986 resultados para Rush Hour.
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BACKGROUND AND OBJECTIVES: Cytochrome P450 (CYP) 3A4 is the main CYP isozyme involved in methadone metabolism. We investigated the influence of grapefruit juice, which contains inhibitors of intestinal CYP3A, on the steady-state pharmacokinetics of methadone. METHODS: For 5 days, 8 patients undergoing methadone maintenance treatment received 200 mL water or grapefruit juice 30 minutes before and again together with their daily dose of methadone. Blood sampling for R-, S-, and R,S-methadone plasma determination was performed over a 24-hour period. CYP3A activity was determined by measuring the plasma 1'-hydroxymidazolam/midazolam ratio. RESULTS: A decrease in the midazolam ratio was measured in all patients after grapefruit juice (mean +/- SD before grapefruit juice, 9.3 +/- 5.9; mean +/- SD after grapefruit juice, 3.9 +/- 1.2; P <.05). Grapefruit juice led to a mean 17% increase in the area under the curve extrapolated to 24 hours for both enantiomers of methadone (range, 3% to 29% [P <.005]; range, -4% to 37% [P <.05]; and range, 1% to 32% [P <.01]; for R-, S-, and R,S-methadone, respectively). A similar increase in peak level and decrease in apparent clearance were measured with grapefruit juice, whereas time to peak level, terminal half-life, and apparent volume during the terminal phase of R-, S-, and R,S-methadone were not affected by grapefruit juice. No symptom of overmedication was either detected by the clinical staff or reported by the patients. CONCLUSIONS: Grapefruit juice administration is associated with a modest increase in methadone bioavailability, which is not expected to endanger patients. However, it cannot be excluded that a much stronger effect may occur in some patients, and thus grapefruit juice intake is not recommended during methadone maintenance treatment, in particular in patients initiating such a treatment.
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One of the main problems in combating tuberculosis is caused by a poor penetration of drugs into the mycobacterial cells. A prodrug approach via activation inside mycobacterial cells is a possible strategy to overcome this hurdle and achieve efficient drug uptake. Esters are attractive candidates for such a strategy and we and others communicated previously the activity of esters of weak organic acids against mycobacteria. However very little is known about ester hydrolysis by mycobacteria and no biological model is available to study the activation of prodrugs by these microorganisms. To begin filling this gap, we have embarked in a project to develop an in vitro method to study prodrug activation by mycobacteria using Mycobacterium smegmatis homogenates. Model ester substrates were ethyl nicotinate and ethyl benzoate whose hydrolysis was monitored and characterized kinetically. Our studies showed that in M. smegmatis most esterase activity is associated with the soluble fraction (cytosol) and is preserved by storage at 5°C or at room temperature for one hour, or by storage at -80°C up to one year. In the range of homogenate concentrations studied (5-80% in buffer), k(obs) varied linearly with homogenate concentration for both substrates. We also found that the homogenates showed Michaelis-Menten kinetics behavior with both prodrugs. Since ethyl benzoate is a good substrate for the mycobacterial esterases, this compound can be used to standardize the esterasic activity of homogenates, allowing results of incubations of prodrugs with homogenates from different batches to be readily compared.
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Objective: To establish if hyperglycaemia and cardiac Troponin I (cTnI) after congenital heart surgery on cardiopulmonary bypass in children could predict outcome in intensive care unit. Methods: retrospective cohort study including 274 children (mean age 4.6 years; range 0 - 17 years-old). CTnI and glucose values were retrieved from our database. Integrated values (area under the curve (AUC)) were calculated for evaluation of sustained hyperglycaemia and then normalised per hour (48h-Gluc/h). Maximal cTnI, fi rst glucose value (Gluc1) and 48h-Gluc/h were then correlated with duration of mechanical ventilation, ICU stay and mortality using cut-off values. Results: The mean duration of mechanical ventilation was 5.1 ± 7.2 days and ICU stay was 11.0 ± 13.3 days, 11 patients (3.9%) died. Hyperglycaemia (>6.1 mmol/l) was present in 68% of children at admission and was sustained in 85% for 48 hours. The mean value of Gluc1 (7.3 ± 2.7 vs. 11.8 ± 6.4 mmol/l, p < 0.0001), 48h-Gluc/h (7.4 ± 1.4 vs. 9.9 ± 4.6 mmol/l/h, p < 0.0001) and cTnI max (16.7 ± 21.8 vs. 59.2 ± 41.4 mcg/l, p < 0.0001) were signifi cantly lower in survivors vs. non survivors. Cut-off values and odds ratio are summarised in Table 1. Analyses for duration of mechanical ventilation and for length of stay in ICU are depicted in Table 2. Conclusions: Hyperglycaemia is frequent after cardiopulmonary bypass and sustained in the fi rst 48 hours. Admission glycaemia and cTnI max are associated with a high risk of mortality, prolonged duration of mechanical ventilation and prolonged length of stay in ICU.
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Introduction: Isocyanates are sensitizing chemicals used in various industries such as polyurethane foam production or paint-related purposes. Acting as haptens recognized by T-lymphocytes, they can cause allergic asthma and rarely hypersensitivity pneumonitis (HP). We aim to present a case report of acute HP due to hexamethylene diisocyanate (HDI) in a paint quality controller, a profession not generally considered at a high risk for work-related Isocyanates exposure. Case report: A 30-yr-old otherwise healthy female, light smoker working as a paint quality controller developed shortness of breath, malaise, sweating and chills at workplace six hours after handling a HDI-based hardener. Upon admission to emergency department, symptoms had progressed to severe respiratory failure. HR computer tomography (HRCT) showed bilateral ground-glass attenuation without pleural effusion. Rapid clinical and radiological improvement occurred under facial oxygen supply and systemic steroid therapy. Occupational medicine investigations revealed regular handling of HDI using latex gloves without respiratory protection. Assessment at workplace showed insufficient air renewal (1.5 times per hour), inadequate local aspiration and HDI exposure at levels of 1-4.25 ppb/m3 (Swiss Occupation Exposure Limit 5 ppb/m3). Biological monitoring after identical work procedure executed by a co-worker showed HDI exposure (5.1 micrograms hexamethylene diamine/g creatinine). Resumption of work was disadvised because of the life-threatening event. Discussion: The diagnosis of occupational HP is highly supported by classical findings on imagery and typical symptoms occurring within approved latency interval, associated with rapid clinical improvement. Although neither broncho-alveolar lavage nor specific IgG diagnosis (en route) were performed during the acute episode, various blood tests managed to rule out evidence of an infection or autoimmune disease. Other causes of HP seem unlikely as the patient did not have any recurrence of symptoms since absence from work. Workplace evaluation provided significant information on HDI exposure and allowed substantial recommendations to diminish Isocyanate exposure for the 20 still healthy laboratory co-workers. Although the entryways (air or skin) and precise mechanism of toxicity remain unclear, the present case clearly shows that Isocyanates may trigger acute HP in susceptible workers in a profession not generally considered at a high risk.
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Introduction: Rotenone is a botanical pesticide derived from extracts of Derris roots, which is traditionally used as piscicide, but also as an industrial insecticide for home gardens. Its mechanism of action is potent inhibition of mitochondrial respiratory chain by uncoupling oxidative phosphorylation by blocking electron transport at complex-I. Despite its classification as mild to moderately toxic to humans (estimated LD50, 300-500 mg/kg), there is a striking variety of acute toxicity of rotenone depending on the formulation (solvents). Human fatalities with rotenone-containing insecticides have been rarely reported, and a rapid deterioration within a few hours of the ingestion has been described previously in one case. Case report: A 49-year-old Tamil man with a history of asthma, ingested 250 mL of an insecticide containing 1.24% of rotenone (3.125 g, 52.1-62.5 mg/kg) in a suicide attempt at home. The product was not labeled as toxic. One hour later, he vomited repeatedly and emergency services were alerted. He was found unconscious with irregular respiration and was intubated. On arrival at the emergency department, he was comatose (GCS 3) with fixed and dilated pupils, and absent corneal reflexes. Physical examination revealed hemodynamic instability with hypotension (55/30 mmHg) and bradycardia (52 bpm). Significant laboratory findings were lactic acidosis (pH 6.97, lactate 17 mmol/L) and hypokalemia (2 mmol/L). Cranial computed tomography (CT) showed early cerebral edema. A single dose of activated charcoal was given. Intravenous hydration, ephedrine, repeated boli of dobutamine, and a perfusor with 90 micrograms/h norepinephine stabilized blood pressure temporarily. Atropine had a minimal effect on heart rate (58 bpm). Intravenous lipid emulsion was considered (log Pow 4.1), but there was a rapid deterioration with refractory hypotension and acute circulatory failure. The patient died 5h after ingestion of the insecticide. No autopsy was performed. Quantitative analysis of serum performed by high-resolution/accurate mass-mass spectrometry and liquid chromatography (LC-HR/AM-MS): 560 ng/mL rotenone. Other substances were excluded by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS/MS). Conclusion: The clinical course was characterized by early severe symptoms and a rapidly fatal evolution, compatible with inhibition of mitochondrial energy supply. Although rotenone is classified as mild to moderately toxic, physicians must be aware that suicidal ingestion of emulsified concentrates may be rapidly fatal. (n=3): stridor, cyanosis, cough (one each). Local swelling after chewing or swallowing soap developed at the earliest after 20 minutes and persisted beyond 24 hours in some cases. Treatment with antihistamines and/or steroids relieved the symptoms in 9 cases. Conclusion: Bar soap ingestion by seniors carries a risk of severe local reactions. Half the patients developed symptoms, predominantly swellings of tongue and/or lips (38%). Cognitive impairment, particularly in the cases of dementia (37%), may increase the risk of unintentional ingestion. Chewing and intraoral retention of soap leads to prolonged contact with the mucosal membranes. Age-associated physiological changes of oral mucosa probably promote the irritant effects of the surfactants. Medical treatment with antihistamines and corticosteroids usually leads to rapid decline of symptoms. Without treatment, there may be a risk of airway obstruction.
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BACKGROUND: We estimated the heritability of three measures of glomerular filtration rate (GFR) in hypertensive families of African descent in the Seychelles (Indian Ocean). METHODS: Families with at least two hypertensive siblings and an average of two normotensive siblings were identified through a national hypertension register. Using the ASSOC program in SAGE (Statistical Analysis in Genetic Epidemiology), the age- and gender-adjusted narrow sense heritability of GFR was estimated by maximum likelihood assuming multivariate normality after power transformation. ASSOC can calculate the additive polygenic component of the variance of a trait from pedigree data in the presence of other familial correlations. The effects of body mass index (BMI), blood pressure, natriuresis, along with sodium to potassium ratio in urine and diabetes, were also tested as covariates. RESULTS: Inulin clearance, 24-hour creatinine clearance, and GFR based on the Cockcroft-Gault formula were available for 348 persons from 66 pedigrees. The age- and gender-adjusted correlations (+/- SE) were 0.51 (+/- 0.04) between inulin clearance and creatinine clearance, 0.53 (+/- 0.04) between inulin clearance and Cockcroft-Gault formula and 0.66 (+/- 0.03) between creatinine clearance and Cockcroft-Gault formula. The age- and gender-adjusted heritabilities (+/- SE) of GFR were 0.41 (+/- 0.10) for inulin clearance, 0.52 (+/- 0.13) for creatinine clearance, and 0.82 (+/- 0.09) for Cockcroft-Gault formula. Adjustment for BMI slightly lowered the correlations and heritabilities for all measurements whereas adjustment for blood pressure had virtually no effect. CONCLUSION: The significant heritability estimates of GFR in our sample of families of African descent confirm the familial aggregation of this trait and justify further analyses aimed at discovering genetic determinants of GFR.
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Embryonic tissue explants of the sand fly Lutzomyia longipalpis (Lutz & Neiva 1912) the main vector of Leishmania chagasi (Cunha and Chagas), were used to obtain a continuous cell line (Lulo). The tissues were seeded in MM/VP12 medium and these were incubated at 28ºC. The first subculture was obtained 45 days after explanting and 96 passages have been made to date. Lulo is composed of epithelioid cells, showed a 0.04 generations/hour exponential growth rate and population doubling time at 24.7 h. The cell line isoenzymatic profiles were determined by using PGI, PGM, MPI and 6-PGDH systems, coinciding with patterns obtained from the same species and colony's pupae and adults. The species karyotype characteristics were recognized (2n = 8), in which pair 1 is subtelocentric and pairs 2, 3 and 4 are metacentric. Lulo was free from bacterial, fungal, mycoplasmic and viral infection. Susceptibility to five arbovirus was determined, the same as Lulo interaction with Leishmania promastigotes.
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Adults and larvae of Triatoma infestans spend daylight hours assembled in shaded places. An assembling factor has been demonstrated in the excrement of this species. We analysed different aspects of the dynamics of the response of bugs. Recently fed insects do not aggregate around faeces. They start to show a significant assembling response from the 8th hour after feeding onwards. Just deposited faeces do not evoke assembling, but a significant rejection instead. This reaction switches 3 h after deposition, when the faeces become attractive to the insects. The attractiveness of faeces persists for about 10 days and can be recovered after this time by rehydration. These findings are discussed in relation to the biological role of faeces and the dynamics of the use of refuges by T. infestans.
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To assess the impact of admission to different hospital types on early and 1-year outcomes in patients with acute coronary syndrome (ACS). Between 1997 and 2009, 31 010 ACS patients from 76 Swiss hospitals were enrolled in the AMIS Plus registry. Large tertiary institutions with continuous (24 hour/7 day) cardiac catheterisation facilities were classified as type A hospitals, and all others as type B. For 1-year outcomes, a subgroup of patients admitted after 2005 were studied. Eleven type A hospitals admitted 15987 (52%) patients and 65 type B hospitals 15023 (48%) patients. Patients admitted into B hospitals were older, more frequently female, diabetic, hypertensive, had more severe comorbidities and more frequent non-ST segment elevation (NSTE)-ACS/unstable angina (UA). STE-ACS patients admitted into B hospitals received more thrombolysis, but less percutaneous coronary intervention (PCI). Crude in-hospital mortality and major adverse cardiac events (MACE) were higher in patients from B hospitals. Crude 1-year mortality of 3747 ACS patients followed up was higher in patients admitted into B hospitals, but no differences were found for MACE. After adjustment for age, risk factors, type of ACS and comorbidities, hospital type was not an independent predictor of in-hospital mortality, in-hospital MACE, 1-year MACE or mortality. Admission indicated a crude outcome in favour of hospitalisation during duty-hours while 1-year outcome could not document a significant effect. ACS patients admitted to smaller regional Swiss hospitals were older, had more severe comorbidities, more NSTE-ACS and received less intensive treatment compared with the patients initially admitted to large tertiary institutions. However, hospital type was not an independent predictor of early and mid-term outcomes in these patients. Furthermore, our data suggest that Swiss hospitals have been functioning as an efficient network for the past 12 years.
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The activity-related energy expenditure mainly depends upon body weight, the type, intensity and duration of the exercise as well as the mechanical efficiency with which the subjects perform the work. Controversy still exist about the role of hypoactivity in the aetiology of obesity both in adolescence and adulthood. A number of experimental studies based on indirect assessment of physical activity (such as pedometers, accelerometers, cinematography and heart rate) have demonstrated a significant reduction in spontaneous physical activity in certain obese groups as compared to lean matched controls. On the other hand, direct measurements of energy expenditure (by indirect calorimetry) have shown a linear relationship between body weight and 24-hour (or activity-related) energy expenditure. It therefore appears that despite the greater placidity characterising some grossly obese subjects, the absolute rate of energy expenditure - particularly in weight bearing activities - is not lower than in lean subjects, since the hypoactivity does not fully compensate for the greater gross energy cost of a given activity.
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In extreme situations, such as hyperacute rejection of heart transplant or major heart trauma, heart preservation may not be possible. Our experimental team works on a project of peripheral extracorporeal membrane oxygenation (ECMO) support in acardia as a bridge to heart transplantation or artificial heart implantation. An ECMO support was established in five calves (58.6 ± 6.9 kg) by the transjugular insertion to the caval axis of a self-expanded cannula, with carotid artery return. After baseline measurements, ventricular fibrillation was induced, great arteries were clamped, heart was excised, and right and left atria remnants, containing pulmonary veins, were sutured together leaving an atrial septal defect over the caval axis cannula. Measurements of pump flow and arterial pressure were taken with the pulmonary artery clamped and anastomosed with the caval axis for a total of 6 hours. Pulmonary artery anastomosis to the caval axis provided an acceptable 6 hour hemodynamic stability, permitting a peripheral access ECMO support in extreme scenarios indicating a heart explantation.
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With the purpose of evaluating the risk of transmission of the Chagas disease in the State of Colima, México, an entomological survey was performed to obtain triatominae and the rate of infection by Trypanosoma cruzi determined by examination of its dejections. Two hundred eighteen houses located in 16 villages were sampled. In each house the intradomestic and peridomestic habitats were examined by the man-hour-house method, sensor boxes and mouse-baited traps. Also, 12 silvatic places were explored around the same areas using the same techniques as the ones sampled. In total, 456 specimens were captured, of which 139 correspond to Triatoma phyllosoma pallidipennis; 80 to T. p. longipennis; one specimen of T. dimidiata and 236 nymphs of Triatoma sp. Two hundred ninety seven insects were captured in the intradomestic habitat, 132 in the peridomestic and 26 in the silvatic. The index of positive houses was 27%, located in the central area of the state. The rate of natural infection with T. cruzi showed 25.6%. This results confirmed the presence of two important vectors of the Chagas disease in Colima. Its preference for the domestic habitat and its high levels of natural infection with T. cruzi suggested the existence of a significant risk for its transmission in this area of the country.
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An entomological and serological survey was performed in three localities of the Department of Concepción, Province of Corrientes, Argentina in 1998 and 1999, to identify triatomines species involved in domestic and wild transmission of Chagas disease. Triatomines were collected by man/hour capture in 32 houses randomly selected and 44 nearby outdoor ecotopes. Trypanosoma cruzi infection in triatomines was assessed by direct microscopic observation (400x) of feces and polymerase chain reaction. Serological techniques used for people were Indirect Hemagglutination Test and Indirect Fluorescent Test. Triatomines were collected in 28.1% of the houses and 31.8% of the wild biotopes. Triatoma infestans (Klug 1834) was exclusively found indoors and T. cruzi infected 60% of them. Triatoma sordida (Stål 1859) was mainly found in extradomestic ecotopes where trypanosome infection rate reached 12.7%. Serological study of 98 local people showed that 29.6% were seroreactive; most of their houses were closed to wild biotopes colonized by T. sordida. Results indicate that there is an active T. infestans mediated transmission of Chagas disease in this zone that yields important human prevalence and that the populations of T. sordida in wild biotopes not only sustain the wild T. cruzi cycle but also represent an actual risk for people living in the area.
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The epidemiology of the transmission of malaria parasites varies ecologically. To observe some entomological aspects of the malaria transmission in an urban environment, a longitudinal survey of anopheline fauna was performed in Boa Vista, Roraima, Brazil. A total of 7,263 anophelines was collected in human bait at 13 de Setembro and Caranã districts: Anopheles albitarsis sensu lato (82.8%), An. darlingi (10.3%), An. braziliensis (5.5%), An. peryassui (0.9%) and An. nuneztovari (0.5%). Nightly 12 h collections showed that An. albitarsis was actively biting throughout the night with peak activities at sunset and at midnight. An. darlingi bit during all night and did not demonstrate a defined biting peak. Highest biting indices, entomological inoculation rates and malaria cases were observed seasonally during the rainy season (April-November). Hourly collections showed host seek activity for all mosquitoes peaked during the first hour after sunset. An. darlingi showed the highest plasmodial malaria infection rate followed by An. albitarsis, An. braziliensis and An. nuneztovari (8.5%, 4.6%, 3% and 2.6%, respectively). An. albitarsis was the most frequently collected anopheline, presented the highest biting index and it was the second most frequently collected infected species infected with malaria parasites. An. albitarsis and An. darlingi respectively, are the primary vectors of malaria throughout Boa Vista.
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The introduction of a maximum 48 hour working week for Non Consultant Hospital Doctors by 2010 will have significant implications for both Doctors in training and service delivery in our hospitals. This report focuses on how this reduction in working hours can be achieved and the many directly related issues that need to be addressed Download the Report here