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1.
Dalton Trans ; 53(11): 4952-4961, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38275106

ABSTRACT

Transition metal complexes exhibiting selective toxicity towards a broad range of cancer types are highly desirable as potential anticancer agents. Herein, we report the synthesis, characterization, and cytotoxicity studies of six new mixed-ligand cobalt(III) complexes of general formula [Co(B)2(L)](ClO4)2 (1-6), where B is a N,N-donor phenanthroline base, namely, 1,10-phenanthroline (phen in 1, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 3, 4), and dipyrido[3,2-a:2',3'-c]phenazine (dppz in 5, 6), and L is the monoanion of 8-hydroxyquinoline (HQ in 1, 3, 5) and 5-chloro-7-iodo-8-hydroxyquinoline (CQ in 2, 4, 6). The X-ray single crystal structures of complexes 1 and 2 as PF6- salts revealed a distorted octahedral CoN5O coordination environment. Complexes demonstrated good stability in an aqueous buffer medium and in the presence of ascorbic acid as a reductant. Cytotoxicity studies using a panel of nine cancer cell lines showed that complex 6, with the dppz and CQ ligands, was significantly toxic against most cancer cell types, yielding IC50 values in the range of 2 to 14 µM. Complexes 1, 3, and 5, containing the HQ ligand, displayed lower toxicity compared to their CQ counterparts. The phenanthroline complexes demonstrated marginal toxicity towards the tested cell lines, while the dpq complexes exhibited moderate toxicity. Interestingly, all complexes demonstrated negligible toxicity towards normal HEK-293 kidney cells (IC50 > 100 µM). The observed cytotoxicity of the complexes correlated well with their lipophilicities (dppz > dpq > phen). The cytotoxicity of complex 6 was comparable to that of the clinical drug cisplatin under similar conditions. Notably, neither the HQ nor the CQ ligands alone demonstrated noticeable toxicity against any of the tested cell lines. The Annexin-V-FITC and DCFDA assays revealed that the cell death mechanism induced by the complexes involved apoptosis, which could be attributed to the metal-assisted generation of reactive oxygen species. Overall, the dppz complex 6, with its remarkable cytotoxicity against a broad range of cancer cells and negligible toxicity toward normal cells, holds significant potential for cancer chemotherapeutic applications.


Subject(s)
Coordination Complexes , Neoplasms , Humans , Phenanthrolines/chemistry , Oxyquinoline/pharmacology , Ligands , Cobalt , HEK293 Cells , Coordination Complexes/chemistry , Copper/chemistry
2.
Indian J Endocrinol Metab ; 24(4): 360-365, 2020.
Article in English | MEDLINE | ID: mdl-33088761

ABSTRACT

BACKGROUND: Disorders of sex development (DSD) are a wide range of relatively rare conditions having diverse pathophysiology. Identification of an underlying cause can help in treating any coexisting hormone deficiencies and can help with anticipating any other immediate or long-term health concerns. OBJECTIVE: To study the clinical and biochemical profile of patients with 46 XY DSD along with androgen receptor (AR) gene mutation status in selected group of patients. METHODS: A cross-sectional study was conducted after enrolling the eligible DSD patients. Thorough elicitation of history and detailed clinical examination was done. Assays for luteinizing hormone, follicle-stimulating hormone, testosterone, dihydrotestosterone, androstenedione, AMH & Inhibin B (where indicated), and human chorionic gonadotropin stimulation were done as per protocol. RESULTS: In total, 48 patients were included in the study. Ambiguous genitalia (58.3%) followed by hypospadias (33.3%) were common presentation. Androgen biosynthetic defect were the most commonly encountered diagnosis followed by androgen insensitivity syndrome (AIS). Swyer syndrome was diagnosed in 4.2% of cases; partial gonadal dysgenesis, ovotesticular DSD, and vanishing testis syndrome contributed to 2% of cases each. Eight cases (16.7%) who presented with isolated proximal and midshaft hypospadias for whom no diagnosis was found were categorized in the "etiology unclear" group. AR gene mutation analysis designed against specific exons did not yield any results. CONCLUSION: 46 XY DSD is a heterogeneous group of patients with a varying age of presentation and a diverse clinical profile. Most patients are reared as males and maintained the same gender identity except in isolated cases. Diagnosis of AIS remains a clinical challenge as a definite hormonal criterion does not exist and genetic mutations in AR gene may be negative. Flanking region sequencing, whole genome sequencing, and promoter region sequencing may reveal pathogenic variants. Variations in other genes regulating AR pathway may also be candidates to be studied.

3.
Dalton Trans ; 46(2): 396-409, 2017 Jan 03.
Article in English | MEDLINE | ID: mdl-27929173

ABSTRACT

Metal complexes with organelle specificity and potent but selective cytotoxicity are highly desirable. In this work, we report the synthesis, characterization and cytotoxicity of six novel copper(ii) complexes of the formula [Cu(R-tpy)(N-O)]NO3 (1-6), where R-tpy is 4'-phenyl-2,2':6',2''-terpyridine (Ph-tpy; 1-3) or 4'-ferrocenyl-2,2':6',2''-terpyridine (Fc-tpy; 4-6), N-O is the anion of 8-hydroxyquinoline (HQ in 1, 4), 5-chloro-7-iodo-8-hydroxyquinoline (CQ in 2, 5) or 5-nitro-8-hydroxyquinoline (NQ in 3, 6). The complex [Cu(Fc-tpy)2](ClO4)2 (7) has also been prepared as a control and structurally characterized. The optimized geometries and the frontier orbitals of the complexes have been obtained from DFT calculations. The ferrocenyl appended complexes having the anticancer active CQ (in 5) and NQ (in 6) ligands show remarkable cytotoxicity, giving the respective IC50 values of 0.75 µM and 0.52 µM in HeLa and 1.3 µM and 2.6 µM in MCF-7 cancer cells. The phenyl appended complexes 2 and 3 are less active than their ferrocenyl analogues in both the cells while the complexes of HQ (in 1, 4) are the least active. Interestingly, complexes 4-6 are significantly less toxic to MCF-10A normal cells. The DCFDA, annexin-V-FITC and propidium iodide nuclear staining assays reveal an apoptotic mechanism of cell death which is attributable to the metal-assisted generation of reactive oxygen species. Imaging experiments on HeLa cells reveals that complex 5 accumulates primarily inside the mitochondria. The complexes bind to calf thymus DNA with moderate affinity giving Kb values in the range of 6.3 × 104-7.4 × 104 M-1 and to HSA protein with significant affinity giving KHSA values in the range of 8.6 × 104-1.3 × 105 M-1. Their affinity for DNA suggests that mitochondrial DNA could be the target while their affinity for HSA suggests that they could be transported by HSA in the blood. This work is the first report to show that the ferrocenyl appended copper(ii) complexes of hydroxyquinoline ligands are remarkably cytotoxic to cancer cells but significantly less toxic to normal cells.


Subject(s)
Copper/chemistry , DNA/metabolism , Ferrous Compounds/chemistry , Metallocenes/chemistry , Mitochondria/metabolism , Organometallic Compounds/metabolism , Organometallic Compounds/pharmacology , Serum Albumin, Human/metabolism , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Cattle , Humans , MCF-7 Cells , Mitochondria/drug effects , Models, Molecular , Molecular Conformation , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Oxyquinoline/chemistry , Protein Binding , Pyridines/chemistry , Reactive Oxygen Species/metabolism , Solubility
4.
Indian J Med Res ; 143(3): 357-61, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27241650

ABSTRACT

BACKGROUND & OBJECTIVES: Vancomycin-resistant enterococci (VRE) have become one of the most challenging nosocomial pathogens with the rapid spread of the multi-drug resistant strain with limited therapeutic options. It is a matter of concern due to its ability to transfer vancomycin resistant gene to other organisms. The present study was undertaken to determine the emergence of vancomycin-resistant enterococci and the vanA gene among the isolates in a tertiary care hospital of North-East India. METHODS: A total of 67 consecutive enterococcal isolates from different clinical samples were collected and identified by using the standard methods. Antibiogram was done by disk diffusion method and VRE was screened by the disk diffusion and vancomycin supplement agar dilution method. The minimum inhibitory concentration (MIC) value for vancomycin was determined by E-test. The VRE isolates were analyzed by PCR for vanA gene. RESULTS: A total of 54 (81%) Enterococcus faecalis and 13 (19%) E. faecium were detected among the clinical isolates and 16 (24%) were VRE. The VRE isolates were multidrug resistant and linezolid resistance was also found to be in three. MIC range to vancomycin was 16-32 µg/ml among the VRE. The vanA gene was found in nine of 16 VRE isolates. INTERPRETATION & CONCLUSIONS: Emergence of VRE and presence of vanA in a tertiary care hospital setting in North-East India indicate toward a need for implementing infection control policies and active surveillance.


Subject(s)
Bacterial Proteins/genetics , Carbon-Oxygen Ligases/genetics , Cross Infection/epidemiology , Enterococcus faecalis/isolation & purification , Vancomycin-Resistant Enterococci/genetics , Bacterial Proteins/blood , Bacterial Proteins/urine , Carbon-Oxygen Ligases/blood , Carbon-Oxygen Ligases/urine , Cross Infection/drug therapy , Cross Infection/genetics , Cross Infection/microbiology , Drug Resistance, Multiple/genetics , Enterococcus faecalis/drug effects , Enterococcus faecalis/pathogenicity , Humans , India , Microbial Sensitivity Tests , Tertiary Care Centers , Vancomycin/therapeutic use , Vancomycin-Resistant Enterococci/isolation & purification , Vancomycin-Resistant Enterococci/pathogenicity
5.
Indian J Exp Biol ; 54(2): 108-14, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26934778

ABSTRACT

Extended-spectrum ß-lactamases (ESBLs) are rapidly evolving group of ß-lactamase enzymes produced by the Gram negative bacteria. In this study, we determined the antimicrobial sensitivity pattern of Escherichia coli isolates and prevalence of TEM, SHV and CTX-M genes in ESBL positive E. coli isolated from the patients admitted to a tertiary care hospital in North-East India. A total of 85 multidrug-resistant isolates of E. coli obtained from clinical samples; urine (n = 80), sputum (n = 3), body fluid (n = 1), vaginal discharge (n = 1) were screened for resistance to third generation cephalosporins. ESBL production in resistant isolates was determined by double disk synergy test (DDST) and phenotypic confirmatory test (PCT). ESBL positive isolates were subjected to PCR for detection of TEM, SHV and CTX-M genes. Imipenem was found to be most effective against E. coli (susceptible isolates 96.47%) while ciprofloxacin was the least effective antibiotic (resistant isolates 60%). Among 33 ESBL positive isolates confirmed via PCT, preponderance in female population (60.6%) was noted. The most prevalent gene was bla(SHV) (63.04%) followed by bla(TEM) and bla(CTX-M) (60.86 and 54.34%, respectively) in ESBL positive E. coli. Most of the extensively used antibiotics, appear to be ineffective against the ever-mutating bacteria. This resistance urges cautious antimicrobial management on priority. Further, it helps in effectively designing the chemotherapeutic regimen for patients of a particular geographic area.


Subject(s)
Escherichia coli/enzymology , beta-Lactamases/analysis , Adult , Drug Resistance, Bacterial , Escherichia coli/drug effects , Female , Humans , Male , Middle Aged , Tertiary Healthcare , beta-Lactamases/genetics
6.
Appl Biochem Biotechnol ; 172(6): 3026-41, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24482282

ABSTRACT

In the past few decades, genome-based approaches have contributed significantly to vaccine development. Our aim was to identify the most conserved and immunogenic antigens of Streptococcus pneumoniae, which can be potential vaccine candidates in the future. BLASTn was done to identify the most conserved antigens. PSORTb 3.0.2 was run to predict the subcellular localization of the proteins. B cell epitope prediction was done for the immunogenicity testing. Finally, BLASTp was done for verifying the extent of similarity to human proteome to exclude the possibility of autoimmunity. Proteins failing to comply with the set parameters were filtered at each step. Based on the above criteria, out of the initial 22 pneumococcal proteins selected for screening, pavB and pullulanase were the most promising candidate proteins.


Subject(s)
Antigens, Bacterial/chemistry , Bacterial Proteins/chemistry , Genome, Bacterial/immunology , Glycoside Hydrolases/chemistry , Streptococcus pneumoniae/genetics , Virulence Factors/chemistry , Amino Acid Sequence , Antigens, Bacterial/genetics , Antigens, Bacterial/immunology , B-Lymphocytes/immunology , B-Lymphocytes/microbiology , Bacterial Proteins/genetics , Bacterial Proteins/immunology , Computational Biology , Conserved Sequence , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/genetics , Epitopes, B-Lymphocyte/immunology , Glycoside Hydrolases/genetics , Glycoside Hydrolases/immunology , Humans , Molecular Sequence Data , Pneumococcal Infections/immunology , Pneumococcal Infections/microbiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/genetics , Pneumococcal Vaccines/immunology , Proteome/genetics , Proteome/immunology , Streptococcus pneumoniae/immunology , Virulence Factors/genetics , Virulence Factors/immunology
7.
Indian J Med Res ; 136(5): 855-61, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23287135

ABSTRACT

BACKGROUND & OBJECTIVES: Haemophilus influenzae is an important cause of mortality and morbidity among young children in developing countries. Increasing incidence of antibiotic resistance especially production of extended spectrum beta lactamase (ESBL) has made treatment and management of H. influenzae infection more difficult. Nasopharyngeal H. influenzae isolates are excellent surrogate for determination of antibiotic resistance prevalent among invasive H. influenzae isolates. In this study, we characterized nasopharyngeal H. influenzae isolates obtained from healthy school going children in Delhi. METHODS: Nasopharyngeal H. influenzae isolates were collected from healthy school going children and subjected to serotyping, fimbrial typing and antibiogram profiling. ESBL production was recorded using phenotypic as well as molecular methods. Multi locus sequence typing (MLST) of 13 representative nasopharyngeal H. influenzae isolates was performed as per guidelines. RESULTS: A significant proportion (26 of 80, 32.5%) of nasopharyngeal isolates of H. influenzae were identified as serotype b. Fimbrial gene (hifA) was detected in 23 (28.75%) isolates. Resistance against commonly prescribed antibiotics (Amp, Tet, Chloro, Septran, Cephalexin) were observed to be high among the nasopharyngeal commensal H. influenzae. Extended spectrum beta lactamase (ESBL) production was observed in a five (6.25%) isolates by both double disk diffusion and molecular typing. MLST identified several novel alleles as well as novel sequence types. INTERPRETATION & CONCLUSIONS: Our findings showed high resistance against common antibiotics and detection of ESBL in nasopharyngeal H. influenzae isolates collected from normal healthy school going children in Delhi. Detection of H. influenzae type b capsular gene and the presence of fimbrial gene (hif A) suggest virulence potential of these isolates. Discovery of novel alleles and presence of new sequence types (STs) among nasopharyngeal H. influenzae isolates may suggest wider genetic diversity.


Subject(s)
Haemophilus influenzae/isolation & purification , Nasopharynx/microbiology , Base Sequence , Carrier State , Child , DNA Primers , Haemophilus influenzae/genetics , Humans , India , Multilocus Sequence Typing , Polymerase Chain Reaction
8.
Radiol Med ; 113(3): 373-84, 2008 Apr.
Article in English, Italian | MEDLINE | ID: mdl-18493774

ABSTRACT

PURPOSE: This study was undertaken to evaluate the incidence of pulmonary embolism (PE) and other clinically relevant thoracic findings discovered on contrast-enhanced multidetector computed tomography (MDCT) examination in patients with a suspicion of acute PE. MATERIALS AND METHODS: We retrospectively reviewed 220 reports of 40-row MDCT exams in consecutive patients (101 men, 119 women; mean age 55 years+/-18) suspected for acute PE. Presenting symptoms and risk factors were recorded. Image quality and incidence of PE and other clinically relevant thoracic findings were evaluated. RESULTS: MDCT were diagnostic in 96.8% of patients. Nineteen patients (8.6%) were positive for PE. Signs and symptoms were present in 82.7% (182) and risk factors in 38.2% (84) of the population. Clinically relevant thoracic findings were detected in 45.9% (101) of the patients. Ten patients had PE and other thoracic findings. Half of the patients (110) had neither PE nor other clinically relevant thoracic findings. CONCLUSIONS: Chest MDCT, with an excellent overall image quality, provided an explanation for the clinical presentation in about 50% of emergency department patients studied and was useful in detecting PE and other thoracic diseases with symptoms mimicking PE. However, half of the exams were negative.


Subject(s)
Pulmonary Embolism/diagnostic imaging , Tomography, Spiral Computed/methods , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Incidence , Italy/epidemiology , Lung Diseases/diagnostic imaging , Male , Middle Aged , Predictive Value of Tests , Pulmonary Embolism/epidemiology , Radiographic Image Enhancement , Retrospective Studies , Sensitivity and Specificity
9.
J Vasc Interv Radiol ; 12(7): 807-12, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11435536

ABSTRACT

Transcatheter endovascular procedures are increasingly used to treat symptomatic peripheral atherosclerosis. This second part of a two-part review assesses the existing supportive evidence for the application of recently introduced transcatheter treatments for lesions that cause cerebrovascular ischemia and stroke. Studies were identified via MEDLINE (January 1993 through April 1999) and reference lists of identified articles. When multicenter prospective randomized trials or other high-quality studies were unavailable, studies with at least 50 patients per treated group and a minimum follow-up duration of 6 months were included. For each application, the authors assessed the quality of evidence (efficacy, safety, and, where available, cost-effectiveness) and made recommendations with appropriate caveats. Although recommendations based on proven efficacy and cost-effectiveness cannot be made in general, the use of transcatheter therapies can be supported in specific circumstances based on expected reduction in procedure-related morbidity and/or mortality. It is hoped that the identification of deficiencies in the literature will inform and inspire critically needed research in this area.


Subject(s)
Arteriosclerosis/therapy , Catheterization , Peripheral Vascular Diseases/therapy , Angioplasty, Balloon , Humans , Stents , Thrombolytic Therapy
10.
J Vasc Interv Radiol ; 12(6): 683-95, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11389219

ABSTRACT

Transcatheter endovascular procedures are increasingly used to treat symptomatic peripheral atherosclerosis. This two-part review identifies the existing evidence supportive of the application of transcatheter treatments for peripheral atherosclerotic lesions. The first part addresses the treatment of obstructive lesions that cause limb claudication and critical ischemia, renovascular hypertension and azotemia, and mesenteric ischemia. Studies were identified via a search of MEDLINE (January 1993 through April 1999) and reference lists of identified articles. When multicenter prospective randomized trials or other high-quality studies were unavailable, a preference was given to studies with at least 50 patients per treated group and a minimum mean follow-up duration of 6 months. Data presented in tables are proportionally weighted averages from included studies. For each application, the authors assessed the quality of evidence (QOE; efficacy, safety, and, where available, cost-effectiveness) and made recommendations with appropriate caveats. There is higher QOE supporting the more established treatments such as lower limb percutaneous transluminal angioplasty (PTA) with stent placement and thrombolysis. Treatments such as renal artery PTA and stent placement and mesenteric and brachiocephalic PTA are in wide use, but high QOE supporting general application is lacking. Blanket recommendations based on established efficacy and cost-effectiveness cannot be made. However, the use of transcatheter therapies can be supported in specific circumstances based on an expected reduction in procedure-related morbidity and/or mortality rates. It is hoped that the identification of deficiencies in the literature will inform and inspire critically needed research in this area.


Subject(s)
Arteriosclerosis/therapy , Catheterization, Peripheral , Angioplasty, Balloon, Coronary , Arteriosclerosis/drug therapy , Fibrinolytic Agents/therapeutic use , Humans , Hypertension, Renovascular/therapy , Kidney Failure, Chronic/therapy , Stents
11.
World J Surg ; 25(3): 312-7; discussion 317-8, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11343183

ABSTRACT

The aim of this paper is to summarize the current status of percutaneous methods for recanalizing peripheral arterial occlusions. Emphasis is placed on the role of peripheral intraarterial thrombolysis (PIAT) in the treatment of acute lower limb ischemia. Results of three prospective, randomized trials comparing PIAT with surgical revascularization are analyzed in the context of the existing, largely retrospective literature. The technique and recommendations for the application of PIAT are reviewed. Percutaneous aspiration thromboembolectomy, a technique that may be used alone or in conjunction with PIAT, is described in detail. We conclude with a brief description of various percutaneous mechanical thrombectomy devices, which may potentially see application in peripheral arterial occlusions.


Subject(s)
Arterial Occlusive Diseases/surgery , Embolectomy , Thrombectomy , Arterial Occlusive Diseases/drug therapy , Embolectomy/methods , Humans , Ischemia/surgery , Leg/blood supply , Thrombectomy/methods , Thrombolytic Therapy
12.
J Vasc Interv Radiol ; 11(1): 5-17, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10693708

ABSTRACT

Animal models have significantly advanced our understanding of the mechanisms of atherosclerosis and restenosis formation and the evaluation of therapeutic options. The current focus of research is on preventive strategies against restenosis and includes pharmacologic and biologic interventions directed primarily against smooth muscle cell proliferation, endovascular devices for recanalization and/or drug delivery, and an integrated approach using both devices and pharmacobiologic agents. Devices aimed at the percutaneous endoluminal exclusion of aortic aneurysms have also generated interest recently. The experience over many decades with animal models in vascular research has established that a single, ideal, naturally available model for atherosclerosis, restenosis, or for that matter aneurysm formation, does not exist. Presently, rabbits and pigs are favored for the former two areas of study, and dogs and sheep appear to provide suitable models for testing devices for endoluminal repair of aneurysms. The development of transgenic variants of currently available models may widen our options in the future. Nevertheless, an appreciation of the individual features of natural or stimulated disease in each species is of the utmost importance for the proper design and execution of relevant experiments.


Subject(s)
Arteriosclerosis , Disease Models, Animal , Stents , Animals , Animals, Genetically Modified , Aortic Aneurysm, Abdominal/etiology , Aortic Aneurysm, Abdominal/physiopathology , Aortic Aneurysm, Abdominal/therapy , Arteriosclerosis/etiology , Arteriosclerosis/physiopathology , Arteriosclerosis/therapy , Recurrence
14.
J Vasc Interv Radiol ; 10(8): 1083-91, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10496712

ABSTRACT

BACKGROUND: The intraarterial administration of thrombolytic agents is associated with clinical benefits in patients with acute peripheral arterial occlusion, and urokinase has been the agent that has become the standard of care in the United States. Recombinant prourokinase (r-ProUK) offers potential as a novel agent with improved fibrin specificity and, as such, may offer advantages as an attractive alternative to urokinase. METHODS: A randomized, double-blind, parallel, phase II, prospective multicenter trial was undertaken to compare three doses of intra-arterial, catheter-directed r-ProUK (2 mg, 4 mg, or 8 mg/hr for 8 hrs, then 0.5 mg/hr) versus one dose of tissue-culture urokinase (4,000 IU/min for 4 hrs, then 2,000 IU/min) for the treatment of acute lower extremity arterial occlusion of 14 days' duration or less (n = 241). The primary endpoint was complete (>95%) lysis of the occluding thrombus after 8 hours of infusion. RESULTS: Increased clot lysis at 8 hours, decreased fibrinogen concentration, and an increased rate of hemorrhagic events were observed as the r-ProUK dose was increased from 2 mg/hr to 8 mg/hr. Similarly, a decreased duration of study drug infusion was seen, decreasing from 16.7 +/- 0.90 hours in the 2 mg/hr group to 12.7 +/- 0.97 hours in the 8 mg/hr group. The results for the urokinase group decreased to a level between those observed for the 2 mg and 8 mg r-ProUK group with respect to clot lysis at 8 hours, fibrinogen decrement, and bleeding complications, approximating those observed in the 4 mg/hr r-ProUK group. These results were achieved with a relatively low rate of major bleeding events and no episodes of intracranial hemorrhage. CONCLUSIONS: The 8 mg/hr dose of r-ProUK was associated with an increased rate of thrombolysis relative to the other treatment groups, associated with a slightly increased frequency of bleeding complications and decrements in fibrinogen concentration. Conversely, the 2 mg/hr r-ProUK dose was associated with a slightly slower rate of thrombolysis, but bleeding complications and fibrinogenolysis were diminished. r-ProUK is a novel thrombolytic agent with a dose-related safety and efficacy profile. As such, it offers potential as a useful tool in the treatment of peripheral vascular occlusion.


Subject(s)
Arterial Occlusive Diseases/drug therapy , Enzyme Precursors/therapeutic use , Fibrinolytic Agents/therapeutic use , Thrombolytic Therapy , Urokinase-Type Plasminogen Activator/therapeutic use , Aged , Angiography , Arterial Occlusive Diseases/blood , Arterial Occlusive Diseases/diagnostic imaging , Double-Blind Method , Enzyme Precursors/administration & dosage , Female , Fibrinogen/metabolism , Fibrinolytic Agents/administration & dosage , Humans , Infusions, Intra-Arterial , Leg/blood supply , Male , Prospective Studies , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Safety , Treatment Outcome , Urokinase-Type Plasminogen Activator/administration & dosage
15.
Med Biol Eng Comput ; 37(1): 64-70, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10396844

ABSTRACT

The effectiveness of substance delivery through catheters is an important issue in interventional radiology, especially for infusion therapies where the pharmacokinetic advantage of local intra-arterial drug administration has been firmly established. In principle, the procedure is used to provide appropriate local concentrations while maintaining low systemic values so as to minimise the global effect and toxicity of the intervention. However, poor drug mixing may produce excessive local concentrations potentially damaging for the surrounding tissues and may lead to unsuccessful therapies. These phenomena have been observed in the infusion therapies of liver cancers through the hepatic artery and with brain tumour therapies through the carotid artery. Many aspects of the drug delivery methodology have been explored in order to determine the infusion conditions that would provide optimal mixing: the catheter tip design is considered one of the most important characteristics to be investigated for this purpose. Interestingly, it turns out that angiographic procedures could also benefit from this, because better mixing properties are associated with designs that provide potentially less harmful flow conditions such as jets, whipping and recoil of the catheter on the vascular wall. A 2D steady numerical model is proposed, to simulate the main physical processes occurring during catheter substance infusion: blood dynamics is taken into account with the Navier-Stokes equations and substance dispersion by the flowing blood with the advection-diffusion equation. The model is used to evaluate mixing properties of certain catheter designs in different flow conditions. In particular, two types of side hole catheter are compared in the context of water bath injection and in the context of vessel injection. The simulations suggest that the improved mixing reported with water bath experiments would not be maintained in the clinical context of arterial circulation.


Subject(s)
Computer Simulation , Infusions, Intra-Arterial , Radiology, Interventional/methods , Catheterization , Equipment Design , Humans , Models, Biological
17.
J Magn Reson Imaging ; 8(6): 1319-22, 1998.
Article in English | MEDLINE | ID: mdl-9848744

ABSTRACT

Open-configuration MRI systems have been recently introduced and hold promise to allow the performance of a variety of minimally invasive procedures. Experience with MR-guided catheter-based luminal interventions is experimental to date. This is the first case of a successful percutaneous nephrostomy tube placement in a patient in an interventional MR system. The procedure was performed completely under MR guidance, and technical aspects are reviewed and compared with other, established techniques for percutaneous nephrostomy placement.


Subject(s)
Kidney Calculi/surgery , Magnetic Resonance Imaging , Nephrostomy, Percutaneous/methods , Ureterocele/surgery , Adult , Female , Humans , Intraoperative Period , Kidney Calculi/complications , Kidney Calculi/pathology , Minimally Invasive Surgical Procedures/methods , Ureterocele/complications , Ureterocele/pathology
18.
J Vasc Interv Radiol ; 9(3): 487-93, 1998.
Article in English | MEDLINE | ID: mdl-9618111

ABSTRACT

PURPOSE: The authors have previously reported that intramural delivery of iloprost during angioplasty suppresses local platelet aggregation at 1 hour in undiseased porcine arteries. In this study, the authors sought to quantify the effect of such treatment on medial vascular smooth muscle cell proliferation, an event implicated in the development of intimal hyperplasia. MATERIALS AND METHODS: Three Yorkshire pigs underwent percutaneous transluminal angioplasty with hydrogel-coated balloons for a total of 10 iloprost-treated (experimental) and 10 saline-treated (control) arterial sites. The balloons were prepared with previously reported techniques and loaded with 2.25 microg of iloprost for the experimental sites. On the eighth day after angioplasty, these sites were harvested and prepared for immunohistochemical staining. Thin (4 microm) sections of the specimens were stained with use of monoclonal antibody to proliferating cell nuclear antigen (PCNA). Appropriate positive and negative controls were used. Approximately 350-500 vascular smooth muscle cells were randomly counted under high power (100x) by an experienced physician who was blinded to the origin of the specimen. A PCNA index (%) was calculated as follows: [(#PCNA [+] cells)/(#PCNA [+] cells + #PCNA [-] cells)]x 100. A paired t test was used for statistical comparison. RESULTS: The PCNA indices for eight (n = 8) paired large vessels (iliac, carotid, subclavian) were 7.98 (+/- 1.8)%, for the iloprost-treated experimental sites, and 14.58 (+/- 3.8)% for the saline-treated control sites. This difference was statistically significant (P = .003). One large vessel pair was not available for analysis. When the pair of renal arteries of animal 3 were included (n = 9), the PCNA indices were 8.32 (+/- 2.3)% for the experimental sites, and 13.79 (+/- 4.2)% for the control sites. The differences were again significant (P = .01). CONCLUSION: Intraarterial site-specific delivery of iloprost during angioplasty with drug-loaded, hydrogel-coated balloons significantly suppresses medial smooth muscle cells in swine at the expected peak period of proliferation of 7 days after angioplasty.


Subject(s)
Angioplasty, Balloon , Iloprost/administration & dosage , Muscle, Smooth, Vascular/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Angioplasty, Balloon/instrumentation , Angioplasty, Balloon/methods , Animals , Carotid Artery, Common , Cell Division/drug effects , Iliac Artery , Iloprost/pharmacology , Muscle, Smooth, Vascular/cytology , Platelet Aggregation Inhibitors/pharmacology , Proliferating Cell Nuclear Antigen/analysis , Subclavian Artery , Swine
19.
Radiology ; 207(1): 139-45, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9530309

ABSTRACT

PURPOSE: To compare "cut-film" (film hard-copy) angiography (CFA) with digital pulmonary angiography in the detection of pulmonary embolism (PE). MATERIALS AND METHODS: Thirty-six adult patients (39 lungs) underwent selective digital pulmonary angiography for suspected PE. Imaging was repeated in one selected projection by using cut film. The standard was consensus interpretation of both CFA and digital angiographic images and clinical course. Three vascular radiologists subsequently reviewed the digital and cut-film images in a blinded fashion and ranked the likelihood of the presence of PE on a five-point scale. The two modalities were compared by means of receiver operating characteristic (ROC) analysis. Image quality (i.e., sharpness, opacification of subsegmental vessels, and exposure) was judged on a three-point scale. The highest-order pulmonary artery branch seen on each study was recorded. RESULTS: ROC curve analyses for all three operators showed similar diagnostic performance for digital pulmonary angiography and CFA, with one operator showing better performance with digital subtraction angiography than with CFA (P = .04). Compared with the final diagnosis, single-plane digital pulmonary angiography had higher sensitivity for the detection of PE than had CFA. The specificity was 100% for both modalities. The mean score in patients with findings positive for PE was higher in the digital pulmonary angiography group than in the CFA group (P < .005). There was no difference in the mean score in patients who did not have a PE. There also was no difference in the smallest detectable subsegmental branch (P = .87) or in the average estimate of image quality. CONCLUSION: Selective digital pulmonary angiography and CFA offer similar diagnostic performance and image quality. Digital pulmonary angiography is a reasonable alternative to CFA in the diagnosis of PE.


Subject(s)
Angiography, Digital Subtraction , Pulmonary Artery/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Adult , Aged , Aged, 80 and over , Angiography/methods , Female , Humans , Male , Middle Aged , ROC Curve , Sensitivity and Specificity
20.
Comput Med Imaging Graph ; 22(6): 447-52, 1998.
Article in English | MEDLINE | ID: mdl-10098892

ABSTRACT

INTRODUCTION: Features of spiral CT (SCT)-fast scanning, dynamic injection of contrast allowing optimal vessel opacification, and supplemental multiplanar imaging-promises to provide increased accuracy in the diagnosis of acute and non acute thoracic vascular disease. Recent work demonstrating the cost effective triage of hemodynamically stable patients after blunt chest trauma for angiography based on dynamic CT findings has prompted an investigation into the accuracy of SCT in this clinical setting. METHODS: A retrospective review of all patients seen in the emergency department over the period of one year for aortic, thoracic, or blunt chest trauma evaluation was performed (74 patients) and all SCT scans available were reviewed and data reformatted for optimal delineation of pathology using maximum intensity projection and multiplanar reformation. The accuracy and predictive positive and negative values of SCT were calculated with respect to angiography, surgical, and/or clinical follow up evaluation. RESULTS: Twenty three (31%) patients went directly to angiography owing to mediastinal widening on chest film and hemodynamic instability, of which four were positive and required emergent surgery. Seven hemodynamically stable patients (9%) had noncontrast SCT owing to mediastinal widening on chest film, all of which had angiography with none having great vessel trauma. Fourty four hemodynamically stable patients (60%) had contrast enhanced SCT (ceSCT), of which five (11%) were abnormal and underwent angiography, four of these were positive for aortic damage, one for a subclavian artery laceration. Of the remaining 39 patients who had normal ceSCT; five had angiography, all of which were normal. Of the remaining 34 patients that had normal ceSCT none had adverse outcome on clinical follow-up, minimum of 12 months. CONCLUSION: The predictive positive value for aortic trauma of ceSCT in blunt trauma is 80%, with a predictive negative value of 100%, indicating that it is feasible for SCT to be a first line exam in blunt chest trauma in the future.


Subject(s)
Aortic Rupture/diagnostic imaging , Thoracic Injuries/diagnostic imaging , Tomography, X-Ray Computed/economics , Tomography, X-Ray Computed/methods , Wounds, Nonpenetrating/diagnostic imaging , Adult , Aortography/methods , Clinical Trials as Topic , Cost-Benefit Analysis , Female , Humans , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed/instrumentation
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