Platelet concentrates stored for 5 days in a reduced volume of plasma maintain hemostatic function and viability

BACKGROUND: Platelet concentrates prepared from whole blood are generally suspended in a standard volume of 50 to 60 mL of plasma and can be stored thus at 20 to 24 degrees C for up to 5 days. In vitro studies suggested that this plasma volume could be reduced to 30 to 35 mL without impairing platelet function. STUDY DESIGN AND METHODS: This study evaluated whether platelets stored for 5 days in a reduced volume (30-35 mL) of plasma maintained their in vivo viability, hemostatic function, and recovery in recipients. Paired autologous platelet survival studies were done in 20 adult volunteers to assess platelet viability. A rabbit ear bleeding-time model was used to compare the hemostatic effectiveness of human platelet concentrates stored for 5 days in the standard or reduced volume of plasma. Platelet recovery was compared in thrombocytopenic hospital patients. RESULTS: Paired platelet survival studies indicated no significant difference between the values in platelet concentrates stored for 5 days in the reduced volume of plasma and the values in those stored in the standard volume. In the animal model, there was no significant difference in the bleeding times achieved by either set of platelet concentrates. The platelet count increments in thrombocytopenic patients were measured. The platelet count increments in patients who received reduced-volume platelet concentrates were as good as the increments achieved in patients given standard-volume concentrates. CONCLUSION: The in vivo viability, recovery, and hemostatic function of platelets collected in polyvinylchloride plastic containers and stored in 30 to 35 mL of plasma for 5 days are maintained as well as those of platelets stored in 50 to 60 mL of plasma.     

Contribution of the β-ureidopropionase (UPB1) gene alterations to the development of fluoropyrimidine-related toxicity

BackgroundAn impairment of the 5-fluorouracil (5-FU) catabolic pathway, represented by alterations in the dihydropyrimidine dehydrogenase (DPYD) gene, is considered a crucial factor contributing to the development of 5-FU-related toxicity. The β-ureidopropionase (BUP1) enzyme catalyzes the final step in the 5-FU catabolic pathway; however, alterations in the UPB1 gene coding for the BUP1 enzyme have not yet been analyzed in fluoropyrimidine (FP)-treated patients suffering from 5-FU-related toxicity.MethodsWe have performed a mutation analysis of the entire coding sequence of UPB1 based on denaturing high-performance liquid chromatography in 113 cancer patients treated by FP-containing regimes. These patients included 67 individuals suffering from severe 5-FU-related toxicity and 46 individuals with excellent tolerance of chemotherapy.ResultsNine UPB1 variants were detected in the subpopulation of patients with severe toxicity, including a novel mutation affecting the coding sequence (c.872_873 + 11del13). An analysis of UPB1 variants on 5-FU-related toxicity in the population of all analyzed patients revealed an association between the c.-80C > G (rs2070474) variant and gastrointestinal toxicity. A strong positive correlation was found between the carriers of the c.-80 GG genotype and the development of severe (grade 3–4) mucositis (OR = 7.5; 95% CI = 2.60 – 21.60; p = 0.0002).ConclusionOur results suggest that UPB1 variants may contribute to the development of 5-FU-related toxicity in some FP-treated patients; however, the role of UPB1 alterations is probably less significant than that of DPYD alterations.     

Anatomic variations of the lacunar–canalicular system influence solute transport in bone

Solute transport in the lacunar–canalicular system (LCS) is essential for bone metabolism and mechanotransduction. Using the technique of fluorescence recovery after photobleaching (FRAP) we have been quantifying solute transport in the LCS of murine long bone as a function of loading parameters and molecular size. However, the influence of LCS anatomy, which varies among animal species, bone type and location, age and health condition, is not well understood. In this study, we developed a mathematical model to simulate solute convection in the LCS during a FRAP experiment under a physiological cyclic flow. We found that the transport rate (the reciprocal time constant for refilling the photobleached lacuna) increased linearly with canalicular number and decreased with canalicular length for both diffusion and convection. As a result, the transport enhancement of convection over diffusion was much less sensitive to the variations associated with chick, mouse, rabbit, bovine, dog, horse, and human LCS anatomy, when compared with the rates of diffusion or convection alone. Canalicular density did not affect transport enhancement, while solute size and the lacunar density had more complicated, non-linear effects. This parametric study suggests that solute transport could be altered by varying LCS parameters, and that the anatomical details of the LCS need systemic examination to further understand the etiology of aged and osteoporotic bones.     

Lamotrigine therapy of epilepsy with Angelman's syndrome

PURPOSE: Angelman syndrome (AS) is a neurogenetic disorder characterized by developmental delay and a frequently refractory epileptic condition. Valproate, clonazepam and/or phenytoin are said to be the most effective antiepileptic drugs (AEDs) against the seizures in AS. Experience with the newer AEDs is very limited despite their better safety profile and tolerability. Considering its favorable side effect profile and its effectiveness against both partial and generalized seizures, we hypothesized that lamotrigine (LTG) might be more efficacious and better tolerated. METHODS: Potential patients for this retrospective study were identified from the epilepsy clinics at Notre-Dame, Sainte-Justine, and Yale New Haven hospitals. Patients were included in the study if they had AS along with refractory seizures. The medical record of each patient was reviewed with interest on seizure types, previous AEDs and response to LTG. RESULTS: Five patients (2M, 3F) were included in this study. Age at LTG ranged from 10 to 33 years old. All had >or=2 seizure types, mainly generalized tonic-clonic, myoclonic seizures, and atypical absences. Previously tried AEDs included valproic acid (5), benzodiazepines (5), phenytoin (4), carbamazepine (3), and topiramate (1). One patient had pancreatitis on phenytoin, one had worsened seizures on carbamazepine, and one developed hepatic encephalopathy on valproic acid. Three patients became seizure-free with LTG (9, 20, and 36 months FU), one was seizure-free for 1 year with subsequent loss of efficacy, and one showed >50% reduction in myoclonic seizures (20 months FU). No side effects were reported. CONCLUSION: LTG can be efficacious and well tolerated in patients with AS.     

Determination of endogenous norepinephrine levels in different chambers of the rat heart by capillary electrophoresis coupled with amperometric detection

Capillary electrophoresis with end-column amperometric detection (CE-EC) was used to determine the regional distribution of norepinephrine (NE) in the hearts of sympathetically innervated (control) and chemically sympathectomized rats. Key features of the method are (i) the sample preparation and clean-up step that involved the application of off-line solid phase extraction (SPE) with a 95% NE recovery and (ii) the use of a diamond microelectrode for detection. NE was quantified in the left and right ventricle, the ventricular septum, and the left and right atrium. The NE concentration in the atria was three to five times higher than in the ventricles and ventricular septum of control rats. Basal NE levels in the left and right ventricle and the ventricular septum were reduced to below the detection limit (0.034 microg/g tissue) in tissues treated with the neurotoxin, 6-hydroxydopamine (6-OHDA), while only a moderate reduction was observed in the left and right atrium. Importantly, the diamond microelectrode provided low and stable background current and low peak-to-peak noise 相似文献   

Use of procalcitonin for early prediction of lethal outcome of postoperative sepsis

BACKGROUND: To develop strategies for the prediction of sepsis outcome systemic procalcitonin (PCT) levels were correlated with various clinical parameters. METHODS: PCT levels and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were assessed on the day of sepsis diagnosis in a large series (n = 160) of patients developing sepsis after major visceral surgery. RESULTS: In multivariate analysis, systemic PCT and the APACHE II score could be identified as independent early predictive indicators of lethal sepsis. Combining both indicators at sepsis onset, a prognosis score could be calculated using binary logistic regression analysis allowing the identification of high- and low-risk groups. While 71% of the high-risk patients died of sepsis, 77% of patients assigned to the low-risk group survived the septic complication (sensitivity 71%, specificity 77%). CONCLUSION: Calculation of the prognosis-score allowed for an early prediction of the septic course with high sensitivity and specificity. This information could aid in deciding on adequate treatment strategies.     

An exploratory pilot study of palliative medicine compared to anesthesia-pain consultation for pain in patients with cancer

Oncologists often manage cancer-associated symptoms including pain. When symptoms are severe, anesthesia-pain medicine (APM) and/or palliative medicine (PM) can effectively treat symptoms. Nevertheless, symptom management may be suboptimal, leading to diminished quality of life (QOL). We assessed the value of PM vs. APM consultation in cancer patients referred for pain management alone. Patients referred to an APM-based Cancer Pain Clinic (CPC) over an 8-month period were evaluated by PM or APM based on the first available appointment. Symptoms and QOL were assessed by the MD Anderson Symptom Inventory and Linear Analog Self-Assessment at baseline and 4-6 weeks after initial encounter. Data were analyzed on an available-case basis. Sixty-two patients (37 PM, 25 APM) completed the initial survey, with 48 patients (31 PM, 17 APM) completing followup. Mean pain score improved from 7.97 to 5.47 in the PM group (P < 0.0001) and from 7.1 to 4.5 (P = 0.29) in the APM group. The PM group demonstrated a clinically significant improvement in 8/19 symptoms vs. 3/19 in the APM group and in 3/5 QOL parameters in the PM group vs. 1/5 in the APM group. Our small sample size weakens our power and ability to detect significant differences between the groups. Only one follow-up symptom-assessment point was obtained. PM consultation is as effective as APM in improving cancer pain but may be more effective with symptom management and improving QOL.