The role of cell-free DNA measured by a fluorescent test in the management of isolated traumatic head injuries

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. In this study a new method to measure cell free DNA (CFD) for the management of TBI is tested. Our hypothesis was that CFD concentrations correlate to the magnitude of brain damage, and may predict the outcome of injured patients. METHODS: Twenty eight patients with isolated head injury were enrolled. Their demographic and clinical data were recorded. CFD levels were determined in patients' sera samples by a direct fluorescence method developed in our laboratory. RESULTS: Mean admission CFD values were lower in patients with mild TBI compared to severe injury (760 ± 340 ng/ml vs. 1600 ± 2100 ng/ml, p = 0.03), and in patients with complete recovery upon discharge compared to patients with disabilities (680 ± 260 ng/ml vs. 2000 ± 2300 ng/ml, p = 0.003). Patients with high CFD values had a relative risk to require surgery of 1.5 (95% CI 0.83 to 2.9) a relative risk to have impaired outcome on discharge of 2.8 (95% CI 0.75 – 10), and a longer length of stay (12 ± 13 days vs. 3.4 ± 4.8 days, p = 0.02). CFD values did not correlate with CT scan based grading. CONCLUSIONS: CFD levels may be used as a marker to assess the severity of TBI and to predict the prognosis. Its use should be considered as an additional tool along with currently used methods or as a surrogate for them in limited resources environment

The role of cell-free DNA measured by a fluorescent test in the management of isolated traumatic head injuries.

BackgroundTraumatic brain injury (TBI) is a major cause of death and disability. In this study a new method to measure cell free DNA (CFD) for the management of TBI is tested. Our hypothesis was that CFD concentrations correlate to the magnitude of brain damage, and may predict the outcome of injured patients.MethodsTwenty eight patients with isolated head injury were enrolled. Their demographic and clinical data were recorded. CFD levels were determined in patients' sera samples by a direct fluorescence method developed in our laboratory.ResultsMean admission CFD values were lower in patients with mild TBI compared to severe injury (760 ± 340 ng/ml vs. 1600 ± 2100 ng/ml, p = 0.03), and in patients with complete recovery upon discharge compared to patients with disabilities (680 ± 260 ng/ml vs. 2000 ± 2300 ng/ml, p = 0.003). Patients with high CFD values had a relative risk to require surgery of 1.5 (95% CI 0.83 to 2.9) a relative risk to have impaired outcome on discharge of 2.8 (95% CI 0.75 - 10), and a longer length of stay (12 ± 13 days vs. 3.4 ± 4.8 days, p = 0.02). CFD values did not correlate with CT scan based grading.ConclusionsCFD levels may be used as a marker to assess the severity of TBI and to predict the prognosis. Its use should be considered as an additional tool along with currently used methods or as a surrogate for them in limited resources environment

The role of cell-free DNA measured by a fluorescent test in the management of isolated traumatic head injuries.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. In this study a new method to measure cell free DNA (CFD) for the management of TBI is tested. Our hypothesis was that CFD concentrations correlate to the magnitude of brain damage, and may predict the outcome of injured patients. METHODS: Twenty eight patients with isolated head injury were enrolled. Their demographic and clinical data were recorded. CFD levels were determined in patients sera samples by a direct fluorescence method developed in our laboratory. RESULTS: Mean admission CFD values were lower in patients with mild TBI compared to severe injury (760 ± 340 ng/ml vs. 1600 ± 2100 ng/ml, p = 0.03), and in patients with complete recovery upon discharge compared to patients with disabilities (680 ± 260 ng/ml vs. 2000 ± 2300 ng/ml, p = 0.003). Patients with high CFD values had a relative risk to require surgery of 1.5 (95% CI 0.83 to 2.9) a relative risk to have impaired outcome on discharge of 2.8 (95% CI 0.75 - 10), and a longer length of stay (12 ± 13 days vs. 3.4 ± 4.8 days, p = 0.02). CFD values did not correlate with CT scan based grading. CONCLUSIONS: CFD levels may be used as a marker to assess the severity of TBI and to predict the prognosis. Its use should be considered as an additional tool along with currently used methods or as a surrogate for them in limited resources environment

Increased Paracetamol Bioavailability after Sleeve Gastrectomy: A Crossover Pre- vs. Post-Operative Clinical Trial

Oral drug bioavailability may be significantly altered after laparoscopic sleeve gastrectomy (LSG), the most popular bariatric procedure worldwide. Paracetamol (acetaminophen) is the post-bariatric analgesic/antipyretic drug of choice. In this work we studied and analyzed the LSG effects on systemic bioavailability and pharmacokinetics of paracetamol after oral administration of solid vs. liquid dosage form. A 4-armed, pharmacokinetic, crossover trial was performed in patients enrolled for LSG. Single paracetamol dose (500 mg), as caplet (n = 7) or syrup (n = 5), was administered before vs. 4–6 months post-LSG. Bioavailability was enhanced after LSG; in the caplet groups, average AUC0–t increased from 9.1 to 18.6 µg·h/mL with AUC0–t difference of 9.5 µg·h/mL (95% CI 4.6–14.5, p = 0.003). Cmax increased from 1.8 (95% CI 1.2–2.5) to 4.2 µg/mL (3.6–4.8) after LSG (p = 0.032). In the syrup groups, AUC0–t increased from 13.4 to 25.6 µg·h/mL, with AUC0–t difference of 12.2 µg·h/mL (95% CI 0.9–23.5, p = 0.049). Cmax changed from 5.4 (95% CI 2.5–8.4) to 7.8 µg/mL (6.1–9.6), and systemic bioavailability was complete (102%) after the surgery. Overall, decreased paracetamol exposure in obesity, with recovery to normal drug levels (caplet) or even higher (syrup) post-LSG, was revealed. In conclusion, attention to paracetamol effectiveness/safety in obesity, and after bariatric surgery, is prudent

The effect of A₁R agonist, in A_2AR^−/− and in the presence of A_2AR antagonist.

<p>Mice were administrated with A₁R agonist (CHA, 0.1 mg/kg) or vehicle 24 prior to bacterial inoculation. 30 min before inoculation the A_2AR antagonist (ZM241385, 1 mg/kg) or the A_2AR agonist (CGS21680, 1 mg/kg) were administered to the same animals or to untreated animals. (A) sera IL-6 and TNFα (12 hours) and (B) lavage fluids IL-6 and TNFα (12 hours). (C) A_2AR⁻^/− mice or their WT littermates were treated with the A₁R agonist (CHA, 0.1 mg/kg) i.p. or vehicle 24 hours prior to bacterial inoculation. 12 hours following inoculation sera were collected and analyzed for IL-6 and TNFα levels. Data are representative of three individual experiments and are expressed as mean±SEM. * <i>p</i><0.05, ** <i>p</i><0.01 between vehicle and CHA or CGS21680 and between CHA with or without ZM241385, <i>n</i> = 5 for each experiment.</p

A₁R and A_2AR expression in peritoneal leukocytes during inflammation <i>in vivo.</i>

<p>Peritonitis was induced in mice by <i>E. coli</i> inoculation at a sub-lethal dose. To examine the dynamic expression of the two high-affinity adenosine receptors, A₁R and A_2AR, peritoneal lavage was performed at indicated time points. A₁R and A_2AR mRNA levels in peritoneal leukocytes were analyzed by real time PCR and normalized to β-actin levels. Data represent three experiments and are expressed as mean±SEM. * <i>p</i><0.05, between expression levels of each receptor to expression at time 0, <i>n</i> = 5 for each experiment.</p