Nanoscale electronic order in iron pnictides.

The charge distribution in RFeAsO1-xFx (R=La,Sm) iron pnictides is probed using As nuclear quadrupole resonance. Whereas undoped and optimally doped or overdoped compounds feature a single charge environment, two charge environments are detected in the underdoped region. Spin-lattice relaxation measurements show their coexistence at the nanoscale. Together with the quantitative variations of the spectra with doping, they point to a local electronic order in the iron layers, where low- and high-doping-like regions would coexist. Implications for the interplay of static magnetism and superconductivity are discussed.

75As NMR studies of superconducting LaFeAsO0.9F0.1.

We have performed 75As nuclear magnetic resonance measurements on aligned powders of the new LaFeAsO0.9F0.1 superconductor. In the normal state, we find a strong temperature dependence of the spin shift and Korringa behavior of the spin lattice relaxation rate. In the superconducting state, we find evidence for line nodes in the superconducting gap and spin-singlet pairing. Our measurements reveal a strong anisotropy of the spin lattice relaxation rate, which suggests that superconducting vortices contribute to the relaxation rate when the field is parallel to the c axis but not for the perpendicular direction.

Psychiatric disorders, HIV infection and HIV/hepatitis co-infection in the correctional setting.

Psychiatric disorders such as bipolar disorder, schizophrenia and depression have long been associated with risk behaviors for HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV). The US prison population is reported to have elevated rates of HIV, hepatitis and most psychiatric disorders. This study examined the association of six major psychiatric disorders with HIV mono-infection, HIV/HCV co-infection and HIV/HBV co-infection in one of the nation's largest prison populations. The study population consisted of 370,511 Texas Department of Criminal Justice inmates who were incarcerated for any duration between January 1, 2003 and July 1, 2006. Information on medical conditions and sociodemographic factors was obtained from an institution-wide electronic medical information system. Offenders diagnosed with HIV mono-infection, HIV/HCV, HIV/HBV and all HIV combined exhibited elevated rates of major depression, bipolar disorder, schizophrenia, schizoaffective disorder, non-schizophrenic psychotic disorder and any psychiatric disorder. In comparison to offenders with HIV mono-infection, those with HIV/HCV co-infection had an elevated prevalence of any psychiatric disorder. This cross-sectional study's finding of positive associations between psychiatric disease and both HIV infection and hepatitis co-infection among Texas prison inmates holds both clinical and public health relevance. It will be important for future investigations to examine the extent to which psychiatric disorders serve as a barrier to medical care, communication with clinicians and adherence to prescribed medical regimens among both HIV-mono-infected and HIV/hepatitis-co-infected inmates.

Transient or occult HIV infections may occur more frequently than progressive infections: changing the paradigm about HIV persistence.

Evidence of transient HIV infections was found in 8 subjects at high-risk for HIV infection among 47 longitudinally studied over 2-5 (average approximately 3.5) years, whereas only two subjects developed progressive infection. All of these subjects developed serum antibodies (Ab) to conformational epitopes of HIV gp41 (termed "early HIV Ab"), but the 8 transiently infected subjects lost this Ab within 4-18 months, and did not seroconvert to positivity in denatured antigen EIA or Western Blot (WB). However, the two progressively infected subjects eventually seroconverted in the EIA and WB tests within one to two months after the appearance of "early HIV Ab". HIV env and nef sequences were directly PCR amplified from the peripheral blood mononuclear cells (PBMCs) of two of the eight transiently infected subjects during the time of "early HIV Ab"-postivity, and these showed significant sequence divergence from the HIV strains in the laboratory, indicating that they were not laboratory contaminants. Genome identity typing ("paternity-typing") of PBMC samples obtained at the time of "early HIV Ab"-positivity, and later when Ab was absent from each of the 8 subjects, showed that blood samples were not mixed-up. This provides further evidence that transient or occult infection with HIV does occur, and perhaps at a greater frequency than do progressive infections.

Thymidine-analog and multi-nucleoside resistance mutations are observed in both zidovudine-naive and zidovudine-experienced subjects with viremia after treatment with stavudine-containing regimens.

OBJECTIVE: The type and frequency of mutations in the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase coding region observed in virus from antiretroviral therapy (ART)-experienced, zidovudine (ZDV)-naive subjects receiving stavudine (d4T)-based therapies were compared with mutations observed in virus from ART-experienced subjects with previous ZDV exposure. METHODS: Plasma HIV-1 RNA was isolated from 67 ART-experienced subjects. Reverse transcriptase mutations were assessed by sequencing polymerase chain reaction products. RESULTS: Thirty-four subjects (51%) were ZDV-experienced (Z(exp)) and 33 (49%) were ZDV-naive and d4T-experienced (d(exp)Z(naive)). Human immunodeficiency virus type 1 from 16 of 33 (48%) d(exp)Z(naive) subjects and from 16 of 34 (47%) Z(exp) subjects had thymidine analog mutations (TAMs). Multi-nucleoside resistance (MNR) mutations were observed in virus from 5 of 33 (15%) d(exp)Z(naive) subjects and 3 of 34 (9%) Z(exp) subjects. At least one TAM or MNR mutation was identified in 18 of 33 (55%) of the former and in 19 of 34 (56%) of the latter group. CONCLUSIONS: These results confirm recent reports that TAMs and MNR mutations can arise in subjects receiving d4T-based therapy who are naive with respect to ZDV.

Comparative studies of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine.

OBJECTIVES: To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine. DESIGN: Two multicenter, open-label, randomized 24-week studies. METHODS: Adults HIV-1 infection, HIV-1 RNA greater than 10000 copies/ml, and no prior lamivudine or protease inhibitor therapy were eligible. In a pilot study (Study A), patients received indinavir at 800 mg every 8 h, 1000 mg every 12 h, or 1200 mg every 12 h. In a subsequent study (Study B), patients received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subjects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An intent-to-treat analysis was used. RESULTS: In Study A, which enrolled 88 patients, neither HIV-1 RNA nor CD4 cell responses differed significantly between treatment groups at 24 weeks when corrected for multiple comparisons. Study B enrolled 433 patients, but was prematurely discontinued when interim analysis suggested greater efficacy of three-times-daily indinavir. Of the first 87 patients reaching week 24, HIV-1 RNA was less than 400 copies/ml in 91% receiving three-times-daily versus 64% receiving two-times-daily indinavir (P < 0.01). CONCLUSION: Three-times-daily indinavir appears more efficacious than two-times-daily dosing when administered with zidovudine and lamivudine. Two-times-daily indinavir dosing should only be considered in situations characterized by favorable pharmacokinetic drug-drug interactions.

Propranolol stereoisomer plasma concentrations and portal haemodynamic response in patients with liver cirrhosis.

BACKGROUND: The haemodynamic effect of propranolol on portal pressure in patients with portal hypertension is highly variable and does not correlate with propranolol racemate plasma concentrations. AIM: To investigate the stereoselective metabolism of the propranolol enantiomers and its impact on portal haemodynamics in patients with liver cirrhosis since only S-propranolol is haemodynamically active. METHODS: Twenty patients with liver cirrhosis and portal hypertension received 40 mg propranolol orally. Portal blood velocity (PBV) and propranolol stereoisomer plasma concentrations were determined. RESULTS: During the 4 h examination period we observed a significant reduction in PBV (18.3 +/- 2.2%, P < 0.0001) vs. baseline. The area under the curve (AUC) during the study period was significantly different for the two isomers (S-propranolol 1217.0 +/- 118.5 nmol.h/L; R-propranolol 728.8 +/- 103.8 nmol.h/L, P < 0.0001). Seven patients (35%) were portal haemodynamic non-responders to propranolol. Propranolol stereoisomer AUC values were no different between responders (S-propranolol 1133. 3 +/- 132.0 nmol.h/L; R-propranolol 718.0 +/- 129.7 nmol.h/L) and non-responders (S-propranolol 1371.8 +/- 250.5 nmol.h/L; R-propranolol 746.9 +/- 200.3 nmol.h/L); neither was there a correlation between propranolol enantiomer plasma concentrations and the portal haemodynamic effect. CONCLUSIONS: Our data demonstrate a stereoselective metabolism of propranolol enantiomers in liver cirrhosis. However, following oral propranolol administration, stereoisomer plasma concentrations do not predict the portal haemodynamic effect.

Quantitative tissue carcinoembryonic antigen (T CEA) assay as a screening test for severe dysplasia in colorectal adenomas.

Relationship between the serum (S CEA) and the tissue (T CEA) carcinoembryonic antigen concentrations with regard to the degree of dysplasia in colorectal adenomas was investigated. Our study included 56 single or multiple colorectal adenomas in 46 patients. The measurements of T CEA concentrations were performed using the quantitative CEA-EIA method (Abbott) modified for wet tissue, obtained from heads of the adenomas. As a control point the mucosa near adenoma and the rectal mucosa were used. Our results suggest that the T CEA concentrations from the head of the adenoma demonstrate a highly significant difference between mild and severe dysplasia (P < 0.001), between mild dysplasia and invasive adenocarcinoma (P < 0.001) and a significant difference between mild and moderate dysplasia (P < 0.05). On the other hand, the S CEA concentrations corresponding to these cases showed no such differences. In conclusion, we suggest the quantitative measurement of T CEA concentrations as a screening test for severe dysplasia in colorectal adenomas.

Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza.

BACKGROUND: Safe and effective antiviral agents are needed to prevent infection with influenza A and B virus. Oseltamivir (GS4104), which can be administered orally, is the prodrug of GS4071, a potent and selective inhibitor of influenzavirus neuraminidases. We studied the use of oseltamivir for long-term prophylaxis against influenza in two placebo-controlled, double-blind trials at different U.S. sites during the winter of 1997-1998. METHODS: We randomly assigned 1559 healthy, nonimmunized adults 18 to 65 years old to receive either oral oseltamivir (75 mg given once or twice daily, for a total daily dose of 75 or 150 mg) or placebo for six weeks during a peak period of local influenzavirus activity. The primary end point with respect to efficacy was laboratory-confirmed influenza-like illness (defined as a temperature of at least 37.2 degrees C accompanied by at least one respiratory and at least one systemic symptom). RESULTS: In the two studies combined, the risk of influenza among subjects assigned to either once-daily or twice-daily oseltamivir (1.2 percent and 1.3 percent, respectively) was lower than that among subjects assigned to placebo (4.8 percent; P<0.001 and P=0.001 for the comparison with once-daily and twice-daily oseltamivir, respectively). The protective efficacy of oseltamivir in the two active-treatment groups combined was 74 percent (95 percent confidence interval, 53 to 88 percent) at all the sites combined and 82 percent (95 percent confidence interval, 60 to 93 percent) at sites in Virginia, where the rate of influenza infection was higher than the overall rate. For culture-proved influenza, the rate of protective efficacy in the two oseltamivir groups combined was 87 percent (95 percent confidence interval, 65 to 96 percent). The rate of laboratory-confirmed influenza infection was lower with oseltamivir than with placebo (5.3 percent vs. 10.6 percent, P<0.001). Oseltamivir was well tolerated but was associated with a greater frequency of nausea (12.1 percent and 14.6 percent in the once-daily and twice-daily groups, respectively) and vomiting (2.5 percent and 2.7 percent, respectively) than was placebo (nausea, 7.1 percent; vomiting, 0.8 percent). However, the frequency of premature discontinuation of drug or placebo was similar among the three groups (3.1 to 4.0 percent). CONCLUSIONS: Oseltamivir administered daily for six weeks by the oral route is safe and effective for the prevention of influenza.

Effect of hemodialysis and antiretroviral therapy on plasma viral load in HIV-1 infected hemodialysis patients.

BACKGROUND: Plasma viral load has become an important test in predicting the progress of HIV-1 infected patients. The higher the viral load the faster is the progression to AIDS. As HIV-1 infected hemodialysis (HD) patients have higher mortality and morbidity than HIV-1 infected non-dialysis patients, and as all the blood tests in the HD patients are drawn during HD, we measured the effect of HD and antiretroviral therapy on viral load in HIV-1 infected HD patients. PATIENTS AND METHODS: We measured plasma viral load pre-dialysis and post-dialysis in 10 HIV-1 infected HD patients. The viral load was measured using an in vitro quantitative nucleic acid amplification test. We also compared viral load in 8 HIV-1 infected HD patients on one antiretroviral drug with 8 HIV-1 patients on two (6) or three (2) antiretroviral drugs. RESULTS: There was a small reduction in plasma viral load postdialysis in all HIV-1 infected HD patients (45% +/- 5.4, 0.3 log +/- 0.05, p < 0.0004). However, HIV-1 RNA could not be detected in the ultrafiltrate. The patients who were on two or three antiretroviral drugs had lower viral load (8915 +/- 3702 vs. 351440 +/- 101237, p < 0.004) and higher CD4 count (355 +/- 81 vs 82 +/- 39, p < 0.009) than patients on only one antiretroviral drug. CONCLUSION: We conclude that there is a small reduction in plasma viral load in HIV-1 infected hemodialysis patients post-dialysis. As no viral RNA could be detected in the ultrafiltrate, the reduction could be due to nonspecific adsorption of the viral RNA to the dialysis membrane. HIV-1 infected hemodialysis patients who are on two or three antiretroviral drugs had significantly lower viral load and higher CD4 count than patients on only single antiretroviral drug. Therefore a single antiretroviral drug should not be used in treating HIV-1 infected HD patients.

Risk factors for colonization or infection due to methicillin-resistant Staphylococcus aureus in HIV-positive patients: a retrospective case-control study.

OBJECTIVE: To determine the risk factors for colonization or infection with methicillin-resistant Staphylococcus aureus in human immunodeficiency virus (HIV)-infected patients. DESIGN: Retrospective matched-pair case-control study. SETTING: Continuity clinic and inpatient HIV service of a university medical center. POPULATION: Patients with HIV infection from the general population of eastern and coastal Texas and from the Texas Department of Criminal Justice. DATA COLLECTION: Patient charts and the AIDS Care and Clinical Research Program Database were reviewed for the following: age, race, number of admissions, total hospital days, presence of a central venous catheter, serum albumin, total white blood cell count and absolute neutrophil count, invasive or surgical procedures, any cultures positive for S. aureus, and a history of opportunistic illnesses, diabetes, or dermatologic diagnoses. Data also were collected on the administration of antibiotics, antiretroviral therapy, steroids, cancer chemotherapy, and subcutaneous medications. RESULTS: In the univariate analysis, the presence of a central venous catheter, an underlying dermatologic disease, lower serum albumin, prior steroid therapy, and prior antibiotic therapy, particularly antistaphylococcal therapy or multiple courses of antibiotics, were associated with increased risk for colonization or infection with methicillin-resistant S. aureus. Multivariate analysis yielded a model that included presence of a central venous catheter, underlying dermatologic disease, broad-spectrum antibiotic exposure, and number of hospital days as independent risk factors for colonization or infection with methicillin-resistant S. aureus. CONCLUSIONS: In our HIV-infected patient population, prior hospitalization, exposure to broad-spectrum antibiotics, presence of a central venous catheter, and dermatologic disease were risk factors for acquisition of methicillin-resistant S. aureus.

Mass spectrometric-selected ion monitoring assay for an oxalate absorption test applying [13C2]oxalate.

In order to assess the significance of the intestinal absorption of oxalate from food for the hyperoxaluria of the individual patient, an oxalate absorption test has been developed using doubly 13C-labelled oxalate and a gas chromatographic selected ion monitoring mass spectrometric assay. This test has been applied to volunteers and patients with urinary stones. The percentage of dose absorbed (range 1-48%) could be determined with a coefficient of variation of 15.2%. The assay to measure doubly 13C-labelled oxalate in the presence of unlabelled oxalate in urine, using the homologue malonic acid as internal standard, is described.

Measuring the effect of risk factors on coronary atherosclerosis: coronary calcium score versus angiographic disease severity.

OBJECTIVES: This study sought to determine whether noninvasive quantification of coronary calcium is comparable to selective coronary angiography in measuring the effect of cardiovascular risk factors on coronary atherosclerosis. BACKGROUND: Electron beam computed tomography (EBCT) allows the delineation of anatomic coronary atherosclerotic disease and may be useful for noninvasively defining the role of established and new cardiovascular risk factors in selected patient groups. METHODS: A total of 211 consecutive patients, 26 to 79 years old, referred for evaluation of suspected or recently diagnosed coronary artery disease were examined. Selective coronary angiography was used to define five angiographic disease categories: normal coronary arteries, nonobstructive disease and one-, two- or three-vessel disease. EBCT was used to calculate coronary calcium scores, and cardiovascular risk, including lipid variables and fibrinogen levels, was assessed. RESULTS: Coronary calcium score and angiographic disease severity categories were largely predicted by identical risk factors (i.e., age, male gender, total/high density lipoprotein cholesterol ratio, fibrinogen) and, to a lesser degree, hypertension. Only smoking predicted angiographic disease severity but not calcium scores. The risk factors together explained a comparable proportion of the variability in angiographic disease categories and in calcium score quintiles (33% vs. 41%, p=0.16 by bootstrap analysis). An overall risk score composed of these risk factors separated angiographic disease categories and calcium score quintiles with a similar area under the receiver operating characteristic curve ([mean+/-SE] 0.81+/-0.03 vs. 0.83+/-0.03, p=NS). CONCLUSIONS: Quantification of coronary calcium is comparable to selective coronary angiography in measuring the effect of established cardiovascular risk factors on coronary atherosclerosis. Thus, EBCT may be useful for the noninvasive evaluation of the relations between conventional or developing cardiovascular risk factors and coronary atherosclerosis.

Effects of prostacyclin substitution on systemic procoagulant turnover and cardiorespiratory variables in experimental hypercoagulability.

Endotoxin infusion (lipopolysaccharide from Escherichia coli 120 micrograms kg-1 i.v.) was titrated to produce hypercoagulability in rabbits and the effects of prostacyclin (PGI2) treatment (continuous infusion of 6 ng kg-1 min-1 i.v.) on coagulation variables, cardiorespiratory variables, and fibrin deposition in the microcirculation of vital organs were studied. PGI2 infusion did not influence the concentration of soluble fibrin, thrombelastographic variables, or systemic platelet aggregability. Fibrin deposition in the microcirculation of the liver and the lungs was reduced to 50% of that observed in untreated animals (p < 0.01). The antiplatelet properties of PGI2 were unable to reduce experimental endotoxin-induced systemic procoagulant turnover but improved organ perfusion during the initial phase of disseminated intravascular coagulation.

Immunotherapy of CMV infections.

Immunotherapy has not only become the accepted standard for some CMV infections, but also remains an area of active investigation for the treatment and prophylaxis of CMV infections. Polyclonal immunoglobulin administration has improved the survival of CMV pneumonitis in BMT recipients, and monoclonal anti-CMV antibodies, notably MSL-109, appear to increase the time to relapse of CMV retinitis in patients with AIDS. The adoptive transfer of CMV-specific CD8 cells is under investigation as another CMV prophylactic strategy in BMT recipients, and it is hopeful that this methodology can be applied to the therapy of established CMV infections.