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Biomedical subjects

Luis Castillo

Publications and source records attributed to Luis Castillo.

At least 19 recordsLinked to original sources
PubMed2007

Improving outcomes for children with cancer in low-income countries in Latin America: a report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO)-Part I.

The difference in survival for children diagnosed with cancer between high- and low-income countries (LIC) continues to widen as curative therapies are developed in the former but not implemented in the latter. In 1996, the Monza International School of Pediatric Hematology/Oncology (MISPHO) was founded in an attempt to narrow this survival gap. During its sixth and seventh meetings, members recognized the problem of lack of affordability of essential drugs to treat childhood cancer in many LIC, and initiated an advocacy program. In 1998, MISPHO spawned a collaboration of Central American pediatric oncology centers: the Asociación de Hemato-Oncología Pediátrica Centroamericana (AHOPCA). AHOPCA members reported preliminary findings from several of the 10 cooperative protocols that are currently in progress. In 2003, a second regional collaborative group was formed that includes seven centers in South America. Twinning programs between MISPHO centers and centers in high-income countries (HIC) have proven invaluable to harness the resources of these centers to improve pediatric oncology care in LIC. MISPHO educational efforts include oncology nursing, supportive care, cancer-specific updates, epidemiology, and clinical research methods. Educational efforts are facilitated by educational content and online conferencing via www.cure4kids.org. Identifying preventable causes of abandonment of therapy and documenting the nutritional status of patients treated at MISPHO centers are areas of active research.

Adolescent↗
PubMed2006

High-volume hemofiltration as salvage therapy in severe hyperdynamic septic shock.

OBJECTIVES: To evaluate the effect of short-term (12-h) high-volume hemofiltration (HVHF) in reversing progressive refractory hypotension and hypoperfusion in patients with severe hyperdynamic septic shock. To evaluate feasibility and tolerance and to compare observed vs. expected hospital mortality. DESIGN AND SETTING: Prospective, interventional, nonrandomized study in the surgical-medical intensive care unit of an academic tertiary center. PATIENTS: Twenty patients with severe septic shock, previously unresponsive to a multi-intervention approach within a goal-directed, norepinephrine-based algorithm, with increasing norepinephrine (NE) requirements (>0.3 microg kg(-1) min(-1)) and lactic acidosis. INTERVENTIONS: Single session of 12-h HVHF. MEASUREMENTS AND RESULTS: We measured changes in NE requirements and perfusion parameters every 4h during HVHF and 6h thereafter. Eleven patients showed decreased NE requirements and lactate levels (responders). Nine patients did not fulfill these criteria (nonresponders). The NE dose, lactate levels, and heart rates decreased and arterial pH increased significantly in responders. Hospital mortality (40%) was significantly lower than predicted (60%): 67% (6/9) in nonresponders vs. 18% (2/11) in responders. Of 12 survivors 7 required only a single 12-h HVHF session. On logistic regression analysis the only statistically significant predictor of survival was theresponse to HVHF (odds ratio 9). CONCLUSIONS: A single session of HVHF as salvage therapy in the setting of a goal-directed hemodynamic management algorithm may be beneficial in severe refractory hyperdynamic septic-shock patients. This approach may improve hemodynamics and perfusion parameters, acid-base status, and ultimately hospital survival. Moreover, it is feasible, and safe.

Adult↗
PubMed2006

Genomic response programs of Candida albicans following protoplasting and regeneration.

Transcription profiling of Candida albicans cells responding to the elimination of the wall (protoplasts) and posterior regeneration was explored. DNA microarrays were used to measure changes in the expression of 6039 genes, and the upregulated genes during regeneration at 28 degrees C were assigned to fourteen categories. A total of 407 genes were upregulated during the process, of which 144 reached a maximum after 1 h. MKC1, a gene encoding a member of the regulatory pathway involved in cell wall integrity was overexpressed. Time-dependent expression divided the genes into 40 clusters. Clusters 1-19 were highly expressed initially (time 0) and downregulated following incubation, whereas transcription of the genes grouped into clusters 20-40 showed the opposite behaviour. These results suggest that the first clusters group genes permitting the cell adaptation to a sub-optimal environment due to removal of the wall, whereas the second group represents genes required for protoplasts regeneration after shifted to optimal conditions from 4 to 28 degrees C.

Candida albicans↗
PubMed2006

Implementation of a norepinephrine-based protocol for management of septic shock: a pilot feasibility study.

BACKGROUND: The subject of the best vasopressor for hemodynamic management of septic shock (SS) is controversial. One of the difficulties in planning such studies is that physicians are reluctant to use one vasopressor exclusively, and there is considerable variation in practice. The aim of this study was to test the feasibility of implementing a single pressor-based algorithm (in this case, norepinephrine [NE]). METHODS: A NE-based algorithm was applied prospectively to 100 consecutive SS patients. A formal training program was implemented before starting the protocol and applied to 72 physicians and nurses involved in intensive care unit (ICU) patient care. Compliance, protocol violations, probable adverse effects, and outcome were evaluated on a daily basis by an independent group of fellows and a research nurse. RESULTS: In 100 patients, there were 7,139 hours of algorithm use. Only 13 protocol violations were observed, mostly in the timing of inotropic drugs. Senior staff physicians or busy night shifts accounted for most of these violations. ICU mortality was 33%, which is comparable to that predicted by Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. Adverse events probably related to NE were not observed. CONCLUSIONS: The present algorithm, applied after a strict training program, obtained an overall good acceptance and compliance with very few protocol violations in more than 7,000 hours of use. Safety was demonstrated by a global mortality comparable to that predicted by severity scores and absence of specific drug-related morbidity. The implementation of a single pressor-based algorithm for SS is feasible and safe.

Adult↗
PubMed2006

[Changes in serum lipids, plasma fibrinogen and other haemostatic parameters induced by ciprofibrate action in hyperlipidemic patients with and without coronary artery disease].

The effects of drugs with hypolipidemic properties in the prevention of the atherothrombotic vascular disease, go further than reducing serum lipids, suggesting that there are other nonlipid-related mechanisms involved; the maintenance of appropriate haemostatic balance being one of them. The objective of this investigation was a drug intervention with ciprofibrat in hyperlipidemic people with high level of plasmatic fibrinogen with the purpose of knowing the effects of the drug over these risk factors and other haemostatic parameters. Forty people, both sexes, 20 of them apparently healthy and the other 20 with clinical and angiographic evidence of coronary artery disease, were randomized to receive 100 mg of ciprofibrat or placebo during an average of 56 weeks. All of them had a clinical exam, EKG and stress test. Laboratory exams included lipid profile, plasma fibrinogen (Fg), VII factor, vonWillebrand factor, protein C (PC) and the tissue plasminogen activator with samples taken every 8 weeks. The Ciprofibrat group showed significant changes of lipids: cholesterol -23%, triglycerides -31%, high-density lipoprotein (HDLc) +24% and very low-density lipoprotein -23%, except low-density lipoprotein -24%. The haemostatic parameters in 40 weeks showed that Fg decreased 21% (p = 0.001), decreasing to 9% at the end of the follow-up. In the placebo group the HDLc showed a 10% increase (p = 0.02), PC reduced to 20% (p = 0.01) and Fg kept blood levels close to basal line, descending 10% at the end of the follow-up. In this study, the use of ciprofibrat in patients with high risk of developing atherothrombotic events, showed efficiency and security in handling hyperlipidemia, such as keeping and appropriate haemostatic balance.

Adolescent↗
PubMed2005

Anchorage of Candida albicans Ssr1 to the cell wall, and transcript profiling of the null mutant.

Incorporation into the wall of Candida albicans Ssr1, a GPI-dependent protein, was investigated by construction of different truncated genes for which the three potential omega sites (S199, S215 and G216) and the corresponding omega+1 and omega+2 were eliminated or modified. Cells of the C. albicans ssr1Delta mutant were transformed with pADH-pl harboring the truncated versions of CaSSR1, pADH-DeltaCaSSR1t(217-234) (lacking a C-terminal hydrophobic stretch of 18 aa including the putative omega+2 and omega+1, omega+2 of S215 and G216) or pADH-DeltaCaSSR1t(199-201) (lacking three serine residues), and their walls were analyzed for the protein. Results suggested that the three serine residues are essential for incorporation of CaSsr1 into the wall beta-glucan. This interpretation was confirmed when the truncated protein CaSsr1pt(199-201) was found in the spent medium. The transcription profile of the 6039 genes in C. albicans ssr1Delta showed that seven genes are upregulated (1.4-fold), including SRP54 (a signal recognition particle subunit), IPF29 (a zinc finger protein) and PTR3 (a transcriptional regulator), whereas 27 genes are downregulated (0.7-fold), including IPF6318 (a beta-glucosidase) and SOU1 (a sorbitol utilization protein). Additional genes showed a reduced increase, or decreased expression, suggesting that some current orphan genes may have unknown cell wall functions. In addition, a compensatory mechanism would appear to occur, as a substantial increase in the amount of beta-1,3-glucan (2.34-fold) was detected in the cell wall of the mutant cells.

Amino Acid Sequence↗
PubMed2005

Oxidative stress and fibrosis in incipient myocardial dysfunction in type 2 diabetic patients.

BACKGROUND: The existence of a diabetic cardiomyopathy has been recently supported by epidemiological studies. Increased oxidative stress and myocardial fibrosis has been hypothesized as etiopathogenic mechanisms. We sought to demonstrate the existence of incipient myocardial dysfunction in type 2 diabetes and its relation with markers of oxidative stress and myocardial fibrosis. METHODS: We studied by echocardiography 25 uncomplicated type 2 diabetic patients and 12 sex- and age-matched control subjects. Stress-corrected endocardial and midwall shortening and systolic and early diastolic velocity of the lateral mitral annulus (Doppler tissue) were used as parameters of myocardial function. Serum levels of glutathione peroxidase and procollagen type I carboxy-terminal peptide were used as markers of oxidative stress and myocardial fibrosis, respectively. RESULTS: Diabetics had significant lower values of corrected endocardial shortening than control subjects (P = 0.029). Both systolic and early diastolic mitral annulus velocities were significantly reduced in diabetics as compared to control subjects (P = 0.008 and P = 0.003, respectively). In diabetic patients, corrected endocardial (r = -0.56) and midwall shortening (r = -0.38) correlated with procollagen type I carboxy-terminal peptide, whereas systolic and early diastolic velocities of the mitral annulus correlated with glutathione peroxidase (both r = 0.44). CONCLUSIONS: In a highly selected group of uncomplicated type 2 diabetic patients, we found evidence of systolic and diastolic myocardial dysfunction, especially with the use of pulsed Doppler tissue imaging. The correlations between parameters of myocardial function and glutathione peroxidase and procollagen type I carboxy-terminal peptide support a mechanistic role for the increased oxidative stress and myocardial fibrosis in the myocardial dysfunction of type 2 diabetes.

Cardiomyopathies↗
PubMed2005

Management of septic shock with a norepinephrine-based haemodynamic algorithm.

UNLABELLED: Management of septic shock (SS) with a norepinephrine (noradrenaline)-based haemodynamic algorithm. INTRODUCTION: The choice of the best vasopressor for haemodynamic management of septic shock is controversial. Nevertheless, very few studies have been focused on evaluating different management algorithms. The aim of this study was to evaluate the performance of a norepinephrine (NE)-based management protocol. Experience with NE as the initial vasopressor, even if not comparative, could bring relevant data for planning future trails. We also wanted to evaluate the compliance of critical care physicians and nurses with haemodynamic management protocol. PATIENTS AND METHOD: A norepinephrine-based algorithm for the management of septic shock that commands different sequential interventions according to its requirements, was applied prospectively to 100 consecutive septic shock patients. RESULTS: Norepinephrine was used as the first vasoactive drug in all patients with a maximum dose of 0.31+/-0.3 microg kg(-1)min(-1) and an ICU mortality of 33%. Physicians applied correctly all the steps of the algorithm in 92% of the patients. Applying the algorithm, avoided the use of pulmonary artery catheter in 31 patients and led to use of lower doses of vasoactive agents than in many other clinical experiences. CONCLUSION: In conclusion, our data support extended use of an algorithm based on norepinephrine for treating septic shock patients. This is the first clinical study that uses NE as the initial vasopressor drug systematically, and although not comparative, the mortality rates adjusted to APACHE II, are comparable to other studies. It also gives support for future clinical trials comparing norepinephrine with dopamine in this setting.

Aged↗
PubMed2004

Effects of positive end-expiratory pressure on gastric mucosal perfusion in acute respiratory distress syndrome.

INTRODUCTION: Positive end-expiratory pressure (PEEP) improves oxygenation and can prevent ventilator-induced lung injury in patients with acute respiratory distress syndrome (ARDS). Nevertheless, PEEP can also induce detrimental effects by its influence on the cardiovascular system. The purpose of this study was to assess the effects of PEEP on gastric mucosal perfusion while applying a protective ventilatory strategy in patients with ARDS. METHODS: Eight patients were included. A pressure-volume curve was traced and ideal PEEP, defined as lower inflection point + 2 cmH2O, was determined. Gastric tonometry was measured continuously (Tonocap). After baseline measurements, 10, 15 and 20 cmH2O PEEP and ideal PEEP were applied for 30 min each. By the end of each period, hemodynamic, CO2 gap (gastric minus arterial partial pressures), and ventilatory measurements were performed. RESULTS: PEEP had no effect on CO2 gap (median [range], baseline: 19 [2-30] mmHg; PEEP 10: 19 [0-40] mmHg; PEEP 15: 18 [0-39] mmHg; PEEP 20: 17 [4-39] mmHg; ideal PEEP: 19 [9-39] mmHg; P = 0.18). Cardiac index also remained unchanged (baseline: 4.6 [2.5-6.3] l min(-1) m(-2); PEEP 10: 4.5 [2.5-6.9] l min(-1) m(-2); PEEP 15: 4.3 [2-6.8] l min(-1) m(-2); PEEP 20: 4.7 [2.4-6.2] l min(-1) m(-2); ideal PEEP: 5.1 [2.1-6.3] l min(-1) m(-2); P = 0.08). One patient did not complete the protocol because of hypotension. CONCLUSION: PEEP of 10-20 cmH2O does not affect gastric mucosal perfusion and is hemodynamically well tolerated in most patients with ARDS, including those receiving adrenergic drugs.

Aged↗
PubMed2004

Role of Pir1 in the construction of the Candida albicans cell wall.

Searches in a Candida albicans database (http://genolist.pasteur.fr/CandidaDB/) identified two Individual Protein Files (IPF 15363 and 19968) whose deduced amino acid sequences showed 42 % and 45 % homology with Saccharomyces cerevisiae Pir4. The two DNA sequences are alleles of the same gene (CaPIR1) but IPF 19968 has a deletion of 117 bases. IPF 19968 encodes a putative polypeptide of 364 aa, which is highly O-glycosylated and has an N-mannosylated chain, four cysteine residues and seven repeats. Both alleles are expressed under different growth conditions and during wall construction by regenerating protoplasts. The heterozygous mutant cells are elongated, form clumps of several cells and are hypersensitive to drugs that affect cell wall assembly. CaPir1 was labelled with the V5 epitope and found linked to the 1,3-beta-glucan of the C. albicans wall and also by disulphide bridges when expressed in S. cerevisiae.

Amino Acid Sequence↗
PubMed2004

[Mechanical ventilation in patients with acute neurological disease: survival and functional outcome].

BACKGROUND: The need of mechanical ventilation among patients with acute neurological diseases is considered a poor prognostic sign. AIM: To determine the mortality and functional recovery of neurological patients requiring mechanical ventilation. PATIENTS AND METHODS: Prospective study of 77 patients (42 men, age 54+/-19 years, with 11+/-4 points of Glasgow coma scale (GCS), 61% with cerebrovascular disease), that were admitted to the intensive care unit with neurological disease and that required mechanical ventilation. Functional recovery was assessed at 18 months with Glasgow outcome scale (GOS) and Barthel index. RESULTS: Thirty percent of patients died during follow up. Among surviving patients, 47% had a good recovery or moderate disability, and 74% had a Barthel index equal to or over 70. Arterial hypertension, age over 70 and mechanical ventilation longer than 6 days were associated with bad functional prognosis. CONCLUSIONS: Neurological patients requiring mechanical ventilation had a lower mortality than previously reported, and half of the survivors have an independent life. This study supports intensive care management in this group of patients.

Acute Disease↗
PubMed2004

[Intra-arterial thrombolysis in basilar artery thrombosis. Recovery of two patients with locked-in syndrome].

Locked-in syndrome is a dramatic clinical condition, the patient is awake, can listen and breath, but is unable to move any muscle, conserving only the vertical eye movements. The most common cause of locked-in syndrome is the thrombosis of the basilar artery and commonly leads to death, frequently due to pneumonia. Intravenous and intra arterial thrombolysis have been used successfully in a selective group of patients with ischemic stroke. There is only one report of two patients with locked-in syndrome who were treated successfully with intra arterial thrombolysis. Other authors, based in their experiences, do not recommend this treatment. We report two female patients aged 63 and 26 years, with Locked-in syndrome due to a basilar thrombosis who were treated successfully with intra arterial thrombolysis using recombinant tissue plasminogen activator (r-TPA). The lapses between the onset of the symptoms and thrombolysis were 5 and 8 hours respectively. A complete recanalization was obtained in both patients during the thrombolysis. One year after, the first patient has only a moderate ataxia, walking with assistance and the other has a normal neurological examination.

Adult↗
PubMed2003

Lung computed tomography during a lung recruitment maneuver in patients with acute lung injury.

OBJECTIVE: To assess the acute effect of a lung recruitment maneuver (LRM) on lung morphology in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). PATIENTS: Ten patients with ALI/ARDS on mechanical ventilation. DESIGN: Prospective clinical study. SETTING: Computed tomography (CT) scan facility in a teaching hospital. INTERVENTIONS: An LRM performed by stepwise increases in positive end-expiratory pressure (PEEP) of up to 30-40 cm H(2)O. Lung basal CT sections were taken at end-expiration (patients 1 to 5), and at end-expiration and end-inspiration (patients 6 to 10). Arterial blood gases and static compliance (C(st)) were measured before, during and after the LRM. MEASUREMENTS AND MAIN RESULTS: Poorly aerated and non-aerated tissue at PEEP 10 cm H(2)O accounted for 60.0+/-29.1% of lung parenchyma, while only 1.1+/-1.8% was hyperinflated. Increasing PEEP to 20 and 30 cm H(2)O, compared to PEEP 10 cm H(2)O, decreased poorly aerated and non-aerated tissue by 16.2+/-28.0% and 33.4+/-13.8%, respectively ( p<0.05). This was associated with an increase in PaO(2) and a decrease in total static compliance. Inspiration increased alveolar recruitment at all PEEP levels. Hyperinflated tissue increased up to 2.9+/-4.0% with PEEP 30 cm H(2)O, and to a lesser degree with inspiration. No barotrauma or severe hypotension occurred. CONCLUSIONS: Lung recruitment maneuvers improve oxygenation by expanding collapsed alveoli without inducing too much hyperinflation in ALI/ARDS patients. An LRM during the CT scan gives morphologic and functional information that could be useful in setting ventilatory parameters.

Adult↗
PubMed2003

Functional analysis of the cysteine residues and the repetitive sequence of Saccharomyces cerevisiae Pir4/Cis3: the repetitive sequence is needed for binding to the cell wall beta-1,3-glucan.

Identification of PIR/CIS3 gene was carried out by amino-terminal sequencing of a protein band released by beta-mercaptoethanol (beta-ME) from S. cerevisiae mnn9 cell walls. The protein was released also by digestion with beta-1,3-glucanases (laminarinase or zymolyase) or by mild alkaline solutions. Deletion of the two carboxyterminal Cys residues (Cys(214)-12aa-Cys(227)-COOH), reduced but did not eliminate incorporation of Pir4 (protein with internal repeats) by disulphide bridges. Similarly, site-directed mutation of two other cysteine amino acids (Cys(130)Ser or Cys(197)Ser) failed to block incorporation of Pir4; the second mutation produced the appearance of Kex2-unprocessed Pir4. Therefore, it seems that deletion or mutation of individual cysteine molecules does not seem enough to inhibit incorporation of Pir4 by disulphide bridges. In fks1Delta and gsc2/fks2Delta cells, defective in beta-1,3-glucan synthesis, modification of the protein pattern found in the supernatant of the growth medium, as well as the material released by beta-ME or laminarinase, was evident. However, incorporation of Pir4 by both disulphide bridges and to the beta-1,3-glucan of the cell wall continued. Deletion of the repetitive sequence (QIGDGQVQA) resulted in the secretion and incorporation by disulphide bridges of Pir4 in reduced amounts together with substantial quantities of the Kex2-unprocessed Pir4 form. Pir4 failed to be incorporated in alkali-sensitive linkages involving beta-1,3-glucan when the first repetitive sequence was deleted. Therefore, this suggests that this sequence is needed in binding Pir4 to the beta-1,3-glucan.

Amino Acid Sequence↗
PubMed2003

Identification and study of a Candida albicans protein homologous to Saccharomyces cerevisiae Ssr1p, an internal cell-wall protein.

After screening of a Candida albicans genome database, the product of an ORF (IPF 3054) that has 62 % homology with Saccharomyces cerevisiae Ssr1p, an internal cell-wall protein, was identified and named CaSsr1p. The deduced amino acid sequence shows that CaSsr1p contains an N-terminal hydrophobic signal peptide, is rich in Ser and Thr amino acids and has a potential glycosylphosphatidylinositol-attachment signal. CaSsr1p is released following degradation of isolated cell walls by zymolyase (mainly a 1,3-beta-glucanase) and therefore seems to be covalently linked to the beta-glucan of the cell walls. Both disruption and overexpression of the CaSSR1 gene caused an increased sensitivity to calcofluor white, Congo red and zymolyase digestion. These results suggest that CaSsr1p has a structural role associated with the cell-wall beta-glucan.

Amino Acid Sequence↗
PubMed2003

[Mechanical ventilation to treat acute respiratory distress syndrome secondary to descending necrotizing mediastinitis. Role of dynamic axial computed tomography of the lung].

Lung computed tomography (CT) is being used increasingly to assess lung morphology in patients on mechanical ventilation. Lung CT under known levels of airway pressure (dynamic CT) can also assess the response of lung parenchyma to ventilatory therapy. We report a patient with acute respiratory distress syndrome secondary to descending necrotizing mediastinitis, in whom lung dynamic CT oriented ventilatory management. Independent lung ventilation improved gas exchange and helped patient recovery.

Acute Disease↗
PubMed2003

Attributable risks for acute myocardial infarction in four countries of Latin America.

This multicenter case control study investigated, in four countries of America, the proportions of acute myocardial infarction (AMI) attributable to cholesterol, smoking, hypertension, body mass index, diabetes and family history of coronary heart disease (attributable risks, AR). AR were estimated using information from 1060 cases of AMI and 1071 controls from Argentina, 323 cases of AMI and 314 controls from Cuba, 200 cases of AMI and 200 controls from Mexico and 266 cases of AMI and 264 controls from Venezuela. AR were obtained from the prevalence of coronary risk factors in the cases and the corresponding Odds Ratio (OR) derived through appropriate multivariate models. The AR for AMI observed for hypercholesterolaemia were the following: Venezuela 27%, Mexico 3%, Cuba 30% and Argentina 36%; for diabetes: Venezuela 10%, Mexico 15%, Cuba 5% and Argentina 7% and for body mass Index: Venezuela 12%, Mexico 3%, Cuba 19% and Argentina 17%. The same risk factor may have a different attributable risk in different populations. Together, hypercholesterolaemia, hypertension, smoking, diabetes, body mass index and family history of coronary heart disease accounted for 76% of all cases of AMI in Venezuela, 70% in Mexico, 81% in Cuba and 79% in Argentina. The knowledge of attributable risks could have important implications for public health strategies, especially in those countries with limited health care resources.

Adult↗