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Oral mucositis is a frequent side effect of myeloablative chemo- and radiotherapy preceding stem cell transplantation. It causes pain, poor food intake, and is a port of entry for infection. We studied whether GM-CSF applied topically in the oral cavity can prevent or ameliorate this mucositis. In 36 consecutive patients undergoing a stem cell transplantation, we performed a double-blind placebo-controlled study of 300 micrograms GM-CSF in a 2% methylcellulose gel daily versus a 2% methylcellulose gel alone. Both were locally applied in the oral cavity. The primary end-point was mucositis as measured by the WHO toxicity scale for mucositis, oral assessment scale, and a subjective pain scale, all scored daily. The secondary end-points were need to give parenteral nutrition and morphine, incidence of fever and infections, and duration of neutropenia and hospitalization. No differences were found in the median subjective pain scores, WHO scores, and oral assessment scores between the placebo and the GM-CSF groups. In both groups, nine patients required morphine for pain control. Ten patients in the placebo group and 11 in the GM-CSF group received parenteral nutrition. Documented infections, use of broad-spectrum antibiotics, and number of days with fever were similar in the placebo and the GM-CSF groups. The duration of neutropenia below 0.5 x 10(9)/l (median 14.5 days in the placebo group versus 17 days in the GM-CSF group) and the duration of hospitalization (28.5 versus 29 days) was also not significantly different. We found no beneficial effect of 300 micrograms GM-CSF dissolved in a 2% methylcellulose gel applied locally for chemo- and radiotherapy-induced mucositis in patients undergoing a stem cell transplantation.

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UNLABELLED: Parenteral nutrition is associated with liver enzyme abnormalities. Until 1993 the incidence of icterus was low in both academic hospitals in Amsterdam, the Netherlands (Academic Medical Centre (AMC) and Academic Hospital of the Free University (AZVU)). In 1993 Intralipid in the nutrition was replaced by Endolipid in the home total parenteral nutrition programme (AMC) and by Lipofundin S in AZVU. Fifty per cent of the patients in the home programme developed severe fatigue, jaundice and thrombocytopenia. These signs and symptoms disappeared over months when parenteral nutrition without fat was given. After reintroduction of Intralipid these signs and symptoms never recurred. In AZVU the incidence of jaundice increased from 21% in 1992 to 79% in 1993 (p = 0.0002). After reintroduction of Intralipid in 1994 the incidence of jaundice decreased to 16%. CONCLUSION: Although the lipid emulsions are equivalent according to the product specification, the described observation suggests that Lipofundin S and Endolipid cause more icterus than Intralipid, possibly caused bij an impurity in the fat emulsion.

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Tumor necrosis factor alpha (TNF-alpha) may be involved in the pathogenesis of metabolic and endocrine changes in HIV infection. Pentoxifylline (PTX) is able to suppress the production of TNF-alpha in vitro. The effect of two dosages of intravenously administered PTX on clinical symptoms and ex vivo LPS-stimulated TNF-alpha production was evaluated in six clinically stable AIDS patients in a saline-controlled study. PTX in a dosage of 1.5 mg/min was tolerated without side effects. PTX in a dosage of 2.1 mg/min resulted in intolerable nausea and necessitated termination of infusion after 30 min. The average plasma concentration of PTX after infusion of 1.5 mg/min for 6 hr was 510+/-56 ng/ml, which is considerably below the concentrations that have been reported to suppress TNF-alpha production in vitro. No effect of PTX infusion (1.5 mg/min) on LPS-stimulated TNF production ex vivo was found. Our conclusion is that the maximally tolerated i.v. dosage of PTX in AIDS patients is 1.5 mg/min. LPS-stimulated ex vivo TNF-alpha production, at the LPS concentrations tested, was not inhibited by the plasma concentration of PTX that could be achieved at this dosage.

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By US standards, about half of African children are malnourished, although most appear clinically normal. It is possible that precursor supply for gluconeogenesis is limited to a greater extent in these seemingly malnourished African children than in healthy children, consequently limiting glucose production. Since in malaria peripheral glucose utilization is increased, precursor supply could play an even more critical role in maintaining glucose production in African children suffering from falciparum malaria. We studied the effect of alanine infusion (1.5 mg/kg/min) on glucose production (measured by infusion of [6,6-2H2]glucose) and plasma glucose concentration in 10 consecutive children with acute, uncomplicated falciparum malaria. By US standards, six children were below the 10th percentile of weight for height and seven were below the 10th percentile of height for age. Plasma concentrations of alanine increased during alanine infusion from 153 +/- 21 to 468 +/- 39 mumol/l, whereas plasma lactate concentrations did not change (1.4 +/- 0.2 vs. 1.3 +/- 0.2 mmol/l). Plasma glucose concentration and glucose production did not change during alanine infusion: 4.6 +/- 0.3 vs. 4.5 +/- 0.3 mmol/l and 5.8 +/- 0.4 vs. 5.7 +/- 0.3 mg/kg/min, respectively. Gluconeogenic precursor supply is sufficient for maintainance of glucose production in African children with uncomplicated malaria who are malnourished by US standards.

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Between 1983 and 1988 we treated 36 patients with sporadic amyotrophic lateral sclerosis (ALS) by an array of antioxidants and added other drugs to the regimen whenever a patient reported deterioration. Our customary prescription sequence was N-acetylcysteine (NAC); vitamins C and E; N-acetylmethionine (NAM); and dithiothreitol (DTT) or its isomer dithioerythritol (DTE). Patients with a history of heavy exposure to metal were also given meso 2,3-dimercaptosuccinic acid (DMSA). NAC, NAM, DTT, and DTE were administered by subcutaneous injection or by mouth or by both routes, the other vitamins and DMSA by mouth alone. The hospital pharmacy supplied NAC and NAM injections fluid as 100 ml bottles of 5.0 and 5.85% solutions, respectively. DTT was delivered in special double-walled capsules of 200 mg. DTT/DTE injection fluid was added to the NAC and NAM bottles, the final DTT/DTE concentrations never exceeding 0.5%. DMSA was provided in 250 mg capsules. All of the 36 patients used NAC and DTT/DTE; 29 also used vitamins C and E; 21 also used NAM; and 7 also used DMSA, DMSA, NAM, vitamins C and E were tolerated well. In many patients, DTT, DTE, NAC and NAM induced pain, redness and swelling at the injection sites in that order of decreasing frequency. DTT and DTE did often and NAC did sometimes cause gastric pain, nausea and other abdominal discomfort. Comparison of survival in the treated group and in a cohort of untreated historical controls, disclosed a median survival of 3.4 years (95% confidence interval: 3.0-4.2) in the treated and of 2.8 (95% confidence interval 2.2-3.1) years in the control patients. This difference may be explained by self-selection of our highly motivated treated group and by its initial survival of diagnosis for an average of 8.5 months before onset of treatment. We conclude that antioxidants neither seem to harm ALS patients, nor do they seem to prolong survival.

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BACKGROUND: Glutamine-supplemented total parenteral nutrition (TPN) improved the nitrogen balance in catabolic situations. In animal studies, parenteral glutamine supplementation appeared to maintain gut integrity. This study was performed to evaluate the possible positive effects of glutamine supplementation in catabolic hematologic patients. METHODS: This was a prospective double-blind placebo-controlled pilot study, in which 20 treatment cycles in unselected hematologic patients with intensive chemotherapy were studied. Glutamine was given as a dipeptide. Patients were randomized per treatment cycle to receive isonitrogenous TPN (0.272 g nitrogen/kg of body weight) and isoenergetic TPN (2200 kcal NPE/day) without or with 40 g L-alanyl-L-glutamine (26 g glutamine) until the neutrophil count was greater than 0.5 x 10(9)/L. The daily oral food intake was recorded and analyzed carefully. Toxicity grades for performance status, mucositis, and diarrhea were scored according to the World Health Organization classification. RESULTS: No differences in neutropenic period, fever, extra antibiotics, and toxicity scores were observed, except for a gain in body weight per treatment cycle in favor of the glutamine-supplemented TPN. No side effects or allergic reactions were noted after the dipeptide administration. CONCLUSION: Supplementation of glutamine dipeptide was safe but had no significant positive clinical effect.

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The maximal allowable concentrations of calcium and phosphate in total parenteral nutrition mixtures for children from one compartment were investigated. Children treated with both chemotherapy and total parenteral nutrition are supplied with high amounts of electrolytes (besides normal nutritive needs) in a restricted volume. Such nutritive mixtures are suspected of precipitation and disintegration of the lipid emulsion by (polyvalent) electrolytes, such as calcium and phosphate. Calcium (range 1.5-150 mmol/l total parenteral nutrition) and phosphate (range 21-300 mmol/l) were added to a test total parenteral nutrition mixture. After storage (24 and 48 h) at both 22 degrees C and 37 degrees C the mixtures were observed by microscopy for the presence of precipitates. The stability of the fat emulsion was visually assessed and the particle size distribution was measured by flow cytometry. The examined total parenteral nutrition mixtures (pH 5.4-5.7) were stable during 48 h at 37 degrees C if the calcium concentration is below 16 mmol/l, the phosphate concentration is below 52 mmol/l and the product of both concentrations is below 250 mmol2/l2.

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This study aimed to investigate the peripheral vein tolerance for total parenteral nutrition (TPN) and to point out the factors which induce phlebitis. TPN was administered from 'all-in-one' bags. Five different types of TPN were investigated, wherein the amounts of amino-acids, dextrose, lipids, osmolarity and volume were varied. Type I (829 mOsm/l) was a low energy (1570 NPE kcal) nutritive mixture of 2425 ml with 9.5 g N. Type II (842 mOsm/l) was an intermediate energy (1800 NPE kcal) mixture of 2525 ml with 9.5 g N. Type III (860 mOsm/l) contained 1800 NPE kcal and 13.5 g N in 2775 ml. Type IV (790 mOsm/l) was only a dilution of Type III with 250 ml water. Type V (1044 mOsm/l) covered normal energy needs (2000 NPE kcal) and 13.5 g N in 2580 ml. All bags contained standard amounts of electrolytes, vitamines, trace elements and heparin (1.000 IE/l). The infusion site was not changed until phlebitis developed or oral feeding could be started. Type I, II, III and IV were given to at least 30 patients, and Type V to only 11 patients because of an unacceptable high phlebitis rate (91% after 2.8 days). The phlebitis rate for Type I, II, III and IV was 4%, 12%, 24% and 27% respectively after 48h increasing to 14%, 37%, 55% and 73% respectively after 14 days. The mean infusion time and phlebitis rate were related to each component of the nutritive mixture. A poor relation was found between the phlebitis rate and the amount of amino-acids, dextrose or lipid respectively. Both osmolarity (with variabl volume) and volume (with variable osmolarity) correlated poorly with the phlebitis rate (r = 0.37 and 0.29 respectively). However, the osmolarity rate, defined as the number of milliOsmols infused per hour, correlated well with the phlebitis rate (r = 0.95). Our results demonstrate that the peripheral route can be used as a practical alternative for central venous administration, if the osmolarity rate is limited.

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