The influence of dose and dose rate of total lymphoid irradiation in the rat cardiac allograft model.

Immunosuppression generated by total lymphoid irradiation (TLI) may be of use in solid organ transplantation. We have investigated the use of TLI in the rat cardiac allograft model. Lewis rats received TLI from a cobalt-60 machine. The daily dose was 1.25 Gy and treatments were administered 4 days per week. We performed experiments to assess the effect of dose rate upon graft survival. The dose rate was varied by changing the source to animal distance and by using a lead attenuator. Cardiac allografts from each ACI donor rat were transplanted to the recipient Lewis rat's abdomen utilizing microvascular surgical technique. Heart graft survival times (GST) were monitored by direct palpation of the cardiac impulse. Immune function was measured by an activity index of the mixed lymphocyte reaction. In the absence of any immunosuppression there was a mean GST of 6.9 +/- 0.3 days. When a graft was placed the day following completion of TLI, there was an increase in GST as the total TLI dose was increased. Mean GST (+/- S.E.) following 5, 10, and 15 Gy were 12.3 +/- 1.3, 14.5 +/- 1.3, and 25.5 +/- 1.1 days, respectively. Following 20 Gy, GST decreased because of irradiation induced pulmonary toxicity and host death. When 3.5 weeks were allowed to elapse between the completion of TLI and transplantation, GST were less than those seen with equivalent doses of TLI and early transplantation. Mean GST following 5, 10, and 15 Gy and a delayed transplant were 7.2 +/- 0.1, 10.7 +/- 1.2, and 19.0 +/- 3.5 days, respectively. We tested the effect of dose rate upon GST.(ABSTRACT TRUNCATED AT 250 WORDS)

Electron microscopy in selection of patients with small cell carcinoma of the lung for medical versus surgical therapy.

Fifty-one cases of small cell carcinoma of the lung were studied by electron microscopy in order to determine if ultrastructural subsets could be found and if these subsets predicted clinical behavior. All of these cases were considered bona fide small cell carcinoma of the lung by light microscopy. Tumors with ultrastructural features of epithelial differentiation were defined by the presence of well-formed, classic desmosomes joining adjacent cells and by additional features of squamous or glandular differentiation. Thirty-one tumors (60%) were considered "typical oat cell" by electron microscopy and 20 (40%) showed features of epithelial differentiation. Fifteen (75%) tumors with epithelial features were considered operable and nine (45%) were resected with curative intent. In contrast, 26 (84%) tumors considered typical oat cell by electron microscopy presented with extensive metastatic disease. The cancer-free 5-year actuarial survival rate of patients whose tumors showed features of epithelial differentiation was 25%. The actuarial survival rate of nine patients who underwent resection of tumors with epithelial features was 38% at 5 years. Only one patient whose tumor was considered typical of oat cell carcinoma by electron microscopy survived 5 years. Our current recommendation is to remove all clinically resectable pulmonary neoplasms with the expectation that these localized small cell tumors are likely to show epithelial features by electron microscopic analysis.

Tertiary hyperparathyroidism after renal transplantation: operative indications.

A retrospective analysis of our renal transplant population between 1981 and 1987 was undertaken to study the natural history of posttransplant hypercalcemia and to review indications and recommendations regarding the timing of parathyroidectomy. During this period, 1158 renal transplant procedures were performed in 1025 patients, with 819 allografts (71%) functioning currently. Posttransplant hypercalcemia greater than 10.5 mg/dl was associated with a longer duration of dialysis and developed in 227 patients, with onset of hypercalcemia occurring in 90% of these patients by 1 year. In 69% of these patients, spontaneous resolution of the hypercalcemia occurred between 6 months and 7 years after transplantation. A total of 42 patients with asymptomatic hypercalcemia are currently being followed up, with a mean serum calcium level of 11.0 +/- 0.41 mg/dl and a mean follow-up interval of 3.3 +/- 1.6 years since transplantation. Nine symptom-free patients with moderate hypercalcemia (12.0 to 12.4 mg/dl) more than 1 year after transplantation were identified. Five of these patients had spontaneous resolution of the hypercalcemia between 2 and 7 years. Fifteen patients with posttransplant hyperparathyroidism (6.6%) required parathyroidectomy--11 for symptomatic and four for asymptomatic hyperparathyroidism. One patient had symptomatic hyperparathyroidism despite the presence of normocalcemia. One symptom-free patient with significant hypercalcemia (serum calcium level, 14.7 mg/dl) underwent parathyroidectomy 3 months after transplantation. The remaining three symptom-free patients had serum calcium determinations of greater than or equal to 12.5 mg/dl more than 1 year after renal transplantation. Patients with pretransplant and posttransplant hypercalcemia required parathyroidectomy more frequently than did patients with only posttransplant hypercalcemia (18% versus 3.0%; p less than 0.001). An unusual finding was the occurrence of a single adenoma in two patients, which represents sporadic primary hyperparathyroidism in the patient undergoing renal transplantation rather than tertiary hyperparathyroidism. We recommend a conservative approach to posttransplant hypercalcemia, with surgery reserved for patients with symptomatic disease and patients with asymptomatic persistent hypercalcemia greater than or equal to 12.5 mg/dl more than 1 year after transplantation.

Combined liver and pancreas procurement with Belzer-UW solution.

Graft availability remains the major limitation to organ transplantation. Belzer-UW solution has been used for multiple organ procurement in 20 consecutive donors. Belzer-UW solution was used for both aortic in situ flush and ex vivo cold storage. From 20 donors, a total of 20 pancreatic grafts, 20 livers, 39 kidneys, and 10 hearts were procured. Mean preservation time was 14.2 hours for the pancreas, 16 hours for the kidney transplanted with the pancreas, 13.8 hours for the liver, and 29.9 hours for the isolated kidneys, which were machine perfused. Graft survival of the organs transplanted at the University of Wisconsin was 100% for kidney and pancreas, 93.3% for the isolated kidney, and 78.5% for the liver. When the organs referred to other centers were included, 84 of 89 procured organs were functioning at 1 month. It is concluded that multiorgan procurement with Belzer-UW solution yields excellent graft function for all abdominal organs.

Hyperphosphatemia from lipid emulsion in a patient on total parenteral nutrition.

The clinical course of a patient is described in whom hyperphosphatemia occurred on total parenteral nutrition with lipid emulsion providing half of the nonnitrogenous caloric support. Renal insufficiency, hypoparathyroidism, pseudohypoparathyroidism, and severe catabolism are excluded as causes of this hyperphosphatemia. Changes in serum phosphate are attributed to metabolism of phospholipid present in the lipid emulsion, the sole phosphate source in this patient. These observations suggest that the phosphate of phospholipids can contribute significantly to the metabolic pool of inorganic phosphate. Lipid emulsion, most commonly thought of as a major caloric source, should not be neglected when one is confronted with hyperphosphatemia during total parenteral nutrition.

The role of magnesium in nucleic-acid and protein metabolism.

Magnesium is an essential cofactor for the synthesis and salvage of purine and pyrimidine nucleotides. It plays important roles in the structure of nucleic acids and affects their interaction with proteins and other ligands. Magnesium is required for DNA replication, transcription into RNA and translation into protein. In spite of the diverse roles of magnesium in these fundamental processes, metabolic regulation by magnesium has not been observed. Its role in the regulation of cell growth, division and differentiation remains uncertain.

Sensitivity and specificity of a monitoring test.

The usefulness of a diagnostic test is generally assessed by calculating the sensitivity and specificity, or the predictive value positive and predictive value negative of the test. When subjects are monitored periodically for evidence of disease, these calculations must incorporate the varying amounts of information per individual. If in addition, the test results lie on a continuous scale, these quantities vary with the cutoff value (cutpoint) used to define a positive test. They are usually calculated for a spectrum of potential cutpoints in order to produce receiver-operator characteristic curves. In this paper we use a partial likelihood solution to the discrete logistic model in order to obtain estimates of the diagnostic test indices and to provide a significance test when the diagnostic test is administered repeatedly to individuals.

Binding of triton X-100 to diphtheria toxin, crossreacting material 45, and their fragments.

Binding of the nonionic detergent [3H]Triton X-100 by diphtheria toxin, by the nontoxic serologically related protein crossreacting material (CRM) 45, and by their respective A and B fragments has been studied. If first denatured in 0.1% sodium dodecyl sulfate, all of the proteins with the exception of fragment A bind increasing amounts of Triton X-100, reaching a maximum of more than 40 mol bound per mol of protein when the detergent concentration exceeds its critical micelle concentration. No measurable amount of Triton X-100 is bound by native toxin or its A fragment of any concentration of the detergent. Undenatured CRM45 or its B45 fragment, on the other hand, readily became inserted into Triton X-100 micelles when the detergent reaches its critical micelle concentration. The results show that the toxin molecule contains a hydrophobic domain located on the portion of the B fragment that is linked to A. This region is masked in native toxin. Based on these findings, a model is proposed to describe how fragment B facilitates the transport of the enzymically active hydrophilic fragment A across the plasma membrane to reach the cytoplasm.

Malpositioned peritoneal dialysis catheters: a critical reappraisal of correction by stiff-wire manipulation.

Tenckhoff peritoneal dialysis (PD) catheter malposition is one of the leading causes of catheter malfunction. Fluoroscopically directed stiff-wire manipulation of malpositioned PD catheters has been advocated as a method of catheter salvage. Two hundred eighty-nine single-cuff PD catheters were placed surgically into 203 patients during this 4-year study. Thirty-three patients developed catheter malfunction attributed to malposition. Forty-eight stiff-wire manipulations were performed on these patients. Thirty-eight (78%) of the manipulations were described as successful at the time of transfer from radiology. However, only 25 (51%) and 12 (25%) resulted in functioning catheters at 1 week and 1 month, respectively. Only 11 of 33 patients who underwent manipulation had functional prolongation of catheter life beyond 1 month. The PD catheter was replaced by a column-disk PD catheter without additional catheter dysfunction in six patients. A second single-cuff Tenckhoff PD catheter was inserted in another six patients. Three of these six catheters again malpositioned. We conclude that stiff-wire manipulation is a useful and safe technique worth using on a limited basis for the initial episode of catheter malposition. Catheters that repetitively malposition should be replaced with a catheter that is resistant to malpositioning.