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Biomedical subjects

G Karam

Publications and source records attributed to G Karam.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Outcome of nephrogenic metaplasia of the bladder in kidney transplant recipients].

OBJECTIVES: To evaluate the risk of recurrence and malignant degeneration of vesical nephrogenic metaplasia in renal transplant recipients. MATERIAL AND METHODS: Fourteen patients with known nephrogenic metaplasia were systematically followed. Vesical biopsies were performed with a resector, stained with eosin haemalun saffron, analysed and compared to initial results. Labelling by anti-EBV and anti-CMV monoclonal antibodies was performed in 5 cases of intense inflammatory reactions. RESULTS: All patients were males, with a median age of 39 years. Nephrogenic metaplasia had been diagnosed 7 to 80 months after renal transplantation (median = 37.8). Twelve patients were reviewed 5 to 116 months after the initial diagnosis (median = 52). Relapse was observed in 83% of cases, but without any malignant degeneration. CONCLUSION: Nephrogenic metaplasia is therefore a benign recurrent disease. The importance of the initial blood supply and fibrosis in the case of recurrence suggest a disorder of the blood supply, probably traumatic in origin. Only symptomatic patients are currently followed.

Adolescent↗
PubMed1994

Isolation, characterization, and kinetic properties of truncated forms of T4 DNA polymerase that exhibit 3'-5' exonuclease activity.

Limited proteolysis of T4 DNA polymerase generated a 45-kDa and 35-kDa protein complex, which had 3'-5' exonucleolytic activity but lacked polymerase activity. After partial chymotryptic digestion of the cloned and expressed 45-kDa protein derived from T4 DNA polymerase, we isolated a 27-kDa fragment (residues 96-331) that still had 3'-5' exonuclease activity, thus demonstrating that the amino acid residues required for catalysis are included within this fragment. We also show that the apparent Km values for the 3'-5' exonuclease activity exhibited by the 27-kDa fragment are considerably greater than the apparent Km values determined for the intact DNA polymerase on deoxyoligonucleotide substrates having more than 3 bases. In contrast, the kcat values for phosphodiester bond hydrolysis of 3'-terminal nucleotides are not very different when comparing intact T4 DNA polymerase with the 27-kDa fragment derived from it. Thus, participation of residues distal to 331 are not required for catalysis, but only for binding, and, based on the similarity of kcat values, the geometry of the residues responsible for catalysis are preserved even in the absence of the carboxyl-terminal 567 residues.

Bacteriophage T4↗
PubMed1994

Prevention of acute rejection episodes with an anti-interleukin 2 receptor monoclonal antibody. I. Results after combined pancreas and kidney transplantation.

A prospective, randomized trial was conducted to evaluate the short-term and long-term effects of induction immunosuppression with the rat IgG 2a monoclonal antibody 33B3.1, directed against the human alpha chain of the interleukin 2-receptor, following primary, cadaveric, combined pancreas and kidney transplantation. Forty patients were randomly assigned to receive 10 mg/day of 33B3.1 (n = 20) or 1.5 mg/kg/day of rabbit antithymocyte globulin (n = 20) for the first 10 postoperative days. Azathioprine, low-dose corticosteroids, and cyclosporine were given in association with either 33B3.1 or ATG. All 40 patients received the entire 10-day bioreagent course and no episode of rejection was observed during this period. Although the incidence of rejection did not significantly differ within the first, second, and third postoperative months (ten 33B3.1 and 6 ATG patients experienced, respectively, 10 and 6 rejection episodes within the first 3 months), the total number of 33B3.1 patients experiencing rejection throughout the follow-up was significantly higher than that of ATG (13 versus 6; P < 0.02). Immunological graft failure accounted for 2 pancreas and 2 kidney losses in the 33B3.1 group versus 1 in the ATG one (P = ns). The total number of infectious episodes was similar in both groups (21 versus 23). Two malignancies were observed in the ATG group (1 responsible for patient's death). One 33B3.1 patient died because of infectious pneumonia and 3 ATG patients died because of 2 cardiovascular diseases and 1 cancer. All patients had functioning grafts at the time of death. The 3-month and 36-month patient, pancreas, and kidney actuarial survival rates were, respectively, 100, 65, and 100%, and 95, 50, and 82% in the 33B3.1 group and 95, 80, and 90%, and 80, 70, and 80% in the ATG one (P = ns). These data suggest that, although a significantly higher rejection episode incidence was observed in patients treated with 33B3.1 monoclonal antibody as compared with ATG, similar long-term results can be obtained following primary cadaveric combined pancreas/kidney transplantation.

Acute Disease↗
PubMed1994

Prevention of acute rejection episodes with an anti-interleukin 2 receptor monoclonal antibody. II. Results after a second kidney transplantation.

The focus of progress in transplantation immunosuppression is to achieve more specific immunosuppression with monoclonal antibodies. We have already shown that the efficacy of 33B3.1, a rat monoclonal Ig2A directed against the human IL-2 receptor, was similar to that of rabbit antithymocyte globulin in the prevention of acute rejection in first kidney transplants. A similar comparative analysis has been made in 40-sec renal transplants. ATG (1 mg/kg/day) or 33B3.1 (10 mg/day) was administered during the first 10 days postgrafting in association with corticosteroids and azathioprine. Cyclosporine was introduced on day 9 and azathioprine/CsA constituted the patient's maintenance treatment after day 45. Rejection treatment consisted of equine antilymphocyte globulin in both cases and of steroid boluses when patients were under Cyclosporine. One patient in each group died. Graft survival was 90%, 85%, and 79% in the ATG group (n = 20) and 100%, 89%, and 89% in the 33B3.1 group (n = 20) at 3, 12, and 24 months, respectively. Of the ATG group patients, 45% and 40% in the 33B3.1 group had at least one rejection episode, half the episodes in the MoAb cohort occurring under 33B3.1, vs. none in the ATG group. Transplant function was similar in both groups. Viral infections appeared to be more frequent with ATG (60%) than with 33B3.1 (12%), with CMV accounting for half of these in the ATG group, and none in the MoAb group. Tolerance of both agents was good. Of the 33B3.1 recipients, 70% developed anti-33B3.1 antibodies. From these data, we conclude that this anti-IL-2 receptor MoAb seems less effective than rabbit ATG as induction treatment in second kidney transplant patients.

Acute Disease↗
PubMed1994

Testicular tumor and the acquired immunodeficiency syndrome.

Immunocompromised patients, particularly those suffering from the acquired immunodeficiency syndrome (AIDS), present an increased risk of tumoral pathology. From the observation of a testicular lymphoma associated with Epstein-Barr virus in a HIV + patient, we review 19 cases of testicular tumor in HIV + patients previously published in the literature. These tumors are either lymphomas (4 cases) or germ cell tumors (15 cases). Their diagnosis was not difficult, although in the first stages enlarged and painful testicles are often wrongly identified as orchiepididymitis and treated as such. Therapy management proves to be delicate as a result of the significant tumor spread seen in these patients with dysfunctional immune systems. Regarding lymphomas, a low-dose multiagent chemotherapy with intrathecal chemotherapy was recommended by Levine. Concerning germ cell tumors, Wilson prefers an instant aggressive treatment with retroperitoneal lymphadenectomy (whether or not combined with chemotherapy) to avoid the risk of recurrence. In fact, tumor relapses will be difficult to control in the progressive stages of immunodeficiency syndrome.

Adult↗
PubMed1994

Renal transplantation from cadaver donors over 60 years old.

The influence of donor age on the short- and long-term outcome of cadaveric kidney transplantation was analyzed at our institution. During a 6-year period, 34 and 806 patients underwent kidney transplantation from cadaver donors over or less than age 60, respectively. Graft and patient survivals were compared throughout follow-up and herewith reported. In addition, main medical and surgical complications among recipients of elderly cadaver donors are detailed.

Adult↗
PubMed1993

Prospective randomized comparison of University of Wisconsin and UW-modified, lacking hydroxyethyl-starch, cold-storage solutions in kidney transplantation.

University of Wisconsin cold storage solution differs from Euro-Collins by the presence of adenosine, allopurinol, and hydroxyethyl starch, which maintains osmotic pressure. It is now experimentally and clinically well established that the use of UW solution is associated with better liver graft recovery parameters after prolonged cold ischemia time. However, it has been also suggested in animal experiments that HES might not be essential for optimal kidney preservation, at least when cold ischemia time remains within 48 hr. Herein, we present a randomized study comparing UW (n = 44) and a modified UW (UW-mod) (n = 44) solution lacking HES, adenosine, and allopurinol on kidney graft recovery parameters. Forty-one consecutive Euro-Collins flushed kidneys, transplanted immediately before this randomized trial, were used as historical controls. The results indicate that UW-mod was as efficient as UW in preserving the kidney in cold ischemia ranges that did not exceed 48 hr. Both solutions (UW and UW-mod) seemed more effective than Euro-Collins, based on the analysis of several parameters including the number of days until the creatinine was < 300 microM (P < 0.05), the level of the serum creatinine at one month (P < 0.02), and the Cockroft index (P < 0.04). Since UW-mod is three times less expensive than UW, we suggest that the simplified solution could be routinely used to preserve kidneys for transplantation.

Adenosine↗
PubMed1993

[Autosomal dominant polycystic kidney disease: urologic complications and results of kidney transplantation: 217 patients].

The authors report a retrospective series of 217 cases of autosomal dominant renal polycystic disease collected over a period of 30 years in the urology and nephrology departments of Nantes university hospital. They study the incidence of urological complications, observed in 87 patients (40%), consisting of calculi (15%), infection (22%, with 4 deaths), intracystic haemorrhages (3.5%) and urinary tract compression (2%). The diagnostic and therapeutic methods are presented and discussed. The results of renal transplantation are also analysed: 39 patients were transplanted, 72% retained a functioning kidney with a mean follow-up of 44.9 months (range: 12-108 months) and three patients died as a result of infectious complications. The 1-year and 3-year actuarial transplant survival rate of 92% was similar to that of renal transplantations performed for another form of renal disease. Preparation for renal transplantation remains an essential problem: the two major indications for pre-transplantation nephrectomy were the size of the kidneys and the presence of infection.

Adolescent↗
PubMed1992

Human fusion proteins between interleukin 2 and IgM heavy chain are cytotoxic for cells expressing the interleukin 2 receptor.

We have constructed a hybrid cDNA coding for a fusion protein between human interleukin 2 and a truncated heavy chain from human immunoglobulin M. The protein encoded by this cDNA contains the entire interleukin 2 sequence including its signal peptide, fused at its C terminus to domains 2 to 4 of the immunoglobulin heavy-chain constant region. Cells transfected with the hybrid cDNA secrete multimeric forms of the fusion protein, which bind specifically to cells bearing high-affinity interleukin 2 receptors. This binding leads either to T-cell proliferation or, if complement is added, to T-cell death. Multimeric forms of the fusion protein with a molecular mass above 500 kDa mediate complement-dependent lysis but trigger proliferation inefficiently when compared with forms with a low molecular mass (< 500 kDa). In contrast, the latter efficiently mediate T-cell proliferation without inducing complement-dependent lysis. The high molecular mass fusion proteins could thus constitute valuable tools for specific immunosuppression in humans.

Base Sequence↗