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Biomedical subjects

A B Cosimi

Publications and source records attributed to A B Cosimi.

At least 199 records · Page 11Linked to original sources
PubMed1981

Use of monoclonal antibodies to T-cell subsets for immunologic monitoring and treatment in recipients of renal allografts.

Using monoclonal antibodies and flow cytometry, wer serially monitored lymphocyte subpopulations in renal-allograft recipients treated with either conventional immunosuppression or a monoclonal antibody. In 29 patients given conventional suppression, highly significant correlations between changes in T-cell subsets and rejection were noted. Normal or elevated ratios of OKT4 (helper/inducer) to OKT8 (suppressor/cytotoxic) cells were associated with rejection unless the donor was HLA identical or the total number of T cells was extremely low. In patients with low ratios, rejection seldom occurred. Two patients treated with OKT3 monoclonal antibody for acute rejection had rapid disappearance of OKT3-reactive cells from the peripheral blood and prompt reversal of rejection. The use of monoclonal antibodies allows the precise determination of changes in T-cell subsets and promises the development of therapeutic protocols that can be designed to manipulate selected lymphocyte populations.

Antibodies↗
PubMed1981

Glomerulopathy associated with cytomegalovirus viremia in renal allografts.

We investigated the relation between cytomegalovirus (CMV) infection and renal-allograft dysfunction in 14 patients. In seven instances (including two successive transplants in one patient), allograft dysfunction occurred during clinically manifest, viremic CMV infection. In five of these, biopsies revealed little or no tubulointerstitial change but a distinctive, diffuse glomerulopathy characterized by enlargement or necrosis of endothelial cells and accumulation of mononuclear cells and fibrillar material in glomerular capillaries. Two of these allografts recovered their function, both with cessation of high-dose immunosuppression. Biopsies in the other 10 patients revealed predominantly tubulointerstitial changes typical of cellular rejection, and most of these patients did not have viremia. One additional patient, studied prospectively, manifested both forms of allograft injury: tubulointerstitial changes occurring two weeks after transplantation and responding to increased immunosuppression, and CMV-associated glomerulopathy occurring seven weeks after transplantation and responding to decreased immunosuppression. We conclude that viremic CMV infection can cause acute glomerular injury and that recovery may be favored by a decreased in immunosuppressants.

Cytomegalovirus Infections↗
PubMed1981

Malignant melanoma patients with positive nodes and relatively good prognoses: microstaging retains prognostic significance in clinical stage I melanoma patients with metastases to regional nodes.

Fifteen variables were tested for their value in predicting recurrent disease in 46 clinical Stage I melanoma patients with metastases to regional nodes. A stepwise proportional hazards general linear model (Cox multivariate analysis) separated these melanoma patients with regional node metastases into at least two risk groups. Twenty patients in the relatively low-risk group had a five-year disease-free survival of 80% (in spite of having nodal metastases). This compares to a five-year disease-free survival of 17.5% for 26 patients in the high-risk group (P less than 0.001, Lee-Desu Statistic). Criteria for the high-risk group required that a patient have only one of the following two values: (1) The number of regional lymph nodes that contained tumor divided by the total number of nodes removed x 100% (percentage of positive nodes) greater than or equal to 20%; or (2) a primary tumor thickness of greater than 3.5 mm (regardless of node percentage). Conversely, patients in the low-risk group had neither of the above features. The high-risk group could further be stratified by the lymphocytic response at the base of the tumor. These findings have direct immediate application to the elective regional node dissection controversy and to adjuvant therapy studies containing these patients.

Adult↗
PubMed1981

Infection in the renal transplant recipient.

The incidence of infection in the renal transplant patient is directly related to the net immunosuppressive effect achieved and the duration of time over which this therapy is administered. A second major factor in the causation of infections in this population is the nosocomial hazards to which these patients are exposed, ranging from invasive instrumentation to environmental contamination with Aspergillus species, Legionella pneumophila, Pseudomonas aeruginosa and other microbial pathogens. Careful surveillance is necessary to identify and eliminate such nosocomial sources of infection. The major types of infection observed can be categorized according to the time period post-transplant in which they occur: postsurgical bacterial infection in the first month after transplantation; opportunistic infection, with cytomegalovirus playing a major role, and transplant pyelonephritis in the period one to four months post-transplant; and a mixture of conventional and opportunistic infections in the last post-transplant period. Conventional infection in this late period occurs primarily in patients with good renal function who are receiving minimal immunosuppressive therapy; opportunistic infection occurs primarily in patients with poor renal function who are receiving higher levels of immunosuppression.

Central Nervous System Diseases↗
PubMed1981

A prognostic model for clinical stage I melanoma of the trunk. Location near the midline is not an independent risk factor for recurrent disease.

Fifteen variables were studied for their usefulness in predicting recurrent disease in 254 patients with clinical stage I melanoma of the trunk. Thickness of the primary tumor correctly predicted outcome with an accuracy of 90 percent or greater in 176 patients with melanoma primaries with a thickness of less than 1.70 mm or 5.5 mm or greater. No other variables significantly increased predictive accuracy over these ranges of thickness. A Cox proportional hazards analysis of the remaining 78 patients with primary tumors 1.70 to 5.49 mm thick demonstrated that the following four variables functioned as independent risk factors for recurrent disease: (1) thickness of the primary tumor (p = 0.0005), (2) mitoses/mm2 greater than 6 (p = 0.006), (3) a nearly absent or minimal lymphocyte response at the base of the tumor (p = 0.009), and (4) location on the upper trunk (p = 0.03). Trunk lesions located near the midline did not have a worse prognosis than more lateral melanomas of similar thickness.

Female↗
PubMed1981

The effect of infection on T lymphocyte subpopulations: a preliminary report.

The effect of cytomegalovirus (CMV) infection on T-lymphocyte subpopulations (employing the monoclonal antibody OKT4 to delineate helper cells and OKT8 for suppressor-cytotoxic cells) was studied in 10 normal individuals with CMV mononucleosis and four renal transplant patients with symptomatic primary CMV disease. In both clinical settings, acute CMV infection is associated with a reversal of the normal helper/suppressor-cytotoxic T cell ratio, with both a relative and absolute decrease in T helper cells and an increase in T suppressor-cytotoxic cells observed. With clinical recovery, there is a return of these cell populations toward normal ranges. In two patients, one with chronic CMV infection and one with chronic Epstein-Barr virus infection, the helper/suppressor-cytotoxic cell ratio was found to be reduced four years after the onset of infection. Five patients with febrile illnesses were also studied: two with viral infection and one with a self-limited febrile illness had decreased helper/suppressor-cytotoxic cell ratios, and two with bacterial infection had increased ratios. Thus, delineation of T lymphocyte subpopulations may be of value not only in evaluating the immunologic effects of a particular infectious agent, but also in the clinical evaluation of the febrile patient.

Animals↗
PubMed1981

A prognostic model for clinical stage I melanoma of the upper extremity. The importance of anatomic subsites in predicting recurrent disease.

Thirteen variables were studied for their relative usefulness in predicting recurrent disease in 107 patients with clinical Stage I melanoma of the upper extremity. After a mean follow-up period of 54 months, the only patents who have had recurrent disease to date are those who primary lesions were located either on the hand or posterior upper arm. The five-year disease-free survival role for 44 patients with melanoma at these sites was 68%. None of 63 patients with melanoma located on the forearm of anterior upper arm have had recurrent disease (i.e., the five-year, disease-free survival rate was 100% (p = 0.00004), compared with the hand or posterior arm group). A Cox proportional hazards (multivariate) analysis demonstrated that two primary tumor histologic variable, thickness in millimeters and ulceration, interacted to produce the best prognostic model for those 44 patients with melanoma of the hand or posterior upper arm. Twenty-one patients with primary lesions at these sites had primary tumors less than 2.25 mm in thickness and no evidence of ulceration histologically. Their five-year, disease-free survival role was 95%. For the remaining 23 patients with primary tumors on the hand or posterior upper arm who had either histologic evidence of ulceration or primary tumors greater than or equal to 2.25 mm, the five-year disease-free survival rate was 37% (p = 0.002, compared with group nonulcerated, thin lesions). The excellent survival rate for patients with melanomas on the forearm or anterior upper arm was not completely explained by pathologic stage, by primary tumor thickness, or by histologic ulceration of the primary tumor.

Arm↗
PubMed1981

Impact of hepatitis on renal transplantation.

In order to delineate the incidence, etiology, and impact of liver disease in renal transplant patients, we reviewed 405 consecutive transplants performed between 1970 and 1980. Hepatic dysfunction of at least 2 weeks' duration was diagnosed in 42 patients (10.4%). Of 28 patients acquiring hepatitis in the first post-transplant year, 26 (92.8%) developed chronic hepatitis; of 14 acquiring hepatitis after the first year, 9 (64.2%) developed chronic hepatitis. Of the 42 patients, 19 (45.2%) died, as compared with 16% of the nonhepatitis patients (P less than 0.001). Only one of these patients died of liver failure, with 15 of the 19 (78.9%) dying of extrahepatic infection. In addition, 12 of the 23 survivors (52.1%) suffered life-threatening infections from which they recovered, as compared with 20% of the nonhepatitis patients (P less than 0.01). Conversely, graft survival was significantly increased among the hepatitis patients (73% 1-year cadaveric allograft survival as compared with 50% for the nonhepatitis patients (P less than 0.01)). The etiology of the liver disease was identified in the minority of patients: 5 (11.9%) with hepatitis B, with none occurring since 1973; 10 (23.8%) with evidence of cytomegalovirus infection; and 1 (2.3%) with azathioprine toxicity. We conclude that the major cause of liver disease in renal transplant patients is non-A, non-B hepatitis, and furthermore, that this disease has a marked immunosuppressing effect resulting in increased allograft survival and a marked increase of life-threatening extrahepatic infection.

Diagnosis, Differential↗
PubMed1981

Treatment of acute renal allograft rejection with OKT3 monoclonal antibody.

Eight cadaver donor renal allograft recipients, who had received azathioprine and prednisone from the day of transplantation, were treated with OKT3 monoclonal antibody (reactive with all mature peripheral blood T cells) at the time of diagnosis of acute rejection. In all cases, loss of essentially all detectable peripheral blood OKT3-reactive cells was noted within minutes after the initial 1- to 5-mg i.v. infusion. Chills and fever invariably occurred following the first or second infusion of monoclonal antibody, but were not noted during the subsequent, 10- to 20-day course of therapy, suggesting rapid cell lysis as the etiology of this toxicity. The established rejection episode was reversed in all cases within 2 to 7 days without addition of any therapy other than OKT3 antibody and despite continued lowering of the steroid dosages. During the subsequent 3- to 12-month follow-up period, further rejection episodes occurred in five of these patients, two of these were irreversible with conventional therapy so that six of the eight allografts continue with excellent renal function. These preliminary observations suggest that homogeneity, limited dosage requirements, and ease of in vitro monitoring of dosage effects should markedly simplify the use of monoclonal antibody to T cell populations in human allograft recipients. This second generation of antilymphocyte preparations offers the potential for not only increased effectiveness but also the possibility of manipulating specific T cell subsets.

Antibodies, Monoclonal↗
PubMed1981

Temporary skin transplantation for the treatment of extensive burns.

Survival of the extensively burned patient depends upon rapid excision of necrotic tissue, and skin grafting to obtain wound closure. When a sufficient supply of autogenous skin is not available to provide wound coverage, allograft skin has been successfully substituted. Although burn patients have been noted to be immunologically hyporesponsive, their immune response to skin allografts has necessitated the administration of immunosuppressive therapy, to assure the retention of the allografts until sufficient autogenous skin can be utilized. The temporary transplantation of skin allografts has proved successful in the treatment of extensively burned children.

Antilymphocyte Serum↗
PubMed1981

A prognostic model for clinical stage I melanoma of the lower extremity. Location on foot as independent risk factor for recurrent disease.

Thirteen variables were studied to determine their usefulness in predicting recurrent disease in 158 patients with stage I melanoma of the lower extremity. A Cox proportional hazards analysis demonstrated that three variables were independent risk factors for recurrent disease in these patients: (1) thickness, in millimeters, of the primary tumor (P = 0.000009), (2) primary tumor location on the foot (P = 0.0003), and (3) the number of mitoses/mm2 (P = 0.0244). Life-table analyses of patient subgroups defined by different combinations of these three variables demonstrated that thick (greater than or equal to 3.0 mm) melanomas of the foot were associated with recurrent disease much more frequently than tumors of similar thickness located on the thigh or calf. These data provide guidelines that can be used to evaluate results of surgical and/or adjuvant therapy studies for patients with melanoma of the lower extremity.

Foot Diseases↗