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- Hahn, Robert, et al.
(författare)
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Plasma volume expansion from the intravenous glucose tolerance test before and after hip replacement surgery
- 2013
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Ingår i: Theoretical Biology and Medical Modelling. - : Springer Science and Business Media LLC. - 1742-4682. ; 10:48
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHyperosmotic glucose is injected intravenously when an intravenous glucose tolerance test (IVGTT) is initiated. The extent and time period of plasma volume expansion that occurs in response to the glucose load has not been studied in the perioperative setting.MethodsTwenty-two non-diabetic patients aged between 57 and 76 years (mean 68) underwent an IVGTT, during which 0.3 g/kg of glucose 30% (1 ml/kg) was injected as a bolus over one minute, one day before and two days after hip replacement surgery. Twelve blood samples were collected over 75 minutes from each patient. The turnover of both the exogenous glucose and the injected fluid volume was calculated by means of mass balance and volume kinetic analysis.ResultsThe IVGTT raised plasma glucose by 9 mmol/L and the plasma volume by 8%. The extracellular fluid volume increased by 320 (SD 60) ml of which 2/3 could be accounted for in the plasma. The half-life of the exogenous glucose averaged 30 minutes before surgery and 36 minutes postoperatively (P < 0.02). The glucose elimination governed 86% of the decay of the plasma volume expansion, which occurred with a half-life of 12 minutes before to 21 minutes after the surgery (median, P < 0.001).ConclusionHyperosmotic glucose translocated intracellular water to the plasma volume rather than to the entire extracellular fluid volume. The preferential re-distribution acts to dilute the plasma concentrations used to quantify insulin sensitivity and ß-cell function from an IVGTT. The greater-than-expected plasma dilution lasted longer after than before surgery.
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| 2. |
- Konkoli, Zoran, 1966, et al.
(författare)
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Fluctuations in Tat copy number when it counts the most: a possible mechanism to battle the HIV latency
- 2013
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Ingår i: Theoretical Biology and Medical Modelling. - : Springer Science and Business Media LLC. - 1742-4682. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The HIV-1 virus can enter a dormant state and become inactive, which reduces accessibility by antiviral drugs. We approach this latency problem from an unconventional point of view, with the focus on understanding how intrinsic chemical noise (copy number fluctuations of the Tat protein) can be used to assist the activation process of the latent virus. Several phase diagrams have been constructed in order to visualize in which regions of the parameter space noise can drive the activation process. Essential to the study is the use of a hyperbolic coordinate system, which greatly facilitates quantification of how the various reaction rate combinations shape the noise behavior of the Tat protein feedback system. We have designed a mathematical manual of how to approach the problem of activation quantitatively, and introduce the notion of an “operating point” of the virus. For both noise-free and noise-based strategies we show how operating point off-sets induce changes in the number of Tat molecules. The major result of the analysis is that for every noise-free strategy there is a noise-based strategy that requires lower dosage, but achieves the same anti-latency effect. It appears that the noise-based activation is advantageous for every operating point.
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| 3. |
- Mehrara, Esmaeil, 1971, et al.
(författare)
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A new method to estimate parameters of the growth model for metastatic tumours.
- 2013
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Ingår i: Theoretical biology & medical modelling. - : Springer Science and Business Media LLC. - 1742-4682. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Knowledge of natural tumour growth is valuable for understanding tumour biology, optimising screening programs, prognostication, optimal scheduling of chemotherapy, and assessing tumour spread. However, mathematical modelling in individuals is hampered by the limited data available. We aimed to develop a method to estimate parameters of the growth model and formation rate of metastases in individual patients. MATERIALS AND METHODS: Data from one patient with liver metastases from a primary ileum carcinoid and one patient with lung metastases from a primary renal cell carcinoma were used to demonstrate this new method. Metastatic growth models were estimated by direct curve fitting, as well as with the new proposed method based on the relationship between tumour growth rate and tumour volume. The new model was derived from the Gompertzian growth model by eliminating the time factor (age of metastases), which made it possible to perform the calculations using data from all metastases in each patient. Finally, the formation time of each metastasis and, consecutively, the formation rate of metastases in each patient were estimated. RESULTS: With limited measurements in clinical studies, fitting different growth curves was insufficient to estimate true tumour growth, even if patients were followed for several years. Growth of liver metastases was well described with a general growth model for all metastases. However, the lung metastases from renal cell carcinoma were better described by heterogeneous exponential growth with various growth rates. CONCLUSION: Analysis of the regression of tumour growth rate with the logarithm of tumour volume can be used to estimate parameters of the tumour growth model and metastasis formation rates, and therefore the number and size distribution of metastases in individuals.
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