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M Abecassis

Publications and source records attributed to M Abecassis.

At least 55 records · Page 3Linked to original sources

[Bone marrow transplantation with major ABO incompatibility. Experience at the bone marrow transplantation unit of the Center of Lisbon at the IPOFG].

Thirteen patients submitted to major ABO incompatible, HLA A and B identical, mixed lymphocyte culture negative bone marrow transplantation (BMT) were retrospectively evaluated. Gravity sedimentation by hydroxyethyl starch was used in almost all cases to deplete erythrocytes from bone marrow (12/13): a removal rate or 90%--corresponding to an erythrocyte residual volume of 27.4 rate ml--and a nucleated cell recovery of 76% (mean values) were obtained. All patients underwent a hyperhydration regimen and received corticosteroid prophylaxis before bone marrow infusion. Considering the most important immunohematological problems associated to this type of transplant we verified that seven patients developed minor complications, and among them only one had long term consequences. In comparison with the control group, ABO identical and with minor incompatibility, the study group had delayed onset of erythropoiesis and needed greater erythrocyte transfusion support. We concluded that major ABO incompatibility does not constitute a drawback to BMT success in most patients.

ABO Blood-Group System↗

Delta and conjugated bilirubin as complementary markers of early rejection in liver-transplant recipients.

For 51 liver allograft recipients, we evaluated whether serum profiles of delta (Bd) and conjugated bilirubins (Bc) could be used to diagnose rejection during the first 30-50 postoperative days, in comparison with histology as the "gold standard." Daily measurements of aspartate aminotransferase, alkaline phosphatase, total bilirubin, Bd, and Bc were made, the last two by liquid chromatography. In 34 patients without any biochemical or histological evidence of rejection, within seven to 10 postoperative days Bd increased to greater than 40-50% of total bilirubin, while Bc decreased to less than 10%. In patients with severe rejections resulting in death, Bc increased rapidly to greater than 50%, while Bd remained less than 30%. In 24 histologically proven episodes of rejection in 17 patients there was either a rapid decrease in Bd or its persistence at 30%, plus either a steep increase in Bc, or its remaining at greater than 50% total bilirubin. Treatment of rejection resulted in a prompt reversal of these trends. Individually promising as prognostic adjuncts to existing liver-function markers, Bd and Bc also complemented each other, rendering the diagnosis of liver rejection much more incisive.

Adult↗

Treatment of primary liver graft nonfunction with prostaglandin E1.

Primary nonfunction following orthotopic liver transplantation is characterized by rapidly rising serum transaminases, minimal bile production, and severe coagulopathy, which can progress to hypoglycemia, hepatic encephalopathy, and acute renal failure. Untreated it has a mortality of over 80% and to date the only treatment has been retransplantation. As a result of the beneficial effect of Prostaglandin E1 infusion in patients with fulminant hepatic failure, this trial was conducted to determine whether PGE1 would be of value in primary nonfunction. We have encountered 16 cases of primary nonfunction in 94 liver transplants, an incidence of 17%. Initially in the program, there were 6 occurrences of nonfunction that did not receive PGE1; 3 underwent retransplantation (2 survivors), 2 died awaiting another liver, and in one recovery of hepatocellular function occurred with supportive care but the patient died of cytomegalovirus infection. Ten patients received PGE1 within 4-34 hr of transplantation. Within 12 hr of treatment, 8 patients responded with a significant fall in the AST (129 U/hr) whereas, in the untreated group, the AST continued to rise (267 +/- 102 U/hr) at the same rate as prediagnosis (337 +/- 95 U/hr). At the conclusion of the infusion (4-7 days) in the 8 responders, there were significant decreases in AST (4386 +/- 546 U/L to 102 +/- 21 U/L), prothrombin time (22 +/- 2 to 12 +/- .4 sec) and partial thromboplastin time (45 +/- 3-29 +/- 4 sec), and significant increases in coagulation factor V (26 +/- 8 to 95 +/- 12%) and factor VII (10 +/- 5 to 61 +/- 4%). No serious side effects occurred, although 2 patients developed diarrhea, and abdominal cramps. Two patients treated with PGE1 were retransplanted at 10-36 hr and were considered nonresponders. Graft survival was 80% in the PGE1-treated group and 17% in the untreated group (P less than 0.05) and patient survival was 90% and 33%, respectively. This study suggests a potential benefit of PGE1 in the treatment of primary nonfunction.

Alprostadil↗

Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report.

The effect of PG on patients with fulminant and subfulminant viral hepatitis (FHF) was studied. 17 patients presented with FHF secondary to hepatitis A (n = 3), hepatitis B (n = 6), and non-A, non-B (NANB) hepatitis (n = 8). 14 of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation the mean aspartate transaminase (AST) was 1,844 +/- 1,246 U/liter, bilirubin 232 +/- 135 mumol/liter, prothrombin time (PT) 34 +/- 18, partial thromboplastin time (PTT) 73 +/- 26 s, and coagulation Factors V and VII 8 +/- 4 and 9 +/- 5%, respectively. Intravenous PGE1 was initiated 24-48 h later after a rise in AST (2,195 +/- 1,810), bilirubin (341 +/- 148), PT (36 +/- 15), and PTT (75 +/- 18). 12 of 17 responded rapidly with a decrease in AST from 1,540 +/- 833 to 188 +/- 324 U/liter. Improvement in hepatic synthetic function was indicated by a decrease in PT from 27 +/- 7 to 12 +/- 1 s and PTT from 61 +/- 10 to 31 +/- 2 s, and an increase in Factor V from 9 +/- 4 to 69 +/- 18% and Factor VII from 11 +/- 5 to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT, and improvement was observed upon retreatment. After 4 wk of intravenous therapy oral PGE2 was substituted. Two patients with NANB hepatitis recovered completely and remained in remission 6 and 12 mo after cessation of therapy. Two additional patients continued in remission after 2 and 6 mo of PGE2. No relapses were seen in the patients with hepatitis A virus and hepatitis B virus infection. Liver biopsies in all 12 surviving patients returned to normal. In the five nonresponders an improvement in hepatic function was indicated by a fall in AST (3,767 +/- 2,611 to 2,142 +/- 2,040 U/liter), PT (52 +/- 25 to 33 +/- 18 s), and PTT (103 +/- 29 to 77 +/- 44 s), but all deteriorated and died of cerebral edema (n = 3) or underwent liver transplantation (n = 2). These results suggest efficacy of PGE for FHF, and further investigation is warranted.

Adolescent↗

Cyclosporin A metabolites suppress T-cell proliferation by concanavalin A and in a mixed lymphocyte reaction.

To ascertain if cyclosporine metabolites (CMs) have immunosuppressive activity, bile, whole blood and urine taken from patients after cholecystectomy and from a liver transplant recipient on cyclosporin A (CsA) were assayed to determine their effect on T-cell proliferation induced by concanavalin A (Con A) and in a two-way mixed-lymphocyte response. Bile and whole blood from the liver transplant patient completely suppressed Con A proliferation and the mixed lymphocyte response (MLR) at dilutions at which normal bile and whole blood have no suppressive activity, but no such activity was noted from the urine. The CMs were separated into six peaks (fractions) by high-pressure liquid chromatography (HPLC). Metabolites were identified by internal standards and HPLC/mass spectrophotometric analysis. Cyclosporine metabolite fractions 2 and 3 from bile and blood had immunosuppressive activity similar to parent CsA whereas fractions 5 and 6 demonstrated less but substantial immunosuppressive activity. Fractions 2, 3 and 5 demonstrated an ability to inhibit two-way MLR similar to parent CsA; the other metabolite fractions were able to inhibit the MLR but to a lesser extent. These results demonstrate that a number of CMs have immunosuppressive effects similar to those of the parent compound, and this may account for the lack of correlation between whole blood CsA levels and immunosuppressive activity.

Chromatography, High Pressure Liquid↗

16, 16 Dimethyl prostaglandin E2 prevents the development of fulminant hepatitis and blocks the induction of monocyte/macrophage procoagulant activity after murine hepatitis virus strain 3 infection.

16, 16 Dimethyl prostaglandin E2 (dmPGE2), a known cytoprotective agent, was examined for its ability to alter the course of fulminant hepatitis in an experimental model of fulminant viral hepatitis, murine hepatitis murine hepatitis type 3 (MHV-3). Fully susceptible BALB/cJ mice, infected with 100 50% lethal doses (LD50) of MHV-3 developed histologic and biochemical evidence of fulminant hepatitis, as evidenced by massive hepatic necrosis with hypoglycemia, metabolic acidosis, and a markedly elevated serum alanine aminotransferase (ALT) (mean, 1,402 +/- 619 IU/liter). In contrast, animals treated with dmPGE2 either before or after infection (up to 48 h) demonstrated a marked reduction in both histologic and biochemical evidence of liver damage as characterized by normal blood glucose, total CO2, and ALT determinations (mean ALT, 63 +/- 40 IU/liter). Treatment of infected mice with PGF2 alpha demonstrated no cytoprotective effects. High titers of infectious virus were recovered from the livers of both dmPGE2-treated and -untreated animals throughout the course of infection. In a parallel in vitro study, dmPGE2 (10(-4)-10(-8) M) demonstrated a similar cytoprotective effect on monolayers of isolated cultured hepatocytes from fully susceptible BALB/cJ mice infected at a multiplicity of infection of 0.1, 1.0, and 10.0. In addition, splenic macrophages recovered from infected and untreated BALB/cJ mice demonstrated a marked augmentation in procoagulant activity (PCA) from a basal 10 +/- 5 mU/10(6) splenic macrophages to a maximum of 615 +/- 102 mU/10(6) splenic macrophages, whereas no increase in macrophage PCA was detected in infected animals treated with dmPGE2. These results suggest that dmPGE2, without detectably altering viral replication or infectivity in vivo, confers a marked cytoprotective effect on hepatocytes both in vivo and in vitro, and prevents the induction of macrophage PCA in vivo in fully susceptible BALB/cJ mice after murine hepatitis virus type 3 infection.

16,16-Dimethylprostaglandin E2↗

Transjugular intrahepatic portosystemic shunt: a nonoperative approach to life-threatening variceal bleeding.

Portosystemic venous shunts may be created nonoperatively with a Grüntzig balloon dilatation catheter using the transjugular route. The authors achieved technical success with this shunt in 15 of 20 patients with life-threatening gastrointestinal bleeding from variceal hemorrhage. All patients but one were considered at high risk for surgery because of end-stage liver disease; the exception was a patient in whom two previous operative portosystemic shunts had failed. An average decrease of 5.9 mm Hg in portal vein pressure was measured in 11 patients for whom sequential pressures could be obtained. Two patients survived longer than 12 months without subsequent operative procedures, and the shunt helped temporize in three other patients who later underwent operation. Nine patients with successful shunts died within 30 days of the procedure, comparing favourably with reported operative death rates of 40% to 80% in emergency shunt procedures. Follow-up portal venograms demonstrated shunt patency in six of nine patients, in one after 8 months. Tract patency was determined in four of seven patients on whom autopsy was performed, up to 6 months after the transjugular intrahepatic portosystemic shunt was created.

Adult↗

Serendipitous adrenal masses: prevalence, significance, and management.

Over a 2 year period, 63 of 1,459 patients examined by computerized tomography were found to have adrenal masses. In 19 patients (1.3 percent of patients examined and 30 percent of patients with adrenal masses), they were unexpected and did not give rise to symptoms or signs. Three patients were explored. Two of the patients had adrenocortical adenomas and a third, a ganglioneuroma. Adrenal function tests were performed in 14 patients and showed evidence of Cushing's syndrome in 1 patients and revealed no abnormalities in 13. The lesions in 10 of 11 nonsurgical patients followed by computerized tomography for 11 to 36 months showed no change. One lesion became significantly smaller. In a review of 988 autopsy reports, grossly visible adrenal masses were present in 73 patients (7.3 percent), including 19 adrenocortical adenomas (1.9 percent) and 50 metastases (5 percent). We conclude that serendipitous adrenal masses are usually small, nonfunctioning, and benign, the most common lesion being adrenocortical adenoma. A protocol has been suggested for management to identify the minority of patients with functioning or malignant lesions and to avoid unnecessary surgery in the others who have benign disease.

Adenoma↗

Sclerotherapy for esophageal varices: preliminary experience.

There has been a resurgence of interest in injection sclerotherapy as a means of controlling and preventing variceal hemorrhage. This report reviews and evaluates the early experience with this procedure at the Toronto General Hospital. From May 1979 to January 1983, 39 patients underwent 73 separate treatment sessions (rigid 23, flexible 50), during active bleeding (3), during hospitalization for variceal hemorrhage but after cessation of bleeding (35) and during elective admission to hospital expressly for sclerotherapy (35). Follow-up was obtained for 38 patients (98%). The overall rate of rebleeding was 27%. Complications occurred in 13 patients (33%). Ten patients died; in 2, death was directly attributable to a complication of sclerotherapy. From this preliminary experience the authors conclude that complications of sclerotherapy are frequent and potentially life-threatening, so more prospective randomized trials are needed before its role in the treatment of bleeding varices is clear.

Adult↗