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N Zuhdi

Publications and source records attributed to N Zuhdi.

At least 19 recordsLinked to original sources

How many endomyocardial biopsies are necessary in the first year after heart transplantation?

Since 1989, the immunosuppressive regimen used in all heart transplant (HTx) patients at our center has consisted of a combination of cyclosporin, azathioprine, and prednisone. No prophylactic cytolytic agents have been given. One hundred consecutive patients were followed for periods of 4-56 months (mean 27 months). The incidence of rejection was so low in the initial 18 patients that we felt confident about reducing the number of routine endomyocardial biopsies (EMBs) that were performed. The mean number of EMBs in this subgroup was 10 (median 11). In the next 20 patients, EMB was performed routinely on only three occasions during the 1st post-transplant year (at 2, 4, and 8 weeks). In the subsequent 62 patients, EMB was performed on post-transplant days 10, 20, 30, and 60. Further EMBs were performed after acute rejection episodes had been treated. No noninvasive methods of diagnosing rejection were employed. In 82 consecutive patients, therefore, the mean number of EMBs within the 1st year was five per patient (median four), with 58% undergoing fewer than five EMBs and 25% requiring more than five EMBs. In the entire group of 100 patients, the mean number of EMBs was 5.9. The incidence of acute rejection requiring increased therapy was 24%. Only 7% required i.v. steroids, two of whom (2%) also required ALG and/or OKT3, with 17% requiring increased oral immunosuppression alone. Actuarial survival was 98% at 30 days, 94% at 1 year, and 92% at 2 years. It is possible that we may have missed acute rejection episodes that resolved spontaneously. However, the excellent medium-term results would suggest that any such rejection episode did not progress to become hemodynamically significant. It may be, therefore, that when an effective immunosuppressive regimen is utilized, the number of EMBs performed at many centers is excessive.

Adolescent

Cardiac transplantation in patients aged 60 years or older.

One hundred eighty-four consecutive patients who underwent heart transplantation from January 1987 to December 1994 have been reviewed. Patients who were 60 years of age or older at the time of transplant (Group A, n = 50) showed improved overall survival when compared with younger patients (Group B, n = 134), though this was not statistically significant. Survivals in groups A and B were 94% and 90%, respectively, at 1 year; 86% and 80% at 5 years; and 86% and 78% at 8 years. Overall survival of older patients in the U.S. and worldwide is inferior when compared with younger patients. More thorough pretransplant evaluation of the older patient and improved compliance post-transplantation may be factors in the good results obtained in this group at our own center.

Adolescent

Cryoglobulinemia: a cause for false negative polymerase chain reaction results in patients with hepatitis C virus positive chronic liver disease.

With the introduction of interferon therapy for liver disease due to chronic viral hepatitis, it has become important to test individuals thought to have hepatitis C virus disease for the presence of the virus. Moreover, the current goal of therapy for hepatitis C virus-positive liver disease is to render the individual patient HCV-RNA negative. Recently, it has been reported that as many as one-third of the patients with hepatitis C virus liver disease test positive for the presence of mixed cryoglobulins. Few of these cryoglobulin-positive patients have overt disease manifestations of cryoglobulinemia, such as nephropathy, peripheral neuropathy and vasculitis. Because the cryoglobulins in patients with hepatitis C virus-positive disease are directed at hepatitis C virus epitopes, the precipitation of cryoglobulins from serum samples also effectively removes virus. When the viral carriage rate is low in terms of the number of genomes/unit serum, as occurs in cases that are partially treated, the serum can test negative for hepatitis C virus even by polymerase chain reaction, despite the presence of persistent viremia, if precautions preventing the precipitation of cryoglobulins prior to the removal of the sample for polymerase chain reaction testing are taken. From a group of 75 patients with hepatitis C virus-positive hepatitis seen at our institution in the last year (all HCV-RNA positive), 35% were found to test positive for the presence of cryoglobulins. Importantly, in all cases, the cryoglobulins collected tested strongly positive for HCV-RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease

Induction therapy with cyclosporine without cytolytic agents results in a low incidence of acute rejection without significant renal impairment in heart transplant patients.

Since 1989, the immunosuppressive regimen used in all heart transplant patients at our center has consisted of (i) cyclosporine induction therapy (pretransplant p.o. 2-6 mg/kg depending on serum creatinine level, with immediate post-transplant i.v. therapy at 1-3 mg/h until p.o. therapy alone maintains a whole blood trough level of 300 ng/ml by RIA); (ii) azathioprine (2.5 mg/kg/d i.v./p.o.); (iii) methylprednisolone i.v. for 24 h and then prednisone p.o. at 1 mg/kg/d, tapering to 0.1 mg/kg/d at 1 yr. No prophylactic cytolytic agents (ALG, OKT3) were given. One hundred consecutive patients have been followed for periods of 4-56 months (mean 27 months). The incidence of acute rejection requiring increased therapy was 24%, with only 7% requiring i.v. steroids, 2 of whom (2%) also required ALG and/or OKT3, and with 17% requiring increased oral immunosuppression alone. Mean creatinine levels (mg/dl) were 1.3 pretransplant, 1.4 on d 7, 1.5 at 30 d, and 1.8 after 2 yr. Only 1 patient required temporary hemodialysis. Survival was 98% at 30 d, 94% at 1 yr, and 92% at 2 yr. We conclude that cyclosporine induction therapy with steroids and azathioprine without any cytolytic agent results in a low incidence of acute rejection without jeopardizing renal function.

Acute Disease

Survival following organ transplantation in an Oklahoma institution, 1985-1993.

Since 1985, a total of 413 patients have undergone 439 solid organ transplants at the authors' institution. The current actuarial one-year survival rate of patients undergoing heart, kidney, lung, or liver transplantation at our center is 94%, 90%, 87%, and 91%, respectively. Five-year survival of heart and kidney recipients is 80% and 75%, respectively. In view of these excellent results and the excellent quality of life that successful organ transplants provide patients with end-stage organ failure, every possible effort should be made to increase organ donation.

Actuarial Analysis

Cardiac allotransplantation across the ABO-blood group barrier by the neutralization of preformed antibodies: the baboon as a model for the human.

The baboon, like the human, expresses A and/or B blood group antigens on its tissues. Anti-A and anti-B antibodies are directed against these antigens, the epitopes of which are carbohydrate structures. Portions of these carbohydrates have been synthesized (trisaccharides A and B, respectively). When infused intravenously, the synthetic trisaccharides form a complex with the specific antibodies and neutralize their activity preventing them from binding to the antigen targets on a transplanted organ. In nonimmunosuppressed, hyperimmunized baboons, the continuous intravenous infusion of the specific trisaccharide alone (for 6 days) inhibited rejection of ABO-incompatible cardiac allografts, extending survival from a mean of 19 min (n = 3) to 8 days (n = 2), at which time the grafts failed from cellular (not vascular) rejection. The combination of long-term pharmacologic immunosuppression plus trisaccharide infusion (for periods of 8 to 19 days) extended survival to a mean of > 28 days (n = 4) with one heart functioning > 52 days. Accommodation clearly occurred in three of the four cases. This form of therapy may permit cadaveric organ allotransplantation across the ABO blood-group barrier in the human.

ABO Blood-Group System

Binding and specificity of major immunoglobulin classes of preformed human anti-pig heart antibodies.

Preformed human anti-pig antibodies isolated from perfused pig hearts were used to analyze the binding of various immunoglobulin classes to cultured pig kidney cells. All anti-pig immunoglobulins (i.e., IgG, IgA, and IgM) were localized on the cell surface by the use of an indirect immunofluorescence technique. Anti-pig immunoglobulins also competed for the pig cell surface epitopes with Griffonia simplicifolia lectin (GS-I-B4), which is specific for alpha-galactosyl residues. This study provides further evidence that preformed human antibodies recognizing alpha-galactosyl-containing epitopes (anti-gal antibodies) could be an important factor in hyperacute rejection of pig organs.

Animals

Methyl methacrylate plate to prevent compression after heart transplantation.

A methyl methacrylate plate was fashioned to maintain the sternum in the open position in a patient with impaired donor heart function after transplantation. Bilateral mammary flaps enabled soft tissue and skin closure. The chest wall fixation obtained allowed extubation and spontaneous breathing. The plate was subsequently removed. The patient remains well almost 3 years later.

Adult

Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man.

Human anti-pig antibodies were obtained by perfusing pig hearts (n = 4) and kidneys (n = 8) with human AB or O plasma followed by elution with 3 M NaSCN. The antibodies were screened against a panel of 132 synthetic carbohydrates conjugated to bovine serum albumin using an enzyme-linked immunoassay. An anti-immunoglobulin antibody was also used to detect immunoglobulin deposits on pig tissues. Four carbohydrate molecules with a terminal alpha-galactose residue bound all but one of the human anti-pig kidney antibodies and most of the anti-pig heart antibodies. These were: (i) alpha Gal(1-->3)beta Gal(1-->4)beta GlcNac (linear B type 2); (ii) alpha Gal(1-->3)beta Gal(1-->4)beta Glc (linear B type 6); (iii) alpha Gal(1-->3)beta Gal(B disaccharide); and (iv) alpha Gal(alpha-D-galactose). Immunoglobulin deposition was documented post-plasma perfusion in all pig hearts and particularly strongly in all pig kidneys. These results suggest that human anti-pig antibodies are mainly directed against alpha-galactosyl structures. Extracorporeal immunoadsorption of human plasma through columns of the specific synthetic carbohydrate(s) might lead to depletion of anti-pig antibodies and allow discordant xenografting in man. Alternatively, the infusion of the specific carbohydrate(s) for a period of several days might result in neutralization of the anti-pig antibodies and allow accommodation to take place.

ABO Blood-Group System

Specific intravenous carbohydrate therapy. A new concept in inhibiting antibody-mediated rejection--experience with ABO-incompatible cardiac allografting in the baboon.

Heterotopic allografting of ABO-incompatible donor hearts in recipient baboons "hyperimmunized" against the incompatible A or B antigen (n = 3) was followed by hyperacute antibody-mediated vascular rejection within a mean of 19 min. The A and B epitopes against which these antibodies are directed are carbohydrates that can be synthesized. The continuous i.v. infusion of the specific synthetic A or B trisaccharide, beginning immediately pre-transplant and continued posttransplant for several days, prolonged allograft survival to a mean of 8 days (n = 2) and prevented antibody-mediated rejection, graft failure resulting from acute cellular rejection. The addition of triple pharmacologic immunosuppressive therapy (n = 4) resulted in prolongation of graft survival to a mean of > 28 days, with one heart still beating at 52 days; all grafts showed features of cellular rejection. "Accommodation" would appear to have developed in several baboons as graft function continued for periods of up to 39 days after discontinuation of carbohydrate therapy. Specific i.v. carbohydrate therapy should allow organ allografting to be performed across the ABO blood group barrier in humans. Furthermore, if the carbohydrate epitopes on the organs of discordant animals (e.g., the pig) against which human xenoreactive antibodies are directed can be confirmed, then this form of therapy might allow successful discordant organ xenotransplantation in man.

ABO Blood-Group System

A suggested technique for "orthotopic" heart transplantation in a patient with situs inversus.

We describe a technique for "orthotopic" heart transplantation in a patient with situs inversus. The left atrial, aortic, and pulmonary artery anastomoses were performed directly, in the usual manner. The recipient's right atrium was converted into a tunnel, and the donor's right atrium was left intact. Anastomoses were therefore required between the 2 inferior venae cavae (by direct end-to-end anastomosis) and the 2 superior venae cavae (necessitating the insertion of a Dacron-graft). We suggest that even simpler techniques, perhaps not requiring the use of an artificial vascular prosthesis, are possible.

Adult