Duration of viral shedding and factors associated with prolonged shedding among inpatients with influenza treated with oseltamivir: a prospective cohort study.

The purpose of this study was to determine the rate of decline in the diagnostic yield of influenza PCR assay after oseltamivir administration, and to identify risk factors for prolonged shedding. This was a prospective observational study. We included adult inpatients with clinical signs of influenza during the influenza seasons 2015 and 2016, who had positive influenza PCR tests and who were treated with oseltamivir. Clinical follow-up and repeat PCR testing were performed on days 2, 4 and 6 after the first positive test. We defined prolonged shedders as patients who still required hospitalization and had a positive PCR assay on day 4. Risk factors for prolonged shedding were assessed in univariate and multivariate analyses. A total of 215 patients were included in our study. The median age was 64 years and 49.3% were men. The main influenza type was H1N1 (50.1%). Rates of PCR positivity among evaluable patients on days 2, 4 and 6 were 142/215 (66%), 50/78 (64.1%) and 20/30 (66.6%), respectively. Independent risk factors for prolonged shedding (50 patients) included hypoxemia [odds ratio (OR) 2.55, 95% confidence interval (1.3-5.1)] and lower diastolic blood pressure [OR 0.94, 95% CI (0.92-0.97)] on admission. Negative PCR tests taken more than 48 h after initiation of treatment had low diagnostic yield. More severe disease, manifested by hypoxemia and lower blood pressure, is associated with prolonged shedding on oseltamivir treatment.

Cardiac troponin-I as a predictor of mortality in patients with first episode acute atrial fibrillation.

BACKGROUND: Recent-onset atrial fibrillation (AF) is a frequent cause for presentation to the emergency department. Recent studies proposed that the addition of biomarker information might improve the prediction of clinical outcomes by enabling identification of patients at high risk. AIM: We aimed to examine the role of cardiac troponin I as a predictor of clinical outcome in patients with first episode acute AF. DESIGN: Patients, 18 years or older, presenting to our hospital with a primary diagnosis of first episode acute AF were included in this retrospective study. METHODS: The association between elevated cTnI with mortality or the composite endpoint (mortality, stroke or heart failure) was examined in a univariate Cox regression model. RESULTS: Of the 274 study patients, 111 had elevated cTnI levels (41%). Increased cTnI was associated with older age, history of myocardial infarction, higher creatinine levels and higher heart rate (All P < 0.01). Elevated cTn was associated with an adjusted hazard ratio of 1.86 [95% confidence interval (CI) 1.17-2.96; P = 0.009] for mortality and 1.89 (95% CI 1.27-2.84; P = 0.002) for the combined endpoint. CONCLUSIONS: Elevated cardiac Troponin I is a significant predictor of mortality and a composite endpoint of mortality, stroke or heart failure in patients presenting with first episode acute AF.

West Nile meningo-encephalitis infection in a kidney transplant recipient.

West Nile virus is an arbovirus known to cause meningo-encephalitis in immuno-competent as well as in immunocompromised patients. Herein, we describe a kidney transplant recipient in whom meningo-encephalitis infection was caused by the West Nile virus. The clinical presentation was fever, headache, photophobia, confusion, neck stiffness, and positive Kerning test. The patient was treated with IV acyclovir, cefuroxime, ampicillin, and fluids. During hospital stay, the patient did not experience any episode of allograft rejection. Fever resolved and at follow up he was doing well. West Nile virus infection should be considered in immunocompromised patients including transplant recipients with meningo-encephalitis, especially during epidemic outbreaks.

Alveolar type 1 cells express the alpha2 Na,K-ATPase, which contributes to lung liquid clearance.

The alveolar epithelium is composed of alveolar type 1 (AT1) and alveolar type 2 (AT2) cells, which represent approximately 95% and approximately 5% of the alveolar surface area, respectively. Lung liquid clearance is driven by the osmotic gradient generated by the Na,K-ATPase. AT2 cells have been shown to express the alpha1 Na,K-ATPase. We postulated that AT1 cells, because of their larger surface area, should be important in the regulation of active Na+ transport. By immunofluorescence and electron microscopy, we determined that AT1 cells express both the alpha1 and alpha2 Na,K-ATPase isoforms. In isolated, ouabain-perfused rat lungs, the alpha2 Na,K-ATPase in AT1 cells mediated 60% of the basal lung liquid clearance. The beta-adrenergic agonist isoproterenol increased lung liquid clearance by preferentially upregulating the alpha2 Na,K-ATPase protein abundance in the plasma membrane and activity in alveolar epithelial cells (AECs). Rat AECs and human A549 cells were infected with an adenovirus containing the rat Na,K-ATPase alpha2 gene (Adalpha2), which resulted in the overexpression of the alpha2 Na,K-ATPase protein and caused a 2-fold increase in Na,K-ATPase activity. Spontaneously breathing rats were also infected with Adalpha2, which increased alpha2 protein abundance and resulted in a approximately 250% increase in lung liquid clearance. These studies provide the first evidence that alpha2 Na,K-ATPase in AT1 cells contributes to most of the active Na+ transport and lung liquid clearance, which can be further increased by stimulation of the beta-adrenergic receptor or by adenovirus-mediated overexpression of the alpha2 Na,K-ATPase.

beta(2)-adrenergic receptor overexpression increases alveolar fluid clearance and responsiveness to endogenous catecholamines in rats.

beta-Adrenergic agonists accelerate the clearance of alveolar fluid by increasing the expression and activity of epithelial solute transport proteins such as amiloride-sensitive epithelial Na(+) channels (ENaC) and Na,K-ATPases. Here we report that adenoviral-mediated overexpression of a human beta(2)-adrenergic receptor (beta(2)AR) cDNA increases beta(2)AR mRNA, membrane-bound receptor protein expression, and receptor function (procaterol-induced cAMP production) in human lung epithelial cells (A549). Receptor overexpression was associated with increased catecholamine (procaterol)-responsive active Na(+) transport and increased abundance of Na,K-ATPases in the basolateral cell membrane. beta(2)AR gene transfer to the alveolar epithelium of normal rats improved membrane-bound beta(2)AR expression and function and increased levels of ENaC (alpha subunit) abundance and Na,K-ATPases activity in apical and basolateral cell membrane fractions isolated from the peripheral lung, respectively. Alveolar fluid clearance (AFC), an index of active Na(+) transport, in beta(2)AR overexpressing rats was up to 100% greater than sham-infected controls and rats infected with an adenovirus that expresses no cDNA. The addition of the beta(2)AR-specific agonist procaterol to beta(2)AR overexpressing lungs did not increase AFC further. AFC in beta(2)AR overexpressing lungs from adrenalectomized or propranolol-treated rats revealed clearance rates that were the same or less than normal, untreated, sham-infected controls. These experiments indicate that alveolar beta(2)AR overexpression improves beta(2)AR function and maximally upregulates beta-agonist-responsive active Na(+) transport by improving responsiveness to endogenous catecholamines. These studies suggest that upregulation of beta(2)AR function may someday prove useful for the treatment of pulmonary edema.

Alveolar fluid reabsorption is impaired by increased left atrial pressures in rats.

Cardiogenic pulmonary edema results from increased hydrostatic pressures across the pulmonary circulation. We studied active Na(+) transport and alveolar fluid reabsorption in isolated perfused rat lungs exposed to increasing levels of left atrial pressure (LAP; 0--20 cmH(2)O) for 60 min. Active Na(+) transport and fluid reabsorption did not change when LAP was increased to 5 and 10 cmH(2)O compared with that in the control group (0 cmH(2)O; 0.50 +/- 0.02 ml/h). However, alveolar fluid reabsorption decreased by approximately 50% in rat lungs in which the LAP was raised to 15 cmH(2)O (0.25 +/- 0.03 ml/h). The passive movement of small solutes ((22)Na(+) and [(3)H]mannitol) and large solutes (FITC-albumin) increased progressively in rats exposed to higher LAP. There was no significant edema in lungs with a LAP of 15 cmH(2)O when all active Na(+) transport was inhibited by hypothermia or amiloride (10(-4) M) and ouabain (5 x 10(-4) M). However, when LAP was increased to 20 cmH(2)O, there was a significant influx of fluid (-0.69 +/- 0.10 ml/h), precluding the ability to assess the rate of fluid reabsorption. In additional studies, LAP was decreased from 15 to 0 cmH(2)O in the second and third hours of the experimental protocol, which resulted in normalization of lung permeability to solutes and alveolar fluid reabsorption. These data suggest that in an increased LAP model, the changes in clearance and permeability are transient, reversible, and directly related to high pulmonary circulation pressures.

Catecholamines increase lung edema clearance in rats with increased left atrial pressure.

During hydrostatic pulmonary edema, active Na(+) transport and alveolar fluid reabsorption are decreased. Dopamine (DA) and isoproterenol (ISO) have been shown to increase active Na(+) transport in rat lungs by upregulating Na(+)-K(+)-ATPase in the alveolar epithelium. We studied the effects of DA and ISO in isolated rat lungs with increased left atrial pressure (Pla = 15 cmH(2)O) compared with control rats with normal Pla (Pla = 0). Alveolar fluid reabsorption decreased from control value of 0.51 +/- 0.02 to 0.27 +/- 0.02 ml/h when Pla was increased to 15 cmH(2)O (P < 0.001). DA and ISO increased the alveolar fluid reabsorption back to control levels. Treatment with the D(1) antagonist SCH-23390 inhibited the stimulatory effects of DA (0.30 +/- 0.02 ml/h), whereas fenoldopam, a specific D(1)-receptor agonist, increased alveolar fluid reabsorption in rats exposed to Pla of 15 cmH(2)O (0.47 +/- 0.04 ml/h). Propranolol, a beta-adrenergic-receptor antagonist, blocked the stimulatory effects of ISO; however, it did not affect alveolar fluid reabsorption in control or DA-treated rats. Amiloride (a Na(+) channel blocker) and ouabain (a Na(+)-K(+)-ATPase inhibitor), either alone or together, inhibited the stimulatory effects of DA. Colchicine, which disrupts the cellular microtubular transport of ion-transporting proteins to the plasma membrane, inhibited the stimulatory effects of DA, whereas the isomer beta-lumicolchicine did not block the stimulatory effects of DA. These data suggest that DA and ISO increase alveolar fluid reabsorption in a model of increased Pla by regulating active Na(+) transport in rat alveolar epithelium. The effects of DA and ISO are mediated by the activation of dopaminergic D(1) receptors and the beta-adrenergic receptors, respectively.

Background diseases in 671 patients with moderate to severe pulmonary hypertension.

BACKGROUND: Data regarding the epidemiology of secondary pulmonary hypertension are scanty. OBJECTIVES: To describe the spectrum and relative incidence of background diseases in patients with significant secondary PHT. METHODS: We identified 671 patients with systolic pulmonary artery pressure of 45 mm Hg or more from the database of the echocardiographic laboratory. Their background diseases were recorded and classified into three subgroups: cardiac, pulmonary and pulmonary vascular disease without pulmonary parenchymal disease. Age at the first echocardiographic study, gender and systolic PAP values were recorded. Data between the three subgroups were compared. RESULTS: The mean age of the patients was 65 +/- 15 years, mean systolic PAP 61 +/- 14 mm Hg and female:male ratio 1.21:1. At the time of diagnosis 85% of the patients were older than 50. PHT was secondary to cardiac disease in 579 patients (86.3%), to PVD without PPD in 54 patients (8%) and to PPD in only 38 patients (5.7%). Mean age and mean systolic PAP did not differ significantly among the three subgroups. There was a significantly higher female:male ratio in patients with PVD without PPD compared with cardiac or pulmonary diseases (1.7:1 vs. 1.2:1 and 1.7 vs. 0.8:1 respectively, P < 0.05). CONCLUSIONS: The majority of patients with significant PHT are elderly with heart disease. PVD without PPD and chronic PPD are a relatively uncommon cause of significant PHT. Since the diagnosis of PHT is of clinical significance and sometimes merits different therapeutic interventions, we recommend screening by Doppler echocardiography for patients with high risk background diseases.

Diffuse alveolar hemorrhage following thrombolytic therapy for acute myocardial infarction.

We describe a 66-year-old patient with hemoptysis, a drop in hematocrit, hypoxemia and new bilateral alveolar infiltrates after receiving streptokinase for acute myocardial infarction. Markedly increased carbon monoxide diffusion capacity suggested a diagnosis of alveolar hemorrhage. Underlying conditions included congestive heart failure. The patient recovered uneventfully within 7 days of conservative treatment. Alveolar hemorrhage is a rare and often unrecognized life-threatening complication of thrombolytic therapy. Particular attention should be paid to the pulmonary status of patients with congestive heart failure scheduled to receive thrombolytic therapy.

Ascites and pleural effusion secondary to extramedullary hematopoiesis.

Extramedullary hematopoiesis in the pleura and peritoneum is rare. It is usually asymptomatic and generally is diagnosed on post mortem examination. Herein we describe a 33-year-old woman with long-standing myelofibrosis who presented with symptomatic ascites and pleural effusion. After complete evaluation, these were found to have been caused by extramedullary hematopoietic implants to the pleura and peritoneum. The pleural effusion responded to low-dose radiotherapy.

Group B streptococcal tricuspid valve endocarditis: a case report and review of literature.

Group B streptococcal endocarditis involving the tricuspid valve is an uncommon disease. We describe herein a young healthy woman who developed this disease following an elective abortion. She was treated with penicillin and gentamycin with no response. The patient was operated urgently and recovered. Few reports have described the disease in the last 25 years (our case is the thirteenth). Five of them were IV drug abusers, four patients suffered from debilitating diseases and in five women endocarditis developed following an obstetric procedure. In general the mortality from tricuspid valve endocarditis is low, indeed 2/13 (15%) died. The drug of choice is penicillin with gentamycin.

Amiodarone-associated granuloma in bone marrow.

BACKGROUND: Amiodarone hydrochloride is classified as a Vaughan Williams class III antiarrhythmic agent, although class I, II, and IV effects may contribute to its favorable antiarrhythmic profile. It is associated with a wide variety of adverse effects, such as hypothyroidism, hyperthyroidism, interstitial pulmonary disease, hepatitis, coagulation disorders, skin photosensitivity, corneal microdeposits, alopecia, peripheral neuropathy, and cardiovascular arrhythmias. SUBJECTS: Bone marrow aspirations and biopsies were performed on two patients treated with amiodarone, on the first during a follow-up for myelofibrosis and on the second for a suspected lymphoproliferative disorder. Several bone marrow granulomas were found in both patients. The bone marrow specimens for tuberculosis and fungal stains were negative. CONCLUSIONS: The temporal relationship between the amoidarone therapy and the development of two cases of asymptomatic bone marrow granuloma suggest the possibility that this antiarrhythmic agent is involved in the etiology of these granulomas.

[Bronchocentric granulomatosis].

We describe a 42-year-old woman with 3 solitary lung lesions in whom the diagnosis of bronchocentric granulomatosis was made by open lung biopsy. She presented with pleuritic chest pain, dry cough and fever. X-ray revealed 2 solitary nodules in the lower lobe of the right lung, and another in the lingula. The pathologic findings included necrotizing granulomatous inflammation, mainly in the bronchi and bronchioles. The lesions of the right lung were resected, resulting in complete recovery from symptoms, while the nodule in the lingula resolved spontaneously.

Effect of gastro-esophageal decongestion on variceal pressure in patients with schistosomal hepatic fibrosis.

This study includes 60 patients having schistosomal hepatic fibrosis and esophageal varices. Splenectomy alone was done for 14 patients having no history of haematemesis and gastroesophageal decongestion with splenectomy was done for the remaining 46 patients with history of haematemesis. Endoscopic variceal pressure measurements were done to all of them peroperatively and 21 days postoperatively. 17 patients, 7 after splenectomy and 10 after gastro-esophageal decongestion, were followed for 18 months post operatively. 21 days postsplenectomy, the variceal pressure dropped insignificantly from 38.09 to 33.27 cm H2O. During the following 18 months, three patients out of seven showed significant increase in variceal pressure. After decongestion with splenectomy, the mean variceal pressure dropped significantly from 42.03 to 29.17 cm H2O. For the 10 patients followed for 18 months, eight of them retained their variceal pressure as low as early postoperative figures. Thus gastro-esophageal decongestion with splenectomy is effective in reducing variceal pressure and in so doing it is better than splenectomy alone.

Septal/free wall curvature ratio: a noninvasive index of pulmonary arterial pressure.

The leftward septal shift, a well-recognized feature of pulmonary hypertension, was used to quantify right ventricular pressure in 16 patients with pulmonary hypertension and 11 control patients, all with normal left ventricular function. Pulmonary pressure was calculated from the tricuspid regurgitation jet and left ventricular pressure was taken by arm cuff measurements. Short-axis echocardiographic images were obtained and the midwall curvatures of the septum and the left ventricular free wall were measured for each frame from end diastole to end systole and averaged. The septal/free-wall curvature ratio (CR) was 0.37 +/- 0.19 in the study group compared with 0.79 +/- 0.06 in the control group (p < 0.0001). A tight relationship between the CR and the transseptal/transmural pressure ratio (CR = 0.057 + 0.89 x transseptal/transmural pressure ratio; r = 0.98; p < 0.001) was obtained by linear regression. Given the systolic arterial pressure, the pulmonary systolic pressure is given by: systolic arterial pressure x (1.064-1.12 x CR). Therefore the CR can be used as a noninvasive index that reflects the level of pulmonary pressure in relationship to the systolic arterial pressure.

Bronchiolitis obliterans organizing pneumonia. Diagnosis by transbronchial biopsy.

Transbronchial biopsy (TBB) has been considered to be inadequate for the diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP). We describe herein two patients with interstitial pulmonary disease in whom the diagnosis of BOOP was achieved by TBB. The two patients presented with progressive dyspnea, cough, tachypnea, and fine end-inspiratory crackles. The radiologic findings disclosed patchy alveolar infiltrates. Pulmonary function tests showed a restrictive pattern and decreased diffusing capacity. The pathologic findings disclosed bronchioles, alveolar ducts, and alveoli infiltrated with mononuclear cells. The lumina were obliterated with fibroblasts and loose granulation tissue. Corticosteroid treatment resulted in significant improvement. Transbronchial biopsy should be considered as a useful diagnostic tool for BOOP.

[Transient liver damage due to prajmalium bitartrate].

3 patients developed transient cholestatic jaundice after administration of prajmalium bitartrate, a class I antiarrhythmic drug. The leukocyte inhibition tests showed 4%, 12% and 15% inhibition, respectively, while eosinophilia was seen in all 3, supporting the assumption that the transient hepatic damage was due to drug exposure. Discontinuing the drug resulted in improvement in the clinical and biochemical findings.