Optimization of combined microwave-hot air roasting of malt based on energy consumption and neo-formed contaminants content.

UNLABELLED: To produce specialty malt, malts were roasted by combined microwave-hot air at various specific microwave powers (SP = 2.5 to 3 W/g), microwave heating times (t(mw) = 3.3 to 3.5 min), oven temperatures (T(oven) = 180 to 220 degrees C), and oven heating times (t(oven) = 60 to 150 min). The response variables, color, energy consumption by microwave (E(mw)) and oven (E(oven)), total energy consumption (E(tot)), quantity of neo-formed contaminants (NFCs), which include hydroxymethylfurfural, furfural, furan, and acrylamide were determined. Response surface methodology (RSM) was performed to analyze and predict the optimum conditions for the specialty malt. Production using combined microwave-hot air roasting process based on minimum energy consumption and level of NFCs. At 95% confident level, SP, T(oven), and t(oven) were the most influencing effects with regard to E(tot), whereas t(mw) did not affect E(tot). T(oven) and t(oven) significantly affected malt color. Only T(oven) significantly influenced the NFCs content. The optimum parameters were: SP = 2.68 W/g for 3.44 min, T(oven) = 206 degrees C for 136 min for coffee malt, SP = 2.5 W/g for 3.48 min, T(oven) = 214 degrees C for 136 min for chocolate malt, and SP = 2.5 W/g for 3.48 min, T(oven) = 211 degrees C for 150 min for black malt. Comparing with conventional process, combined microwave-hot air reduced E(tot) by approximately 40%, 26%, and 26% for coffee, chocolate, and black malts, respectively, and reduced HMF, furfural, furan, and acrylamide contents by 40%, 18%, 23%, and 95%, respectively, for black malt. PRACTICAL APPLICATION: An important goal for research institutions and the brewery industry is to produce colored malt by combining microwave and hot air roasting, while saving energy, getting desirable color, and avoiding the formation of carcinogenic and toxic neo-formed contaminants (NFCs). Therefore, one objective of this study was to compare energy consumption and content of NFCs during roasting of malt by hot air-only and combined microwave-hot air processes as well as to determine the effect of specific power, microwave processing time, oven temperature, and oven processing time during combined microwave-hot air roasting. Another objective was to predict the optimum conditions for the production of coffee, chocolate, and black malts.

Depuration of highway runoff water into grass-covered embankments.

The management of polluted road runoff water is an important issue in environmental protection. A strategy could be to perform local depuration by infiltration into the soils of the embankment, but knowledge for designing such systems is lacking. This study aims at discussing the relevant soil properties, by estimating the long-term depuration of road runoff water infiltrating into the sandy soil embankment of the A9 highway in Wallis, Switzerland. This was done by estimating the heavy metals (HM) mass balance of two sites 23 and 12 years old, respectively. The accumulated HM were estimated by soil and GB analyses. The HM input was estimated by average water quality and traffic. The results were discussed using two-dimensional simulation of infiltration and a 14 months in situ monitoring of the runoff from the pavement to the embankment and at the bottom of the embankment. The soil properties were appropriate for both small particle adsorption and filtration. A good match between input and stored pollutant charges was found, and the HM profiles accorded well with infiltration simulation and monitoring results, which showed that 80-100% of the runoff water infiltrated into the embankment. Replacement of the cracked concrete gutters by an infiltration channel made of similar soil is recommended. These results oppose the Swiss guidelines for road-polluted water infiltration, as much more clayey soils are recommended. These later soils are difficult to find in Switzerland, and may allow for preferential flow through macro pores, in contrast to the studied site.

Evidence of the glycation and denaturation of LTP1 during the malting and brewing process.

The influence of malting and brewing processes on the chemical and structural modifications occurring on LTP1 was investigated by mass spectrometry and circular dichroism. Proteins were first purified from malt, and samples were collected at various steps of beer processing performed on two barley cultivars. The levels of LTP1 found in malt were not significantly different from the amounts in barley seed. However, in malt, both LTP1b, a post-translational form of LTP1, and a third isoform named LTP1c were isolated. Moreover, both of these proteins were found to be heterogeneously glycated but still exhibited an alpha-helix structure. Both glycated LTP1 and LTP1b were recovered during mashing. It was also shown that glycated LTP1 was unfolded during heat treatment of wort boiling, which is in agreement with the denatured form previously isolated from beer.

Purification and structural characterization of LTP1 polypeptides from beer.

We report on the purification of lipid transfer proteins (LTP) from barley seeds and beer with the aim of investigating the chemical modifications that occur during the brewing process. In seeds, the well-known LTP of 9 kDa (LTP1) has been found together with a second form named LTPb that displays comparable amino acid composition but was not fully sequenced. These two forms have been recovered in beer with marked chemical modifications including disulfide bond reduction and rearrangement and especially glycation by Maillard reaction. The glycation is heterogeneous with variable amounts of hexose units bound to LTPs. Circular dichroism shows that glycated LTP1 having all their disulfide bridges reduced are totally unfolded. These results provide a first basis for understanding how barley LTPs become foam-promoting agents during the malting and brewing process.

Pregnancy-induced changes in lower extremity superficial veins: an ultrasound scan study.

OBJECTIVE: The purpose of this study was to follow changes in superficial veins of the lower extremities during pregnancy and the postpartum period in women with varicose veins. METHODS: This was a prospective study with the use of duplex scanning during the first and third trimesters of pregnancy and postpartum period. Competent veins were defined as veins with an absence of reflux, and incompetent veins were defined as veins with reflux. The diameter of the competent or incompetent greater saphenous vein (GSV) and lesser saphenous vein (LSV) was measured. The diameter of the largest varicose dilatations was measured in all three networks: GSV and its tributaries, LSV and its tributaries, and nonsaphenous varicose veins. RESULTS: Sixty-six women were studied prospectively (mean age, 32.2 +/- 4 years; 85 affected extremities). The diameter of competent and incompetent GSVs and competent LSVs increased between the first and third trimester (P <.001) and decreased between the third trimester and the postpartum period (P <.001). The diameter of the largest varicose dilatations of the GSV and its tributaries and nonsaphenous networks increased between the first and third trimester (P <.001) and decreased between the third trimester and the postpartum period (P <.001). No statistically significant variation of the diameter was demonstrated for any of these veins between the first trimester and the postpartum period. CONCLUSION: The diameters of competent and incompetent superficial veins increased during pregnancy and decreased during the postpartum period to return to their baseline values.

Suppression of CDA II expression in a homozygote.

The CDAN2 gene, responsible for congenital dyserythropoietic anaemia, type II (CDA II), was recently mapped to 20q11.2. We report data on an additional member of a previously studied CDA II family. This member had always been regarded as haematologically normal. Unexpectedly, she had the same microsatellite assortments around the CDAN2 alleles as her three sisters with CDA II. In particular, she was a homozygote for microsatellites D20S863 and D20S841. This prompted an analysis of all facets of her phenotype. The Ham test was negative. The bone marrow smears contained a normal proportion of binucleate erythroblasts. Electron microscopy revealed the absence of extensive stretches of cisternae beneath and parallel to the inner surface of the erythroblast plasma membrane. Proteins of the endoplasmic reticulum, which contaminate the reticulocyte plasma membrane in CDA II patients, were missing. Only the shape of the band 3 peak appeared slightly altered. This case exemplifies that homozygosity (or compound heterozygosity) for a deleterious gene may be silenced, or almost completely silenced. In recessively inherited diseases, suppressed phenotypes tend to be overlooked in siblings where both patients and unaffected individuals are expected.

Heterogenous band 3 deficiency in hereditary spherocytosis related to different band 3 gene defects.

Among 80 hereditary spherocytosis (HS) kindreds studied using denaturing electrophoretic separation of solubilized eythrocyte membrane proteins, we recognized three prominent subsets: HS with isolated spectrin deficiency, HS with combined spectrin and ankyrin deficiency, and HS with band 3 deficiency These three subsets represent more than 80% of the HS kindreds studied. In this study, eight dominant HS kindreds with band 3 deficiency were investigated for band 3 mutations. In three of these kindreds, linkage analyses confirmed the band 3 gene as the culprit gene. In an attempt to identify the responsible mutations, denaturing gradient gel electrophoresis (DGGE) was used to explore the coding exons (exons 2-20) of band 3 gene. Five different mutations were found in the eight kindreds. In five kindreds we identified substitutions of highly conserved residues, positioned at boundaries of putative transmembrane segments: a C --> T substitution at codon 490 changed arginine (CGC) to cysteine (TGC) in three kindreds, a C --> T substitution at codon 837 changed threonine (ACG) to methionine (ATG) in two kindreds. In the sixth kindred a G deletion was found in a stretch of five G starting at position 1475, leading to a stop codon either at position 1527 or 1565. In the seventh kindred a T deletion at position 1600 resulted in a stop codon at position 1733 and in the last kindred a T deletion was identified at position 355, leading to a stop codon at position 447. The mutant transcript was present in HS patients bearing missense mutations, whereas only the normal transcript was found in HS patients with frameshift mutations. In the latter group the mean decrease in membrane band 3 content was significantly lower, leading to speculation that missense mutations may have some sort of dominant negative effect.

Study of human erythrocyte membrane protein interactions by selective solubilization of Triton-skeletons.

The membrane skeleton, responsible for shape and mechanical properties of the red cell, was purified by the Triton extraction procedure in presence of 5 mM, 150 mM or 600 mM NaCl. The proportion of spectrin, protein 4.1 and actin present in erythrocyte skeletons does not depend on the molarity of NaCl used. In contrast ankyrin, protein band 3 and protein 4.2 are removed from skeletons as the ionic strength increased. Solubilization assays of membrane skeletons were used to study protein interactions inside the skeleton. Solubilization was performed by Tris, a non-selective disruptive reagent, or by p-mercuribenzene sulfonic acid (PMBS), which principally release spectrin and actin. Tris action was assessed by calculation of the percentage of solubilized proteins, which increased proportionally with Tris molarity. PMBS action was kinetically determined as the decrease in skeleton turbidity. With these two reagents, we observed a lower dissociation of skeletons prepared with high ionic strength buffer. Erythrocyte pretreatment with okadaic acid, an inhibitor of serine-threonine phosphatases, revealed a phosphorylation-induced skeleton gelation and a better resistance to Tris-solubilization.

Identification of three novel spectrin alpha I/74 mutations in hereditary elliptocytosis: further support for a triple-stranded folding unit model of the spectrin heterodimer contact site.

Six individuals with hereditary elliptocytosis (HE) or hereditary pyropoikilocytosis (HPP) from three unrelated families were evaluated. Defects in the ability of spectrin (Sp) to undergo self-association were present, and associated with increased recovery of the Sp alpha I 74-kD fragment after limited tryptic digestion (Sp alpha I/74 variant). Because mutations associated with the Sp alpha I/74 variant described to date have been localized to the 5' coding region of the alpha-Sp gene (exon 2) or at the 3' coding end of the beta-Sp gene (exon 30), the polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) method was used to detect mutations in these two regions. In one family with HE, an abnormal pattern of migration of PCR-amplified fragments containing exon 2 was observed, and led to the detection of a new mutation (Ile24Ser) in helix 3 of repeating segment alpha 1. In the two other families, an abnormal pattern of migration of PCR-amplified fragments containing exon 30 was observed in affected individuals, and sequencing led to the identification of two new mutations (Ala2023Val and Trp2024Arg) in helix 1 of repeating segment beta 17. The elliptogenic potential of these mutations emphasizes the importance of the conformational integrity of each of the three helices involved in the formation of the Sp heterodimer contact site, and will help identify critical amino acids involved in this interaction.

Importance of the familial factor in varicose disease. Clinical study of 134 families.

BACKGROUND: The role of heredity in the development of varicose veins of the lower limbs has been raised many times in the literature. When evaluating this role, most authors only question the patients, without examining their relatives. As shown in other papers, the subjectivity of this type of data throws doubt on the results. OBJECTIVE: This problem was evaluated by means of a prospective study based on clinical examination of all immediate family members. METHODS: In the case-control study, the female or male patients had to satisfy the following criteria: 1. Varicose veins in their legs. 2. Age between 30 and 40 years (meaning that, in most cases, their parents were still alive). 3. No history of deep vein thrombosis. To limit the influence of certain confusing factors (diet, life-style), the control group was composed of the patients' spouses, who were not suffering from varicose veins. The parents of the cases and the parents of the controls were also examined. For each case-control couple and for the four parents, we recorded the history of venous disease, the life-style, and the results of clinical examination, including the results of palpation and percussion of the various varicose vein territories. RESULTS: One hundred and thirty-four families were examined: 67 patients and their parents and 67 controls and their parents. A total of 402 subjects were examined. The results demonstrated a prominent role of heredity in the development of varicose veins (P < .001). The risk of developing varicose veins for the children was 90% when both parents suffered from this disease, 25% for males and 62% for females when one parent was affected, and 20% when neither parent was affected.

Molecular basis of clinical and morphological heterogeneity in hereditary elliptocytosis (HE) with spectrin alpha I variants.

The impaired ability of spectrin dimers to self-associate into tetramers is one of the most frequent defects associated with hereditary elliptocytosis (HE) and its more serious form, hereditary pyropoikylocytosis (HPP). We previously described four proteic variants of the spectrin (Sp) alpha I tryptic domain associated with the Sp dimer self-association defect (Sp alpha I/78, Sp alpha I/74, Sp alpha I/65, Sp alpha I/46 variants). Following the characterization of proteic variants, genomic molecular defects were identified and most of the mutations appeared to lie either in or near the self-association site, i.e. in the alpha I tryptic domain or in the beta I tryptic domain. The clinical severity of these different mutations varies considerably and ranges from asymptomatic to severe haemolytic disease such as in heterozygous HPP patients and in some homozygous HE patients. Studies of 113 patients from 61 HE families showed a correlation among parameters and showed which factors modulate the clinical expression of the molecular defect. Our analysis indicated that the clinical expression was directly correlated with the severity of the spectrin dimer self-association defect as evaluated by the increase in the Sp dimer percentage found in the 4 degrees C extract. A critical threshold of 40-50% of unassembled Sp dimer was determined; above that, patients exhibited severe haemolysis requiring splenectomy. The percentage of Sp dimer depends, in turn, on two factors: (i) the nature of the variant in relation to the position of the mutation versus the tetramerization site; (ii) the relative amount of mutant spectrin present in the membrane (ranging from 15% to 80% in heterozygous patients). As for the severity of haemolysis, the ghost mechanical stability to shear stress, as measured by ektacyometer, was also found to depend on the Sp dimer self-association defect. In contrast, the decrease in erythrocyte deformability was not related to the amount of unassembled Sp dimer but appeared to be correlated with the amount of mutant spectrin whatever the variant. Concerning erythrocyte morphology and the number of elliptocytes, the Sp alpha I/65 variant appears to be the most 'elliptocytogenic' variant, indicating that erythrocyte shape abnormality is not linked to the Sp dimer self-association defect.

Spectrin alpha IIa variant in dominant and non-dominant spherocytosis.

Several polymorphic mutations are located on the spectrin alpha-chain; among these the variant termed alpha IIa is characterized by an acid shift in the isoelectric point of the tryptic digest peptides 46 kDa and 35 kDa. In this variant a single amino acid substitution (alanine to aspartic acid) occurred at position 972 of the spectrin alpha-chain due to a point mutation (GCT to GAT) in the DNA. This variant, which seemed very rare in normal people, could be related to the recessive form of hereditary spherocytosis (HS) and could be absent in the dominant form of the disease. We have studied the alpha IIa variant by denaturing electrophoresis of the spectrin tryptic digest peptides from 179 subjects: 46 controls, 78 patients with dominant (d) or non-dominant (nd) HS and 55 relatives of the patients. The confirmation of the results was obtained at the DNA level in 41 subjects. The frequency of the chromosome bearing the alpha IIa mutation was 7.6% in controls and higher (about 12-14%) in members of families with dHS as well ndHS. However, the family trees clearly showed that the mutation and the HS disease gene(s) were located on different chromosomes and inherited independently from each other. Furthermore, our study allows the conclusion that in most (if not all) cases of dHS, the alpha IIa the variant is not the cause, is not a marker, and does not influence the phenotypic expression of the disease.

Prognostic value of clinical and radiological status on day 28 of life for subsequent course in very low birthweight (< 1,500g) babies with bronchopulmonary dysplasia.

To test the hypothesis that the short-term (approximately 6 months) course of babies with bronchopulmonary dysplasia (BPD) could be predicted from the clinical and radiological status on day 28 of life, we retrospectively examined the medical records of 79 infants born between 1985 and 1988 who required supplemental oxygen and/or ventilatory support on day 28. Chest roentgenographs taken close to day 28 (+/- 7 days) were scored on a scale of 0-10. Four babies died from causes not related to BPD. Four of the remaining 75 died from BPD, and the rest are alive. Forty-six of 71 were weaned from supplementary oxygen by 37 weeks corrected gestational age, and only 13/71 remained on supplemental oxygen after 40 weeks gestational age. To determine which variables contributed most to the outcome, defined as total days on supplemental oxygen, a multiple regression analysis was performed, including only those variables the tolerance of which exceeded 0.7 (sex, FiO2, ventilatory mode, and infectious status). FiO2 and ventilatory mode together predicted 15% of the variability in outcome, so that a high FiO2 and ventilator dependence on day 28 of life were highly correlated with a prolonged need for supplemental oxygen (F = 4.28, P < 0.05).

[Hematopoietic growth factor (GM-CSF) after autologous bone marrow transplantation. A randomized, double-blind, multicenter study in 91 cases of non-Hodgkin's malignant lymphomas]. / Facteur de croissance hématopoïétique (GM-CSF) après autogreffe de moelle osseuse. Etude randomisée multicentrique en double aveugle dans 91 cas de lymphomes malins non hodgkiniens.

To a great extent, the risks of autologous bone marrow transplantation are related to neutropenia. Although the efficacy of the recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) on neutrophil recovery has appeared in numerous open trials, only a few randomized studies have hitherto been published. Ninety-one patients with non-Hodgkin's malignant lymphoma treated with ablative chemotherapy followed by purged or unpurged bone marrow transplantation were entered in a placebo-controlled, double-blind randomized study; 44 patients received GM-CSF (E. coli) in doses of 250 micrograms/m2/day, and 47 received a placebo. Treatment was administered daily as continuous infusion started on the day of transplantation and pursued until the absolute number of neutrophils reached 0.5 x 10(9)/l during 7 days or, if this failed, during 30 days. The median time of neutrophil recovery was 14 days in patients on rhu GM-CSF and 21 days in patients on placebo (P < 0.0001). Patients who received a mafosfamide-purged bone marrow also had a rapid neutrophil recovery (median: 16 days versus 20.5 days; P = 0.013). The stay in hospital was shorter in the rhu GM-CSF group (median: 23 days versus 28 days; P < 0.05). No significant difference in the number of days with fever, infections, antibiotics administered and overall survival was detected between the two groups. The main toxicity ascribable to rhu GM-CSF was a capillary leakage syndrome found in 3 patients. Thus, after purged or unpurged autologous bone marrow transplantation rhu GM-CSF significantly reduces the duration of both neutropenia and hospital stay.

Indications, procedure and results for the treatment of polycythaemia vera by bleeding, pipobroman and hydroxyurea.

The present report is based on an analysis of the evolution of 720 cases of Polycythaemia vera treated with pipobroman and 624 cases treated with hydroxyurea. General modes of treatment are identical for the two drugs, consisting of initial therapy at relatively high dose aimed at obtaining complete remission and maintenance therapy essential to conserve the improved clinical status. Both types of treatment must be adapted to suit the patient. Complete remission is achieved in 95 to 100% of cases with pipobroman and in 80 to 90% of cases with hydroxyurea. Incidents which may occur during initial therapy include cytopenia, more frequent and severe under treatment with hydroxyurea, rare transitory digestive troubles and cutaneous and mucous eruptions. Subject to control of the blood cell count every three to four months, maintenance therapy may be continued for many years and while the time lapse is as yet insufficient for hydroxyurea, resistance to pipobroman does not appear to develop even after more than 20 years of treatment. Although neither of these two drugs entirely avoids the occurrence of acute leukaemia which appears in 5 to 8% of subjects irrespective of the duration of therapy, on the contrary to observations in patients treated by bleeding alone, myeloid splenomegaly with myelofibrosis is rare and develops in no more than 2% of cases. The frequency of visceral cancers is not increased by either drug. Provided Polycythaemia vera is maintained in complete remission, thrombotic accidents occur no more often than in a normal population of the same age bracket.(ABSTRACT TRUNCATED AT 250 WORDS)

Purification of erythrocyte protein 4.1 by selective interaction with inositol hexaphosphate.

Protein 4.1 is a multifunctional structural protein occupying a strategic position in the erythrocyte membrane. It is present in the erythrocyte membrane skeleton and in many nonerythroid cells. This report describes a novel method for purifying this protein based on its selective interaction with inositol hexaphosphate dimagnesium tetrapotassium salt. This interaction was discovered in the course of chromatography of high-salt extract of inside-out membrane vesicles on Procion orange MX-2R-Sepharose. The new procedure is simple and selective and produces protein 4.1 with better yield than that obtained with a previously published procedure. The purified protein 4.1 has the same immunoreactivity and the same alpha-chymotryptic digest profile as protein 4.1 purified by published methods and is fully functional in enhancing the interaction between F-actin and spectrin dimers.

[Evaluation of the results of the curative treatment of varices using 3 scoring systems: clinical, Doppler and echographic]. / Evaluation des résultats des thérapeutiques curatives des varices par trois scores: clinique, Döppler et échographique.

There have been many studies reporting results of curative treatment of varicose veins. Four methodological errors are nevertheless often committed: groups of varicose vein patients not comparable with regard to the degree of venous dilatation; insufficient objective parameters; population inadequately followed up; retrospective studies. It was felt necessary to develop systems for the quantification of varicose disease. These systems provide three grades: a clinical grade, a Doppler grade and an ultrasonographic grade. Clinical grade essentially involves the maximum diameter of varicose veins found by palpation and expressed in millimetres. The Doppler grade takes into account the maximum duration of the reflux wave in compression-decompression manoeuvres. The ultrasonographic grade also involves the maximum diameter of the varicose system. These grades enable the numerical assessment of the results of curative treatment of varicose veins, as well as forming the basis for statistically satisfactory epidemiological surveys.

Inherited haemolytic anaemia created by insertional inactivation of the alpha-spectrin gene.

In the process of generating transgenic mice, inserted foreign DNA can cause insertional inactivation of the flanking genetic locus and simultaneously provide a molecular tag for localizing and cloning the inactivated gene. We describe the case of an insertional mutation leading, in animals homozygous for the insertion, to severe anaemia that was lethal within a few days after birth. The haemolytic anaemia and microspherocytosis of the red cells strongly suggested membrane abnormalities of the erythrocytes. By in situ localization of the integration site, protein analysis of the red cell membranes, northern and Southern blot analyses, we were able to demonstrate that the integrated transgene had affected the alpha-spectrin gene locus.

Recombinant human granulocyte-macrophage colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation with unpurged and purged marrow in non-Hodgkin's lymphoma: a double-blind placebo-controlled trial.

The toxicity of autologous bone marrow transplantation (ABMT) is correlated to neutropenia. Although recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) seems to hold promise in accelerating neutrophil recovery, few analyses from randomized studies are presently available. Ninety-one patients with non-Hodgkin's lymphoma receiving high-dose ablative chemotherapy followed by ABMT with unpurged or purged marrow were included in a randomized, double-blind, placebo-controlled trial. Forty-four patients received 250 micrograms rhu GM-CSF (Escherichia coli)/m2 and 47 patients received placebo. Treatment was administered daily as continuous infusion from day of ABMT until the absolute neutrophil count (ANC) reached 0.5 x 10(9)/L for 7 days or until day 30, whichever was first. With rhu GM-CSF, 50% of the patients reached an ANC count greater than 0.5 x 10(9)/L at day 14 as opposed to day 21 with placebo (P less than .0001). Patients transplanted with marrow purged by mafosfamide also recovered earlier when treated with rhu GM-CSF (16 v 20.5 days, P = .013). The hospitalization duration was shorter in the rhu GM-CSF group (median, 23 v 28 days, P less than .05). No difference was observed in fever, number of infections, and antibiotic administration between the two groups. The major adverse event ascribed to rhu GM-CSF was a capillary leak syndrome in three patients graded as severe in two patients, moderate in one, and reversible in all three patients. In addition, one patient in the rhu GM-CSF group died suddenly with no explanation. In long term follow-up, the relapse rate was identical in both groups and there was no significant difference in the number of deaths at 1 year (12 with rhu GM-CSF v 9 with placebo), although deaths seemed to occur slightly earlier in the rhu GM-CSF group. We conclude that after ABMT with purged or unpurged marrow, rhu GM-CSF (E coli) significantly reduces neutropenia duration and hospitalization stay. A positive causative relation between the study drug and/or its mode of application with an increased toxicity as compared with GM-CSF from other sources and/or other modes of application cannot be deduced from the experiences in this study. Additional randomized trials would be necessary for an appropriate answer.