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Background: Clinical trials suggest an increased frequency of restenosis after coronary intervention in left anterior descending (LAD) compared to the left circumflex or right coronary arteries. Experimental studies correlate stent-induced arterial injury and the extent of neointima formation. This study investigates whether the coronary artery affects the relationship between arterial injury and neointima hyperplasia in the porcine stent model., Methods: Non-lipemic farm pigs underwent stent placement in the LAD (n = 26) and the right coronary artery (RCA; n = 30). Quantitative coronary angiography (QCA) was performed before and after stent placement, and at follow-up; quantitative histomorphometry and injury score were analyzed at 30-day follow-up., Results: Initial procedure balloon/artery ratios (LAD 1.17 +/- 0.11 vs RCA 1.17 +/- 0.09, P = NS), and minimal stent lumen diameters (MLD; LAD 2.91 +/- 0.31 vs RCA: 2.93 +/- 0.28 mm, P = NS) were similar suggesting no difference in deployment technique. At follow-up there was more restenosis in the LAD (diameter stenosis: 55.0 +/- 26.4% vs 37.3 +/- 18.1%, and MLD: 1.24 +/- 0.78 mm vs. 1.71 +/- 0.57 mm, P < 0.05 for both comparisons). No differences were seen for injury score (1.09 +/- 0.51 vs 1.01 +/- 0.57; LAD vs RCA) or stent area (6.13 +/- 0.99 vs 6.55 +/- 1.42 mm2). Histomorphometry demonstrated smaller lumen area (2.15 +/- 0.94 vs 2.96 +/- 1.29 mm2) and thicker neointima (0.63 +/- 0.25 vs 0.51 +/- 0.17 mm; all P < 0.05) in the LAD. Multiple linear regression analysis identified the LAD as an independent predictive factor for increased neointima formation., Conclusions: These observations establish an animal model that is consistent with clinical experience showing that restenosis after stenting is more common in the LAD. The findings may be useful for understanding and developing systemic and local antirestenotic strategies.

Background: The mechanisms underlying the reduced neointimal proliferation (NP) by intracoronary brachytherapy (ICBT) are unknown. We hypothesized that ICBT inhibits NP by reducing expression of macrophage colony-stimulating factor (M-CSF)., Methods and Results: Thirty coronary arteries from 10 pigs were divided into 3 groups of 10 each: control (C), balloon injury (BI), and BI followed by ICBT (16 Gy at 0.5-mm tissue depth with a (32)P balloon system). Pigs were killed at 24 hours (n=3) and at 7 (n=4) and 14 (n=3) days. Expression of M-CSF was assessed by Western blot, ELISA, and quantitative immunostaining. Persistently increased levels of M-CSF after BI (to 1.4+/-0.2 nmol/L [ELISA] and 29.4+/-4.9% of cross-sectional area stained [immunocytochemistry]; P< 0.001 versus control for both) were observed in the injured arteries. Treatment of BI arteries with ICBT reduced M-CSF expression compared with BI alone (to 0.7+/-0.1 nmol/L [ELISA] and 13.5+/-2.9% of cross-sectional area stained [immunocytochemistry]; P<0.001 versus BI and P=NS versus control for both) and remained similar to control M-CSF expression for the 14-day study period. Neointimal thickness increased after BI (to 4.8+/-2.9 mm(2); P<0.001 versus control), but this was reduced by ICBT (1.4+/-0.4 mm(2); P<0.001 versus BI)., Conclusions: In porcine coronary arteries, BI is associated with increased expression of M-CSF and NP, but neither occurs after ICBT. The beneficial effects of ICBT on NP involve inhibition of M-CSF expression.

Biosurfactants are valuable microbial amphiphilic molecules with effective surface-active and biological properties applicable to several industries and processes. Microbes synthesize them, especially during growth on water-immiscible substrates, providing an alternative to chemically prepared conventional surfactants. Because of their structural diversity (i.e., glycolipids, lipopeptides, fatty acids, etc.), low toxicity, and biodegradability, these molecules could be widely used in cosmetic, pharmaceutical, and food processes as emulsifiers, humectants, preservatives, and detergents. Moreover, they are ecologically safe and can be applied in bioremediation and waste treatments. They can be produced from various substrates, mainly renewable resources such as vegetable oils, distillery and dairy wastes, which are economical but have not been reported in detail. In this review, we report advances made in using renewable substrates for biosurfactant production and their newer applications.

Aims of the Study: As per WHO (1993) the assessment and analysis of local problems and an appropriate epidemiological information system is an essential part of a control programme before embarking any control activity., Methodology: Four hundred and fourty one (441) adults of strictly defined admitted cerebral malaria patients were studied. Detailed clinical/neurological examination was done at the time of admission, daily thereafter, at the time of regaining consciousness, at the time of discharge and at weekly intervals in those having neurological sequelae. All patients were treated by i.v./oral quinine and specific syndromes were managed according to WHO guidelines., Results: Apart from fever and unconsciousness in all the patients, other features were convulsion (21.31%), neck rigidity (19%), psychosis (5.21%), conjugate deviation of eyes (2.26%), extrapyramidal rigidity (2.25%), trismus (1.31%), decorticate rigidity (1.13%) and decerebrate rigidity (0.90%). One hundred forty five (32.87%) patients expired and mortality was highest in pregnant ladies (39.28%). The important neurological sequelae in survivors were psychosis in 15 (5.06%), cerebellar ataxia in 14 (4.72%), hemiplegia in five (1.68%), extrapyramidal rigidity (EPR) in four (1.35%), peripheral neuropathy in three (1.01%), EPR with trismus in one (0.33%) and isolated sixth nerve palsy in one (0.33%) patients and all showed complete recovery in further follow up., Conclusion: The important observations of this study were stormy presentation, increased incidence of haemoglobinuria and jaundice, presence of neck rigidity, no prognostic relation to fundus abnormalities and high incidence of cerebellar ataxia and psychosis as neurological sequelae in survivors. Knowledge of self-limiting course of neurological sequelae may be helpful in reducing economic strain of expensive investigations and treatment.

In a previous meta-analysis of intracoronary brachytherapy (ICBT) studies, we identified the target tissue at 0.6 to 0.7 mm tissue depth and we developed two models, describing the relationship between dose and ICBT effectiveness. The purpose of the present study was to validate the identified target tissue depth and the developed dose models, using the results of 1) two prospective animal studies with ICBT, 2) a retrospective analysis of animal studies with external beam irradiation and 3) results of recent clinical ICBT trials. ICBT effectiveness in the porcine restenosis studies was quantified as inhibition of neointima proliferation. The results of these studies were correlated with the developed dose-effectiveness model. Finally, the agreement of the restenosis rates of the recent clinical trials with the developed dose-restenosis model was tested. The porcine restenosis studies demonstrated a dose-related inhibition of neointima proliferation. The radiation effectiveness of both prospective studies and the effectiveness of the studies with external beam irradiation demonstrated the best agreement with the developed dose model at a tissue depth of 0.6 mm. Furthermore, the restenosis rates of the recent clinical ICBT studies were in concordance with the developed dose-restenosis model. In conclusion, the current study validated the localization of the target tissue for ICBT at a tissue depth of 0.6 to 0.7 mm as well as the relationship between dose and ICBT effectiveness at this depth. The data provide a rationale for setting a common dose prescription point at 0.6 to 0.7 mm tissue depth.

A multicomponent protein complex containing manganese (II)-dependent peroxidase, laccase and beta-glucosidase was isolated from culture extracts of the white rot basidiomycete Lentinula edodes. This protein complex showed a single protein band on native polyacrylamide gel electrophoresis (PAGE). On sodium dodecyl sulfate (SDS)-PAGE, however, it displayed three major bands and several additional minor bands ranging in size from 60 kDa to 180 kDa, suggesting it being a complex of six to eight different proteins. The molecular mass of this complex was estimated to be approximately 660 kDa from the elution position of gel filtration. This enzyme complex was effective in transforming environmentally persistent xenobiotics, pentachlorophenol and 2,5-dichlorophenol.

Patients with severely symptomatic hypertrophic obstructive cardiomyopathy (HOCM) have several alternatives when drugs do not help. Surgical septal myotomymyectomy, though effective, is an open-heart surgical procedure and can be associated with some complications. The less invasive dual chamber pacing has not lived up to its early promise. Percutaneous transluminal septal myocardial ablation (PTSMA) is a relatively simple, less complicated nonsurgical procedure that can provide an effective and sustained relief of left ventricular outflow tract (LVOT) obstruction. Should it gain wider acceptance?

We are reporting the first case of an accidental radioactive 188Re leakage of a liquid-filled balloon system. Different analytical methods estimated that approximately 4 mCi 188Re were released. The radiation burden was reduced considerably by the combined therapy with perchlorate and forced volume diuresis. Estimated exposures to all organs were very low with 1.8 rad. A total body nuclear scintigraphy demonstrated uniform 188Re distribution, without specific organ concentration.

Background: Restenosis within stents may be prevented by ionizing radiation from an intravascular source., Methods and Results: A liquid beta(-) radiation ((188)Re) balloon was evaluated in a randomized and blinded porcine coronary model of stent restenosis. Group A pigs (n=17) received 0,16, 22, or 29 Gy at 0.5-mm depth, followed by stenting. Restenosis was quantified by angiography, ultrasound, and histomorphometry at 30 days. Group B (n=7) was stented first and then treated with 0 or 29 Gy with follow-up at 60 days. There was a measurable effect at 16 Gy, which improved with increasing doses. At 29 Gy, the histological stenotic area was reduced by 67% (22% versus 66% in controls, P<0.001). Radiation after stenting was equally effective; the stenotic area was reduced (21% versus 65%, P<0.001). At 16 Gy, the vessel just distal to the stent was significantly smaller than control vessels because of intimal thickening (P=0.003). Radiated vessels had distinctive histology consisting of neointimal fibrin and reduced smooth muscle cells and matrix (P<0.0001)., Conclusions: (188)Re balloon brachytherapy in porcine coronary arteries results in dose-dependent and injury-independent inhibition of stent restenosis for up to 60 days. Restenosis at the borders of the irradiated zone is a potential limitation and may be related to underdosing. Brachytherapy with the (188)Re balloon appears to be safe and feasible for clinical studies.

Surfactants are surface-active compounds capable of reducing surface and interfacial tension at the interfaces between liquids, solids and gases, thereby allowing them to mix or disperse readily as emulsions in water or other liquids. The enormous market demand for surfactants is currently met by numerous synthetic, mainly petroleum-based, chemical surfactants. These compounds are usually toxic to the environment and non-biodegradable. They may bio-accumulate and their production, processes and by-products can be environmentally hazardous. Tightening environmental regulations and increasing awareness for the need to protect the ecosystem have effectively resulted in an increasing interest in biosurfactants as possible alternatives to chemical surfactants. Biosurfactants are amphiphilic compounds of microbial origin with considerable potential in commercial applications within various industries. They have advantages over their chemical counterparts in biodegradability and effectiveness at extreme temperature or pH and in having lower toxicity. Biosurfactants are beginning to acquire a status as potential performance-effective molecules in various fields. At present biosurfactants are mainly used in studies on enhanced oil recovery and hydrocarbon bioremediation. The solubilization and emulsification of toxic chemicals by biosurfactants have also been reported. Biosurfactants also have potential applications in agriculture, cosmetics, pharmaceuticals, detergents, personal care products, food processing, textile manufacturing, laundry supplies, metal treatment and processing, pulp and paper processing and paint industries. Their uses and potential commercial applications in these fields are reviewed.

We are reporting the first case of an accidental radioactive 188Re leakage of a liquid-filled balloon system. Different analytical methods estimated that approximately 4 mCi 188Re were released. The radiation burden was reduced considerably by the combined therapy with perchlorate and forced volume diuresis. Estimated exposures to all organs were very low with 1.8 rad. A total body nuclear scintigraphy demonstrated uniform 188Re distribution, without specific organ concentration.

The efficacy of abciximab and moderate dose heparin in attaining reperfusion in acute MI was tested in a multicenter pilot study. Patients with acute MI of less than 6-hr onset triaged to primary PTCA received intravenous abciximab bolus and infusion and heparin (70 u/kg) in the emergency room. Mean time to angiography from administration of abciximab was 34 +/- 23 min. TIMI flow rates were: grade 0-62%, grade I-20%, grade II-9%, and grade III-9%. Primary PTCA was performed with 100% success rate. Access site bleeding occurred in 10% of patients with no incidence of intracranial bleeding. TIMI II/III flow rates were 50% in a patient subset where angiography was delayed by 45 min. While not an alternative to thrombolytics in AMI, abciximab administration in the emergency room in patients triaged to PTCA may be beneficial in situation where door to needle time is delayed as TIMI II/III flows may be attained in some patients. Cathet. Cardiovasc. Intervent. 48:430-434, 1999., (Copyright 1999 Wiley-Liss, Inc.)

The aging process is accompanied by a series of anatomical and physiological cardiovascular changes, including a generalised loss of vascular compliance, neuroendocrine alterations and endothelial dysfunction. Superimposed on this, there is an age-related increase in common cardiovascular disorders, such that the majority of deaths and much disability in older populations are caused by coronary artery disease. Most acute vascular events are mediated by thrombosis in which the formation of platelet aggregates forms an integral part. Research over recent years has led to the characterisation of the platelet glycoprotein (GP) IIb/IIIa receptor as the ultimate mechanism by which activated platelets cross-link by binding fibrinogen and other ligands. This knowledge has resulted in novel pharmacological strategies targeting this receptor which have proven to be potent inhibitors of thrombosis. The prototype drug, abciximab, is a chimeric monoclonal antibody directed against GP IIb/IIIa. Synthesis of new drugs has followed, based on the identification of the molecular sequences to which GP IIb/IIIa is attracted. This includes the emergence of oral agents which can be used for long term therapy. Clinical trials with these agents in the setting of percutaneous coronary interventions and unstable ischaemic syndromes have demonstrated a beneficial effect on thrombosis-related end-points. Trials of GP IIb/IIIa antagonists for direct percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction have also shown benefit, while their use in combination with fibrinolytic drugs is currently being evaluated. Other potential indications including neurovascular disease and primary haematological disorders are also being explored.

Background: The major limitation of coronary stenting is restenosis due to exaggerated neointimal thickening. We evaluated a positron-emitting V48 nitinol stent in a porcine coronary model of restenosis., Methods and Results: Pigs (n = 16) received a control nonradioactive and a V48 stent (1.5 or 10.6 muCi) randomized to the left anterior descending artery (LAD) and right coronary artery (RCA). Histology, morphometric variables, and strut injury scores were evaluated after 32 days. Peristrut fibrinoid deposits were greater in the high-dose group (p < 0.0001). Control stent area stenosis (AS) and mean neointimal thickness (NIT) correlated with injury (r = 0.81 and 0.79, respectively). Higher-dose stents reduced AS by 20% (0.57 +/- 0.13 vs. 0.71 +/- 0.16; p = 0.029) and mean NIT by 35% (0.44 +/- 0.16 vs. 0.71 +/- 0.24mm; p = 0.001) compared with controls. Lower-dose 1.5-muCi stents did not differ from controls. NIT over individual struts was reduced in the high-dose group compared with controls by 0.18 mm for grade 1 injury, 0.31 mm for grade 2, and 0.38 mm for grade 3 (p < 0.02 for all comparisons)., Conclusions: 1.5-muCi V48 nitinol stents did not influence vessel histology or restenotic parameters in pig coronary arteries. In contrast, 10.6-muCi stents created a distinctive histological picture consisting of increased fibrinoid deposits on the neointimal-facing side of the struts without cellular organization. Higher dose radioactive stents significantly reduced AS and mean NIT. The reduction in neointimal thickening was greatest when the depth of strut penetration into the vascular wall was most severe.

Background: Stent-induced coronary restenosis is a major clinical and public health problem. Proliferating cell nuclear antigen (PCNA) is an important regulator of cell division, and blocking of its expression after angioplasty may limit intimal proliferation., Methods and Results: We cloned the porcine PCNA gene and constructed a chimeric hammerhead ribozyme to a segment of the gene with human homology. In vitro studies with both cultured porcine and human vascular smooth muscle cells demonstrated uptake of ribozyme within the nucleus and significant inhibition of cellular proliferation. The ribozyme was then delivered locally into pig coronaries in a stent model. At 30 days, histomorphometric analysis showed neointimal thickness of 0.51+/-0.20 mm in the ribozyme group versus 0.71+/-0.27 and 0.66+/-0.25 mm in stent controls and scrambled ribozyme control, respectively (P=0.002, P=0.03). Quantitative angiographic analysis showed late loss of 1.4+/-0.5 mm for ribozyme versus 1.9+/-0.4 and 2.0+/-0.4 mm for the controls (P=0.05 and P=0. 02)., Conclusions: Chimeric hammerhead ribozyme to PCNA inhibits smooth muscle cell proliferation in vitro and reduces both histomorphometric and angiographic restenosis in the porcine coronary stent model when delivered locally.

The interest in industrial biotechnology and its importance opens up challenging possibilities of research in this area. Surfactants have long been among the most versatile of process chemicals. Their market is extremely competitive and manufacturers will have to expand their arsenal to develop products for the year 2000 and beyond. Biosurfactants are one of the most promising compounds in this regard. A review of the literature reveals that studies on oil-degrading and biosurfactant-producing microorganisms deal almost exclusively with their synthesis in moderate environments. Biosurfactants and the microbes that produce them have numerous industrial, medical and environmental applications, which frequently involve exposure to extremes of temperatures, pressure, ionic strength, pH and organic solvents. Hence, there is a continuing need to isolate microbes that are able to function under extreme conditions. There is an urgent need to explore these extremophiles for their ability to produce biosurfactants that can function suitably under the conditions prevailing when they are applied.

Aims: Use of ticlopidine in coronary stenting is limited by delayed onset of action. We studied the effects of clopidogrel, a rapidly acting analog of ticlopidine alone, and in combination with aspirin, in inhibiting stent thrombosis., Methods: Unpolished nitinol stents were deployed in a porcine ex vivo arteriovenous shunt and exposed to flowing arterial blood at a shear rate of approximately 1500. s-1. Stent thrombus, platelet aggregation and bleeding times were measured at baseline and after treatment., Results: Intravenous clopidogrel produced a rapid (within 30 min) and dose-dependent inhibition of stent thrombosis, with 87% reduction at a dose of 10 mg.kg-1 (P < 0.001). Aspirin alone (10 mg.kg-1) was minimally effective (20% inhibition P > 0.05) in inhibiting stent thrombosis. Combined treatment with clopidogrel and aspirin produced 95-98% inhibition of stent thrombosis, even at low doses of clopidogrel (2.5-5.0 mg.kg-1) (P < 0.0001). At effective doses both clopidogrel and combined therapy produced significant prolongation of bleeding time (P < 0.05) and inhibition of platelet aggregation (P < 0.05)., Conclusion: Clopidogrel, either alone or combined with aspirin, may have a potential role in preventing stent thrombosis in high-risk clinical situations.

The primary invasive granulomatous form of fungal sinusitis, due to inhalation of aspergillus spores, is commonest in the Sudan and the Gulf states. This condition often presents clinically as a chronic, severe sinusitis which has not responded to antibiotics. On CT scanning, the major feature is a soft tissue mass, which is either homogeneous or has lower attenuation components. There may be erosion or expansion of the bony margins of the sinuses. Intraorbital and/or intracranial extension sometimes occur.

Objectives: We sought to provide short- and long-term clinical outcomes of a high risk cohort treated with stents in saphenous vein grafts (SVGs)., Background: Data on the long-term outcome of SVG stenting in high risk patients are limited., Methods: Johnson & Johnson stents were implanted in the SVGs of 186 patients (302 stents, 244 lesions). Ninety percent of patients presented with myocardial infarction (MI) or unstable angina (mean +/- SD ejection fraction [EF] 44 +/- 11%, patient age 71 +/- 9 years, graft age 9.4 +/- 5 years). Using a risk score classification, 155 patients (83%) were defined as high risk for repeat surgical repair or angioplasty., Results: The procedural success rate was 97.3%, with 2.7% major complications (death, Q wave MI, coronary artery bypass graft surgery [CABG]). Clinical follow-up was obtained in 177 patients (mean 19.1 +/- 13.5 months, range 7 to 59). Event rates were 10% for death; 9% for MI; 11% for repeat CABG; and 15% for repeat angioplasty (total events 45%). Kaplan-Meier estimated survival and event-free survival at 4 years were 0.79 +/- 0.06 and 0.29 +/- 0.07, respectively. Predictors of death were congestive heart failure (p < 0.01) and EF <44% (p < 0.05). Predictors of combined events of death, MI and CABG were low EF (p < 0.01) and high SVG age (>10 years, p < 0.01). There were 66 revascularization procedures (35% of patients), 24% of which were in nontarget lesions. Fifty-three percent of the cardiac events occurred during the first year of follow-up. Of the 160 survivors, 36% were free of angina, 49% were in Canadian Cardiovascular Society functional class I or II, and 15% were in class III or IV. Sixty-nine percent of patients were in class I or II according to the Specific Activity Scale, and 31% of patients were in class III or IV., Conclusions: Balloon-expandable stent implantation in the SVGs of high risk patients is associated with a low early complication rate. Expected survival rates are good, as are the anginal and functional classifications, but there is a high rate of recurrent events and need for repeat revascularization. Vein graft stenting is an acceptable palliative option in many high risk patients.

Background: Thrombosis is an important limitation of metallic coronary stents, especially in smaller vessels in which shear rates are high. Monoclonal antibody to platelet glycoprotein IIb/IIIa receptor (7E3) has been shown to inhibit shear-induced platelet aggregation. In this study, we compared the effects of 7E3, heparin, and aspirin on stent thrombosis in an ex vivo arteriovenous shunt model of high-shear blood flow., Methods and Results: An ex vivo arteriovenous shunt was created in 10 anesthetized dogs. Control rough-surface slotted-tube nitinol stents (n = 72) expanded to 2 mm in diameter in a tubular perfusion chamber were interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100s-1 for 20 minutes. The animals were treated with intravenous murine 7E3 (Fab')2 (0.2, 0.4, and 0.8 mg/kg), heparin (100 U/kg), or aspirin (10 mg/kg). Effects of the test agents on thrombus weight, platelet aggregation, platelet P-selectin expression, bleeding time, and activated clotting time (ACT) were quantified. 7E3 reduced stent thrombosis by 95% (20 +/- 1 to 1 +/- 1 mg, P < .001) and platelet aggregation by 94% (14 +/- 2 to 1 +/- 1 omega, P < .001) at the highest dose (0.8 mg/kg). 7E3 significantly prolonged bleeding time but had no effect on ACT and platelet P-selectin expression. Heparin prolonged ACT but had no significant effect on stent thrombosis or platelet aggregation. Aspirin, although it inhibited platelet aggregation by 65%, had no effect on stent thrombosis (19 +/- 2 versus 20 +/- 1 mg in controls)., Conclusions: 7E3 produced a dose-dependent inhibition of acute stent thrombosis under high-shear flow conditions. Stent thrombosis was resistant to heparin and aspirin. Thus, 7E3 may be an effective agent for preventing stent thrombosis.

Background: Coronary stenting is limited by subacute thrombosis, especially in smaller-diameter vessels, in which shear rates are high. The objective of the present study was to determine whether local delivery of a new type of NO donor, the NO adduct of N,N'-dimethylhexanediamine (DMHD/NO), inhibits acute stent thrombosis (ST) at high-shear flow., Methods and Results: Effects of local infusion of DMHD/NO; intravenous aspirin, and heparin on ST were evaluated in an ex vivo porcine AV shunt model. Nitinol stents (2 mum in diameter, n = 120) were placed in a tubular chamber and perfused with blood from pigs (n = 13) at a shear rate of 2100s-1 for 20 minutes. ST was quantified by measurement of dry thrombus weight(TW). Effects on platelet aggregation (PA), blood pressure, bleeding time, and activated clotting time (ACT) were also examined. There was a dose-dependent inhibition of ST and PA by DMHD/NO. TW was reduced by 95% (1 +/- 2 versus 16 +/- 4 mg control, mean +/- SD, P < .001), and PA was reduced by 75% (4 +/- 3 versus 14 +/- 9 omega/min control, P < .05) at the highest dose of 10 mumol/L. DMHD/NO had no effects on bleeding time, ACT, or blood pressure. In contrast, aspirin (10 mg/kg), despite inhibiting PA, had no effects on TW (12 +/- 5 versus 16 +/- 8 mg control, P = .3). Heparin (200 U/kg) reduced TW by 33% (14 +/- 4 versus 21 +/- 3 mg control, P < .05) and prolonged ACT., Conclusions: Local delivery of DMHD/NO produced a 15-fold inhibition of acute ST at high-shear flow without producing adverse systemic hemostatic or hemodynamic effects. Thus, treatment with DMHD/NO may be an effective strategy for prevention of stent thrombosis.

Somatosensory evoked potentials were recorded in patients of cerebral malaria by (R) median nerve stimulation. Important observations of this study were delayed absolute latency of N20, increased N13-N20 IPL i.e. central conduction time and distorted and dispersed waveforms of N9 and N20 peaks. The possible pathologic mechanism is discussed.

Somatosensory evoked potentials, sensory and motor nerve conduction velocity were studied in 25 patients of chronic renal failure and the results were compared with 15 healthy persons. The values more than +/- 3 S.D. were considered abnormal. SNCV was reduced in 11/25 patients; average reduction being 18 m/s (highly significant, p < 0.001); MNCV was reduced in 11/25 patients, average reduction being 20 m/s (highly significant, p < 0.001). Both SNCV and MNCV in same person were reduced in 6/25 patients. In SSEP N9, N13 and N20 were delayed in almost all the patients (highly significant, p < 0.001). Amplitude of N20 and N13 were reduced in 1 and 4 patients respectively but amplitude of N9 was normal. Out of different IPLS, Ebw-N9 was delayed in 5/25 patients (p < 0.9, insignificant); N9-N13 was delayed in 8/25 patients (p < 0.001, highly significant); N13-N20 was delayed in 1/25 patients (p < 0.01, significant). The evidence of these neurophysiological abnormalities collectively suggest the presence of central-peripheral axonopathy in this disease.

Experimentally, heparin inhibits mechanisms that promote fibrosis, neointimal cellular proliferation, and thrombin bound to fibrin at the surface of intraluminal thrombus, but only in relatively high concentrations. A preliminary hypothesis was tested and confirmed in vitro that initial binding of 3H-heparin to mechanically injured porcine aorta is concentration-dependent over a 1,000-50,000 units/ml range (r = 0.9). The hypothesis was then tested in vitro that thermal exposure during contact of heparin to arterial tissue and to clot would enhance binding of the drug. 3H-heparin binding to clot, whole blood particulates, and washed erythrocytes was markedly enhanced by exposure to temperatures > 70 degrees C. Thermal exposure (80 degrees C x 40 s) also enhanced tissue persistence of the drug within porcine aorta subjected to a shear rate of 1,100(-1) in an annular Baumgartner chamber perfused with normal saline at 37 degrees C for 48 h. Heparin in vitro anticoagulant activity persisted after thermal exposure and binding to tissues. A new method was developed for local application of a heparin film that provides a maximum concentration with a tolerable systemic dose during an angioplasty procedure. In an in vivo rabbit model of mural fibrosis after iliac artery angioplasty, the 1-month mean angiographic luminal diameter loss (23% compared to the acute postangioplasty result by computer image analysis) in response to conventional balloon angioplasty (BA) and laser balloon angioplasty (LBA) was the same (P > 0.05). Local application of a heparin film (3,000 units at a concentration > 100,000 units/g), however, reduced the mean % loss in diameter 1 month after LBA (12%), but not after BA (29%), compared to arteries subjected to angioplasty without local heparin (P < .05). The results are consistent with the hypothesis that thermal energy enhances heparin binding to tissues and that local application of a heparin film favorably modulates arterial luminal responses to LBA, but not to BA, in this animal model.

Objective: To test the hypothesis that female prevalence is greater than expected among reported cases of torsades de pointes associated with cardiovascular drugs that prolong cardiac repolarization., Data Sources: A MEDLINE search of the English-language literature for the period of 1980 through 1992, using the terms torsade de pointes, polymorphic ventricular tachycardia, atypical ventricular tachycardia, proarrhythmia, and drug-induced ventricular tachycardia, supplemented by pertinent references (dating back to 1964) from the reviewed articles and by personal communications with researchers involved in this field., Study Selection: Ninety-three articles were identified describing at least one case of polymorphic ventricular tachycardia (with gender specified) associated with quinidine, procainamide hydrochloride, disopyramide, amiodarone, sotalol hydrochloride, bepridil hydrochloride, or prenylamine. A total of 332 patients were included in the analysis following application of prospectively defined criteria (eg, corrected QT [QTc] interval of 0.45 second or greater while receiving drug)., Data Extraction: Clinical and electrocardiographic descriptors were extracted for analysis. Expected female prevalence for torsades de pointes associated with quinidine, procainamide, disopyramide, and aminodarone was conservatively estimated from gender-specific data reported for antiarrhythmic drug prescriptions in 1986, as derived from the National Disease and Therapeutic Index, a large pharmaceutical database; expected female prevalence for torsades de pointes associated with sotalol, bepridil, and prenylamine was assumed to be 50% or less since these agents are prescribed for male-predominant cardiovascular conditions., Results: Women made up 70% (95% confidence interval, 64% to 75%) of the 332 reported cases of cardiovascular-drug-related torsades de pointes, and a female prevalence exceeding 50% was observed in 20 (83%) of 24 studies having at least four included cases. When analyzed according to various descriptors, women still constituted the majority (range, 51% to 94% of torsades de pointes cases), irrespective of the presence or absence of underlying coronary artery or rheumatic heart disease, left ventricular dysfunction, type of underlying arrhythmia, hypokalemia, hypomagnesemia, bradycardia, concomitant digoxin treatment, or level of QTc at baseline or while receiving drug. When cases of torsades de pointes were analyzed by individual drug, observed female prevalence was always greater than expected, representing a statistically significant difference (P < .05) for all agents except procainamide., Conclusions: These findings strongly suggest that women are more prone than men to develop torsades de pointes during administration of cardiovascular drugs that prolong cardiac repolarization. The pathophysiological basis for, and therapeutic implications of, this gender disparity should be further investigated.

Virulent Mah type 1 poliovirus and the attenuated Sab types 1, 2 and 3 poliovirus do not efficiently produce plaques or grow as efficiently with Vero cells as with HeLa cells. All viruses attach poorly to simian cells on monolayer and, except for Mah and Sab1, eclipse poorly. Additionally, all three attenuated viruses block initiation of Vero cell protein synthesis less effectively than HeLa cell protein synthesis. The lower rates of attachment and eclipse of these viruses with Vero cells and their limited capacities to block cellular protein synthesis and thereby provide ribosomes for translation of viral RNA probably contribute to their more restricted growth in Vero cells.