Diagnosis, Clinical Presentation, and In-Hospital Mortality of Severe Malaria in HIV-Coinfected Children and Adults in Mozambique

Background.?Severe falciparum malaria with human immunodeficiency virus (HIV) coinfection is common in settings with a high prevalence of both diseases, but there is little information on whether HIV affects the clinical presentation and outcome of severe malaria. Methods.?HIV status was assessed prospectively in hospitalized parasitemic adults and children with severe malaria in Beira, Mozambique, as part of a clinical trial comparing parenteral artesunate versus quinine (ISRCTN50258054). Clinical signs, comorbidity, complications, and disease outcome were compared according to HIV status. Results.?HIV-1 seroprevalence was 11% (74/655) in children under 15 years and 72% (49/68) in adults with severe malaria. Children with HIV coinfection presented with more severe acidosis, anemia, and respiratory distress, and higher peripheral blood parasitemia and plasma Plasmodium falciparum histidine-rich protein-2 (PfHRP2). During hospitalization, deterioration in coma score, convulsions, respiratory distress, and pneumonia were more common in HIV-coinfected children, and mortality was 26% (19/74) versus 9% (53/581) in uninfected children (P?相似文献   

Prooxidant-Antioxidant Balance and Antioxidized LDL Antibody Level Values and Cardiac Function in Patients with Coronary Artery Disease

Objectives: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). Methods: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. Results: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = -0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). Conclusion: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB.     

Respiratory symptoms in rheumatoid arthritis: relation to pulmonary abnormalities detected by high-resolution CT and pulmonary functional testing

Pulmonary disease is the most frequent and among the most severe extra-articular manifestation of rheumatoid arthritis (RA). However, this issue has not been sufficiently studied in Egyptian patients. The objectives of the present study are to investigate the prevalence and types of pulmonary involvement using high-resolution computed tomography scan (HRCT) and pulmonary function tests (PFT) and evaluate the association between respiratory symptoms and RA-lung disease in a group of Egyptian RA patients. Thirty-six RA patients were recruited; 34 females (94.4%) and 2 males (5.6%) with median age of 48.5?years, and none of them was smoker. Detailed medical and drug histories were obtained. PFT, plain X-ray of the chest, and HRCT were performed to all subjects involved. Nearly 64% of RA patients demonstrated abnormalities in PFT and 47% in HRCT. Mixed restrictive and obstructive pattern was the commonest. Nearly two-thirds of our patients reported one or more pulmonary symptom whether dyspnea, cough, wheezing, or phlegm. Dyspnea was the most frequent symptom. Respiratory symptoms were statistically more common in patients with lung disease. The advanced age, high radiological score, and severity of rheumatoid disease were found to be predictive of lung involvement. Among respiratory symptoms, dyspnea and cough were associated with any pulmonary abnormalities. When specific pulmonary abnormalities were considered, only dyspnea was identified as predictor for restriction. For obstructive abnormality, both cough and wheezing provided valid prediction. We conclude that pulmonary involvement is a common manifestation in Egyptian RA patients, and the pattern of involvement is generally consistent with other studies that were performed worldwide. Specific respiratory symptoms could be used as practical, easy, and cost-effective method, especially in older and with more severe RA patients, to discriminate patients in need of subsequent PFT and HRCT imaging.     

Epigenetic induction of adaptive immune response in multiple myeloma: sequential azacitidine and lenalidomide generate cancer testis antigen-specific cellular immunity

Patients with multiple myeloma (MM) undergoing high dose therapy and autologous stem cell transplantation (SCT) remain at risk for disease progression. Induction of the expression of highly immunogenic cancer testis antigens (CTA) in malignant plasma cells in MM patients may trigger a protective immune response following SCT. We initiated a phase II clinical trial of the DNA hypomethylating agent, azacitidine (Aza) administered sequentially with lenalidomide (Rev) in patients with MM. Three cycles of Aza and Rev were administered and autologous lymphocytes were collected following the 2nd and 3rd cycles of Aza‐Rev and cryopreserved. Subsequent stem cell mobilization was followed by high‐dose melphalan and SCT. Autologous lymphocyte infusion (ALI) was performed in the second month following transplantation. Fourteen patients have completed the investigational therapy; autologous lymphocytes were collected from all of the patients. Thirteen patients have successfully completed SCT and 11 have undergone ALI. Six patients tested have demonstrated CTA up‐regulation in either unfractionated bone marrow (n = 4) or CD138+ cells (n = 2). CTA (CTAG1B)‐specific T cell response has been observed in all three patients tested and persists following SCT. Epigenetic induction of an adaptive immune response to cancer testis antigens is safe and feasible in MM patients undergoing SCT.     

Routine Coronary Arteriography Following Thrombolytic Therapy for Acute Myocardial Infarction: An Unsettled Controversy

Although coronary artery disease remains the leading cause of death in industrialized countries, the management of patients recovering from acute myocardial infarction varies significantly. The issue of routine arteriography and revascularization following thrombolytic therapy remains controversial despite substantial evidence associating infarct-related artery patency with improved cardiac function and survival. Randomized trials of routine intervention after myocardial infarction have generally failed to demonstrate advantages of this invasive approach but methodological problems limit their application to current practice. High-risk patients should be referred for arteriography. While awaiting definitive trials addressing the influence of routine arteriography on patient survival and its cost effectiveness, the management of other patient groups must be individualized.     

Behavioral Similarities and Differences among Alcohol-Preferring and -Nonpreferring Rats: Confirmation by Factor Analysis and Extension to Additional Groups

Thirteen behavioral variables from six tasks were measured in alcohol-preferring (AA, FH, and P) and -non-preferring (ANA, FRL, and NP) rat lines/strains and subjected to Factor Analysis. Four independent factors accounted for >90% of the variance. Defecation in the open field and ultrasonic vocalizations after an air puff were negatively correlated with alcohol intake and preference, whereas the increase in daily fluid intake in the presence of saccharin was positively correlated. Other factors could be labeled Activity, Emotionality, and Immobility Factors, and each was independent of the Alcohol Factor. When an additional alcohol-preferring rat line (HAD) and two additional non-preferring groups (LAD and ACI) were tested, they were found to differ on most behaviors that were associated with alcohol intake and preference in the Factor Analysis: vocalizations and saccharin-induced increase in fluid intake, but not defecation. A new Factor Analysis was then performed incorporating these three new groups and including five new behavioral measures. The following measures had high loadings on the Alcohol Factor: alcohol intake under choice conditions; alcohol preference; forced alcohol intake; alcohol acceptance (forced alcohol intake/basal water intake × 100); ultrasonic vocalization; saccharin intake; saccharin-induced increase in daily fluid intake; defecation in the open field test; and immobility in a modified forced swim test. These findings indicate that there are indeed certain behavioral characteristics that are common among alcohol-preferring rat lines/strains, but there are also substantial group differences on other behavioral measures. For those behavioral measures reflecting emotionality (defecation and ultrasonic vocalization) that loaded highly on the Alcohol Factor, the alcohol-preferring rats had lower scores.     

Selective Inhibition of Alcohol Intake in Diverse Alcohol-Preferring Rat Strains by the 5-HT2A Antagonists Amperozide and FG 5974

The present studies sought to elucidate the role of 5-HT_2A receptor antagonists in suppressing alcohol intake by comparing the effects of amperozide and FG 5974 on alcohol, food, and water intake in strains of alcohol-preferring rats: P, Alko Alcohol (AA), and Fawn-Hooded (FH). Both amperozide and FG 5974 have 5-HT_2A receptor antagonist properties, but FG 5974 also shows presynaptic 5-HT_1A receptor agonist activity. After establishment of stable baselines for intake measures in a two-bottle continuous access paradigm, rats ( n = 10) were injected with 1 of 5 doses (0, 1.0, 2.5, 5.0, and 10.0 mg/kg, sc) of amperozide or FG 5974 at weekly intervals. Amperozide dose-dependently reduced alcohol intake, total fluid intake, and alcohol preference in all three strains under continuous access conditions, whereas FG 5974 was less effective. Food intake was also suppressed by amperozide at higher doses, whereas it was increased by FG 5974. Amperozide also dose-dependently reduced alcohol intake when it was available for only 1 hr/day, but FG 5974 tended to increase it. After oral administration, amperozide was also more effective than FG 5974 in reducing alcohol intake. Despite these differences in efficacy in suppressing alcohol intake, both compounds produced taste aversion to a novel saccharin solution. These complex findings suggest that biochemical properties other than 5-HT_2A receptor antagonism (e.g., 5-HT_1A receptor agonism) may be involved in the effects of amperozide and FG 5974 on alcohol intake and other consummatory behaviors.     

A family of secreted proteins contains homology to the cysteine-rich ligand-binding domain of frizzled receptors

This paper describes the identification of a new family of mammalian genes that encode secreted proteins containing homology to the cysteine-rich ligand-binding domain found in the frizzled family of transmembrane receptors. The secreted frizzled-related proteins (sFRPs) are approximately 30 kDa in size, and each contains a putative signal sequence, a frizzled-like cysteine-rich domain, and a conserved hydrophilic carboxy-terminal domain. The sFRPs are not the products of differential splicing of the known frizzled genes. Glycosylphosphatidylinositol-anchored derivatives of sFRP-2 and sFRP-3 produced in transfected human embryonic kidney cells confer cell-surface binding by the Drosophila Wingless protein. These observations suggest that sFRPs may function in vivo to modulate Wnt signaling, or, alternatively, as novel ligands for as yet unidentified receptors.     

Chronic eosinophilic pneumonia associated with cutaneous T-cell lymphoma

Cutaneous T-cell lymphomas (CTCL) are diseases characterized by cutaneous infiltrates of malignant clonally expanded T cells. CTCL cells exhibit a cytokine profile consistent with T helper-2 type (TH₂) cells. Eosinophilic pneumonias are individual syndromes characterized by eosinophilic pulmonary infiltrates and commonly peripheral blood eosinophilia. CTCL and chronic eosinophilic pneumonia are rare clinical entities. We report a patient with the association of CTCL and chronic eosinophilic pneumonia. To understand the mechanism leading to the eosinophilia, we examined the patient's cytokine profile. This was consistent with a high TH₂ activity. Her interleukin (IL) 5, 6, and 10 levels were extremely high, while her IL-2 and interferon-γ (IFN-γ) levels (TH₁ profile) were low. We believe that eosinophilic pneumonia in this patient is probably secondary to high TH₂ cytokine levels induced by tumor cells. We suggest that eosinophilic pneumonia should be considered as a possible diagnosis in patients with CTCL who have respiratory complaints. Am. J. Hematol. 60:143–147, 1999. © 1999 Wiley-Liss, Inc.     

Is propofol safe for procedural sedation in children? A prospective evaluation of propofol versus ketamine in pediatric critical care

OBJECTIVES: To compare propofol with ketamine sedation delivered by pediatric intensivists during painful procedures in the pediatric critical care department (PCCD). DESIGN: Prospective 15-month study. SETTING: An 18-bed multidisciplinary, university-affiliated PCCD. INTERVENTIONS: All children were randomized to the propofol or ketamine protocol according to prescheduled procedure dates. Propofol was delivered by continuous infusion after a loading bolus dose and a minidose of lidocaine (PL). Ketamine was given as a bolus injection together with midazolam and fentanyl (KMF). Repeated bolus doses of both drugs were given to achieve the desired level of anesthesia. The studied variables included procedures performed, anesthetic drug doses, procedure and recovery durations, and side effect occurrence. The patient's parents, PCCD nurse and resident physician, pediatric intensivist, and the physician performing the procedure graded the adequacy of anesthesia. MEASUREMENTS AND MAIN RESULTS: Of the 105 procedures in 98 children, PL sedation was used in 58 procedures, and KMF was used in 47. Recovery time was 23 mins for PL and 50 mins for KMF, and total PCCD monitoring was 43 mins for PL and 70 mins for KMF. Five children (10.6%) in the KMF group and in none in the PL group experienced discomfort during emergence from sedation. Transient decreases in blood pressure, partial airway obstruction, and apnea were more frequent in the PL than in the KMF sedation. All procedures were successfully completed, and no child recalled undergoing the procedure. The overall sedation adequacy score was 97% for PL and 92% for KMF (p <.05). CONCLUSIONS: Both PL and KMF anesthesia are effective in optimizing comfort in children undergoing painful procedures. PL scored better by all evaluators, recovery from PL anesthesia after procedural sedation was more rapid, total PCCD stay was shorter with PL, and emergence from PL was smoother than with KMF. Because transient respiratory depression and hypotension are associated with PL, it is considered safe only in a monitored environment (e.g., a PCCD).