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S Todo

Publications and source records attributed to S Todo.

At least 199 records · Page 11Linked to original sources

Incidence and risk factors associated with the development of cytomegalovirus disease after intestinal transplantation.

From May 1990 to March 1993, 38 patients (21 adults and 17 children) received 40 allografts that included the small bowel (14 isolated small bowel, 21 small bowel and liver, and 5 multivisceral transplantations). Fifteen patients (39%) had 26 episodes of CMV disease: 7 with one episode, 6 with two, and 1 each with three and four. CMV enteritis accounted for 21 (81%) of the episodes, hepatitis and pneumonitis for 2 each, and a viral syndrome for 1. Cox's proportional hazards univariate and multivariate analyses showed that significant first-episode risk factors were: CMV seropositive donors for negative recipients (relative risk [RR], 3.86; P = 0.02), the average daily plasma trough level of tacrolimus (RR, 2.15; P = 0.04), and total amount of steroid boluses (RR, 2.90; P = 0.02). CMV disease recurrence factors were: CMV seronegative recipients (RR, 8.60; P = 0.02) and total amount of steroid bolus pulses (RR, 12.39; P = 0.004). Because long courses of ganciclovir prophylaxis could not prevent the development of CMV disease, avoidance of CMV seropositive grafts in seronegative recipients and new strategies to prevent heavy immunosuppression without the penalty of rejection will be necessary to ameliorate this problem in intestinal transplant recipients.

Adolescent↗

Serum and urine beta-2-microglobulin in hemophagocytic syndrome.

BACKGROUND: Previous reports suggesting a correlation between lymphoproliferative disease and serum levels of beta-2-microglobulin (beta-2M) and in vitro data indicating a role of cytokines in the production of beta-2M prompted a study of serum and urine beta-2M concentration in patients with hemophagocytic syndrome (HPS), because no data were previously available for HPS, a pathologic state associated with excessive cytokines secreted from activated reactive/malignant lymphocytes and histiocytes. METHODS: Serum and urine beta-2M levels were measured in six children with HPS during active and convalescent phase and in other diseases. RESULTS: Serum and urine beta-2M levels during active phase HPS were significantly high not only in serum (median, 7.5 mg/l; range, 2.3-16.0 mg/l; P < 0.01), but also in urine (median, > 31,650 micrograms/gram Creatinine (gCr); range, 8179-236,333 micrograms/gCr; P < 0.01), compared with levels during convalescent phase HPS (median, 2.0 mg/l; range, 0.9-2.5 mg/l in serum and median, 338 micrograms/gCr; range, 223-585 micrograms/gCr in urine) and in control subjects with diseases such as acute lymphocytic leukemia (median, 2.3 mg/l; range, 1.0-2.8 mg/l in serum and median, 327 micrograms/gCr; range, 48-2684 micrograms/gCr in urine), infectious mononucleosis (median, 2.9 mg/l; range, 2.5-5.5 mg/l in serum and median, 348 micrograms/gCr; range, 80-1325 micrograms/gCr in urine), and Kawasaki disease (median, 2.8 mg/l; range, 1.5-3.3 mg/l in serum and median, 1016 micrograms/gCr; range, 214-4500 micrograms/gCr in urine). Noteworthy was the observation that urine beta-2M levels correlated closely with HPS disease activity. CONCLUSIONS: Urine beta-2M appears to be a useful marker for assessing disease activity in patients with HPS.

Adolescent↗

Abdominal multivisceral transplantation.

Under FK506-based immunosuppression, 13 abdominal multivisceral transplantations were performed in 6 children and 7 adults. Of the 13 recipients, 7 (53.8%) are alive and well with functioning grafts after 9 to 31 months. Six recipients died: three from PTLD, one from rejection, one from sepsis, and one from respiratory failure. In addition to rejection, postoperative complications occurring in more than isolated cases included PTLD (n = 6), abdominal abscess formation (n = 5), pancreatitis (n = 3), and ampullary dysfunction (n = 2). In addition, infection by enteric microorganisms was common during the early postoperative period. Currently, all 7 survivors are on an oral diet and have normal liver function. Two recipients (one insulin-dependent) require antidiabetes treatment, in one case following distal pancreatectomy and in the other after two episodes of pancreatic rejection. Thus, abdominal multivisceral transplantation is a difficult but feasible operation that demands complex and prolonged posttransplantation management. It is not yet ready for application and awaits a better strategy of immune modulation.

Abdomen↗

Assessment of hepatic viability during cold ischemic preservation.

A reliable and easy method for assessing the viability of a cold ischemia-preserved donor liver prior to transplantation into the recepient is needed. Based on an earlier study, we hypothesized that liver free fatty acid (FFA) leakage into the preservation fluid may be a useful, atraumatic indicator of irreversible ischemic injury. The aim of the present study was to determine the time course and magnitude of liver FFA release into the preservation solution and its correlation with the duration of cold ischemic preservation compatible with survival after transplantation. Rat livers (n = 48) were flushed and preserved with University of Wisconsin (UW) solution at 4 degrees C for 0, 12, 24, and 48 h. Thereafter, half of the livers were analyzed for preservation fluid FFA (gas-liquid chromatography) and protein. The other half were perfused with Krebs-Henseleit (KH) solution at 37 degrees C for 1 h. Bile secretion and liver enzyme release (SGOT, SGPT, and LDH) were measured in addition to perfusate FFA and protein. Total FFA in the preservation fluid was 24 micrograms/g wet tissue after 12 h; it increased sharply 2.6-fold after 24 h and 3.7-fold after 48 h of preservation. Bile production was normal after 12 h of preservation but fell by 20% and 54% after 24 h and 48 h, respectively. LDH release rose from a value of 20 U/l at 0 time to 120 U/l and 260 U/l after 24 h and 48 h of preservation. These results suggest that liver viability declines sharply between 12 and 24 h of cold ischemic preservation, which corresponds with a sharp decrease in the 1-week survival from 100% to 33% after 12 h and 24 h, respectively, of cold ischemic preservation. We conclude that measuring FFA and LDH in the preservation solution of donor livers may be a useful means of assessing the quality of the cold-preserved liver before insertion into the recipient. We also speculate that a "threshold" FFA level in the UW preservation fluid indicating irreversible damage may be in the order of 35 micrograms total FFA/g liver. Studies on the clinical applicability of our findings are currently under way.

Adenosine↗

Acute pancreatitis after liver transplantation: incidence and contributing factors.

In order to assess the incidence and possible predisposing and contributing factors in the development of acute pancreatitis after liver transplantation, we reviewed the medical records of all 1832 adult patients who underwent 2161 orthotopic liver transplantation (OLTx) procedures in our center between January 1987 and September 1992. Of these patients, 55 (3% incidence) developed clinical pancreatitis and 247 (13.4% incidence) developed hyperamylasemia (biochemical pancratitis). Overall mortality in cases of clinical pancreatitis was 63.6%. The mortality in cases of hyperamylasemia was similar to that found in the general liver transplant population (i.e., 23%). A strong correlation was found between pancreatitis after liver transplantation and end-stage liver disease due to hepatitis B (30% of the cases, P = 0.00001). Extensive surgical dissection around the pancreas (P < 0.05), the type of biliary reconstruction following liver transplantation (P < 0.05), and the number of liver grafts received by the same patient (P = 0.00001) appeared to be possible contributing factors as did the duration of venovenous bypass and the quantity of IV calcium chloride administered intraoperatively.

Acute Disease↗

Orthotopic liver transplantation for ornithine transcarbamylase deficiency with hyperammonemic encephalopathy.

Ornithine transcarbamylase (OTC) deficiency is an X chromosome-linked disorder causing hyperammonemic encephalopathy with a very poor prognosis. We describe here two patients with OTC deficiency, one a late on-set female patient (case 1) and the other a neonatal-onset male patient (case 2), who were successfully treated with orthotopic liver transplantation (OLTx). The OTC activity in the excised liver was 10% and 0% of control, respectively. Hyperammonemic encephalopathy was controlled with medical therapy in case 1 until the of 5 years, but the complicated course in case 2 in which hyperammonemia required peritoneal dialysis and hemodialysis in the neonatal period necessitated OLTx with a reduced-size liver at the age of 80 days. Both patients had restoration of serum ammonia level to normal in 2 and 3 days after liver replacement, and both patients have normal neurological and developmental status after 2 and 0.5 years of postoperative follow-up. These cases illustrate not only the metabolic cure of this disorder, but also the need to preserve neurological integrity by aggressive medical management of the hyperammonemia preoperatively and early surgical intervention when indicated, even if this is required very early in life.

Ammonia↗

Amelioration of intestinal dysmotility and stasis by octreotide early after small-bowel autotransplantation in dogs.

BACKGROUND: Intestinal dysmotility and stasis after intestinal transplantation are considered to promote bacterial overgrowth and translocation. Two prokinetic agents, KW5139 (13-leu-motilin) and the somatostatin analogue octreotide acetate, were studied to determine whether they can ameliorate intestinal dysmotility during the early postoperative period. MATERIALS AND METHODS: Motility was recorded by multiple extraluminal strain-gauge transducers in 6 dogs on postoperative days 1, 3, 7, and 14. A barium meal study was performed with a separate group of 8 dogs on postoperative days 3 and 7. RESULTS: The agent KW5139 induced brief, weak contractions in the graft and had little effect on the dilated bowel; however, octreotide induced motor activity that propelled accumulated intestinal contents into the colon and reduced dilation of the transplanted bowel. CONCLUSION: Octreotide, but not KW5139, ameliorates intestinal dysmotility associated with bowel autotransplantation during the early postoperative period. Short-term administration of octreotide may be useful for the treatment of dysmotility following intestinal transplantation.

Animals↗

Endorectal pull-through of transplanted colon as part of intestinal transplantation.

BACKGROUND: Two children with life-threatening disorders underwent intestinal transplantation; one multivisceral transplantation excluding the liver, and the second transplantation of the liver, small bowel, and colon. METHODS: Involvement of the native rectum necessitated resection and replacement with the transplanted allograft. To prevent a permanent colostomy, a pull-through of the allograft colon was performed. RESULTS: Both patients had a stormy early postoperative course, mainly because of the complexities of intestinal transplantation, but with eventual recovery, including improvement of rectal function. CONCLUSIONS: These are the first two known cases in which a transplanted large intestine was used for a pull-through procedure.

Colon↗

Outcome analysis of 71 clinical intestinal transplantations.

OBJECTIVE: The aim of the study was to determine risk factors associated with graft failure and mortality after transplantation of the intestine alone or as part of an organ complex. SUMMARY BACKGROUND DATA: Even with modern immunosuppressive therapies, clinical intestinal transplantation remains a difficult and unreliable procedure. Causes for this and solutions are needed. METHODS: Between May 1990 and February 1995, 71 intestinal transplantations were performed in 66 patients using tacrolimus and low-dose steroids. The first 63 patients, all but one treated 1 to 5 years ago, received either isolated grafts (n = 22), liver and intestinal grafts (n = 30), or multivisceral grafts (n = 11). Three more recipients of allografts who recently underwent surgery and one undergoing retransplantation were given unaltered donor bone marrow cells perioperatively as a biologic adjuvant. RESULTS: Of the first 63 recipients, 32 are alive: 28 have functioning primary grafts and 4 have resumed total parenteral nutrition after graft enterectomy. Thirty-five primary grafts were lost to technical and management errors (n = 10), rejection (n = 6), and infection (n = 19). Regression analysis revealed that duration of surgery, positive donor cytomegalovirus (CMV) serology, inclusion of graft colon, OKT3 use, steroid recycle, and high tacrolimus blood levels contributed to graft loss. All four intestine and bone marrow recipients are alive for 2-3 months without evidence of graft-versus-host disease. CONCLUSION: To improve outcome after intestinal transplantation with previous management protocols, it will be necessary to avoid predictably difficult patients, CMV seropositive donors, and inclusion of the graft colon. Bone marrow transplantation may further improve outcome by ameliorating the biologic barriers of rejection and infection and allowing less restrictive selection criteria.

Adult↗

Myelodysplasia and acute myeloid leukaemia in cases of aplastic anaemia and congenital neutropenia following G-CSF administration.

Myelodysplasia and acute myeloid leukaemia (MDS/AML) developed in three cases of severe aplastic anaemia (SAA) and one case of congenital neutropenia (CN, Kostmann's disease) who received recombinant human granulocyte colony-stimulating factor (G-CSF) are reported. In these four MDS/AML cases, age at diagnosis of SAA/CN was 0-13 years, the cumulative dose of G-CSF was 98 micrograms/kg to 10 mg/kg over 1-57 months, and the interval from initiation of G-CSF to MDS/AML was 25, 23, 31 and 57 months, respectively. These results suggest a link between SAA/CN and MDS/AML in relation to G-CSF administration; however, large studies are necessary to determine if such a risk is significant in patients with SAA/CN who are treated with G-CSF.

Adolescent↗

Comparison of warm and cold ischemia of the canine small intestine.

Warm and cold ischemia-reperfusion injuries to canine small intestine was compared. In the warm ischemic model, the superior mesenteric artery of mongrel dogs was clamped for 2 h and then released (group A). As a cold ischemia model, canine small intestines were harvested with cold lactated Ringer solution, preserved for 24 h in cold LR solution and then autotransplanted (group B). After ischemia and during reperfusion, activities of maltase (MAL), myeloperoxides (MPO), xanthine dehydrogenase (XD) and xanthine oxidase (XO) were measured as well as hypoxanthine (HX) concentration. MAL activities were not changed during warm or cold ischemia, whereas it was remarkably decreased after revascularization in both the groups. Neutrophil infiltration after reperfusion was shown by the increase of MPO activities to 8 and 1.5 U/mg protein in groups A and B respectively from a normal value of 0.35 U/mg protein. During warm ischemia, %XO (XO/XD + XO) was increased from 18.4 to 84.9% for 2 h. In contrast, %XO was not changed for 24 h of cold ischemia. Tissue accumulation of HX was increased 2.8 times from a normal value of 1.06, 2 h after warm ischemia, but there was almost neither accumulation of HX nor the conversion of XD to XO in 24 h cold ischemia. It was observed that warm and cold ischemia caused similar injury after reperfusion in spite of the striking difference in the conversion of XD to XO and accumulation of HX. Thus, it is suggested that the XO system is not always necessary for ischemia-reperfusion injury.

Animals↗

Endotoxemia is associated with renal dysfunction in liver transplantation recipients during the first postoperative week.

The effect of endotoxemia on renal function was studied in 76 orthotopic liver transplant patients. In the preoperative period, a high preoperative serum creatinine level (> 2.0 mg/dl) was significantly associated with postoperative endotoxemia. The serum total bilirubin level was significantly greater in the patients with high serum creatinine levels than in those with lower serum creatinine levels (< 2.0 mg/dl). On the 7th postoperative day (POD), the serum creatinine level was significantly associated with an increased plasma endotoxin level. The serum total bilirubin and AST levels did not differ significantly between the patients with high and those with low serum creatinine levels. Based upon these data postoperative endotoxemia is suspected as being the principal cause of early postoperative renal dysfunction. A synergistic effect on renal function between cyclosporine and endotoxin may be important in the pathogenesis of the renal dysfunction seen after successful liver transplantation.

Adult↗