Lung histopathological findings in fatal pandemic influenza A (H1N1) / Resultados histopatológicos pulmonares en la gripe a (H1N1) pandémica letal

Objective: To describe the lung pathological changes in influenza A (H1N1) viral pneumonia. We studied morphological changes, nitro-oxidative stress and the presence of viral proteins in lung tissue. Methods and patients: Light microscopy was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1) viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine, inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP)(for analysis under confocal microscopy) was also studied in lung tissue specimens. Results: Age ranged from 15 to 50 years. Three patients were women, and 5 had preexisting medical conditions. Diffuse alveolar damage (DAD) was present in 5 cases (as evidenced by hyaline membrane formation, alveolo-capillary wall thickening and PMN infiltrates), and interstitial fibrosis in one case. In the fluorescence studies there were signs of oxygen radical generation, increased NOS2 protein and protein nitration in lung tissue samples, regardless of the duration of ICU admission. Viral NP was found in lung tissue samples from three patients. Type I pneumocytes and macrophages harbored viral NP, as evidenced by confocal immunofluorescence microscopy. Conclusions: Lung tissue from patients with pandemic influenza A (H1N1) viral pneumonia shows histological findings consistent with DAD. Prolonged nitro-oxidative stress is present despite antiviral treatment. Viral proteins may remain in lung tissue for prolonged periods of time, lodged in macrophages and type I pneumocytes (AU)

Objetivo: Describir la histopatología pulmonar de pacientes que fallecieron con neumonía por virus de la influenza A (H1N1), el tipo celular infectado por el virus y la presencia de stress oxidativo y nitrosativo. Métodos: Hemos examinado tejido pulmonar de 6 pacientes fallecidos en la UCI con el diagnóstico de infección por el virus influenza A (H1N1) (15-50 años de edad) mediante (i) microscopía óptica, (ii) microscopia confocal con tinciones específicas para diferentes tipos celulares (aquoporina 5, factor Von Willebr and, proteína D del surfactante), (iii) inmunofluorescencia (IF) parasonda de dihidroetidio oxidado, óxido nítrico sin tasa inducible (NOS2), anti-3-nitrotirosina y nucleoproteína (NP) del virus de la influenza A (H1N1).Resultados: (1) En 5 casos se encontró daño alveolar difuso (DAD), evidenciado mediante la observación de membranas hialinas, engrosamiento de la pared alveolo-capilar e infiltración de PMN, asociado con hemorragia intensa en un paciente. Un caso presentó fibrosis intersticial.(2) Se demostró en todos los casos aumento de la inmuno-reactividad para DHE oxidado, NOS2y 3-nitrotirosina independientemente de la duración de la estancia en la UCI. (3) Se encontró NP viral en tres pacientes. (4) El virus se localiza en los neumocitos tipo I y en macrófago salveolares. Conclusiones: El tejido pulmonar de pacientes fallecidos con neumonía por virus de la influenza A (H1N1) evidencia hallazgos histológicos compatibles con DAD. El estrés nitro-oxidativo prolongado está presente a pesar del tratamiento antiviral. Las proteínas virales pueden permanecer en el tejido pulmonar durante períodos prolongados de tiempo, albergándose en los macrófagos y neumocitos tipo I (AU)

Lung histopathological findings in fatal pandemic influenza A (H1N1).

OBJECTIVE: To describe the lung pathological changes in influenza A (H1N1) viral pneumonia. We studied morphological changes, nitro-oxidative stress and the presence of viral proteins in lung tissue. METHODS AND PATIENTS: Light microscopy was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1) viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine, inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP) (for analysis under confocal microscopy) was also studied in lung tissue specimens. RESULTS: Age ranged from 15 to 50 years. Three patients were women, and 5 had preexisting medical conditions. Diffuse alveolar damage (DAD) was present in 5 cases (as evidenced by hyaline membrane formation, alveolo-capillary wall thickening and PMN infiltrates), and interstitial fibrosis in one case. In the fluorescence studies there were signs of oxygen radical generation, increased NOS2 protein and protein nitration in lung tissue samples, regardless of the duration of ICU admission. Viral NP was found in lung tissue samples from three patients. Type I pneumocytes and macrophages harbored viral NP, as evidenced by confocal immunofluorescence microscopy. CONCLUSIONS: Lung tissue from patients with pandemic influenza A (H1N1) viral pneumonia shows histological findings consistent with DAD. Prolonged nitro-oxidative stress is present despite antiviral treatment. Viral proteins may remain in lung tissue for prolonged periods of time, lodged in macrophages and type I pneumocytes.

Acute kidney injury in critically ill patients with 2009 influenza A (H1N1) viral pneumonia: an observational study.

OBJECTIVE: To describe the incidence, risk factors, and impact on mortality of acute kidney injury (AKI) in patients with 2009 influenza A (H1N1) viral pneumonia requiring mechanical ventilation. DESIGN: Observational cohort study. PATIENTS AND METHODS: AKI was defined as risk, injury or failure, according to the RIFLE classification. Early and late AKI were defined as AKI occurring on intensive care unit (ICU) day 2 or before, or after ICU day 2, respectively. Demographic data and information on organ dysfunction were collected daily. RESULTS: Of 84 patients, AKI developed in 43 patients (51%). Twenty (24%) needed renal replacement therapy. Early and late AKI were found in 28 (33%) and 15 (18%) patients, respectively. Patients with AKI, as compared with patients without AKI, had higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and ICU mortality (72% versus 39%, p < 0.01) and presented on admission more marked cardiovascular, respiratory, and hematological dysfunction. Patients with early but not late AKI presented on admission higher APACHE II score and more marked organ dysfunction, as compared with patients without AKI. ICU mortality was higher in late versus early AKI (93% versus 61%, p < 0.001). On multivariate analysis, only APACHE II score and late but not early AKI [odds ratio (OR) 1.1 (95% confidence interval 1.0-1.1) and 15.1 (1.8-130.7), respectively] were associated with mortality. CONCLUSIONS: AKI is a frequent complication of 2009 influenza A (H1N1) viral pneumonia. AKI developing after 2 days in ICU appears to be associated with different risk factors than early AKI, and is related to a higher mortality rate.

Enfermedad de Creutzfeldt-Jakob esporádica: dos casos en medicina intensiva / Sporadic Creutzfeldt-Jakob disease: two cases in intensive care

Las enfermedades priónicas o encefalopatías espongiformes son una familia de raras patologías neurodegenerativas caracterizadas por periodos de incubación prolongados asociados a una lenta, irreversible e invariablemente mortal evolución. En humanos se las clasifica en esporádica, adquirida y hereditaria o genética. Realizar el diagnóstico de «enfermedad de Creutzfeldt-Jakob» es un verdadero desafío para el médico intensivista dada la variabilidad en la presentación clínica y su baja incidencia. Se presentan 2 pacientes admitidos en la UCI en los que, tras descartar varias patologías, se diagnosticó con un nivel de «probabilidad», de acuerdo a la clasificación de la OMS, enfermedad de Creutzfeldt-Jakob esporádica. Se analizan aspectos diagnósticos clínicos y analíticos de la enfermedad resaltando la utilidad de la identificación de la proteína 14-3-3 en el líquido cefalorraquídeo (AU)

Prion diseases or spongiform encephalopathies are a family of rare neurodegenerative diseases characterized by long incubation periods associated with slow, irreversible and invariably fatal evolution. In humans, they are classified as sporadic, acquired and hereditary or genetic. Diagnosing sporadic "Creutzfeldt-Jakob Disease" (sCJD) is a real challenge for the intensive care physician, given the variability in its clinical presentation and its low incidence. The cases of two patients admitted to the Intensive Care Unit are presented. After ruling out other diseases, they were diagnosed with sCJD with a likelihood level according to the World Health Organization Classification. Clinical and laboratory diagnostic aspects of the disease were analyzed, highlighting the utility of 14-3-3 protein identification in the cerebrospinal fluid (AU)

[Sporadic Creutzfeldt-Jakob disease: two cases in intensive care]. / Enfermedad de Creutzfeldt-Jakob esporádica: dos casos en medicina intensiva.

Prion diseases or spongiform encephalopathies are a family of rare neurodegenerative diseases characterized by long incubation periods associated with slow, irreversible and invariably fatal evolution. In humans, they are classified as sporadic, acquired and hereditary or genetic. Diagnosing sporadic "Creutzfeldt-Jakob Disease" (sCJD) is a real challenge for the intensive care physician, given the variability in its clinical presentation and its low incidence. The cases of two patients admitted to the Intensive Care Unit are presented. After ruling out other diseases, they were diagnosed with sCJD with a likelihood level according to the World Health Organization Classification. Clinical and laboratory diagnostic aspects of the disease were analyzed, highlighting the utility of 14-3-3 protein identification in the cerebrospinal fluid.

Enfermedad de Marchiafava-Bignami en Uruguay / Marchiafava-Bignami disease in Uruguay

Introducción. La enfermedad de Marchiafava-Bignami(EMB) es una rara complicación del alcoholismo crónico, caracterizadapor desmielinización y necrosis del cuerpo callosoy usualmente con mal pronóstico. Actualmente, la tomografíacomputarizada (TC) y la resonancia magnética (RM)permiten diagnosticarla en vida.Casos clínicos. Describimos los dos primeros casos deEMB en Uruguay. La depresión de conciencia, la hipertonía ylos signos frontales fueron los signos clínicos dominantes.Un paciente asoció una neuropatía óptica. El otro caso presentóalteraciones neuropsiquiátricas, precediendo a la instalacióndel coma, y asociaba lesiones dérmicas pelagroides.La TC y RM evidenciaron lesiones de sustancia blanca localizadasfundamentalmente en el cuerpo calloso.Conclusiones. La potencial existencia de la EMB debeinvestigarse en todo paciente con alcoholismo crónico quese presente con síndrome confusional prolongado, estupor ocoma. La presencia de alteraciones neuropsiquiátricas puedeconstituir un pródromo, por lo cual deberían explorarse exhaustivamentelas funciones neurosicológicas, incluyendo labúsqueda de signos de desconexión interhemisférica. Laatenta observación del cuerpo calloso en la imagen es fundamentalpara el diagnóstico de esta enfermedad probablementesubdiagnosticada (AU)

Introduction. Marchiafava-Bignami disease (MBD)is a rare complication of chronic alcoholism characteri characterizedby demyelination and necrosis of the corpus callosumthat usually has a poor prognosis. It has an extensiveclinical spectrum presentation and can presently bediagnosed in vivo with the computed tomography (CT)and magnetic resonance imaging (MRI).Clinical cases. We describe two cases of MBD diseasewith fatal outcome that presented with acute onsetcoma. Impairment of consciousness, hypertonia, andfrontal release signs were the dominant clinical signs.One of the patients had optic neuropathy and the otherhad neuropsychiatric symptoms before onset of comaand pellagra-like skin lesion. The CT scan and MRI showedlesions of the white matter that were fundamentallyin the corpus callosum.Conclusions. The possibility of the existence of MBDshould be investigated in all patients with chronic alcoholismwho have prolonged confusional syndrome, stuporor coma. A prodromal stage with neuropsychiatricsymptoms should be thoroughly investigated with a neuropsychologicalexploration including interhemisphericdisconnection signs. Careful attention should be given tothe corpus callosum in the image for the diagnosis ofthis probably underdiagnosed disease (AU)

[Marchiafava-Bignami disease in Uruguay]. / Enfermedad de Marchiafava-Bignami en Uruguay.

INTRODUCTION: Marchiafava-Bignami disease (MBD) is a rare complication of chronic alcoholism characterized by demyelination and necrosis of the corpus callosum that usually has a poor prognosis. It has an extensive clinical spectrum presentation and can presently be diagnosed in vivo with the computed tomography (CT) and magnetic resonance imaging (MRI). CLINICAL CASES: We describe two cases of MBD disease with fatal outcome that presented with acute onset coma. Impairment of consciousness, hypertonia, and frontal release signs were the dominant clinical signs. One of the patients had optic neuropathy and the other had neuropsychiatric symptoms before onset of coma and pellagra-like skin lesion. The CT scan and MRI showed lesions of the white matter that were fundamentally in the corpus callosum. CONCLUSIONS: The possibility of the existence of MBD should be investigated in all patients with chronic alcoholism who have prolonged confusional syndrome, stupor or coma. A prodromal stage with neuropsychiatric symptoms should be thoroughly investigated with a neuropsychological exploration including interhemispheric disconnection signs. Careful attention should be given to the corpus callosum in the image for the diagnosis of this probably underdiagnosed disease.

Propofol vs midazolam for ICU sedation : a Canadian multicenter randomized trial.

STUDY OBJECTIVES: To determine whether sedation with propofol would lead to shorter times to tracheal extubation and ICU length of stay than sedation with midazolam. DESIGN: Multicenter, randomized, open label. SETTING: Four academic tertiary-care ICUs in Canada. PATIENTS: Critically ill patients requiring continuous sedation while receiving mechanical ventilation. INTERVENTIONS: Random allocation by predicted requirement for mechanical ventilation (short sedation stratum, < 24 h; medium sedation stratum, > or = 24 and < 72 h; and long sedation stratum, > or = 72 h) to sedation regimens utilizing propofol or midazolam. MEASUREMENTS AND RESULTS: Using an intention-to-treat analysis, patients randomized to receive propofol in the short sedation stratum (propofol, 21 patients; midazolam, 26 patients) and the long sedation stratum (propofol, 4 patients; midazolam, 10 patients) were extubated earlier (short sedation stratum: propofol, 5.6 h; midazolam, 11.9 h; long sedation stratum: propofol, 8.4 h; midazolam, 46.8 h; p < 0.05). Pooled results showed that patients treated with propofol (n = 46) were extubated earlier than those treated with midazolam (n = 53) (6.7 vs 24.7 h, respectively; p < 0.05) following discontinuation of the sedation but were not discharged from ICU earlier (94.0 vs 63.7 h, respectively; p = 0.26). Propofol-treated patients spent a larger percentage of time at the target Ramsay sedation level than midazolam-treated patients (60.2% vs 44.0%, respectively; p < 0.05). Using a treatment-received analysis, propofol sedation either did not differ from midazolam sedation in time to tracheal extubation or ICU discharge (sedation duration, < 24 h) or was associated with earlier tracheal extubation but longer time to ICU discharge (sedation duration, > or = 24 h, < 72 h, or > or = 72 h). CONCLUSIONS: The use of propofol sedation allowed for more rapid tracheal extubation than when midazolam sedation was employed. This did not result in earlier ICU discharge.

Thoracic complications of Lemierre syndrome.

Lemierre syndrome is a severe, septicemic illness most commonly caused by the anaerobic Gram-negative bacillus Fusobacterium necrophorum. It is characterized by an acute oropharyngeal infection, with secondary septic thrombophlebitis of the internal jugular vein and frequent metastatic infections. This report of a patient with the Lemierre syndrome is complemented by a review of the literature on the subject.

The vitamin D analogue EB 1089 prevents skeletal metastasis and prolongs survival time in nude mice transplanted with human breast cancer cells.

1,25-Dihydroxyvitamin D has potent antiproliferative and anti-invasive properties in vitro in cancer cells. However, its calcemic effect in vivo limits its therapeutic applications. Here, we report the efficacy of EB 1089, a low calcemic analogue of vitamin D, on the development of osteolytic bone metastases after intracardiac injection of the human breast cancer cell line MDA-MB-231 in nude mice. Animals injected with tumor cells were implanted simultaneously with osmotic minipumps containing either EB 1089 or vehicle. Both groups remained normocalcemic for the duration of the experiment. The total number of bone metastases, the mean surface area of osteolytic lesions, and tumor burden within bone per animal were markedly decreased in EB1089-treated mice. Furthermore, longitudinal analysis revealed that mice treated with EB1089 displayed a marked increase in survival and developed fewer bone lesions and less hind limb paralysis over time as compared with untreated animals. These results suggest that EB1089 may be beneficial in the prevention of metastatic bone lesions associated with human breast cancer.

The effect of sodium citrate in arterial catheters on acid-base and electrolyte measurements.

OBJECTIVE: To compare the effects of heparin or sodium citrate used to anticoagulate indwelling arterial catheters on acid-base and electrolyte measurements. DESIGN: Randomized controlled trial. SETTING: Medical-surgical university-affiliated intensive care unit. SUBJECTS: Twenty patients with indwelling arterial catheters. INTERVENTIONS: Patients were randomly allocated to have ten 1-mL aliquots of blood sampled serially from an arterial catheter maintained with either heparin or sodium citrate. A sample then obtained by arterial puncture provided true measurement values. Acid-base and electrolyte measurements of whole blood were obtained from each sample by means of a Coming 860 analyzer. MEASUREMENTS AND MAIN RESULTS: Contamination with sodium citrate lowered ionized calcium and pH but increased glucose and Pco2. Heparin produced negligible effects on those measurements. When sodium citrate was used, reliable measurements were not obtained for ionized calcium, pH, and glucose, even after 9 mL of blood had been discarded. However, reliable P(CO2) measurements were obtained after 2 mL of blood was discarded. CONCLUSIONS: Sodium citrate used to maintain arterial catheters can contaminate blood samples. The result of that contamination can mimic severe hypocalcemia, metabolic acidosis, and mild hyperglycemia. Failure to recognize the effects of sodium citrate on acid-base and electrolyte measurements may lead to changes in treatment that could affect patient outcome adversely.

How accurate is spirometry at predicting restrictive pulmonary impairment?

OBJECTIVE: To determine the accuracy with which spirometric measurements of FVC and expiratory flow rates can diagnose the presence of a restrictive impairment. DESIGN: The pulmonary function tests of 1,831 consecutive white adult patients who had undergone both spirometry and lung volume measurements on the same visit over a 2-year period were analyzed. The probability of restrictive pulmonary impairment, defined as a reduced total lung capacity (TLC) below the lower limit of the 95% confidence interval, was determined for each of several categoric classifications of the spirometric data, and additionally for each of several interval levels of the FVC and the FEV1/FVC ratio. SETTING: A large clinical laboratory in a university teaching hospital using quality-assured and standardized spirometry and lung volume measurement techniques according to American Thoracic Society standards. RESULTS: Two hundred twenty-five of 1,831 patients (12.3%) had a restrictive defect. The positive predictive value of spirometry for predicting restriction was relatively low; of 470 patients with a low FVC on spirometry, only 41% had restriction confirmed on lung volume measurements. When the analysis was confined to the 264 patients with a restrictive pattern on spirometry (ie, low FVC and normal or above normal FEV1/FVC ratio), the positive predictive value was 58%. Conversely, spirometry had a very favorable negative predictive value; only 2.4% of patients (32 of 1,361) with a normal vital capacity (VC) on spirometry had a restrictive defect by TLC measurement. The probability of a restrictive defect was directly and linearly related to the degree of reduction of FVC when the FVC was < 80% of predicted (p = 6.002). Combining the FVC and the FEV1/FVC ratio improved the predictive ability of spirometry; for all values of FVC < 80% of the predicted amount, the likelihood of restrictive disease increased as the FEV1/FVC ratio increased. CONCLUSIONS: Spirometry is very useful at excluding a restrictive defect. When the VC is within the normal range, the probability of a restrictive defect is < 3%, and unless restrictive lung disease is suspected a priori, measurement of lung volumes can be avoided. However, spirometry is not able to accurately predict lung restriction; < 60% of patients with a classical spirometric restrictive pattern had pulmonary restriction confirmed on lung volume measurements. For these patients, measurement of the TLC is needed to confirm a true restrictive defect.

[Epidemic of gastroenteritis of viral origin associated with eating imported raspberries]. / Epidémie de gastro-entérite d'origine virale associée à la consommation de framboises importées.

Several episodes of food poisoning affected the region of Quebec City in July and August 1997. In the first two episodes, the analysis of two cohorts (A and B) demonstrated that the consumption of a raspberry mousse with raspberry sauce increased the risk of contracting gastroenteritis (A, RR = 2.6 p = 0.001; B, RR = 4.7 p = 0.02). More than 200 people were sick after eating a raspberry dessert. The common ingredient of all those desserts was raspberries imported from Bosnia. Viral studies on the raspberry sauce (2) and stool samples (5) using the genome amplification method by PCR indicated the presence of genomic material compatible with a virus of the Caliciviruses family. Southern hybridization and sequence analysis showed that the nucleotide sequences found in the raspberry sauce and in the stool samples were identical. It is important to maintain active surveillance to detect and limit the spread of this kind of outbreak.

Functional magnesium deficiency in critically ill patients identified using a magnesium-loading test.

OBJECTIVE: To determine the feasibility of the magnesium-loading test in the critically ill and to validate serum ionized magnesium assay using the magnesium-loading test as a reference in this same patient population. DESIGN: Double-blind, randomized, controlled clinical investigation. SETTING: Tertiary level intensive care unit. PATIENTS: Forty-four consecutive critically ill patients without evidence of renal insufficiency. INTERVENTION: Patients were randomly allocated to receive 30 mmol (7.5 g) of magnesium sulfate daily for 3 days, or an equivalent amount of normal saline. MEASUREMENTS AND MAIN RESULTS: We recorded baseline characteristics, and serial serum biochemical measurements included creatinine, glucose, sodium, potassium, phosphate, total calcium, ionized calcium, total magnesium, and ionized magnesium. Serum assays were accompanied by 24-hr urine collections of creatinine and magnesium over the 3-day period. Baseline characteristics were comparable in both groups. In patients receiving magnesium, serum ionized magnesium and total magnesium concentrations were increased by 43% (p = .0001) and 59% (p = .0002), respectively, on day 1 as compared with the control group. Magnesium excretion in the control group averaged 4.8 +/- 2.3 mmol/day during the 3-day study period, while the magnesium excretion in the magnesium-loaded group was significantly increased to 22.7 +/- 10.9 mmol/day (p < .0001). Following day 1 magnesium loading, patients who excreted < 70% of the total magnesium (30 mmol infused magnesium plus 4.8 mmol basal excretion) were termed as functionally magnesium-deficient retainers (n = 12), and patients who excreted > 70% of the total magnesium were termed as nonretainers (n = 7). In addition, magnesium retainers on day 2 (nine of ten patients) and day 3 (five of six patients) excreted > 70% of the total magnesium, indicating a replenishment of body magnesium stores. In contrast, nonretainers on day 2 (four of five patients), and day 3 (four of four patients) continued to excrete excess amounts of magnesium. In the retainer group, only two patients had a low serum ionized magnesium concentration, while two other patients had low total serum magnesium values. In addition, magnesium retention was associated with low ionized calcium and high phosphate values. CONCLUSIONS: The magnesium-loading test is feasible and appears to be valid based on its performance during the 3-day evaluation. Using the magnesium-loading test as a reference, serum ionized magnesium appears to be an insensitive biochemical marker of functional hypomagnesemia. Larger cohort studies using the magnesium-loading test will help establish the true prevalence of magnesium deficiency and its associated risk factors in critically ill patients.

Contribution of water condensation in endotracheal tubes to contamination of the lungs.

We postulated that water condensate in endotracheal tubes (ETTs) transports bacteria in the ETTs into the lungs during mechanical ventilation. Thirty-two ETTs obtained from freshly extubated patients were studied under wet and dry conditions using a physiologic lung model. All bacteria expelled from the ETTs were collected on culture plates positioned beneath the ETT. The lung model was ventilated with saturated air at 37 degrees C over two time periods (60 min each), one in which condensation formation was prevented and the second in which condensation formed within the ETT. A mean of 457.6 colony-forming units (CFU)/h were expelled with condensation compared to a mean of 2.4 CFU/h without condensation. We concluded that bacteria were continuously transported from the ETT into the lungs during mechanical ventilation in water droplets. Prevention of water condensation abolishes this constant bacterial inoculation in a lung model.

Health service support in Operations Desert Shield and Desert Storm.

Operations Desert Shield and Desert Storm have brought into focus a number of difficulties with the medical support of U.S. Army tactical forces. These difficulties include inadequate preparation of Medical Corps officers for command, inadequate medical training of field medical unit personnel, and problems utilizing available equipment to support Operation Desert Storm tactical operations. This paper will discuss these difficulties, potential solutions for these difficulties, and some unresolved issues created by or despite these potential solutions.