神经生长因子对小鼠突触体内Ca^2＋水平的调节作用

观察了多次海马内微注射ＮＧＦ对小鼠突触体内游离钙水平的影响，并在离体情况下观察ＮＧＦ对ＥＧＴＡ和ＣａＣｌ２分别造成突触体内低钙和高钙状态的调节作用。结果如下：（１）在体实验表明，一定剂量的ＮＧＦ可显著降低老年小鼠海马突触体内游离钙水平（Ｐ＜００５）；（２）离体实验表明，当突触体游离钙水平降低时，适当剂量的ＮＧＦ具有升高游离钙水平的作用；而突触体内游离钙水平升高时，则ＮＧＦ有降低游离钙水平的作用。提示ＮＧＦ对游离钙水平的双向调节作用可能是ＮＧＦ改善老年性记忆衰退的作用机制。     

High dose chemotherapy and hematopoietic stem cell transplantation: a study of treatment preference in patients with rheumatoid arthritis and rheumatologists

OBJECTIVE: Patients with intractable rheumatoid arthritis (RA) may benefit from treatment with high dose chemotherapy followed by rescue with autologous hematopoietic peripheral blood stem cell transplant (HSCT). We investigated whether the risks of this approach are acceptable to patients with RA and rheumatologists and whether risk taking by patients was associated with disease characteristics, socioeconomic variables, and/or personality traits. METHODS: A survey in the outpatient clinic was conducted among 2 cohorts of 45 (cohort A) and 51 (cohort B) RA patients with active disease. Patients received information about the potential benefit of HSCT (2/3 chance of a good clinical response, 1/3 no response) and treatment related morbidity and mortality. Cure was assumed not to be a realistic perspective. Cohort A was asked to choose between their own disease state for an indefinite time or HSCT. Nonparametric tests were performed to evaluate putative predictive factors that led patients to accept transplant related mortality (TRM): swollen joint count, tender joint count, visual analog scale (VAS) measures of disease activity and pain, erythrocyte sedimentation rate, Health Assessment Questionnaire (HAQ), socioeconomic variables, RA Quality of Life Questionnaire (RAQoL), and the Life Orientation Test. Cohort B was asked to consider a worst case scenario with respect to their disease activity. The minimal duration of benefit was assessed, given a TRM of 0.01% and 2%. To evaluate treatment preference of physicians, 96 Dutch rheumatologists responded to a hypothetical clinical case analogous to the interviews with RA patients. The minimum duration of benefit was assessed, given a TRM of 2% and the maximal TRM acceptable to rheumatologists if duration of benefit was 2 years in 2/3 patients. RESULTS: In cohort A, 5 of 45 patients were willing to accept risk of death. VAS disease activity (p = 0.006), VAS pain (p = 0.021), and HAQ (p = 0.05) were significantly higher in patients willing to accept risk of death. Religiosity (p = 0.093), a higher Ritchie Articular Index (p = 0.096), and low quality of life (by RAQoL) (p = 0.133) showed trends toward risk taking. In cohort B, 22 of 50 patients (44%) were willing to accept a risk of TRM related to HSCT. For the 22 patients the median required duration of benefit given a TRM of 2% was 5 years (range 1-15). Physicians also required a median duration of benefit of 5 years. CONCLUSION: We evaluated risk taking in patients with RA and physicians based on a realistic perspective in which the tradeoff between short term risks and possible longterm benefit of HSCT was investigated. Based on current efficacy data for HSCT (2 years improvement in 2/3 patients), half the patients would accept the current TRM of 2%, based on registry results. Patients willing to accept TRM had higher VAS disease activity, VAS pain, and HAQ. Doctors were more willing to accept mortality in the treatment of RA.     

Projected whole-body career doses for radiation workers in Canada

Projected whole-body career doses have been calculated from Canadian exposure data contained in the National Dose Registry, using the straight extrapolation of accumulated annual doses to a 40-y period, as described in the 1977 UNSCEAR report (UNSCEAR77). The calculations are broken down by type of employment. The results are compatible with earlier publications. Double regressions provided trends of projected career doses with increasing length of employment and with progressing date of enrollment into the registry. The career doses fit a log-normal or a hybrid log-normal distribution for occupations with low and high exposures, respectively.     

Endoscopic ultrasound added to mediastinoscopy for preoperative staging of patients with lung cancer

Context  Up to 40% of thoracotomies performed for non–small cell lung cancer are unnecessary, predominantly due to inaccurate preoperative detection of lymph node metastases and mediastinal tumor invasion (T4). Mediastinoscopy and the novel, minimally invasive technique of transesophageal ultrasound–guided fine-needle aspiration (EUS-FNA) target different mediastinal lymph node stations. In addition, EUS can identify tumor invasion in neighboring organs if tumors are located adjacent to the esophagus. Objective  To investigate the additional value of EUS-FNA to mediastinoscopy in the preoperative staging of patients with non–small cell lung cancer. Design, Setting, and Patients  Prospective, nonrandomized multicenter trial performed in 1 referral and 5 general hospitals in the Netherlands. During a 3-year period (2000-2003), 107 consecutive patients with potential resectable non–small cell lung cancer underwent preoperative staging by both EUS-FNA and mediastinoscopy. Patients underwent thoracotomy with tumor resection if mediastinoscopy was negative. Surgical-pathological staging was compared with preoperative findings and the added benefit of the combined strategy was assessed. Intervention  The EUS-FNA examination was performed as an additional staging test to mediastinoscopy in all patients. Main Outcome Measure  Detection of mediastinal tumor invasion (T4) and lymph node metastases (N2/N3) comparing the combined staging by both EUS-FNA and mediastinoscopy with staging by mediastinoscopy alone. Results  The combination of EUS-FNA and mediastinoscopy identified more patients with tumor invasion or lymph node metastases (36%; 95% confidence interval [CI], 27%-46%) compared with either mediastinoscopy alone (20%; 95% CI, 13%-29%) or EUS-FNA (28%; 95% CI, 19%-38%) alone. This indicated that 16% of thoracotomies could have been avoided by using EUS-FNA in addition to mediastinoscopy. However, 2% of the EUS-FNA findings were false-positive. Conclusion  These preliminary findings suggest that EUS-FNA, when added to mediastinoscopy, improves the preoperative staging of lung cancer due to the complementary reach of EUS-FNA in detecting mediastinal lymph node metastases and the ability to assess mediastinal tumor invasion.      

Pulmonary function impairment in children following hematopoietic stem cell transplantation

BACKGROUND: Deterioration of pulmonary function after hematopoietic stem cell transplantation (SCT) is a well-known late effect of this treatment, but the course of pulmonary function over time is less clear. The aim of our study was to establish both the prevalence and course of pulmonary function abnormalities in children following SCT. METHODS: Thirty-nine of 106 patients, who visited a post-SCT late effects clinic and who underwent a pulmonary function test (PFT) both before and at least twice after SCT were included in this study. Forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and total lung diffusion capacity (TLCO) were determined and recorded as percentage predicted for age, sex, and length matched controls. Values of less than 80% of predicted were considered abnormal. Change in PFT parameters over time was determined by comparing the mean PFT parameter in our group at three different time points: pre-SCT, < or =1 year post-SCT (SCTpost1) and >1 year post-SCT (SCTpost2). RESULTS: After SCT restrictive and/or diffusion abnormalities are most prevalent (45% and 76% at SCTpost1, respectively). A significant decrease of TLC (-9.7%) and TLCO (-20.3%) was observed during the first year after SCT, with improvement over time, but no normalization. Obstructive lung disease was less common (6% at SCTpost1). Clinical signs of lung function impairment were rare. CONCLUSIONS: Restrictive and diffusion lung function disorders are common after SCT. They improve over time but do not normalize. As only a few patients with pulmonary function abnormalities had clinical signs of lung function impairment, the clinical relevance of performing long-term follow-up of PFT is questionable.     

Implementation and evaluation of a nurse-centered computerized potassium regulation protocol in the intensive care unit - a before and after analysis

Background  

Potassium disorders can cause major complications and must be avoided in critically ill patients. Regulation of potassium in the intensive care unit (ICU) requires potassium administration with frequent blood potassium measurements and subsequent adjustments of the amount of potassium administrated. The use of a potassium replacement protocol can improve potassium regulation. For safety and efficiency, computerized protocols appear to be superior over paper protocols. The aim of this study was to evaluate if a computerized potassium regulation protocol in the ICU improved potassium regulation.     

Effect of medial arch-heel support in inserts on reducing ankle eversion: a biomechanics study

Background  

Excessive pronation (or eversion) at ankle joint in heel-toe running correlated with lower extremity overuse injuries. Orthotics and inserts are often prescribed to limit the pronation range to tackle the problem. Previous studies revealed that the effect is product-specific. This study investigated the effect of medial arch-heel support in inserts on reducing ankle eversion in standing, walking and running.     

Tongue and oropharynx: findings on MR imaging

Ten healthy subjects and 44 patients with diseases of the tongue or oropharynx were studied with magnetic resonance (MR) imaging. Axial, coronal, and sagittal images with a thickness of 4 mm were obtained with a pixel size of 0.75 X 0.75 mm on a 256 matrix. Nineteen of the patients underwent computed tomography (CT). Nine of those patients later had surgery, and the specimens were obtained for organ sectioning. These three studies as well as clinical history and physical examination findings were correlated. MR imaging was equal to or better than CT in those patients having both examinations. However, neither CT nor MR allowed recognition of histologic features or detection of microscopic spread of disease. Direct coronal and sagittal imaging planes on MR imaging allowed visualization of intrinsic tongue musculature, not possible with CT; this was important in recognizing subtle tumor extension. For these reasons, MR is the imaging method of choice for studying diseases of the tongue and oropharynx.     

The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy

BACKGROUND: The administration of blood components from donors who subsequently develop Creutzfeldt-Jakob disease has raised the issue of blood as a possible vehicle for iatrogenic disease. STUDY DESIGN AND METHODS: We examined infectivity in blood components and Cohn plasma fractions in normal human blood that had been "spiked" with trypsinized cells from a scrapie-infected hamster brain, and in blood of clinically ill mice that had been inoculated with a mouse-adapted strain of human transmissible spongiform encephalopathy. Infectivity was assayed by intracerebral inoculation of the blood specimens into healthy animals. RESULTS: Most of the infectivity in spiked human blood was associated with cellular blood components; the smaller amount present in plasma, when fractionated, was found mainly in cryoprecipitate (the source of factor VIII) and fraction I+II+III (the source of fibrinogen and immunoglobulin); almost none was recovered in fraction IV (the source of vitamin-K-dependent proteins) and fraction V (the source of albumin). Mice infected with the human strain of spongiform encephalopathy had very low levels of endogenous infectivity in buffy coat, plasma, cryoprecipitate, and fraction I+II+III, and no detectable infectivity in fractions IV or V. CONCLUSION: Convergent results from exogenous spiking and endogenous infectivity experiments, in which decreasing levels of infectivity occurred in cellular blood components, plasma, and plasma fractions, suggest a potential but minimal risk of acquiring Creutzfeldt-Jakob disease from the administration of human plasma protein concentrates.