ABSTRACT
OBJECTIVES: People living with HIV (PWH) are at elevated risk of cardiac disease compared to the general population. Methamphetamine use has been associated with structural heart disease and increased mortality from cardiovascular disease but has not been explored as a cause of cardiac disease among PWH. We sought to evaluate the association of methamphetamine use and cardiac disease among PWH. METHODS: We performed a case-control study of participant data in the HIV Neurobehavioral Research Program. Cases were defined as PWH with a history of myocardial infarction or a history of heart failure (systolic or diastolic). Covariates, including methamphetamine abuse/dependence, were assessed using multiple logistic regression. RESULTS: Among 3747 PWH, there was a history of myocardial infarction in 115 subjects (3.1%), and a history of heart failure in 41 (1.1%). Current or prior methamphetamine abuse/dependence was reported in 1036 (27.9%) and was not associated with myocardial infarction (P = 0.27) or heart failure (P = 0.84). In addition to traditional risk factors, variables associated with myocardial infarction included the presence of HIV infection (P = 0.01) and duration of HIV infection (P = 0.05). Variables associated with heart failure among PWH included older age, hypertension and myocardial infarction. CONCLUSIONS: No association between methamphetamine abuse/dependence and a diagnosis of myocardial infarction or heart failure was found among PWH. Significant covariates for myocardial infarction and heart failure included traditional risk factors, the presence of HIV infection and the duration of HIV infection, emphasizing the need for optimal traditional cardiovascular risk factor management among PWH.
Subject(s)
Amphetamine-Related Disorders/epidemiology , HIV Infections/epidemiology , Heart Failure/epidemiology , Hypertension/epidemiology , Myocardial Infarction/epidemiology , Adult , Age Factors , Amphetamine-Related Disorders/complications , Case-Control Studies , Female , Heart Failure/chemically induced , Humans , Logistic Models , Male , Methamphetamine/adverse effects , Middle Aged , Myocardial Infarction/chemically induced , Risk FactorsABSTRACT
We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.
Subject(s)
Decision Support Techniques , Epidemiologic Research Design , HIV Infections/complications , Myocardial Infarction/diagnosis , Adult , Aged , Aged, 80 and over , Cohort Studies , False Positive Reactions , Female , Humans , Male , Middle Aged , Myocardial Infarction/etiology , Predictive Value of Tests , Sensitivity and Specificity , Single-Blind MethodSubject(s)
Cholesterol, LDL/blood , Cholesterol, LDL/standards , Coronary Disease/blood , Coronary Disease/drug therapy , Atorvastatin , Cohort Studies , Coronary Artery Bypass/statistics & numerical data , Coronary Disease/mortality , Follow-Up Studies , Heptanoic Acids/therapeutic use , Humans , Japan , Male , Practice Guidelines as Topic/standards , Pravastatin/therapeutic use , Pyrroles/therapeutic use , Randomized Controlled Trials as Topic/statistics & numerical data , Treatment Outcome , United StatesABSTRACT
Cholesterol lowering with statins reduces coronary events in a primary-prevention setting and in patients with stable coronary disease. However, where the risk of a coronary event is highest, in the early months after an episode of unstable angina or non-Q-wave infarction, the effect of statin therapy has not been evaluated until recently. The lack of an early benefit in the 3 main statin trials in stable coronary disease may have discouraged this type of investigation. Yet, evidence suggests that intensive cholesterol lowering can rapidly influence several mechanisms intimately related to the pathogenesis of acute coronary syndromes; specifically, improvement in endothelial function, decreased propensity for platelet thrombus formation, and reduced inflammation. Furthermore, 3 nonrandomized, observational studies have recently reported an improved outcome in statin-treated compared with untreated patients after acute coronary syndromes.
Subject(s)
Angina, Unstable/drug therapy , Anticholesteremic Agents/therapeutic use , Coronary Artery Disease/drug therapy , Heptanoic Acids/therapeutic use , Hypercholesterolemia/drug therapy , Myocardial Infarction/drug therapy , Pyrroles/therapeutic use , Angina, Unstable/blood , Anticholesteremic Agents/adverse effects , Atorvastatin , Cholesterol/blood , Clinical Trials as Topic , Coronary Artery Disease/blood , Follow-Up Studies , Heptanoic Acids/adverse effects , Humans , Hypercholesterolemia/blood , Myocardial Infarction/blood , Pyrroles/adverse effects , Treatment OutcomeABSTRACT
Since 1990, vancomycin-resistant enterococci have emerged as important nosocomial pathogens. Invasive infections caused by these organisms have challenged most physicians because they are resistant to multiple antibiotics. We analyzed the clinical characteristics of adult patients with invasive vancomycin-resistant enterococci infections in the National Taiwan University Hospital from January 1993 through December 2000. A total of 11 adult patients were identified, 9 of whom had bacteremia (7 caused by vancomycin-resistant Enterococcus faecalis and 2 by vancomycin-resistant Enterococcus faecium) and one each had thoracic empyema (vancomycin-resistant E. faecium) and peritonitis (vancomycin-resistant E. faecium). Five patients had rectal swab cultures positive for vancomycin-resistant enterococci; 4 of them had underlying malignancies. The majority (91%) of these patients had prolonged hospitalization and prior long-term use of broad-spectrum cephalosporins (ceftriaxone, ceftazidime, or cefepime) or anti-anaerobic agents (clindamycin or metronidazole). The crude mortality rate was 64%. In conclusion, invasive infection caused by vancomycin-resistant enterococci is an emerging problem among hospitalized patients in Taiwan, particularly those with severe underlying diseases and exposure to multiple antibiotics.
Subject(s)
Enterococcus faecalis/drug effects , Enterococcus faecium/drug effects , Gram-Positive Bacterial Infections/drug therapy , Vancomycin/therapeutic use , Adult , Aged , Drug Resistance, Bacterial , Female , Humans , Male , Middle Aged , Prospective Studies , Vancomycin/pharmacologyABSTRACT
D-Lactate dehydrogenase (D-LDH) is a membrane-associated respiratory enzyme of Escherichia coli. The protein is composed of 571 amino acid residues with a flavin adenine dinucleotide (FAD) cofactor, has a molecular weight of approximately 65,000, and requires lipids or detergents for full activity. We used NMR spectroscopy to investigate the structure of D-LDH and its interaction with phospholipids. We incorporated 5-fluorotryptophan (5F-Trp) into the native enzyme, which contains five tryptophan residues, and into mutant enzymes, where a sixth tryptophan is substituted into a specific site by oligonucleotide-directed mutagenesis, and studied the 5F-Trp-labeled enzymes using 19F-NMR spectroscopy. In this way, information was obtained about the local environment at each native and substituted tryptophan site. Using a nitroxide spin-labeled fatty acid, which broadens the resonance from any residue within 15 A, we have established that the membrane-binding area of the protein includes the region between Tyr 228 and Phe 369, but is not continuous within this region. This conclusion is strengthened by the results of 19F-NMR spectroscopy of wild-type enzyme labeled with fluorotyrosine or fluorophenylalanine in the presence and absence of a nitroxide spin-labeled fatty acid. These experiments indicate that 9-10 Phe and 3-4 Tyr residues are located near the lipid phase.
Subject(s)
Escherichia coli/enzymology , L-Lactate Dehydrogenase/chemistry , Lactate Dehydrogenases , DNA Mutational Analysis , Escherichia coli/genetics , Fluorine/chemistry , Kinetics , L-Lactate Dehydrogenase/genetics , L-Lactate Dehydrogenase/metabolism , Magnetic Resonance Spectroscopy , Membranes, Artificial , Mutagenesis, Site-Directed , Spin Labels , Tryptophan/analogs & derivatives , Tryptophan/chemistry , Tyrosine/analogs & derivatives , Tyrosine/chemistryABSTRACT
A combination of site-specific mutagenesis and 19F nuclear magnetic resonance has been used to investigate the structural properties of D-lactate dehydrogenase, a membrane-associated enzyme of Escherichia coli. The protein (65,000 Da) has been labeled with 5-fluorotryptophan for 19F nuclear magnetic resonance studies. Tryptophan has been substituted for individual phenylalanine, tyrosine, isoleucine, and leucine residues at various positions throughout the enzyme molecule, and the fluorinated native and substituted tryptophan residues have been used as probes of the local environment. All 24 mutants thus generated are expressed in E. coli. Ten are fully active and purfiable following the usual procedure, while 14 either are inactive or produce low levels of activity. The amount of active enzyme produced from the low-yield mutants is dependent on the temperature at which synthesis is carried out, with more active enzyme produced at 18 degrees C than at 27, 35, or 42 degrees C. Cells grown at 27 degrees C and then incubated at 42 degrees C retain 90-100% of their activity. All of the expressed protein from the inactive mutants is Triton-insoluble, aggregated, and not readily purfiable; the inactive mutant protein appears to be improperly folded. Most of the expressed D-lactate dehydrogenase from the partially active mutants is also Triton-insoluble; a small fraction, however, is soluble in Triton and can be purified to yield active enzyme. All the purified enzymes from these low-yield mutants of D-lactate dehydrogenase have essentially normal VmaxS, and all but two have normal KmS. Once purified, the low-yield mutant enzymes are stable at 42 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)