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At least 1,063 records · Page 59Linked to original sources
PubMed1991

Optimal antibody-radionuclide combinations for clinical radioimmunotherapy: a predictive model based on mouse pharmacokinetics.

A theoretical comparison was made of radioimmunotherapy (RIT) dosimetry estimates for eight radionuclides (90Y, 105Rh, 131I, 153Sm, 186Re, 188Re, 198Au, 211At) conjugated to IgG, F(ab')2, and Fab antibody forms. Antibody pharmacokinetics, derived from a nude mouse animal model were combined with appropriate physical data and S values to evaluate absorbed dose to a 0.5 kg centrally located tumor, total body and kidney. Radioimmunoconjugates of F(ab')2 with 90Y, 153Sm and 186Re were predicted to be the most promising for RIT.

Animals↗
PubMedDate not supplied

Model predicting the teratogenic potential of retinyl palmitate, using a combined in vivo/in vitro approach.

Retinyl palmitate (RP) is a known laboratory animal teratogen inducing abnormalities of the second visceral arch when administered on day 9 of gestation in the rat. However, there are significant problems when attempting to extrapolate this result to the human. A combined in vivo/in vitro model was developed to assist in human risk assessment. The in vitro teratogenic threshold concentration of a number of retinyl palmitate metabolites was established. Serum concentrations of retinyl palmitate metabolites following a single teratogenic dose of RP in the pregnant rat were also measured. These dosed sera were also used to culture rat embryos. Our hypothesis was that malformations would only be induced by the dosed sera in vitro if the threshold concentration(s) of one or more metabolites was exceeded. Using this approach, it was determined that the teratogenicity of the sera were best predicted by serum retinol levels, with some indication that all-trans-retinoic acid and 4-oxo-all-trans-retinoic acid could be involved in some cases. The available human data suggest that threshold concentrations of these retinoids were unlikely to be exceeded following vitamin A supplements of 25,000 IU/day. While the proposed model does not take into account species differences, protein binding, and transfer to the embryo, it does have potential for human risk assessment.

Animals↗
PubMed2000

Evaluation of intradialytic solute and fluid kinetics. Setting Up a predictive mathematical model.

A mathematical model of solute kinetics for the improvement of hemodialysis treatment is presented. It includes a two-compartment description of the main solutes and a three-compartment model of body fluids (plasma, interstitial and intracellular). The main model parameters can be individually assigned a priori, on the basis of body weight and plasma concentration values measured before beginning the session. Model predictions are compared with clinical data obtained in vivo during 11 different hemodialysis sessions performed on 6 patients with a profiled sodium concentration in the dialysate and a profiled ultrafiltration rate. In all cases, the agreement between the time pattern of model solute concentrations in plasma and the in vivo data proves fairly good as to urea, sodium, chloride, potassium and bicarbonate kinetics. Only in two sessions was blood volume directly measured in the patient, and in both cases the agreement with model predictions was good. In conclusion, the model allows a priori computation of the amount of sodium removed during hemodialysis, and makes it possible to predict the plasma volume changes and plasma osmolarity changes induced by a given sodium concentration profile in the dialysate and by a given ultrafiltration profile. Hence, it can be used to improve clinical tolerance to the dialysis session taking the characteristics of individual patients into account, in order to minimize intradialytic hypotension.

Bicarbonates↗
PubMed1997

Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model.

Previous studies have shown that approximately 40% of patients with myelodysplastic syndrome (MDS) and anaemia respond to treatment with human recombinant granulocyte-CSF (G-CSF) plus erythropoietin (epo). The present study was designed to investigate pre-treatment variables for their ability to predict erythroid responses to this treatment. 98 patients with MDS (30 RA, 31 RARS, 32 RAEB, five RAEB-t) were treated with a combination of G-CSF (0.3-3.0 microg/kg/d, s.c.) and epo (60-300 U/kg/d, s.c.) for at least 10 weeks. Minimum criteria for erythroid response was a 100% reduction of red blood cell (RBC) transfusion need or an increase in haemoglobin level of > or = 1.5 g/dl. 35 patients (36%) showed responses to treatment. Medium duration of response was 11-24 months. In multivariate analysis, serum erythropoietin levels and initial RBC-transfusion need retained high statistical significance (P < 0.01). Using pre-treatment serum epo levels as a ternary variable (< 100, 100-500 or > 500 U/l) and RBC transfusion need as a binary variable (< 2 or > or = 2 units per month), the analysis provided a predictive score for erythroid response. This score divided patients into three groups: one group with a high probability of erythroid responses (74%), one intermediate group (23%) and one group with poor responses to treatment (7%). This predictive scoring system could be used in decisions regarding use of these cytokines for treating the anaemia of MDS, both for defining patients who should not be given the treatment and for selecting patients for inclusion in prospective trials.

Aged↗
PubMed1993

Serologic determinants of survival in patients with head and neck cancer: validating a clinical prediction model.

Quantitative measurements of serum C1q-binding macromolecules (C1qBM) and immunoglobulin A (IgA) were done on 162 patients using previously described methodology. The measurements were compared to a previously described head and neck cancer population. Using the Cox Proportional Hazards model, the prognostic implications regarding high C1qBM and subsequent death with disease (P = .02), and regional recurrence (P = .0094) were validated, but not our previous IgA-related prognostic implications. When both study populations were combined, C1qBM was predictive of survival in those patients treated with induction chemotherapy (P = .0001). C1qBM was not a significant predictor of survival in patients treated with surgery plus postoperative radiation therapy in either this second "test" population or in the original "training" population. The findings demonstrate the confounding influence of treatment modalities and the importance of model validation.

Age Factors↗
PubMed2006

Modeling predicted that tobacco control policies targeted at lower educated will reduce the differences in life expectancy.

BACKGROUND AND OBJECTIVE: To estimate the effects of reducing the prevalence of smoking in lower educated groups on educational differences in life expectancy. METHODS: A dynamic Markov-type multistate transition model estimated the effects on life expectancy of two scenarios. A "maximum scenario" where educational differences in prevalence of smoking disappear immediately, and a "policy target-scenario" where difference in prevalence of smoking is halved over a 20-year period. The two scenarios were compared to a reference scenario, where smoking prevalences do not change. Five Dutch cohort studies, involving over 67,000 participants aged 20 to 90 years, provided relative mortality risks by educational level, and smoking habits were assessed using national data of more than 120,000 persons. RESULTS: In the reference scenario, the difference in life expectancy at age 40 between highest and lowest educated groups was 5.1 years for men and 2.7 years for women. In the "maximum scenario" these differences were reduced to 3.6 years for men and 1.7 years for women (reduction approximately 30%), and in the "policy target-scenario" differences were 4.7 years for men and 2.4 years for women (reduction approximately 10%). CONCLUSION: Theoretically, educational differences in life expectancy would be reduced by 30% at maximum, if variations in smoking prevalence were eliminated completely. In practice, tobacco control policies that are targeted at the lower educated may reduce the differences in life expectancy by approximately 10%.

Adult↗
PubMed2000

A mathematical outcome prediction model in severe head injury: a pilot study.

103 patients of head injury, with a Glasgow coma scale (GCS) score of 8 or less, were studied prospectively. GCS score, brain stem reflexes, motor score, reaction level scale, and Glasgow Liege scale were evaluated as prognostic variables. Linear logistic regression analysis was used to obtain coefficients of these variables and mathematical formulae developed to predict outcome in individual patients.

Adult↗
PubMed1996

Model prediction of vibration effects on human subject seated on various cushions.

Vertical and horizontal vibrations of a 100 kg seated human body on cushions of various mechanical parameters have been investigated. The vibration inputs were from (a) steering, (b) cushion and (c) a combination of the two. A previously developed model has been used in this study. Resonance frequencies and gains of body segments have been found. The results obtained have been tabulated and presented in graphical manner. It is found that each body segment response depends on the source (steering, cushion or a combination of the two) and the kind (vertical or horizontal) of vibrations as well as the mechanical parameters (mass, stiffness, and damping) of the cushion.

Biomechanical Phenomena↗
PubMed2004

Model predictions of the recruitment of lung units and the lung surface area-volume relationship during inflation.

Experimental evidence suggests that the lung behaves as if it is composed of a large population of units which are recruited and derecruited during lung expansion and contraction. This study combines two previous models in order to estimate the probability distribution function describing lung unit opening pressures and the resulting alveolar surface area-volume relationship of the excised rat lung during inflation. Results indicate that the opening pressures of lung units during inflation can be described by a normal distribution. The end-expiratory pressure (EEP) has a large effect on the number of lung units that open during inflation and the properties of the area-volume relationship of the lung, but the distribution of opening pressures of individual lung units is fairly consistent regardless of EEP. This study also presents evidence that when the normalized lung area-volume relationship is represented by the equation [A(L)]N = [phiV(L)]N(n) during inflation from the closed state, the expansion coefficient n is between 0.86 and 1. This result supports the theory that, for inflation from EEPs below 4 cmH2O, lung expansion occurs in part by the recruitment of lung units and not solely by the expansion of open units.

Adaptation, Physiological↗
PubMed2004

A computational tensegrity model predicts dynamic rheological behaviors in living cells.

Rheological properties of living cells play a key role in the control of cell shape, growth, movement, and contractility, yet little is known about how these properties are governed. Past approaches to understanding cell mechanics focused on the contributions of membranes, the viscous cytoplasm, and the individual filamentous biopolymers that are found within the cytoskeleton. In contrast, recent work has revealed that the dynamic mechanical behavior of cells depends on generic system properties, rather than on a single molecular property of the cell. In this paper, we show that a mathematical model of cell mechanics that depicts the intracellular cytoskeleton as a tensegrity structure composed of a prestressed network of interconnected microfilaments, microtubules, and intermediate filaments, and that has previously explained static cellular properties, also can predict fundamental dynamic behaviors of living cells.

Actin Cytoskeleton↗
PubMed1987

Toward a predictive model of suicidal ideation and behavior: some preliminary data in college students.

Within a multivariate statistical design, the relationship of various interpersonal, emotional, and cognitive variables to suicidal ideation and behavior in college students was examined. A total of 158 subjects (58 males, 100 females) completed self-report measures of life stress, faulty cognitions, loneliness, depression, hopelessness, family cohesiveness, adaptive reasons for living, and suicidal ideation and behavior. The results of a multiple-regression analysis, forward-inclusion algorithm, indicated that a predictive equation consisting of loneliness, irrational beliefs, and low adaptive reasons for living best accounted for suicidal behavior scores. To determine the basic structures and power of the predictor variables under study, a factor analysis and composite regression were employed, resulting in a predictive equation consisting of three factors: Social/Emotional Alienation, Cognitive Distortions, and Deficient Adaptive Resources. Results are discussed in terms of an interactional model of suicidal behavior.

Adult↗
PubMed1995

Bilateral isokinetic variables of the shoulder: a prediction model for young men.

Clinicians frequently want to know the pre-injury strength of an uninjured limb. The purpose of this study was to delineate the differences in bilateral isokinetic peak torque (PT) at 60 degrees and 240 degrees, and torque acceleration energy (TAE), average power (AP) and total work (TW) at 240 degrees during shoulder extension and flexion movements, and to develop a method to determine the expected maximal isokinetic variables of the dominant shoulder based upon isokinetic measurements from the non-dominant shoulder. Shoulder isokinetic measurements were obtained from 30 normal young male adults. While bilateral correlation was significant (P < 0.01), results also suggest significant bilateral differences P < 0.01). Thus, it is inappropriate to use the uninjured extremity to predict the pre-injured strength of the injured side without adjustment. In this investigation models were developed relating the expected maximal isokinetic measurement of the dominant shoulder to the non-dominant shoulder measurements.

Acceleration↗
PubMed2006

A statistical model predicting high hepatocyte proliferation index and the risk of developing hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.

BACKGROUND: Incidence of hepatocellular carcinoma in hepatitis C virus-related cirrhosis is 4% per year. Although cost-effective, current screening could be improved. AIM: To develop a statistical model including non-invasive parameters able to identify patients at high risk of developing hepatocellular carcinoma. METHODS: One hundred and fifty-eight patients (73F:85M) with compensated chronic hepatitis C virus liver disease underwent evaluation, including argyrophilic nucleolar organizer regions proliferation index, and were followed up for 56.18 +/- 1.44 months. RESULTS: Fifty-six patients had chronic hepatitis without cirrhosis and low argyrophilic nucleolar organizer regions proliferation index (< or =25%), 65 had hepatitis C virus-related cirrhosis and low argyrophilic nucleolar organizer regions proliferation index and 37 had hepatitis C virus-related cirrhosis and high argyrophilic nucleolar organizer regions proliferation index (>25%). Groups were similar for gender and viral genotype distribution. None of the patients with chronic hepatitis without cirrhosis developed hepatocellular carcinoma, compared with 6.1% of low argyrophilic nucleolar organizer regions proliferation index and 30.6% of high argyrophilic nucleolar organizer regions proliferation index (P = 0.002). By multivariable logistic regression analysis, the following parameters were independently associated with hepatocellular carcinoma development and used for the development of the statistical model: platelets (OR 0.98), gamma-globulins (OR 0.111), alanine aminotransferase/aspartate aminotransferase ratio (OR 0.07), serum ferritin (OR 1.0) and ultrasonographic pattern (coarse OR 2.9, coarse nodular OR 10.12). The statistical model properly allocated 95.9% of patients with low argyrophilic nucleolar organizer regions proliferation index and 72.2% of patients with high argyrophilic nucleolar organizer regions proliferation index. CONCLUSIONS: The model, to be validated in large prospective studies, may help tailoring screening according to the risk of hepatocellular carcinoma development.

Adult↗
PubMed2003

Infusion reactions to infliximab in children and adolescents: frequency, outcome and a predictive model.

BACKGROUND: Crohn's disease commonly affects children and adolescents, however the majority of research into the safety and efficacy of therapies for inflammatory bowel disease, including infliximab, has occurred only in adults. AIM: To determine the rate of reactions in children following infliximab infusions, and to identify variables that might be predictive of those reactions. METHODS: We performed a retrospective review of all infliximab infusions performed at Columbus Children's Hospital from December 1998 through September 2001. RESULTS: Fifty-seven children received 361 infusions. Three hundred and fifty-five of the 361 infusions (98.3%) were completed. Fifty children had 304 repeat infusions. There were a total of 35 infusion related reactions. Female gender and the use of immunosuppressive medications for less than 4 months were risk factors for a reaction to infusion number 2. A reaction to infusion 2 and immunosuppressive use for less than 4 months were risk factors for infusion number 3. CONCLUSIONS: The rate of infusion reactions in children receiving infliximab is similar to that in adults. Female gender, immunosuppressive use for less than 4 months and prior infusion reactions may be risk factors for subsequent infusion reactions in children.

Adolescent↗
PubMed2005

A medical bioinformatics approach for metabolic disorders: biomedical data prediction, modeling, and systematic analysis.

UNLABELLED: During the past century, studies of metabolic disorders have focused research efforts to improve clinical diagnosis and management, to illuminate metabolic mechanisms, and to find effective treatments. The availability of human genome sequences and transcriptomic, proteomic, and metabolomic data provides us with a challenging opportunity to develop computational approaches for systematic analysis of metabolic disorders. In this paper, we present a strategy of bioinformatics analysis to exploit the current data available both on genomic and metabolic levels and integrate these at novel levels of understanding of metabolic disorders. PathAligner is applied to predict biomedical data based on a given disorder. A case study on urea cycle disorders is demonstrated. A Petri net model is constructed to estimate the regulation both on genomic and metabolic levels. We also analyze the transcription factors, signaling pathways and associated disorders to interpret the occurrence and regulation of the urea cycle. AVAILABILITY: PathAligner's metabolic disorder analyzer is available at http://bibiserv.techfak.uni-bielefeld.de/pathaligner/pathaligner_MDA.html. Supplementary materials are available at http://www.techfak.uni-bielefeld.de/~mchen/metabolic_disorders.

Animals↗