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Biomedical subjects

G R Hafez

Publications and source records attributed to G R Hafez.

At least 19 recordsLinked to original sources

Increased beta 2-microglobulin (B2M) is useful in the detection of post-transplant lymphoproliferative disease (PTLD).

This study examines whether changes in beta 2-microglobulin (B2M) serum levels are useful in the early detection of post-transplant lymphoproliferative disease (PTLD). Serum B2M is monitored daily post-transplant at our center as a marker of change in lymphocyte activation. We identified 16 cases (16/1359; 1.2%) of PTLD from among 1359 kidney and kidney-pancreas transplants. Those with CNS lymphoma (two patients) and titer change only (one) were not included in this review. Thirteen patients had serum titer and clinical evidence of EBV activity; 12 of these patients had histological evidence of PTLD (lymph node 6, kidney 3, and generalized disease 3). Three patients died with disseminated PTLD infection. Nine are alive but only two have the original transplant kidney. All patients received quadruple immunosuppression for induction, and 11 were subsequently treated with OKT3 or ALG for rejection. The mean number of days of induction ALG therapy was 14.8 d (20 mg/kg/d). The mean number of days of OKT3 therapy for rejection was 14.4 d (5 mg/d). During rejection the highest mean creatinine level was 6.8 mg/dL, and the highest mean B2M level was 16.4. With PTLD, the highest mean creatinine level was 7.0 mg/dL and the highest mean B2M level was 32.3 mg/L. The difference in creatinine levels was not significant, but the difference in B2M levels was significant (p < 0.01). We conclude that B2M levels are useful markers in differentiating rejection from PTLD.

Adult

The correlation between the loss of chromosome 14q with histologic tumor grade, pathologic stage, and outcome of patients with nonpapillary renal cell carcinoma.

BACKGROUND: Conventional pathologic classifications of human renal cell carcinoma (RCC) give little insight into oncogenesis and little assistance in predicting the clinical behavior of this disease. Identification of specific genetic alterations involved in the development of RCC using fluorescence in situ hybridization (FISH) however, may help provide foundations for classification, prognosis, and clinical management of the patients. METHODS: Archival, paraffin embedded tissue sections from 30 human non-papillary RCCs were examined with a dual color FISH technique for loss of chromosomes 3p and 14q. Telomeric DNA probes from 3p or 14q and an internal ploidy control probe, centromeric probe of chromosome 2, were applied directly to the tumor sections. The correlations between loss of 3p or 14q, and tumor ploidy, with tumor grade, pathologic stage, and patient outcome were assessed. RESULTS: Ninety percent of the patients (27) lost chromosome 3p, and 36.7% of the patients (11) had chromosome 14q deletions. The loss of 3p in the samples tested was unrelated to patient age, gender, outcome, tumor stage, or histologic grade. However, the deletion of 14q was significantly correlated with higher stage (P = 0.01), histologic grade (P = 0.01), and patient outcome (P < 10(-4)). CONCLUSION: The close correlation of 14q loss with higher stage, higher histologic grade, and poorer outcome for patients with nonpapillary RCC indicates that it may be a promising prognostic marker.

Adult

Retroperitoneal masses, adenopathy, and adrenal glands.

The diagnosis of primary retroperitoneal masses is approached best by CT scan-guided transretroperitoneal core biopsy or by open biopsy. Excisional or wedge biopsy is the preferred method for undiagnosed lymphadenopathy. Resection without biopsy is indicated for large or enlarging nonfunctional primary adrenal masses.

Adrenal Gland Neoplasms

Prolongation of canine intestinal allograft survival with RS-61443, cyclosporine, and prednisone.

The efficacy of RS-61443 and cyclosporine utilized either alone or in combination was assessed in both a segmental heterotopic and total orthotopic canine intestinal transplant model. Twenty-eight dogs underwent segmental (150-cm) heterotopic intestinal transplants and five dogs total orthotopic transplants. Five heterotopic groups were compared: group 1, no immunosuppression; group 2, cyclosporine and prednisone; group 3, RS-61443, cyclosporine and prednisone; group 4, RS-61443 and prednisone; and group 5, RS-61443 and subtherapeutic cyclosporine. Group 3 animals achieved a median survival of 136 days, while the median survivals of groups 1, 2, 4, and 5 were < or = 10 days (P < .001). Twenty deaths in groups 1 through 5 were secondary to allograft rejection, two were due to infection, and two were unexplained. Four animals in group 3 were sacrificed, one at 83 days due to diarrhea and weight loss and three at the termination of the study. The median survival of five dogs undergoing total orthotopic transplantation (group 6) was 27.0 days and was significantly longer than groups 1, 4, and 5 (P < .01). No dog in this group had intestinal rejection--however, four were sacrificed due to weight loss and one died of malnutrition. The combination of RS-61443 and cyclosporine significantly prolonged intestinal allograft survival in both the heterotopic and orthotopic transplant models. Clinically, this combination may be promising for both combined liver-intestinal and isolated intestinal transplantation.

Animals

Dedifferentiated chondrosarcoma of the larynx with regional and distant metastases.

Chondrosarcoma of the larynx is an unusual tumor, with only approximately 200 cases having been reported. This tumor is relatively nonaggressive and tends to remain localized in the larynx. Two cases with aggressive clinical behavior manifested by regional or distant metastasis are presented. In the first case, cervical node metastasis appeared 6 months after total laryngectomy. A dedifferentiated chondrosarcoma was identified by pathologic examination. In the other case, clavicular metastasis developed 7 years after initial local excision. Despite additional treatments, the patient later developed cervical node, lung, and vertebral metastasis. Transformation from low-grade to dedifferentiated chondrosarcoma was verified by pathologic examination. We believe this case to be the first reported laryngeal chondrosarcoma with bone metastasis. A review of the literature regarding regional and/or distant metastasis of laryngeal chondrosarcoma, including the present observations, reveals a total of 20 cases. In all cases, tumor grade has been directly correlated with the development of metastasis.

Chondrosarcoma

Liver transplantation for alcoholic liver disease.

BACKGROUND: Alcoholism is the leading cause of end-stage liver failure in the United States, but the application of liver transplantation to the treatment of alcoholic liver disease remains controversial because of medical and ethical concerns. Information about the outcome of patients who undergo transplantation for alcoholic cirrhosis would help to resolve these concerns. METHODS: The results of 41 patients (Group 1) with alcoholic liver disease were compared with those of patients who underwent liver transplantation for other medical problems (group 2) at this center. Thirty of the 32 survivors from group 1 and 30 matched subjects from group 2 were interviewed to assess substance dependence, recidivism, and activity level. RESULTS: Compared with control subjects, patients with alcoholic liver disease had equivalent patient and graft survival rates and achieved an equal level of postoperative health. These results were achieved even though patients with alcoholic liver disease had significantly worse liver failure and more morbidity before surgery, and one third of the patients in this group were not abstinent before transplantation. CONCLUSIONS: We conclude that patients with alcoholic liver disease merit equal consideration for liver transplantation compared with other causes of liver failure. Treatment of the addictive disorder should be included before and after surgery.

Actuarial Analysis

The predictive value of donor liver biopsies for the development of primary nonfunction after orthotopic liver transplantation.

Methods of accurately assessing the suitability of donor livers prior to transplantation are required if the incidence of primary nonfunction (PNF) is to be reduced. This study evaluated the ability of donor liver biopsies to predict the development of primary nonfunction after transplantation. From June 1987 until May 1990, 170 liver transplants were performed in 147 patients. A total of 124 donor liver biopsies were obtained and divided into three groups. Group 1 biopsies (n = 77) were obtained after revascularization of the liver, group 2 biopsies (n = 19) were obtained prior to donor hepatectomy but examined only after implantation, and group 3 biopsies (n = 28) were obtained as in group 2, but were examined prior to implantation. Three of 89 (3.4%) livers interpreted as having normal histology developed primary nonfunction, while one of 26 (3.8%) biopsies interpreted as having a minimal or moderate amount of fatty infiltration developed primary nonfunction. PNF occurred in 7 of 8 livers with severe fatty infiltration (3), hydropic degeneration (3), and centrilobular necrosis (1). A fourth liver with hydropic degeneration and poor function ultimately failed requiring retransplantation 8 weeks later. Analysis of liver function revealed progressive elevation in aspartate-aminotransferase, alanine-aminotransferase, lactate dehydrogenase, and serum ammonia (NH3) with increasing degrees of fatty infiltration. Donor age and weight was also found to be significantly higher in livers with fatty infiltration. This study suggests that donor liver biopsies demonstrating normal histology or minimal-to-moderate fatty infiltration function adequately, but that donor livers with severe fatty infiltration or hydropic degeneration function poorly and should not be transplanted.

Biopsy

Delayed hemorrhage of a persistent ectopic pregnancy following laparoscopic salpingostomy and methotrexate therapy.

This report describes the first known case of delayed hemorrhage of a persistent ectopic pregnancy following surgical and medical therapy. A 2.5-cm ampullary pregnancy without cardiac activity was removed by laparoscopic salpingostomy. The serum beta-hCG level before laparoscopy was 1542 mIU/mL, increasing to 3163 mIU/mL by the eighth postoperative day. Administration of methotrexate and citrovorum factor caused a 48% decline in the level of serum beta-hCG over 72 hours, but did not prevent delayed hemorrhage by the tubal gestation. This case emphasizes that close surveillance during the treatment of persistent ectopic pregnancy should continue until serum beta-hCG is undetectable.

Adult

The effects of interleukin-2 on bone marrow engraftment in a murine model.

Strategies have been developed to rid bone marrow of microscopic tumor prior to infusion in the autologous bone marrow transplant setting. We have previously demonstrated that recombinant human interleukin-2 (IL-2) is effective in such an experimental setting involving a methylcholanthrene-induced fibrosarcoma in mice. The purpose of the current work was to determine whether IL-2 treatment after, or before and after bone marrow transplantation would influence bone marrow engraftment or degree of hematologic reconstitution. We found that stem cell number (CFU-S) and posttransplant marrow cellularity were comparable in IL-2-treated or saline-treated mice. Furthermore, after engraftment, marrow stem cell and myeloid progenitor cell numbers were greater in the IL-2 treatment group. These results suggest that IL-2 will prove to be safe when administered in bone marrow transplant patients.

Animals

Longitudinal tibial epiphyseal bracket in Nievergelt syndrome.

A patient is described with lower extremity mesomelic dwarfism associated with bilateral congenital elbow, hip, and knee dislocations. Rhomboid-shaped tibiae and delayed ossification of the primary fibular ossification centers were demonstrated at birth. Plain films and magnetic resonance imaging revealed that the tibial deformities were due to the presence of longitudinal epiphyseal brackets. These brackets were observed at surgery and confirmed histologically. Recognition of the longitudinal epiphyseal bracket and its relationship to the tibial deformities seen in this patient with Nievergelt syndrome is important for planning surgical treatment.

Child, Preschool