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Biomedical subjects

D Jäger

Publications and source records attributed to D Jäger.

At least 55 records · Page 3Linked to original sources
PubMed2000

Identification of NY-ESO-1 epitopes presented by human histocompatibility antigen (HLA)-DRB4*0101-0103 and recognized by CD4(+) T lymphocytes of patients with NY-ESO-1-expressing melanoma.

NY-ESO-1 is a member of the cancer-testis family of tumor antigens that elicits strong humoral and cellular immune responses in patients with NY-ESO-1-expressing cancers. Since CD4(+) T lymphocytes play a critical role in generating antigen-specific cytotoxic T lymphocyte and antibody responses, we searched for NY-ESO-1 epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules. Autologous monocyte-derived dendritic cells of cancer patients were incubated with recombinant NY-ESO-1 protein and used in enzyme-linked immunospot (ELISPOT) assays to detect NY-ESO-1-specific CD4(+) T lymphocyte responses. To identify possible epitopes presented by distinct HLA class II alleles, overlapping 18-mer peptides derived from NY-ESO-1 were synthetized and tested for recognition by CD4(+) T lymphocytes in autologous settings. We identified three NY-ESO-1-derived peptides presented by DRB4*0101-0103 and recognized by CD4(+) T lymphocytes of two melanoma patients sharing these HLA class II alleles. Specificity of recognition was confirmed by proliferation assays. The characterization of HLA class II-restricted epitopes will be useful for the assessment of spontaneous and vaccine-induced immune responses of cancer patients against defined tumor antigens. Further, the therapeutic efficacy of active immunization using antigenic HLA class I-restricted peptides may be improved by adding HLA class II-presented epitopes.

Alleles↗
PubMed2000

[Health promotion and cardiovascular risk factors. The level of knowledge among 510 inpatients of an acute coronary care unit].

PATIENTS AND METHODS: A total of 510 patients hospitalized on a cardiologic ward were questioned on cardiovascular disease risk factors using a questionnaire. The knowledge on these risk factors was assessed with a score system. RESULTS: Knowledge of patients on cardiovascular disease risk factors was generally low: One out of 5 did not know about the consequences of obesity, high blood cholesterol or smoking on the coronary vessels. Over 30% did not name hypertension. Only 1 out of 3 patients mentioned diabetes mellitus as a risk factor. There was no change in the knowledge during the hospital stay despite a standardized and intensive information program. The results of the second survey on the day of discharge were equal to the results of the admission day. Hospital stays in the past had no influence on the knowledge. Patients with a diagnosed coronary heart disease had the same results in the survey as patients with other diseases. The presence of risk factors had hardly any influence on the knowledge of these patients. CONCLUSION: The result of this study emphasizes the need for better health information for patients. The repetitive information on health related issues during inpatient treatment does not seem to have a positive effect on patients' knowledge. Therefore other ways of health education have to be introduced and evaluated in acute care.

Adult↗
PubMed2000

Heterogeneity of cardiac rat and human elongation factor 2.

Elongation factor 2 (EF-2) catalyses the last step of the elongation cycle, translocation, in the course of protein biosynthesis. A system for analyzing post-translational modifications of EF-2, which is a single polypeptide of 857 amino acids, is reported and its application to cytosolic extracts of cultured neonatal rat heart myocytes, neonatal and adult rat cardiac tissue, and extracts of human left ventricular myocardium is described. Comparing different pH ranges in immobilized pH gradient-isoelectric focusing (IPG-IEF), a range of pH 3 - 10 and 4 - 9 resulted in a highly defined and reproducible resolution of six different EF-2 variants of all extracts in the first dimension. These six variants were detected by the "imaging plate" (phosphor radiation image sensor) after specific labeling with Pseudomonas exotoxin A catalyzed [32P]ADP-ribosylation. This finding could be confirmed in Western blot analysis with a specific polyclonal rabbit antibody. Using two-dimensional polyacrylamide gel electrophoresis (2-D-PAGE), five to six EF-2 variants could be demonstrated in all extracts. By application of a second IPG indicator strip to the 2-D gel, they could be aligned with corresponding spots in a silver-stained 2-D separation of human myocardial tissue, revealing that the EF-2 variants belong to the group of low-abundance proteins.

Adenosine Diphosphate Ribose↗
PubMed2000

Cancer immunotherapy in clinical oncology.

The identification of tumor-associated antigens recognized by cellular or humoral effectors of the immune system has opened new perspectives for cancer therapy. Different groups of cancer-associated antigens have been described as targets for cytotoxic T lymphocytes (CTLs) in vitro and in vivo: 1) cancer-testis (CT) antigens, which are expressed in different tumors and normal testis; 2) melanocyte differentiation antigens; 3) point mutations of normal genes; 4) antigens that are overexpressed in malignant tissues; and 5) viral antigens. Clinical studies with peptides derived from these antigens have been initiated to induce specific CTL responses in vivo. Immunological and clinical parameters for the assessment of peptide-specific reactions have been defined, i.e., delayed-type hypersensitivity (DTH), CTL, autoimmmune, and tumor regression responses. Preliminary results demonstrate that tumor-associated peptides alone elicit specific DTH and CTL responses leading to tumor regression after intradermal injection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was proven effective in enhancing peptide-specific immune reactions by amplification of dermal peptide-presenting dendritic cells. Long-lasting complete tumor regressions have been observed after induction of peptide-specific CTLs. However, in single cases with disease progression after an initial tumor response, either a loss of the respective tumor antigen targeted by CTLs or of the presenting major histocompatibility complex (MHC) class I allele was detected as a mechanism of immune escape under immunization. Based on these observations, cytokines to enhance antigen and MHC class I expression in vivo are being evaluated to prevent immunoselection. Recently, a strategy utilizing spontaneous antibody responses to tumor-associated antigens (SEREX) has led to the identification of a new CT antigen, NY-ESO-1, which is regarded as one of the most immunogenic antigens known today inducing spontaneous immune responses in 50% of patients with NY-ESO-1-expressing cancers. Clinical studies involving antigenic constructs that induce both antibody and CTL responses will show whether these are more effective for immunotherapy of cancer.

Animals↗
PubMed1999

[Problems of clinical evaluation of hemodynamics at rest and during exercise in chronic heart disease. Value of cardiac catheterization and problems of clinical classification].

BACKGROUND: NYHA classification is mostly used for graduation of clinical limitation due to cardiac failure. Right heart catheterization is not generally used to evaluate hemodynamics and to define the effects of drugs in patients with chronic cardiac failure. Clinical data and results from echocardiography, stress tests or nuclear cardiology seem to be sufficient. Our aim was to demonstrate subjectivity of a classification system (NYHA) comparing the graduation done by physicians and by patients and to represent the difficulty to prognosticate hemodynamic data of patients with heart failure. PATIENTS AND METHODS: Limitation of 53 patients with heart diseases was classified by physicians and patients using NYHA classification. Pulmonary capillary wedge pressure (PCWP), stroke volume (SV) and cardiac output were predicted by physicians; they were allowed to utilize all examination data they could get. Predicted hemodynamic data were compared with the results of measurement at rest and during exercise. RESULTS: Patients classified themselves significantly worse than physicians did: 2.68 +/- 0.64 vs. 2.23 +/- 0.74 (p = 0.0012). Similarity in NYHA classification was found in 29/53 cases. Correlation of predicted and measured hemodynamic data was low: PCWP (at rest) r = 0.346; PCWP (during exercise) r = 0.232; SV (at rest) r = 0.476; SV (during exercise) r = 0.445; HMV (at rest) r = 0.412; HMV (during exercise) r = 0.538. CONCLUSION: Clinical classification systems like NYHA are subjective, classification by physicians differs significantly from classification by patients. Prediction of hemodynamics is not possible despite all examination data had been available. Right heart catheterization is necessary to define hemodynamics at rest and during exercise.

Cardiac Catheterization↗
PubMed1999

Cancer-testis antigens and ING1 tumor suppressor gene product are breast cancer antigens: characterization of tissue-specific ING1 transcripts and a homologue gene.

SEREX (serological analysis of recombinant tumor cDNA expression libraries) has been applied to several different tumor types and has led to the identification of a wide range of tumor antigens. In this study, a breast cancer library and a normal testicular library were analyzed using autologous and allogeneic breast cancer sera. Thirty genes were isolated, including 27 known genes and 3 previously unknown genes. Among the known genes, two cancer-testis (CT) antigens, NY-ESO-1 and SSX2, previously defined by SEREX analysis, were found. In addition, ING1, a candidate breast cancer suppressor gene, was isolated. This ING1 gene product was also recognized by 2 of 14 allogeneic sera from breast cancer patients but not 12 normal adult sera. Comparison of ING1 cDNA from normal and tumor tissues showed no mutation in the index breast cancer case and revealed the presence of at least three different mRNA transcripts with variable transcription initiation sites and exon usage. Tissue-specific expression of these transcripts was found in normal tissues and tumor cell line mRNAs. Furthermore, a novel gene, designated as ING2, sharing 76% nucleotide homology with ING1 was identified in the breast cancer cDNA library. The basis of the immunogenicity of ING1 and the biological role of ING1 and ING2 need further exploration.

Alternative Splicing↗
PubMed1999

Antigens recognized by autologous antibody in patients with renal-cell carcinoma.

The screening of cDNA expression libraries derived from human tumors with autologous antibody (SEREX) is a powerful method for defining the structure of tumor antigens recognized by the humoral immune system. Sixty-five distinct antigens (NY-REN-1 to NY-REN-65) reactive with autologous IgG were identified by SEREX analysis of 4 renal cancer patients and were characterized in terms of cDNA sequence, mRNA expression pattern, and reactivity with allogeneic sera. REN-9, -10, -19, and -26 have a known association with human cancer. REN-9 (LUCA-15) and REN-10 (gene 21) map to the small cell lung cancer tumor suppressor gene locus on chromosome 3p21.3. REN-19 is equivalent to LKB1/STK11, a gene that is defective in Peutz-Jeghers syndrome and cancer. REN-26 is encoded by the bcr gene involved in the [t(9:22)] bcr/abl translocation. Genes encoding 3 of the antigens in the series showed differential mRNA expression; REN-3 displays a pattern of tissue-specific isoforms, and REN-21 and REN-43 are expressed at a high level in testis in comparison to 15 other normal tissues. The other 62 antigens were broadly expressed in normal tissues. With regard to immunogenicity, 20 of the 65 antigens reacted only with autologous sera. Thirty-three antigens reacted with sera from normal donors, indicating that their immunogenicity is not restricted to cancer. The remaining 12 antigens reacted with sera from 5-25% of the cancer patients but not with sera from normal donors. Seventy percent of the renal cancer patients had antibodies directed against one or more of these 12 antigens. Our results demonstrate the potential of the SEREX approach for the analysis of the humoral immune response against human cancer.

Aged↗
PubMed1999

Humoral immune responses of cancer patients against "Cancer-Testis" antigen NY-ESO-1: correlation with clinical events.

Humoral immune responses against the "Cancer-Testis" (CT) antigen NY-ESO-1 are frequently observed in patients with NY-ESO-1 expressing tumors. This is in contrast to other known tumor antigens (TA) defined by antibody or cytotoxic T cell (CTL) reactivity, i.e., MAGE-1, MAGE-3, SSX2, Melan A, and tyrosinase. No NY-ESO-1 antibody has been detected in healthy controls and patients with NY-ESO-1 negative tumors. In this study, we have assessed the NY-ESO-1 serum antibody response in patients with NY-ESO-1 positive tumors of different histological types and stages using Western blotting and an ELISA. Of the 12 patients analyzed, 10 had demonstrable NY-ESO-1 antibodies at the start of the study. All patients were followed for changes in NY-ESO-1 antibody titers during the course of tumor treatment and clinical evolution. In 4 patients, an increase of NY-ESO-1 antibody titer was observed with progression of disease or extensive tumor necrosis under treatment. One patient showed a stable NY-ESO-1 antibody titer over 3 years along with gradual regression of a large tumor mass. In 5 patients, a decrease of NY-ESO-1 antibody was detected: in 1 patient after curative tumor resection, in 3 patients with partial regression of metastatic disease under chemo- and immunotherapy, and in another patient with a NY-ESO-1 negative tumor relapse. Our results indicate that the induction and maintenance of NY-ESO-1 antibody is dependent on the presence of NY-ESO-1 expressing tumors. Furthermore, changes in NY-ESO-1 antibody titers correlate with the evolution of NY-ESO-1 positive disease.

Adult↗
PubMed1999

[RIS modality interfaces. From proprietary solutions to DICOM worklist management].

Radiologic information systems (RIS) and picture archiving and communication systems (PACS) are becoming increasingly widespread. This leads to new demands on the integration of the individual, formerly independent information systems (RIS, modalities, PACS). Possible ways of integrating individual systems are introduced. Besides the detailed description of different realizations of system communication, its role in the PACS at the university hospital in Freiburg is explained. The integration of different information systems still requires the use of proprietary interfaces. An appropriate integration generally has been realized in Freiburg. In the near future DICOM basic worklist management will standardize system integration and render an interdepartmental workflow concept possible. Even though an available communication standard exists, not all problems in the RIS-modality interface are solved. Different data models in the various RI systems and modalities demand certain degrees of freedom in the standard. Thus a satisfactory workflow cannot be guaranteed even when all involved systems conform with the standard.

Germany↗
PubMed1999

[Modern network technologies for data communication in the hospital].

Modern network technologies provide the basic infrastructure for information and communication systems in the hospital today. The goal to build up a universal network infrastructure which meets the broadly varied requirements. Analysis of data communication in the hospital and the evaluation of established network technologies, as well as new developments, leads to the switching concept as the suitable solution. Two technologies play the major role in building enterprise networks: the Ethernet family, based on frame switching, and ATM, based on cell switching. Orientation on established standards is the key to free system choice and grants interoperability between systems from different manufacturers. However, the network design must meet the application and system architecture of the information technology in order to achieve successful mapping of the involved communication profiles. This means scaling of the bandwidth as needed, suitable segmenting of the network and resilient links. In a further step, policy-based networking takes advantages of prioritizing critical applications and therefore reduces interdependencies across the network.

Computer Systems↗
PubMed1999

Comparison of the efficacy and safety of aspirin alone with coumadin plus aspirin after provisional coronary stenting: final and follow-up results of a randomized study.

BACKGROUND: The antithrombotic benefit of the conventional treatment with coumadin after coronary stenting is limited by bleeding complications. However, the superiority of an antiplatelet therapy with aspirin alone compared with coumadin plus aspirin has not been proven by randomized studies. The efficacy and safety of treatment with aspirin alone in comparison to coumadin plus aspirin were evaluated in this randomized study. METHODS: Out of 164 patients aged 59.7 +/- 9.2 years, 79 patients were randomly assigned to receive 100 mg aspirin daily (group A) and 85 patients randomly assigned to coumadin plus aspirin (group CA) after provisional coronary stenting with a high-pressure technique. The primary end point was defined as the absence of death, subacute closure of the target vessel, myocardial infarction, urgent coronary bypass surgery, repeated coronary angioplasty, and peripheral vascular complications requiring transfusion or surgery. High-pressure inflation technique was used, but ultrasound guidance was not. RESULTS: During hospitalization (median 8 days), 135 patients (82. 3%) were free of events (A, 84.8%; CA, 80.8%; P =.42). Eleven (6.7%) subacute closures occurred (A, 10.1%; CA, 3.5%; P =.09); 2 of them were lethal in the aspirin group. Emergency bypass surgery was performed in 1 patient in each group. Peripheral vascular complications were observed in 13 patients (7.9%) (A, 1.3%; CA, 14. 1%; P <.01). At 3-month follow-up, 15 (9.1%) elective revascularization procedures (A, 7.6%; CA, 10.6%; P =.51) were performed. CONCLUSION: Aspirin alone at the low dose of 100 mg administered or the combination of coumadin and aspirin after high-pressure coronary stenting does not prevent adverse clinical events when ultrasound guidance is not used.

Angioplasty, Balloon, Coronary↗
PubMed1999

CTL-defined cancer vaccines: perspectives for active immunotherapeutic interventions in minimal residual disease.

The characterization of tumor-associated antigens recognized by cellular or humoral effectors of the immune system has opened new perspectives for cancer therapy. Several categories of cancer-associated antigens have been described as targets for cytotoxic T lymphocytes (CTL) in vitro and in vivo: (1) 'Cancer-Testis' (CT) antigens expressed in different tumors and normal testis, (2) melanocyte differentiation antigens, (3) point mutations of normal genes, (4) antigens that are overexpressed in malignant tissues, and (5) viral antigens. Clinical studies with peptides derived from these antigens have been initiated to induce specific CTL responses in vivo. Immunological and clinical parameters for the assessment of peptide-specific reactions have been defined, i.e. induction of DTH-, CTL-, autoimmune-, and tumor-regression responses. Preliminary results demonstrate that tumor-associated peptides alone elicit specific DTH- and CTL-responses leading to tumor regression after intradermal injection. GM-CSF was proven effective to enhance peptide-specific immune reactions by amplification of dermal peptide-presenting dendritic cells. Long lasting complete tumor regressions have been observed after induction of CTL by peptide immunization. Based on these results, active immunotherapy with tumor-associated antigens may be a promising approach for patients with minimal residual disease, who are at high risk for tumor recurrence. However, in single cases with disease progression after an initial tumor response either a loss of the respective tumor antigen targeted by CTL or of the presenting MHC class I molecule was detected as mechanisms of immune escape under immunization in vivo. Based on these observations, cytokines to enhance antigen- and MHC-class I expression in vivo are being evaluated to prevent immunoselection. Recently, a strategy utilizing spontaneous antibody responses to tumor-associated antigens (SEREX) has led to the identification of a new CT antigen, NY-ESO-1. In a melanoma patient with high titer antibody against NY-ESO-1 also a strong HLA-A2 restricted CTL reactivity against the same antigen was found. Clinical studies involving tumor antigens that induce both antibody- and CTL-responses will show whether these are better candidates for immunotherapy of cancer.

Cancer Vaccines↗
PubMed1999

Distribution and antimicrobial activity of ciprofloxacin in human soft tissues.

Interstitial ciprofloxacin concentrations in soft tissues were measured by microdialysis following intravenous administration of 200 mg to each of eight healthy volunteers. Interstitial ciprofloxacin concentrations were significantly lower than corresponding total serum drug concentrations; the interstitium-to-serum concentration ratios ranged from 0.55 to 0.73. An in vitro simulation based on interstitial pharmacokinetics showed a substantially lower antimicrobial activity than did the simulation based on serum pharmacokinetics. Thus, ciprofloxacin concentrations at the site of effect may be subinhibitory although effective concentrations are attained in serum.

Adult↗
PubMed1998

[Costs and fees in health care. Evaluation and assessment by cardiological patients].

PATIENTS AND METHOD: In a pilot study 70 patients treated in the Department of Cardiology were asked to asses the cost of coronary angiography, PTCA, heart transplantation, pacemakers and prosthetic heart valves. Salaries of physicians and nurses should be estimated, and causes of increase of costs in health care be defined. RESULTS: 91.7% patients criticized health care as too expensive but reasonable with regard to output and efficacy. As most important reasons for increase of cost were given "expensive drugs" (70.6%), "great number of drugs" (56.9%) and "increased number of old patients" (56.9%). Costs of coronary angiography were overestimated (twice) and those of PTCA were underestimated (half). Two thirds of the patients guessed the price of pacemakers and prosthetic heart valves much to low. Salaries of physicians had been estimated near the upper reference value, those of nurses near the lower reference value. CONCLUSION: Most of our patients were insufficiently informed about costs in health care. Clarification and more transparency are needed.

Adult↗
PubMed1998

Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes.

A growing number of human tumor antigens have been described that can be recognized by cytotoxic T lymphocytes (CTLs) in a major histocompatibility complex (MHC) class I-restricted fashion. Serological screening of cDNA expression libraries, SEREX, has recently been shown to provide another route for defining immunogenic human tumor antigens. The detection of antibody responses against known CTL-defined tumor antigens, e.g., MAGE-1 and tyrosinase, raised the question whether antibody and CTL responses against a defined tumor antigen can occur simultaneously in a single patient. In this paper, we report on a melanoma patient with a high-titer antibody response against the "cancer-testis" antigen NY-ESO-1. Concurrently, a strong MHC class I-restricted CTL reactivity against the autologous NY-ESO-1-positive tumor cell line was found. A stable CTL line (NW38-IVS-1) was established from this patient that reacted with autologous melanoma cells and with allogeneic human histocompatibility leukocyte antigen (HLA)-A2(-), NY-ESO-1-positive, but not NY-ESO-1-negative, melanoma cells. Screening of NY-ESO-1 transfectants with NW38-IVS-1 revealed NY-ESO-1 as the relevant CTL target presented by HLA-A2. Computer calculation identified 26 peptides with HLA-A2-binding motifs encoded by NY-ESO-1. Of these, three peptides were efficiently recognized by NW38-IVS-1. Thus, we show that antigen-specific humoral and cellular immune responses against human tumor antigens may occur simultaneously. In addition, our analysis provides a general strategy for identifying the CTL-recognizing peptides of tumor antigens initially defined by autologous antibody.

Aged↗
PubMed1998

Strategies for the development of vaccines to treat breast cancer.

The characterization of tumor-associated antigens recognized by cellular or humoral effectors of the immune system has opened new perspectives for cancer therapy. Several categories of cancer-associated antigens have been described as targets for cytotoxic T lymphocytes (CTLs) in vitro and in vivo: "cancer-testis" (CT) antigens expressed in different tumors and normal testis, melanocyte differentiation antigens, point mutations of normal genes, antigens that are overexpressed in malignant tissues, and viral antigens. Clinical studies using peptides derived from these antigens have been initiated to induce specific CTL responses in vivo. Immunological and clinical parameters for the assessment of peptide-specific reactions have been defined, i.e., induction of delayed-type hypersensitivity (DTH), CTL, autoimmune, and tumor regression responses. Preliminary results demonstrate that tumor-associated peptides alone elicit specific DTH and CTL responses leading to tumor regression after intradermal injection. GM-CSF was proved to be effective in enhancing peptide-specific immune reactions by amplification of dermal peptide-presenting dendritic cells. Long-lasting complete tumor regressions have been observed after induction of CTLs by peptide immunization. However, in a few cases where there was disease progression after initial tumor response, loss of either the tumor antigen targeted by CTLs or of the presenting MHC class I molecule was detected as the mechanism of immune escape under immunization in vivo. Based on these observations, cytokines to enhance antigen and MHC class I expression in vivo are being evaluated to prevent immunoselection. Recently, a strategy utilizing spontaneous antibody responses to tumor-associated antigens (SEREX) has led to the identification of a new CT antigen, NY-ESO-1. In a melanoma patient with high titer antibody against NY-ESO-1, strong HLA-A2-restricted CTL reactivity against the same antigen was also found. Clinical studies involving tumor antigens that induce both antibody and CTL responses will show whether these are better candidates for immunotherapy of cancer.

Antigen-Antibody Reactions↗
PubMed1998

Direct assessment of peripheral pharmacokinetics in humans: comparison between cantharides blister fluid sampling, in vivo microdialysis and saliva sampling.

AIMS: Skin blister fluid sampling, in vivo microdialysis and saliva sampling are commonly employed as surrogates for the measurement of drug concentrations in peripheral compartments. Although expected to exhibit comparable results, data derived from these techniques have never been directly compared. Thus, the aim of the present study was to evaluate the comparability of these techniques. METHODS: Paracetamol, a model drug with low protein binding, was administered to seven healthy volunteers at an oral dose of 2000 mg. Subsequently, tissue kinetics were measured simultaneously in cantharides induced skin blisters, microdialysates of subcutaneous- and skeletal muscle-tissue and saliva and compared to serum concentrations. RESULTS: Mean ratio (AUCblister/AUCserum) was 0.88 (95% CI, 0.50-1.26), mean ratio (AUCmuscle/AUCserum) was 1.08 (0.67-1.49), mean ratio (AUCsubcutaneous/AUCserum) was 0.96 (0.41-1.51) and mean ratio (AUCsaliva/AUCserum) was 1.83 (1.39-2.27). In this study the concentration profiles after single oral administration differed among the three methods. The time course of the concentration (peripheral compartment)/concentration (serum)-ratios showed that cantharides blister and microdialysate concentrations closely paralleled serum levels. An equilibration period of less than 2 h had to be taken into account for blister measurements. In contrast, saliva concentrations were significantly higher than corresponding serum concentrations. CONCLUSIONS: Skin blister sampling and microdialysis closely mirrored corresponding serum concentrations and, thus, proved to be suitable techniques for the assessment of peripheral compartment pharmacokinetics. In contrast, saliva data overestimated the corresponding serum concentrations.

Acetaminophen↗