Chronic obstructive pulmonary disease.
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Anti-Bacterial Agents↗
Biomedical subjects
S Sethi
Publications and source records attributed to S Sethi.
Modulation of polymorphonuclear leukocytes function by nitric oxide.
Recognition of the endothelium-derived relaxation factor as nitric oxide (NO) gave rise to an impression that NO was synthesised only by the endothelial lining of the vessel wall. Later it was found that NO is synthesized constitutively by the enzyme nitric oxide synthase (NOS) in various cells. However, inflammatory cytokines can induce NOS (known as inducible NOS [iNOS]) activity in all the somatic cells. Blood cells, such as eosinophils, platelets, neutrophils, monocytes, and macrophages, also synthesize NO. Among them, polymorphonuclear leukocytes (PMNs) constitute an important proportion and are also the major participants in a number of pathological conditions with suggestive involvement of NO. PMNs can synthesize NO at rates similar to endothelial cells, thus suggesting the importance of PMN-derived NO in various physiological and pathological conditions. Most of the studies so far focus on the peripheral PMNs, while studies on PMNs after emigration are limited, thus warranting systematic studies on PMNs from both sources. The role of the endothelial NOS (eNOS) and functions of NO derived from the endothelial cells has been studied extensively. However, understanding of the PMNs NOS and its regulatory role in their function is unraveling. The present review summarizes the modulatory role of NO on PMNs functions and points out the discrepancies relating to presence of NOS in PMNs. This information will be helpful in understanding the importance of NO in physiological and pathological conditions associated with PMNs.
Animals↗
Mechanisms involved in the augmentation of arachidonic acid-induced free-radical generation from rat neutrophils following hypoxia-reoxygenation.
Polymorphonuclear leukocytes are known to play an important role in hypoxia/ischemia and reoxygenation injury. The present study was undertaken to investigate the involvement of protein kinase C, calmodulin, and cyclic adenosine monophosphate in the augmentation of the free-radical generation observed after hypoxia-reoxygenation (H-R). Free-radical generation from the rat polymorphonuclear leukocytes was measured as the arachidonic acid (1-5x10(-5) M)-induced luminol-dependent chemiluminescence response, which was augmented following H-R. The increase in free-radical generation after H-R was completely blocked by the pretreatment of cells with PKC inhibitor H(7), whereas indomethacin (a cyclo-oxygenase inhibitor) or forskolin (an adenylate cyclase activator) failed to modulate the H-R-dependent response. However, W(7)-a calcium/calmodulin (Ca(2+)/CaM) antagonist-partially reduced the augmented free-radical generation observed in the H-R cells. Results obtained thus suggest the possible involvement of protein kinase C and calcium in the augmentation of the free-radical generation response following H-R.
Adenylyl Cyclases↗
Regulatory interactions of alphabeta and gammadelta T cells in glomerulonephritis.
BACKGROUND: Several lines of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis. METHODS: The roles of alphabeta and gammadelta T cells in the pathogenesis of glomerulonephritis were investigated in a model of nephrotoxic nephritis in mice deficient in either T-cell population [T-cell receptor (TCR)beta and TCRdelta knockout mice]. The model, induced by the injection of rabbit anti-mouse glomerular basement membrane antibody, is characterized by the development of proteinuria and glomerular damage over a 21-day observation period in wild-type mice. RESULTS: Mice deficient in either alphabeta or gammadelta T cells developed minimal proteinuria and glomerular lesions and had a significant reduction in macrophage accumulation compared with wild-type mice. In gammadelta T-cell-deficient mice, circulating levels and glomerular deposition of autologous IgG were comparable to wild-type levels, while alphabeta T-cell-deficient mice had no autologous IgG production. Autologous antibody production was not required for the development of glomerulonephritis since mice that lack IgG and B cells (micro-chain-/-) developed similar proteinuria to that observed in wild-type mice. CONCLUSIONS: These studies suggest a proinflammatory role for both alphabeta and gammadelta T cells in glomerular injury, independent of the humoral response. This is the first demonstration, to our knowledge, that both T-cell subsets contribute to the progression of a disease, and it suggests that complex regulatory interactions between alphabeta and gammadelta T cells play a role in glomerular injury.
Animals↗
Three unusual siblings with Harlequin icthyosis in an Indian family.
Harlequin fetuses occurring as three siblings in an Indian family are described here. All three were preterm, low birth weight, and did not survive. There was no history of consanguinous marriage in the parents or in the family. Thus autosomal recessive inheritance appears to be a remote possibility, although not impossible or, as recently described, these recurrent harlequin fetuses could be the result of new dominant mutations with parental mosaicism.
Female↗
Bacterial infection and the pathogenesis of COPD.
Bacterial infection of the lower respiratory tract can impact on the etiology, pathogenesis, and the clinical course of COPD in several ways. Several recent cohort studies suggest that lung growth is impaired by childhood lower respiratory tract infection, making these individuals more vulnerable to developing COPD on exposure to additional injurious agents. Impairment of mucociliary clearance and local immune defense in smokers allows bacterial pathogens to gain a foothold in the lower respiratory tract. These pathogens and their products can cause further impairment of mucociliary clearance due to enhanced mucus secretion, disruption of normal ciliary activity, and airway epithelial injury, and thus persist in the lower respiratory tract. This chronic colonization of the lower respiratory tract by bacterial pathogens could induce a chronic inflammatory response with lung damage. Nontypeable Haemophilus influenzae, usually regarded as an extracellular mucosal pathogen, has been demonstrated to cause intracellular infections of the upper and lower respiratory tract respiratory tissue. Increased incidence of chronic Chlamydia pneumoniae infection of the respiratory tract has been associated with COPD. These chronic infections of respiratory tissues could contribute to the pathogenesis of COPD by altering the host response to cigarette smoke or by inducing a chronic inflammatory response. Application of newer molecular and immunologic research techniques is helping us define precisely the role of bacterial infection in COPD.
Bacteria↗
Infectious etiology of acute exacerbations of chronic bronchitis.
Infectious agents are a major cause of acute exacerbations of chronic bronchitis (AECB) and COPD. Several respiratory viruses are associated with 30% of exacerbations, with or without a superimposed bacterial infection. Atypical bacteria, mostly Chlamydia pneumoniae, have been implicated in < 10% of AECB. The role of bacterial pathogens when isolated from the respiratory tract during AECB has become better defined by application of several newer investigative techniques. Bacterial pathogens can be isolated in significant concentrations from distal airways in 50% of AECB. Specific immune responses to surface exposed antigens of the infecting pathogen have been shown to develop after an exacerbation. Emerging evidence from molecular epidemiology and measurement of airway inflammation further support the role of bacteria in AECB. When properly defined, 80% of AECB are likely to be infectious in origin.
Acute Disease↗
The role of bacteria in exacerbations of COPD. A constructive view.
The role of infection in exacerbations of COPD remains controversial and incompletely understood. Although some investigators believe that bacteria are not important for patients with exacerbation, we disagree and believe that patients with at least two of the three cardinal symptoms of exacerbation should receive antibiotic therapy. With an open-minded view of the area, we review the data, showing that bacteriologic studies, pathologic investigations, and clinical trials all support roles for bacteria and antibiotic therapy in this disease. Still, many questions remain, and future studies will be needed to better define the mechanisms of bacterial invasion in the bronchitic patient and to develop effective vaccines to prevent exacerbations. In the meantime, we must rely on antibiotic therapy, and we will need prospective studies to corroborate preliminary findings showing that different patients may require different therapies; thus, patient subsetting may be vital in the selection of antibiotic therapy for exacerbations of COPD.
Anti-Bacterial Agents↗
Airway inflammation and etiology of acute exacerbations of chronic bronchitis.
STUDY OBJECTIVES: The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50% of acute exacerbations of chronic bronchitis (AECB) is controversial. If bacterial pathogens cause these AECB, they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations. DESIGN: This hypothesis was tested by comparing levels of interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, and neutrophil elastase (NE) in 81 sputum samples obtained from 45 patients with AECB. Four groups were compared. In the first three groups, nontypable Haemophilus influenzae (n = 20), Haemophilus parainfluenzae (n = 27), and Moraxella catarrhalis (n = 14) were isolated as sole pathogens, respectively. In the fourth group, only normal flora was isolated (n = 20). Paired samples, obtained from individual patients at different times, that differed in their culture results were also compared. SETTING: An outpatient research clinic at a Veterans Affairs Medical Center. PATIENTS: These patients were participating in a prospective, longitudinal study of the dynamics of bacterial infection in chronic bronchitis, for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: H influenzae exacerbations were associated with significantly higher sputum IL-8, TNF-alpha, and NE. M catarrhalis exacerbations demonstrated significantly higher sputum TNF-alpha and NE when compared to pathogen-negative exacerbations. H parainfluenzae-associated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations. Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB. CONCLUSIONS: Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB.
Acute Disease↗
Septic arthritis due to Ureaplasma urealyticum.
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Arthritis, Infectious↗
Role of HER-2/neu oncogene amplification in determination of outcome of patients with cancer.
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Adenocarcinoma↗
Evaluation of E test for susceptibility testing of Mycobacterium tuberculosis to primary anti tubercular drugs.
BACKGROUND & OBJECTIVES: Antimicrobial susceptibility tests for tuberculosis take weeks and delayed therapy can lead to an increase in disease incidence. The E test is a new concept for minimum inhibitory concentrations (MIC) determinations for antimicrobial agents that is based on a predefined antibiotic gradient on a plastic strip calibrated with a continuous logarithmic MIC scale covering 15 two-fold dilutions. The present study was undertaken to evaluate E test strips for susceptibility testing of Mycobacterium tuberculosis. METHODS: Twenty five clinical isolates of M. tuberculosis were tested for the four first line antitubercular drugs by E test and were compared with standard proportion method. The inoculum turbidity was adjusted to McFarland 3.0 standard and agar plates (Middle brook 7H11 agar) were inoculated and preincubated (37 degrees C in 7-10% CO2) for 24 h after which time, the E test strips were placed on the agar surface which were incubated under same conditions. The MIC was interpreted as the point at which the ellipse intersected the 'E test' strip as described in E test technical guide. RESULTS: Of the 25 strains, susceptibility as determined by both methods for isoniazid (INH), rifampin, ethambutol and streptomycin was found in 22 (88%), 20 (80%), 24 (96%) and 18 (72%) strains respectively. Agreement between E test and proportion method was 96 per cent for INH, 92 per cent for rifampin and 100 per cent for ethambutol and streptomycin each. However, sensitivity could be predicted after 7-10 days by E test and exact MIC could also be determined. INTERPRETATION & CONCLUSIONS: E test method was found to be rapid, accurate, reliable and easy to perform. It can be employed for routine susceptibility testing for antitubercular drugs.
Antitubercular Agents↗
Evaluation of leukergy test as an indicator of infection in hip joint in children.
This new blood test (leukergy) for infection is based on the fact that white cells agglomerate in peripheral blood of patients with inflammatory diseases. We evaluated leukergy in 25 children with proven septic arthritis of hip. It was found to be the efficient and earliest indicator of septic arthritis than the erythrocyte sedimentation rate (ESR), total leucocyte count (TLC), polymorphs and C-reactive protein (CRP). It also correlated well with the clinical severity of infection and the prognosis of disease. Thus leukergy is a simple, rapid and inexpensive slide test which was found as the best indicator profile for the presence of septic arthritis.
Arthritis, Infectious↗
Nitric oxide-mediated augmentation of polymorphonuclear free radical generation after hypoxia-reoxygenation.
Polymorphonuclear leukocytes (PMNLs), nitric oxide (NO), calcium, and free radicals play an important role in hypoxia/ischemia and reoxygenation injury. In the present study, NO donors, sodium nitroprusside (SNP), and diethylamine-NO (DEA-NO) at low concentrations (10 and 100 nmol/L) potentiated, while higher (10 micromol/L to 10 mmol/L) concentrations inhibited free radical generation response in the rat PMNLs. Free radical generation response was found to be significantly augmented when hypoxic PMNLs were reoxygenated (hypoxia-reoxygenation [H-R]). This increase in free radical generation after reoxygenation or SNP (10 nmol/L) was blocked in the absence of extracellular calcium. SNP (10 nmol/L) or H-R-mediated increases in the free radical generation were prevented by the pretreatment of PMNLs with NO scavenger (hemoglobin), the polyadenine diphosphate (ADP)-ribosylation synthase inhibitor (benzamide) or the calcium channel antagonist (felodipine). A significant augmentation in the nitrite and intracellular calcium levels was observed during hypoxia. Hemoglobin pretreatment also blocked the increase in intracellular calcium levels due to SNP (10 nmol/L) or hypoxia. Thus, increased availability of NO during SNP treatment or H-R, may have led to an ADP-ribosylation-mediated increase in intracellular calcium, thereby increasing the free radical generation from the rat PMNLs.
Animals↗
Retroperitoneal ganglioneuroma: report of a case diagnosed by fine-needle aspiration cytology, with review of the literature.
A case of ganglioneuroma presenting as a retroperitoneal mass in a 5-yr-old girl was diagnosed by preoperative fine-needle aspiration cytology. The cytologic smears predominantly showed clusters of Schwann cells, with scattered mature ganglion cells. The cytologic diagnosis of ganglioneuroma was subsequently confirmed on histopathologic examination. To date, very few reports on the cytologic features of this tumor exist. The importance of considering a confident diagnosis by cytology, and of the uncommon age group that may be affected, is stressed. Diagn. Cytopathol. 1999;21:194-196.
Biopsy, Needle↗
Value of histochemical stains for copper in the diagnosis of paediatric copper storage disorders.
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Child↗
Simultaneous respiratory tract colonization by multiple strains of nontypeable haemophilus influenzae in chronic obstructive pulmonary disease: implications for antibiotic therapy.
Nontypeable Haemophilus influenzae often causes exacerbations of chronic obstructive pulmonary disease (COPD), and these exacerbations are frequently treated with oral antibiotics. The goals of this study were to determine the frequency of the simultaneous presence of multiple strains of H. influenzae in sputum and to measure the MICs of antibiotics for the isolates. In a prospective study, adults with COPD were seen monthly. Sputum cultures were obtained, and individual colonies were subjected to genomic DNA typing and MIC determinations. Multiple strains of H. influenzae were present simultaneously in the sputum of 26.3% of adults with COPD. In 64.5% of these, MICs of >/=1 antibiotic varied by >/=4-fold among the strains. Therefore, multiple strains of H. influenzae are frequently present simultaneously in the sputum of adults with COPD, and the antimicrobial susceptibility of different strains in the same sputum sometimes differs.
Aged↗
Infectious exacerbations of chronic bronchitis: diagnosis and management.
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.
Bacterial Infections↗