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Biomedical subjects

F Vargas

Publications and source records attributed to F Vargas.

At least 73 records · Page 4Linked to original sources

Severe respiratory failure requiring ICU admission in bone marrow transplant recipients.

Two groups of bone marrow transplant (BMT) recipients with febrile noncardiogenic respiratory failure requiring intensive care unit (ICU) admission, in the early phase of bone marrow transplantation were compared: those who had proven infectious pneumonia and those in whom bronchoalveolar lavage (BAL) failed to establish a diagnosis. Thirty-eight consecutive neutropenic BMT recipients admitted to an ICU with febrile noncardiogenic respiratory failure were enrolled. All of them underwent a BAL with viral, fungal, bacterial, and histopathological examinations. Lung biopsies were performed in nonsurviving patients in order to compare with BAL results. Haematological, biological, respiratory failure and other organ failure parameters, infectious results, outcome, and lung biopsy results were evaluated. BAL allowed an infectious diagnosis to be established in 16 BMT recipients. No aetiology was proven in 22 patients. Without a significant difference in respiratory failure parameters on ICU admission, noninvasive continuous positive airway pressure ventilation, which was given to 11 patients in each group, was significantly more successful in patients with proven infectious pneumonia (6 of 11 versus 0 of 11 patients) and enabled endotracheal intubation to be avoided in significantly more patients with infectious disease (10 of 16 versus 22 of 22 patients). The evolution of patients without diagnosis was significantly different with more frequent renal failure, hepatic failure, and death (20 of 22 versus 9 of 16 patients). Post mortem biopsies confirmed the absence of micro-organisms, but endothelial damage and fibrosis was found in 14 of the 22 patients. In conclusion, in the early phase of bone marrow transplantation the recipients without proven aetiology of pneumonia have a worse outcome than grafted patients with proven infectious pneumonia.

Adult↗

Lutzomyia nuneztovari anglesi (Le pont & Desjeux, 1984) as a vector of Leishmania amazonensis in a sub-Andean leishmaniasis focus of Bolivia.

Recently, a new Leishmania amazonensis focus was described in a sub-Andean region (1,450-2,100 meters above sea level) of Bolivia. In this area, three anthropophilic sandfly species were identified: Lutzomyia nuneztovari anglesi Le Pont & Desjeux, 1984, which represented 86-99% of the captures, Lu. galatiae Le Pont et al., 1998, and Lu. shannoni Dyar 1929. Only Lu. nuneztovari anglesi was found naturally infected by flagellates (16 of 1,715 females). Three Leishmania stocks were isolated and analyzed by isoenzyme electrophoresis at 11 loci. No significant isoenzymatic differences were demonstrated between them and 7 stocks isolated from patients from the same area, and previously characterized as L. amazonensis. Moreover, in a simplified protocol, the experimental infection of Lu. nuneztovari anglesi by L. amazonensis was successful in 92% of the surviving specimens. These data are discussed in relation to the Killick-Kendrick criteria. These results strongly suggest that Lu. nuneztovari anglesi is the vector of L amazonensis at Cajuata, Inquisivi, La Paz, Bolivia.

Animals↗

Study of the photochemical and in vitro phototoxicity of chlortalidone [2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl)benzene sulfonamide].

The photodegradation process of the phototoxic diuretic drug chlorthalidone was studied. The products of its photolysis under UV-B were isolated and identified. Chlorthalidone was found to be active when examined by photohemolysis on human erythrocytes, but not in the presence of the isolated photoproducts. Inhibition of the photohemolysis process induced by chlorthalidone on addition of reduced glutathione (GSH) or ascorbic acid suggests the involvement of radicals species. The inhibition with 1,4-diazabycyclo [2.2.2] octane (DABCO), sodium azide (NaN3) sowie 2,5-dimethylfuran proof the participation of singlet oxygen (1O2) in this process.

Chlorthalidone↗

Trypanosoma cruzi genotypes associated with domestic Triatoma sordida in Bolivia.

Triatoma sordida is the second species of Triatominae considered of epidemiological significance in Bolivia. Associated with Triatoma infestans in various regions, it is as yet the only triatomine species established in human dwellings in localities of Velasco province, Department of Santa Cruz. This domestication is considered as primary. Flagellate parasites were detected in 16.2% of domiciliary T. sordida and the kDNA-PCR confirmed the presence of Trypanosoma cruzi. Frequencies of T. cruzi clonets 20 and 39, common clonets in Bolivian domestic cycle (T. infestans), were established by their direct detection in feces using PCR and hybridization. These clonets present low frequencies in T. sordida and synanthropic mammals. Forty-six stocks were isolated and analysed by multilocus enzyme electrophoresis (MLEE). The MLEE showed a higher clonal diversity than in T. infestans domestic cycle and the genotypes were clustered in the two principal lineages of T. cruzi. Within each lineage, a broad variability was observed. Mixture of genotypes was mostly observed in mammals. The large diversity of T. cruzi in this cycle should be related to its sylvatic origin. Moreover, the current limited sample of stocks suggests a lineage association with specific hosts.

Animals↗

A new focus of cutaneous leishmaniasis due to Leishmania amazonensis in a Sub Andean region of Bolivia.

We detected a new outbreak focus with high incidence of cutaneous leishmaniasis in the Sub Andean region of La Paz. This area was never considered previously as an endemic zone of leishmaniasis. Leishmania stocks from human lesions were isolated: three stocks were explored by pulse field gradient electrophoresis, showing evidence for their affiliation to the L. mexicana complex. Eight stocks were submitted to isoenzyme electrophoresis and compared with five reference strains: L. amazonensis, L. braziliensis, L. chagasi, L. mexicana and L. pifanoi. Close genetic proximity was evidenced between newly isolated parasites and the reference stock of L. amazonensis, whereas high divergence was observed between them and either the L. pifanoi, L. mexicana, L. braziliensis and L. chagasi reference strains.

Animals↗

Use of misoprostol during pregnancy and Möbius' syndrome in infants.

BACKGROUND: Patients with upper gastrointestinal ulceration may be treated with misoprostol, but it is not recommended for pregnant women because it may stimulate uterine contractions and cause vaginal bleeding and miscarriage. Recent data from Brazil, where misoprostol is used orally and vaginally as an abortifacient, have suggested a relation between the use of misoprostol by women in an unsuccessful attempt to terminate pregnancy and Möbius' syndrome (congenital facial paralysis) in their infants. METHODS: We compared the frequency of misoprostol use during the first trimester by mothers of infants in whom Möbius' syndrome was diagnosed and mothers of infants with neural-tube defects in Brazil. All diagnoses in infants were made between January 16, 1990, and May 31, 1996, by clinical geneticists at seven hospitals who also interviewed the mothers and recorded information about the administration of misoprostol, among other data. RESULTS: We identified 96 infants with Möbius' syndrome and matched them with 96 infants with neural-tube defects. The mean age at the time of the diagnosis of Möbius' syndrome was 16 months (range, 0.5 to 78), and the diagnosis of neural-tube defects was made within 1 week of birth in most cases. Among the mothers of the 96 infants with Möbius' syndrome, 47 (49 percent) had used misoprostol in the first trimester of pregnancy, as compared with 3 (3 percent) of the mothers of the 96 infants with neural-tube defects (odds ratio, 29.7; 95 percent confidence interval, 11.6 to 76.0). Twenty of the mothers of the infants with Möbius' syndrome had taken misoprostol only orally (odds ratio, 38.8; 95 percent confidence interval, 9.5 to 159.4), 20 had taken misoprostol both orally and vaginally, 3 had taken the drug vaginally, and 4 did not report how they took the drug. CONCLUSIONS: Attempted abortion with misoprostol is associated with an increased risk of Möbius' syndrome in infants.

Abortifacient Agents, Nonsteroidal↗

Endotoxin contamination may be responsible for the unexplained failure of human pancreatic islet transplantation.

Clinical transplantation of human islets has a disappointingly low rate of success. We report here the identification of a possible causative factor: endotoxin present in the collagenase preparations used to disperse the pancreatic tissue before islet purification and transplantation. Supporting evidence includes (1) detection of unexpectedly high levels of endotoxin in most collagenase solutions currently used to digest human pancreases; (2) demonstration that supernatants generated during islet separation are able to induce the inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in macrophages; and (3) induction of IL-1, IL-6, and TNF-alpha in the islets during the separation procedure. Cytokine expression was assessed by reverse transcription-polymerase chain reaction and, for TNF-alpha, confirmed by enzyme-linked immunoabsorbent assay. It is proposed that endotoxin and locally induced cytokines carried over with the graft activate the endothelium and promote lymphomonocytic infiltration of grafted islets and surrounding liver tissue favoring primary nonfunction and early rejection. These results also have implications for the numerous experimental procedures that use collagenase, and they point to possible ways to improve islet preparation and transplantation protocols.

Adolescent↗

Airway occlusion pressure at 0.1 s (P0.1) after extubation: an early indicator of postextubation hypercapnic respiratory insufficiency.

OBJECTIVE: To examine variables associated with postextubation respiratory distress in chronic obstructive pulmonary disease (COPD) patients. DESIGN: Prospective, clinical investigation. SETTING: Intensive care unit of a university hospital. PATIENTS: Forty COPD patients, considered ready for extubation. MEASUREMENTS AND MAIN RESULTS: We recorded, from the digital display of a standard ventilator, breathing frequency (f), tidal volume (VT) and f/VT for the respiratory pattern, airway occlusion pressure at 0.1 s (P0.1) for the respiratory drive and measured blood gases: i) before extubation, following 30 min of a 6 cm H2O pressure support (PS) ventilation trial, ii) 1 h after extubation, at the 30th min of a face mask 4 cm H2O PS ventilation trial. According to the weaning outcome, the patients were divided into two groups: respiratory distress, and non-respiratory distress within 72 h of the discontinuation of mechanical ventilation. The respiratory distress was defined as the combination of f more than 25 breaths/min, an increase in PaCO2 of at least 20% compared with the value measured after extubation, and pH lower than 7.35. We determined whether those patients who developed respiratory distress after extubation differed from those who did not. Respiratory pattern data and arterial blood gases recorded, either before or after extubation, and P0.1 recorded before extubation, were inadequate to differentiate the two groups. Only P0.1 recorded 1 h after the discontinuation of mechanical ventilation differentiated the patients who developed respiratory distress from those who did not (4.2+/-0.9 vs 1.8+/-0.8, p < 0.01). CONCLUSIONS: P0.1 recorded after extubation may be a good indicator of postextubation respiratory distress. Measuring P0.1 and/or the analysis of the evolution of this parameter could facilitate decisions during the period following extubation.

Aged↗

Inhibition by (-)-cicletanine of the vascular reactivity to angiotensin II and vasopressin in isolated rat vessels.

In pithed rats, the levorotatory (-)-enantiomer of cicletanine reduces the pressor responses to angiotensin II (AII) and also, to a lesser extent, those to arginine-vasopressin (AVP). Here we have attempted to characterize further these inhibitory effects by studies of isolated perfused rat kidney and mesenteric vascular beds. In the isolated rat kidney, (-)-cicletanine behaves as a noncompetitive antagonist of AII- and AVP-receptor stimulation, with Ki values of 9.6 and 208 micromol/L respectively. In the isolated mesenteric vascular bed, (-)-cicletanine antagonized both AII dependent contractions with an inhibitory concentration (IC50) of 54.0 +/- 20.5 micromol/L (n = 6), and AVP dependent contractions with an IC50 of 31.6 +/- 5.0 micromol/L (n = 8). In conclusion, (-)-cicletanine antagonizes AII more effectively in rat kidney than in mesenteric vascular beds. Moreover, in rat kidney vascular beds (-)-cicletanine is more potent in blocking the pressor responses to AII than in blocking those to AVP. A selective blockade of AII induced contractions in kidney vascular beds can be one factor explaining both the greater antagonistic potency of (-)-cicletanine against AII compared with AVP in pithed rats, and the renal protective properties of cicletanine in both hypertensive and aged rats.

Angiotensin II↗

Photodegradation and phototoxicity studies of furosemide. Involvement of singlet oxygen in the photoinduced hemolysis and lipid peroxidation.

The phototoxic diuretic drug furosemide (1), a 5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)-amino] benzoic acid is photolabile under aerobic and anaerobic conditions. Irradiation of a methanol solution of 1 under oxygen produces photoproducts 2, 3, 4 and singlet oxygen, while under argon the photoproducts 2 and 4 were isolated. A peroxidic unstable photoproduct was detected during the photolysis under oxygen atmosphere. The formation of singlet oxygen by photolysis of 1 was evidenced by trapping with 2,5-dimethylfuran (GC-mass), furfuryl alcohol and 1,3-cyclohexadiene-1,4-diethanoate (HPLC) as 1O2 scavengers and by the histidine test. Furosemide was screened in vitro at different concentrations for UV-Vis-induced phototoxic effects in a photohemolysis test, in the presence and absence of different radical scavengers, singlet oxygen and hydroxyl radical quenchers. However, furosemide photosensitized the peroxidation of linoleic acid, as monitored by the UV-detection of dienic hydroperoxides and it also photosensitized the oxidation of histidine. The photodegradation was catalyzed in the presence of human serum albumin. Studies on peripheral blood mononuclear and polymorphonuclear cells (lymphocytes and neutrophils) demonstrated no phototoxicity on these cell lines.

Dermatitis, Phototoxic↗

Activities of aminopeptidases in a rat saline model of volume hypertension.

Aminopeptidase activity plays a role in the metabolism of several peptides that could be involved in blood pressure control. This activity has been implicated in the pathogenesis of hypertension, essentially in spontaneously hypertensive rats. However, few studies have examined aminopeptidase activities in animal models other than genetic hypertension. To analyze the aminopeptidase response to the specific conditions of the reduced renal mass saline model of arterial hypertension, aminopeptidase A activity (glutamyl- and aspartyl-aminopeptidase), aminopeptidase M activity (alanyl-aminopeptidase), aminopeptidase B activity (arginyl-aminopeptidase), pyroglutamyl-aminopeptidase and cystinyl-aminopeptidase were measured in the neurohypophysis, in the adrenal gland and in serum of this model of hypertension. In the neurohypophysis, there was a significant increase of soluble cystinyl-, alanyl-, arginyl-, pyroglutamyl- and membrane-bound aspartyl-aminopeptidase activities in hypertensive animals. In the adrenal gland, soluble cystinyl-, alanyl-, arginyl- and pyroglutamyl-aminopeptidase activities were also higher in hypertensive rats than in normotensive controls. No differences were found in serum levels of aminopeptidase activities between both groups of animals. A highly significant positive correlation between the neurohypophysis and the adrenal gland was observed for soluble cystinyl- and alanyl-aminopeptidase activities in the model of hypertension, whereas no correlation was observed in normotensive rats. Our results suggest that aminopeptidase activities could be involved in the regulatory response to the reduced renal mass hypertension and also suggest a coordinate response between the adrenal gland and the neurohypophysis, to the specific metabolic conditions of this model of hypertension.

Adrenal Glands↗

Smallness of the panmictic unit of Triatoma infestans (Hemiptera: Reduviidae).

The population genetic structure of Triatoma infestans (Klug), the principal vector of the causative agent of Chagas disease in Bolivia, was investigated by enzyme electrophoresis at 15 loci, of which 3 were polymorphic. A total of 1,286 adults and nymphs was collected from 19 localities of the Cochabamba (high endemicity) and La Paz (low endemicity) departments. Previous results were confirmed, including a low level of polymorphism (0.20), low genetic distance between geographic areas, and a population structure compatible with an isolation by distance model. However, a high proportion (26.3%) of the surveyed localities showed a significant excess of homozygotes, disputing previous conclusions that considered the village as the probable panmictic unit. The excess of homozygotes was reduced when smaller subunits, such as individual houses or chicken coops, were considered, indicating a Wahlund effect.

Animals↗

Microbiology of acute otitis media in Costa Rican children.

BACKGROUND: Because of the increasing number of resistant middle ear pathogens reported from different centers worldwide, an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required for proper antimicrobial recommendations among different regions of the world. OBJECTIVE: To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media. METHODS: Between 1992 and 1997 a diagnostic tympanocentesis was performed in 398 Costa Rican patients with acute otitis media. Middle ear fluid was obtained for culture and minimal inhibitory concentrations were determined by the E-test technique in those isolates obtained between October, 1995, and January, 1997. RESULTS: The most common pathogens cultured were Streptococcus pneumoniae (30%), Haemophilus influenzae (14%), Staphylococcus aureus (4%) and Streptococcus pyogenes (4%). Moraxella catarrhalis was uncommon. Beta-lactamase production was low (3.7%) among the H. influenzae isolates but frequent among the Staphylococcus aureus (57.1%) and M. catarrhalis (100%) strains. Overall 9 of 46 S. pneumoniae isolates (19.6%) exhibited decreased susceptibility to penicillin of which 8 isolates (17.4%) showed intermediate and one strain (2.2%) high level resistance. Among the penicillin-susceptible S. pneumoniae isolates, susceptibility to the following antimicrobials was: 81%, azithromycin; 89%, clarithromycin; and 100%, ceftriaxone and trimethoprim-sulfamethoxazole (TMP-SMX). Among the penicillin-resistant S. pneumoniae isolates the percentage of susceptible strains was 89% for azithromycin, clarithromycin and ceftriaxone and 67% for TMP-SMX. CONCLUSIONS: Based on this microbiologic information the agents considered first line drugs in the treatment of acute otitis media in Costa Rica remain amoxicillin or TMP-SMX.

Acute Disease↗

Severe infection caused by Stomatococcus mucilaginosus in a neutropenic patient: case report and review of the literature.

A 24-year-old female, in neutropenic phase after chemotherapy for acute myelogenous leukemia (on day 15) was admitted in intensive care unit for infectious pneumonia. Two strains of Stomatococcus mucilaginosus were isolated from peripheral blood cultures. No microorganisms were yielded from bronchoalveolar lavage. Patient's condition improved with prompt instigation of effective antibiotic therapy. This was the first case of septicemia and pneumonia, due to Stomatococcus mucilaginosus, in our unit. Only 26 cases occurring in neutropenic patients with underlying hematologic malignancies were reported in the literature and among these, only five cases with pneumonia were described. The complications of this normal inhabitant of the human oral cavity can be serious and fatal: septic shock, meningitis, acute respiratory distress syndrome. This study illustrate the possible virulence of Stomatococcus mucilaginosus in neutropenic patients.

Acute Disease↗

Early infectious complications after bone marrow transplantation requiring medical ICU admission.

The objective of this study was to define the type, the incidence and the outcome of early infectious complications (mean interval between day 1 post-BMT and the onset of fever was 9+/-3 days) occurring in granulocytopenic bone marrow transplant recipients, requiring medical intensive care unit admission. Over a five-years period, forty-one patients with microbiologically confirmed infection were enrolled, with a statistically significant higher frequency of allogeneic marrow transplant recipients (51%, p < 0.02). Infectious pneumonia occurred in 24 patients (59%), septicemia with septic shock in ten patients (24%), catheter-related infection in 5 patients (12%) and meningitis in 2 patients (5%) (p < 0.001). Twenty-six patients died (63%). Among the patients with confirmed infectious pneumonitis, which occurred most frequently in allogeneic marrow recipients (p < 0.02), 16 died (67%). This poor outcome was related to the requirement of mechanical ventilation. Eight patients (80%) with septicemia and septic shock and the two patients with meningitis died. Bacteria (Pseudomonas aeruginosa and Staphylococcal species) were the most common isolated in bronchoalveolar lavage fluid and blood cultures. We found a lower incidence of fungal or viral infections compared to previous studies. Empiric antimicrobial therapy in the cases of patients admitted in ICU may be included antibiotics anti-Pseudomonas and anti-Staphylococcus, as the ecology of hematology unit. The requirement of mechanical ventilation is the main adverse prognostic factor in transplanted patients. At ICU admission, patients with hepatic failure combined with respiratory failure represented a subgroup with a dismal prognosis.

Adult↗

Renal aminopeptidase activities in animal models of hypertension.

Aminopeptidase activity (AP) has been implicated in the metabolism of renal and circulating vasoactive peptides. This activity is involved in the pathogenia of hypertension, essentially in spontaneously hypertensive rats. However, no other animal models, which develop hypertension by other different ways, have been used to study the possible role of aminopeptidase activity. To investigate the role of this activity in the pathogenesis of hypertension, angiotensinase A activity (glutamyl-AP and aspartyl-AP), aminopeptidase M activity (alanyl-AP), aminopeptidase B activity (arginyl-AP), pyroglutamyl-AP, and cystinyl-AP were measured in the serum and kidney of two experimental animal models of renovascular hypertension: Goldblatt two-kidney one clip (G2K-1C) and low renal mass rats (LRM). No differences were found in serum levels of AP in LRM or G2K-1C in comparison with their respective controls. In LRM rats there was a significant decrease in membrane-bound angiotensinase A (glutamyl-AP), arginyl-AP and alanyl-AP activities. In G2K-1C rats there was a significant decrease in soluble and membrane-bound angiotensinase A activity (aspartyl-AP). Our results suggest that AP activities play a role in the regulation of renal vasoactive peptides, and respond differently depending on the cause of hypertension.

Aminopeptidases↗