Anti-viral strategies of cytotoxic T lymphocytes are manifested through a variety of granule-bound pathways of apoptosis induction.
(9/2922)
Cytotoxic T cells and natural killer cells together constitute a major defence against virus infection, through their ability to induce apoptotic death in infected cells. These cytolytic lymphocytes kill their targets through two principal mechanisms, and one of these, granule exocytosis, is essential for an effective in vivo immune response against many viruses. In recent years, the authors and other investigators have identified several distinct mechanisms that can induce death in a targeted cell. In the present article, it is postulated that the reason for this redundancy of lethal mechanisms is to deal with the array of anti-apoptotic molecules elaborated by viruses to extend the life of infected cells. The fate of such a cell therefore reflects the balance of pro-apoptotic (immune) and anti-apoptotic (viral) strategies that have developed over eons of evolutionary time. (+info)
In search of a cause of cryptogenic fibrosing alveolitis (CFA): one initiating factor or many?
(10/2922)
The history of patients with idiopathic pulmonary fibrosis (IPF) shows that the disease may be preceded by a viral-like illness. Although viruses have not been demonstrated, it is possible that viruses were not detected in culture because they do not replicate during latency. We investigated the presence of adenovirus in IPF and interstitial pneumonia associated with collagen vascular disease (CVD-IP), using the nested polymerase chain reaction (PCR) and in situ hybridization (ISH) for the E1A region of the adenovirus genome. Studies were performed on lung tissues obtained by transbronchial lung biopsy from 19 patients with IPF, 10 patients with CVD-IP and, for comparison, 20 patients with sarcoidosis. The E1A DNA was present in 3 out of 19 (16%) cases of IPF, in 5 of 10 (50%) cases of CVD-IP, and in 2 of 20 (10%) cases of sarcoidosis. The incidence of E1A DNA in CVD-IP was significantly higher than that in sarcoidosis (p < 0.05). In patients with IPF and CVD-IP, E1A DNA was more prevalent in patients treated with corticosteroids (6 out of 9 cases; 67%) than in those without it (2 out of 20 cases; 10%) (p < 0.01). ISH studies showed that 1 out of 8 cases of IPF and CVD-IP, in which E1A DNA was detected by PCR, was positive for E1A DNA. We conclude that adenovirus E1A is unlikely to be aetiologically involved in the pathogenesis of idiopathic pulmonary fibrosis or interstitial pneumonia associated with collagen vascular disease. However, a latent adenovirus infection may be reactivated or may newly infect the host following corticosteroid administration. (+info)
Relative bradycardia is not a feature of enteric fever in children.
(11/2922)
We investigated pulse-temperature relationships in 66 children with enteric fever (group 1) and in 76 with other infections (group 2). Group 1 children were older than group 2 children (mean age +/- SD, 91 +/- 36 vs. 66 +/- 32 months, respectively; P < .001) and had mean oral temperatures +/- SD similar to those of group 2 children (38.3 +/- 1.0 vs. 38.3 +/- 0.9 degrees C, respectively; P > .2); however, group 1 children had lower mean baseline pulse rates +/- SD than did group 2 children (119 +/- 25 vs. 127 +/- 28 beats/min, respectively; P < .001). In a multiple linear regression model, pulse rate was independently associated with age (inversely; P < .001) and oral temperature (positively; P < .006) but not with diagnostic group or gender (P > .5). After adjustment of the mean initial pulse rate +/- SD to age of 72 months, there was no difference between group 1 and group 2 children (126 +/- 24 vs. 126 +/- 20 beats/min, respectively; P > .5). From 4 to 72 hours after commencement of treatment, the mean oral temperature in group 1 patients was approximately 0.3 degrees C higher than that in group 2 patients, and the age-adjusted pulse rate was 5 beats/min higher in group 1 children than in group 2 children. These data suggest that relative bradycardia is not characteristic of enteric fever in children. (+info)
Infectious exacerbations of chronic bronchitis: diagnosis and management.
(12/2922)
Chronic bronchitis is an increasing cause of significant morbidity and mortality. Despite treatment, respiratory tract infection is the most common identifiable cause of death for patients with chronic obstructive pulmonary disease. Repeated infectious exacerbations may ultimately cause acute and chronic lung injury. The most common bacterial aetiologies of acute exacerbations of chronic bronchitis (AECB) include Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae. Pseudomonas aeruginosa is often a nosocomial pathogen and is becoming more prevalent in patients with severe underlying disease. Viruses are responsible for approximately one-third of acute exacerbations overall. Atypical pathogens are causative pathogens in < 10% of episodes. The diagnosis of AECB is often based on clinical impression, although suspicion of bacterial infection can be enhanced by quantitative Gram's stains from appropriately obtained sputum specimens. However, a specific microbiological diagnosis is only needed in certain specific situations. Management of AECB involves non-drug interventions (e.g. smoking cessation) and antibiotic treatment. Recommendations for antibiotic use in patients with known or highly suspected AECB are still evolving. The selection of an antibiotic for treatment of an infectious episode must consider underlying patient co-morbidities, likely pathogens, resistance issues and individual antibiotic properties. Cephalosporins, beta-lactam/beta-lactamase inhibitor combinations and macrolides are all reasonable choices. However, due to the increasing prevalence of resistance to standard antibiotics among common respiratory pathogens, and increased incidence of Pseudomonas spp., fluoroquinolones should be a first-line treatment for AECB in patients who have chronic bronchitis complicated by co-morbid illness, severe obstruction (FEV1 < 50%), old age (> 65 years) or have recurrent exacerbations. In patients who do not have these risk factors (i.e. those with simple chronic bronchitis), agents such as co-trimoxazole remain useful. (+info)
Reye's syndrome in the United States from 1981 through 1997.
(13/2922)
BACKGROUND: Reye's syndrome is characterized by encephalopathy and fatty degeneration of the liver, usually after influenza or varicella. Beginning in 1980, warnings were issued about the use of salicylates in children with those viral infections because of the risk of Reye's syndrome. METHODS: To describe the pattern of Reye's syndrome in the United States, characteristics of the patients, and risk factors for poor outcomes, we analyzed national surveillance data collected from December 1980 through November 1997. The surveillance system is based on voluntary reporting with the use of a standard case-report form. RESULTS: From December 1980 through November 1997 (surveillance years 1981 through 1997), 1207 cases of Reye's syndrome were reported in patients less than 18 years of age. Among those for whom data on race and sex were available, 93 percent were white and 52 percent were girls. The number of reported cases of Reye's syndrome declined sharply after the association of Reye's syndrome with aspirin was reported. After a peak of 555 cases in children reported in 1980, there have been no more than 36 cases per year since 1987. Antecedent illnesses were reported in 93 percent of the children, and detectable blood salicylate levels in 82 percent. The overall case fatality rate was 31 percent. The case fatality rate was highest in children under five years of age (relative risk, 1.8; 95 percent confidence interval, 1.5 to 2.1) and in those with a serum ammonia level above 45 microg per deciliter (26 micromol per liter) (relative risk, 3.4; 95 percent confidence interval, 1.9 to 6.2). CONCLUSIONS: Since 1980, when the association between Reye's syndrome and the use of aspirin during varicella or influenza-like illness was first reported, there has been a sharp decline in the number of infants and children reported to have Reye's syndrome. Because Reye's syndrome is now very rare, any infant or child suspected of having this disorder should undergo extensive investigation to rule out the treatable inborn metabolic disorders that can mimic Reye's syndrome. (+info)
Microbiological safety of drinking water: United States and global perspectives.
(14/2922)
Waterborne disease statistics only begin to estimate the global burden of infectious diseases from contaminated drinking water. Diarrheal disease is dramatically underreported and etiologies seldom diagnosed. This review examines available data on waterborne disease incidence both in the United States and globally together with its limitations. The waterborne route of transmission is examined for bacterial, protozoal, and viral pathogens that either are frequently associated with drinking water (e.g., Shigella spp.), or for which there is strong evidence implicating the waterborne route of transmission (e.g., Leptospira spp.). In addition, crucial areas of research are discussed, including risks from selection of treatment-resistant pathogens, importance of environmental reservoirs, and new methodologies for pathogen-specific monitoring. To accurately assess risks from waterborne disease, it is necessary to understand pathogen distribution and survival strategies within water distribution systems and to apply methodologies that can detect not only the presence, but also the viability and infectivity of the pathogen. (+info)
Incidence of upper respiratory tract Mycoplasma pneumoniae infections among outpatients in Rhone-Alpes, France, during five successive winter periods.
(15/2922)
In this prospective study, nasal swab samples from patients with acute respiratory infections were evaluated for the presence of Mycoplasma pneumoniae. This PCR-plus-hybridization-based detection was associated with the detection of other viral agents. During the five winter surveillance periods, 3,897 samples were collected by 75 medical practitioners participating in the Groupe Regional d'Observation de la Grippe surveillance network in Rhone-Alpes (France). M. pneumoniae was detected in 283 samples (7.3%); its rate of detection ranged from 10.1 to 2.0% over the five periods, and it was the second most frequently isolated pathogen during the survey, after influenza A. Three high-prevalence winters were observed, yielding an early winter peak of M. pneumoniae infection which was observed in all age groups. No statistically significant difference was detected between rates of infections in the different age groups, but M. pneumoniae infection was significantly related to lower respiratory tract infection during periods of high prevalence. This study defined the frequency of M. pneumoniae detection from nasal swab specimens in patients with acute respiratory infections, confirming its high prevalence and the presence of large outbreaks due to this pathogen. (+info)
Improving diagnostic accuracy of bacterial pharyngitis by near patient measurement of C-reactive protein (CRP)
(16/2922)
BACKGROUND: Sore throat or pharyngitis is an extremely prevalent condition in primary care. There is a diagnostic dilemma in differentiating bacterial and non-bacterial infections for adequate use of antibiotics. Standard diagnostic procedures take too long for an immediate decision. AIM: To evaluate, if near patient C-reactive protein measurement in the general practice surgery improves diagnostic accuracy. METHOD: One hundred and seventy-nine consecutive patients with sore throat, from 15 general practitioners (GPs) in southern Germany (phase 1) and 161 consecutive patients from 14 GPs (phase 2), were examined physically and a throat-swab was taken and white blood-cell count (WBC) and CRP-measurement were performed. In phase 1, CRP was measured centrally to assess the method's diagnostic value and the adequate threshold. In the second phase, near patient CRP was measured and CRP values were used to make a diagnosis. RESULTS: Using relative operating characteristics (ROC) analysis, the diagnostic value of CRP measurement was much better than WBC count (area under curve = 0.85 versus 0.68). All diagnostic parameters improved when using the near patient CRP measurement. Sensitivity went up from 0.61 (95% confidence interval = 0.45-0.75) to 0.78 (0.61-0.90), specificity went up from 0.73 (0.65-0.81) to 0.82 (0.73-0.88). Positive and negative predictive value improved significantly as well. Diagnostic accuracy went up from 70.1% to 81.0%. Out of 1000 theoretical patients with sore throat, 109 more will be treated correctly when using CRP measurement as a diagnostic tool. CONCLUSIONS: Use of near patient CRP measurement can improve diagnostic accuracy in the differentiation of bacterial and non-bacterial pharyngitis in primary care, and potentially results in a more adequate use of antibiotics. (+info)