Comparison of vasoconstrictor actions of norepinephrine and potassium chloride before and after damage of endothelium by saponin

Summary Using isolated and perfused mesenteric arterial preparations of dogs, vasoconstrictor responses to intraluminal norepinephrine and potassium chloride were investigated in the presence and absence of the endothelium. Intraluminal administration of saponin readily removed the endothelium. Saponin (1–3 mg) caused an increase in perfusion pressure, and then approximately 20 min later perfusion pressure became stable at a somewhat higher level than that of the control. A larger dose of saponin (10 mg) caused a tremendous but temporary increase of perfusion pressure. KCl-induced vasoconstriction was significantly enhanced by pretreatment with 0.3, 1, and 3 mg saponin, but norepinephrine-induced constriction was not modified significantly. Moreover, it was demonstrated that diltiazem, a potent Ca antagonist, inhibited the KCl-induced vasoconstriction more readily in the absence than in the presence of the endothelium.     

Readmissions after continuous flow left ventricular assist device implantation

Continuous flow left ventricular assist device (CF-LVAD) therapy has improved the survival of patients with advanced heart failure. However, the readmission rate of CF-LVAD patients is still relatively high. A total of 90 patients who received CF-LVADs between April 2011 and March 2016 at our institute and were discharged home were analyzed retrospectively. They were followed up through March 2017. Clinical data, including frequency, length and etiology of readmission, were obtained from medical records. The mean observation period after initial discharge was 713 ± 322 days. In total, 73 patients (81%) had 236 readmissions, 214 unplanned and 22 planned. The overall and unplanned readmission rates were 1.34 and 1.22 per patient-year, respectively. The rate of freedom from unplanned first readmission at 1 year after initial discharge was 39%. The median interval between the previous hospital discharge and first and second readmissions was 311 and 213 days, respectively (log-rank test, p = 0.117). The rate of readmission after more than three readmissions was significantly higher than that of first or second readmission (log-rank test, p < 0.001). The most common etiology of readmission was driveline infection (DLI) (36%), followed by stroke (9%). The median length of hospital stay due to DLI was 23 days. The patients with repeated unplanned readmissions had significantly lower EuroQol 5 dimensions questionnaire utility score than those with no or just one readmission. Readmission was common in CF-LVAD patients, and the most common etiology of readmissions was DLI. The interval to the next readmission seemed shorter for patients with repeated readmissions.     

Histological alterations following fine-needle aspiration for parathyroid adenoma: Incidence and diagnostic problems

This study aimed to clarify the histological alterations following fine-needle aspiration for parathyroid adenoma and discuss the occurrence of diagnostic problems. Among the 392 patients with parathyroid adenoma who underwent resection, fine-needle aspiration was performed for 21 (5.1%) parathyroid adenoma nodules. Histological findings that were significantly more frequent in cases that underwent fine-needle aspiration were considered histological alterations following fine-needle aspiration for parathyroid adenoma, including the following six findings: thick fibrous capsule (71.4%), multilayered fibrous capsules (14.3%), capsular pseudo-invasion (42.9%), fibrous bands (57.1%), hemosiderin deposition (14.3%), and tumor implantation (14.3%). Eighteen parathyroid adenoma nodules (85.7%) exhibited one or more of the six findings. Tumor cells and adipocytes entrapped within the thick fibrous capsule were occasionally observed. The fibrous bands were frequently connected to the thick fibrous capsule. The number of passes, duration between fine-needle aspiration and resection, tumor size, and purpose of fine-needle aspiration were not related to the incidence of histological findings. Because of the histological alterations following fine-needle aspiration for parathyroid adenoma that can be easily mistaken for signs of atypical adenoma or parathyroid carcinoma, we recommend that the six findings be excluded from pathological findings indicating atypical adenoma or parathyroid carcinoma in patients with preoperative fine-needle aspiration.     

Cytologic findings and differential diagnoses of primary thyroid MALT lymphoma with striking plasma cell differentiation and amyloid deposition

We report two cases of thyroid mucosa‐associated lymphoid tissue (MALT) lymphoma with associated amyloid protein deposition. While other primary thyroid neoplasms sush as medullary carcinoma and plasmacytoma with associated amyloid protein are known to occur and have been previously described by fine‐needle aspiration cytology (FNAC), to our knowledge, the current cases are the first of thyroid MALT lymphoma with amyloid deposition to be detailed in the cytopathology literature. Case 1 was a 73‐year‐old female with chronic thyroiditis. FNAC suspected MALT lymphoma. The amyloid material was not noticed, nevertheless it existed. Case 2 was a 71‐year‐old female with a nodule of the thyroid. Malignant lymphoma and medullary carcinoma were suspected by FNAC. The possibility of medullary carcinoma was excluded by a measurement of serum calcitonin and carcinoembryonic antigen. After follow‐up for two years, the nodule was diagnosed as MALT lymphoma associated with plasma cell differentiation and amyloidosis by the fourth FNAC. When we encounter small round cell tumors associated with amyloid in thyroid FNAC, we should consider not only medullary carcinoma but also MALT lymphoma. Diagn. Cytopathol. 2014;42:73–77. © 2013 Wiley Periodicals, Inc.     

Clinical,cytological, and pathological characteristics of metastatic renal cell carcinoma to the thyroid: A study of 14 cases at a Japanese single institution

A preoperative diagnosis of metastatic renal cell carcinoma to the thyroid (MRCCT) is important for determining clinical management but is challenging even in cases with a clinical history of renal cell carcinoma (RCC). This study aimed to elucidate the clinical, cytological, and pathological characteristics of MRCCT. Fourteen MRCCT cases extracted from 18 320 malignant thyroid tumors were included in this study. Twelve MRCCT (85.7%) occurred as solitary lesions and the most frequently suspected lesions on ultrasonography were follicular tumors. On cytology, 46.2% of cases were reported as RCC or suspected RCC; a medical history of RCC and immunocytochemistry were helpful in interpretation. RCC metastasized to a follicular adenoma in 50.0% of the solitary lesions. MRCCTs with a long interval from the initial presentation, solitary lesion, and Ki-67 labeling index <10% showed significantly longer disease-free survival. MRCCT is characterized by a long interval from the initial presentation of RCC, appearance as a solitary nodule, ultrasonographic similarity to follicular tumors, sharing cytological findings with primary thyroid tumors, and high frequency of metastasis within follicular adenoma. A long interval from the initial presentation, occurrence as a solitary lesion, and low Ki-67 labeling index may be favorable prognostic factors.     

Severe tricuspid regurgitation after mitral valve surgery: the risk factors and results of the aggressive application of prophylactic tricuspid valve repair

Purpose

This study aimed to examine the risk factors for severe postoperative tricuspid regurgitation (TR) in patients undergoing mitral valve surgery. We also studied the effects of prophylactic tricuspid valve repair (TVR) on severe postoperative TR.

Methods

We retrospectively studied 125 patients without severe TR who underwent mitral valve surgery from 1987 to 2006. Patients did not undergo TVR before 1998 (the early period, n = 54). In 1998 (the late period, n = 71), patients with a preoperative tricuspid annular diameter of ≥35 mm underwent TVR using an annuloplasty ring (n = 52).

Results

In the analysis of the early period, the rates of freedom from severe TR at 10 and 20 years after surgery were 76 and 59 %, respectively. A multivariate analysis identified moderate preoperative TR as a significant risk factor for severe TR. In the late period, none of the 52 patients who underwent TVR developed severe TR. However, 4/19 patients who did not undergo TVR developed severe TR, and all of these four patients had a preoperative tricuspid annular diameter of ≤35 mm.

Conclusions

Moderate preoperative TR is a significant risk factor for severe postoperative TR in patients undergoing mitral valve surgery. The aggressive application of TVR can prevent severe postoperative TR; however, tricuspid annular dilatation might not be a good indicator for TVR.

     

Genetic manipulation of key determinants of ion flow in glutamate receptor channels in the mouse

Glutamate receptor channels are built around an ancient pore loop structure which defines the inner channel environment and which is connected to structures for channel gating. This pore loop, which corresponds to the M2 region of the receptor subunits, enters the lipid bilayer from the intracellular side in an alpha-helical configuration, then kinks to form a random coil and exits the lipid bilayer at the intracellular side. The narrow constriction of the channel is formed by amino acid residues that occupy a position shortly after the end of the alpha-helical part of M2. These residues determine ion selectivity and conductance properties of the glutamate-gated channel. The critical residues are asparagines for NMDA receptor subunits and glutamine or arginine for AMPA and kainate receptor subunits. Presence of arginine in the critical channel position of AMPA and kainate receptors is controlled by site-selective RNA editing. To study the importance of these critical channel residues in the mouse, we introduced codon changes in the endogenous genes for NMDA and AMPA receptor subunits. Our results show that changes in the critical channel position are not tolerated, but lead to early death. Therefore, the impact on adult synaptic function and plasticity by glutamate receptor channels with changed ion selectivity and conductance needs to be addressed by conditional expression of the mutant receptors.     

Silymarin enhanced cytotoxic effect of anti-Fas agonistic antibody CH11 on A375-S2 cells

Silymarin is a polyphenolic flavonoid from milk thistle (Silybum marianum), which has anti-inflammatory, cytoprotective as well as antioxidant effects. Our previous study demonstrated that silymarin has anti-apoptotic effect against UV irradiation. In this study, we assessed the effect of silymarin on anti-Fas agonistic antibody CH11-treated human malignant melanoma, A375-S2 cells. Pretreatment with silymarin (3 × 10^- 4 mol/L) significantly induced cell apoptosis in CH11-treated A375-S2 cells. Mitochondrial transmembrane potential (ΔΨ_m) was also down-regulated by silymarin pretreatment. Caspase-8, -9, -3 and pan-caspase inhibitors partially reversed silymarin-induced apoptosis of CH11-treated cells. The expression of Fas-associated proteins with death domain (FADD), a downstream molecule of the death receptor pathway, was increased by silymarin pretreatment, followed by cleavage of procaspase-8, whose activation induced cell apoptosis. Moreover, cleavage of procaspase-3 and digestion of its substrate, the inhibitor of caspase-activated DNase (ICAD), were also increased by silymarin pretreatment. These results suggested that silymarin could also exaggerate the apoptotic effect of anti-Fas agonistic antibody CH11 on A375-S2 cells.