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Biomedical subjects

A B Cosimi

Publications and source records attributed to A B Cosimi.

At least 181 records · Page 10Linked to original sources
PubMed1983

Effects of interferon-alpha on cytomegalovirus reactivation syndromes in renal-transplant recipients.

We have previously demonstrated that six weeks of prophylaxis with interferon-alpha delays cytomegalovirus excretion and decreases viremia in recipients of kidney transplants. In a double-blind trial to evaluate the effects of a longer course of prophylaxis, we gave either 3 X 10(6) units of interferon or placebo intramuscularly to 42 patients before transplant surgery was performed. After surgery, doses were given three times a week for six weeks and then twice a week for eight weeks (total of 102 X 10(6) units). Clinical signs of cytomegalovirus infection were markedly reduced in interferon recipients. These signs developed in 7 of 22 placebo recipients and 1 of 20 interferon recipients (P = 0.03). Opportunistic superinfections (Aspergillus fumigatus and Pneumocystis carinii) occurred only in patients given placebo. Cytomegalovirus-associated glomerulopathy developed in one interferon recipient and three placebo recipients. Survival of patients and grafts was equivalent in both treatment groups, and minimal toxicity was observed with interferon. In seropositive renal-transplant recipients, interferon-alpha affords effective prophylaxis against serious cytomegalovirus infections.

Adult↗
PubMed1983

Association of herpesvirus infections with T-lymphocyte-subset alterations, glomerulopathy, and opportunistic infections after renal transplantation.

We studied the interrelation among herpes-virus infections, T-lymphocyte subsets, opportunistic infections, and renal histopathology in 28 recipients of renal allografts. All primary or reactivated herpesvirus infections occurring in the first three months after transplantation in recipients of cadaveric grafts accompanied persistent inversions in the ratio of OKT4 (helper/inducer) to OKT8 (cytotoxic/suppressor) lymphocytes. In the less heavily immunosuppressed recipients of organs of living related donors, these inversions were seen only in association with clinically apparent cytomegalovirus infections. Five of seven opportunistic infections occurred in patients with OKT4/OKT8 ratios of less than 1.0. Biopsy specimens from patients with renal dysfunction occurring in association with a low OKT4/OKT8 ratio frequently revealed glomerular damage rather than acute cellular rejection. Monitoring of T-lymphocyte subsets provides early evidence of herpesvirus infections and identifies patients at increased risk for opportunistic infection after renal transplantation.

Biopsy↗
PubMed1983

Antithymocyte globulin, pretransplant blood transfusion, and tissue typing in cadaver kidney transplantation.

Three hundred forty-seven recipients of primary cadaver kidney transplants were analyzed in relation to ATG therapy, pretransplant transfusion, HLA-A, -B and -DR antigen matches, and level of PRA to the panel. Prophylactic ATG treatment increased transplant survival significantly when compared with the non-ATG group. The beneficial effect of pretransplant blood transfusions was not apparent when the recipients received prophylactic ATG treatment. No correlation was noted between HLA-A and -B antigen matches and transplant survival. There was no significant difference in the transplant survival between patients with zero DR antigen match kidneys and those with one DR antigen-match kidney. The number of transplants with two DR antigen-match kidneys was too small to be conclusive. The recipients in whom PRA did not develop despite pretransplant blood transfusions seemed to have better transplant survival than those in whom PRA did develop in response to blood transfusions.

Antilymphocyte Serum↗
PubMed1983

Immunological monitoring of diabetic and nondiabetic recipients of renal allografts.

Peripheral blood T-lymphocyte populations were monitored sequentially in diabetic recipients of renal allografts. Unfractionated buffy coat preparations were reacted with the murine monoclonal antibodies, OKT3 (all circulating T-cells), OKT4 (helper/inducer/regulatory T-cells), and OKT8 (cytotoxic/suppressor cells). Levels of peripheral blood lymphocyte subpopulations of diabetic patients monitored prior to transplantation revealed no significant abnormalities. Following transplantation, but prior to any therapy for acute rejection, the mean percentage of OKT3, 4, and 8 reactive cells in diabetic recipients closely resembled those observed in nondiabetic recipients. After treatment for acute rejection, a marked decrease in the mean OKT4/OKT8 ratio from normal (1.90 +/- 0.7) was observed in both diabetic (1.04 +/- 0.5), and nondiabetic (1.35 +/- 0.5) allograft recipients. Eleven of thirteen diabetic recipients with long-term functioning allografts were found to have a depressed OKT4/OKT8 ratio (mean 1.03 +/- 0.6). T-cell subset monitoring of diabetics with end-stage renal failure failed to reveal any significant differences from nondiabetic, uremic patients. The high incidence (75%) of allograft rejection noted in these diabetic allograft recipients similarly suggests normal immunocompetence. Following successful completion of rejection therapy, however, reduction in the ratio of OKT4 to OKT8 reactive cells suggests that an alteration in immune responsiveness has occurred. Immunological monitoring of these long-term diabetic recipients with functioning allografts suggests that the observation of a consistently depressed OKT4/OKT8 ratio may (1) be useful in predicting continued allograft function and (2) prompt the more rapid reduction of steroid medication to maintenance dosage since this pattern may be indicative of subclinical viral infection.

Adult↗
PubMed1983

New approaches to donor crossmatching and successful transplantation of highly sensitized patients.

A class I HLA molecule may bear not only a private or unique determinant, but a shared, yet discrete, public epitope. These public determinants occur with a much higher frequency in the random donor population than the associated private determinants--and thus, are encountered more often in random donor blood transfusions and in renal transplantation. Sera from highly sensitized dialysis patients have been reported to contain a restricted number of antibodies to public determinants rather than a diverse array of antibodies directed against the private HLA-AB epitopes. As detailed in this report, comprehensive serum analysis of the public antibodies in highly sensitized transplant candidates has optimized identification of potential crossmatch-compatible donors and has avoided needless crossmatches. During the past two years, the incidence of renal transplantation from cadaveric donors to highly sensitized recipients has doubled at this institution. At 10-25 months following transplantation, 70% of these allografts are functioning. Private HLA class I antigen incompatibility was not a barometer for exclusion in the final donor crossmatch of these highly sensitized recipients. Furthermore, positive donor T cell crossmatches with sera obtained more than six months prior to transplantation may not represent an impediment to successful transplantation. We conclude that the approach of detailed antibody analysis can result in an improved outlook for successful transplantation of more dialysis patients who are highly sensitized to the class I HLA alloantigens.

Antibodies↗
PubMed1983

Monitoring immunosuppression following renal transplantation.

Renal allograft recipients were given azathioprine and prednisone for immunosuppression following transplantation. In addition, pulses of steroids or courses of treatment with antithymocyte globulin (ATG) or PAN.OKT3 were employed to combat acute rejection episodes. Our results support the concept that ATG and PAN.OKT3 are useful in the treatment of acute kidney allograft rejection. In our experience, ATG often reversed acute kidney allograft rejection episodes and then provided relatively long-lasting immunosuppression with stable graft function. In contrast, PAN.OKT3 was more effective in reversing acute rejection, but subsequent rejection episodes occurred more frequently. In patients treated with PAN.OKT3, cells reacting with OKT3, OKT4 and OKT8 were removed from the circulation within minutes following the initial treatment, and the levels of these cells remained dramatically depressed during the first few days of treatment. Subsequently, peripheral blood cells which reacted with OKT4 or OKT8, but not OKT3, could be detected in most patients, even though treatment continued and excess circulating PAN.-OKT3 was present. Experiments in which these cells were cultured for 24 or 72 hr indicated that antigenic modulation by OKT3 had occurred in vivo. These results raise interesting questions about the mode of action of PAN.OKT3, and suggest that the combination of PAN.OKT3 with an agent which can establish long-lasting immunosuppression may be more effective than either agent given alone.

Antibodies, Monoclonal↗
PubMed1982

Prognostic factors for melanoma patients with lesions 0.76 - 1.69 mm in thickness. An appraisal of "thin" level IV lesions.

Fourteen variables were tested for their prognostic usefulness in 203 patients with clinical Stage I melanoma and primary tumor 0.76-169 mm thick. Only two variables, primary tumor location and level of invasion, were useful in predicting death from melanoma for these patients. Of the 12 deaths from melanoma, 11 occurred in patients with primary tumors located on the upper back, posterior arm, posterior neck, and posterior scalp (=BANS). There has been only one death from melanoma in 136 patients with melanoma located at other sites (11/67 vs 1/136, p less than 0.0001 Fisher's Exact Test). Of the 67 BANS patients, 51 had level II or level III lesions and five (10%0 died of melanoma. This compared with six deaths from melanoma in 16 patients (37.5%) with level IV BANS lesions (5/51 vs 6/16, p = 0.01 Fisher's Exact Test). The relatively high incidence of both melanoma deaths and regional node metastases for the BANS group merits consideration for testing the efficacy of elective regional node dissection for these patients.

Adult↗
PubMed1982

Prognostic factors for patients with clinical stage I melanoma of intermediate thickness (1.51 - 3.39 mm). A conceptual model for tumor growth and metastasis.

Fourteen variables were tested for their ability to predict visceral or bony metastases in 177 patients with clinical Stage I melanoma of intermediate thickness (1.51 - 3.39 mm). A Cox multivariate analysis yielded a combination of four variables that best predicted bony or visceral metastases for these patients: 1) mitoses greater than 6/min 2 (p = 0.0007), 2) location other than the forearm of leg) p = 0.009, 3) ulceration width greater than 3 mm (p = 0.04), 4) microscopic satellites (p = 0.05). The overall prognostic model chi square was 32.40 with 4 degrees of freedom (p less than 10 (-5). Combinations of the above variables were used to separate these patients into at least two risk groups. The high risk patients had at least a 35% or greater chance of developing visceral metastases within five years, while the low risk group had greater than an 85% chance of being disease free at five years. Criteria for the high risk group were as follows: 1) mitoses greater than 6/mm 2 in at least one area of the tumor, irrespective of primary tumor location, or 2) a melanoma located at some site other than the forearm or leg and histologic evidence in the primary tumor of either ulceration greater than 3 mm wide or microscopic satellites. The low risk group was defined as follows: 1) mitoses less than or equal to 6/mm 2 and a location on the leg or forearm, or 2) mitoses less than or equal to 6/mm 2 and the absence in histologic sections of the primary tumor of both microscopic satellites and ulceration greater then 3 mm wide. The number of patients in this series who did not undergo elective regional node dissection (N = 47) was probably too small to detect any benefit from this procedure. Based on survival rates from this and other studies, it is estimated that approximately 1500 patients with clinical Stage I melanoma of intermediate thickness in each arm of a randomized clinical trial would be needed to detect an increase in survival rates from elective regional node dissection.

Adult↗
PubMed1982

A multivariate analysis of prognostic factors for melanoma patients with lesions greater than or equal to 3.65 mm in thickness. The importance of revealing alternative Cox models.

Fourteen prognostic factors were examined in 79 patients with clinical Stage I melanoma greater than or equal to 3.65 mm in thickness. All nine patients with melanoma of the hands or feet died of melanoma. A Cox proportional hazards (multivariate) analysis of the remaining 70 patients showed that a combination of the following four variables best predicted bony or visceral metastases: 1) a nearly absent or minimal lymphocyte response at the base of the tumor, 2) histologic type other than superficial spreading melanoma, 3) location on the trunk, and 4) positive nodes or no initial node dissection. Ulceration and/or ulceration width were not useful in predicting outcome either singly or in combination with other variables. Patients with negative lymph nodes and primary tumors of the trunk, hands, and feet did not do better than patients with positive nodes at those sites. Conversely, non of 16 patients with negative lymph nodes and extremity melanomas (excluding the hands and feet) or head and neck melanomas developed visceral or bony metastases (i.e., five-year disease-free survival rate 100%).

Adult↗
PubMed1982

Experience with pyeloureterostomy in renal transplantation.

Pyeloureterostomy was used as the preferred method of urinary tract reconstruction in 260 of 371 consecutive renal allograft procedures performed between September 1967 and December 1980. Initially chromic catgut suture was used for the anastomosis in 96 patients with ten complications developing (10.4%). Because of the high incidence of anastomotic leakage (8.3%) with chromic catgut suture, the next 101 pyeloureterostomies were constructed using 7-0 Tevdek. Although urinary leakage occurred in only five of these patients (4.9%), late stone formation occurred along the suture material in three patients (2.9%), influencing the conversion to 7-0 Prolene for this anastomosis. With this suture material, only two complications have occurred in 63 subsequent pyeloureterostomies (3.1%), neither related to the anastomosis. In comparison, eight complications developed in 111 patients who underwent reconstruction with the Politano-Leadbetter method of ureteroneocystostomy (7.2%). The currently recommended method for pyeloureterostomy, as described, when combined with meticulous attention to technical details has made pyeloureterostomy a safe and effective method of urinary tract reconstruction in renal transplant recipients, with morbidity indistinguishable from that of ureteroneocystostomy.

Humans↗
PubMed1982

Monoclonal antibodies to human T cell subsets: use for immunological monitoring and immunosuppression in renal transplantation.

Sequential monitoring of peripheral blood T cell populations was performed in normal control individuals and in 55 renal allograft recipients. In addition, 66 patients exhibiting prolonged renal allograft survival were each evaluated at least once with the same monoclonal antibodies. A normal or elevated OKT4:OKT8 ratio, especially in the presence of rising numbers of OKT4+ cells was predictive of possible future graft rejection. This observation, when followed by rising serum creatinine values coupled with biopsy evidence of glomerulopathy, was found in at least 15% of graft recipients. In a small number of patients, graft rejection episodes were successfully suppressed by administration of therapeutic doses of OKT3 antibody. However, production of anti-OKT3 antibodies was observed and may be expected to limit administration of this agent to a single short course in each patient.

Acute Disease↗