Between one and six cultured human fetal pancreata were allografted into five insulin-dependent diabetic recipients and their progress monitored for a year on each occasion. To prevent rejection the tissue was cultured for 1-3 weeks before transplantation, the HLA-DR antigens of the donor tissue were matched with those of the recipient when a single pancreas was used, and four of the recipients were immunosuppressed, three because of coexisting renal grafts. Graft function was observed transiently in one of the recipients. In three others human fetal pancreas was recovered 9-14 months after transplantation, although it was being slowly rejected during this time. Beta cells were present in the graft but did not function adequately to enable immunoreactive C-peptide to be measured in peripheral blood. The issues of rejection and immaturity of the human fetal pancreas will need to be surmounted if the potential of the human fetal pancreas to normalize blood glucose levels in diabetic man is ever to be realized.

A series of 60 cases of prostatic adenocarcinoma and 34 cases of benign prostatic hyperplasia were examined quantitatively after immunoperoxidase staining for prostate-specific antigen (PSA), prostate-specific acid phosphatase (PSAP), carcino-embryonic antigen (CEA), epithelial membrane antigen (EMA), alpha fetoprotein (AFP), and human chorionic gonadotrophin (HCG). The tumors were graded I to IV according to the MDAH grading system recently proposed. Fifty-nine of the 60 tumors were positive for PSA and 58 were positive for PSAP. The one PSA and PSAP negative case was CEA negative and weakly EMA positive. Grade I to III tumors stained more tumor cells and more diffusely for PSA and PSAP than grade IV tumors. There was no significant difference in the intensity or extent of staining between grade I and grade II-III tumors for PSA and PSAP. A comparison of PSA and PSAP showed that PSA stained more intensely and more extensively than PSAP. Benign prostatic tissue and low-grade prostatic tumors did not stain for CEA but three of the 20 grade IV tumors and one of the 23 grade II-III tumors did. Staining for EMA was focal and showed no relation to tumor grade. Benign and malignant lesions failed to stain for AFP and HCG.

Nephrotoxicity is a major side effect of cyclosporin A (CSA) when used in renal transplantation, and the distinction between nephrotoxicity and rejection is important in patient management. One hundred twenty-five renal biopsies were examined from 56 patients entered into a controlled clinical trial aimed at comparing the efficacy of CSA therapy alone to a combination of prednisone, azathioprine, and antilymphocyte globulin (AZA). In order to define the histopathology of rejection and nephrotoxicity, all the biopsies were evaluated in a semiquantitative manner by an observer unaware of the clinical state of the patient. Comparison of the morphological appearances of 32 biopsies from patients on CSA, and 22 biopsies from AZA-treated patients performed during clinically apparent rejection episodes showed that the histological patterns of rejection were the same in both treatment groups. Comparison of the morphological features of 34 biopsies from patients receiving CSA and 13 from patients receiving AZA, performed during prolonged periods of post-transplant renal failure, who eventually recovered on continuation of original therapy, showed that there were no morphological features specific to the CSA-treated group. Five patients on CSA had oliguria which was prolonged by CSA nephrotoxicity. Thirteen biopsies from all five patients showed a diffuse interstitial fibrosis that was peculiar to this group of patients.

The transplantation of human fetal pancreas has been suggested as a means of treatment of insulin-dependent diabetes in man. We have obtained human fetal pancreata during the second trimester of pregnancy and transplanted 1-mm3 explants subcutaneously (s.c.) into both diabetic and nondiabetic nude mice, some of the tissue being cultured in vitro before implantation. These implants coalesced and grew. They were removed at intervals up to 37 wk later and showed selective differentiation of endocrine tissue that normally occurs in the fetus and neonate, with formation of bipolar, mantle, and mature islets. There was growth of this endocrine tissue with significantly more islets than in the freshly stained fetal pancreas assuming an average dimension larger than 150 micron, which is the reported mean diameter of a neonatal islet. Duct and fibrous tissue remained viable, but there was no definitive acinar tissue seen. The pancreata uncultured before implantation reached a larger size than that attained by those implants cultured before being transplanted, the difference probably being the amount of ductular and mesenchymal tissue still present. Of those glands cultured before transplantation, the longer the period of culture, the smaller the size the implants reached. Culture beyond 3 wk in vitro made it difficult to macroscopically locate the implant. These data show that, in human fetal pancreas removed from its usual environment, both selective differentiation of the endocrine component and growth of the islets can occur.

Some factors influencing the detection of malignant cells in sputum samples were evaluated in 449 consecutive cases of primary lung carcinoma seen between 1959 and 1974. Diagnostic accuracy increased during the years under study; the reasons are discussed. The overall accuracy was 82.8%. Detection of malignant cells was 85% for small-cell carcinoma, squamous-cell carcinoma and large-cell carcinoma, 75% for adenocarcinoma, bronchioloalveolar carcinoma and adenosquamous carcinoma and 64% for the uncommon tumors. Accuracy was 87% for central tumors and 42% for peripheral lesions. Tumors less than 2 cm in diameter yielded only 39% accuracy as compared to 90% for larger tumors. The specificity of diagnosis of cell type in those specimens with malignant cells was 95% for small-cell carcinoma and squamous-cell carcinoma, more than 80% for adenocarcinoma and large-cell carcinoma, 65% for bronchioloalveolar-cell carcinoma and adenosquamous carcinoma and less than 30% for the uncommon tumors. Diagnostic accuracy was optimal in those cases with three or more sputum samples: 83% for those with three samples and 90% for those with five or more samples per case. The use of both sputum and bronchial specimens was complementary and increased the accuracy further. Reasons for unsatisfactory specimens included no deep cough, limited cellular material, excessive blood or leukocytes and drying artifacts; the first two were the most common causes.