The treatment of relapsed or refractory intermediate grade non-Hodgkin's lymphoma with autologous bone marrow transplantation followed by cyclosporine and interferon.

In an effort to decrease the relapse rate following autologous bone marrow transplantation for non-Hodgkin's lymphoma, patients were given cyclosporine and interferon following autologous marrow transplantation. Forty patients with intermediate grade non-Hodgkin's lymphoma that was relapsed or refractory to standard chemotherapy underwent autologous marrow transplantation. The preparative regimen consisted of cyclophosphamide 6.8 g/m2, etoposide 1600 mg/m2, and carmustine 400 mg/m2 over 4 days followed by reinfusion of bone marrow. Intravenous cyclosporine was started on day -1 as a 16 mg/kg loading dose followed by 3.6 mg/kg/day for 28 days after transplant. Patients were begun on alpha-interferon (starting dose, 0.5 million units s.c. every other day) following platelet engraftment (median day 24 post-transplant) and continued on 1.5 million units s.c. daily for 2 years. Regimen-related toxicities resulted in four (10%) deaths. Twenty-one (53%) patients developed marked erythema of the palms, soles, and arms. Biopsies of the erythema were consistent with grade I GVHD. Patients who did not develop rashes were not biopsied. The erythema persisted for a median of 10 days and resolved in all cases without treatment. Visceral GVHD was not apparent. All patients have been followed for a median of 24 months (range 12-54 months). To date, only five patients (13%) have relapsed after bone marrow transplant. Multivariant analysis could not identify risk factors for relapse post-transplant. Disease-free survival of all patients is 77% (95% confidence interval, 67-93%). The results of this pilot study suggest that the administration of cyclosporine and interferon may decrease the relapse rate of relapsed/refractory non-Hodgkin's lymphoma following autologous bone marrow transplantation.

NADP-specific isocitrate dehydrogenase from the citric acid-accumulating fungus Aspergillus niger.

NADP-specific isocitrate dehydrogenase [threo-DS-isocitrate: NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42] was purified 200-300-fold from the citric acid-accumulating fungus Aspergillus niger. The enzyme consists of a single polypeptide chain with a molecular mass of 60 +/- 4 kDa and has a pI of 5.9 +/- 0.2. Only a single enzyme protein was found, although the enzyme appears to occur both in the mitochondrion and in the cytoplasm. Growth on organic acids as carbon sources or on NO3- as nitrogen source led to increased activities, whereas the presence of amino acids led to lower activities. The enzyme exhibits hyperbolic kinetics with respect to its substrates isocitrate and NADP+. Mn2+ and Mg2+ are obligatory for enzyme activity. The enzyme is inhibited by its products alpha-oxoglutarate and NADPH. Among various metabolites, ATP and citrate appear to inhibit the enzyme at a concentration considered to occur intracellularly. In both cases, however, the mechanism is a removal of the metal ion cofactor from the substrates. It is concluded that under physiological conditions, where the Mg2+ content is around 10 mM, the observed inhibition by ATP or citrate is of poor regulatory significance.

Practicing pathology in New Jersey.

The author of this article presents a pathologist's perspective of practicing under New Jersey's DRG system.

Effects of carbon monoxide inhalation on ventricular fibrillation.

Since, in a previous study, inhalation of carbon monoxide resulted in demonstrable electrocardiographic effects on the myocardium, it was of interest to determine the effects of reduced hemoglobin oxygen content following carbon monoxide inhalation on the vulnerability of the heart to fibrillation. Normal monkeys and monkeys subjected to myocardial infarction were exposed to 100 ppm (115 mg/cu m) carbon monoxide for six hours, and the vulnerability of the heart to induced fibrillation was evaluated. The mean carboxyhemoglobin (COHb) concentration attained was 9.3%. The voltage required to induce fibrillation was highest for normal, air-breathing animals and lowest for infarcted animals inhaling carbon monoxide. Infarction alone and carbon monoxide alone each required significantly less voltage for fibrillation, and when the two were combined, the effects were additive.