肝硬化门脉高压症门脉血流动力学变化及其与食管静脉？…

目的 探讨肝硬化门脉高压症血流动力学变化及其与食管静脉曲张出血（ＥＶＢ）的关系。方法 运用彩色多普勒流速剖面（ＣＤＶＰ）技术检测６９例肝硬化门脉高压症患者和４６例正常人门静脉主干（ＰＴ）,右前支（ＲＡＢ）及脾静脉（ＳＶ）的最大截面平均流速（ＣＳ－Ｖｍａｘ）,流量,瘀血指数（ＣＩ）,剖面参数ｎ值和流量历时变化曲线,比较ＥＶＢ史阳性和阴性两组间的血流动力学差异,多元线性回归分析与ＥＶＢ相关的因素。结果     

Resistance to pefloxacin in Pseudomonas aeruginosa.

Mechanisms of resistance to pefloxacin were investigated in four isogenic Pseudomonas aeruginosa strains: S (parent isolate; MIC, 2 micrograms/ml), PT1 and PT2 (posttherapy isolates obtained in animals; MICs, 32 and 128 micrograms/ml, respectively), and PT2-r (posttherapy isolate obtained after six in vitro subpassages of PT2; MIC, 32 micrograms/ml). [2-3H]adenine incorporation (indirect evidence of DNA gyrase activity) in EDTA-permeabilized cells was less affected by pefloxacin in PT2 and PT2-r (50% inhibitory concentration, 0.27 and 0.26 microgram/ml, respectively) than it was in S and PT1 (50% inhibitory concentration, 0.04 and 0.05 microgram/ml, respectively). Reduced [14C]pefloxacin labeling of intact cells in strains PT1 and PT2 correlated with more susceptibility to EDTA and the presence of more calcium (P less than 0.05) and phosphorus in the outer membrane fractions. Outer membrane protein analysis showed reduced expression of protein D2 (47 kDa) in strains PT1 and PT2. Other proteins were apparently similar in all strains. The addition of calcium chloride (2 mM) to the sodium dodecyl sulfate-solubilized samples of outer membrane proteins, before heating and Western blotting, probed with monoclonal antibody anti-OmpF showed electrophoretic mobility changes of OmpF in strains PT1 and PT2 which were not seen in strain S. Calcium-induced changes were reversed with ethyleneglycoltetraacetate. Decreased [14C]pefloxacin labeling was further correlated with an altered lipopolysaccharide pattern and increased 3-deoxy-D-mannooctulosonic acid concentration (P less than 0.01). These findings suggested that resistance to pefloxacin is associated with altered DNA gyrase in strain PT2-r, with altered permeability in PT1, and with both mechanisms in PT2. The decreased expression of protein D2 and the higher calcium and lipopolysaccharide contents of the outer membrane could be responsible for the permeability deficiency in P. aeruginosa.     

Standard indicators of pneumotachometry and the Votchal-Tiffeneau index in the evaluation of external respiratory function in adolescents

A study was made of the indices of pneumotachometry (PT): PT of exhalation, PT of inhalation and their ratio--in 263 adolescents (125 boys and 138 girls) with normal physical and sexual development. Direct correlation of sex, age and height with PT indices was established. Linear regression equations were made up for the calculation of standard parameters. It was shown that the ratio of PT of exhalation/PT of inhalation less than I in clinically healthy adolescents could not be a sign of disorder of bronchial permeability. The spirographic Votchal Tiffeneau index was-studied in 260 of them (125 boys and 135 girls). The lower permissible normal limit for the Metatest-1 spirograph was 76.5 +/- 0.4%.     

Characteristics and association with disease of two major subclones of Shiga toxin (Verocytotoxin)-producing strains of Escherichia coli (STEC) O157 that are present among isolates from patients in Germany

Shiga toxin (Verocytotoxin) producing E. coli (STEC) O157 were isolated from 168 patients living in different parts of Germany. Most isolates were from sporadic cases and seven small outbreaks with STEC O157 were identified. The 168 strains were examined for phenotypic and genotypical traits in order to identify major types of STEC O157 occurring in Germany. Phage typing (PT) revealed PT8 (n = 54) and PT2 (n = 48) strains as most frequent (60.7%) among the isolates. Carriage of the stx(2) gene by STEC O157 was closely associated with hemolytic uremic syndrome (100%) and with bloody diarrhea (61.7%). The stx(2) gene was frequent in PT88, PT47 (both 100%), PT2 (91.5%) and PT4 (87.5%) strains and more rarely (33.3%) found in strains belonging to the other PTs. PT8 and PT2 strains formed two groups which differed from each other in their motility, stx-genotypes and the severity of the illness they caused. Pulsed-field gel electrophoresis of PT2 and PT8 strains and hybridization of XbaI digested DNA with stx(1) and stx(2) specific gene probes revealed similarities among epidemiologically unrelated strains belonging to the same PT. The results indicate that STEC O157 PT2 and PT8 strains form two distinct subclones which are dominating in Germany and other European countries.     

Patterns of rehabilitation utilization after hip fracture in acute hospitals and skilled nursing facilities

BACKGROUND: Hospitalized hip fracture patients may receive physical therapy (PT) in acute and/or postacute settings. Patterns of PT use may vary by patient, clinical, and hospital characteristics. These patterns can be analyzed if the acute and postacute stays are linked. OBJECTIVES: We classified the following patterns of PT use: acute PT only, skilled nursing facility (SNF) PT only, acute and SNF PT, and no PT. For each pattern, we compared (1) characteristics of hip fracture patients, (2) length of stay (LOS), and (3) discharge outcomes. SUBJECTS: The study included 187,990 hospitalized hip fracture patients derived from Medicare administrative data. MEASURES: Dependent variables were PT use patterns, acute hospital and SNF LOS, total episode days of care, and discharge destination. Independent variables were demographic, clinical, and facility characteristics. PT use patterns were also used as independent variables in the LOS and discharge destination models. RESULTS: Patterns of PT use were influenced by demographic and clinical characteristics such as age, race, and surgery type. Similarly, different LOS measures and discharge destinations varied by the PT use patterns. Patients receiving acute PT had longer acute LOSs; however, those patients who were subsequently transferred to SNFs had shorter SNF LOSs and total episode days of care. Patients utilizing PT were more likely to be discharged to home after the acute or SNF stay. CONCLUSIONS: Disparities in PT use exist for subgroups of patients such as the elderly and blacks. Providers should determine the most appropriate setting for initiation of PT to achieve better discharge outcomes with efficient use of resources.     

Preterm birth results in alterations in neural connectivity at age 16 years

Very low birth weight preterm (PT) children are at high risk for brain injury. Employing diffusion tensor imaging (DTI), we tested the hypothesis that PT adolescents would demonstrate microstructural white matter disorganization relative to term controls at 16 years of age. Forty-four PT subjects (600-1250 g birth weight) without neonatal brain injury and 41 term controls were evaluated at age 16 years with DTI, the Wechsler Intelligence Scale for Children-III (WISC), the Peabody Picture Vocabulary Test-Revised (PPVT), and the Comprehensive Test of Phonological Processing (CTOPP). PT subjects scored lower than term subjects on WISC full scale (p=0.003), verbal (p=0.043), and performance IQ tests (p=0.001), as well as CTOPP phonological awareness (p=0.004), but scored comparably to term subjects on PPVT and CTOPP Rapid Naming tests. PT subjects had lower fractional anisotropy (FA) values in multiple regions including bilateral uncinate fasciculi (left: p=0.01; right: p=0.004), bilateral external capsules (left: p<0.001; right: p<0.001), the splenium of the corpus callosum (p=0.008), and white matter serving the inferior frontal gyrus bilaterally (left: p<0.001; right: p=0.011). FA values in both the left and right uncinate fasciculi correlated with PPVT scores (a semantic language task) in the PT subjects (left: r=0.314, p=0.038; right: r=0.336, p=0.026). FA values in the left and right arcuate fasciculi correlated with CTOPP Rapid Naming scores (a phonologic task) in the PT subjects (left: r=0.424, p=0.004; right: r=0.301, p=0.047). These data support for the first time that dual pathways underlying language function are present in PT adolescents. The striking bilateral dorsal correlations for the PT group suggest that prematurely born subjects rely more heavily on the right hemisphere than typically developing adults for performance of phonological language tasks. These findings may represent either a delay in maturation or the engagement of alternative neural pathways for language in the developing PT brain.     

Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D.

Secondary hyperparathyroidism is characterized by an increase in parathyroid (PT) cell number, and parathyroid hormone (PTH) synthesis and secretion. It is still unknown as to what stimuli regulate PT cell proliferation and how they do this. We have studied rats with dietary-induced secondary hyper- and hypoparathyroidism, rats given 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and rats after 5/6 nephrectomy for the presence of PT cell proliferation and apoptosis. PT cell proliferation has been measured by staining for proliferating cell nuclear antigen (PCNA) and apoptosis by in situ detection of nuclear DNA fragmentation and correlated with serum biochemistry and PTH mRNA levels. A low calcium diet led to increased levels of PTH mRNA and a 10-fold increase in PT cell proliferation. A low phosphate diet led to decreased levels of PTH mRNA and the complete absence of PT cell proliferation. 1,25 (OH)2D3 (25 pmol/d x 3) led to a decrease in PTH mRNA levels and unlike the hypophosphatemic rats there was no decrease in cell proliferation. There were no cells undergoing apoptosis in any of the experimental conditions. The secondary hyperparathyroidism of 5/6 nephrectomized rats was characterized by an increase in PTH mRNA levels and PT cell proliferation which were both markedly decreased by a low phosphate diet. The number of PCNA positive cells was increased by a high phosphate diet. Therefore hypocalcemia, hyperphosphatemia and uremia lead to PT cell proliferation, and hypophosphatemia completely abolishes this effect. Injected 1,25 (OH)2D3 had no effect. These findings emphasize the importance of a normal phosphate and calcium in the prevention of PT cell hyperplasia.     

Long-term effect of body weight-supported treadmill training in Parkinson's disease: a randomized controlled trial

OBJECTIVE: To investigate whether body weight-supported treadmill training (BWSTT) is of long-term benefit for patients with Parkinson's disease (PD). DESIGN: Randomized controlled trial. SETTING: Inpatient rehabilitation unit for neurologic diseases in Japan. PARTICIPANTS: Twenty-four patients (Hoehn and Yahr stages 2.5 or 3) who were not demented (Mini-Mental State Examination score, >27). INTERVENTIONS: Patients were randomized to receive either a 45-minute session of BWSTT (up to 20% of body weight supported) or conventional physical therapy (PT) for 3 days a week for 1 month. MAIN OUTCOME MEASURES: Outcome measures were evaluated at baseline and at 1, 2, 3, and 6 months. Measures included the Unified Parkinson's Disease Rating Scale (UPDRS), ambulation speed (s/10 m), and number of steps taken for a 10-m walk as a parameter for stride length. RESULTS: Four patients needed modification of medications in the follow-up period. Twenty patients (BWSTT, n=11; PT, n=9) without modified medications were analyzed for functional outcome. Age, duration of PD, gender, and doses of medications were comparable. There was no difference in the baseline UPDRS (BWSTT=33.3; PT=32.6), speed (BWSTT=10.8; PT=11.5), and steps (BWSTT=23.4; PT=22.8). The BWSTT group had significantly greater improvement than the PT group (Mann-Whitney U test, Bonferroni adjustment for multiple comparison) in ambulation speed at 1 month (BWSTT=8.5; PT=10.8; P<.005); and in the number of steps at 1 (BWSTT=20.0; PT=22.7; P<.005), 2 (BWSTT=19.5; PT=22.4; P<.005), 3 (BWSTT=20.1; PT=23.1; P<.005), and 4 months (BWSTT=21.0; PT=23.0; P=.006). CONCLUSIONS: BWSTT has a lasting effect specifically on short-step gait in PD.     

Glucose-6-phosphate transporter gene therapy corrects metabolic and myeloid abnormalities in glycogen storage disease type Ib mice

Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate transporter (G6PT), an endoplasmic reticulum-associated transmembrane protein that is ubiquitously expressed. GSD-Ib patients suffer from disturbed glucose homeostasis and myeloid dysfunctions. To evaluate the feasibility of gene replacement therapy for GSD-Ib, we have infused adenoviral (Ad) vector containing human G6PT (Ad-hG6PT) into G6PT-deficient (G6PT(-/-)) mice that manifest symptoms characteristics of the human disorder. Ad-hG6PT infusion restores significant levels of G6PT mRNA expression in the liver, bone marrow and spleen, and corrects metabolic as well as myeloid abnormalities in G6PT(-/-) mice. The G6PT(-/-) mice receiving gene therapy exhibit improved growth; normalized serum profiles for glucose, cholesterol, triglyceride, uric acid and lactic acid; and reduced hepatic glycogen deposition. The therapy also corrects neutropenia and lowers the elevated serum levels of granulocyte colony-stimulating factor. The development of bone and spleen in the infused G6PT(-/-) mice is improved and accompanied by increased cellularity and normalized myeloid progenitor cell frequencies in both tissues. This effective use of gene therapy to correct metabolic imbalances and myeloid dysfunctions in GSD-Ib mice holds promise for the future of gene therapy in humans.     

Influence of exogenous thiols on inorganic mercury-induced injury in renal proximal and distal tubular cells from normal and uninephrectomized rats.

Inorganic mercury (Hg(2+)) induced time- and concentration-dependent cellular injury in freshly isolated proximal tubular (PT) and distal tubular (DT) cells from normal (control) rats or uninephrectomized (NPX) rats. PT cells from NPX rats were more susceptible than PT cells from control rats, and DT cells were slightly more susceptible than PT cells to cellular injury induced by Hg(2+) (not bound to a thiol). Preloading cells with glutathione increased Hg(2+)-induced cellular injury in PT cells from control rats. However, coincubation of PT or DT cells from control or NPX rats with Hg(2+) and glutathione (1:4) provided significant protection relative to incubations with Hg(2+) alone. No support was obtained for a role for gamma-glutamyltransferase in glutathione-dependent protection. However, the organic anion carrier does appear to play a role in accumulation and toxicity of mercuric conjugates of cysteine in PT cells from control, but not NPX, rats. Coincubation with Hg(2+) and cysteine (1:4) had little effect on, or slightly enhanced, Hg(2+)-induced cellular injury at low concentrations of Hg(2+) in all cells studied. Coincubation with Hg(2+) and albumin (1:4) markedly protected PT and DT cells from control and NPX rats at all concentrations except the highest concentration of Hg(2+) in DT cells from NPX rats. 2,3-Dimercapto-1-propanesulfonic acid protected cells both when preloaded or added simultaneously with Hg(2+). Thus, renal cells from NPX rats are more susceptible to Hg(2+)-induced injury, PT and DT cells respond differently to exposure to Hg(2+), and thiols can significantly modulate the toxic response to Hg(2+).     

Mercuric chloride-induced cytotoxicity and compensatory hypertrophy in rat kidney proximal tubular cells.

Previous work showed that uninephrectomized (NPX) rats are more susceptible to the nephropathy induced by some doses of HgCl2 than sham-operated (SHAM) rats. The aim of the present study was to investigate the cytotoxic effects of HgCl2 in proximal tubular (PT) cells isolated from the kidney(s) of both NPX and SHAM rats. The study was designed to test if isolated PT cells that have undergone compensatory hypertrophy in vivo are more sensitive to the cytotoxic effects of HgCl2 in vitro than PT cells isolated from the kidneys of control animals. PT cells were purified from suspensions of renal cortical cells by Percoll density gradient centrifugation. The cellular content of protein (mg/10(6) cells) was 68% higher and the cellular specific activity (mU/10(6) cells) of lactate dehydrogenase was 56% higher in PT cells isolated from NPX rats than in PT cells isolated from SHAM rats. The cytotoxicity of HgCl2, as assessed by inhibition of lactate dehydrogenase activity, exhibited a steep concentration dependence. In the presence of bovine serum albumin, PT cells from both NPX and SHAM rats displayed no signs of cellular injury at concentrations of HgCl2 less than or equal to 0.1 mM. At concentrations of HgCl2 greater than or equal to 0.25 mM, cellular necrosis occurred rapidly in all PT cells. In the absence of bovine serum albumin, cellular injury and death occurred at concentrations of HgCl2 as low as 0.01 mM. PT cells from NPX rats exhibited signs of cellular injury at lower concentrations of HgCl2 than PT cells from SHAM rats when BSA was absent from the extracellular medium. Preincubation of PT cells from both NPX and SHAM rats with glutathione provided the cells with concentration-dependent protection from the cytotoxic effects of HgCl2. Preincubation of PT cells from both NPX and SHAM rats with the chelating agent 2,3-dimercapto-1-propane sulfonate provided cells with complete protection from the cytotoxic effects of HgCl2 when the concentration of 2,3-dimercapto-1-propane sulfonate was slightly below or higher than the concentration of HgCl2. Results of this study demonstrate the usefulness of freshly isolated PT cells from NPX rats as an in vitro model system to investigate biochemical mechanisms by which compensatory renal growth alters susceptibility to chemical-induced nephrotoxicity.     

样本存放时间对凝血指标影响的实验评估

目的研究标本放置时间对部分血凝检测结果的影响,为规范分析前过程提供实验依据。方法随机选取100份枸橼酸钠抗凝外周血标本分别在室温放置1、2、4、6、8和10h后进行血浆凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）和纤维蛋白原（Fbg）含量的测定。根据不同检测项目和时间段分组,使用SAS统计软件包对上述4项指标在放置2、4、6、8、10h所得到的检测结果与放置1h内检测的结果进行配对t检验。结果胛、PT、TT测定在标本采集1h内的结果与2和4h后检测结果差异无统计学意义（P〉0．05）,与6h后检测的结果之间差异有统计学意义（P〈0．01）。APTY测定在标本采集1h内检测的结果与2、4、6、8和10h后检测的结果之间差异有统计学意义（P〈0．01）。Fbg测定在标本采集1h内的结果与2h检测的结果差异无统计学意义（P〉0．05）,而与之后的结果差异有统计学意义（P〈0．01）。结论用于凝血试验的标本在室温存放一段时间后,对不同检测项目均造成一定影响,标本采集后应在1h内检测,如不能做到也应在2h内检测完毕,否则会对检测结果造成明显影响。     

Variability of prothrombin time and activated partial thromboplastin time in the diagnosis of increased surgical bleeding

BACKGROUND: Prothrombin time (PT) and activated partial thromboplastin time (APTT) are used to diagnose causes of increased surgical bleeding and to guide treatment of acquired coagulation factor deficiency. This study compared the sensitivity of various commercial PT and APTT tests in patients with dilutional coagulopathy. STUDY DESIGN AND METHODS: A prospective study was used to identify patients who experienced increased surgical bleeding during elective extensive (>10 spinal segments) spinal fusion and instrumentation. In patients with clinical signs of increased bleeding, blood was obtained to compare the sensitivity of various commercial PT and APTT tests. PT, PT ratio, the International Normalized Ratio (INR), APTT, and APTT ratio were compared for their sensitivity in the diagnosis of a dilutional coagulopathy. RESULTS: Sixteen patients experienced increased bleeding during surgery. Mean estimated blood volume lost exceeded 1 blood volume (1.14 +/− 0.28). PT and APTT test results varied markedly. In the most sensitive PT and APTT tests, the results were 1.5 times the mean reference range values in all but on of the patients. The least sensitive combination of tests had results that were 1.5 times the mean reference range values in only 2 of 16 patients. Variability among tests was not reduced by the use of the PT or the APTT ratio, by the use of INR, or by incorporation of a measure of PT or APTT test sensitivity to factor-deficient serum. CONCLUSION: In surgical patients with dilutional coagulopathy, diagnostic and treatment decisions could depend on which PT and APTT test was used to determine the etiology of increased bleeding. This study indicates that the relationship between increased bleeding and an increased PT and APTT may be more difficult to define than is suggested by current practice guidelines. Each laboratory must establish guidelines based on reagent and instrument sensitivity to coagulation factor dilution.     

Patient Characteristics and Temporal Trends in Police Transport of Blunt Trauma Patients: A Multicenter Retrospective Cohort Study

Background: Police transport (PT) of penetrating trauma patients has the potential to decrease prehospital times for patients with life-threatening hemorrhage and is part of official policy in Philadelphia, Pennsylvania. We hypothesized that rates of PT of bluntly injured patients have increased over the past decade. Methods: We used Pennsylvania Trauma Outcomes Study registry data from 2006–15 to identify bluntly injured adult patients transported to all 8 trauma centers in Philadelphia. PT was compared to ambulance transport, excluding transfers, burn patients, and private transport. We compared demographics, mechanism, and injury outcomes between PT and ambulance transport patients and used multivariable logistic regression to identify independent predictors of PT. We also identified physiological indicators and injury patterns that might have benefitted from prehospital intervention by EMS. Results: Of 28 897 bluntly injured patients, 339 (1.2%) were transported by police and 28 558 (98.8%) by ambulance. Blunt trauma accounted for 11% of PT and penetrating trauma for 89%. PT patients were younger, more likely to be male, and more likely to be African American or Asian and were more often injured by assault or motor vehicle crash. There were no significant differences presenting physiology between PT and EMS patients. In multivariable logistic regression analysis, male sex (OR 1.89, 95%CI 1.40–2.55), African American race (OR 1.71 95%CI 1.34–2.18), and Asian race (OR 2.25, 95%CI 1.22–4.14) were independently associated with PT. Controlling for injury severity and physiology, there was no significant difference in mortality between PT and EMS. Overall, 64% of PT patients had a condition that might have benefited from prehospital intervention such as supplemental oxygen for brain injury or spine stabilization for vertebral fractures. Conclusions: PT affects a small minority of blunt trauma patients, and did not appear associated with higher mortality. However, PT patients included many who might have benefited from proven, prehospital intervention. Clinicians, EMS providers, and law enforcement should collaborate to optimize use of PT within the trauma system.     

广东省凝血酶原时间测定的室间质量评价

目的 探讨广东省临床实验室监测凝血酶原时间（PT）的检测状况及影响PT测定室间可比性的因素.方法 通过每年两次定期向全省参评实验室寄发质控样品（每次5个样品）,然后对其回报的数据进行统计分析,作出实验室检验水平的评价.结果 近年来全省实验室间PT（INR）测定结果的CV值尽管有逐渐下降的趋势,但室间变异仍然相当高.同一凝血活酶试剂的测定结果,PT（INR）的CV明显大于PT（sec）的CV,特别是对异常水平质评物的测定.结论 凝血活酶试剂敏感度指数（ISI）值标定的不准确性和INR计算不正确的是引起广东省临床实验室间凝血酶原时间测定变异大的主要原因.     

样本存放时间对凝血指标影响的实验评估

目的研究标本放置时间对部分血凝检测结果的影响,为规范分析前过程提供实验依据。方法随机选取100份枸橼酸钠抗凝外周血标本分别在室温放置1、2、4、6、8和10 h后进行血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)和纤维蛋白原(Fbg)含量的测定。根据不同检测项目和时间段分组,使用SAS统计软件包对上述4项指标在放置2、4、6、8、10 h所得到的检测结果与放置1 h内检测的结果进行配对t检验。结果PT、TT测定在标本采集1 h内的结果与2和4 h后检测结果差异无统计学意义(P>0.05),与6 h后检测的结果之间差异有统计学意义(P<0.01)。APTT测定在标本采集1 h内检测的结果与2、4、6、8和10 h后检测的结果之间差异有统计学意义(P<0.01)。Fbg测定在标本采集1 h内的结果与2 h检测的结果差异无统计学意义(P>0.05),而与之后的结果差异有统计学意义(P<0.01)。结论用于凝血试验的标本在室温存放一段时间后,对不同检测项目均造成一定影响,标本采集后应在1 h内检测,如不能做到也应在2 h内检测完毕,否则会对检测结果造成明显影响。     

Differentiation of thymus-derived cells from precursors in mouse bone marrow

An experimental model system was developed to study the differentiation of thymus-derived (T) cells from progenitors in bone marrow. In this system transplantation of bone marrow cells depleted of T cells gave rise to T cells in the spleens of irradiated recipients within 15 days of transplantation. Thus, normal bone marrow contains a class of cells that are progeniotrs of T cells (PT cells). PT cells are different from T cells since PT cells are incapable of responding to alloantigen, are θ resistant, and band in a lighter density region than do T cells. The density profile of PT cells is different from that of hematopoietic stem cells (CFU-S); PT cells band in a denser region of the gradient than do CFU-S.     

Cell loss and recovery in umbilical cord blood processing: a comparison of postthaw and postwash samples

BACKGROUND: Engraftment after umbilical cord blood (UCB) transplantation is highly dependent on nucleated cell (NC) and CD34+ cell content. Current standard postthaw (PT) processing includes a wash step to remove dimethyl sulfoxide (DMSO), lysed red cells, and stroma. The contribution of the wash step to cell loss and ultimately the dose of cells available for transplant have yet to be systematically reported. This study examines the effect of the wash step as well as that of PT storage on various quality control variables of UCB units. STUDY DESIGN AND METHODS: Ten units were thawed and washed based on the New York Blood Center method. Samples were removed from each unit at six time points: prefreeze (PF), immediately PT, immediately postwash (PW), and 1, 2, and 5 hours PW. On each sample, total nucleated cell (TNC) count, CD34+ cell enumeration, colony-forming unit (CFU)-granulocyte-macrophage, and viability assays (fluorescence microscopy [acridine orange/propidium iodide, or AO/PI] and flow cytometry [7-aminoactinomycin]) were obtained. RESULTS: TNC counts decreased PT and at subsequent time points; the PT TNC recovery was 89 percent compared to 82 percent PW (p < 0.01). TNC recovery decreased to 90 percent of PW (82% of PT) values (p < 0.01) and 83 percent of PW (76% of PT) values (p < 0.001), at 2 and 5 hours PW, respectively. CD34+ cell loss PT was not significant. Viability by AO/PI decreased PT and plateaued over time. In contrast, viability by flow cytometry remained higher and increased slightly over time. CFUs were significantly lower PT, recovering PW. CONCLUSIONS: Our data indicate that the thawing and washing results in a substantial loss of cells, with TNC loss approaching 20 percent when compared with PF counts; the wash step was responsible for nearly half of the cell loss. The reduced PT viability was expected. Elapse of time PW resulted in further loss of NCs but no detectable significant changes in CD34+ cell content and viability and/or CFU.     

Absolute Pitch and Planum Temporale

An increased leftward asymmetry of the planum temporale (PT) in absolute-pitch (AP) musicians has been previously reported, with speculation that early exposure to music influences the degree of PT asymmetry. To test this hypothesis and to determine whether a larger left PT or a smaller right PT actually accounts for the increased overall PT asymmetry in AP musicians, anatomical magnetic resonance images were taken from a right-handed group of 27 AP musicians, 27 nonmusicians, and 22 non-AP musicians. A significantly greater leftward PT asymmetry and a significantly smaller right absolute PT size for the AP musicians compared to the two control groups was found, while the left PT was only marginally larger in the AP group. The absolute size of the right PT and not the left PT was a better predictor of music group membership, possibly indicating "pruning" of the right PT rather than expansion of the left underlying the increased PT asymmetry in AP musicians. Although early exposure to music may be a prerequisite for acquiring AP, the increased PT asymmetry in AP musicians may be determined in utero, implicating possible genetic influences on PT asymmetry. This may explain why the increased PT asymmetry of AP musicians was not seen in the group of early beginning non-AP musicians.     

The calcimimetic compound NPS R-568 suppresses parathyroid cell proliferation in rats with renal insufficiency. Control of parathyroid cell growth via a calcium receptor.

Parathyroid (PT) cell hyperplasia is a common consequence of chronic renal insufficiency (CRI). NPS R-568 is a phenylalkylamine compound that acts as an agonist (calcimimetic) at the cell surface calcium receptor (CaR). To test the hypothesis that the CaR plays a role in PT hyperplasia in CRI, we tested the effect of NPS R-568 on PT cell proliferation in rats with renal insufficiency. Rats were subjected to 5/6 nephrectomy and then infused intraperitoneally with 5-bromodeoxyuridine (BrdU) to label S-phase cells. Two groups of nephrectomized rats received NPS R-568 by gavage twice daily for 4 d (1.5 and 15 mg/kg body wt). On day 5, the number of BrdU-positive PT cells of vehicle-treated nephrectomized rats was 2.6-fold greater than that of the sham-operated control. Low and high doses of NPS R-568 reduced the number of BrdU-positive PT cells by 20 and 50%, respectively. No changes in staining, however, were observed in ileal epithelial cells (CaR-negative) or in thyroidal C-cells (CaR-positive). Furthermore, the effect of NPS R-568 could not be explained by changes in serum 1,25(OH)2D3 or phosphorus. These results indicate that NPS R-568 suppresses PT cell proliferation in rats with renal insufficiency, and lend support to the linkage between the CaR and PT hyperplasia in CRI.