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Biomedical subjects

D Ashkin

Publications and source records attributed to D Ashkin.

15 recordsLinked to original sources
PubMed2006

Cellular immune response to pulmonary infections in HIV-infected individuals hospitalized with diverse grades of immunosuppression.

The lymphocyte profile of 521 HIV-infected subjects hospitalized at Jackson Memorial (2001-2002) was compared across main respiratory diseases. Study data included medical history and all laboratory evaluations performed during hospitalization. Community-acquired pneumonias (CAP, 52%), Pneumocystis jiroveci pneumonia (PCP, 24%), tuberculosis (TB, 9%) and non-tuberculous mycobacterial diseases (NTM, 12%) were the most frequent causes of admission. Patients hospitalized with PCP and NTM exhibited the lowest CD4 counts (P=0.003). PCP patients had the highest B-cell percentages (P=0.04). CAP patients had the highest CD8 and CD4 percentages and the lowest percentage of Natural Killer (NK) cells and viral burdens. TB patients exhibited the lowest NK-cell (11.4+/-6.3) and B-cell percentages (13.6+/-12) and the highest CD8 (59+/-14) percentage. NTM patients, in contrast, had the highest NK-cell percentages of the groups (19.1+/-11.6, P=0.01). Additionally, immune responses associated with respiratory pathogens differed in HIV-infected patients with CD4(+) cells above and below 200 counts.

Adult↗
PubMed2004

Pharmacokinetics of ethambutol in children and adults with tuberculosis.

SETTING: Five hospitals in the United States. OBJECTIVE: To describe ethambutol pharmacokinetics in children and adults with active tuberculosis (TB). DESIGN: Prospective, open-labeled study in 56 adults and 14 children with active tuberculosis who received ethambutol as part of their multidrug TB regimens. RESULTS: Most serum samples were collected up to 10 h post dose and assayed using a validated gas chromatography assay with mass selective detection (GC/MS). Concentration data were analyzed using non-compartmental and population pharmacokinetic methods. Drug exposure increased with dose, but less than proportionally at doses >3000 mg. Lower than expected maximum serum concentrations (Cmax <2 microg/ml) were common in adults. Very low Cmax (<1 microg/ml) were common in children, as was delayed absorption (time to Cmax >3 h). Many Cmax were at or below typical TB minimal inhibitory concentrations. Cmax values for HIV-positive patients were 20% lower than HIV-negative patients with daily doses, but were similar with larger twice-weekly doses. CONCLUSIONS: Adult TB patients often had lower than expected ethambutol serum concentrations, and most pediatric TB patients had very low ethambutol serum concentrations. Higher doses and therapeutic drug monitoring may be indicated for many of these patients.

Absorption↗
PubMed2002

Ofloxacin population pharmacokinetics in patients with tuberculosis.

SETTING: Two tuberculosis hospitals in the United States. OBJECTIVE: To determine the population pharmacokinetic (PK) parameters of ofloxacin following multiple oral doses. DESIGN: A total of 73 patients with tuberculosis (TB) participated in the study. Subjects received multiple doses of ofloxacin as part of their treatment. They also received concurrent medications based on in vitro susceptibility data. Serum samples were collected over 10 h and assayed by a validated high performance liquid chromatography (HPLC) assay. Concentration-time data were analyzed using population methods. RESULTS: Ofloxacin concentrations increased linearly with increasing oral doses. Delayed absorption was seen at least once in 29% of patients. Ofloxacin elimination decreased with declining renal function and increasing age. Higher daily doses were well tolerated, and appeared to maximize the peak concentration to minimal inhibitory concentration ratio (Cmax:MIC). CONCLUSION: Ofloxacin PK parameters were comparable to those previously published for other patient populations. Higher daily doses may offer pharmacodynamic advantages for the treatment of TB.

Administration, Oral↗
PubMed2001

Treatment experience of multidrug-resistant tuberculosis in Florida, 1994-1997.

OBJECTIVE: To study the clinical characteristics and results of patients with diagnoses of multidrug-resistant tuberculosis (MDR-TB) in the state of Florida. METHODS: Retrospective chart review of all patients (n = 81) with diagnoses of MDR-TB in Florida between January 1, 1994, and July 31, 1997. RESULTS: The average number of resistant drugs was 4.8 (range, 2 to 11). Of 81 patients, 46 patients (57%) completed adequate therapy, 26 patients (32%) died, and 9 patients (11%) never completed a satisfactory course of treatment. Patients who received at least part of their therapy at A. G. Holley State Hospital, a specialized tuberculosis (TB) treatment center, had significantly higher treatment completion rates (79%) than those treated as outpatients alone (48% treatment completion rate, p < 0.001), even after the exclusion of patients who were acutely ill and died within 2 months of diagnosis. CONCLUSION: In Florida, a specialized TB care program for MDR-TB, including at least partial inpatient therapy, yielded higher treatment completion rates compared to outpatient treatment alone.

Adult↗
PubMed2000

Use of rifabutin with protease inhibitors for human immunodeficiency virus-infected patients with tuberculosis.

Drug interactions between rifamycins and highly active antiretroviral therapy (HAART) have raised concerns in the treatment of human immunodeficiency virus (HIV)-infected patients with tuberculosis. We conducted a study of this interaction by measuring serum drug levels of all HIV-infected patients with tuberculosis who were admitted to A. G. Holley State Tuberculosis Hospital (Florida) from October 1997 through December 1998, who were concomitantly treated with rifabutin and HAART. All 25 patients studied became culture-negative within 2 months of initiation of therapy for tuberculosis and remained negative for a median of 13 months follow-up after completion of therapy. HIV viral loads (mean+/-SEM) decreased significantly from 4.95+/-0.21 log10 copies/mL before initiation of HAART to 2.77+/-0.07 log10 copies/mL before discharge (P<.001); 20 of 25 patients achieved viral loads of <500copies/mL. In summary, the concomitant use of rifabutin and HAART can lead to successful treatment of HIV-infected patients with tuberculosis without increased side effects.

Adult↗
PubMed2000

Mesothelial cells in tuberculous pleural effusions of HIV-infected patients.

The scarcity of mesothelial cells is a well-known characteristic of tuberculous pleural effusions. We report three HIV-infected patients with tuberculous pleural effusions, in which mesothelial cells were found in significant numbers in the pleural fluid. Clinicians should be aware that the altered immune responses that occur in HIV-infected patients may affect the cytologic profile of tuberculous pleural effusions, and they should be cautious not to exclude this diagnosis based solely on the presence of mesothelial cells in the fluid.

AIDS-Related Opportunistic Infections↗
PubMed2000

Phthisiology at the dawn of the new century.

Tuberculosis (TB) has been and continues to be one of the most significant pathogens in terms of human morbidity and mortality. Although the resurgence of TB has been held in check in most developed countries, the epidemic rages on in most developing countries of the world. The specter of drug resistance is becoming a more credible challenge in many parts of the world, dimming the prospects of eventual elimination. However, great opportunities are arising as well, with an unprecedented focus on the global aspects of TB control. This article will review the status of TB today and put into perspective the prospects for its elimination in the coming century.

Cause of Death↗
PubMed2000

Pulmonary tuberculosis in AIDS patients: transient chest radiographic worsening after initiation of antiretroviral therapy.

OBJECTIVE: Immune function and inflammatory responses often increase in AIDS patients who receive antiretroviral therapy. We evaluated the occurrence and nature of transient worsening on chest radiographs in AIDS patients with tuberculosis after initiation of antiretroviral therapy and compared these findings with chest radiographs of patients undergoing antituberculous therapy alone. MATERIALS AND METHODS: A retrospective review of sequential chest radiographs was performed of 87 patients undergoing therapy for pulmonary tuberculosis: AIDS patients receiving antiretroviral therapy (n = 31), HIV-positive patients not receiving antiretroviral therapy (n = 26), and HIV-negative patients (n = 30). Pulmonary consolidations, thoracic lymphadenopathy, and pleural effusions were evaluated for worsening, stability, or improvement. Patients with concurrent pulmonary infections were excluded. RESULTS: Transient worsening on radiography was observed in 14 (45%) of 31 AIDS patients receiving antiretroviral therapy, including seven patients (23%) who showed severe worsening. Of 56 patients in the other two groups, 11 (20%) showed worsening (p = 0.023), two of whom showed severe worsening (p = 0.009). Worsening was first noted between 1 and 5 weeks after initiation of antiretroviral therapy, with improvement occurring between 2 weeks and 3 months later. Four patients with severe worsening converted their tuberculin purified protein derivative responses from anergic to positive after antiretroviral treatment. CONCLUSION: Transient worsening is frequently seen on chest radiography in AIDS patients with tuberculosis who subsequently undergo antiretroviral therapy. This phenomenon may be related to improved immune function.

AIDS-Related Opportunistic Infections↗
PubMed1998

Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and the human immunodeficiency virus.

Until recently it was thought that age greater than 35 yr was the main risk factor for the development of drug-induced hepatitis (DIH) in patients receiving antituberculosis therapy. We conducted a study to determine whether infection with either the hepatitis C virus or the human immunodeficiency virus (HIV) were significant risk factors for the development of DIH in patients receiving antituberculosis therapy. Our study consisted of two parts. In the first part, 134 consecutive patients admitted for the treatment of tuberculosis (TB) were followed for the development of DIH. All of these patients were also screened for the presence of hepatitis C and HIV. In the second part of the study, those patients who were hepatitis C positive and who developed DIH on repeated reintroduction of the anti-TB drugs were offered a liver biopsy. If active inflammation, which may be suggestive of hepatitis C infection, was present on the biopsy specimen, treatment with alpha-interferon was begun and the anti-TB drugs were subsequently reintroduced. During the 18 mo of the study, 22 patients developed DIH. The relative risk of developing DIH if the patient was hepatitis C or HIV positive was fivefold and fourfold, respectively (p < 0.05). If a patient was coinfected with both hepatitis C and HIV the relative risk of developing DIH was increased 14.4-fold (p < 0.002). In the treatment part, four patients were treated with alpha-interferon, and all were able to undergo the reintroduction of anti-TB therapy without reoccurrence of DIH. Infection with hepatitis C and HIV are independent and additive risk factors for the development of DIH during TB therapy. The treatment of hepatitis C with alpha-interferon may allow the reintroduction of anti-TB agents in those who previously developed DIH when exposed to these drugs.

Adolescent↗
PubMed1998

Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS.

Transient worsening of tuberculous symptomatology and lesions following antituberculous therapy (paradoxical response) has previously been described as a rare occurrence. To determine the incidence of paradoxical responses in patients with AIDS and TB who are treated with antituberculous therapy and subsequently with combination antiretroviral therapy (ARV), we conducted a prospective study of 33 HIV-seropositive TB patients treated with anti-TB therapy and antiretroviral therapy (Group 1) compared with 55 HIV-seronegative TB patients treated with anti-TB therapy (Group 2) and 28 HIV-seropositive TB patients treated with anti-TB therapy but not on antiretrovirals (historical control; Group 3). In Group 1 patients, paradoxical responses were temporally more related to the initiation of ARV than to the initiation of anti-TB therapy (mean +/- SD: 15 +/- 11 d versus 109 +/- 72 d [p < 0.001]) and occurred much more frequently (12 of 33; 36%) compared with Group 2 (1 of 55; 2%) (p < 0.001) or with Group 3 (2 of 28; 7%) (p = 0.013). The majority of patients who experienced paradoxical responses and received tuberculin purified protein derivative (PPD) in Group 1 had their tuberculin skin tests convert from negative to strongly positive after ARV. These observations suggest that a paradoxical response associated with enhanced tuberculin skin reactivity may occur after the initiation of ARV in HIV-infected TB patients. Furthermore, the skin test conversion after the initiation of ARV may have important public health implications.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Inhibition of antigen-induced acute bronchoconstriction, airway hyperresponsiveness, and mast cell degranulation by a nonanticoagulant heparin: comparison with a low molecular weight heparin.

Inhaled heparin prevents antigen-induced bronchoconstriction and inhibits anti-IgE-mediated mast-cell degranulation. We hypothesized that the antiallergic action of heparin may be dependent on molecular weight and related to its nonanticoagulant properties. Therefore, in the present investigation we studied the effects of a nonanticoagulant fraction of heparin (LA-heparin) on antigen-induced bronchoconstriction, airway hyperresponsiveness (AHR), and mast-cell degranulation, and compared its antiallergic activity with that of a low molecular weight heparin (LMW-heparin, fragmin). Specific lung resistance (SRL) was measured in 15 sheep before, immediately after, and serially for as long as 2 h after airway challenge with Ascaris suum antigen, without and after pretreatment with inhaled fractionated heparins at doses of 2.5 and 5 mg/kg. Airway responsiveness was estimated before, and 2 h after antigen as the cumulative provocating dose (PD400) of carbachol in breath units, which increased SRL by 400% (one breath unit was defined as one breath of 1% carbachol solution). LA-heparin caused a dose-dependent inhibition of antigen-induced bronchoconstriction, and a 5-mg/kg nebulized dose caused a 67% inhibition of allergic bronchoconstriction, whereas a 2.5-mg/kg dose was ineffective (20% inhibition). Inhaled fragmin was more potent than LA-heparin, as shown by 84% (2.5 mg/kg) and 82% (5 mg/kg) inhibition of allergic bronchoconstriction. Fragmin (5 mg/kg) also attenuated the postantigen AHR, whereas LA-heparin was ineffective. In vitro, preincubation with both LA-heparin and fragmin inhibited the anti-IgE-induced degranulation of rat peritoneal mast-cells in a dose-dependent fashion. LA-heparin was fourfold more potent than fragmin, with IC50 of 80 and 320 microg/ml, respectively. These data suggest that: (1) fractionated heparins attenuate antigen-induced acute bronchoconstriction, (2) nonanticoagulant fractions mediate the antiallergic activity of inhaled heparin, and (3) antiallergic activity of nonanticoagulant heparin and LMW-heparin may be related to prevention of mast-cell degranulation.

Acute Disease↗