Initial experience with a new femoral artery closure device following percutaneous coronary intervention with glycoprotein IIb/IIIa inhibition.

The aim of the study was to determine the safety and efficacy of a novel femoral artery closure device (StarClose, Abbott Vascular Devices, Redwood City, CA) following percutaneous coronary intervention employing aspirin, heparin, and glycoprotein (GP) IIb/IIIa inhibition. A prospective nonrandomized single-center pilot study of the StarClose device included a subset of patients undergoing percutaneous coronary intervention utilizing GP IIb/IIIa inhibitors. Those that fulfilled the inclusion criteria (age < 80, no periprocedural haematoma, puncture above the superficial femoral and profunda femoralis artery bifurcation, no significant femoral artery disease) underwent closure of the femoral artery puncture site with a StarClose device immediately on completion of the procedure. Time to hemostasis (TTH), bleeding, mobilization, and short-term clinical follow-up data were collected, and an ultrasound scan of the femoral artery was performed 2 weeks later. Twenty-five patients were recruited, of whom 23 underwent percutaneous coronary intervention (PCI). Their mean age was 58 +/- 12 years, 84% were male, and 63% had unstable angina. All were on aspirin 100-150 mg daily and all PCI patients received i.v. heparin 4-10,000 units at commencement of the procedure and clopidogrel 600 mg on completion. Two patients were on a tirofiban infusion and 23 received a double bolus of eptifibatide, each 0.18 mg/kg, separated by 10 min. The procedural success was 100% and device success 23/25 (92%), with 1 failure due to technical error. The median device delivery time was 36 sec (range, 11-178) and median TTH 37 sec (range, 10-509 sec). There were no major adverse events. In 10 patients, a moderate amount of tract ooze required a short period of adjunctive manual compression. Follow-up ultrasound femoral artery scans revealed no compromise of the vessel lumen. Femoral artery closure with the device following coronary angiography and intervention using glycoprotein IIb/IIIa receptor inhibitors is safe and effective. A randomized trial of a larger number of patients is warranted.     

Concomitant overexpression of mir‐182‐5p and mir‐182‐3p raises the possibility of IL‐17–producing Treg formation in breast cancer by targeting CD3d,ITK, FOXO1, and NFATs: A meta‐analysis and experimental study

T cells are polarized toward regulatory T cells (Tregs) in tumor microenvironment by the shuttling of microRNAs that target T cell–activating signaling pathways. We evaluated the expression of the miR‐182 cluster (miR‐96, 182, and 183) in peripheral blood mononuclear cells (PBMCs) of patients with breast cancer (BC), and T cell polarization by the expression of FOXO1, NFATs, ITK, TCR/CD3 complex, and IL‐2/IL‐2RA. Twenty‐six microRNAs overexpressed in tumor tissues and sera of these patients were extracted by a meta‐analysis. Then, the expression of the miR‐182 cluster was investigated in PBMCs and sera of these patients and correlated with their targets in PBMCs. Finally, miR‐182 was cloned into Jurkat cells to evaluate its effects on T cell polarization. FOXO1, CD3d, ITK, NFATc3, NFATc4, and IL‐2RA were targeted by miR‐182, due to which their expression decreased in PBMCs of patients. Although IL‐6, IL‐17, and TGF‐β increased after miR‐182 transduction, IL‐2 dramatically decreased. We revealed CD4⁺FOXP3⁺ T cell differentiation in the miR‐182–transduced group. Although miR‐182 has inhibitory effects on T cells by the inhibition of FOXO1, TCR/CD3 complex, NFATs, and IL‐2/IL‐2RA signaling pathways, it increases FOXP3, TGF‐β, and IL‐17 expression to possibly drive T cell deviation toward the transitional state of IL‐17–producing Tregs and Treg formation in the end.     

Extraction of challenging intracoronary thrombi: multi-device strategies using guide catheters, distal vascular protection devices and aspiration catheters

Patients with large intracoronary thrombi represent a difficult management problem for the interventional cardiologist. We report 10 cases of challenging thrombi treated percutaneously using varying combinations of deep guide catheter engagement, guide aspiration, dedicated catheter aspiration and withdrawal of a distal filter vascular protection device. These cases demonstrate interventional options which may be considered for such patients.     

Vasopressin-dependent and -independent control of the release of adrenocorticotropin

We tested the possibility that vasopressin mediates the responses of adrenocorticotropin (ACTH) to electrical stimulation of various areas of the hypothalamus. Thirty-three cats were anesthetized with chloralose-urethane, immobilized with gallamine, and respired artificially. Plasma ACTH was measured by RIA. Intraventricular administration of antiserum to vasopressin blocked the release of ACTH induced by electrical stimulation of the paraventricular nucleus (PVN), suggesting a role for the vasopressinergic projection from PVN to the external zone of the median eminence. In contrast, the release of ACTH induced by stimulation of areas ventral to PVN was unaffected by the antiserum. Thus, there is at least one corticotropin releasing factor released from nuclei other than PVN that is distinct from vasopressin.     

Pruritus in Chronic Hepatitis C (Association with High Serum Bile Acids, Advanced Pathology, and Bile Duct Abnormalities)

Pruritus is a common symptom of chroniccholestatic liver diseases but is considered rare inchronic hepatitis. We observed pruritus to be anunusually common complaint in patients with advancedchronic hepatitis C. We reviewed the records of 175chronic hepatitis C patients to identify patients withsevere, diffuse, unexplained pruritus; 12 consecutiveprospective patients undergoing liver biopsy for chronic hepatitis C served as controls.Assessment included laboratory biochemical tests andassessment of liver pathology by stage, grade, hepaticactivity index, and a bile duct score. Pruritus waspresent in nine (5.1%) patients. Serum AST, ALT,alkaline phosphatase, GGTP, total bilirubin, andferritin were similar in pruritics and controls.Pruritics had higher serum bile acids (2028.4 ±223.1 mmol/liter vs 423.1 ± 194.3, P < 0.001), highertransferrin saturation (57.5 ± 6.8% vs 33.2± 3.3, P < 0.01), and lower HCV RNA by bDNA(24.5 ± 12.7 ± 10 vs 172.7 ± 54.1× 10⁵, P < 0.05). Pathology revealedcirrhosis in 6/9 (66.6%) pruritics vs 1/12 (8.3%) controls (P < 0.01).Pruritics had higher pathologic stage (3.7 ± 0.2vs 2.2 ± 0.4, P < 0.01), grade (4.4 ±0.2 vs 2.1 ± 0.2, P < 0.001), activity index(14.3 ± 1.9 vs 8.6 ± 1.9, P < 0.025),and bile duct score (7.6 ± 0.6 vs 4.7 ± 0.4, P <0.01). Of eight pruritics treated withIFN-_2b, two had complete ALT responseand one relapsed. Pruritus followed a relapsing courseand only three patients partially responded despite a variety of interventions. Inconclusion, pruritus is a common complication ofadvanced CHC. Its presence is associated with high serumbile acids, advanced pathology and bile ductabnormalities. The clinical course of pruritus is relapsingand response to therapy is inconsistent. These featuressuggest that pruritus in CHC has a pathogenesis that mayvary from that of chronic cholestaticdiseases.     

The natural course of multiple endocrine neoplasia type IIb. A study of 18 cases.

BACKGROUND--Multiple endocrine neoplasia (MEN) type IIb is an autosomal dominantly inherited disorder associated with medullary thyroid cancer, pheochromocytoma, and a characteristic phenotype. The present study was performed to investigate the natural course of the syndrome and to describe its expression. METHODS--The medical records of 18 patients with MEN IIb, seven male and 11 female, were reviewed. RESULTS--The mean age at diagnosis of MEN IIb was 18 years (range, 8 to 41 years). All 18 patients had medullary thyroid cancer. In three patients, medullary thyroid cancer was diagnosed via screening. In two of these patients, the calcitonin value normalized after thyroidectomy. One patient died of metastases from medullary thyroid cancer at the age of 20 years (median duration of follow-up, 10 years). Eight of the 18 patients had pheochromocytomas. All of our patients had neuromas and bumpy lips, and all but one had a marfanoid habitus. A large proportion of the patients had intestinal abnormalities (75%), thickened corneal nerves (69%), skeletal abnormalities (87%), and delayed puberty (43%). CONCLUSIONS--The course of medullary thyroid cancer in MEN IIb is not always as aggressive as is generally thought. Periodic examination of relatives who are at risk may lead to early diagnosis and curative treatment. Intestinal abnormalities, skeletal abnormalities, and delayed puberty are commonly found in association with MEN IIb.     

Effect of microtubule disorganizing or overstabilizing drugs on the proliferation of rat 3T3 cells and their virally induced transformed derivatives

Drugs that disorganize or overstabilize cytoplasmic microtubules (colchicine, vinblastine, griseofulvin, or taxol) can at certain concentrations totally block proliferation of SV40 and polyoma virus transformants with only a minimal effect on the proliferation of the parental rat 3T3 cells. This difference in sensitivity is not due to a more active drug uptake by transformed cells. Examination of cytoplasmic microtubules in actively proliferating normal or transformed cells reveals two categories in each case: cells with microtubules and cells without distinct microtubules. The proportion of cells without distinct microtubules did not differ much between normal and transformed cells. However, transformed cells with a clear microtubule network appear to have fewer microtubules than normal cells. This may contribute to the higher sensitivity of transformed cells. These results render even more rational the use of antimicrotubule drugs in cancer chemotherapy.