Protection of murine bone marrow by dexamethasone during cytotoxic chemotherapy

Corticosteroids have the ability to suppress the production of growth factors and cytokines and are thus implicated in the negative regulation of hematopoiesis. We have shown that the corticosteroids, prednisolone and dexamethasone, were able to effectively protect progenitor cells in four strains of mice against cell-cycle-specific antimetabolic chemotherapy agents. The highest levels of protection against 5-fluorouracil (FU; 200 mg/kg) were achieved when two or three intraperitoneal injections of dexamethasone were administered between - 7 and +3 hours at a dose of 7.5 mg/kg/injection (optimal dose) or by continuous infusion between -4 and +20 hours. This protective effect is manifested as an increase in the number of high proliferative potential colony-forming cells that survive in the bone marrow 3 days after treatment with FU from between 0.5% and 11% to between 10% and 34% of normal. The bone marrow progenitors and blood cell numbers return to normal from 3 to 5 days and 1 to 2 days earlier, respectively. Less dexamethasone than prednisolone is required to give an equivalent protective effect, which is consistent with their anti-inflammatory potency. These findings are further evidence of the negative regulatory role played by corticosteroids, and indicate that the treatment schedules of corticosteroids during cancer therapy need to be reexamined to obtain the maximum benefit from their use.     

Conjugated dihydroxy bile salt inhibition of glucose influx in rat jejunumin vitro

Effects of bile salts on intestinal glucose transfer differ in diverse animal preparations exposed to various bile acids. Radiolabeled glucose influx into rat jejunum in vitro was studied in buffer and compared to taurodeoxycholate, taurochenodeoxycholate, taurocholate, and deoxycholate. Jejunum was obtained from intact, bile-diverted, and colestipoltreated rats and in similar categories after abdominal x-irradiation. Taurodeoxycholate but not taurocholate inhibited glucose influx only in bile-fistula and colestipol-treated rats. Bile diversion increased and colestipol decreased glucose uptake from buffer. Added inhibitory effects of irradiation and bile salts were seen in bile-fistula animals. These data suggest that normal exposure to bile is chronically inhibiting jejunal glucose transport and that dihydroxy bile salts are responsible for this effect. They do not provide an explanation for the role of bile in the intestinal radiation syndrome.This work was supported in part by contract No. AT-(40-1) 3882 from the U.S. Atomic Energy Commission.These data were presented in part at the annual meeting of the Southern Society for Clinical Investigation, New Orleans, La. February, 1975.     

Prolactin and its 16-kDa N-terminal fragment: are higher in patients with precapillary pulmonary hypertension than in a healthy control group

We sought to determine whether patients with precapillary pulmonary hypertension show elevated serum levels of prolactin (PRL) and its 16-kDa N-terminal fragment (16-kDa PRL) and whether there is any correlation to measures of prognosis.Twenty-eight patients with idiopathic pulmonary artery hypertension, 15 with peripheral chronic thromboembolic pulmonary hypertension, and 4 with portopulmonary hypertension Child-Pugh class A were included. Our control subjects were 56 blood donors. Total prolactin was measured with an immunoluminometric assay. Antibodies against epitope C detected only the intact prolactin before it was split. The 16-kDa PRL was calculated from the difference between total and intact prolactin.Prolactin was significantly (P=0.009) higher in the study group (median, 190 mU/L; interquartile range, 162 mU/L) than in the control group (median, 140 mU/L; interquartile range, 91 mU/L). The 16-kDa PRL was significantly elevated in the study group (P=0.046). Prolactin and 16-kDa PRL correlated inversely with the 6-minute-walk distance (P <0.01) and with peak oxygen uptake during exercise (P <0.005).Serum levels of prolactin and 16-kDa PRL were significantly higher in patients with precapillary pulmonary hypertension and were inversely correlated with 6-minute-walk distance and peak oxygen uptake.These results indicate that prolactin and 16-kDa PRL might play a role in the pathophysiology of precapillary pulmonary hypertension.     

POEMS syndrome treated with melphalan high-dose therapy and autologous blood stem cell transplantation: a single-institution experience

The acronym POEMS syndrome stands for a rare multi-system disorder, comprised of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. Here, we present a single-center report of a series of five POEMS patients treated with melphalan high-dose therapy (HDT) with subsequent autologous blood stem cell transplantation (ABSCT). After a median follow-up of 52 months from time of diagnosis (range, 15-192) and a median follow-up of 18 months after ABSCT (range, 11-120), all patients were alive. Overall, no severe transplantation-associated complications such as engraftment syndrome or peri- or post-transplant death were noted. In two cases, HDT followed by ABSCT resulted in a complete hematologic response; in the additional three cases, partial responses (PR) were achieved including one very good hematologic PR. Only one patient with initial PR developed progressive disease nearly 2.5 years after transplantation. Consequently, a second HDT with ABSCT was successfully applied resulting in clinical improvement and hematologic PR. In line with previous single-center reports, melphalan HDT followed by ABSCT proved to be a first-line treatment option with tolerable side effects in severely affected POEMS patients with progressing symptoms.