Soluble Fas ligand and atherosclerosis in hypertensive patients

BACKGROUND : The Fas-Fas ligand (FasL) system is involved in apoptosis in many types of cells. Recently, the expression of FasL on endothelial cells was reported. FasL is cleaved by a metalloproteinase and released in serum as soluble FasL (sFasL). Vasoactive substances, including metalloproteinase, are modulated by endothelial dysfunction. Advanced atherosclerosis and impaired endothelial function are seen in hypertensive patients. The inflammatory response has an important role in the development of atherosclerosis, whereas C-reactive protein (CRP) is associated with the presence and severity of atherosclerosis. OBJECTIVE : To measure the intima-media thickness of the common carotid artery and evaluate the relationship between atherosclerosis and serum sFasL concentrations in hypertensive patients. PATIENTS AND MAIN OUTCOME MEASURES : Forty-seven patients with hypertension participated in the study. The intima-media thickness of the common carotid artery was evaluated by ultrasound imaging. Serum concentrations of sFasL were measured by enzyme-linked immunosorbent assay. RESULTS : Intima-media thickness correlated positively with age (r = 0.362, P = 0.012) and sFasL concentrations (r =0.332, P = 0.022), and negatively with creatinine clearance (r = -0.399, P = 0.0055). A general linear model analysis with atherosclerotic risk factors and sFasL revealed that age, sFasL, high-density lipoprotein-cholesterol and systolic blood pressure were significantly associated with intima-media thickness. Furthermore, we demonstrated that serum sFasL is directly associated with CRP concentration (r = 0.316, P = 0.030). CONCLUSIONS : These results indicated that serum sFasL concentration is associated with atherosclerosis and inflammatory disease, in patients with hypertension.     

Diagnosis and management of acute obstetrical DIC

Obstetrical disseminated intravascular coagulation (DIC) is usually a very acute, serious complication of pregnancy. The DIC diagnostic criteria in obstetrics (the obstetrical DIC score) help with making a prompt diagnosis and starting treatment early. These DIC diagnostic criteria, in which higher scores are given for clinical parameters than for laboratory parameters, have three components: (1) the underlying disease, (2) clinical symptoms, and (3) laboratory findings. It is justified that it is appropriate to initiate therapy for DIC when the obstetrical DIC score reaches 8 points or more before obtaining the results of coagulation tests. Management: (1) Control of the underlying disease: because prolongation of exposure to the triggering factors worsens DIC, it is important to eliminate the etiologic factors as rapidly as possible. Elimination of the cause of DIC can be easily performed in obstetrics, for example, by cesarean section. (2) Antithrombin (AT) therapy: AT monotherapy (1,500 to 3,000 units/day, 2 days) is preferably employed instead of heparin monotherapy or heparin-AT therapy because of the hemorrhagic side effects of heparin. (3) Synthetic serine protease inhibitors: continuous infusion ofgabexate mesilate (FOY) or nafamostat mesilate (FUT) is effective for DIC. Controlled multicenter trials showed a significant improvement not only in clinical response but also in platelet counts and prothrombin time (PT) in the AT group compared with the FOY group. (4) Activated protein C (APC) can inhibit thrombin generation and accelerate fibrinolytic activity. APC (5,000 to 10,000 units) is administered for 2 days in patients with placental abruption complicated by DIC. APC is a very safe, effective, and useful agent for the treatment of DIC.     

An atypical case of "Takotsubo cardiomyopathy" during alcohol withdrawal: abnormality in the transient left ventricular wall motion and a remarkable elevation in the ST segment

A 64-year-old man was admitted due to hypokalemia-related myopathy. He was heavy drinker. He felt the stress of alcohol withdrawal during his hospitalization. The patient suffered a cardiopulmonary arrest lasting approximately 5 minutes on the fifth hospital day. One day later, ST-segment elevation was observed in leads I, aV(L), and V(2-6). Emergent cardiac catheterization was performed for suspicion of acute myocardial infarction. Normal coronary arteries with anterior akinesis of the left ventricle were revealed during the procedure. The present case may be an atypical form of "Takotsubo cardiomyopathy" in which the left ventricular contraction is due to focal anterior wall motion abnormalities.     

Hinesol,a compound isolated from the essential oils of Atractylodes lancea rhizome,inhibits cell growth and induces apoptosis in human leukemia HL-60 cells

Hinesol is a unique sesquiterpenoid isolated from the Chinese traditional medicine, Atractylodes lancea rhizome. In a previous study, we screened various natural products in human leukemia HL-60 cells and identified an essential oil fraction from A. lancea rhizome that exhibited apoptosis-inducing activity in these cells; hinesol was subsequently shown to be the compound responsible for this apoptosis-inducing activity. In this study, we describe the cytotoxic effects and molecular mechanisms of hinesol in HL-60 cells. The antitumor effect of hinesol was associated with apoptosis. When HL-60 cells were treated with hinesol, characteristic features of apoptosis, such as nuclear fragmentation and DNA fragmentation, were observed. These growth-inhibitory and apoptosis-inducing activities of hinesol in leukemia cells were much stronger than those of β-eudesmol, another compound isolated from the essential oil fraction. Furthermore, hinesol induced activation of c-Jun N-terminal kinase (JNK), but not p38, prior to the onset of apoptosis. These results suggested that hinesol induced apoptosis through the JNK signaling pathway in HL-60 cells. Therefore, hinesol may represent a novel medicinal drug having indications in the treatment of various cancers, including leukemia.

     

Efficacy of thromboelastography in the management of anticoagulation for veno-venous extracorporeal membrane oxygenation in a coronavirus disease 2019 patient: A case report

Rationale:In coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome refractory to optimal conventional management, we should consider the indication for veno-venous extracorporeal membrane oxygenation (V-V ECMO). Growing evidence indicates that COVID-19 frequently causes coagulopathy, presenting as hypercoagulation and incidental thrombosis. For these reasons, a multifactorial approach with several anticoagulant markers should be considered in the management of anticoagulation using heparin in COVID-19 patients on V-V ECMO.Patient concerns:A 48-year-old man was infected with COVID-19 with a worsening condition manifesting as acute respiratory distress syndrome.Diagnoses:He was refractory to conventional therapy, thus we decided to introduce V-V ECMO. We used heparin as an anticoagulant therapy for V-V ECMO and adjusted the doses of heparin by careful monitoring of the activated clotting time (ACT) and activated partial thromboplastin time (APTT) to avoid both hemorrhagic and thrombotic complications. We controlled the doses of heparin in the therapeutic ranges of ACT and APTT, but clinical hemorrhaging and profound elevation of coagulant marker became apparent.Interventions:Using thromboelastography (TEG; Haemonetics) in addition to ACT and APTT, we were able to clearly detect not only sufficient coagulability of COVID19 on V-V ECMO (citrated rapid thromboelastography-R 0.5 min, angle 75.5°, MA 64.0 mm, citrated functional fibrinogen-MA 20.7 mm) but also an excessive effect of heparin (citrated kaolin -R 42.7 min, citrated kaolin with heparinase 11.7 min).Outcomes:Given the TEG findings indicating an excessive heparin effect, the early withdrawal of ECMO was considered. After an evaluation of the patient''s respiratory capacity, withdrawal from V-V ECMO was achieved and then anticoagulation was stopped. The hemorrhagic complications and elevated thrombotic marker levels dramatically decreased.Lessons:TEG monitoring might be a useful option for managing anticoagulation in COVID-19 patients on V-V ECMO frequently showing a hypercoagulative state and requiring massive doses of heparin, to reduce both hemorrhagic and thrombotic complications.     

Risk factors of thrombotic recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism

Journal of Thrombosis and Thrombolysis - Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed...     

The role of transcarinal needle aspiration in the diagnosis and staging of lung cancer: computed tomographic correlates of a positive result

BACKGROUND: Transbronchial needle aspiration (TBNA) is used most frequently to assess subcarinal nodes because of its technical ease. OBJECTIVES: We conducted a prospective observational clinical study to define the indications for TBNA use for subcarinal nodes (transcarinal needle aspiration, TCNA) related to the nodal size by computed tomography (CT) of the chest. METHODS: One hundred and eight consecutive patients with lung cancer underwent TCNA at the time of initial diagnostic bronchoscopy within a 22-month period. RESULTS: TCNA was positive in 21 of the patients. Only 1 of 75 patients (1%) with subcarinal nodes less than 10 mm in short-axis diameter by CT had a positive result. TCNA for enlarged nodes, 10 mm or greater, had a high positive yield of 61% (20/33). The procedure provided the only evidence of unresectable non-small cell lung cancer (stage IIIA-N2 disease) in 3 patients and the sole pathological evidence for malignancy in 5 patients. CONCLUSIONS: The high yield of positive TCNA results for enlarged subcarinal nodes contributes to the improvement of the overall diagnostic yield of bronchoscopy. We recommend that TCNA for enlarged subcarinal nodes on CT in patients with presumptive lung cancer should be performed routinely at the time of initial diagnostic bronchoscopy.     

Mucosal bile duct carcinoma with superficial spread

We describe a case of mucosal bile duct carcinoma with superficial spread in a 69-year-old man with gallstone pancreatitis. The patient was seen at the hospital because of abdominal pain, fever, and jaundice. Endoscopic retrograde cholangiography (ERC) demonstrated a protruding lesion in the lower third of the common bile duct (CBD) showing wall irregularity suggestive of malignancy. Percutaneous transhepatic cholangioscopy (PTCS) disclosed a papillary tumor with granular mucosa extending continuously to the middle third of the CBD. Cholangioscopic biopsy specimens taken from both the papillary tumor and surrounding granular mucosa revealed papillary adenocarcinoma. After this assessment of extent of cancer by PTCS, we performed pancreatoduodenectomy with extrahepatic bile duct resection and regional lymph node dissection. Pathology examination revealed papillary adenocarcinoma limited to the mucosal layer. The resected margin of the bile duct was free of tumor. We also reviewed 25 cases of early mucosal bile duct carcinoma described in detail in the Japanese literature, and we discuss the diagnostic advantages of PTCS.     

A case of pseudoxanthoma elasticum associated with sick sinus syndrome

Typical angioid streaks were found on routine ophthalmologic examination in a 42-year-old female with yellowish, coalescing papules on her neck without any symptoms. Biopsy of the cutaneous lesion showed degeneration and fragmentation of the elastic fibers and many basophilic-stained calcifications in mid-dermis, which are consistent with pseudoxanthoma elasticum. Twenty-four-hour Holter electrocardiography (ECG) showed sinus arrest for 2.5 seconds, and an electrophysiological study revealed sinus nodal dysfunction (sick sinus syndrome), whereas all of the coronary arteries were intact, despite a treadmill stress ECG test showing significant ST depressions. The association of pseudoxanthoma elasticum and sick sinus syndrome is very rare. One possible explanation for this association here is that the degeneration of elastic fiber in endomysium of the sino-atrial node may have affected heart conduction systems, resulting in sick sinus syndrome.Part of this work was presented at the 76th Japanese Circulation Society Kyushu Meeting, Japan, June 18, 1994     

Prevalence of diabetes mellitus in individuals with airflow obstruction in a Japanese general population: The Yamagata-Takahata Study

Background

Diabetes has been reported as a comorbidity of chronic obstructive pulmonary disease (COPD) in Western countries, but it has not been demonstrated in epidemiological reports in Japan. The purpose of this study was to clarify whether the relationship between airflow obstruction and diabetes can be confirmed in a Japanese general population.