A randomised, double-blinded, placebo-controlled, pilot study of parenteral glutamine for allogeneic stem cell transplant patients.

We conducted a prospective, randomised, double-blinded, placebo-controlled pilot study of parenteral nutrition (PN) supplemented with 0.57 g/kg glutamine-dipeptide in a homogeneous group of 32 allogeneic stem cell transplant (SCT) recipients to determine its effect on mucosal barrier injury (MBI). All patients had been prepared with idarubicin, cyclophosphamide and total body irradiation. PN (by continuous infusion) started on SCT day -6 for a median of 19 days. MBI measured by sugar permeability tests, daily mucositis score, daily gut score, and citrulline concentrations was not reduced by glutamine-dipeptide. However, the daily gut score was significantly lower for the glutamine group on SCT +7 (p = 0.001) whilst citrulline was lower (p = 0.03) for the placebo group on SCT day +21. Albumin was significantly lower in the placebo group on SCT day +21 (32+/-4 versus 37+/-3, p = 0.001) whilst CRP was higher (74+/-48 versus 34+/-38, p = 0.003). Other transplant-related complications (infections, acute graft-versus-host disease) were less common although this did not reach statistical significance nor translate into a reduced length of hospital stay or lower mortality. These results indicate that it would be worthwhile conducting a larger trial to see whether or not giving glutamine-dipeptide reduces the 100-day allogeneic transplant-related complications.

Effect of dietary fish oil supplementation on peroxidation of serum lipids in patients with non-insulin dependent diabetes mellitus.

Lipid peroxidation may be important in the development of cardiovascular disease, a common cause of mortality and morbidity in non-insulin dependent diabetes mellitus (NIDDM). We assessed the degree of lipid peroxidation by measuring plasma malondialdehyde, as thiobarbituric acid reacting substances (TBARS), in 23 non-insulin diabetic patients. Plasma levels of standardised alpha-tocopherol (vitamin E), lipid content of whole plasma and lipoprotein fractions, glycosylated haemoglobin, glycosylated low density lipoprotein (LDL) and fasting blood glucose were also measured. On completion of the baseline studies patients randomly received either fish oil or matching olive oil capsules in a double blind crossover fashion for 6 weeks followed by a 6 week washout period and a final 6 week treatment phase. Studies, identical to the initial baseline studies, were performed at the end of the of the active treatment periods at 6 and 18 weeks. Treatment with olive oil did not change levels of TBARS, vitamin E or indices of glycaemic control compared with baseline. Total cholesterol and triglyceride (TG) content of plasma and lipoprotein fractions were not significantly altered. Treatment with fish oil resulted in elevation of TBARS (P < 0.001) and reduction of vitamin E (P < 0.01) compared with baseline and olive oil treatment. Plasma cholesterol was unchanged. A reduction in plasma TG compared with baseline occurred but failed to reach significance (P =0.07). Changes in apo B containing lipoproteins induced by fish oil failed to reach significance. No significant changes were observed in concentration or composition of high density lipoprotein (HDL). Fish oil treatment showed no change in glycaemic control as assessed by glycosylated haemoglobin and LDL although a rise in fasting blood glucose just failed to reach significance (P = 0.06). Lipid peroxidation in NIDDM can be exacerbated by dietary fish oil. This potentially adverse reaction may limit the therapeutic use of fish oils in such patients.

Selective oral antimicrobial prophylaxis for the prevention of infection in acute leukaemia-ciprofloxacin versus co-trimoxazole plus colistin. The EORTC-Gnotobiotic Project Group.

230 leukaemic patients were entered into a randomised, prospective, multicentre trial of either ciprofloxacin (1 g/day) or co-trimoxazole (1920 mg/day) plus colistin (800 mg/day) for the prevention of infection during granulocytopenia. Bacteraemia due to resistant gram-negative rods occurred only in the co-trimoxazole-colistin group though both regimens were effective for selective gastrointestinal tract decontamination. However, there were fewer patients without any infective complications (31% vs. 18%: P = 0.02), fewer febrile days [mean (S.D.) 5.9 (1.1) vs. 8.2 (1.4): P = 0.0242], a lower proportion of infective events (0.9 (0.16) vs. 1.2 (0.18): P = 0.005) and fever occurred later (median 19 vs. 14 days: 0.025 less than P less than 0.05) in the co-trimoxazole-colistin group. The choice of prophylactic regimen therefore appears to depend upon whether or not protection against gram-negative infection is required or better systemic prophylaxis overall.

Options and limitations of long-term oral ciprofloxacin as antibacterial prophylaxis in allogeneic bone marrow transplant recipients.

The efficacy and safety of ciprofloxacin as long-term antibacterial prophylaxis after allogeneic bone marrow transplantation were assessed prospectively. Eighty-nine recipients of lymphocyte-depleted marrow grafts were each given ciprofloxacin orally, 500 mg twice daily. Fever developed in 71 out of 78 evaluable patients (91%) and was accompanied by positive blood cultures in 42 cases (59%). 'Viridans' streptococci, all but one with reduced in vitro susceptibility to ciprofloxacin, accounted for 35 episodes of bacteraemia. Thirty-three episodes occurred in patients given anthracyclines compared with only two episodes in other patients (chi 2 = 5.58: p less than 0.05). All bacteraemic fevers occurred within 11 days post-transplant. Gram-negative sepsis did not occur in any patient. Sixteen patients died but none due to a bacterial cause. Allergy to ciprofloxacin was registered in three out of 76 assessable cases (4%).

Prevention of infection in acute leukemia.

In a randomized study comparing cotrimoxazole plus colistin with ciprofloxacin, each in combination with nonabsorbable antimycotics, the incidence of major infections in terms of septicemias and pneumonias as well as of minor infections and episodes of unexplained fever (FUO) was higher in patients treated with ciprofloxacin. In cases of microbiologically documented infections, gram-positive cocci dominated by far. In surveillance cultures of oral washings and of feces, gram-negative enterobacteria were only rarely detected; however, large numbers of cultures were positive for Acinetobacter species. There were four cases of documented Pneumocystis carinii pneumonia in patients not receiving cotrimoxazole. The incidence of documented mycotic infections as well as the detection of fungi in surveillance cultures was similar in both treatment groups. A decrease in the number of adverse events, especially of allergic reactions, could not be achieved by the administration of ciprofloxacin. In conclusion, cotrimoxazole plus colistin in combination with nonabsorbable antimycotics remains the standard regimen for prevention of infection in patients with acute leukemia undergoing aggressive remission induction therapy. A detailed analysis of study II will be prepared for publication.