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2.
J Forensic Leg Med ; 29: 30-3, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25572082

ABSTRACT

The present study was carried out to analyze various factors associated with death due to hanging among adolescents and to identify the areas of intervention for preventing such deaths. A retrospective study was carried out on 51 cases of adolescent deaths due to hanging, the autopsies of which were conducted by the Department of Forensic Medicine, Dr Shankarrao Chavan Government Medical College, Nanded, Maharashtra State (India), during the period between 1 January 2001 and 31 December 2010. In the present study, death by hanging among the adolescent age group was most commonly suicidal (96.08%) in nature, and only two (3.92%) cases of deaths due to accidental hanging were observed. Of the total number of suicidal deaths due to hanging among adolescents, the majority (80.39%) were among the older adolescent (15-19 years) age group. Rope and clothing items were commonly used ligature materials for committing suicide by hanging. Females outnumbered male victims (M:F ratio 1:1.13) among adolescents, contrary to the male preponderance observed among victims of the older age group (M:F ratio 1:0.44). Most of the suicidal deaths due to hanging (83.67%) among adolescents were observed at the victims' home. The predisposing and precipitating factors observed were domestic strife, examination-related stress, and physical and psychological illness.


Subject(s)
Asphyxia/mortality , Neck Injuries/mortality , Suicide/statistics & numerical data , Adolescent , Child , Family Conflict , Female , Forensic Medicine , Health Status , Humans , India/epidemiology , Male , Mental Disorders/psychology , Retrospective Studies , Sex Distribution , Stress, Psychological , Young Adult
3.
Eur J Vasc Endovasc Surg ; 46(2): 175-90, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23721817

ABSTRACT

OBJECTIVE/BACKGROUND: Classification systems for aortic dissection provide important guides to clinical decision-making, but the relevance of traditional categorization schemes is being questioned in an era when endovascular techniques are assuming a growing role in the management of this frequently complex and catastrophic entity. In recognition of the expanding range of interventional therapies now used as alternatives to conventional treatment approaches, the Working Group on Aortic Diseases of the DEFINE Project developed a categorization system that features the specific anatomic and clinical manifestations of the disease process that are most relevant to contemporary decision-making. METHODS AND RESULTS: The DISSECT classification system is a mnemonic-based approach to the evaluation of aortic dissection. It guides clinicians through an assessment of six critical characteristics that facilitate optimal communication of the most salient details that currently influence the selection of a therapeutic option, including those findings that are key when considering an endovascular procedure, but are not taken into account by the DeBakey or Stanford categorization schemes. The six features of aortic dissection include: duration of disease; intimal tear location; size of the dissected aorta; segmental extent of aortic involvement; clinical complications of the dissection, and thrombus within the aortic false lumen. CONCLUSION: In current clinical practice, endovascular therapy is increasingly considered as an alternative to medical management or open surgical repair in select cases of type B aortic dissection. Currently, endovascular aortic repair is not used for patients with type A aortic dissection, but catheter-based techniques directed at peripheral branch vessel ischemia that may complicate type A dissection are considered valuable adjunctive interventions, when indicated. The use of a new system for categorization of aortic dissection, DISSECT, addresses the shortcomings of well-known established schemes devised more than 40 years ago, before the introduction of endovascular techniques. It will serve as a guide to support a critical analysis of contemporary therapeutic options and inform management decisions based on specific features of the disease process.


Subject(s)
Aortic Aneurysm/classification , Aortic Aneurysm/diagnosis , Aortic Dissection/classification , Aortic Dissection/diagnosis , Decision Support Techniques , Terminology as Topic , Adult , Aortic Dissection/complications , Aortic Dissection/diagnostic imaging , Aortic Dissection/therapy , Aortic Aneurysm/complications , Aortic Aneurysm/diagnostic imaging , Aortic Aneurysm/therapy , Aortic Rupture/etiology , Aortic Rupture/prevention & control , Aortography/methods , Endovascular Procedures , Female , Humans , Male , Middle Aged , Patient Selection , Predictive Value of Tests , Prognosis , Risk Factors , Severity of Illness Index , Thrombosis/etiology , Time Factors , Tomography, X-Ray Computed
4.
Radiol Med ; 118(1): 74-88, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22466875

ABSTRACT

Malperfusion syndrome is a complication of aortic dissection caused by branch-vessel involvement and resulting in end-organ ischaemic dysfunction. Clinical diagnosis is mandatory, and imaging plays a critical role in confirmation and treatment planning. Radiologists must focus on detecting complications (findings of aortic dilation, rupture, organ ischaemia, etc.) and defining vascular compromise and associated malperfusion mechanisms. All these factors guide the multidisciplinary discussion concerning patient management and the suitability of endovascular treatment. Application of dedicated imaging protocols is mandatory in order to answer clinical and anatomical questions. Endovascular therapy has taken a predominant role in the therapeutic management of malperfusion syndrome with aortic fenestration, peripheral stenting and stent-grafting, all of which are procedures within the domain of expertise of current interventional radiologists. The purpose of this editorial is to present a when, what and how-to guide for all radiologists who encounter complicated aortic dissection.


Subject(s)
Aortic Aneurysm, Thoracic/complications , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/complications , Aortic Dissection/diagnostic imaging , Aortic Dissection/surgery , Ischemia/diagnostic imaging , Ischemia/etiology , Ischemia/surgery , Angiography , Blood Vessel Prosthesis Implantation , Cardiac-Gated Imaging Techniques , Contrast Media , Humans , Syndrome , Tomography, X-Ray Computed
5.
AJNR Am J Neuroradiol ; 33(8): 1615-20, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22517280

ABSTRACT

BACKGROUND AND PURPOSE: CCSVI hypothesizes an association between impaired extracranial venous drainage and MS. Published sonographic criteria for CCSVI are controversial, and no MR imaging data exist to support the CCSVI hypothesis. Our purpose was to evaluate possible differences in the extracranial venous drainage of MS and healthy controls using both TOF and contrast-enhanced TRICKS MRV. MATERIALS AND METHODS: Healthy subjects (n = 20) and patients with MS (n = 19) underwent axial 2D-TOF neck MRV (to assess flattening) and TRICKS MRV (to assess collaterals) at 3T. Two neuroradiologists blinded to cohort status scored IJV flattening and the severity of non-IJV collaterals by using a 4-point qualitative scale (normal = 0, mild = 1, moderate = 2, severe = 3). κ was used to assess reader agreement. Comparisons between groups were performed by using the Wilcoxon rank sum test. The Spearman rank correlation was used to assess the relationship between IJV flattening and collateral scores and, in patients with MS, EDSS scores. RESULTS: The 2 groups were matched for age and sex (MS, 45 ± 8 years, 79% female; healthy controls, 47 ± 10 years, 65% female). Reader agreement for IJV flattening and collateral severity was good (κ = 0.74) and moderate (κ = 0.58), respectively. While IJV flattening was seen in both patients with MS and healthy controls, scores for the patients with MS were significantly higher (P = .002). Despite a trend, there was no significant difference in collateral scores between groups (P = .063). There was a significant positive correlation between flattening and collateral scores (ρ = 0.32, P = .005) and EDSS and flattening scores (ρ = 0.45, P = .004) but not between EDSS and collateral scores (ρ = 0.01, P = .97). CONCLUSIONS: These results indicate that patients with MS have greater IJV flattening and a trend toward more non-IJV collaterals than healthy subjects. The role that this finding plays in the pathogenesis or progression of MS, if any, requires further study.


Subject(s)
Collateral Circulation , Magnetic Resonance Angiography , Multiple Sclerosis/pathology , Neck/blood supply , Veins/pathology , Female , Humans , Jugular Veins/pathology , Male , Middle Aged
6.
AJNR Am J Neuroradiol ; 32(8): 1482-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21757521

ABSTRACT

BACKGROUND AND PURPOSE: MRV has been proposed as a possible screening method to identify chronic cerebrospinal venous insufficiency, which may play a role in MS. We report our initial experience comparing MRV and CV in MS patients to evaluate venous stenosis and collateral venous drainage. MATERIALS AND METHODS: Time-of-flight and time-resolved imaging of contrast kinetics MRV and CV were performed in 39 MS patients. The presence and severity of both IJ vein caliber changes and non-IJ collaterals were graded by using a 4-point scale by 2 radiologists in an independent and blinded manner. RESULTS: Both studies frequently showed venous abnormalities, most commonly IJ flattening at the C1 level and in the lower neck. There was moderate-to-good agreement between the modalities (κ = 0.55; 95% CI, 0.45%-0.65%). For collaterals, agreement was only fair (κ = 0.30; 95% CI, 0.09%-0.50%). The prevalence of IJ segments graded mild or worse on CV was 54%. If CV was considered a standard, the sensitivity and specificity of MRV was 0.79 (0.71-0.86) and 0.76 (0.67-0.83), respectively. Degree of stenosis was related to the severity of collaterals for CV but not for MRV. CONCLUSIONS: IJ caliber changes were seen in characteristic locations on both MRV and CV in MS patients. Agreement between modalities was higher for stenosis than for collaterals. If CV is considered a standard, MRV performance is good but may require additional improvement before MRV can be used for screening.


Subject(s)
Magnetic Resonance Imaging , Multiple Sclerosis/diagnostic imaging , Phlebography/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Neck , Young Adult
7.
J Ind Microbiol Biotechnol ; 37(7): 701-6, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20373126

ABSTRACT

Glycogen, a major reservoir of energy in Saccharomyces cerevisiae, is found to be present as soluble and membrane-bound insoluble pools. Yeast cells can store excess glycogen when grown in media with higher concentration of sugar or when subjected to nutritional stress conditions. Saccharomyces cerevisiae NCIM-3300 was grown in media having ethanol concentrations up to 12% (v/v). The effects of externally added ethanol on glycogen and other carbohydrate content of yeast were studied by using alkali digestion process. Fermentative activities of cells grown in the presence of various ethanol concentrations (2-8% v/v) exhibited increase in values of glycogen and other carbohydrate, whereas cells grown with higher concentrations of ethanol (10-12% v/v) exhibited depletion in glycogen and carbohydrate content along with decrease in cell weight. Such inhibitory effect of ethanol was also exhibited in terms of reduction in total cell count of yeast grown in media with 2-16% (v/v) ethanol and 8% (w/v) sugar. These data suggest that, as the plasma membrane is a prime target for ethanol action, membrane-bound insoluble glycogen might play a protective role in combating ethanol stress. Elevated level of cell-surface alpha-glucans in yeast grown with ethanol, as measured by using amyloglucosidase treatment, confirms the correlation between ethanol and glycogen.


Subject(s)
Carbohydrate Metabolism , Ethanol/metabolism , Glycogen/metabolism , Saccharomyces cerevisiae/metabolism , Cell Membrane/metabolism , Saccharomyces cerevisiae/growth & development
8.
Pediatr Cardiol ; 28(4): 305-8, 2007.
Article in English | MEDLINE | ID: mdl-17530323

ABSTRACT

Endovascular stent grafts have become an established therapy in adults for descending thoracic aortic disease. We report a case of a 13-year-old boy with a hemodynamically significant traumatic aortopulmonary window following angioplasty of pulmonary artery stent. Endovascular stent graft implantation into the ascending aorta was performed to seal off the communication, with dramatic hemodynamic improvement.


Subject(s)
Aortic Diseases/surgery , Blood Vessel Prosthesis Implantation , Pulmonary Artery , Stents , Vascular Fistula/surgery , Adolescent , Aortic Diseases/etiology , Aortic Diseases/physiopathology , Cardiac Surgical Procedures , Dilatation , Echocardiography, Transesophageal , Heart Failure/etiology , Humans , Male , Prosthesis Failure , Retreatment , Stents/adverse effects , Transposition of Great Vessels/surgery , Vascular Fistula/etiology , Vascular Fistula/physiopathology
9.
Cardiovasc Intervent Radiol ; 27(2): 158-63, 2004.
Article in English | MEDLINE | ID: mdl-15259812

ABSTRACT

We attempted to evaluate the in vitro behavior and performance of balloon-expandable endoprosthetic metallic stents subjected to over-expansion (OE). Seventy-two balloon-expandable endoprosthetic stents, representing 22 models from six manufacturers, were overexpanded in vitro. Stents were initially expanded to their maximum manufacturer- recommended diameter and then over-expanded incrementally to their endpoints. Endpoints for OE were either stent disarticulation or an inability to undergo further expansion despite balloon insufflation to maximum burst pressure. Measurements of stent dimensions were recorded at each overexpanded diameter and comparisons were made to manufacturer's specifications. A total of 288 balloon-driven expansions were performed on 72 stents. Sixteen stents were expanded to large diameters (> or = 16 mm), 20 stents underwent OE of 50% or greater. One model tended to disarticulate after OE greater than 50%. There were five models that had a tendency to disarticulate after minimal OE. Five models were resistant to OE (25% or less OE) but did not disarticulate. Nearly all stents showed some degree of foreshortening with OE, while 36 stents underwent foreshortening of 30% or more. Models that are not recommended for OE include Intrastent, Intrastent DoubleStrut, NIR Royale and Omniflex. Good candidates for OE include Intrastent DoubleStrut LD, Palmaz large, Medtronic Extra Support Biliary Plus and Medtronic Flexible Biliary. Palmaz XL remains the only model available for expansion from 20 to 28 mm in diameter. For the remaining stents, OE is possible, however, caution should be used.


Subject(s)
Catheterization/instrumentation , Stents/standards , Equipment Failure , Equipment Failure Analysis , Equipment Safety/standards , In Vitro Techniques
11.
Tissue Eng ; 8(3): 395-407, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12167226

ABSTRACT

The objective of this work was to develop a platform to evaluate and deliver putative therapeutic agents for in-stent restenosis. Arterial stenting is applied in more than 60% of balloon angioplasties for treating cardiovascular disease. However, stented arteries encounter accelerated rates of restenosis. No prior platform has allowed evaluation or local management of in-stent restenosis without perturbing the very system being examined. A stainless steel, balloon-expandable stent was modified to serve as an ablumenal drug delivery platform. Several combinations of bioerodible polymer microspheres and gels were evaluated for channel retention under in vitro flow and in vivo conditions. A stent-anchored hybrid system prevented material embolization under all conditions. Unlike prior platforms, these stents do not alter local inflammation or in-stent plaque formation relative to conventional Palmaz-Schatz stents after in vivo deployment. The system also proved sensitive enough to detect plaque reduction with an antirestenotic agent. We conclude that a platform to evaluate and deliver therapeutic agents for in-stent restenosis has been achieved.


Subject(s)
Coronary Restenosis/prevention & control , Stents , Animals , Coronary Restenosis/etiology , Coronary Restenosis/pathology , Drug Delivery Systems , Equipment Design , Gels , Humans , Inflammation/etiology , Inflammation/pathology , Inflammation/prevention & control , Male , Microspheres , Rabbits , Stents/adverse effects , Tissue Engineering
12.
Mol Ther ; 4(6): 586-92, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11735343

ABSTRACT

A potential consequence of systemic administration of viral vectors is the inadvertent introduction of foreign DNA into recipient germ cells. To evaluate the safety of in vivo recombinant adeno-associated virus (rAAV) mediated gene transfer approaches for hemophilia B, we explored the risk of germline transmission of vector sequences following intramuscular (IM) injection of rAAV in four species of male animals (mouse, rat, rabbit and dog). In vector biodistribution studies in mice and rats, there is a dose-dependent increase in the likelihood that vector sequences can be detected in gonadal DNA using a sensitive PCR technique. However, in dogs DNA extracted from semen is negative for vector sequences. To address this discrepancy, studies were done in rabbits, and both semen and testicular DNAs were analyzed for the presence of vector sequences. These studies showed that no AAV vector sequences were detected in DNA extracted from rabbit semen samples collected at time points ranging from 7 to 90 days following IM injection of 1 x 10(13) vector genomes rAAV (vg) per kg. In contrast, DNA extracted from gonadal tissue was positive for vector sequences, but the positive signals diminished in number and strength with time. By FISH analysis, AAV signals were localized to the testis basement membrane and the interstitial space; no intracellular signal was observed. We observed similar findings following hepatic artery administration of rAAV in rats and dogs, suggesting that our findings are independent of the route of administration of vector. Attempts to transduce isolated murine spermatogonia directly with AAV-lacZ were unsuccessful. In clinical studies human subjects injected IM with an AAV vector at doses up to 2 x 10(12) vg/kg have shown no evidence of vector sequences in semen. Together, these studies suggest that rAAV introduced into skeletal muscle or the hepatic artery does not transduce male germ cells efficiently. We conclude that the risk of inadvertent germline transmission of vector sequences following IM or hepatic artery injection of AAV-2 vectors is extremely low.


Subject(s)
Dependovirus/genetics , Hemophilia B/genetics , Muscle, Skeletal/metabolism , Spermatozoa/virology , Animals , DNA Primers/chemistry , DNA, Viral/analysis , Dogs , Factor IX/genetics , Gene Transfer Techniques , Genetic Therapy/methods , Genetic Vectors , Hemophilia B/pathology , Hemophilia B/therapy , In Situ Hybridization, Fluorescence , Injections, Intramuscular , Male , Mice , Polymerase Chain Reaction , Rabbits , Rats , Recombinant Proteins/genetics , Semen/virology , Testis/virology
13.
J Vasc Interv Radiol ; 12(10): 1203-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11585887

ABSTRACT

PURPOSE: Alpha-1-antitrypsin (AAT) is the major circulating elastase inhibitor. Deficiency of elastase inhibition leads to emphysema and vascular abnormalities including accelerated neointima. Because recent evidence suggests that tissue AAT levels determine inhibitory function, the authors hypothesize that local tissue-based expression of AAT limits elastase activity sufficiently to guide arterial response to injury. MATERIALS AND METHODS: Rabbit common femoral arteries were injured by mechanical overdilation and treated with buffer, viral control, or an adenovirus expressing AAT (Ad/AAT). After 3 and 28 days, intima-to-media (I/M) ratios were evaluated. Additionally, early changes in elastase inhibition potential (3 d), extracellular elastin and collagen content (3 d), and local macrophage and neutrophil infiltration (7 d) were determined. RESULTS: Ad/AAT significantly decreased neointima formation after mechanical dilation injury after 28 days: buffer controls exhibited mean I/M ratios of 0.76 +/- 0.06, whereas viral controls reached 0.77 +/- 0.09; in contrast, Ad/AAT reduced I/M ratios to 0.44 +/- 0.06. Both early elastin and collagen content were preserved in the Ad/AAT group relative to controls. The Ad/AAT group also reversed the local inflammation that characterized viral controls. CONCLUSIONS: This strategy demonstrates that local increases in elastase inhibition potential promote a neointima-resistant small-caliber artery, which may offer new promise in management of patients undergoing angioplasty.


Subject(s)
Extracellular Matrix/metabolism , Pancreatic Elastase/antagonists & inhibitors , Tunica Intima/drug effects , alpha 1-Antitrypsin/genetics , Angioplasty , Animals , Femoral Artery/injuries , Femoral Artery/metabolism , Femoral Artery/pathology , Gene Transfer Techniques , Male , Pancreatic Elastase/metabolism , Rabbits , Tunica Intima/physiopathology , alpha 1-Antitrypsin/pharmacology , alpha 1-Antitrypsin/therapeutic use
14.
Eur J Radiol ; 39(1): 42-9, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11439230

ABSTRACT

The traditional standard therapy for descending thoracic aortic aneurysm (TAA) is open operative repair with graft replacement of the diseased aortic segment. Despite important advances in surgical techniques, anesthetic management, and post-operative care over the last 30 years, the mortality and morbidity of surgery remains considerable, especially in patients at high risk for thoracotomy because of coexisting severe cardiopulmonary abnormalities or other medical diseases. The advent of endovascular stent-graft technology provides an alternative to open surgery for selected patients with TAA. The initial experience suggests that stent-graft therapy potentially may reduce the operative risk, hospital stay and procedural expenses of TAA repair. These potential benefits are especially attractive for patients at high risk for open TAA repair. Current results of endovascular TAA therapy document operative mortalities of between 0 and 4%, aneurysm thrombosis in 90 and 100% of cases, and paraplegia as a complication in 0 and 1.6% of patients. The early success of stent-graft repair of TAA has fostered the application of these devices for the management of a wide variety of thoracic aortic pathologies, including acute and chronic dissection, intramural hematoma, penetrating ulcer, traumatic injuries, and other diseases. The results of prospective controlled trials that compare the outcomes of stent-graft therapy with those of surgical treatment in patients with specific types of aortic disease are anxiously awaited before recommendations regarding the general use of these new devices can be made with confidence.


Subject(s)
Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis , Minimally Invasive Surgical Procedures , Stents , Aortic Aneurysm, Thoracic/complications , Humans
15.
J Vasc Interv Radiol ; 12(7): 879-81, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11435545

ABSTRACT

The authors attempted to describe the clinical manifestations of portal-systemic myelopathy (PSM) after transjugular intrahepatic portosystemic shunt (TIPS) creation. PSM was developed in four of 212 (1.89%) patients who underwent TIPS procedures in our hospital. Three men and one woman, ranging in age from 41 to 56 years, with a history of posthepatitis cirrhosis and recurrent bleeding from gastroesophageal varices had intrahepatic shunts created with 10-mm-diameter Wallstents. Shunt patency was confirmed by color Doppler ultrasonography (US) in each patient after TIPS creation. Progressive spastic paraparesis involving the lower extremities occurred between 5 weeks and 5 months after TIPS creation in the four patients. Neurologic examination showed evidence of spasticity in all cases, with ankle clonus, extensor plantar responses, and lower extremity hyperreflexia. All sensory modalities remained intact. Cytologic examination of cerebrospinal fluid from each patient was normal. There was no evidence of spinal cord compression on the imaging studies. PSM is a rare syndrome that includes spastic paraparesis with intact sensation. Initially noted in patients who have undergone surgical placement of a portacaval shunt, it also may occur after TIPS creation.


Subject(s)
Portacaval Shunt, Surgical/adverse effects , Spinal Cord Diseases/etiology , Adult , Esophageal and Gastric Varices/surgery , Female , Humans , Liver Cirrhosis/surgery , Male , Middle Aged , Paraparesis, Spastic , Postoperative Complications
16.
Hepatogastroenterology ; 48(39): 851-3, 2001.
Article in English | MEDLINE | ID: mdl-11462940

ABSTRACT

Pulmonary metastasis is frequently seen in patients with advanced hepatocellular carcinoma. However, information is limited concerning life-threatening complications and effective treatment of pulmonary metastasis because of the poor prognosis of patients with advanced hepatocellular carcinoma. Recent remarkable progress in detection and treatment of hepatocellular carcinoma has improved prognosis, making management of pulmonary metastasis an important clinical issue. We describe a 68-year-old man with pulmonary metastasis of hepatocellular carcinoma and sudden onset of hemoptysis from bronchial invasion. Transcatheter embolization was performed successfully via the bronchial artery with disappearance of bloody sputum. Peribronchial pulmonary metastasis of hepatocellular carcinoma can cause life-threatening hemoptysis. Transcatheter arterial embolization may be one of therapeutics for hemoptysis from invasive pulmonary metastasis of hepatocellular carcinoma.


Subject(s)
Carcinoma, Hepatocellular/secondary , Embolization, Therapeutic , Hemoptysis/therapy , Liver Neoplasms/therapy , Lung Neoplasms/secondary , Aged , Bronchial Arteries/diagnostic imaging , Carcinoma, Hepatocellular/therapy , Hemoptysis/etiology , Humans , Lung Neoplasms/therapy , Male , Neoplasm Invasiveness , Radiography , Recurrence
17.
J Vasc Interv Radiol ; 12(6): 731-7, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11389225

ABSTRACT

PURPOSE: To increase the dose of drug delivered to a tumor while maintaining tolerable systemic side effects, an interventional technique of isolated lower extremity infusion was investigated. MATERIALS AND METHODS: Experiments were performed in eight dogs. Four dogs were treated by a combination of intraarterial (IA) femoral cisplatin infusion at a dose of 2.0 mg/kg with drug removal from the ipsilateral extremity venous blood by a dialyzer. The other four dogs comprised the control group. In these animals, left femoral arterial IA cisplatin infusion was performed without dialysis. Leukocyte and platelet counts, blood urea nitrogen (BUN) levels, and serum creatinine levels were recorded before and after the treatment. Subsequently, two human patients with inoperable osteosarcoma were treated with the isolated infusion. RESULTS: In the experiments, 85%-90% of the free platinum that entered the dialyzer was removed. The peak systemic plasma cisplatin concentrations in animals undergoing dialysis were reduced by 81.25% compared to those in animals undergoing femoral IA infusion without hemodialysis. There were no significant changes in the hematologic profiles or BUN and serum creatinine levels in the experimental animals. However, in the control group, all dogs developed myelosuppression and severe renal toxicity after IA infusion of the same dose of cisplatin. Clinically, immediate relief of symptoms related to the primary tumor was achieved in both human patients after the combination of isolated IA infusion and embolotherapy. CONCLUSION: Single-pass hemodialysis removed a significant amount of cisplatin after regional IA infusion, reduced systemic toxicity, and permitted survival of the experimental animals. In two patients with osteosarcoma, percutaneous isolated lower extremity chemotherapeutic infusion therapy and embolotherapy were performed safely with partial responses.


Subject(s)
Bone Neoplasms/drug therapy , Infusions, Intra-Arterial , Leg/pathology , Osteosarcoma/drug therapy , Adolescent , Adult , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Blood Urea Nitrogen , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cisplatin/blood , Creatinine/blood , Dialysis , Disease Models, Animal , Dogs , Female , Follow-Up Studies , Humans , Leg/blood supply , Leukocyte Count , Leukopenia/etiology , Male , Models, Animal , Platelet Count , Thrombocytopenia/etiology
18.
J Am Coll Cardiol ; 37(7): 1975-80, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11401141

ABSTRACT

OBJECTIVES: We studied enhancement of local gene delivery to the arterial wall by using an endovascular catheter ultrasound (US). BACKGROUND: Ultrasound exposure is standard for enhancement of in vitro gene delivery. We postulate that in vivo endovascular applications can be safely developed. METHODS: We used a rabbit model of arterial mechanical overdilation injury. After arterial overdilation, US catheters were introduced in bilateral rabbit femoral arteries and perfused with plasmidor adenovirus-expressing blue fluorescent protein (BFP) or phosphate buffered saline. One side received endovascular US (2 MHz, 50 W/cm2, 16 min), and the contralateral artery did not. RESULTS: Relative to controls, US exposure enhanced BFP expression measured via fluorescence 12-fold for plasmid (1,502.1+/-927.3 vs. 18,053.9+/-11,612 microm2, p < 0.05) and 19-fold for adenovirus (877.1+/-577.7 vs. 17,213.15+/-3,892 microm2, p < 0.05) while increasing cell death for the adenovirus group only (26+/-5.78% vs. 13+/-2.55%, p < 0.012). CONCLUSIONS: Endovascular US enhanced vascular gene delivery and increased the efficiency of nonviral platforms to levels previously attained only by adenoviral strategies.


Subject(s)
Angioscopy , Arteries , Genetic Therapy/methods , Ultrasonography, Interventional , Animals , Male , Rabbits
19.
J Am Coll Cardiol ; 37(8): 2126-30, 2001 Jun 15.
Article in English | MEDLINE | ID: mdl-11419898

ABSTRACT

OBJECTIVES: This study was designed to evaluate the impact of recombinant human vascular endothelial growth factor165 (rhVEGF) on atherosclerotic plaque progression. BACKGROUND: Therapeutic angiogenesis represents a promising treatment for ischemic diseases. However, angiogenesis may impact atherosclerosis. METHODS: Albumin or rhVEGF was administered by a single intramuscular injection (2 microg/kg body weight) to New Zealand White rabbits fed with a 0.25% cholesterol diet beginning three weeks before therapy. Subsets of rabbits from each group underwent perfusion-fixation and harvesting of the thoracic aorta for morphometric and immunohistochemical analyses at 7 or 21 days. RESULTS: The mean plaque area was 15.75+/-2.28% and 22.00+/-3.24% with VEGF and 0.67+/-0.22% and 1.17+/-0.34% with albumin at 7 and 21 days, respectively. The plaque circumference was 13.00+/-2.58% and 23.75+/-2.86% with VEGF and 2.50+/-0.65% and 6.25+/-1.88% with albumin at 7 and 21 days, respectively. The maximal plaque thickness was 0.11+/-0.002 and 0.15+/-0.007 mm with VEGF and 0.04+/-0.009 and 0.07+/-0.003 mm with albumin at 7 and 21 days, respectively. The endothelial density (reported as percent total plaque area) was 31.75+/-4.42% and 63.00+/-8.45% with VEGF and 7.75+/-1.65% and 12.75+/-1.93% with albumin at 7 and 21 days, respectively. The macrophage density was 4.5+/-0.86 and 19.25+/-1.54 with VEGF and 4.26+/-0.75 and 6.00+/-1.08 with albumin at 7 and 21 days, respectively. CONCLUSIONS: Recombinant human VEGF increases the rate and degree of atherosclerotic plaque formation in the thoracic aorta in a cholesterol-fed rabbit model.


Subject(s)
Aortic Diseases/pathology , Arteriosclerosis/pathology , Endothelial Growth Factors/adverse effects , Lymphokines/adverse effects , Protein Isoforms/adverse effects , Animals , Aorta, Thoracic , Arteriosclerosis/physiopathology , Disease Progression , Immunohistochemistry , Macrophages , Neovascularization, Physiologic , Rabbits , Recombinant Proteins , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
20.
J Vasc Interv Radiol ; 12(3): 347-50, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11287513

ABSTRACT

PURPOSE: Insulin-like growth factor-1 (IGF-1) is a potent chemoattractant to vascular smooth muscle cells (SMCs). The authors hypothesize that perivascular release of IGF-1 in vivo can direct migration of SMCs away from the lumen and reduce neointima formation in a rabbit model of arterial balloon injury. MATERIALS AND METHODS: Balloon angioplasty of the common femoral arteries was performed in adult male New Zealand White rabbits (n = 8 per treatment group) and controlled release microspheres delivering either IGF-1 or blank control treatment were implanted perivascularly at the angioplasty site prior to surgical closure. At 7 days, five arteries per group were harvested and cross-sections were subjected to anti-PCNA (proliferating cell nuclear antigen) immunostaining to determine the number and distribution of proliferating SMCs. At 28 days, the remaining three arteries per group were harvested and sections were evaluated for intima-to-media (I/M) ratios by means of VVG-Masson staining. One-way analysis of variance with Fisher protected least significant difference post hoc testing was used to determine statistical significance at P < .05. RESULTS: At 7 days, PCNA(+) medial SMCs assumed a significantly more peripheral (ie, further from lumen) distribution in the vessel wall with use of perivascular IGF-1 than with use of blank treatment (P < .05). Overall SMC proliferation was not significantly different, thus the change in distribution was likely due to directionally altered SMC migration. At 28 days, perivascular IGF-1 significantly decreased I/M ratios by 44% relative to control treatment (P < .05). CONCLUSIONS: Perivascular release of IGF-1 can directionally guide SMC migration away from the lumen and reduce neointima in the balloon-injured artery. This novel strategy might have implications in the development of antirestenosis therapies.


Subject(s)
Angioplasty, Balloon , Insulin-Like Growth Factor I/pharmacology , Muscle, Smooth, Vascular/drug effects , Tunica Intima/growth & development , Animals , Cell Division , Cell Movement/drug effects , Femoral Artery/injuries , Insulin-Like Growth Factor I/administration & dosage , Male , Microspheres , Muscle, Smooth, Vascular/physiology , Rabbits , Time Factors
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