Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration.

There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spine morphology. We also determined whether acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders.

Left atrium function by 2D speckle tracking in aortic valve disease.

BACKGROUND: A paucity of data exists about left atrium (LA) function in aortic valve stenosis (AS) or regurgitation (AR). Two-dimensional speckle tracking echocardiography allows the noninvasive study of LA functional disturbances in aortic valve disease and their impact in the development of pulmonary hypertension (PH). METHODS: Consecutive patients with moderate or severe AS or AR were included. Left ventricle (LV) and LA speckle tracking strain quantification was performed. We included 42 patients with AS and 30 with AR. Differences were not found in LA volumes and strain in AS or AR. The LA volumetric derangements parallel the decrease in LA longitudinal strain. Maximum LA volume, minimum LA volume, and indexed LA volume were higher in severe valvular disease (SVD) than in moderate [23 cc (P=.018, IC95% : 4-41), 16 cc (P=.035, IC95% : 2-31), and 14 cc (P=.022, IC95% : 2-25), respectively], occurred in the same way with LA strain in the conduit (6.3%, P=.034, IC95% : 1-12) and reservoir (7.1%, P=.04, IC95% : 2-14) phases. In multivariable model, strain of reservoir phase was the variable mainly associated with PH; each decrease in one unit of strain of reservoir phase increased 6% the PH probability (OR: 1.06, P=.01). CONCLUSIONS: This study demonstrates that in patients with AS and AR, the LA has a similar behavior and that exist a close correlation between LA volumetric and functional parameters. The variable mainly associated with PH was LA strain of reservoir phase.

Combined application of polyacrylate scaffold and lipoic acid treatment promotes neural tissue reparation after brain injury.

PRIMARY OBJECTIVE: The aim of this study was to investigate the reparative potential of a polymeric scaffold designed for brain tissue repair in combination with lipoic acid. RESEARCH DESIGN: Histological, cytological and structural analysis of a combined treatment after a brain cryo-injury model in rats. METHODS AND PROCEDURES: Adult Wistar rats were subjected to cryogenic brain injury. A channelled-porous scaffold of ethyl acrylate and hydroxyethylacrylate, p(EA-co-HEA) was grafted into cerebral penumbra alone or combined with intraperitoneal LA administration. Histological and cytological evaluation was performed after 15 and 60 days and structural magnetic resonance (MRI) assessment was performed at 2 and 6 months after the surgery. MAIN OUTCOMES AND RESULTS: The scaffold was suitable for the establishment of different cellular types. The results obtained suggest that this strategy promotes blood vessels formation, decreased microglial response and neuron migration, particularly when LA was administrated. CONCLUSIONS: These evidences demonstrated that the combination of a channelled polymer scaffold with LA administration may represent a potential treatment for neural tissue repair after brain injury.

FERTILITY PATTERN AND FITNESS OF THE SPANISH-MEXICAN COLONISTS OF CALIFORNIA (1742-1876).

The analysis of fertility in colonizing populations is of great interest, since its individuals experience a major environmental change, and fertility rates can reflect the level of adaptation of the population to its new conditions. Using Northrop's genealogical compilations, this paper examines the fertility pattern of California's early Spanish-Mexican colonists between 1742 and 1876, their fitness levels and their trend across time throughout the colonizing period. A total of 197 women from 599 compiled families who had completed their reproductive period and had at least one child were analysed. The correlations among variables were also analysed in order to infer the relationship between longevity and fertility, and the influence of fertility determinants. The results show a natural fertility pattern, with a very young age at marriage and birth of first child (17.2 and 19.1 years respectively), and also a young age at last childbirth (38.8 years). The population's fitness showed greater values than for contemporary European populations, with 8 of 9.2 children surviving to adulthood, in comparison with 55% of newborns in Finland for the same period, suggesting a good adaptation of the population to their new environmental conditions. No relationship between fertility and lifespan was observed, as has been reported by other authors and in opposition to classical theories. A temporal trend in the number of children, consisting of three different phases, was observed, in accordance with the stability of living conditions in the region.

PstS-1, the 38-kDa Mycobacterium tuberculosis glycoprotein, is an adhesin, which binds the macrophage mannose receptor and promotes phagocytosis.

Mycobacterium tuberculosis, the primary causative agent of tuberculosis, infects macrophages and transforms the hostile intracellular environment into a permissive niche. M. tuberculosis infects macrophages using a variety of microbial ligand/cell receptor systems. In this study, binding assays with biotin-labelled mycobacterial cell wall proteins revealed five Concanavalin A-reactive proteins that bind macrophages. Among these proteins, we identified PstS-1, a 38-kDa M. tuberculosis mannosylated glycolipoprotein, and characterized it as an adhesin. Inhibition assays with mannan and immunoprecipitation demonstrated that PstS-1 binds the mannose receptor. We purified PstS-1 to 95.9% purity using ion exchange chromatography. The presence of mannose in purified PstS-1 was demonstrated by Concanavalin A interaction, which was abolished in the presence of sodium m-periodate and α-D-mannosidase. Gas chromatography revealed that purified PstS-1 contained 1% of carbohydrates by weight, which was mainly mannose. Finally, we used fluorescent microbeads coated with purified PstS-1 in phagocytosis assays and discovered that microbead uptake was inhibited by the pre-incubation of cells with GlcNAc, mannan and α-methyl mannoside. The interaction of PstS-1 coated beads with the mannose receptor was confirmed by confocal colocalization studies that showed high Pearson and Manders's colocalization coefficients. Our findings contribute to a better understanding of the strategies M. tuberculosis uses to infect host cells, the critical first step in the pathogenesis of tuberculosis.

Regulatory role of PI3K-protein kinase B on the release of interleukin-1ß in peritoneal macrophages from the ascites of cirrhotic patients.

Great effort has been paid to identify novel targets for pharmaceutical intervention to control inflammation associated with different diseases. We have studied the effect of signalling inhibitors in the secretion of the proinflammatory and profibrogenic cytokine interleukin (IL)-1ß in monocyte-derived macrophages (M-DM) obtained from the ascites of cirrhotic patients and compared with those obtained from the blood of healthy donors. Peritoneal M-DM were isolated from non-infected ascites of cirrhotic patients and stimulated in vitro with lipopolysaccharide (LPS) and heat-killed Candida albicans in the presence or absence of inhibitors for c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 1 (MEK1), p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). The IL1B and CASP1 gene expression were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of IL-1ß and caspase-1 were determined by Western blot. IL-1ß was also assayed by enzyme-linked immunosorbent assay (ELISA) in cell culture supernatants. Results revealed that MEK1 and JNK inhibition significantly reduced the basal and stimulated IL-1ß secretion, while the p38 MAPK inhibitor had no effect on IL-1ß levels. On the contrary, inhibition of PI3K increased the secretion of IL-1ß from stimulated M-DM. The activating effect of PI3K inhibitor on IL-1ß release was mediated mainly by the enhancement of the intracellular IL-1ß and caspase-1 content release to the extracellular medium and not by increasing the corresponding mRNA and protein expression levels. These data point towards the role of MEK1 and JNK inhibitors, in contrast to the PI3K-protein kinase B inhibitors, as potential therapeutic tools for pharmaceutical intervention to diminish hepatic damage by reducing the inflammatory response mediated by IL-1ß associated with liver failure.

Morbimortality associated to acute kidney injury in patients admitted to pediatric intensive care units.

AIM: To describe the morbimortality associated to the development of acute kidney injury (AKI) defined by the pediatric adaptation of the RIFLE criteria in a Pediatric Intensive Care Unit (PICU). DESIGN: A retrospective cohort study was carried out. SETTING: Children admitted to a PICU in a tertiary care hospital. Patients or participants A total of 320 children admitted to a tertiary care hospital PICU during the year 2011. Neonates and renal transplant patients were excluded. Primary endpoints AKI was defined and classified according to the pediatric adaptation to the RIFLE criteria. PICU and hospital stays, use of mechanical ventilation and mortality were used to evaluate morbimortality. RESULTS: A total of 315 children met the inclusion criteria, with a median age of 19 months (range 6-72). Of these patients, 128 presented AKI (73 reached the Risk category and 55 reached the Injury and Failure categories). Children with AKI presented a longer PICU stay (6.0 [4.0-12.5] vs. 3.5 [2.0-7.0] days) and hospital stay (17 [10-32] vs. 10 [7-15] days), and a greater need for mechanical ventilation (61.7 vs. 36.9%). The development of AKI was an independent factor of morbidity, associated with a longer PICU and hospital stay, and with a need for longer mechanical ventilation, with a proportional relationship between increasing morbidity and the severity of AKI. CONCLUSION: The development of AKI in critically ill children is associated with increased morbimortality, which is proportional to the severity of renal injury.

Cross-sensitization between cocaine and acute restraint stress is associated with sensitized dopamine but not glutamate release in the nucleus accumbens.

Repeated administration of psychostimulant drugs or stress can elicit a sensitized response to the stimulating and reinforcing properties of the drug. Here we explore the mechanisms in the nucleus accumbens (NAc) whereby an acute restraint stress augments the acute locomotor response to cocaine. This was accomplished by a combination of behavioral pharmacology, microdialysis measures of extracellular dopamine and glutamate, and Western blotting for GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor (AMPAR). A single exposure to restraint stress 3 weeks before testing revealed that enduring locomotor sensitization to cocaine was paralleled by an increase in extracellular dopamine in the core, but not the shell subcompartment, of the NAc. Wistar rats pre-exposed to acute stress showed increased basal levels of glutamate in the core, but the increase in glutamate by acute cocaine was blunted. The alterations in extracellular glutamate seem to be relevant, as blocking AMPAR by 6-cyano-7-nitroquinoxaline-2,3-dione microinjection into the core prevented both the behavioral cross-sensitization and the augmented increase in cocaine-induced extracellular dopamine. Further implicating glutamate, the locomotor response to AMPAR stimulation in the core was potentiated, but not in the shell of pre-stressed animals, and this was accompanied by an increase in NAc GluR1 surface expression. This study provides evidence that the long-term expression of restraint stress-induced behavioral cross-sensitization to cocaine recapitulates some mechanisms thought to underpin the sensitization induced by daily cocaine administration, and shows that long-term neurobiological changes induced in the NAc by acute stress are consequential in the expression of cross-sensitization to cocaine.

[Adherence to copper and stainless steel metal coupons of common nosocomial bacterial strains]. / Actividad bactericida de superficies de cobre frente a bacterias asociadas a infecciones nosocomiales, en un modelo in vitro de adherencia y sobrevivencia.

BACKGROUND: Copper has a bactericidal activity against a series of bacterial strains. AIM: To measure resistance to bacterial adherence of copper (Cu) and stainless steel (SS) metal coupons. MATERIAL AND METHODS: Bacterial strains causing nosocomial infections in Chile were analyzed. Bacterial adherence was studied using a previously described method based on a system of metal coupons that are immersed in culture media containing the bacteria of interest at room temperature. RESULTS: Adherence to Cu and SS coupons was different for Methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae and Acinetobacter baumannii strains. For these strains, no adherence to Cu coupons occurred during the 48 h observation period compared to a rapidly increasing adherence to SS coupons, with a final colony count of 1.00 E + 07 cfu/mL. For two different Pseudomonas aeruginosa clinical strains, inhibition of adherence was not observed on Cu coupons, and colony counts were similar for Cu and SS using the standard inoculum (2-3 x lO7 cfu).A partial decrease in adherence was observed for Cu but not for SS coupons, when a lower inoculum was used. CONCLUSIONS: Copper surfaces represent an interesting option to reduce bacterial contamination in the hospital environment due to its resistance to bacterial adhesión of most of the common nosocomial bacterial strains.

Hybrid AuNPs-3MPS-MTX nanosystem and its evaluation for treating cervical cancer and melanoma.

This research presents an evaluation of a hybrid material based on gold nanoparticles (AuNPs), stabilized with the thiol 3-mercapto-propanesulfonate (3MPS) and loaded with the methotrexate drug (MTX). The AuNPs-3MPS-MTX nanosystem was tested for the treatment of cervical cancer and melanoma, using the B16-F10 melanoma and HeLa cell lines. The tests performed on cell cultures assessed the efficiency of the studied nanosystem on tumor cells, as well as its toxicology.

Modulation of amoebic hepatic abscess by the parasympathetic system.

The neuro-immune network, in which the vagus nerve is involved, provides feedback between its afferent branches for signalling central nervous system from sites of injury through cytokines and its efferent branches, which release acetylcholine, an anti-inflammatory neurotransmitter. For gain insight into the parasympathetic mechanisms participating in the inflammatory response in the liver, we studied the effects of a vagotomy on the innate immune response in hamsters with amoebic liver abscess. At 7 days post-infection, compared to the control, liver parasympathectomy resulted in a larger abscess size, a greater production of collagen fibres, fewer trophozoites, increased serum levels of IL-10 and IFN-γ and increased numbers of IL-10 and IFN-γ-positive cells in situ, with no change in the number of macrophages and NK cells. Data indicate that the vagotomy disrupted the inflammatory response, causing an increase in the response against infection, then could favour the innervation of the liver by the sympathetic nervous system and would then take the control of the immune response by stimulating the conversion of macrophages to epithelioid cells; and through increased IL-10 production would induce the hepatic stellar cells to become myofibroblast collagen producer cells, thus forming a barrier of collagen and blocking trophozoite migration.

Influence of nuchal cord on ductus venosus assessment at 11 to 13 + 6 weeks' gestation.

OBJECTIVES: To assess the influence of the presence of nuchal cord (NC) on the evaluation of the fetal ductus venosus flow velocity waveform (DV-FVW). METHODS: This prospective study included 1174 normal non-selected singleton pregnancies between 11 and 13 + 6 weeks' gestation. We recorded the presence or absence of NC around the fetal neck, and assessed its relationship with the qualitative assessment and quantitative measurement of the DV-FVW. RESULTS: We observed NC around the fetal neck in 6.73% of cases and detected reversed flow of the a-wave of the DV-FVW in 2.98% of cases. In the group without NC, 21 of 1095 had reversed flow in the DV-FVW (1.9%; 95% CI, 1.28-3.02), whereas in the group with NC, 14 of 79 had reversed flow in the DV-FVW (17.7%; 95% CI, 16.67-40.35). We found a lower pulsatility index in fetuses without NC in comparison to those with NC (P < 0.001). We also found an association between the presence of NC and an increased occurrence of absent and reversed a-wave of the flow velocity waveforms (P < 0.001). On multivariate logistic regression analysis, a much higher occurrence of reversed DV-FVW a-wave was detected in fetuses with NC and smaller crown-rump length, and a much higher occurrence of absent DV-FVW a-wave was found in fetuses with NC and a higher maternal body mass index. CONCLUSIONS: The presence of NC modifies the sonographic findings in the qualitative and quantitative evaluation of the DV-FVW.

Mycobacterium tuberculosis 38-kDa lipoprotein is apoptogenic for human monocyte-derived macrophages.

Mycobacterium tuberculosis is the main aetiologic agent of tuberculosis, a disease of great concern in less-developed regions. Apoptosis is a conspicuous event in macrophages infected in vitro with mycobacteria, a phenomenon also observed in vivo in granulomas of patients with tuberculosis. To determine its significance, it is important to define the mycobacterial moieties involved and how they cause apoptosis. Here we show that the 38-kDa lipoprotein induces macrophage caspase-dependent apoptosis involving TNF-alpha and FasL and, interestingly, with the upregulation of cell-death receptors TNFR1, TNFR2 and Fas. A role for the Toll-like receptor 2 was also demonstrated. In conclusion, the ability to induce apoptosis of host cells is another property of the 38-kDa lipoprotein, a molecule that has focused attention for being an immunodominant antigen that participates in phosphate transport.

Multiple myeloma-associated amyloidosis is an independent high-risk prognostic factor.

Several prognostic factors have been recognized in patients with multiple myeloma (MM). Among the most important are: the serum levels of beta2-microglobulin, albumin, and LDH; the labeling index; and an abnormal karyotype. Patients with amyloidosis (AL) have poor prognosis; however, little is known concerning the prognostic significance of AL associated to MM. In 201 consecutive patients with de novo MM, we performed a fat-pad biopsy needle aspiration (FPBNA) that was stained with Congo red. Sixty eight (34%) patients had AL and a poorer prognosis disease: lower performance status, presence of B symptoms, higher LDH and calcium values, and worse response to chemotherapy. Cox regression model for overall survival detected three variables having independent prognostic significance: the presence of AL (RR = 3.4, P < 0.004), serum albumin levels <3.5 g/dl (RR 3.2, p < 0.005), and patients not achieving complete remission or very good partial remission (RR 2.9, p < 0.02). In 28% of patients with de novo MM, FPBNA was useful to detect incidental amyloidosis. During follow-up, 69% of these patients had symptoms of AL. Excluding 16 patients with obvious symptoms of AL at diagnosis, overall survival was worse in patients who developed later symptoms of AL. MM-associated AL represents a poorer prognosis disease even in the absence of symptoms at diagnosis, and this specific association may be considered as an independent high-risk prognostic factor. The routine study of periumbilical fat-pad tissue should be mandatory in all patients with MM.

[Percutaneous transluminal septal myocardial ablation in patients with obstructive septal hypertrophic myocardiopathy. Acute results and 3-year follow-up]. / Ablación miocárdica septal transluminal percutánea en pacientes con miocardiopatía hipertrófica septal obstructiva. Resultados agudos y seguimiento a 3 años.

OBJECTIVE: To report the acute and Long term results of percutaneous transluminal septal myocardial ablation (PTSMA), for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). PTSMA has been considered as an alternative to surgical treatment in patients with HOCM and drug-refractory symptoms or unresponsive to the implantation of a pacemaker. Acute response is generally satisfactory, but long term results have not been sufficiently described. METHODS: We did PTSMA in eight patients, with functional class III-IV of NYHA, and with a transaortic gradient at rest > or = 40 mmHg. ALcohol was administered to seven of them, and small absorbant gelatin sponge particles in the other. Acute and long term clinical and echocardiographical follow-up was done. RESULTS: During the procedure the left ventricular outflow tract (LVOT) gradient at rest was reduced significantly and the systolic anterior motion of the mitral valve (SAM) also. Five remained on functional class I, and two in class II. One patient died one year later of sepsis unrelated to the cardiopathy. CONCLUSIONS: PTSMA is an excellent non surgical option to reduce the LOVT gradient and the consequent symptoms in this patients. Long term follow-up shows they remain in a good functional class and their evolution is free of cardiovascular complications.

High Fibre Gluten-Free Fresh Pasta with Tiger Nut, Chickpea and Fenugreek: Technofunctional, Sensory and Nutritional Properties.

Gluten-free pasta production with a low glycaemic index and improved nutritional profile is still a challenge for the food industry. In this study, pasta was produced from fenugreek (FF), chickpea (CPF) and tiger nut (TNF) flours. CPF and FF are interesting for a balanced contribution of soluble and insoluble fibre by combining the health benefits of each type of fibre that promotes health. TNF, also rich in insoluble fibre, can provide additional healthy properties. The partial substitution of TNF for FF (0, 2.5, 5, 7.5 and 10% w/w solids) was assessed, and the relation linking chemical composition, structure, cooking and rheological properties and predictive in-vitro starch digestion (eGI, expected glycaemic index) was analysed. The results revealed that FF, rich in galactomannans, not only improves the nutritional profile and lowers the eGI but also helps to naturally enhance the structure of the pasta product and, thus, cooking behaviour (higher swelling index and fewer cooking losses).

High fibre tiger nut pasta and xanthan gum: cooking quality, microstructure, physico-chemical properties and consumer acceptance.

The feasibility of replacing wheat semolina by tiger nut flour (20 and 40%) and xanthan gum (1%) in order to obtain high fibre dry pappardelle with fair techno-functional, structural and sensory attributes, was assessed. The cooking properties, texture, colour and sensory acceptance of uncooked and cooked pasta were evaluated. The proximate chemical composition of the raw materials, and the microstructure of the dry pasta were also assessed. The results in this manuscript address the improved nutritional value in terms of its dietary fibre, mineral content, oleic and linoleic acids, and the positive effects on the textural characteristics and cooking behaviour achieved on dry tiger nut based pappardelle using 1% of xanthan gum as a structural agent. Micrographs revealed in fact that the gluten network was better formed when xanthan gum was used. Furthermore, the obtained results seem to support that consumers would prefer pappardelle with 40% tiger nut flour.

Micronised bran-enriched fresh egg tagliatelle: Significance of gums addition on pasta technological features.

The aim of the work was to produce fibre-enriched fresh pasta based on micronised wheat bran and durum wheat semolina with appropriate techno-functional properties. Wheat semolina was replaced with fine particle size (50% below 75 µm) wheat bran - up to 11.54% (w/w). A Box-Behnken design with randomised response surface methodology was used to determine a suitable combination of carboxymethylcellulose, xanthan gum and locust bean gum to improve pasta attributes: minimum cooking loss, maximum values for water gain and swelling index, as well as better colour and texture characteristics before and after cooking. The proximate chemical composition of wheat semolina and bran was determined and the microstructure of uncooked pasta was observed as well. From the response surface methodology analysis, it is recommended to use: (i) xanthan gum over 0.6% w/w as it led to bran-enriched pasta with a better developed structure and superior cooking behaviour, (ii) a combination of xanthan gum (0.8% w/w) and carboxymethylcellulose (over 0.6% w/w) to enhance uncooked pasta yellowness.

Diacylglycerol kinase synthesized by commensal Lactobacillus reuteri diminishes protein kinase C phosphorylation and histamine-mediated signaling in the mammalian intestinal epithelium.

Lactobacillus reuteri 6475 (Lr) of the human microbiome synthesizes histamine and can suppress inflammation via type 2 histamine receptor (H2R) activation in the mammalian intestine. Gut microbes such as Lr promote H2R signaling and may suppress H1R proinflammatory signaling pathways in parallel by unknown mechanisms. In this study, we identified a soluble bacterial enzyme known as diacylglycerol kinase (Dgk) from Lr that is secreted into the extracellular milieu and presumably into the intestinal lumen. DgK diminishes diacylglycerol (DAG) quantities in mammalian cells by promoting its metabolic conversion and causing reduced protein kinase C phosphorylation (pPKC) as a net effect in mammalian cells. We demonstrated that histamine synthesized by gut microbes (Lr) activates both mammalian H1R and H2R, but Lr-derived Dgk suppresses the H1R signaling pathway. Phospho-PKC and IκBα were diminished within the intestinal epithelium of mice and humans treated by wild-type (WT) Lr, but pPKC and IκBα were not decreased in treatment with ΔdgkA Lr. Mucosal IL-6 and systemic interleukin (IL)-1α, eotaxin, and granulocyte colony-stimulating factor (G-CSF) were suppressed in WT Lr, but not in ΔdgkA Lr colonized mice. Collectively, the commensal microbe Lr may act as a "microbial antihistamine" by suppressing intestinal H1R-mediated proinflammatory responses via diminished pPKC-mediated mammalian cell signaling.

Autologous peripheral blood stem cell transplantation in multiple myeloma using oral versus I.V. melphalan.

Autologous peripheral blood stem cell transplantation is the therapy of choice for the treatment of multiple myeloma (MM) patients younger than 70 years old. Between August 1993 and November 2004, 54 patients with MM were autografted after conditioning with high-dose oral melphalan 140 mg/m(2) in combination with etoposide and carmustine (28 patients) or with high-dose melphalan 200 mg/m(2) I.V. (26 patients). The oral and IV melphalan groups were comparable. There were no significant differences in disease-free survival (DFS) and overall survival (OS) between the groups; however, in patients transplanted in remission, OS and DFS were better in the I.V. melphalan group. Four good-prognostic factors were identified: interval between diagnosis and transplant <18 months, number of prior chemotherapy lines < or =2, remission status (complete or partial), and the use of I.V. melphalan. In conclusion, I.V. melphalan is the therapy of choice for conditioning patients with MM who are in remission.