Lactic dehydrogenase and metabolism of human leukocytes in vitro.

During transformation and division of lymphocytes in culture, the lactic dehydrogenase isozymes migrate increasingly toward the cathode. With extension of the time in culture, the mitotic index declines, and the isozyme pattern reverts to dominance of those bands that move toward the anode, despite the cellular tendency to anaerobic metabolism. These findings suggest that synthesis of the more slowly migrating lactic dehydrogenase isozymes in this system is related to mitotic activity, and not to the aerobic or anaerobic conditions of cell culture.

Biochemically marked lymphocytoid lines: establishment of Lesch-Nyhan cells.

Two lymphocytoid cell lines have been established from a patient with the Lesch-Nyhan syndrome. The cells are deficient in hypoxanthine-guanine phosphoribosyltransferase, as demonstrated by their failure to incorporate [H(3)]hypoxanthine and by their inability to grow in medium in which they were nutritionally dependent upon exogenous hypoxanthine. This represents the first establishment of presumptively permanent human lymphocytoid cell lines that are deficient in a specific enzyme.

Immunoglobulin production by human lymphocytoid lines and clones: absence of genic exclusion.

Immunoglobulin production was studied in established lines of normal human lymphocytes. Three lines which produced both immunoglobulin G and immunoglobulin M were cloned. Among the 25 immunoglobulin-producing clones, 23 produced both classes of immunoglobulins. These findings suggest that the phenomenon of genic exclusion does not hold for immunoglobulin production in lymphocytoid cells in culture.

Effects of cyclosporin on insulin and C-peptide secretion in healthy beagles.

Plasma glucose, C-peptide, and insulin responses to intravenous glucose (intravenous glucose tolerance test [IVGTT], 0.5 g/kg), glucagon (1 mg i.v.), and oral glucose (oral glucose tolerance test [OGTT], 1 g/kg) were assessed in six normal beagles before, during, and 1 and 4 mo after the administration of cyclosporin A (CsA) in doses previously shown to be required for uniform prevention of canine islet-allograft rejection (20 mg/kg; mean trough radioimmunoassay serum levels greater than or equal to 500 ng/ml). Insulin secretion in response to intravenous glucose and glucagon was significantly inhibited during the administration of CsA (areas under insulin-response curves, pmol.min-1.L-1; IVGTT, pre-CsA, 11,127 +/- 1285; during CsA, 5954 +/- 1147, P less than .05; glucagon tolerance test, pre-CsA, 18,617 +/- 2807; during CsA, 4401 +/- 486, P less than .05 vs. pretreatment levels). These secretory defects persisted 4 mo after CsA was discontinued (IVGTT, 4358 +/- 659; glucagon tolerance test, 10,567 +/- 2479, P less than .05). C-peptide responses paralleled these changes. Plasma glucose disposal in response to these secretagogues, however, returned to normal 1 mo after discontinuation of CsA. In contrast to the findings for IVGTT and glucagon, insulin-response curves to OGTT were not statistically different during CsA administration. We conclude that, although glucose disappearance rates are normal after discontinuation of the CsA administration, CsA causes irreversible impairment in islet secretory responses detectable with IVGTT and glucagon but not with OGTT. These results suggest that short-term CsA in doses required to prevent islet-allograft rejection in dogs can result in permanent loss of functionally competent beta-cells.

Management of gallstones in diabetic patients.

The management of gallstones in diabetic patients has traditionally been considered problematic. Autopsy findings and uncontrolled studies have documented a higher prevalence of cholelithiasis in diabetics, and early reports showed dramatically increased perioperative morbidity and mortality for treatment of diabetics with acute cholecystitis. As a result, some authorities have recommended prophylactic cholecystectomy for diabetic patients with asymptomatic gallstones, which is in contrast to recommendations for nondiabetics. More recent investigators have shown comparable rates of operative morbidity and mortality for biliary surgery in diabetics when compared with the general population. Recent studies have questioned whether diabetes is an independent risk factor for gallstone formation. Decision analyses using these new data have shown that prophylactic cholecystectomy is not of clear benefit and should not be routinely recommended for diabetics with asymptomatic gallstones. We believe that available data, although limited, indicate that asymptomatic patients with diabetes do not benefit from screening for gallstones and that cholecystectomy should only be performed in cases of symptomatic cholelithiasis, as is the case in the general population.

Extension of survival of rat parathyroid allografts by depletion of Ia donor cells plus preoperative cyclosporine.

Methods that avoid chronic immunosuppression of transplant recipients must be developed to eliminate the various risk factors associated with such treatment (e.g., increased infections and malignancies). Pretransplant treatment of the graft with anti-Ia serum plus complement to eliminate "passenger cells" is one such method. An alternative approach is short-term treatment of the recipients with cyclosporine (CsA). In this study, parathyroid glands from Lewis X Brown Norway rats were cultured for one week at 37 degrees C and treated with anti-Ia and complement. Treated glands were transplanted into parathyroidectomized, hypocalcemic Wistar-Furth recipients that had received 30 mg/kg of CsA once a day for the three days prior to transplant. At 1 year posttransplant, 67% of the recipients had functional parathyroid allografts. Control rats (no CsA; fresh, untreated glands) rejected their grafts within 28 days. Controls given three days of CsA and transplanted with fresh, untreated glands all had functional grafts for greater than 56 days (median survival: 80.5 days). Prolongation of allograft survival with short-term, preoperative CsA demonstrates the efficacy of immunosuppression given only at the time of antigen presentation. This course of CsA allowed for indefinite graft survival when the recipient received a graft previously cultured and treated with Ia antiserum. These results are encouraging and should be evaluated further to determine whether similar approaches will be useful in human transplants.

Indefinite survival of rat parathyroid allografts without postoperative immunosuppression.

Methods that avoid long-term immunosuppression must be developed for human parathyroid allotransplantation to be feasible. Pretransplant treatment of the graft to eliminate passenger cells is one such method. An alternative approach is short-term treatment of the recipients with cyclosporine (CsA). In this study, parathyroid glands from Lewis X Brown Norway rats were cultured for 1 week and treated with antiserum directed against class II major histocompatibility complex antigens. Treated glands were transplanted into hypocalcemic Wistar-Furth recipients that previously received 30 mg/kg of CsA once a day for 3 days before transplantation. At 280 days after transplantation, 67% of the recipients had functional parathyroid allografts. Control rats (no CsA; fresh, untreated glands) rejected these grafts within 28 days. Control rats given 3 days of CsA and transplanted with fresh, untreated glands had functional grafts for greater than 56 days (median survival, 80.5 days). Prolongation of allograft survival with short-term, preoperative CsA demonstrates the efficacy of immunosuppression given at the time of antigen presentation. This course of CsA is even more effective when the recipient receives a graft whose passenger cells are eliminated.

Determination of malignancy of thyroid nodules with positron emission tomography.

BACKGROUND: Current noninvasive evaluation techniques of thyroid nodules are nonspecific. We studied the use of a new noninvasive imaging modality, positron emission tomography (PET), in the evaluation of thyroid nodules. METHODS: Nineteen patients were studied before operation with PET with [18F]-2-deoxy-2-fluoro-D-glucose (FDG). Twelve patients had solitary thyroid nodules and seven had multinodular goiters. Fourteen overlapping transverse slices were acquired through the thyroid gland. A region of interest was drawn around the abnormal area and the maximum pixel value was calculated and corrected to produce a normalized value for FDG uptake. RESULTS: Four of the 12 nodules were malignant (three papillary and one follicular carcinoma), with the others being follicular adenomas. All of the multinodular goiters were benign. All of the malignancies had an FDG greater than 8.5 and all of the benign nodules had an FDG less than 7.6. The dose uptake ratio of FDG was 10.8 +/- 3.2 (mean +/- SD) for the malignancies and was significantly greater than the dose uptake ratio of either the follicular adenomas (4.3 +/- 2.0) or the dominant nodule in multinodular goiters (3.0 +/- 2.0). CONCLUSIONS: The FDG uptake as measured by PET scanning successfully discriminated between all benign and malignant tumors. This technique appears useful in the evaluation of thyroid nodules.

Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: evaluations of 108 chemicals.

Results from the testing of 108 coded chemicals in Chinese hamster ovary (CHO) cells for the induction of chromosome aberrations and sister chromatid exchanges (SCEs) are presented. All chemicals were tested with and without exogenous metabolic activation, using protocols designed to allow testing up to toxic doses. Cell harvest times could also be extended if chemical-induced cell cycle delay was seen. Chromosome aberrations were induced by 43 of the chemicals, and 66 induced SCEs; 37 of the chemicals were positive for both endpoints.

A technique of direct percutaneous jejunostomy tube placement.

A technique for replacement of a feeding jejunostomy tube using endoscopic direct visualization is described herein. It can be used in patients who have had a previously placed open jejunostomy tube removed after recovery from resection of the gastrointestinal tract. This is accomplished quite easily using local anesthesia with intravenous sedation using an upper endoscope, guide wire, peel-away sheath and a standard Silastic catheter.

Positron emission tomography of thyroid masses.

Nine patients with suspicious thyroid nodules were studied with positron emission tomography (PET) following the administration of [18F]-2-deoxy-2-fluoro-D-glucose (FDG) prior to surgical excision. Three patients were ultimately determined to have papillary carcinoma, four were shown to have follicular adenomas, and two were proven to have multinodular goiters with dominant nodules. All three malignancies and four of the six benign lesions were easily detected visually as areas of increased FDG uptake. While visual analysis alone did not discriminate between the benign and malignant lesions, all three malignancies had dose uptake ratios (DURs) for FDG in excess of 8.5 while the DURs for benign lesions ranged between 1.9 and 6.3. The mean FDG DUR for the three papillary carcinomas (10.9 +/- 3.9; mean +/- SD) was significantly greater (p = 0.0019) than that of the six benign lesions (3.2 +/- 1.7). There was no significant difference between the FDG DUR for the follicular adenomas and the dominant nodules of multinodular goiters. Further research is needed to confirm the usefulness of PET in the differential diagnosis of thyroid nodules, and, in particular, whether or not PET can discriminate between benign and malignant follicular neoplasms.

Sister chromatid exchanges and chromosome aberration frequencies in plutonium workers.

Peripheral blood lymphocytes from controls and from a small population of plutonium workers with internal plutonium depositions, cumulative chronic external irradiation, and occupational exposure to single or multiple chemicals, were analysed for the frequency of sister chromatid exchanges (SCE) and chromosome aberrations. SCE are sensitive to some chemical mutagens, while chromosome aberrations are induced by moderate to high doses of ionizing radiation, and therefore these different cytogenetic end-points are complementary. We analysed the frequency data from workers grouped by internal systemic burdens of plutonium (less than 148, 148-740 and greater than 740 Bq) and to those exposed to five chemicals in the workplace: perchloroethylene, beryllium, carbon tetrachloride, benzene, and trichloroethylene. A significant increase in chromosome aberrations compared with the control frequency was observed only in cells of workers with greater than 740 Bq of internalized plutonium. Based on prior studies, the lack of a dose-response indicator from internal plutonium was not unexpected because of the small sample and the low frequency of aberrations induced at the lower plutonium burdens. There were no significant increases in the SCE mean frequencies when analysed by estimated internal plutonium or from exposure to any of the chemicals.

Pitfalls in ambulatory treatment of inguinal hernias in adults.

Careful patient selection and preparation for ambulatory inguinal herniorrhaphy combined with monitored local anesthesia result in a safe procedure with excellent patient acceptance. Factors contributing to early and late complications are presented, and the common methods of their treatment are reviewed.

Gallstone ileus.

Twenty patients with gallstone ileus were treated over a 20-year period. The demographics were typical: mean age 76, female to male ratio of 5:1, and 60 per cent incidence of concomitant medical ailments. An 85 per cent preoperative diagnostic rate was unusually high. An analysis of the study halves demonstrated a stable preoperative diagnostic rate, decrease in preoperative delay (7.5 vs. 4.7 days), and a rise in mortality rate (0 vs. 11%) without an unfavorable effect from a 26 per cent incidence of single-stage procedures (0% mortality). Gallstone ileus still carries a mortality rate of five to ten times that of all other nonmalignant mechanical small bowel obstructions. Anticipated improvements related to augmented preoperative diagnostic yields shortened preoperative delays, and selective surgical management have not been substantiated. Improved mortality rates may await refinements in resuscitation, monitoring, and surgical skills.