within 2 months after diagnosis, and Kaplan-Meir analysis for all cases predicted the overall disease-free patient survival at 4 years from the onset of disease to be 57.2% (95% confidence interval (CI), 45.1% to 69.3%). There was a slightly, but not statistically significant, poorer prognosis for the younger patients: 44.2% (95% CI, 26.0% to 62.4%) survival for the infant group versus 67.2% (95% CI, 51.8% to 82.6%) survival for the older group (p = 0.0569). CONCLUSIONS: Refinement of the treatment is mandatory to improve the outcome of HLH in both infants and older pediatric patients.

Adolescent↗