Schwannoma of the nasal septum presenting as a multicentric neuronal tumour.

PROBLEM: Schwannomas (neurilemmomas) are benign primary tumours that arise from Schwann cells. Schwannomas arising from the nasal septum are exceptionally rare. Here, we report a unique case of schwannoma of the nasal septum presenting as a multicentric neuronal tumour. RESULTS: A 40-year old male sustained intermittent left tinnitus. Magnetic resonance imaging revealed masses near the nasal septum and upper cervical cord in addition to a tumour in the left cerebellopontine (CP) angle. The tumour in the nasal septum was completely resected by endoscopic endonasal surgery and diagnosed as a typical schwannoma. The CP angle tumour was treated with stereotactic radiosurgery, while the asymptomatic cord lesion showed no significant growth and remains under observation. CONCLUSION: Endoscopic endonasal surgery is useful for the resection of schwannomas of the nasal septum. Schwannomas of the nasal septum may present as multiple neuronal tumours.

Evaluation of two Japanese regulatory actions using medical information databases: a 'Dear Doctor' letter to restrict oseltamivir use in teenagers, and label change caution against co-administration of omeprazole with clopidogrel.

WHAT IS KNOWN AND OBJECTIVE: The implementation of appropriate epidemiological methodology using medical information databases (MIDs) to evaluate the effects of regulatory actions has been highly anticipated. To assess scientific methods for active pharmacovigilance using MIDs, we conducted a quantitative assessment of the impact of two regulatory actions by the Japanese government: (i) restriction of use of oseltamivir in teenagers in March 2007 and (ii) caution against the co-administration of omeprazole (OPZ) with clopidogrel (CPG) in April 2010. METHODS: Data were obtained from four hub hospitals in Japan. We measured the seasonal proportion of patients prescribed oseltamivir to those prescribed neuraminidase inhibitors for the 2002/2003 to 2010/2011 seasons. The monthly proportion of patients co-administered OPZ and CPG (OPZ+CPG) to those prescribed CPG was measured from May 2009 to April 2011. We evaluated the changes observed with implementation of the regulatory actions. To estimate the impact of the actions, we conducted segmented regression analysis using interrupted time series data. The impact was assessed by two parameter estimates of the regression model: the change in level for short-term effects and change in trend for long-term effects. RESULTS AND DISCUSSION: The use of oseltamivir in the target 10-19 years age group showed a significant and large decline (63·16%) immediately after the intervention (P = 0·0008). No change was observed in OPZ+CPG, although there was a relative inhibitory trend for OPZ+CPG compared with co-administration of lansoprazole or rabeprazole with CPG as the control group. When restricted to new users of CPG, the stratified results were consistent with the overall results. WHAT IS NEW AND CONCLUSION: The current analysis demonstrates the effectiveness of two regulatory actions. The results of the current study indicate that MID research can contribute to assessing and improving pharmacovigilance activities.

Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice.

AIMS/HYPOTHESIS: Hyperlipidaemia is an independent risk factor for the progression of diabetic nephropathy, but its molecular mechanism remains elusive. We investigated in mice how diabetes and hyperlipidaemia cause renal lesions separately and in combination, and the involvement of Toll-like receptor 4 (TLR4) in the process. METHODS: Diabetes was induced in wild-type (WT) and Tlr4 knockout (KO) mice by intraperitoneal injection of streptozotocin (STZ). At 2 weeks after STZ injection, normal diet was substituted with a high-fat diet (HFD). Functional and histological analyses were carried out 6 weeks later. RESULTS: Compared with treatment with STZ or HFD alone, treatment of WT mice with both STZ and HFD markedly aggravated nephropathy, as indicated by an increase in albuminuria, mesangial expansion, infiltration of macrophages and upregulation of pro-inflammatory and extracellular-matrix-associated gene expression in glomeruli. In Tlr4 KO mice, the addition of an HFD to STZ had almost no effects on the variables measured. Production of protein S100 calcium binding protein A8 (calgranulin A; S100A8), a potent ligand for TLR4, was observed in abundance in macrophages infiltrating STZ-HFD WT glomeruli and in glomeruli of diabetic nephropathy patients. High-glucose and fatty acid treatment synergistically upregulated S100a8 gene expression in macrophages from WT mice, but not from KO mice. As putative downstream targets of TLR4, phosphorylation of interferon regulatory factor 3 (IRF3) was enhanced in kidneys of WT mice co-treated with STZ and HFD. CONCLUSIONS/INTERPRETATION: Activation of S100A8/TLR4 signalling was elucidated in an animal model of diabetic glomerular injury accompanied with hyperlipidaemia, which may provide novel therapeutic targets in progressive diabetic nephropathy.

Angiographic restenosis and its clinical impact after infrapopliteal angioplasty.

OBJECTIVE: To assess 3- and 12-month angiographic restenosis rates and their clinical impact after infrapopliteal angioplasty. DESIGN: Prospective multicenter study. MATERIALS AND METHODS: We analyzed 68 critical ischemic limbs (tissue loss: 58 limbs) from 63 consecutive patients due to isolated infrapopliteal lesions who underwent angioplasty alone. Primary endpoint was 3-month angiographic restenosis rate; secondary endpoints were 12-month angiographic restenosis rate, and 3- and 12-month rates of mortality, major amputation and reintervention. Three- and 12-month frequency of ambulatory status and of freedom from ischemic symptoms, and time to wound healing in the ischemic wound group, were compared between restenotic and non-restenotic groups. Angiographic restenosis predictors were assessed by multivariable analysis. RESULTS: 95% of cases had 3-month angiography; restenosis rate was 73%: 40% restenosis and 33% re-occlusion. Twelve-month follow-up angiography was conducted for the patients without 3-month angiographic restenosis, and restenosis rate at 12 months was 82%. Non-administration of cilostazol and statin, and chronic total occlusion were 3-month angiographic restenosis predictors. Three- and 12-month mortality was 5% and 12%, respectively. Despite no patients having undergone amputation, 15% had persistent ischemic symptoms, and 48% of limbs underwent reintervention within 12 months. During the same study period, ambulatory status and limbs with complete healing were more frequently observed in the non-restenosis group than in the restenosis group. In the tissue loss group, time to wound healing in the restenosis group was longer than in the non-restenosis group (127 days vs. 66 days, p = 0.02). CONCLUSION: The extremely high angiographic restenosis rate after infrapopliteal angioplasty may adversely impact clinical status improvement.

Calcified nodule in the buccal submucosa: a case report.

A 34-year-old man developed an ovoid swelling in the right buccal submucosa adjacent to Stensen's duct. Computed tomography revealed a 25 x 20 mm, well-demarcated calcified mass. The excised mass was encapsulated by soft tissues and contained a calcified nodule measuring 15 x 15 x 10 mm. Histopathologic examination revealed the absence of neoplastic cells. The peripheral wall of the mass was infiltrated by inflammatory cells and contained hemorrhages with minimal calcifications. The central portion of the mass was composed of foreign body granuloma-like changes and multiple calcified nodules that were diffusely hyalinized with fibrous connective tissue. The patient has been followed for six years with no recurrence. Accurate diagnosis is important to avoid unnecessary and mutilating surgery. To our knowledge, this is the first reported case of a calcified nodule in the buccal submucosa of an adult.

Role of interleukin-17A in the eosinophil accumulation and mucosal remodeling in chronic rhinosinusitis with nasal polyps associated with asthma.

BACKGROUND: Interleukin (IL)-17A is a highly inflammatory cytokine with a robust effect on stromal cells in many tissues. Although IL-17A is known to be associated with inflammatory lung disorders by triggering an accumulation of neutrophils, the effect of IL-17A on the upper airway is still uncertain. The expression of IL-17A and its role were investigated in the nasal polyps of chronic rhinosinusitis associated with asthma. METHODS: IL-17A was detected by immunohistochemistry and quantitative real-time RT-PCR. The cellular source of IL-17A was examined by double staining with EG2, CD4 and neutrophil elastase. The tissue remodeling of the nasal polyps was evaluated by assessing the epithelial damage and basement membrane thickness. RESULTS: Both the immunoreactivity and mRNA of IL-17A were significantly detected in the nasal polyps in comparison with control normal sinus mucosa. The localization of IL-17A expression predominantly coincided with eosinophils and CD4-positive lymphocytes. Furthermore, the number of IL-17A-positive cells correlated with tissue eosinophils, but not with neutrophils. The degree of epithelial damage and basement membrane thickness was dependent on the number of infiltrated IL-17A-positive cells. CONCLUSION: The present study suggests, for the first time, that IL-17A plays an important role in the eosinophil accumulation in the nasal polyps and the remodeling of the nasal polyps of chronic rhinosinusitis associated with asthma.

Clinical statistics of endogenous uveitis: comparison between general eye clinic and university hospital.

We compared uveitis patients who attended a general eye clinic (n = 183) with those who attended the ophthalmology department of a university hospital (n = 550) to examine factors that affect the clinical statistics of uveitis outpatients. We observed that diabetic iritis and herpetic iritis were significantly more frequent in the clinic whereas Vogt-Koyanagi-Harada disease and Behcet's disease were significantly more common in the university hospital. Among the so-called three leading uveitis, Behcet's disease and Vogt-Koyanagi-Harada disease were relatively rare in the general clinic; they might be concentrated in the university hospital setting because these diseases require treatment at specialist hospitals. In addition, uveitis secondary to underlying diseases such as diabetic iritis and transient non-granulomatous iridocyclitis was generally not referred to specialist hospitals. These factors may account for the differences in disease frequencies observed between the two facilities.

Immunocyte Ca2+ influx system mediated by LTRPC2.

We characterized an activation mechanism of the human LTRPC2 protein, a member of the transient receptor potential family of ion channels, and demonstrated that LTRPC2 mediates Ca2+ influx into immunocytes. Intracellular pyrimidine nucleotides, adenosine 5'-diphosphoribose (ADPR), and nicotinamide adenine dinucleotide (NAD), directly activated LTRPC2, which functioned as a Ca2+-permeable nonselective cation channel and enabled Ca2+ influx into cells. This activation was suppressed by intracellular adenosine triphosphate. These results reveal that ADPR and NAD act as intracellular messengers and may have an important role in Ca2+ influx by activating LTRPC2 in immunocytes.

Relationship between epithelial damage or basement membrane thickness and eosinophilic infiltration in nasal polyps with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps is characterized by eosinophilic infiltration. This study hypothesized that the aggregation of the mucosal pathology during remodeling is related to infiltrating eosinophils in patients with such nasal polyps. OBJECT: To clarify the pathogenetic role of eosinophils in patients with CRS with nasal polyps, this study investigated the relationship between epithelial damage or basement membrane (BM) thickening and the epithelial infiltration of eosinophils in these nasal polyps. METHODS: The number of eosinophils that infiltrated into the epithelial and subepithelial layers of sinonasal tissues was counted. The staging of epithelial damage allowed the quantification of epithelial loss. RESULTS: Both epithelial damage and BM thickness in CRS, which were correlated with the number of infiltrated eosinophils, were significantly greater than in the control group. Neither parameter showed significant differences between the asthma and non-asthma groups. There was a significantly correlation in the eosinophilic infiltration between the subepithelial and epithelial layers. CONCLUSION: It is suggested that eosinophils that infiltrate into both the epithelial and subepithelial layers play a part in the process of mucosal remodeling of CRS with nasal polyps.

Overexpression of connective tissue growth factor in podocytes worsens diabetic nephropathy in mice.

Connective tissue growth factor (CTGF) is a potent inducer of extracellular matrix accumulation. In diabetic nephropathy, CTGF expression is markedly upregulated both in podocytes and mesangial cells, and this may play an important role in its pathogenesis. We established podocyte-specific CTGF-transgenic mice, which were indistinguishable at baseline from their wild-type littermates. Twelve weeks after streptozotocin-induced diabetes, these transgenic mice showed a more severe proteinuria, mesangial expansion, and a decrease in matrix metalloproteinase-2 activity compared to diabetic wild-type mice. Furthermore, diabetic transgenic mice exhibited less podocin expression and a decreased number of diffusely vacuolated podocytes compared to diabetic wild-type mice. Importantly, induction of diabetes in CTGF-transgenic mice resulted in a further elevation of endogenous CTGF mRNA expression and protein in the glomerular mesangium. Our findings suggest that overexpression of CTGF in podocytes is sufficient to exacerbate proteinuria and mesangial expansion through a functional impairment and loss of podocytes.

Adrenomedullin inhibits connective tissue growth factor expression, extracellular signal-regulated kinase activation and renal fibrosis.

Systemic administration of the potent vasodilating peptide adrenomedullin reduces cardiac and renal fibrosis in hypertensive animals. Here, we investigated the effects of kidney-specific adrenomedullin gene delivery in normotensive rats after unilateral ureteral obstruction, an established model of renal tubulointerstitial fibrosis. Overexpression of exogenous adrenomedullin in the renal interstitium following ureteral obstruction significantly prevented fibrosis and proliferation of tubular and interstitial cells. In this model, there is upregulation of connective tissue growth factor (CTGF) mRNA expression and extracellular signal-regulated kinase (ERK) phosphorylation, and adrenomedullin overexpression suppressed both of these activities without altering the blood pressure. In NRK-49F renal fibroblasts, adrenomedullin reduced transforming growth factor-beta-induced CTGF and fibronectin mRNA upregulation through the cyclic AMP/protein kinase A signaling pathway, and suppressed ERK phosphorylation and cell proliferation. In the kidneys with an obstructed ureter, adrenomedullin receptor gene expression was upregulated along with cyclic AMP production in kidney slices. The latter effect was partially blocked by a neutralizing antibody to adrenomedullin, indicating that an endogenous peptide-receptor system was activated. Our results show that overexpression of exogenous adrenomedullin in the ureteral-obstructed kidney prevents tubulointerstitial fibrosis and cell proliferation through the cyclic AMP-mediated decrease of CTGF induction and ERK phosphorylation.

Automatic DPC code selection from electronic medical records: text mining trial of discharge summary.

OBJECTIVES: We extracted index terms related to diseases recorded in hospital discharge summaries and examined the capability of the vector space model to select a suitable diagnosis with these terms. METHODS: By morphological analysis, we extracted index terms and constructed an original dictionary for the discharge summary analysis. We chose 125 different DPC (Japanese DRG system) codes for the diseases, each of which had more than 20 cases. We divided them into two groups. One group consisted of 5927 cases from 2004 fiscal year and was used to generate the document vector space according to the DPC. The other group of 3187 cases was collected to verify the automatic DPC selection by using data from 2005 fiscal year. The top 200 extracted index terms for each disease were used to calculate the weight of each disease. RESULTS: The DPC code obtained by the calculated similarity was compared with the original codes of patients for 125 DPCs of 3187 cases. Eighty percent of the cases matched the diagnosis of the DPC (first six digits) and 56% of the cases completely matched all 14 digits of the DPC. CONCLUSIONS: We demonstrated that we could extract suitable terms for each disease and obtain characteristics, such as the diagnosis, from the calculated vectors. This technique can be used to measure the qualification of discharge summaries and to integrate discharge summaries among different facilities. By the text mining technique, we can characterize the contents of electronic discharge summaries and deduce diagnoses with the data.

Study on the introduction of hazard analysis and critical control point (HACCP) concept of the water quality management in water supply systems.

In the latest revision in 2004, the 3rd edition, the Water Safety Plans (WSP) was newly introduced into the World Health Organization (WHO) Guidelines for Drinking Water Quality. The Hazard analysis and critical control point (HACCP) is a basic concept that underlies the WSPs, and is also known as the product quality management method in the field of food and the medical manufacturing industries. In the amendments of the Drinking Water Quality Standards in Japan, water suppliers are required to reasonably achieve both safe water and efficient water quality management. Therefore, the HACCP concept is focused as an adequate management method covering a whole process of water supply systems, in a systematic way. The purpose of this study is to investigate a practical procedure in introducing the HACCP into water quality management in Japan. In comparison to conventional applications of the HACCP, unmanageable variations of raw water quality, continuous treatment and supply, and numerous standards of water quality items need to be considered. The HACCP system is expected to achieve a quick response to improvements in water quality, accountability towards consumers and a decrease in accidents.

Expression of a novel isoform of Vav, Vav-T, containing a single Src homology 3 domain in murine testicular germ cells.

Vav is a signal transducing molecule containing C-terminal Src homology 3 (SH3)-SH2-SH3 domains, and has been thought to be expressed exclusively in hematopoietic and trophoblastic cells. By Northern blot analysis, vav transcripts of unique sizes, 4.8 kb and 1.0 kb, were detected in the testis among various tissues examined. From a mouse spermatocyte cDNA library, a novel isoform of vav (vav-T) was cloned, which corresponded to a part of the 4.8 kb transcript. Vav-T had an alternative 5' sequence up to the middle of SH2-coding region, and encoded 163 amino acids with a single SH3 domain. Northern blot analysis of fractionated testicular cells and in situ hybridization histochemistry demonstrated that vav-T transcripts were expressed in the differentiating germ cells, especially spermatocytes. A 24 kD protein was detected by anti-Vav antibodies in the testis, but not in the spleen or bone marrow. Transcripts of heterogeneous nuclear ribonucleoprotein K, known to associate with the most C-terminal SH3 domain of Vav, were also detected in the differentiating male germ cells. These results demonstrate expression of previously nondescribed Vav-isoform in the testicular germ cells, and suggest that it interacts with RNA-binding proteins and plays an important role in spermatogenesis.

Serial angiographic follow-up after Palmaz-Schatz stent implantation: comparison with conventional balloon angioplasty.

OBJECTIVES: Serial angiographic follow-up study was designed to evaluate the temporal mode of lumen diameter changes after Palmaz-Schatz stent implantation, and the results were compared with those from a cohort of patients undergoing balloon angioplasty. BACKGROUND: Restenosis remains a major limitation of balloon angioplasty. The Palmaz-Schatz balloon expandable coronary stent is now under clinical investigation to evaluate its efficacy in preventing restenosis. METHODS: Serial angiographic follow-up study was performed the day after stent implantation and at 1, 3 and 6 months after the procedure. The stent group consisted of 96 patients who had 97 lesions with a single stent. A cohort of 179 patients with 192 lesions were selected as the balloon group by the criteria of final balloon size > or = 3 mm and lesion length < 20 mm. RESULTS: A significantly larger lumen diameter was obtained immediately after stent implantation (2.9 +/- 0.4 mm [mean +/- SD] in the stent group vs. 2.1 +/- 0.5 mm in the balloon group, p < 0.001). At 3 to 6 months of follow-up, a significantly larger lumen diameter was maintained in the stent group (2.2 +/- 0.6 vs. 1.5 +/- 0.7 mm, p < 0.001). The late restenosis rate according to a binary definition was significantly lower in the stent group (13% vs. 39%, p < 0.001). Stenosis exacerbation, frequently observed within 24 h after balloon angioplasty, was not found after stenting. Between the next day and 1 month, regression was dominant in the balloon group, whereas progression of stenosis was observed in the stent group. The greatest tendency to restenosis was observed in both groups between 1 and 3 months after the procedure. Between 3 and 6 months, significantly greater diameter loss was found in the stent group. CONCLUSIONS: The Palmaz-Schatz stent was effective in reducing the restenosis rate in this highly selected cohort of patients. Reduction in restenosis rate was dependent on a larger lumen obtained immediately. Late loss of diameter was significantly greater after stenting. The restenosis rate after stenting should be evaluated by follow-up angiography at 6 months rather than at 3 months, which is adequate after conventional balloon angioplasty.

Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients.

Histopathologic examination was performed in 20 patients undergoing antemortem coronary angioplasty. Thirty-four lesions were dilated and the interval between coronary angioplasty and death ranged from several hours to 4 years. Intimal proliferation of smooth muscle cells, as a major cause of restenosis, was observed in 83% to 100% of 28 lesions examined 11 days to 2 years after coronary angioplasty. In 20 lesions examined within 6 months, proliferating smooth muscle cells were predominantly of the synthetic type and there was abundant extracellular matrix substance chiefly composed of proteoglycans. In eight lesions examined between 6 months and 2 years, contractile type smooth muscle cells were dominant and extracellular matrix was composed chiefly of collagen. In three lesions examined after 2 years, evidence of antemortem coronary angioplasty was hardly identifiable and these lesions were almost indistinguishable from conventional atherosclerotic plaque. These temporal changes in histologic pattern provide a pathologic background for clinical reports that restenosis is predominantly found within 6 months after coronary angioplasty. Morphometric analysis revealed that the extent of intimal proliferation was significantly greater in lesions with evidence of medial or adventitial tears than in lesions with no or only intimal tears.

Relation of saphenous vein graft obstruction to serum cholesterol levels.

OBJECTIVES: To determine the potential of lipid-lowering therapy to reduce saphenous vein graft obstruction, we retrospectively studied the association between graft obstruction and serum cholesterol levels. BACKGROUND: Atherosclerosis is the major cause of vein graft obstruction. Approximately 50% of grafts are occluded by 10 years after operation. It remains to be established whether lipid control affects long-term graft survival. METHODS: We carried out a retrospective review of all 284 patients who had undergone coronary artery bypass graft surgery at Juntendo University Hospital between 1976 and 1991 and met the following additional criteria: at least one saphenous vein graft, repeat coronary arteriography at some point after coronary artery bypass graft surgery and a serum cholesterol level > or = 200 mg/dl before operation. Saphenous vein graft obstruction rates were compared among three groups classified by serum cholesterol levels at follow-up arteriography: group I < 200 mg/dl; group II 200 to 239 mg/dl; group III > or = 240 mg/dl. A vein graft was considered obstructed if it was narrowed by > or = 70%. RESULTS: In group I, 88% of grafts were not obstructed 7 years after operation. The respective rates were 61% in group II and 57% in group III (p < 0.005). This relation was true for vein grafts to the left anterior descending and other coronary arteries. CONCLUSIONS: Lower serum cholesterol levels are associated with lower rates of vein graft obstruction for up to 7 years. This suggests that cholesterol-lowering therapy may improve long-term saphenous vein graft survival after coronary artery bypass surgery.

Restenosis after successful percutaneous transluminal coronary angioplasty: serial angiographic follow-up of 229 patients.

To further understand the temporal mode and mechanisms of coronary restenosis, 229 patients were studied by prospective angiographic follow-up on day 1 and at 1, 3 and 6 months and 1 year after successful percutaneous transluminal coronary angioplasty. Quantitative measurement of coronary stenosis was achieved by cinevideodensitometric analysis. Actuarial restenosis rate was 12.7% at 1 month, 43.0% at 3 months, 49.4% at 6 months and 52.5% at 1 year. In 219 patients followed up for greater than or equal to 3 months, mean stenosis diameter was 1.91 +/- 0.53 mm immediately after coronary angioplasty, 1.72 +/- 0.52 mm on day 1, 1.86 +/- 0.58 mm at 1 month and 1.43 +/- 0.67 mm at 3 months. In 149 patients followed up for greater than or equal to 6 months, mean stenosis diameter was 1.66 +/- 0.58 mm at 3 months and 1.66 +/- 0.62 mm at 6 months. In 73 patients followed up for 1 year, mean stenosis diameter was 1.65 +/- 0.56 mm at 6 months and 1.66 +/- 0.57 mm at 1 year. Thus, stenosis diameter decreased markedly between 1 month and 3 months after coronary angioplasty and reached a plateau thereafter. In conclusion, restenosis is most prevalent between 1 and 3 months and rarely occurs beyond 3 months after coronary angioplasty.

Progression of coronary atherosclerosis: is coronary spasm related to progression?

A total of 239 patients undergoing serial coronary angiography with a concomitant ergonovine provocation test were studied between July 1974 and June 1987. The progression of coronary artery disease was evaluated in relation to risk factors, especially coronary artery spasm. Patients were classified into three groups: 1) new myocardial infarction group (39 patients); 2) progression without infarction group (90 patients); and 3) nonprogression group (110 patients). To assess how risk factors and coronary spasm are related to the occurrence of new myocardial infarction and progression without infarction, 11 variables in the three groups were examined: age, gender, the time interval between the studies, fasting blood sugar, systolic blood pressure, diastolic blood pressure, smoking, serum cholesterol, triglyceride, uric acid and a positive response to the ergonovine provocation test. Multiple regression analysis selected three independent predictors of progression without infarction: cholesterol (p less than 0.01), systolic blood pressure (p less than 0.05) and a positive response to the ergonovine provocation test (p less than 0.001). Multiple regression analysis also selected three independent predictors of the occurrence of new myocardial infarction: fasting blood sugar (p less than 0.01), systolic blood pressure (p less than 0.05) and a positive response to the ergonovine provocation test (p less than 0.001). A positive response to the ergonovine provocation test was the strongest factor for occurrence of both new myocardial infarction and progression without infarction. To evaluate segmental arterial changes, 3,275 coronary artery segments were analyzed in the 239 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Effectiveness of an antioxidant in preventing restenosis after percutaneous transluminal coronary angioplasty: the Probucol Angioplasty Restenosis Trial.

OBJECTIVES: The Probucol Angioplasty Restenosis Trial was a prospective, randomized, controlled study that investigated the effectiveness of probucol therapy in reducing the rate of restenosis after percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Antioxidants have an inhibitory effect on smooth muscle cell growth in experiments in vitro and in vivo, which suggests a possible pharmacologic effect on restenosis after PTCA. METHODS: One hundred one patients were randomly assigned to receive 1,000 mg/day of probucol or control (no lipid-lowering) therapy 4 weeks before PTCA. After 4 weeks of premedication, both groups underwent PTCA. Probucol was continued until follow-up angiography 24 weeks after PTCA. Angiographic results were analyzed at a core laboratory by quantitative coronary angiography. RESULTS: Dilation was successful in 46 of 50 patients in the probucol group and 45 of 51 in the control group. At follow-up angiography 24 weeks after angioplasty, angiographic restenosis occurred in 9 (23%) of 40 patients in the probucol group and 22 (58%) of 38 in the control group (p = 0.001). Minimal lumen diameter was 1.49 +/- 0.75 mm (mean +/- SD) in the probucol group and 1.13 +/- 0.65 mm in the control group (p = 0.02). Percent diameter stenosis at follow-up angiography in the probucol group was significantly lower than that in the control group (43.9% vs. 56.4%, p = 0.009). The late loss was 0.37 +/- 0.69 mm in the probucol group and 0.60 +/- 0.62 mm in the control group (p = 0.13). The loss/gain ratio was 0.32 +/- 0.74 in the probucol group and 0.56 +/- 0.81 in the control group (p = 0.059). Net gain was greater in the probucol group than in the control group (0.77 +/- 0.70 vs. 0.48 +/- 0.59 mm, p = 0.053). CONCLUSIONS: Probucol administered beginning 4 weeks before PTCA appears to reduce restenosis rates.