Biomedical subjects

Anton F Doubell

Publications and source records attributed to Anton F Doubell.

7 recordsLinked to original sources

PubMed2005

Characterization of the immunological features of tuberculous pericardial effusions in HIV positive and HIV negative patients in contrast with non-tuberculous effusions.

OBJECTIVE: To investigate the immunopathogenesis of pericardial tuberculosis (TB) and the influence of human immunodeficiency virus (HIV) on the anti-tuberculous immune response. DESIGN: Consecutive patients presenting with large pericardial effusions were subjected to a full clinical examination and pericardiocentesis. Aspirated fluid was sent for biochemistry, differential leukocyte count, flow cytometric analysis and determination of cytokine levels. Pericardial tissue was sent for TB culture and histopathological evaluation. Diagnoses were made according to pre-determined criteria. RESULTS: Fifty-six patients were included and divided into HIV positive TB (n = 22), HIV negative TB (n = 21) and non-tuberculous effusions (n = 13). Peripheral blood neutrophil, lymphocyte and monocyte counts were significantly lower in HIV positive TB patients. Lymphocytes were the dominant cell type in tuberculous pericardial effusions. CD4+ cells dominated in HIV negative tuberculous effusions, whereas CD8+ cells dominated in HIV positive TB. The difference in the concentration of IFN-gamma levels in the tuberculous and non-tuberculous pericardial effusions was statistically significant. Despite significant differences in pericardial CD4+ cell counts, IFN-gamma levels were similarly elevated in HIV negative and HIV positive tuberculous effusions. Highest levels of pericardial IL-10 were observed in samples associated with least tissue necrosis, suggesting the possibility of a tissue protective immunoregulatory role for IL-10. CONCLUSIONS: Tuberculous pericardial effusions result from a T helper1 (Th1)-dominant immune response. IFN-gamma producing CD4+ lymphocytes dominate in HIV negative patients, whereas CD8+ seem to play a more important role in HIV positive patients. Infection with HIV leads to the depletion of immunocompetent cells such as monocytes, NK cells and neutrophils.

AIDS-Related Opportunistic Infections↗

PubMed2005

Tuberculous pericarditis.

BACKGROUND: The incidence of tuberculous pericarditis is increasing in Africa as a result of the human immunodeficiency virus (HIV) epidemic. The primary objective of this article was to review and summarize the literature on the pathogenesis, diagnosis, and management of tuberculous pericarditis. METHODS AND RESULTS: We searched MEDLINE (January 1966 to May 2005) and the Cochrane Library (Issue 1, 2005) for information on relevant references. A "definite" diagnosis of tuberculous pericarditis is based on the demonstration of tubercle bacilli in pericardial fluid or on a histological section of the pericardium; "probable" tuberculous pericarditis is based on the proof of tuberculosis elsewhere in a patient with otherwise unexplained pericarditis, a lymphocytic pericardial exudate with elevated adenosine deaminase levels, and/or appropriate response to a trial of antituberculosis chemotherapy. Treatment consists of the standard 4-drug antituberculosis regimen for 6 months. It is uncertain whether adjunctive corticosteroids are effective in reducing mortality or progression to constriction. Surgical resection of the pericardium remains the appropriate treatment for constrictive pericarditis. The timing of surgical intervention is controversial, but many experts recommend a trial of medical therapy for noncalcific pericardial constriction, and pericardiectomy in nonresponders after 4 to 8 weeks of antituberculosis chemotherapy. CONCLUSIONS: Research is needed to improve the diagnosis, assess the effectiveness of adjunctive steroids, and determine the impact of HIV infection on the outcome of tuberculous pericarditis.

Africa↗

PubMed2005

Cardiac sarcoidosis evaluated with gadolinium-enhanced magnetic resonance and contrast-enhanced 64-slice computed tomography.

Sarcoidosis is a multi-system granulomatous disorder of unknown etiology with symptomatic cardiac involvement in up to 7% of patients. The clinical features of sarcoid heart disease include congestive heart failure, arrhythmias, conduction disturbances, and sudden death. We evaluated the value of contrast-enhanced multi-detector computed tomography in delineating myocardial scar and granulomatous inflammation by comparing our findings with gadolinium magnetic resonance in a patient diagnosed with cardiac sarcoidosis.

Adult↗

PubMed2002

Role of biochemical tests in the diagnosis of large pericardial effusions.

STUDY OBJECTIVES: To determine the biochemical characteristics of large pericardial effusions in various disease states, and to assess their utility as diagnostic tools. SETTING: An academic university hospital in the Western Cape, South Africa. DESIGN: Consecutive, prospective case series. PATIENTS: One hundred ten hospital patients > 12 years old, who presented to the echocardiography department with large pericardial effusions, and 12 control subjects who underwent open-heart surgery (coronary artery bypass graft or aortic valve replacement). MEASUREMENTS: Fluid was sent for examination of biochemistry, adenosine deaminase, microbiology, hematology, and cytology. The etiology of each pericardial fluid sample was established using predetermined criteria. RESULTS: The biochemistry of pericardial exudates differed significantly from pericardial transudates. Light' s criteria (whereby an exudate is defined as having one or more of the following: pleural fluid/serum protein ratio > 0.5; pleural fluid/serum lactate dehydrogenase [LDH] ratio > 0.6; and/or pleural fluid LDH level > 200 U/L) were applied to pericardial fluids and demonstrated to be the most reliable diagnostic tool for identifying pericardial exudates. The corresponding sensitivity was 98%. CONCLUSION: Although laboratory tests are a useful guideline when assessing the etiology and pathophysiology of pericardial effusions, the majority of large, clinically significant pericardial effusions result from exudative causes.

Bilirubin↗

PubMed2002

The use of adenosine deaminase and interferon-gamma as diagnostic tools for tuberculous pericarditis.

BACKGROUND: Traditional diagnostic tests for pericardial tuberculosis (TB) are insensitive and often require long culture periods, and this has led to more emphasis being placed on biochemical tests such as the pericardial adenosine deaminase (ADA) test. However, controversy exists as to its diagnostic utility. In addition, the use of interferon (IFN)-gamma, which is a reliable indicator of pleural and peritoneal TB, has not been explored in pericardial effusions. We investigated ADA and IFN-gamma levels in pericardial effusions of different etiologies. METHODS AND RESULTS: A prospective study was carried out from February 1995 to February 1998 at Tygerberg Hospital (South Africa), with pericardial taps being performed under echocardiographic guidance. During this period, 110 consecutive patients presenting with large pericardial effusions were included in the study. Diagnoses were made according to predetermined criteria, and they included TB (n = 64), malignancy (n = 12), nontuberculous infections (n = 5), other effusions (n = 19), and effusions of uncertain origin (n = 10). The median ADA level in the tuberculous group was 71.7 U/L (range, 10.3 to 303.6 U/L), which was significantly higher than that in any other group (p < 0.05). With a cutoff level for ADA activity of 30 U/L, sensitivity was 94%, specificity was 68%, and positive predictive value was 80%. IFN-gamma levels were determined in 30 subjects. The median IFN-gamma concentration in the tuberculous group was > 1,000 pg/L, which was significantly higher than in any other diagnostic group (p < 0.0005). A cutoff value of 200 pg/L for IFN-gamma resulted in a sensitivity and specificity of 100% for the diagnosis of pericardial TB. CONCLUSION: Pericardial fluid levels of ADA and IFN-gamma are useful in the diagnosis of tuberculous pericarditis.

Adenosine Deaminase↗

PubMedDate not supplied

Adenosine deaminase activity--more than a diagnostic tool in tuberculous pericarditis.

AIM: To improve the understanding of factors that influence adenosine deaminase ( ADA) activity in large pericardial effusions. METHODS: A prospective study was carried out at Tygerberg Academic Hospital, South Africa. Patients underwent echocardiographically guided pericardiocentesis. ADA activity, as well as biochemistry, haematology, cytology, and in some cases, histology, were determined. Human immunodeficiency virus (HIV) status was assessed in all patients. RESULTS: Two hundred and thirty-three patients presented to Tygerberg Hospital with large pericardial effusions requiring pericardiocentesis. Tuberculous pericarditis accounted for 162 effusions (69.5%). An ADA cut-off level of 40 U/l resulted in a test sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic efficiency of 84.0%, 80.0%, 91.0%, 66.0% and 83.0%, respectively. Pericardial exudates with an ADA activity > or = 40 U/l were associated with increased total leukocyte and neutrophil counts. Patients with tuberculous pericarditis and ADA > or = 40 U/l also had increased lymphocyte counts. Pericardial ADA activity < 30 U/l was associated with severe depletion of CD4 cell counts in HIV-positive patients. ADA levels were higher in cases with histological evidence of granulomatous inflammation than in cases with serofibrinous pericarditis. CONCLUSIONS: An ADA cut-off level of 40 U/l results in best diagnostic test results. ADA production appears to be influenced by factors associated with the antituberculous immune response.

Adenocarcinoma↗

PubMedDate not supplied

Experience with adjunctive corticosteroids in managing tuberculous pericarditis.

OBJECTIVES: To compare the efficacy of intrapericardial corticosteroid therapy to either oral corticosteroid therapy or intrapericardial placebo in addition to closed pericardiocentesis and anti-tuberculous therapy in patients with tuberculous pericarditis. METHODS: Patients with large pericardial effusions requiring pericardiocentesis were included. A short-course anti-tuberculous regimen was initiated and patients were randomised to one of three treatment groups: 200 mg intrapericardial triamcinolone hexacetonide; oral prednisone plus intrapericardial placebo; or 5 ml intrapericardial 0.9% saline (placebo). Patients were followed up for at least one year. RESULTS: Fifty-seven patients were included in the study; 21 tested HIV positive (36.8%). Forty (70.0%) had microbiological and/or histological evidence of tuberculosis, and 17 (30.0%) had a diagnosis based on clinical and laboratory data. All patients responded well to initial pericardiocentesis. However, nine patients (16.0%) were lost to follow up. The hospitalisation duration for the steroid groups was shorter than for the placebo group. This difference was not significant. Complications were similar for all arms. CONCLUSIONS: Intrapericardial and systemic corticosteroids were well tolerated but did not improve the clinical outcome. The standard six-month regimen was effective regardless of HIV infection. The potential benefits from adjunctive corticosteroids in the management of effusive tuberculous pericarditis could not be demonstrated in this three-year study.

Administration, Oral↗