Biomedical subjects

M A Delgado

Publications and source records attributed to M A Delgado.

At least 19 recordsLinked to original sources

PubMed2006

Antihypertensive effect of peptides obtained from Enterococcus faecalis-fermented milk in rats.

Previous studies have demonstrated that milk fermented with Enterococcus faecalis decreases the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of spontaneously hypertensive rats. In this study, we evaluated the antihypertensive activity of the following peptide sequences: LHLPLP, LHLPLPL, LVYPFPGPIPNSLPQNIPP, VLGPVRGPFP, and VRGPFPIIV. These peptides isolated from E. faecalis-fermented milk showed in vitro angiotensin I-converting enzyme-inhibitory activity. Because the most potent angiotensin I-converting enzyme-inhibitory sequences were LHLPLP and LVYPFPGPIPNSLPQ-NIPP, we administered different doses of these peptides to spontaneously hypertensive rats. High doses of the remaining sequences were also administered to these animals. Water served as a negative control and captopril as a positive control. All products were administered orally. The SBP and DBP were measured before administration and also at 2, 4, 6, 8, and 24 h after administration. Before administration of the different products, spontaneously hypertensive rats showed SBP and DBP values of 218 +/- 2.5 and 157 +/- 5.9 mmHg, respectively (n = 30). The sequences LHLPLP, LVYPF-PGPIPNSLPQNIPP, VLGPVRGPFP, and VRGPFPIIV caused clear and significant decreases in SBP, DBP, or both in the animals. In particular, the antihypertensive effect could be clearly established when 2 or 3 mg/kg of LHLPLP was administered. These 2 doses of LHLPLP showed similar antihypertensive properties. Four hours after administration of captopril or the highest doses of the different peptides, the decreases in the SBP and the DBP (mmHg) were as follows: captopril (SBP = 52 +/- 5.8, DBP = 38.8 +/- 3.8), 3 mg/kg of LHLPLP (SBP = 25.3 +/- 8.2, DBP = 29.5 +/- 7.6), 6 mg/kg of LVYPFPGPIP-NSLPQNIPP (SBP = 14.9 +/- 3.7, DBP = 8.7 +/- 4.4), 10 mg/kg of LHLPLPL (SBP = 7.7 +/- 4.1, DBP = 9.4 +/- 3.1), 10 mg/kg of VLGPVRGPFP (SBP = 16.2 +/- 5.8, DBP = 21.64 +/- 3.2), and 10 mg/kg of VRGPFPIIV (SBP = 16.05 +/- 2.74, DBP = 9.19 +/- 3.49). The results obtained suggest that the sequences LHLPLP, LVYPFPGPIPNSLPQ-NIPP, VLGPVRGPFP, and VRGPFPIIV could be responsible, at least in part, for the antihypertensive properties described for E. faecalis-fermented milk.

Animals↗

PubMed2006

Determination of the antihypertensive peptide LHLPLP in fermented milk by high-performance liquid chromatography-mass spectrometry.

Among different lactic acid bacteria isolated from raw milk, 4 Enterococcus faecalis strains have stood out as producers of fermented milk with potent antihypertensive activity. The peptide beta-casein f(133-138), LHLPLP, was identified as one of the major peptides responsible for the activity of these fermented milk products. A simple method was developed to quantify this peptide in fermented milk using high-performance liquid chromatography coupled in line with mass spectrometry. This procedure does not require any previous sample fractionation or extraction, and direct analysis of the water-soluble extract obtained from the fermented milk can be performed. Validation studies showed sufficient specificity, reproducibility, linearity, and recovery, demonstrating that this method can be used for the routine quantification of LHLPLP during the production of fermented milk products. The developed method was readily applied to quantify the peptide LHLPLP under different fermentation conditions and with different aromatized products.

Animals↗

PubMed2005

Changes in arterial blood pressure in hypertensive rats caused by long-term intake of milk fermented by Enterococcus faecalis CECT 5728.

We have evaluated the changes in arterial blood pressure caused in spontaneously hypertensive rats (SHR) by long-term intake of an Enterococcus faecalis CECT 5728-fermented milk with significant angiotensin-converting enzyme (ACE)-inhibitory activity. After being weaned, male 3-week-old SHR were randomized into five groups. Until the 20th week of life, rats in each group were given one of the following drinking fluids: tap water (negative control 1), a fermented milk without ACE-inhibitory activity (negative control 2), captopril (100 mg/kg) (positive control), the E. faecalis CECT 5728-fermented milk that had significant ACE-inhibitory activity, or Ca-enriched E. faecalis CECT 5728-fermented milk. Animals in the different groups were then given tap water as drinking fluid from the 20th to 25th week of life. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured weekly in the rats, from the 6th to 25th week of life, by the tail-cuff method. A definite decrease in SBP and DBP could be observed in the rats treated with captopril and also in the rats that received the E. faecalis CECT 5728-fermented milks. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the Ca-enriched fermented milk was slightly more accentuated and more constant than the effect of the E. faecalis CECT 5728-fermented milk that had not been enriched in Ca. SBP and DBP increased in the treated SHR when the corresponding antihypertensive treatment was removed. Fermentation of milk with E. faecalis CECT 5728 may therefore be a successful strategy to produce a functional food with antihypertensive activity.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2004

[Abdominal aortic injury as a complication of laparoscopic cholecystectomy].

A 58-year-old woman with a history of high blood pressure and cesarean section by median laparotomy underwent elective laparoscopic cholecystectomy under general anesthesia. After initiation of pneumoperitoneum, hemodynamic instability developed (blood pressure 75/40 mm Hg, heart rate 47 beats/min) and resolved after volume replacement and administration of vasoactive drugs. The rest of the procedure was completed without further adverse events. After extubation, the patient was transferred to the anesthetic recovery ward, where she tended to hypotension that was unresponsive to volume replacement, with a hematocrit of 18% and hemoglobin concentration of 6.9 g/dL. Hemoperitoneum was suspected, and an emergency median laparotomy revealed 300 cc of blood in the peritoneal cavity, a large hematoma putting pressure on retroperitoneal structures, and 2 infrarenal aortic lesions (anterior and posterolateral). During the reoperation the patient required multiple transfusions and vasoactive drugs to maintain hemodynamic stability. Recovery in the postanesthetic care unit was uneventful. After transfer to the ward, on the 20th day after surgery she developed septic shock with intraabdominal fluid requiring surgical drainage and admission to the intensive care unit. Abdominal aortic injury during laparoscopic surgery usually occurs upon introduction of trocars for initiating pneumoperitoneum. The technique must be performed correctly and monitored properly to assure early detection of adverse events associated with high mortality.

Aorta, Abdominal↗

PubMed2002

Effects of transcutaneous short-term electrical stimulation on M. vastus lateralis characteristics of healthy young men.

Fifteen healthy, untrained male subjects (mean age +/- SD, 22 +/- 5 years) were used to examine the plasticity of myosin heavy chain phenotype, size, oxidative capacity and capillarization of skeletal muscle fibre types with short-term electrical stimulation (ES). Ten subjects were electro-stimulated on both quadriceps muscles with a frequency of 45-60 Hz, with 12 s of stimulation followed by 8 s of recovery for a total of 30 min per day, 3 days per week for 6 weeks. The remaining five subjects served as controls. Two vastus lateralis muscle biopsy samples were removed from each subject before (week 0) and after (week 6) ES training. A standardized exercise test on a cycle ergometer was performed by each subject before and after the experimental period and several indicators of whole-body aerobic capacity were estimated. The so-called electromyographic threshold was also determined during the tests. Muscle biopsy samples were analysed by electrophoresis, immunohistochemistry and quantitative histochemistry. Myosin heavy chain (MHC) composition, muscle fibre type distribution, fibre areas, oxidative capacity and capillaries of each fibre type were estimated. Muscular changes with ES revealed an increase of fibres expressing MHC-IIA, and a decrease of fibres expressing MHC-IIX and MHC-I, as well as an increase of the oxidative capacity and mean number of capillaries of fast-twitch (type II) fibres with minimal muscle fibre hypertrophy. These adaptations seem related to a bi-directional transformation from both MHC isoforms I and IIX towards the MHC-IIA isoform. The aerobic performance and electromyographic variables at the whole-body level were not altered by ES. These results indicate that the particular short-term ES training protocol tested in the present study induces significant adaptations in histochemical and metabolic machineries of human skeletal muscle. The results also offer new perspectives for realistic applications of ES in various clinical situations and sport training.

Adult↗

PubMed2001

Holoprosencephaly due to mutations in ZIC2: alanine tract expansion mutations may be caused by parental somatic recombination.

We report on the prevalence of mutations in the zinc finger transcription factor gene, ZIC2, in a group of 509 unrelated individuals with isolated holoprosencephaly (HPE) and normal chromosomes. Overall, we encountered 16 HPE patients (from 15 unrelated families) with ZIC2 mutations. Thus, ZIC2 mutation was the apparent cause of HPE in 3-4% of cases. Seven mutations were frameshifts that were predicted to result in loss of function, further supporting the idea that ZIC2 haploinsufficiency can result in HPE. One mutation, an alanine tract expansion which is caused by the expansion of an imperfect trinucleotide repeat, occurred in seven patients from six different families. In three of those families, the father was found to be apparently mosaic for the mutation. We hypothesize that this mutation can arise through errors in somatic recombination, an extremely unusual mutation mechanism. In addition, one mutation resulted in a single amino acid change and one mutation was an in-frame deletion of 12 amino acids. The central nervous system malformations seen in patients with ZIC2 mutations ranged from alobar HPE (most common) to middle interhemispheric fusion defect (one case). Although severe facial anomalies are common in HPE, all of the patients with ZIC2 mutations had relatively normal faces, suggesting that ZIC2 mutations represent a large proportion of HPE cases without facial malformation.

Alanine↗

PubMed2001

Escherichia coli RNA polymerase is the target of the cyclopeptide antibiotic microcin J25.

Escherichia coli microcin J25 (MccJ25) is a plasmid-encoded, cyclic peptide antibiotic consisting of 21 unmodified amino acid residues. It is primarily active on gram-negative bacteria related to the producer strain, inducing cell filamentation in an SOS-independent way. A mutation causing resistance to MccJ25 was isolated. Genetic analysis indicated that it resided in the rpoC gene, encoding the beta' subunit of RNA polymerase, at 90 min on the E. coli genetic map. The mutation was genetically crossed on to a plasmid containing the wild-type rpoC gene. The presence of the recombinant plasmid conferred complete resistance to otherwise sensitive strains. Nucleotide sequencing of the plasmid-borne, mutant rpoC gene revealed a ACC (Thr)-to-ATC (Ile) change at codon 931, within homology block G, an evolutionarily conserved region in the large subunits of all RNA polymerases. MccJ25 decreased RNA synthesis both in vivo and in vitro. These results point to the RNA polymerase as the target of microcin action. We favor the possibility that the filamentous phenotype induced by MccJ25 results from impaired transcription of genes coding for cell division proteins. As far as we know, MccJ25 is the first peptide antibiotic shown to affect RNA polymerase.

Alleles↗

PubMed2001

Growth-phase-dependent expression of the cyclopeptide antibiotic microcin J25.

Microcin J25 is a 2,107-Da, plasmid-encoded, cyclopeptide antibiotic produced by Escherichia coli. We have isolated lacZ fusions to mcjA (encoding the 58-amino-acid microcin precursor) and mcjB and mcjC (which are required for microcin maturation), and the regulation of these fusions was used to identify factors that control the expression of these genes. The mcjA gene was found to be dramatically induced as cells entered the stationary phase. Expression of mcjA could be induced by resuspending uninduced exponential-phase cells in spent supernatant obtained from an early-stationary-phase culture. Induction of mcjA expression was not dependent on high cell density, pH changes, anaerobiosis, or the buildup of some inducer. A starvation for carbon and inorganic phosphate induced mcjA expression, while under nitrogen limitation there was no induction at all. These results taken together suggest that stationary-phase induction of mcjA is triggered by nutrient depletion. The mcjB and mcjC genes were also regulated by the growth phase of the culture, but in contrast to mcjA, they showed substantial expression already during exponential growth. Induction of the microcin genes was demonstrated to be independent of RpoS, the cyclic AMP-Crp complex, OmpR, and H-NS. Instead, we found that the growth-phase-dependent expression of mcjA, mcjB, and mcjC may be explained by the concerted action of the positively acting transition state regulators ppGpp, Lrp, and integration host factor. Measurements of microcin J25 production by strains defective in these global regulators showed a good correlation with the reduced expression of the fusions in such mutant backgrounds.

Anaerobiosis↗

PubMed2000

Hemodynamic, biochemical and morphological changes induced by aminoguanidine in normal and septic sheep.

OBJECTIVE: To define the acute hemodynamic, metabolic, and morphological changes induced by aminoguanidine, a selective iNOS inhibitor, in septic sheep. DESIGN: Prospective, nonrandomized animal study. SETTING: Animal research facility in a University Hospital. INTERVENTIONS: Adult sheep, sedated and mechanically ventilated, were monitored with a pulmonary arterial catheter and an ultrasonic blood flow probe in the mesenteric artery, to measure the systemic (Q(TOT)I) and the mesenteric (Q(MES)I) blood flow indices, and an ileal tonometer. Four groups of sheep were studied: nonseptic, septic, nonseptic treated with aminoguanidine, and septic treated with aminoguanidine (100 mg kg(-1) h(-1)) (n = 6 for each group). Sepsis was induced by the intravenous administration of E. coli. Hemodynamic and biochemical parameters were measured during 300 min. Histological changes in the liver and small intestinal mucosa were analyzed at the end of the experiment. MEASUREMENTS AND MAIN RESULTS: In nonseptic animals, aminoguanidine slightly increased mean systemic arterial pressure (MAP), decreased Q(TOT)I, and increased vascular resistance index (SVRI) and pulmonary vascular resistance index. Q(MEs)I did not change and Q(MES)I/Q(ToT)I increased. Aminoguanidine also induced intestinal intramucosal hypercarbia, hyperlactatemia, acidemia, hypoglycemia, and morphological signs indicative of tissue ischemia in the small intestinal mucosa. In septic sheep, aminoguanidine increased SVRI and MAP only at 4 h after the septic challenge and thereafter, and worsened gas exchange. CONCLUSIONS: In this model, exogenous administration of aminoguanidine induces beneficial hemodynamic effects 4 h after the septic challenge. In normal animals, however, aminoguanidine was associated with hypoglycemia, acidosis, hyperlactatemia, and intestinal mucosal ischemia.

Acidosis↗

PubMed1999

Modulation of systemic hemodynamics by exogenous L-arginine in normal and bacteremic sheep.

OBJECTIVE: To investigate whether exogenous L-arginine, the substrate for nitric oxide synthase, modulates systemic hemodynamics in sepsis. DESIGN: Prospective, controlled study in a sheep model of sepsis. SETTING: Animal research facility in a university hospital. SUBJECTS: Adult sheep weighing between 35 and 55 kg. INTERVENTIONS: Adult sheep sedated and mechanically ventilated, were monitored with a pulmonary arterial catheter and an ileal tonometer. Four groups of sheep were studied: nonseptic, septic, nonseptic treated with L-arginine, and septic treated with L-arginine. Sepsis was induced by the intravenous administration of Escherichia coli (1.5x10(8) colony-forming units/kg for 30 mins). L-arginine was administered as an intravenous bolus (200 mg/kg for 10 mins) before the septic challenge followed by 200 mg/kg/hr for 300 mins. MEASUREMENTS AND MAIN RESULTS: Sepsis induced a state of acidosis, hyperlactatemia, hypoxemia, and gastric intramucosal acidosis. During the first 30 mins after the septic challenge, there was a decrease in cardiac index and blood pressure, and an increase in systemic vascular resistance. Thereafter, blood pressure returned to baseline values, and systemic vascular resistance fell. Treatment with L-arginine in nonseptic sheep did not induce any biochemical or hemodynamic effect. In septic sheep, treatment with L-arginine was associated with a greater increase in systemic vascular resistance during the first 30 mins, and a more marked decrease in blood pressure and systemic vascular resistance after 180 mins. CONCLUSIONS: Exogenous administration of L-arginine does not induce hemodynamic effects in normal animals, exacerbates the acute vasoconstriction associated with the intravenous infusion of E. coli and potentiates the sepsis-induced vasodilation. Our results suggest that a) nitric oxide production is not constitutively modulated by exogenous L-arginine, b) L-arginine probably enhances the sepsis-induced sympathetic discharge, and c) L-arginine becomes rate-limiting for the formation of nitric oxide at approximately 3 hrs after the initiation of the septic challenge.

Acidosis↗

PubMed1999

Escherichia coli outer membrane protein TolC is involved in production of the peptide antibiotic microcin J25.

A Tn5 insertion in tolC eliminated microcin J25 production. The mutation had little effect on the expression of the microcin structural gene and presumably acted by blocking microcin secretion. The tolC mutants carrying multiple copies of the microcin genes were less immune to the microcin. TolC is thus likely a component of a microcin export complex containing the McjD immunity protein, an ABC exporter.

ATP-Binding Cassette Transporters↗

PubMed1999

Paediatric life support instructors courses in Spain. Spanish Paediatric and Neonatal Resuscitation Group.

Between October 1996 and February 1998 we have provided five PLS instructors courses for 127 physicians. The instructor course takes 20-24 h over in 3 days, with 20-36 students per course. Theory classes last 5 h and practical stations between 14 and 18 h. Theory classes include: types and organisation of paediatric courses, resuscitation material, methodology of education, didactic methods, and methods of evaluation. The practical classes include techniques of oral expression, resuscitation material, and methodology, and evaluation of basic life support, airway and ventilation, venous and intraosseous access, diagnosis and treatment of arrythmias, neonatal resuscitation and advanced resuscitation. At the end of the course the students perform an anonymous written evaluation of the course with scores between 1 (very bad), 2, 3, 4 and 5 (very good). Theoretical aspects practical classes, methodology, and organisation of the PLS instructors courses are considered satisfactory by the students. We conclude that PLS instructors courses are important for assuring the uniformity and quality of paediatric life support courses.

Cardiopulmonary Resuscitation↗

PubMed1999

Systemic amyloidosis associated with hepatocellular carcinoma. Case report and literature review.

We describe the case of a male patient with biopsy-proven non-resectable liver adenoma at age 32 who presented 17 years later with hepatocellular carcinoma and nephrotic syndrome. Autopsy demonstrated systemic amyloidosis A. Review of the medical literature disclosed only three previous published cases of liver tumors associated with systemic amyloidosis. The association of non-hematologic neoplasias with systemic amyloidosis is rare and our literature review revealed only three cases of systemic amyloidosis in patients with liver tumors. We present here the case of a patient with apparent transition of liver adenoma to hepatocellular carcinoma with associated systemic amyloidosis.

Adenoma↗

PubMed1998

Prevention of nosocomial infection in a pediatric intensive care unit (PICU) through the use of selective digestive decontamination.

OBJECTIVE: To assess the effectiveness of selective digestive decontamination (SDD) on the control of nosocomial infection (NI) in critically ill pediatric patients. DESIGN: A prospective, randomized, non-blinded and controlled clinical microbiology study. SETTING: The pediatric intensive care unit (PICU) of a tertiary level pediatric university hospital. CRITERIA FOR INCLUSION: Patients 1 month to 14 years old, who underwent some kind of manipulation or instrumentation (mechanical ventilation, vascular cannulation, monitoring of intracranial pressure, thoracic or abdominal drainage, bladder catheterization, peritoneal dialysis, etc.) and/or presented a neurological coma requiring a stay in the PICU of 3 or more days. PATIENTS: Over a period of 2 years, 244 patients met the inclusion criteria; 18 patients were withdrawn because of protocol violation. The treatment group comprised 116 patients and the control group, 110 patients. INTERVENTION: The treatment group received a triple therapy of colimycin, tobramycin and nystatin administered orally or via nasogastric tube every 6 hours. All patients with mechanical ventilation or immune-depression received decontamination treatment of the oropharyngeal cavity with hexitidine (Oraldine 0.5 mg/ml) every 6-8 hours in accordance with the PICU's conventional protocol. METHOD: Up to 10 types of nosocomial infection were diagnosed following criteria of the Centers for Disease Control (CDC). The severity and manipulation of the patients on admission was assessed using the therapeutic intervention scoring system (TISS) and multi-organ system failure scores (MOSF). MEASUREMENTS AND MAIN RESULTS: UNIVARIANT ANALYSIS: SDD did not significantly reduce the incidence of NI, antibiotic use, the length of stay, or mortality; although a small percentage of respiratory and urinary tract infections was detected, catheter-related bacteremia was the most common infection. MULTIVARIANT ANALYSIS: Controlling the risk factors for each child through log regression showed that SDD acted as a protective factor for more than 90% of the sample with respect to the appearance of respiratory and urinary tract infections, reducing the risk of such infections to 1/5 and 1/3, respectively. CONCLUSIONS: SDD was effective in controlling respiratory and urinary tract infections in children admitted to the PICU, but it did not reduce the incidence of other types of nosocomial infection.

Adolescent↗

PubMed1998

Activity of fludarabine in previously treated Waldenström's macroglobulinemia: a report of 71 cases. Groupe Coopératif Macroglobulinémie.

PURPOSE: There is no consensus on the treatment of patients with Waldenström's macroglobulinemia (WM) who develop primary or secondary resistance to frontline therapies. We report our experience on the activity and toxicity of fludarabine in 71 patients with WM resistant to prior chemotherapy regimens. PATIENTS AND METHODS: From January 1991 to June 1995, 71 patients were included in this retrospective study. The median age, median time from diagnosis to treatment, median immunoglobulin M (IgM) level, and median number of previous treatments were 68 years (range, 42 to 81), 5.9 years (range, 0.6 to 20), 35 g/L (range, 5 to 126), and two (range, one to four), respectively. RESULTS: Seventy-one patients received a median of six courses of fludarabine. Twenty-one (30%) responded with a partial response and 50 (70%) were considered as treatment failures. Forty-six patients died: 10 in the responder group and 36 in the failure group. Twenty-five patients were alive with a median follow-up time of 34 months. The overall median survival time of all treated patients was 23 months. The time to treatment failure was 32 months. The only factor that favorably influenced the response to fludarabine was a longer interval between the first treatment and the start of fludarabine. Pretreatment factors associated with shorter survival in the entire population were hemoglobin level less than 95 g/L (P = .02) and platelet count less than 75 x 10(9)/L (P = .02). CONCLUSION: The responses rate in this population with a poor prognosis is close to that reported in shorter series. Patients with WM who are resistant to alkylating agents should be identified early, so that salvage therapy with nucleoside analogs can be started without delay.

Adult↗

PubMed1998

Plasmatic amino acids in kidney transplantation in children.

We studied the evolution of plasma amino acid levels in children with chronic kidney failure after undergoing a renal transplantation. Plasma amino acid profile was studied in 10 children just before surgery, at admission in paediatric intensive care unit and 4, 8, 12, 24, 48 and 72 h after transplantation. Previous to the graft, plasma levels of glutamic acid (p < 0.01), hydroxyproline (p < 0.01), citrulline (p < 0.01) and arginine (p < 0.05) were significantly increased, whereas plasma levels of serine (p < 0.01), glutamine (p < 0.03), threonine (p < 0.01), tyrosine (p < 0.01), valine (p < 0.01), leucine (p < 0.01), tryptophan (p < 0.01), branched amino acids (BCAA) (p < 0.01), aromatic amino acids (AAA) (p < 0.01) and essential amino acids (EAA) (p < 0.01) were decreased in relation to control children. The amino acid profile evolution run parallel to the settle down of renal function parameters. Within 72 h after surgery, even before in some cases, all amino acids except tryptophan and arginine reached normal levels.

Adolescent↗

PubMed1997

Analysis of costs in a pediatric ICU.

OBJECTIVE: To analyze the actual cost of pediatric intensive care and its different components, particularly the differences between various patient groups, with special reference to the variable cost and the elements included in it. DESIGN: Prospective, observational study. SETTING: Multidisciplinary 12-bed pediatric intensive care unit (PICU) in a tertiary university hospital. PATIENTS: 495 admissions to the unit over 17 consecutive months; 64.2% were medical patients and 35.8% were surgical patients; the mean (SE) stay in the PICU was 6.6 +/- 0.4 days. MEASUREMENTS AND RESULTS: The fixed cost per day per patient was calculated, including the costs of physicians, nurses, auxiliary and other personnel who worked during the study period, and the costs of structural depreciation, maintenance, consumption, and disposable material. The variable cost was individually calculated from the costs of routine procedures and also included expenditure on pharmaceuticals, blood products, biochemical, hematological, and bacteriologic tests, radiology, image diagnosis procedures, and other procedures. The Physiologic Stability Index (PSI) was obtained in the first 24 h after admission. The mean fixed cost per patient per day was u.s. $608, which represents 72% of the total patient cost during this study; 86% of this amount was for personnel (58% for nurses and auxiliary staff). Variable costs came to 28% of the total amount, and were $218 +/- 100 (M +/- SEM) per patient per day. In addition to the costs of their longer stay in the PICU, the daily variable costs of nonsurvivors were higher than those of survivors ($542 +/- 52 vs $179 +/- 7; p < 0.001). We classified the patients into four groups according to their PSI score in the first 24 h; variable daily costs increased (p < 0.05) in all comparisons with the PSI level: group I: < 4 points ($155 +/- 0.5), group II: 5-9 points ($210 +/- 13), group III: 10-14 points ($324 +/- 54), group IV: > 15 points ($480 +/- 42). However, this pattern was not found for all resources: the cost of treatment techniques and biochemical and hematological tests increased, but the consumption of antibiotics, parenteral nutrition, blood products, and bacteriologic tests reached their maximum level in groups I-III and radiology was not significantly influenced by PSI level. CONCLUSIONS: The cost of personnel was the biggest factor in intensive care costs: 62.4% of the total costs. Nonsurvivors generated 3 times the mean variable daily expenditure on survivors and had longer stays in the PICU. The increase in PSI score on the first day was associated with a global increase in variable costs. The cost of treatment techniques significantly increased as the illness became more severe but consumption of antibiotics and parenteral nutrition and use of bacteriologic tests and radiology did not.

Adolescent↗

PubMed1997

Thymostimulin increases natural cytotoxic activity in patients with breast cancer.

The effect of thymostimulin on the Natural Killer (NK) cytotoxic activity of peripheral blood mononuclear cells (PBMC) was investigated in 15 patients with breast cancer after finishing or during chemotherapy (CAF) and in 10 healthy controls. PBMC from these subjects were incubated in the presence of thymostimulin for varying periods of time (18 h or 5 days), and then used as effector cells against 51Cr-radiolabeled NK-sensitive (K-562) and NK-resistant (JY) target cells in cytotoxicity assays. No significant differences were observed between the NK-activity from breast cancer patients and healthy controls. Thymostimulin induced a dose- and time-dependent cytotoxic enhancing effect on the cytotoxic activity of PBMC from these patients against NK-sensitive K562 target cells. The thymostimulin (1000 ng/ml) significantly enhanced cytotoxic activity in PBMC from breast cancer patients who had previously received chemotherapy (p = 0.0277) against NK-sensitive cells. This increase was not statistically significant neither in PBMC from patients receiving chemotherapy nor in healthy controls (p > 0.05 in both cases). The incubation of PBMC from patients with breast cancer was not associated to a significant enhancement of the cytotoxic activity against NK-resistant target cells (p > 0.05). We also found that thymostimulin could synergize with interleukin-2 in inducing NK cytotoxic activity in PBMC after 18 h of culture (p = 0.0277). In conclusion, we have demonstrated that thymostimulin enhances the natural killer cytotoxic activity of PBMC from patients with breast cancer who have previously received chemotherapy.

Adjuvants, Immunologic↗