Treatment of intracardiac thrombi with argatroban

Intracardiac thrombi are well known complications associated with diverse cardiac diseases and venous thromboembolism. Therapeutic recommendations like thrombolysis, surgical thrombectomy, or treatment with low molecular heparin and intravenous unfractionated heparin based on small numbers of patients or retrospective case series have failed to reach a consensus. We report on the use of argatroban, a new direct thrombin inhibitor in 4 patients with intracardiac thrombi. Therapy was effective in all patients with complete resolution of thrombi. Treatment was complicated by recurrent strokes with complete neurological recovery in one patient. Therapy of intracardiac thrombi by argatroban is safe and effective. The drug requires no dosage adjustments for age, sex, or renal impairment, including in dialysis-dependent patients. Argatroban has been found to increase predictably activated partial thromboplastin time (aPTT) and activated clotting time (ACT) in a dose-dependent manner.     

Embolic protection devices for carotid artery stenting: better results than stenting without protection?

AIMS: Carotid artery stenting (CAS) for carotid artery stenoses has become an alternative to carotid endarterectomy. However, CAS itself can cause cerebral ischaemic events. Embolic protection devices (PD) promise to reduce the incidence of these events. METHODS AND RESULTS: From July 1996 to March 2003, 1483 patients from 26 hospitals were included in the prospective CAS Registry of the ALKK study group. A PD was used in 668 of 1483 patients (45%). The use of a PD has grown rapidly over the years and reached 100% in 2003. Patients treated with a PD had prior carotid artery dilatation more often (3.5% versus 1%, p < 0.001), a prior myocardial infarction (34% versus 27.4%, p = 0.007) and a history of arterial hypertension (89.9% versus 78.6%, p = 0.007) compared to patients treated without a PD. A thrombus was more often visible in patients treated under distal protection (16.5% versus 8%, p < 0.001). The use of a PD led to a 10-min longer intervention (45 min versus 35 min median, p < 0.001). Patients treated with a PD had a lower rate of ipsilateral stroke (1.7% versus 4.1%, p = 0.007) and a lower rate of all non-fatal strokes and all deaths (2.1% versus 4.9%, p = 0.004) during the hospital stay. This was confirmed by multiple logistic regression analysis (adjusted OR = 0.45, 95% CI: 0.23-0.91, p = 0.026). A similar reduction could be found for symptomatic as well as asymptomatic carotid artery stenoses. CONCLUSION: Since 1996 there has been a steady increase in the use of PDs for CAS, with a 100% use in 2003. The use of a PD may lower the rate of ipsilateral strokes during CAS.     

Surgical treatment of piles

PURPOSE: The present prospective, randomized clinical trial compares the outcome of surgical hemorrhoidectomy according to Parks and Milligan-Morgan in terms of hospital stay, duration of incapacity to work, symptom relief, length of morbidity, and patient convenience. METHODS: Thirty-four consecutive patients with third or fourth degree internal hemorrhoids were randomly allocated to the two groups. Before surgery, all patients were interviewed using a standard questionnaire, followed by rectal examination. All patients underwent a follow-up interview and examinations 1, 2, 4, 8, and 12 weeks after the operation. RESULTS: No serious postoperative complications were seen. Length of hospital stay (3.2 days for Parks hemorrhoidectomyvs. 4.6 days for Milligan-Morgan hemorrhoidectomy; 95 percent confidence interval, 0.2 and 2.6, respectively;P=0.02) and mean duration of incapacity to work (12.3 days for Parks hemorrhoidectomyvs. 20.2 days for Milligan-Morgan hemorrhoidectomy; 95 percent confidence interval, 5.7 and 10.2, respectively;P<0.001) differed significantly between the Milligan-Morgan and Parks patients. Until two weeks after the operation, Milligan-Morgan hemorrhoidectomy patients experienced significantly more pain. CONCLUSIONS: Our study confirms that both operations are safe, easy to perform, and lead to satisfactory results. However, the Parks procedure is the preferred option, because it minimizes patients' postoperative discomfort, is more economic, has a significantly reduced hospital stay, and has a shorter time for return to work.     

Quantification of cells in islets of langerhans using DNA determination

Summary DNA content seems to be an ideal reference parameter for data on secretory function or metabolism of pancreatic islets. The approved fluorometric DNA assay with diaminobenzoic acid (DABA) of Kissane and Robins comprises repeated ethanol extractions of the tissue for removal of lipids from which some DABA-reactive aldehydes may originate. In the present study it is demonstrated that only negligible amounts of DABA-positive material are extractable from islets of Langerhans. Furthermore, it is shown that various substances used in experiments on the endocrine pancreas do not interfere with the DABA-DNA reaction. A modification of the original DABA procedure which does not include ethanol extractions and which is thus more simple and accurate is described for application to pancreatic islets in the absence as well as in the presence of incubation medium. A close linear correlation between islet dry weight and islet DNA content is demonstrated. Islets from rats, normal mice, and ob/ob mice contain 38.3–39.2 ng DNA per g dry weight.     

卒中的抗凝治疗

1引言 所谓抗凝治疗是用适当的药物(即抗凝剂)来抑制血液凝固的控制疗法.抗凝剂在脑缺血治疗中的作用仍处在发展之中.业已证明,没有一种单一的治疗方法能够有效地防治所有类型的脑缺血,包括肝素、肝素类似物和华法林等.尽管抗凝治疗可能会引起出血并发症,但在过去10年中,已经有多项随机对照研究有助于确定哪些患者可能从抗凝治疗中受益.     

Hepatocyte cytoskeleton during ischemia and reperfusion--influence of ANP-mediated p38 MAPK activation

AIM: To determine functional consequences of this activation, whereby we focused on a potential regulation of the hepatocyte cytoskeleton during ischemia and reperfusion. METHODS: For in vivo experiments, animals received ANP (5 μg/kg) intravenously. In a different experimental setting, isolated rat livers were perfused with KH-buffer ±ANP (200 nmol/L)±SB203580 (2 μmol/L). Livers were then kept under ischemic conditions for 24 h, and either transplanted or reperfused. Actin, Hsp27, and phosphorylated Hap27 were determined by Western blotting, p38 MAPK activity by in vitro phosphorylation assay. F-actin distribution was determined by confocal microscopy. RESULTS: We first confirmed that ANP preconditioning leads to an activation of p38 MAPK and observed alterations of the cytoskeleton in hepatocytes of ANP-preconditioned organs. ANP induced an increase of hepatic F-actin after ischemia, which could be prevented by the p38 MAPK inhibitor SB203580 but had no effect on bile flow. After ischemia untreated livers showed a translocation of Hsp27 towards the cytoskeleton and an increase in total Hsp27, whereas ANP preconditioning prohibited translocation but caused an augmentation of Hsp27 phosphorylation. This effect is also mediated via p38 MAPK, since it was abrogated by the p38 MAPK inhibitor SB203580. CONCLUSION: This study reveals that ANP-mediated p38 MAPK activation leads to changes in hepatocyte cytoskeleton involving an elevation of phosphorylated Hsp27 and thereby for the first time shows functional consequences of ANP-induced hepatic p38 MAPK activation.     

Recurrent deletion of 3p13 targets multiple tumour suppressor genes and defines a distinct subgroup of aggressive ERG fusion‐positive prostate cancers

Deletion of 3p13 has been reported from about 20% of prostate cancers. The clinical significance of this alteration and the tumour suppressor gene(s) driving the deletion remain to be identified. We have mapped the 3p13 deletion locus using SNP array analysis and performed fluorescence in situ hybridization (FISH) analysis to search for associations between 3p13 deletion, prostate cancer phenotype and patient prognosis in a tissue microarray containing more than 3200 prostate cancers. SNP array analysis of 72 prostate cancers revealed a small deletion at 3p13 in 14 (19%) of the tumours, including the putative tumour suppressors FOXP1, RYBP and SHQ1. FISH analysis using FOXP1‐specific probes revealed deletions in 16.5% and translocations in 1.2% of 1828 interpretable cancers. 3p13 deletions were linked to adverse features of prostate cancer, including advanced stage (p < 0.0001), high Gleason grade (p = 0.0125), and early PSA recurrence (p = 0.0015). In addition, 3p13 deletions were linked to ERG⁺ cancers and to PTEN deletions (p < 0.0001 each). A subset analysis of ERG⁺ tumours revealed that 3p13 deletions occurred independently from PTEN deletions (p = 0.3126), identifying tumours with 3p13 deletion as a distinct molecular subset of ERG⁺ cancers. mRNA expression analysis confirmed that all 3p13 genes were down regulated by the deletion. Ectopic over‐expression of FOXP1, RYBP and SHQ1 resulted in decreased colony‐formation capabilities, corroborating a tumour suppressor function for all three genes. In summary, our data show that deletion of 3p13 defines a distinct and aggressive molecular subset of ERG⁺ prostate cancers, which is possibly driven by inactivation of multiple tumour suppressors. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

OCT evaluation of the internal adaptation of ceramic veneers depending on preparation design and ceramic thickness

ObjectivesIn-vitro evaluation of the influence of preparation design and thickness of ceramic veneers on the interfacial bond using optical coherence tomography (OCT).MethodsSixty-four central incisors were randomly assigned to four preparation designs differing from no to complete dentine exposure (n = 16 each): non-prep (NP), minimal-invasive (MI, no dentine exposure), semi-invasive (SI, 50% dentine) and invasive (I, 100% dentine). Ceramic veneers (IPS InLine Veneer) of two thicknesses (0.2?0.5 mm (T1) and > 0.5–1.2 mm (T2)) were etched, silanized, and adhesively luted (Optibond FL, Variolink Veneer). After water storage (37 °C, 21d), thermocycling (2000 cycles, 5°-55 °C), and mechanical loading (2 + 1 million cycles, 50 + 100 N) specimens were imaged by spectral-domain OCT (Telesto II, Thorlabs). Adhesive defects at the ceramic-composite and tooth-composite interfaces were quantified on 35 equidistantly distributed OCT B-scans (length, %). Statistical differences were verified with Wilcoxon-/Mann-Whitney-U-test (α = 0.05).ResultsAdhesive defects appeared in all groups at both interfaces, albeit to differing extents (0.1 – 31.7%). NP and MI veneers showed no significant differences at the interfaces (p_i > 0.05). In groups, SI and I, significantly more adhesive defects appeared at the tooth-composite compared to the veneer-composite interface (p_i ≤ 0.039). The following preparation designs and veneer thicknesses showed differences (p_i ≤ 0.021): Veneer-composite: NP-T1 < I-T1, MI-T1 < I-T1, I-T1 > I-T2; Tooth-composite: NP-T1 < SI-T1, NP-T1 < I-T1, NP-T2 > MI-T2, MI-T1 < SI-T1, MI-T1 < I-T1, SI-T1 < I-T1, MI-T2 < SI-T2, MI-T2 < I-T2.SignificanceThe interface adhesion of ceramic veneers was influenced by the preparation design and the veneer thickness. A ceramic thickness of at least 0.5 mm and a preparation without exposing dentine is advantageous for the interfacial bond.