家兔腓肠肌在电刺激下力学行为的实验研究

目的 获得肌肉收缩力学特性与其电生理特性间的实验关系。方法 用肌电仪发出不同波宽、不同强度的脉冲电流，对家兔的胫神经进行刺激，记录其复合动作电位及收缩力。结果 得到了收缩力与各种肌电信号的实验关系曲线。结论收缩力与刺激电流之间呈正相关关系、与复合动作电位幅值(CAMP)之间呈线性关系，且收缩力与肌电积分值之间也呈较好的线性关系。     

Regeneration in grafts of normal and denervated rat muscles

Summary The soleus or extensor digitorum longus muscles of young rats were freely grafted into the bed of the corresponding contralateral muscle. The grafts were of normal muscle or muscles which had been denervated for 14 days. Grafts of normal muscle were characterized by little or no contractile activity for the first 2–4 days after transplantation. In contrast, denervated grafts contracted weakly, but consistently, throughout this early period. The patterns of contraction were complex. In early transplants, the contractions were due entirely to surviving muscle fibers in the graft, and the contractile characteristics were those of denervated muscle fibers. After the first week, contractions of newly regenerating muscle fibers within the grafts were superimposed upon and later took over those from the fibers that survived the original transplantation. The contraction time approached those of the normal soleus or extensor muscles during the second month after grafting, and the grafts contracted like fast or slow muscles.     

Intracellular mechanism of quinidine action on muscle contraction

Summary The mechanism of quinidine action on rabbit cardiac and skeletal muscle was examined with functionally skinned muscle-fiber preparations. By using these preparations we could correlate measurements of muscle tension with the effect of quinidine on the Ca²⁺ activation of the contractile proteins and on the Ca²⁺ uptake and release from the sarcoplasmic reticulum (SR). Effect of quinidine on the contractile proteins. Quinidine concentrations above 0.5 mmol/l increased the maximal Ca²⁺-activated tension development 12% for papillary muscle and 5% for soleus (slow-twitch). Adductor magnus (fast-twitch) showed no significant change. Quinidine (0.1–1.0 mmol/l) also increased the submaximal Ca²⁺-activated tension development for the three muscle types (papillary muscle=soleus>adductor magnus) and shifted the [Ca²⁺]-tension curves to the left in a dose-dependent fashion. Effects of quinidine on the Ca ²⁺ uptake and release from the SR. Sarcoplasmic reticulum of skinned fibers was loaded with Ca²⁺ (uptake phase), then Ca²⁺ was released by 25 mmol/l caffeine (release phase) giving a tension transient. The area under the tension transient was used to estimate the amount of Ca²⁺ released. Quinidine (>0.5 mmol/l) decreased the Ca²⁺ uptake (soleus>adductor magnus>papillary muscle) and increased the Ca²⁺ release [papillary muscle=soleus adductor magnus (only at 1.5 mmol/l, the highest concentration tested)] from the SR of all three muscles in a dose-dependent manner. Quinidine at low concentration (0.1 and 0.5 mmol/l) increased the caffeine-induced tension transient of papillary muscle and higher quinidine concentrations (1.0 and 1.5 mmol/l) decreased the caffeine-induced tension transient of soleus and adductor magnus during both the uptake and release phases. The decreased Ca²⁺ uptake of papillary muscle in 1.5 mmol/l quinidine was antagonized by increasing the free Mg²⁺ from 0.032 to 0.32 mmol/l.In summary, quinidine has similar mechanisms of action in all three muscles: increased Ca²⁺ activation of the contractile proteins, decreased Ca²⁺ uptake and increased Ca²⁺ release from the SR in functionally skinned muscle fibers. We conclude that quinidine-induced decreases in Ca²⁺ uptake by the SR could be responsible for quinidine-induced myocardial depression and that quinidine-induced increases in Ca²⁺ activation of the contractile proteins and Ca²⁺ release from the SR could be responsible for the increases in skeletal muscle contraction caused by quinidine.     

The recovery of α-adrenoceptor function and binding sites after phenoxybenzamine

Summary The recovery of peripheral -adrenoceptor function and binding sites was studied in male New Zealand white rabbits after treatment with the irreversible adrenoceptor antagonist phenoxybenzamine. Phenoxybenzamine (5 mg/kg) was administered intravenously and the animals studied 30 min to 12 days later. Pressor dose response curves to intravenous phenylephrine, noradrenaline and guanabenz were constructed in vivo in conscious animals. The contractile response of abdominal aorta and renal artery to phenylephrine and noradrenaline was examined in vitro and the recovery of specific prazosin and clonidine binding to spleen membranes investigated in radioligand binding studies.The half life (t _1/2) for recovery of maximum pressor response in vivo ranged from 0.9±0.2 days for phenylephrine to 1.4±0.1 days for guanabenz. The t _1/2 for recovery of ED₅₀ was not significantly different to t _1/2 for recovery of maximum pressor response and ranged from 0.8±0.2 days for noradrenaline to 1.3±0.3 days for phenylephrine.Half life for recovery of maximum response and EC₅₀ in the isolated tissues was similar to that obtained in vivo for recovery of pressor responses and ranged from 0.4±0.1 days for the EC₅₀ of noradrenaline in the renal artery to 1.2±0.6 days for maximum response to phenylephrine in the abdominal aorta.The rate of recovery of specific clonidine binding did not differ significantly from the rate of recovery of pressor responses to the ₂-selective agonist guanabenz. t _1/2 for maximum number of specific clonidine binding sites, B _max was 1.6±0.9 days. However t _1/2 for recovery of specific prazosin binding was significantly longer than recovery of responses to phenylephrine and noradrenaline, t _1/2 for B _max was 3.6 ±0.1 day.     

Successful kidney transplantation in a patient with pre-existing chronic myeloid leukemia treated with imatinib

Active malignancy is an absolute contraindication to kidney transplantation. As for chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal into a manageable chronic disease with a close-to-normal life expectancy. To date it is unknown whether kidney transplantation can be safely performed in patients with pre-existing CML. We describe the clinical course of a 57-year-old male patient with chronic kidney disease caused by reflux nephropathy. This patient had undergone first kidney transplantation 20 years earlier and had again been on chronic hemodialysis for 6 years when CML was diagnosed. First-line therapy with 400 mg imatinib daily was well tolerated and induced an optimal cytogenetic and molecular response 3 months after initiation. One and a half years after CML diagnosis, a second kidney transplantation from a deceased donor was performed. Immunosuppression included basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids. Currently, 2 years posttransplant, renal allograft function is stable (serum creatinine 1.09 mg/dL, estimated glomerular filtration rate 75 mL/min per 1.73 m²), and CML remains in deep molecular remission with imatinib. Imatinib-treated CML in deep molecular remission could be regarded as inactive malignancy and may therefore not be viewed as an absolute contraindication to kidney transplantation.     

A world-wide survey on kidney transplantation practices in breast cancer survivors: The need for new management guidelines

Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons’ knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer.     

Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein–Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow-up duration of 23 807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV− PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199–1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751–6.521], p = .150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077–0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.     

Distinct immunopathological mechanisms of EBV-positive and EBV-negative posttransplant lymphoproliferative disorders

EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4⁺<300 cells/mm³, p <  .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm³) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.     

血细胞分析仪的工作原理及其近期发展

本文简要介绍了血细胞分析仪的主要工作原理，各主要厂家在血细胞分析仪上采用的白细胞分类技术及业界的技术进展。     

新鲜全血在不同系列血液分析仪校准中的应用

目的应用新鲜全血对实验室不同系列血液分析仪进行校准。方法以可溯源的规范操作的检测系统对新鲜全血的WBC、RBC、HB、HCT和PLT进行定值,再用定值新鲜全血对2台不同型号的仪器进行校准,并比较校准前后的偏差变化。结果校准后偏差超过允许范围的测定参数为30%(3/10),较校准前的偏差超过允许范围测定参数80%(8/10)明显降低。结论定值新鲜全血适用于不同系列血液分析仪的校准。