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Biomedical subjects

M Kavuru

Publications and source records attributed to M Kavuru.

14 recordsLinked to original sources

NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response.

A wealth of evidence supports increased NO (NO.) in asthma, but its roles are unknown. To investigate how NO participates in inflammatory airway events in asthma, we measured NO. and NO. chemical reaction products [nitrite, nitrate, S-nitrosothiols (SNO), and nitrotyrosine] before, immediately and 48 h after bronchoscopic antigen (Ag) challenge of the peripheral airways in atopic asthmatic individuals and nonatopic healthy controls. Strikingly, NO(3)(-) was the only NO. derivative to increase during the immediate Ag-induced asthmatic response and continued to increase over 2-fold at 48 h after Ag challenge in contrast to controls [P < 0.05]. NO(2)(-) was not affected by Ag challenge at 10 min or 48 h after Ag challenge. Although SNO was not detectable in asthmatic airways at baseline or immediately after Ag, SNO increased during the late response to levels found in healthy controls. A model of NO. dynamics derived from the current findings predicts that NO. may have harmful effects through formation of peroxynitrite, but also subserves an antioxidant role by consuming reactive oxygen species during the immediate asthmatic response, whereas nitrosylation during the late asthmatic response generates SNO, safe reservoirs for removal of toxic NO. derivatives.

Adult↗

Our new understanding of pulmonary alveolar proteinosis: what an internist needs to know.

Pulmonary alveolar proteinosis (PAP; the accumulation of surfactant lipids and proteins in the alveoli) has a number of infectious and environmental causes but is usually idiopathic. The clinical presentation of PAP is nonspecific; thus, the diagnosis is frequently missed, leading to inappropriate therapy and unnecessary morbidity. Recent advances suggest that a deficiency in granulocyte-macrophage colony-stimulating factor (GM-CSF) activity may lead to this surfactant accumulation. Anti-GM-CSF antibodies have been found in PAP patients, fueling speculation that PAP may be an autoimmune disease. These findings are being translated into novel forms of therapy.

Adolescent↗

Rapid loss of superoxide dismutase activity during antigen-induced asthmatic response.

Loss of superoxide dismutase activity occurs within minutes of an acute asthmatic response to segmental antigen instillation into the lung of individuals with atopic asthma. Decreased activity undoubtedly contributes to airway inflammation and injury through increased formation of reactive oxygen and nitrogen species, and suggests that enrichment of lung antioxidants is therapeutic for asthma.

Adult↗

Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Many patients with persistent asthma need both long-acting bronchodilators and inhaled corticosteroids for optimal asthma control. OBJECTIVE: Our purpose was to compare the efficacy and safety of salmeterol 50 microg combined with fluticasone 100 microg (in a combination dry powder product) with that of placebo, fluticasone, or salmeterol alone. METHODS: A 12-week randomized, double-blind, multicenter study was conducted in 356 patients aged 12 years or older with asthma. After a 14-day screening period, patients were randomized to treatment with salmeterol 50 microg combined with fluticasone 100 microg (combination product), salmeterol 50 microg, fluticasone 100 microg, or placebo administered in the Diskus dry powder inhaler (GlaxoWellcome, UK) twice daily. RESULTS: Mean change in FEV(1) at end point was significantly (P < or =.003) greater with the combination product (0.51 L) compared with placebo (0.01 L), salmeterol (0.11 L), and fluticasone (0.28 L). The combination product significantly increased (P < or =.013) area under the curve compared with placebo and fluticasone on day 1 and compared with placebo, salmeterol, and fluticasone at week 1 and week 12. Patients in the combination product group were less likely to withdraw from the study because of worsening asthma compared with those in the other groups (P < or =.020). The combination product significantly increased (P < or =.012) morning PEF (combination, 52.5 L/min; placebo, -23.7 L/min; salmeterol, -1.7 L/min; fluticasone, 17.3 L/min) and evening PEF at end point compared with the other groups. The combination product significantly (P < or =.025) reduced symptom scores and albuterol use compared with the other treatments and increased the percentage of nights with no awakenings and the percentage of days with no symptoms compared with placebo and salmeterol. All treatments were equally well tolerated. CONCLUSION: Salmeterol 50 microg and fluticasone 100 microg combined in the Diskus powder delivery device offers significant clinical advantages over salmeterol or fluticasone alone at the same doses.

Administration, Inhalation↗

A controlled trial of twice daily triamcinolone oral inhaler in patients with mild-to-moderate asthma.

BACKGROUND: National and international guidelines recommend inhaled anti-inflammatory medications for patients with all but the mildest forms of asthma. Patients may also be more compliant with twice daily dosing. OBJECTIVE: To evaluate the efficacy and safety of triamcinolone acetonide (triamcinolone acetonide), 400 microg bid, in mild-to-moderate asthma patients. METHODS: A multicenter, randomized, double-blind, placebo-controlled study with a 7- to 21-day baseline and 6-week treatment period. Adult mild-to-moderate asthma patients poorly controlled by beta2-agonists alone were randomized to receive placebo (48) or triamcinolone acetonide (53). Patients recorded daytime and nighttime asthma symptoms, albuterol use, and morning and evening peak expiratory flow (PEF) rates on diary cards. Clinic spirometry measures included FEV1, FEF25-75%, FVC, FEV1/FVC, and PEF. RESULTS: Triamcinolone acetonide treatment resulted in improvement from baseline of 17% for FEV1 (P < .0001); 44% for albuterol use (P = .0009); 9% for FVC (P = .0185); 19% for PEF (P = .0011); 42% for FEF25-75% (P < .0001); 8% for FEV1/FVC (P = .0016); 36% for daytime, 39% for nighttime, and 38% for total asthma symptoms (P < or = .0001); and 12% for morning, and 10% for evening PEF (P < or = .001). These changes were highly significant when compared with placebo (P < or = .0185). Significant improvement for all variables was demonstrated within 1 to 2 weeks of active treatment, and maintained for most variables over the 6-week treatment phase. Both treatments were well tolerated. Respiratory adverse events occurred more frequently with placebo; pharyngitis was reported more frequently with triamcinolone acetonide. CONCLUSIONS: Triamcinolone acetonide, administered twice daily, can effectively and safely treat patients with milder forms of asthma. In these patients, triamcinolone acetonide improves asthma symptoms and decreases the need for as-needed beta2-agonists.

Administration, Inhalation↗

Albuterol delivered by metered-dose inhaler (MDI), MDI with spacer, and Rotahaler device--a comparison of efficacy and safety.

A randomized double-blind, triple crossover study was conducted on 20 asthmatic patients (7 males and 13 females; age 40.9 +/- 14.2 Caucasians, 11 blacks, and 1 oriental. Criteria for admission included FEV1 < or = 80% of predicted when inhaled beta-agonists were witheld for at least 6 hrs and oral beta-agonists for 12 hr, in addition to at least 15% increase in FEV1, 15 min after treatment with albuterol with spacer delivery. Each of the study patients were tested on each of 3 separate days (within the same week) at baseline, 15, 30, 60, 120, 180, 240, 300, and 360 min post treatment. On each day albuterol was delivered by one of the 3 delivery devices and the other two methods delivered placebo. Albuterol was administered at the maximum recommended dosages of two puffs for MDI. Two puffs for MDI with spacer, and two capsules for Rotahaler. Spirometry, blood pressure and heart rate were measured at each testing interval. The mean percentage in FEV1 was higher in Rotahaler group compared to MDI with spacer (p < 0.001) and no significant difference in FEV1 was found between Rotahaler and MDI alone (p = 0.31). No significant changes in heart rate or blood pressure were associated with albuterol delivery by any of the three methods. Albuterol inhaled as a microfine powder was more effective than the same drug delivered as an aerosol by either MDI or MDI with spacer.

Adult↗

Inhaled corticosteroids and beta-agonists inhibit oxidant production by bronchoalveolar lavage cells from normal volunteers in vivo.

To study the anti-inflammatory mechanisms of inhaled corticosteroids and beta-agonist therapies, we evaluated basal and stimulus-induced superoxide production by human airway inflammatory cells obtained by bronchoalveolar lavage from normal volunteers before and after 3 weeks of an inhaled corticosteroid (flunisolide) and beta-agonist (metaproterenol). Assay of superoxide production by the bronchoalveolar lavage cells was performed in the presence of media alone or media containing phorbol ester by optical density determination of reduced ferricytochrome c at 550 nm. Interleukin-1 beta released from unstimulated cells and cells stimulated with lipopolysaccharide was quantitated by enzyme immunoassay. Interestingly, phorbol ester-stimulated superoxide production was strikingly inhibited (P < 0.05) by inhaled therapies, while stimulus induced Interleukin-1 beta production was not significantly affected (P = 0.12). Suppression of oxidant production by airway inflammatory cells may be a major mechanism for the beneficial anti-inflammatory effects of inhaled corticosteroids and beta-agonists.

Administration, Inhalation↗

Empiric prednisone therapy for pulmonary toxic reaction after high-dose chemotherapy containing carmustine (BCNU).

STUDY OBJECTIVE: To determine pretreatment factors that predict for pulmonary toxic reactions after high-dose chemotherapy containing carmustine (BCNU) and to determine the utility of prednisone in preventing pulmonary toxic reactions. DESIGN: Retrospective review. SETTING: Tertiary care referral center. PATIENTS: Forty-five patients with relapsed or refractory lymphoma and 27 patients with breast cancer with normal cardiopulmonary function were treated with one of two high-dose combination chemotherapeutic regimens containing the same dose of BCNU. MEASUREMENTS: Recorded pretreatment patient characteristics included previous chemotherapy or radiation therapy, history of pulmonary metastases, history of chronic obstructive pulmonary disease, and history of smoking. Spirometry and single-breath carbon monoxide diffusing capacity (DCO) were obtained before and after high-dose chemotherapy. INTERVENTIONS: Patients were treated with prednisone for a 5% or more drop in postchemotherapy DCO whether or not symptoms were present. RESULTS: Fifty-nine patients were evaluable. No pretreatment characteristic predicted for declines in pulmonary function postchemotherapy. The FEV1/FVC ratio did not change significantly after high-dose chemotherapy, but the DCO decreased 12.1% (p < 0.001). Of the 59 evaluable patients, 30 were treated with prednisone for declines in postchemotherapy DCO. Sixteen (53%) of these 30 patients were asymptomatic. The DCO increased 10.3% in patients treated with prednisone compared with a decrease of 2.3% in patients not treated (p = 0.017). There was no statistically significant difference in FEV1/FVC in patients treated with prednisone compared with those not treated. Regression analysis of pretreatment characteristics, type of high-dose chemotherapy received, and treatment with prednisone identified only treatment with prednisone as a significant variable in predicting an increase in DCO (p = 0.03; regression coefficient = +11.5%, SE = +/- 5.2%) after high-dose chemotherapy containing BCNU. CONCLUSIONS: High-dose BCNU-containing chemotherapeutic regimens cause decreases in DCO that are often asymptomatic and likely represent subclinical pulmonary toxic reactions. Pretreatment clinical parameters cannot predict which patients will manifest pulmonary toxic reactions after high-dose chemotherapy. Empiric treatment with prednisone will reverse chemotherapy-induced decreases in DCO. Earlier institution of glucocorticoids for evidence of pulmonary dysfunction is recommended.

Adult↗

Three-dimensional imaging of the lung in vivo: work in progress.

It has previously been demonstrated that three-dimensional (3D) displays of the lung and bronchial tree can be generated from computed tomography (CT) scans of lung specimens. Subsequent refinement of the reconstruction algorithms has allowed high-resolution reconstructions of lungs in vivo. With the introduction of low-dose CT scan protocols, use of the technique may become more common in the radiologic community. The many potential clinical applications for 3D imaging of the lung include an aid to bronchoscopy and improved surgical planning. We present the technical details for 3D imaging of the lungs in vivo as well as three representative case studies.

Adult↗

Pseudomembranous colitis: CT evaluation of 26 cases.

Pseudomembranous colitis (PMC) is an infectious colitis usually occurring as a complication of antibiotic use. The computed tomographic (CT) appearances of 26 patients with PMC were reviewed. Twenty-three patients demonstrated an abnormal bowel wall, with an average wall thickness of 14.7 mm (range, 3-32 mm); in three patients, bowel wall thickness was normal. Contrast material trapped between thickened folds corresponded to the broad transverse bands described on plain radiographs. Pancolonic involvement was seen in 13 cases, while seven patients had right-sided involvement only; three patients had bowel wall thickening limited to the rectosigmoid only. Although the CT appearance of PMC is not highly specific, the diagnosis may be suggested in the proper clinical setting.

Adolescent↗

Pneumocystis carinii pneumonia: spectrum of parenchymal CT findings.

Computed tomographic (CT) scans of the chest in 39 patients with Pneumocystis carinii pneumonia (PCP) were reviewed to determine the spectrum and frequency of CT manifestations of PCP. Parenchymal disease was categorized as either bilateral or unilateral, symmetric or asymmetric, and diffuse or patchy. Infiltrates were classified as interstitial, airspace, or mixed. On this basis, three CT patterns of involvement were identified: a ground-glass patchwork pattern in 22 of 39 (56%), and an interstitial pattern in seven of 39 patients (18%). Atypical CT features of PCP included nodules and nodular components in seven of 39 (18%) and cavities in three of 39 patients (8%). Associated CT findings included cystic spaces and bullae in 15 of 39 (38%), pneumothorax in five of 39 (13%), adenopathy in seven of 39 (18%), and pleural effusions in seven of 39 patients (18%). It is concluded that although PCP may exhibit a variety of CT appearances, certain patterns are more common than others. In the appropriate clinical setting, these findings are highly suggestive of PCP. The identification of cavities or nodular components in addition to infiltrates should raise the suspicion of a second disease process or mixed infection affecting the lungs.

Adolescent↗