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D Paar

Publications and source records attributed to D Paar.

At least 19 recordsLinked to original sources
PubMed2005

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.

Gene Products, env↗
PubMed2000

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.

Adult↗
PubMed1999

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.

Administration, Oral↗
PubMed1999

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.

Adrenergic beta-Antagonists↗
PubMed1999

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.

Adenoma↗
PubMed1999

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.

Adult↗
PubMed1998

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.

Adult↗
PubMed1996

[Percutaneous puncture technique for portofemorosubclavicular venovenous bypass in orthotopic liver transplantation].

UNLABELLED: Portofemoro-axillary bypass systems are commonly used to treat adverse haemodynamic effects during the anhepatic phase of orthotopic liver transplantation (OLT). However, low shunt flows may reduce the efficacy of these bypass systems. In order to improve veno-venous bypass management, a percutaneous cannulation technique (PCT) was used to insert large-bore catheters (21 F) into the left femoral and subclavian veins. This study prospectively addresses the complications of the PCT in 195 adult patients undergoing 203 OLTs. METHODS: The left femoral and subclavian veins were cannulated preoperatively with 21 F single-lumen catheters (DLP, Grand Rapids, MN, USA) using a Seldinger technique. Intra-operatively, the centrifugal pump (Biopump, Biomedicus, Minnesota, USA) and the portal part of the bypass were connected with the femoral and subclavian catheters. Coagulation profiles, shunt flows, haemodynamic parameters, and complications during OLT associated with the bypass system were recorded. RESULTS: Percutaneous cannulation of the left subclavian and femoral veins was successful in 198 (97.6%) patients. Mean portofemoro-subclavian shuntflow was 4.3 (SD 1.3 l min-1). Although cardiac index (shunt 3.91 [SD 1.1] vs pre-shunt 4.42 [SD 1.0] l min-1 m-2, P < 0.05) and oxygen delivery (shunt 496 [SD 111] vs. pre-shunt 562 [SD 153] ml ml-1.m-2, P < 0.05) were not maintained at pre-shunt levels, renal perfusion pressure stayed above 50 mm Hg during the anhepatic phase. Two intra-operative air embolism (0.98%) and one myocardial infarction (0.49%) at the beginning of the anhepatic phase were observed. There were no bleeding complications. CONCLUSIONS: The portofemoro-subclavian bypass can be performed by percutaneous cannulation without additional complications in patients undergoing OLT. Although haemorrhagic complications following central venous catheterisation are reported to occur in patients with haemostatic defects, none of them was observed in this study. Two events of air embolism and one cardiac arrest could not be related to the PCT. In conclusion, femoro-subclavian percutaneous cannulation is a simple, rapid, and safe alternative to commonly used veno-venous bypass systems.

Adult↗
PubMed1996

The influence of C1-esterase inhibitor substitution on coagulation and cardiorespiratory parameters in an endotoxin-induced rabbit model of hypercoagulability.

In a short-time model of endotoxin-induced (lipopolysaccharide from Escherichia coli, 120 micrograms kg-1 i.v.) hypercoagulability in rabbits, the therapeutic effects of C1-esterase inhibitor (C1I) substitution (bolus 400 U kg-1 i.v. followed by continuous infusion of 400 U kg-1 4 h-1 i.v.) were studied. When compared to endotoxin-challenged untreated animals, C1I substitution significantly stabilized mean arterial pressure (p < 0.01), increased central venous oxygen saturation (p < 0.05), prevented the decrease of antithrombin III (p < 0.05), and reduced fibrin deposition in the microcirculation of the liver and the lungs to approximately 30% of that observed in the untreated animals (p < 0.01). Although C1I substitution did not reduce systemic procoagulant turnover, the improvement of blood pressure and blood flow and local inhibitory actions in the coagulation and complement cascade prevented fibrin deposition in the microcirculation of vital organs. This study supports the beneficial role of C1I substitution during early disseminated intravascular coagulation.

Animals↗
PubMed1995

Deep venous thrombosis and pulmonary artery embolism in high-grade non Hodgkin's lymphoma: incidence, causes and prognostic relevance.

To analyse incidence, risk factors, causes and prognostic significance of venous thromboembolism (VTE) in high-grade non-Hodgkin's lymphoma (HG-NHL) a prospective clinical trial (N = 593), also undertaken to analyse other aspects of HG-NHL, a study of haemostasis (N = 25) and a post-mortem analysis (N = 70) were performed. Clinical analysis documented a 6.6% incidence of VTE, and 77% of all cases occurred before or within the first 3 months of chemotherapy. Ann Arbor stage IV and B-mediastinal clear cell histology were risk factors for VTE, while rapid changes in tumour load or application of consolidation chemotherapy were not. Vessel compression by HG-NHL was the leading cause of VTE, whereas a significant (paraneoplastic or chemotherapy-induced) thrombophilic state was not disclosed by haemostatic tests. While VTE-related fatality was found to be low in the clinical trial (1.7%) and at necropsy (8.5%), the occurrence of VTE was associated with an unsatisfactory response of HG-NHL to chemotherapy and a high incidence of treatment-related mortality due to diffuse alveolitis. Thus, fatal VTE in HG-NHL is rare, but VTE is associated with an unfavourable clinical course of HG-NHL.

Adolescent↗
PubMed1995

Short-time rabbit model of endotoxin-induced hypercoagulability.

We describe a short-time endotoxin-induced rabbit model of hypercoagulability for the study of the coagulation cascade and the therapeutic effects of coagulation inhibitors. Cardiorespiratory function was maintained in rabbits under general anesthesia and standardized mechanical ventilation (tidal volume, 6 ml/kg; 60 breaths/min) via tracheostomy and low-dose inotropic support. Coagulation parameters such as prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, platelet count, fibrin monomers, D-dimers, antithrombin III and factor XIII activities, thrombelastography, and platelet aggregometry were measured during a 4-h period after sequential double endotoxin administration (80 and 40 micrograms/kg of body weight, intravenously). Mean arterial pressure and arterial and central venous blood gas tensions were monitored. Global clotting, activation parameters of coagulation, and leukocyte count deteriorated significantly in the endotoxin-treated animals but was mainly unaltered in controls (P < 0.05). Tissue specimens of the lungs, liver, brain, and kidneys were examined. Endotoxin-induced, disseminated fibrin deposition was found in the lungs and liver (P < 0.01). We conclude that this short-time model of hypercoagulability in rabbits reliably induced disseminated intravascular coagulation. Tracheostomy and mechanical ventilation provided a reproducible model in which the differences between the controls and the endotoxin-treated animals were exclusively due to administration of endotoxin and not to unforeseen complications of the respiratory system. This model allows the study of therapeutic effects of coagulation inhibitors on endotoxin-induced changes.

Animals↗
PubMed1994

[The effect of substitution with AT III- and PPSB-concentrates in patients with terminal liver insufficiency].

UNLABELLED: Patients with end-stage liver disease frequently develop combined coagulopathies due to increased procoagulant and fibrinolytic turnover as well as thrombocytopenia. The onset of clinical symptoms of a haemorrhagic diathesis requires balanced substitution of coagulation factors, since fresh frozen plasma alone does not always maintain a sufficient haemostatic potential in these patients. This substitution commonly follows standard rules based on the assumption that 0.5-1 IU of a coagulation factor or inhibitor concentrate given per kg body weight will increase its endogenous activity by 1%. We set out to investigate the validity of this standard regime in patients with end-stage liver disease scheduled for orthotopic liver transplantation. PATIENTS AND METHODS: Fifty-one adult patients were prospectively studied. In 37 patients with antithrombin III (AT III) activity < 70%, an AT III preparation (Kybernin, Behring, Marburg, Germany) was given preoperatively (mean dose 2616 +/- 207 IU) following standard calculations in order to increase endogenous activity to 80%. Twenty-seven of the patients had chronic hepatic failure (CHF group) with histologically proven cirrhosis and 10 had acute hepatic failure (AHF group). Blood samples were drawn prior to a 15-min infusion of AT III concentrate and 30 min thereafter. In 14 patients with prothrombin time (PT) < 40%, AT III levels had been corrected earlier during the clinical course to achieve activities > 70%. Prothrombin complex (PPSB, Beriplex, Behring, Marburg, Germany) was substituted (mean dose 2304 +/- 289 IU) to increase procoagulant activity to PT > 60%. Blood samples were drawn in the same fashion as in the AT III group. The amounts of AT III and PPSB concentrates (delta AT III, [IU/kg]; delta PPSB [IU/kg]) required to increase AT III activity and PT, respectively, by 1% were calculated. RESULTS: Standard calculations for AT III substitution indicated AT III recovery in all 37 patients who received AT III concentrate. However, there was a statistically significant difference between patients with CLF and ALF. In patients with CLF, delta AT III was found to be 0.8 IU/kg (+/- 0.1 SEM) and in those with ALF it was 1.5 IU/kg (+/- 0.1 SEM) (P < 0.05, t-test). In patients treated with PPSB concentrate, delta PPSB was 1.6 U/kg (+/- 0.2 SEM) for both CLF and ALF groups. CONCLUSIONS: In patients with end-stage liver disease standard rules for substitution with AT III-concentrate are adequate only for patients with CLF. In patients with ALF higher AT III doses are required to achieve the expected effect on endogenous AT III activity. Procoagulant activity, as reflected by PT, can be increased by 1% when 1.6 IU/kg PPSB concentrate is given. However, this study shows the effects of coagulation concentrates only 30 min after administration. An increased volume of distribution and increased turnover may explain the poor recovery of AT III activity in the ALF group, indicating that the dose of coagulation concentrate should be estimated against the background of the patient's clinical symptoms and diagnosis.

Adult↗
PubMed1994

[Diagnosis and therapy of disseminated intravascular coagulation].

Consumptive coagulation disorders are frequently observed in critically ill patients secondary to other underlying diseases. Initial hypercoagulability leads to subsequent hypocoagulability due to consumption of procoagulant proteins, inhibitors, and platelets. This process evolves in three distinct phases: an initial increase in coagulation activity is characterised by the activation of coagulation factors and platelets without any clinical symptoms of a haemorrhagic diathesis. The ongoing process of activation and accelerated consumption of coagulation factors and inhibitors causes a critical reduction in the haemostatic potential. The time of onset of the clinical symptoms of bleeding depends on the patient's underlying disease and its pharmacological management. Coagulation processes that are restricted locally under normal conditions become disseminated when the inhibitory potential--mainly represented by antithrombin III (AT III)--is exhausted. Therefore, thrombin formation occurs, especially in the microcirculation, where fibrin clot deposition begins to cause inhomogeneities of blood flow and thus to reduce oxygen delivery to the tissues. Hypocoagulability, reactive hyperfibrinolysis, and diffuse bleeding lead to an irreversible systemic breakdown of haemostatic mechanisms (disseminated intravascular coagulation, DIC). The laboratory diagnosis of accelerated consumption is based on the course of global coagulation tests (e.g., prothrombin time, activated partial thromboplastin time, platelet count) and more sensitive ("dynamic") activation parameters such as prothrombin fragment F1 + 2, thrombin-AT III complex, fibrin monomers, or d-dimer. Measurements of plasminogen, tissue plasminogen activator, plasminogen activator inhibitor 1, and alpha 2-antiplasmin-plasmin complex provide information on fibrinolytic turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Critical Care↗