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.     

Should every patient undergo cardiac catheterization after myocardial infarction?

During the past few decades, management of patients with myocardial infarction has dramatically evolved. High-risk patients are now identified by a variety of noninvasive tests, and aggressive use of reperfusion strategies has improved clinical outcomes. Despite the benefits of reperfusion, only a few patients are eligible to receive thrombolytic therapy. Mortality rates among patients excluded from thrombolytic trials (15% to 20%) have been far greater than those eligible for treatment (3% to 10%). Because most deaths occur within the first few days of infarction, interventions designed to reduce mortality should be performed acutely. Immediate catheterization allows identification of high-risk anatomy that may benefit from surgery and allows coronary angioplasty to be performed as a reperfusion strategy (when appropriate). Furthermore, catheterization allows documentation of ejection fraction, vessel patency, number of diseased vessels, and residual stenosis, all of which have been predictive of prognosis. Conversely, frequently repeated noninvasive diagnostic tests are associated with increased cost, are generally performed in low-risk patients, and 60% to 80% of patients with myocardial infarction ultimately require catheterization anyway. It is possible that early catheterization and percutaneous transluminal coronary angioplasty when indicated may effectively risk stratify patients (eliminating the need for noninvasive testing), may reduce morbidity and mortality, and shorten the length of hospital stay.     

C3 Deposition in IgA Nephropathy in Children and Adolescents

The aim of this study was to assess the significance of C3 deposition in IgA nephropathy in children and adolescents. One hundred and two patients aged 5–21 years (57 male and 45 female) were studied. The findings of C3 deposition were classified into 8 groups by immunofluorescent (IF) pattern and intensity as follows: group MC3+ (N = 12): mesangiocapillary pattern and 3+ in intensity; group MC2+ (N = 13): mesangiocapillary and 2+; group MC1 + (N = 4): mesangiocapillary and 1 +; group M3+ (N = 11): mesangial and 3+; group M2+ (N = 24): mesangial and 2+; group M1 + (N=18): mesangial 1 +; group S (N = 12): only segmentally positive; and group N (N = 8): negative. Histological changes were scored semiquantitatively as an activity index (cellular proliferation, necrosis, interstitial cell infiltration, and cellular crescents) and a chronicity index (mesangial sclerosis, segmental and global glomerular sclerosis, fibrous crescents, adhesion and tubulo-interstitial change). IF findings were scored semiquantitatively and laboratory findings were also studied. The following results were obtained: 1) The scores of total activity index in MC groups were higher than in the M, S or N groups, and the greater the degree of C3 deposition, the higher the score; 2) Such result was not evident in the chronicity index; 3) High IF scores of IgG and IgM were found in the MC3+ and MC2+ groups; 4) Hematuria was more severe in MC3+ and MC2+ than in other groups, and proteinuria was more prominent in the MC than other groups. Thus the degree of C3 deposition was parallel with histological activity and urinary findings.     

Role of nuclear cardiology for determining management of patients with stable coronary artery disease

Both radionuclide angiography and myocardial perfusion imaging provide important insights that determine the management of patients with stable coronary artery disease. Both nuclear cardiology procedures have clearly demonstrated use in the noninvasvie identification of severe (left main or three-vessel) coronary artery disease and the noninvasive assessment of prognosis and thereby determine which patients should be sent to coronary angiography. Both radionuclide angiography and myocardial perfusion imaging provide prognostic information that is independent of resting left ventricular function and coronary anatomy and thereby influence the decision regarding which patients should be sent to coronary revascularization. This review considers the evidence supporting the uses of these nuclear cardiology procedures and provides suggestions regarding their cost-effective application.     

Phorbol ester, not growth hormone releasing factor, consistently stimulates growth hormone release from somatotroph adenomas in culture

In order to study the mechanism of GH secretion from somatotroph adenoma cells, we have compared the effect of 12–O-tetradecanoyl phorboi-13-acetate (TPA) with that of growth hormone releasing factor (GRF) on GH secretion from human somatotroph adenoma cells cultured in monolayer. Pituitary adenoma cells were obtained from 13 patients with acromegaly undergoing surgery. On the 7th day of culture, the cells were exposed for 2 h to secretagogues. All 13 adenoma cell cultures (100%) responded to TPA (1·6–16·0 nmol/I) with a two- to six-fold increase in GH release (240·37% Increase of control: mean±SE). The response was detectable within 10 min, and was maximal at 2 h. Phosphollpase C (7·7 mmol/I) also stimulated a two-to ten-fold Increase In GH release in all four adenomas examined (100%). GH release was stimulated by GRF (2·0 nmol/I) in eight out of 12 adenoma cells (67%), but the magnitude of the responses to GRF (60·18% Increase of control: mean ± SE) were much smaller than that of TPA. Five out of 13 adenomas secreted detectable amount of PRL Into the medium and these five adenomas (100%) responded to TPA (16·0 nmol/I) with a two- to six-fold Increase. These observations indicate that the activation of protein kinase C is the consistent stimulator in GH and PRL secretion In human somatotroph adenoma cells. However, It is not determined whether the protein kinase C     

Educating the Public About Stroke

Acute stroke affects large numbers of people worldwide. It causes significant morbidity and mortality. Data support the hypothesis that the public is not familiar with either the risk factors or the signs of stroke. Educating the public about stroke may result in a lower incidence of the disease as individuals modify their risk factors, and in improved outcomes as a result of reductions in delays to treatment. There is clear and convincing evidence that reducing delays to treatment of patients with acute stroke results in improved outcomes. Public education programs should be broad-based, tailored to individual audiences, and carry a common theme.