Intracellular calcium transients and arrhythmia in isolated heart cells

Intracellular calcium ([Ca2+]i) elevation may mediate cardiac arrhythmias. However, direct measurement of the rapid alterations of [Ca2+]i on a beat-to-beat basis using fast temporal resolution and without signal averaging in the spontaneously beating in vivo heart is lacking. Furthermore, data from an isolated spontaneously beating myocyte preparation that develops arrhythmia similar to that in the in vivo heart are unavailable. We measured rapid changes of [Ca2+]i with fast temporal resolution in isolated spontaneously beating neonatal rat ventricular myocytes with cell-to-cell communication and characterized the interrelation between [Ca2+]i and arrhythmia. An elevated extracellular calcium ([Ca2+]o) concentration of 10.8 mM induced premature beats, a rapid beating rate (tachyarrhythmia), and chaotic or fibrillatory beating activity in a small group of myocytes. [Ca2+]i levels during systole increased from the nanomolar to micromolar concentration range before arrhythmia development. Spontaneous oscillations of [Ca2+]i during diastole could evoke a spontaneous tachyarrhythmia. In the presence of [Ca2+]i elevation, a spontaneous tachyarrhythmia could induce severe [Ca2+]i overload. Reduction of [Ca2+]i with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid AM (5 microM) in the presence of 10.8 mM [Ca2+]o reversed the arrhythmia. In single ventricular myocytes superfused with 10.8 mM [Ca2+]o, oscillations of membrane potential characteristic of transient inward current occurred that were prevented by ryanodine (0.1 microM), an inhibitor of Ca2+ flux across the sarcoplasmic reticulum. This study characterizes 1) an isolated multicellular myocyte model of arrhythmia similar to that evident in in vivo hearts, 2) elevation of [Ca2+]i with systolic [Ca2+]i levels of 1-3 microM and diastolic [Ca2+]i oscillations before the initiation of arrhythmia, 3) tachyarrhythmia as a cause of severe [Ca2+]i overload, which may be important in the perpetuation and degeneration of arrhythmias, and 4) reversal of arrhythmia with reduction of [Ca2+]i. The results in the isolated myocyte model may have relevance to the generation and perpetuation of certain cardiac arrhythmias associated with calcium overload.     

Granulocyte Transfusions in Patients with Chronic Granulomatous Disease Undergoing Hematopoietic Cell Transplantation or Gene Therapy

Journal of Clinical Immunology - Granulocyte transfusions are sometimes used as adjunctive therapy for the treatment of infection in patients with chronic granulomatous disease (CGD). However,...     

The use of immunohistochemistry in the diagnosis of metastatic clear cell renal cell carcinoma: a review of PAX-8, PAX-2, hKIM-1, RCCma, and CD10

The diagnosis of metastatic clear cell renal cell carcinoma may be difficult in some cases, particularly in the small image-guided biopsies that are becoming more common. As targeted therapies for renal cell carcinoma are now standard treatment, the recognition and diagnosis of renal cell carcinoma has become even more critical. Many adjunctive immunohistochemical markers of renal epithelial lineage such as CD10 and RCCma have been proposed as aids in the diagnosis of metastatic renal cell carcinoma, but low specificities often limit their utility. More recently described markers (PAX-2, PAX-8, human kidney injury molecule-1, hepatocyte nuclear factor-1-β, and carbonic anhydrase-IX) offer the potential for greater sensitivity and specificity in this diagnostic setting; however, knowledge of their expected staining in other neoplasms and tissues is critical for appropriate use. In this review, we discuss the most widely used immunohistochemical markers of renal lineage with an emphasis on their sensitivity and specificity for metastatic clear cell renal cell carcinoma. Subsequently, we present a variety of organ-specific differential diagnostic scenarios in which metastatic clear cell renal cell carcinoma might be considered and we propose immunopanels for use in each situation.     

Sequential multiplex PCR approach for determining capsular serotypes of Streptococcus pneumoniae isolates

Accurate serotyping is essential to monitor the changes in the seroepidemiology of Streptococcus pneumoniae. We devised a simple and schematic sequence-based system of seven multiplex PCRs, in a sequence order based upon Active Bacterial Core surveillance (ABCs) serotype distribution during 2002 to 2003, to reliably deduce specific pneumococcal serotypes. A total of 421 isolates from ABCs were randomly chosen to evaluate this system. Two hundred twenty-nine of the isolates (54.3%) were specifically assigned 1 of 17 serotypes by the multiplex PCR system, with the results in complete concordance with conventional serotyping. One hundred seventy-two additional isolates (40.9%) were assigned to 11 specific sets of 2 to 4 serotypes that with one exception (serotypes 6A and 6B) consisted of the single frequently occurring targeted serotype and 1 to 3 additional rare serotypes primarily within the same serogroup as the targeted serotype. Only 20 isolates (4.8%) could not be assigned specific serotypes or serotype sets, since they were either of rare serotypes not included in the assay design or were nonserotypeable. Overall, we found this system to be highly reliable, with the potential to greatly reduce our reliance upon conventional serotyping. Especially important is the capability of this system to give serotype-determining potential to any facility that lacks the expensive typing sera and expertise needed for conventional serotyping yet has the modest equipment necessary for DNA amplification and electrophoresis.     

Bilateral angiosarcoma breast diagnosed by fine needle aspiration cytology

Concurrent or synchronous angiosarcoma (AS) of breast is a rarity. Specific recognition of this neoplasm in cytological specimens is difficult and conclusive diagnosis in the absence of ancillary methods is achieved only uncommonly. Herein, we present a case of bilateral AS of breasts in a 32-year-old lady diagnosed by fine needle aspiration (FNA) cytology, thus enabling a definitive surgical approach. This case report emphasizes that when aspiration smears show vasoformative features consisting of microacini, arborizing microtissue fragments and intracytoplasmic lumen against a bloody background, diagnosis can be made conclusively by FNA with immunohistochemical confirmation.     

16例应激性溃疡的临床诊治体会

目的 报告应激性溃疡的临床诊治体会。方法 全组16例,男12例,女4例。术前均无溃疡病史,血红蛋白检查均正常。术后早期应用糖皮质激素9例,出血前发生肺不张、严重呼吸道感染、呼吸功能不全6例,低血容量休克5例,急性重症出血坏死性胰腺炎4例,食管癌、贲门癌术后6例,严重烧伤(80％(?)Ⅱ°)1例。14例保守治疗,2例保守治疗无效而手术治疗。结果14例经治疗后(2例手术治疗)痊愈出院,2例死亡。结论 应激性溃疡大出血患者多病情危重,难以忍受二次手术,死亡率约为50％,因此应采取有效的保守治疗,对于保守治疗无效、大出血休克或胃肠穿孔者应及时手术治疗。     

Outcomes of Unrelated Donor Stem Cell Transplantion with Post-Transplant Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients with Severe Sickle Cell Disease

Unrelated donor (URD) hematopoietic cell transplantation (HCT) in children with sickle cell disease (SCD) is associated with a high incidence of rejection and graft-versus-host disease (GVHD). We report on the first 4 patients with severe SCD who underwent URD HCT using a novel myeloablative and immunosuppressive regimen composed of busulfan, fludarabine, and antithymocyte globulin with a single dose of post-transplant cyclophosphamide along with tacrolimus and mycophenolate mofetil for GVHD prophylaxis. Three patients engrafted and remain disease-free after a median follow-up period of 2.5 years. One patient had primary graft failure attributed to low stem cell content of the graft. Of interest, none of the engrafted patients developed acute or chronic GVHD. This preparative regimen along with the use of post-transplant cyclophosphamide offers a promising approach for unrelated donor transplants in patients with SCD and needs further corroboration in larger number of patients.     

Renovascular Hypertension Treated by Renal Artery Embolization

Renovascular hypertension is caused by narrowing of the arteries supplying the kidneys. There are several methods to treat renal artery stenosis, such as medications, percutaneous transluminal renal angioplasty, and atherosclerosis. A boy presented to our hospital with severe hypertension. Computed tomography angiogram revealed severe narrowing of the left renal artery and hypoplastic left kidney. Total renal artery embolizaton was performed to make a complete occlusion of the left renal artery. Follow-up renin and aldosterone levels were gradually decreased. The main advantage of renal artery embolization is that it is minimally invasive compared with extensive surgical procedures. Therefore, renal artery embolization should be considered as an alternative to surgical nephrectomy in pediatric patients with renovascular hypertension.