Impact of antiretroviral treatment on (13) C-methionine metabolism as a marker of hepatic mitochondrial function: a longitudinal study.

OBJECTIVES: Uncontrolled viral replication and antiretroviral treatment (ART) may independently contribute to hepatic mitochondrial toxicity. The present study was designed to explore the longitudinal effects of treatment modifications on hepatic mitochondrial function by means of noninvasive (13) C-methionine breath test (MeBT) diagnostics. METHODS: A total of 113 HIV-infected patients underwent two consecutive MeBTs over an interval of 11.8±3.5 months. Forty-nine patients remained on stable ART or no therapy; 28 participants switched ART; 27 patients (re)initiated ART, and nine individuals underwent a structured treatment interruption (STI) of ART between MeBTs 1 and 2. Breath test results were expressed as cumulative percentage dose of (13) CO(2) recovered after 1.5 h test time (cPDR(1.5h) ). RESULTS: Initiation of ART in treatment-naïve individuals and patients on STI was associated with a significant improvement of hepatic mitochondrial function (P<0.05). Cessation of ART or a prolonged delay in initiating therapy in treatment-naïve patients in turn led to a significant decline of (13) C-exhalation compared with baseline (P<0.05). A marked increase in (13) C-exhalation was observed in individuals who switched from stavudine or ddI to tenofovir or abacavir (+170%; P<0.001), while no differences between MeBTs 1 and 2 were found in individuals on ART who had remained on stable regimens or in those who changed a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) component. CONCLUSION: The present data suggest that hepatic mitochondrial function in HIV disease is a dynamic process with a high regenerative capacity and highlight the pathogenic relevance of HIV replication. Our findings suggest that modern ART per se does not negatively impact hepatic mitochondrial function.

Disease- and treatment-related predictors of hepatic mitochondrial dysfunction in chronic HIV infection assessed by non-invasive (13)C-methionine breath test diagnostic.

OBJECTIVES: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons are due to hepatic complications. Hepatitis coinfection, antiretroviral treatment and co-occurrence of metabolic risk factors contribute to hepatic mitochondrial damage manifesting in hepatic steatosis and steatohepatitis. The aim was to assess disease- and treatment-related predictors on hepatic mitochondrial dysfunction in HIV infection by means of a new (13)C-methionine breath test (MeBT). PATIENTS AND METHODS: 148 HIV positive individuals with and without antiretroviral treatment (ART) [44 therapy-naives; 89 patients on combination ART and 15 patients on structured treatment interruption (STI)] and 20 HIV-negative controls were studied prospectively by MeBT. RESULTS: A decay of (13)C-methionine metabolism, expressed as cumulated percentage dose recovered over 1.5h (cPDR(1.5h)), in the subgroups of treatment-naives and patients on STI compared to controls was detected (cPDR(1.5h): 3.4 +/- 1.3% and 4.0 +/- 2.4% vs. 6.3 +/- 1.2%; p<0.01). Multivariate analyses including metabolic, treatment- and disease-related variables showed that antiretroviral treatment with stavudine, didanosine or zalcitabine and treatment-naivety were best predictors of a reduced MeBT result (cPDR(1.5h)) (beta = -0.56 and -0.50, p<0.05). CD4 count had only a minor association (beta = 0.15, p<0.05). No other variable including disease and treatment duration was associated with MeBT outcome. These factors explained 39% of the variance of MeBT results (p<0.05). CONCLUSIONS: Therapy naivety and treatment with d-drugs were the best predictors of poor MeBT outcome. MeBT may be proposed as a feasible, noninvasive diagnostic instrument for clinical assessment of hepatic mitochondrial function and early detection of drug-induced mitochondriotoxity in chronic HIV infection.

Five-year study on the injury of the great thoracic vessels after penetrating chest injury.

In the cases of penetrating injury of the heart and the great thoracic vessels, 80% of the patients die before reaching the hospital care, nevertheless patients with sufficient vital functions can be rescued. Between 01. 01. 1994 and 31. 12. 1998 four patients were operated for penetrating injuries of the great vessels in the 2nd Department of Surgery, University Medical School of Debrecen. The left subclavian vein, arcus aortae and the pulmonary artery (2 cases) were injured. In this study authors report a detailed case operated for gunshot injury of the pulmonary artery. On the base of the situation of the projectile on X-ray picture and on the base of the entrance wound of the projectile on the skin we supposed the injury of the great thoracic vessels and we performed an urgent operation. After thoracotomy we found haemopericardium, bleeding wounds on the anterior and posterior haemorrhagic wall of the left pulmonary artery. We found the projectile inside the wall of the bronchus impacted. The bleeding wounds were finger-tamponaded and sutured. On the tenth postoperative day the patient was discharged from our clinic without complaint. The surgical approach to specific thoracic great vessels is also described.

[Lincomycin concentration in human serum and pulmonary tissue]. / Issledovanie kontsentratsii linkomitsina v syvorotke krovi i legochnoi tkani cheloveka

Lincomycin levels in the blood serum and lung tissue were determined in 17 patients after surgical operations because of the lung diseases, the drug being administered in a dose of 500 mg. In 45 to 330 minutes after administration of the antibiotic its concentration in the blood serum and lung tissue was 4.6 +/- 10 lambda/ml(average 7.7 lambda/ml) and 1.4-8 lambda/gm (average 4.4 lambda/gm) respectively. The lincomycin level in the lung tissue amounted to 61 per cent of that in the blood setum. The concentration of lincomycin the lung tissue was several times higher than the minimum level necessary for inhibition of the strains included in the antibiotic antibacterial spectrum. Therefore, lincomycin is an important drug in the treatment of infections of the respiratory tract.