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Biomedical subjects

V Dev

Publications and source records attributed to V Dev.

At least 19 recordsLinked to original sources

Sustained local drug delivery to the arterial wall via biodegradable microspheres.

This study was designed to evaluate the feasibility of applying locally delivered polylactic acid microspheres for drug delivery to the arterial wall. To study drug persistence, rhodamine-loaded microspheres were infused into one carotid artery of 14 rabbits and plain rhodamine solution into the other by using a porous balloon. To study tissue response, plain microspheres and dexamethasone-loaded microspheres were infused into the carotid arteries of another group of rabbits. To study the antiproliferative effects of locally delivered drug, 20 rabbits were subjected to overstretch balloon injury to both carotid arteries and divided into 4 groups: injury alone, plain microspheres, dexamethasone-loaded microspheres, and microspheres containing colchicine and dexamethasone. Fluorescent microspheres persisted in the vessel wall for 4 wk, whereas rhodamine without microspheres disappeared at 72 h. Histopathologic studies in arteries infused with unloaded microspheres showed inflammatory cell infiltrate with polymorphonuclear cells at 1 wk and macrophages and giant cells at 4 wk. Arteries infused with dexamethasone-loaded microspheres did not show any inflammatory cell infiltrate. Local delivery of dexamethasone or dexamethasone plus colchicine did not result in significant change in the intima-to-media ratio or in residual lumen following balloon injury. Polylactic acid microspheres may be used for prolonged delivery of drugs or other bioactive agents locally to the arterial wall. They induce an inflammatory reaction that is suppressable by dexamethasone in the microspheres. Dexamethasone or dexamethasone and colchicine delivered via this system, however, failed to reduce the degree of intimal hyperplasia after overstretch balloon injury to the rabbit carotid arteries.

Angioplasty, Balloon, Coronary

Subacute thrombosis and vascular injury resulting from slotted-tube nitinol and stainless steel stents in a rabbit carotid artery model.

BACKGROUND: Our objectives were to quantify the thrombogenicity and extent of vascular injury created by slotted-tube geometry stainless steel and nitinol coronary stents in a rabbit carotid artery model. METHODS AND RESULTS: Stents were implanted in rabbit right carotid arteries without antiplatelet therapy. Stainless steel stents were implanted for 4 days while nitinol stents were placed for 4 and 14 days (n = 8, 8, and 6, respectively). Stent thrombosis was assessed by thrombus weight, grading thrombus encroachment of the lumen, and by blood flow in the stented and contralateral arteries. Stainless steel stents at 4 days contained more thrombus than 4- and 14-day nitinol stents (20.0 +/- 5.9 versus 2.5 +/- 0.6 and 2.7 +/- 0.3 mg, respectively; P < .000001). Stainless steel stents were more often occluded by thrombus (6 of 8) or contained more subocclusive thrombus (2 of 8) than nitinol stents (0 of 14, P < .002). Resting blood flow was reduced in arteries with stainless steel stents compared with 4- and 14-day nitinol stents (1.5 +/- 2.8 versus 24.0 +/- 2.0 and 25.5 +/- 1.9 mL/min, respectively, P < .000001). Stainless steel stents were less uniformly expanded, had deeper strut penetration into the vascular wall, and were associated with more extensive medial smooth muscle cell necrosis. There were strong correlations (r = .77 to .95) between variables of thrombosis extent (thrombus weight and grade) and histologically determined vascular injury (strut penetration and medial necrosis). CONCLUSIONS: Slotted-tube stainless steel stents were more thrombogenic and created more extensive vascular injury than nitinol stents in a rabbit carotid artery model. The mechanisms underlying these differences probably are related to metallurgic and design geometry properties of the two stent types.

Acute Disease

Anopheles minimus: its bionomics and role in the transmission of malaria in Assam, India.

Indoor, day-resting collections of Anopheles minimus mosquitos from human dwellings in the study area in Assam, India, indicated that these insects were prevalent throughout the year and that their maximum abundance occurred from March to August. A. minimus was identified as a vector of malaria, and sporozoite infections were recorded every month of the year, with the highest rating occurring in October. The mosquito was highly anthropophilic and fed on human hosts (indoor) all through the night, but feeding was more pronounced between 01:00 and 04:00, the person-biting rate was 13.7 per night. Breeding occurred throughout the year in slow-flowing streams with grassy banks. A. fluviatilis was also identified as a vector of malaria in the study area but occurred in low density, and sporozoite infections were only seasonal.

Animals

Malaria survey in Tarajulie tea estate and adjoining hamlets in Sonitpur District, Assam.

Malaria survey in Tarajulie tea estate (TE) and its adjoining hamlets revealed that Pf was the predominant parasite species (79%) and morbidity was alarming. Malaria positive cases were recorded in all age groups including infants. However, morbidity was much pronounced in the hamlets than among garden dwellers. Mostly Anopheles minimus were recorded in the day resting collections from human dwellings (indoor) and in overnight man biting catches in the hamlets. From these collections. An. minimus was incriminated and the sporozoite infection rate was found to be 4.23 per cent. An. minimus were not recorded in the garden premises. Thus morbidity in the garden population was attributed to the movement of labourers to and fro between hamlets and the garden premises. The hamlets served as reservoirs for malaria infection.

Adolescent

Morbidity and mortality due to malaria in Tarajulie Tea Estate, Assam, India.

Beginning 1991, a sudden rise of malaria cases were recorded in Tarajulie TE (Assam) coupled with mortality due to malaria. Deaths were confirmed due to Plasmodium falciparum (Pf) infections and were recorded in all age groups excluding infants. Malaria positives were recorded in all months of the year, however, there was a increased hospital attendance due to fever/malaria positives during May to September. During the years (1991-1993), the slide positive rate was as high as 33.04%, mostly being Pf infections (69%), and the annual parasite index ranged between 6 to 304 per thousand population. Morbidity and mortality due to malaria were attributed to labor movements to and fro from garden premises to adjoining hamlets, the latter being the site of acquisition of the infections.

Adolescent

Kinetics of drug delivery to the arterial wall via polyurethane-coated removable nitinol stent: comparative study of two drugs.

Polymer-coated removable stents were used to deliver 14C-labeled etretinate and 3H-labeled forskolin to the vessel wall in 31 New Zealand White rabbits to study their kinetics. Stents loaded with etretinate (n = 8) and forskolin (n = 14) were implanted in the rabbit carotid arteries, and the animals were euthanized at different time intervals. Drug levels were measured in the media and adventitia of the stented segment, in distant tissues, and in blood. In four rabbits, forskolin-loaded stents were percutaneously retrieved 2 hr after implantation in the carotid artery, and the tissue and blood levels were determined 2 and 24 hr after retrieval. In seven rabbits etretinate-loaded stents were retrieved 72 hr after implantation in abdominal aorta, and drug levels were measured in the tissues and blood immediately after and at 1 and 4 days after retrieval. Levels of etretinate in the vessel wall peaked at 24 hr (250 ng/mg) and remained high up to 72 hr (185 ng/mg) after stent placement. Levels of forskolin peaked within 2 hr of stent placement (135 ng/mg) and rapidly declined to 4.9 ng/mg at 24 hr with the stent in situ. About 50% (1.4 mg) of the original etretinate remained in the stent at 72 hr compared to about 5% (0.08 mg) of forskolin at 24 hr. Ratio of peak drug levels in the vessel wall to those in the blood was 6,000 for etretinate and 780 for forskolin. (ABSTRACT TRUNCATED AT 250 WORDS)

Alloys

Deltamethrin impregnated bednets against Anopheles minimus transmitted malaria in Assam, India.

Of the 20 Anopheles species caught in villages in Sonapur, Assam, only An. minimus was incriminated as a malaria vector by finding sporozoites in the salivary glands. It was found to be endophagic and endophilic in Assam and because its biting peaked after midnight it was a suitable target for insecticide impregnated bednets. After the withdrawal of DDT spraying and collecting a year's baseline data, deltamethrin impregnated nets were distributed in 3 villages, untreated nets were distributed in 6 villages and 3 were held as untreated controls. The population of each of these groups of villages was about 1700. The nets were well received by the local tribal population. Human landing catches with baits unprotected or under partially lifted nets showed that the nets provided a high degree of personal protection against all the local species of human biting mosquito. In addition, there was evidence for suppression of the An. minimus population in a village with treated nets. Malaria was monitored by weekly active surveillance in all the villages. In the untreated control villages the slide positivity rate and monthly parasite index rose significantly during the trial. In the villages with untreated nets, these parameters showed no significant change, but in the villages with treated nets they declined significantly. On the basis of these results, the widespread distribution of impregnated nets was recommended to the state health authorities.

Animals

Susceptibility of Plasmodium falciparum to chloroquine in tea garden tribes of Assam, India.

P. falciparum was the predominant parasite ( > 80%) species in malaria ridden tea estates of Assam. A simplified 3 day in vivo test to determine chloroquine sensitivity in tea garden tribes revealed that the majority of the cases (85%) were S/RI, 7% were RI, and 3% were RII and 5% were RIII, respectively. Early case detection and treatment were deemed necessary to reduce morbidity and mortality due to P. falciparum in these tea estates.

Adolescent

Current status and prospects for the use of temporary stents.

Temporary stenting appears to be an attractive potential therapy that combines some of the benefits of permanent stenting without the need for permanent endovascular prostheses and oral anticoagulation. The devices used for temporary stenting are still evolving. The Flow Support Catheter showed promise in the early clinical trial phase but is not being pursued by the original manufacturer because the device was associated with a high rate of thrombosis and suboptimal overall success rate. The experience with the Instent is limited and the removal of its unattached version relies upon catching the end of the stent in the retrieval device (a wire loop); also, its safety and reliability still need to be proved. The HARTS device is currently in the preclinical phase, but available data from animal studies show it to be a feasible device for coronary use. Its potential applications include use as a permanent stent, a temporary stent, a repositionable stent, a primary lesion-dilating device, or a local drug-delivery vehicle. Clinical trials are likely to commence in the foreseeable future for one or more of these applications.

Administration, Oral

Localized arterial wall drug delivery from a polymer-coated removable metallic stent. Kinetics, distribution, and bioactivity of forskolin.

BACKGROUND: Coronary stenting is associated with two major complications: subacute thrombosis and neointimal proliferation resulting in restenosis. Our hypothesis is that the biocompatibility of metallic stents can be improved by coating with a polymer membrane that delivers agents that favorably modify the local arterial microenvironment. This study evaluates the kinetics, distribution, and bioactivity of the model drug forskolin delivered to the local arterial wall by a polyurethane-coated removable metallic stent. METHODS AND RESULTS: Stents were used in rabbit carotid arteries (n = 20) for as long as 24 hours. The quantity of forskolin bound to the stent decreased exponentially with a half-life of 5.8 hours. Blood concentrations peaked at 140 +/- 39 pg/microL at 4 hours. The adjacent arterial media contained 60 +/- 39 ng/mg, which was 380- and 460-fold greater than the contralateral carotid media and the systemic blood, respectively (P < .0001). Media forskolin concentrations declined exponentially over time with a tissue half-life of 5.0 hours. Drug distributed throughout the vessel wall with decreasing gradients in the radial and axial dimensions consistent with a diffusion process. Removal of the stent was associated with a 100-fold decline in media forskolin concentration within 2 hours. Forskolin release was associated with a sustained 92% increase in carotid blood flow and a 60% decrease in local arterial resistance compared with coated control stents (P < .005). In another set of rabbits (n = 14) using a carotid crush injury, flow-reduction model, forskolin prolonged the time to flow variation and occlusion by 12-fold compared with the use of bare metal stents and 5-fold compared with the use of polyurethane-coated stents (P < .0001). CONCLUSIONS: A polymer-coated metallic stent can deliver forskolin to the local arterial wall in high concentrations relative to the blood or other tissues. High local drug concentrations are dependent on maintaining stent-to-tissue gradients. The delivered drug is biologically active, demonstrating vasodilating and antiplatelet properties.

Alloys

Management of hepatic venous outflow obstruction.

Hepatic venous outflow obstruction (HVOO) is a rare cause of portal hypertension and conservative treatment is usually ineffective. A large series of patients gave us an opportunity to devise a management protocol for this disorder. Between 1978 and 1992, we prospectively studied 75 patients with HVOO. The obstruction was in the hepatic vein in 24, in the inferior vena cava (IVC) in 44, and in both in 7. For hepatic vein obstruction proximal splenorenal shunts were done in 7 (2 died postoperatively); 4 shunts blocked and only 1 patient became completely symptom free. In 2 patients with partial obstruction we performed balloon dilatation of the right hepatic veins but within 6 months the obstruction recurred. In the next 6 patients we constructed a side-to-side portocaval shunt; 2 died of encephalopathy after discharge and 4 are alive and well. For IVC obstruction, after surgical procedures had yielded poor results in 14 patients, we changed to balloon angioplasty which was successful in 28 of the 30 other patients; restenosis occurred in 4. Of the 7 patients with a combined block, 3 have had balloon angioplasty followed by a side-to-side portocaval shunt; 1 died, 2 are well, and the remainder have not completed treatment. Of our 75 patients, 22 have died (5 in hospital and 17 after discharge), 7 have not completed treatment, and 2 have been lost to follow-up. However, 44 are symptom free. We did not encounter any case of hepatocellular carcinoma. We suggest that patients with HVOO should be actively managed with a side-to-side portocaval shunt for hepatic vein obstruction, balloon angioplasty for inferior vena caval obstruction, and perhaps both procedures for those with combined obstructions.

Adolescent

Left ventricular diastolic function in end-stage renal disease and the impact of hemodialysis.

Twenty-one patients (17 men and 4 women, aged 20 to 40 years) with end-stage renal disease (creatinine clearance persistently < 5 ml/min for > 3 months) were evaluated for left ventricular (LV) diastolic function by Doppler echocardiography before and after hemodialysis. Fifteen patients were on maintenance hemodialysis (group A) and 6 were studied before and after their first hemodialysis (group B). The following indexes of LV diastolic function were studied: (1) isovolumic relaxation time; and (2) Doppler indexes from mitral inflow signal--peak early velocity, peak late velocity (atrial), deceleration of early filling phase, and deceleration time of early filling phase. LV systolic function in groups A and B (LV ejection fraction 68 +/- 6 and 77 +/- 5%, fractional shortening 0.39 +/- 0.06 and 0.46 +/- 0.05%) was normal and did not change after hemodialysis. Group A had a prolonged isovolumic relaxation time of 80 +/- 22 ms, which decreased to 57 +/- 14 ms (p < 0.005). Deceleration time decreased from 248 +/- 58 to 184 +/- 38 ms (p < 0.00005) and the deceleration slope increased from 4.3 +/- 1.8 to 5.1 +/- 1.6 m/s2 (p < 0.005) after hemodialysis. In group B, isovolumic relaxation time decreased from 87 +/- 21 to 73 +/- 15 ms (p < 0.05), deceleration time decreased from 256 +/- 43 to 185 +/- 34 ms (p < 0.05), and deceleration slope increased from 3.5 +/- 0.8 to 4.2 +/- 1.1 m/s2 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Pulmonary balloon valvotomy for severe valvular pulmonic stenosis with congestive heart failure beyond infancy.

Isolated valvular pulmonic stenosis (PS) in association with tricuspid regurgitation and congestive heart failure (CHF) is rarely encountered after infancy, and there is very little information available regarding the application of pulmonary balloon valvotomy (PBV) for this subset of patients. Since 1985, 10 patients (5 males, 5 females; mean age: 12.4 +/- 7.5 years, range 4-25 years) underwent PBV for severe valvular PS with CHF in our institution. All patients had associated tricuspid regurgitation and cardiomegaly. Before PBV, the mean peak systolic gradient across the right ventricular outflow was 131 +/- 36 mmHg and the mean right atrial pressure was 14.4 +/- 5.4 mmHg. Specific modifications in the PBV technique included the sequential use of progressively larger balloon catheters and the use of an extra stiff guidewire to support the dilatation assembly. One patient underwent PBV via the right internal jugular vein. Problems encountered during PBV included hypotension and bradycardia (2 patients) and respiratory arrest, which was transient in one patient, and prolonged and eventually fatal in one patient. A successful outcome was achieved in 8 patients (4 of these required 2 PBV attempts) with a final residual gradient of 40 mmHg or less, mean 28 +/- 7; range: 21-38 mmHg) and complete resolution of CHF. One patient has had no significant change in gradients and awaits repeat dilatation. Patients with isolated severe valvular PS with TR and CHF represent a relatively high risk group for PBV. A successful outcome is, however, feasible if a carefully planned and cautious approach is used.

Catheterization

Determinants of immediate and follow-up results of pulmonary balloon valvuloplasty.

The data of 93 patients (age 11.4 +/- 9.4 years, range 8 months-56 years) who underwent pulmonary balloon valvuloplasty (PBV) for valvular pulmonic stenosis (PS) in our institution are reviewed. The patients were classified into three groups: Group I (34 patients) had a right ventricular (RV) to aortic systolic pressure ratio of < 1, Group II (39 patients) had suprasystemic RV systolic pressures, and Group III (20 patients) included patients with elevated mean right atrial (RA) pressures irrespective of the RV systolic pressures. The percentage drop in immediate postdilatation peak systolic gradients (PSG) and the follow-up PSG were similar in the three groups and were not influenced by any predilatation patient characteristics. A balloon-annulus ratio < 1 predicted a poorer follow-up outcome. Nine patients, eight of Group III and one of Group II, experienced difficult procedures requiring sequential use of progressively larger balloon catheters. Eleven patients, six of Group II and five of Group III, experienced procedure-related events (hypotension, bradycardia/asystole, hypoxia, apnea, tachyarrhythmias, and seizures) and one patient (Group II) died. Although changes in immediate and follow-up gradients after PBV are not influenced by the severity of PS, difficult procedures and procedure-related events are particularly common in patients with severe PS and elevated RA pressures. A cautious and planned approach is therefore indicated in these patients.

Adolescent