EFFECTS OF LOCALLY ADMINISTERED ARGATROBAN ON RESTENOSIS AFTER BALLOON ANGIOPLASTY: EXPERIMENTAL AND CLINICAL STUDY

1. This study was undertaken to evaluate the preventive effects of locally administered argatroban, a competitive inhibitor of thrombin-induced platelet activation, on restenosis after balloon angioplasty. 2. A hydrogel-coated balloon catheter was immersed three times in argatroban/saline solution (1 mg/mL) for 60 s, inflated to a pressure of 606 kPa and left in the rabbit common carotid artery for 1 min. The same procedure was performed, without drug, as a control. The pharmacokinetics of delivered argatroban in the arterial wall were assessed using [¹⁴C]-argatroban. Platelet deposition 2h after balloon injury was quantified by fluorescence studies using antiplatelet antibody. Vascular smooth muscle cell (VSMC) proliferation 3 days after balloon injury was assessed by immunohistochemical staining for proliferative cell nuclear antigen (PCNA). In a clinical study, we divided 50 elective patients into two groups: argatroban and control. 3. In the experimental study, the mean quantities of argatroban at 0, 2 and 6 h after deflation wer. 24.63, 0.49 and 0.11 nmol/g wet weight of artery, respectively. Argatroban was undetected 24 h after deflation. Two hours after deflation, argatroban-treated arteries showed less platelet adhesion than saline-treated controls. The mean number of PCNA-positive cells was 16.9 and 43.8% in the argatroban and control groups, respectively (P < 0.01). In the clinical study, the mean late gain loss was 8.2 and 27.3% in the argatroban and control groups, respectively (P < 0.05). The mean late restenosis rate was 11.1 and 41.4% in the argatroban and control groups, respectively (P<0.05). 4. These data suggest that blood coagulation plays a significant role in VSMC proliferation after balloon injury and that locally administered argatroban using hydrogel-coated balloon catheter may prevent post-percutaneous transluminal coronary angioplast. restenosis.     

Thoracoscopic closure of a congenital partial pericardial defect

We describe our technique for performing direct thoracoscopic closure of a congenital partial pericardial defect, which was successfully employed in a 15-year-old boy. This is the first such report of a procedure that is noninvasive and may therefore become the treatment of choice for patients with a small congenital pericardial defect.     

Long-term results of open reduction for residual subluxation in congenital dislocation of the hip: A new open reduction method involving 360° circumferential capsulotomy

We report satisfactory results with a new operative treatment, conducted via an extensive anterolateral approach, involving 360 degree circumferential capsulotomy, for residual subluxation in congenital dislocation of the hip (CDH). Long-term radiographic results of this procedure (group A) were compared retrospectively with the results of partial capsulotomy (group B), which preserved the posteroinferior joint capsule. The mean center edge angle in group A (22.5°) was greater than that in group B (16.0°). Satisfactory results were achieved in 11 of 15 hips (73%) (Severin class I or II) in group A, and in 5 of 12 hips (42%) in group B. These results suggest that whole circumferential capsulotomy can remove obstacles to complete reduction, and that acetabular development can be expected in hips reduced by the procedure, without the performance of innominate osteotomy. We believe that our technique is a useful alternative for the treatment of residual subluxation in CDH.     

Computed tomography features immediately after replacement of haematoma with oxygen through percutaneous subdural tapping for the treatment of chronic subdural haematoma in adults

Summary In an effort to achieve a simple and less invasive method for the treatment of chronic subdural haematoma, replacement of the haematoma with oxygen by percutaneous subdural tapping was employed in 36 patients. This study was conducted on 23 haematomas in 20 patients, whose computed tomography (CT) scans immediately following the treatment were available for evaluation, with particular regard to distinguishing between their findings and those seen with tension pneumocephalus. The CT features werde divided into two patterns according to the location of oxygen; a convexity type (19 haematomas) and an interhemispheric type (4 haematomas). Analysis of the CT appearances revealed the oxygen was exclusively confined to the haematoma cavity, distinguishing it from the findings in tension pneumocephalus. This observation indicates the safety of replacement of the haematoma with oxygen when combined with our percutaneuous subdural tapping technique which prevents lesions of the inner haematoma membrane.     

Jejunal carcinoma with adenoma —Report of a case and review of the Japanese literature—

A rare case of jejunal carcinoma coexisting with adenoma, situated 120 cm distal to the ligament of Treitz in a 53 year old male, is reported herein. We also review cases of adenoma and carcinoma in the jejunum and ileum from the Japanese literature, and discuss the histogenesis of carcinoma of the jejunum and ileum.     

Presynaptic α2-adrenoceptor-mediated modulation of norepinephrine release from vascular adrenergic neurons in reduced renal mass salt hypertensive rats

The present study was designed to investigate the presynaptic alpha 2-adrenoceptor function to inhibit norepinephrine (NE) release in blood vessels of reduced renal mass salt hypertensive rats (Na-loaded HT). Isolated perfused mesenteric vasculatures were prepared from Na-loaded HT and normotensive control rats (NT-control), and the NE release and vascular responsiveness were examined. Periarterial nerve stimulation caused a significantly greater release of NE and pressor responses in Na-loaded HT than in NT-control. Yohimbine, a potent alpha 2-adrenoceptor antagonist, demonstrated the facilitatory effects on NE release during nerve stimulation. The effects were significantly attenuated in Na-loaded HT compared with NT-control. These results demonstrate that vascular sympathetic nervous activity might be enhanced in Na-loaded HT. Furthermore, the increased NE release from vascular adrenergic neurons in Na-loaded HT could partially depend on impaired presynaptic alpha 2-adrenoceptor-mediated modulation, which might contribute to the pathogenesis and maintenance of this form of salt-dependent hypertension.     

Maffucci’s syndrome associated with spindle cell hemangioendothelioma

 The case of a 49-year-old man with Maffucci’s syndrome, who developed multiple spindle cell hemangioendotheliomas, is presented. The case provides support for recent reports suggesting an association between this peculiar vascular lesion and skeletal enchondromatosis.     

Thrombin Inhibition in discordant xenograft rejection

Abstract: Microvascular thrombosis and the associated platelet and endothelial cell activation are prominent observations in xenograft rejection. This pathological picture could be related to the excessive generation of thrombin in the context of either inflammation or putative inter-species molecular incompatibilities between activated coagulation factors and their natural anticoagulants. Relatively selective thrombin Inhibition with the serine protease inhibitor SDZ MTH 958 (MTH-958) are independent of heparinoids and anti-thrombin III. MTH-958 has been shown to significantly prolong porcine cardiac function during perfusion with human blood in an ex vivo model. The aim of this study was to validate the role of thrombin generation in a rodent model of discordant xenograft rejection in vivo. The effect of thrombin inhibition with MTH-958 was tested in both hyperacute rejection (HAR) and delayed xenograft rejection (DXR) after decomplementation with cobra venom factor (CVF) in normal Lewis (Lew) rats and Intrinsic C6 deficiency In PVG (C6-/PVG) recipient rats. Recipient rats received heterotopic guinea pig cardiac xenografts and were treated with titrated doses of MTH-958 until the time of graft rejection. Plasma samples at selected time points were examined to confirm effective thrombin inhibition, and rejected grafts were analyzed by immunohistology. MTH-958 significantly improved graft survival in HAR albeit the extent of prolongation was not marked, but the agent failed to prolong survival In CVF-treated Lew rats. In C6-/PVG rats receiving MTH-958, a significantly reduced graft survival time was observed when compared with C6-/PVG controls. The grafts from MTH-958-treated animals showed dense deposits of C3, IgM, and IgG with fibrin levels similar to controls. The thrombin antagonist tested could prolong xenograft survival during HAR but had no benefit in DXR. The relative non-specificity of the serine protease inhibitor MTH-958 with the potential activation of alternative pathway of complement via the inhibition of factor I could account for the failure to prolong xenograft survival in DXR. The pathogenetic significance of thrombin generation in this situation remains to be determined by the use of more selective and pharmacologically acceptable I anti-thrombin agents.