The role of viruses in the aetiology of community-acquired pneumonia in adults

BACKGROUND: The role of viruses in community-acquired pneumonia may have been previously underestimated. We aimed to study the incidence and clinical characteristics of community-acquired pneumonia (CAP) due to respiratory viruses in adults adding PCR to routine conventional laboratory tests. METHODS: Consecutive adult patients diagnosed of CAP from January 2003 to March 2004 were included. Conventional tests including cultures of blood, sputum, urine antigen detection of Streptococcus pneumoniae and Legionella pneumophila, and paired serologies were routinely performed. Nasopharyngeal swabs were processed for study of respiratory viruses through antigen detection by indirect immunofluorescence assay, isolation of viruses in cell culture and detection of nucleic acids by two independent multiplex RT-PCR assays. According to the aetiology, patients were categorized in 4 groups: group 1, only virus detected; group 2, only bacteria detected; group 3, viral and bacterial; and group 4, unkown aetiology. RESULTS: Of 340 patients diagnosed with CAP, 198 had nasopharyngeal swabs available and were included in this study. Aetiology was established in 112 (57%) patients: group 1, n=26 (13%); group 2, n=66 (33%); group 3, n=20 (10%). The most common aetiological agent was S. neumoniae (58 patients, 29%), followed by respiratory viruses (46 patients, 23%). Forty-eight respiratory viruses were identified: influenza virus A (n=16), respiratory syncytial virus A (n=5), adenovirus (n=8), parainfluenza viruses (n=5), enteroviruses (n=1), rhinoviruses (n=8) and coronavirus (n=5). There were two patients coinfected by two respiratory viruses. Serology detected 6 viruses, immunofluorescence 8, viral culture 12, and PCR 45. For the viruses that could be diagnosed with conventional methods, the sensitivity and specificity of RT-PCR was 85% and 92%, respectively. The only clinical characteristic that significantly distinguished viral from bacterial aetiology was a lower number of leukocytes (P=0.004). CONCLUSION: PCR revealed that viruses represent a common aetiology of CAP. There is an urgent need to reconsider routine laboratory tests for an adequate diagnosis of respiratory viruses, as clinical characteristics are unable to reliably distinguish viral from bacterial aetiology.     

Expression profiling of T-cell lymphomas differentiates peripheral and lymphoblastic lymphomas and defines survival related genes.

PURPOSE: T-Cell lymphomas constitute heterogeneous and aggressive tumors in which pathogenic alterations remain largely unknown. Expression profiling has demonstrated to be a useful tool for molecular classification of tumors. EXPERIMENTAL DESIGN: Using DNA microarrays (CNIO-OncoChip) containing 6386 cancer-related genes, we established the expression profiling of T-cell lymphomas and compared them to normal lymphocytes and lymph nodes. RESULTS: We found significant differences between the peripheral and lymphoblastic T-cell lymphomas, which include a deregulation of nuclear factor-kappaB signaling pathway. We also identify differentially expressed genes between peripheral T-cell lymphoma tumors and normal T lymphocytes or reactive lymph nodes, which could represent candidate tumor markers of these lymphomas. Additionally, a close relationship between genes associated to survival and those that differentiate among the stages of disease and responses to therapy was found. CONCLUSIONS: Our results reflect the value of gene expression profiling to gain insight about the molecular alterations involved in the pathogenesis of T-cell lymphomas.     

Assessment of Segregation Potential of Powder Blends

Pharmaceutical blends consist of several components each with its own unique characteristics, with different size, shape, density, and particle-particle interactions. With so many degrees of complexity, prediction of segregation behavior becomes intractable. The objective of this study was to develop a segregation test method or a segregation tool that would assess the segregation potential of blends. Literature reports generally seek to predict the segregation behavior based on only one mechanism by which the segregation occurs, primarily sifting or fluidization. This study makes an attempt to combine both of these mechanisms by which segregation occurs. A test is developed and used to assess the segregation behavior of blends at large scale and compare the content uniformity results of tablets with the results of the segregation test. The segregation testing model was successful in predicting the segregation tendency of the formulation and also in rank ordering large scale formulation blends based on their segregation potential. A segregation risk classification system is proposed to assess the potential of segregation at large scale.     

Reproductive and behavioral effects of diisononyl phthalate (DINP) in perinatally exposed rats

Diisononyl phthalate (DINP) is a plasticizer abundantly used in consumer products as a substitute for other plasticizers prohibited in certain products due to reproductive toxicity. As anti-androgenic effects of DINP are suspected, DINP effects on reproduction and sexually dimorphic behavior were studied. Pregnant Wistar rats were gavaged from gestation day 7 to postnatal day (PND) 17 with vehicle, 300, 600, 750 or 900 mg DINP/kg bw/day. In fetal testes histopathological effects typical of phthalates were observed. In male offspring, DINP caused increased nipple retention, reduced anogenital distance, reduced sperm motility and increased sperm count. DINP affected spatial learning as female offspring performed better than controls and similarly to control males in the Morris Water Maze, indicating masculinization of behavior in DINP exposed females. These results show that DINP causes anti-androgenic effects on reproductive development, though less potent than DEHP, DBP and BBP, and further safety evaluation of DINP appears warranted.     

Perceived psychosocial outcomes of gastric bypass surgery: a qualitative study

Background: Attempts to understand postoperative psychosocial changes in the lives of individuals who have undergone gastric bypass surgery for morbid obesity have 1) been guided by constructs emanating from the assumptions of researchers, and 2) have resulted in fragmented conclusions that catalogue changes without theoretically integrating them. Materials and Methods: Using unstructured and semi-structured interviews and in-depth focus groups, 31 patients were asked in an open-ended fashion about the ways, if any, in which gastric bypass surgery had affected their lives. Grounded theory methodology was utilized in order to identify emergent themes and their interrelations, and build a meaningful, comprehensive theory of life after gastric bypass. Results: Patients' report of a rebirth/transformation was identified as the core process of the theory. The changes marking this process were clearly conceptualized in dichotomous terms comparing pre to postsurgical life. Patients reported changes that they regarded as unequivocally positive, a number of which had not been previously reported in the literature. Unique to this particular study was the finding of numerous life changes that generated tension and posed challenges in various aspects of patients' lives. Conclusion: The grounded theory proposes that the extent to which patients successfully negotiate tension-generating changes may be a major determinant in the long-term outcome of gastric bypass, both weight loss and psychosocial adjustment.     

Characterization of complement factor H binding to Yersinia enterocolitica serotype O:3

A number of bacteria bind factor H (FH), the negative regulator of the alternative complement pathway, to avoid complement-mediated killing. Here we show that a gram-negative enteric pathogen, Yersinia enterocolitica serotype O:3, uses two virulence-related outer membrane (OM) proteins to bind FH. With Y. enterocolitica O:3 mutant strains displaying different combinations of surface factors relevant to complement resistance, we demonstrated that the major receptor for FH is the OM protein YadA. Another OM protein, Ail, also contributes to FH binding provided that it is not blocked by distal parts of the lipopolysaccharide (i.e., the O antigen and the outer core hexasaccharide). Importantly, we demonstrated that surface-bound FH was functional; both YadA- and Ail-bound FH displayed cofactor activity for factor I-mediated cleavage of C3b. With truncated recombinant FH constructs, we located the binding site of Ail specifically to short consensus repeats 6 and 7 of FH, while YadA showed a novel type of FH-binding pattern and appears to bind FH throughout the entire FH molecule. We thus conclude that Y. enterocolitica, via YadA and Ail, recruits functionally active FH to its surface. FH binding appears to be an important mechanism of the complement resistance of this pathogen.     

Ambulatory diastolic blood pressure: a marker of comorbidity in elderly fit hypertensive individuals?

BACKGROUNDMasked diastolic hypotension is a new blood pressure (BP) pattern detected by ambulatory blood pressure monitoring (ABPM) in elderly hypertensives. The aim of this study was to relate ABPM and comorbidity in a cohort of fit elderly subjects attending an outpatient hypertension clinic.METHODSComorbidity was assessed by Charlson comorbidity index (CCI) and CHA₂DS₂VASc score. All subjects evaluated with ABPM were aged ≥ 65 years. CCI and CHA₂DS₂VASc score were calculated. Diastolic hypotension was defined as mean ambulatory diastolic BP < 65 mmHg and logistic regression analysis was carried out in order to detect and independent relationship between comorbidity burden and night-time diastolic BP < 65 mmHg. RESULTSWe studied 174 hypertensive elderly patients aged 72.1 ± 5.2 years, men were 93 (53.4%). Mean CCI was 0.91 ± 1.14 and mean CHA₂DS₂VASc score of 2.68 ± 1.22. Subjects with night-time mean diastolic values < 65 mmHg were higher in females [54.7% vs. 45.3%, P = 0.048; odds ratio (OR) = 1.914, 95% CI: 1.047−3.500]. Logistic regression analysis showed that only CHA₂DS₂VASc score was independently associated with night-time mean diastolic values < 65 mmHg (OR = 1.518, 95% CI: 1.161−1.985; P = 0.002), but CCI was not. CONCLUSIONSABPM and comorbidity evaluation appear associated in elderly fit subjects with masked hypotension. Comorbid women appear to have higher risk for low ambulatory BP.

The global population is ageing, and the number of subjects with long-term disorders is increasing, with heavy consequences on medical commitment and health-care systems burden.^[1] Moreover, multimorbidity is associated with a higher mortality,^[2,3] and hypertension represents a frequent condition involving patients with multiple diseases.^[1] The relationship between multimorbidity and hypertension is bidirectional. Hypertension could cause organ damage and then development of comorbidity; on the other hand, comorbidity could worsen hypertension and its consequences. In elderly subjects, hypertension could cause brain damage that could be the cause of cognitive decline;^[4] moreover, systemic atheroembolic syndrome could worsen blood pressure (BP) variability leading to cardiovascular disease (CVD).^[5]Hypertension, both complicated or not complicated, is a variable taken into consideration in a series of risk scores applied to the general population to estimate the mortality risk, such as the Cumulative Illness Rating Scale,^[6] the Charlson comorbidity index (CCI),^[7] and the Elixhauser index.^[8] The CHA₂DS₂VASc score is widely used as predictor of the risk of stroke in patients with atrial fibrillation, it includes hypertension among the factors considered for score calculation and its importance is underlined by the same weight assigned to congestive heart failure (CHF), age > 75 years, and diabetes mellitus (1 point). ^[9] However, CHA₂DS₂VASc score has also been suggested to be able to stratify adverse clinical events in hypertensive patients.^[10]In patients with comorbidities, out-of-office monitoring of BP has been shown to be associated with reduced systolic BP (SBP) compared to usual care, representing a very useful tool in routine clinical practice.^[11] However, the discrepancy of measures between office and out-of-office BP measures, such as ambulatory blood pressure monitoring (ABPM), is known since two decades,^[12] and these two approaches have pros and cons depending also on type of patients. In untreated older patients with isolated systolic hypertension, for example, ambulatory SBP was a significant predictor of cardiovascular risk over and above conventional BP.^[13,14]It is widely accepted that ABPM is a crucial informative tool for the evaluation of BP behaviour in everyday clinical practice,^[15] and is recommended to identify white-coat hypertension and masked hypertension.^[15,16] However, its importance goes greatly beyond due to its capacity to provide information for clinical use.^[15] In fact, night-time evaluation of BP is crucial to detect abnormal patterns of night-time behaviour, such as non-dipping, inverse dipping, extreme dipping and the morning surge,^[17] and asleep SBP is a significant BP derived risk factor for CVD events.^[18,19]Recently, a novel BP pattern defined masked diastolic hypotension, frequently found in older patients under antihypertensive treatment, has raised attention.^[20] Knowledge related to clinical use of ABPM in elderly subjects is still a matter of debate, and information about BP components and circadian profiles in subjects with high comorbidity burden is scarce.^[21]The aim of this study was investigate the possible relationship between the BP components (recorded by ABPM) and the comorbidity burden (assessed by means of CCI and CHA₂DS₂VASc score) in a cohort of fit elderly subjects attending an outpatient hypertension clinic.