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1.
Georgian Med News ; (199): 29-34, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22155803

ABSTRACT

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) by an unknown pathogenesis. MR venography and postmortem studies have demonstrated a topographic correspondence between multiple sclerosis (MS) plaques and the cerebral venous system pathology. In recent observational studies performed on patients from distinctive gene pools, the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in MS ranged from 56% to 100%. Endovascular treatment (percutaneous transluminal angioplasty (PTA) with or without stenting) of CCSVI was reported to be feasible with a minor complication rate. In 4 patients with different forms of multiple sclerosis venography was performed that revealed stenosis of the proximal region of the jugular vein (right or left). Percutaneous transluminal balloon angioplasty (PTA) was performed in all patients. There were no complications and mean stenosis was reduced after PTA from 59.75% to 36.75%. Follow-up included clinical observations and magnetic resonance imaging (MRI). In all the cases we observed positive remission of the disease, the first ever documented case of MRI index improvement. PTA seems to be an effective treatment for patients with CCVI and multiple sclerosis, However, randomized studies are warranted to establish the efficacy of this new treatment for MS.


Subject(s)
Angioplasty/methods , Brain/blood supply , Brain/pathology , Cerebral Veins/pathology , Constriction, Pathologic/therapy , Endovascular Procedures/methods , Multiple Sclerosis/therapy , Autopsy , Brain/diagnostic imaging , Cerebral Angiography/methods , Cerebrovascular Circulation , Constriction, Pathologic/diagnosis , Constriction, Pathologic/pathology , Humans , Jugular Veins/diagnostic imaging , Jugular Veins/pathology , Magnetic Resonance Imaging , Multiple Sclerosis/diagnosis , Multiple Sclerosis/pathology , Phlebography
2.
Georgian Med News ; (191): 12-8, 2011 Feb.
Article in Russian | MEDLINE | ID: mdl-21436472

ABSTRACT

The purpose of our study was to determine MDCT diagnostic possibility in blunt abdominal trauma. Our work was based on MDCT results of 84 blunt abdominal trauma patients with stable hemodynamic status (28 (33.3%) female and 56 (66.6%) male). Age ranges from 17 up to 64 years. The CT scan showed obvious organ and system injuries in 82 poly-trauma patients. Injuries of craniocerebral region, also of facial bones, chest and spine were determined in two patients; in one of which, however, it was not possible to differentiate subcapsular spleen hematoma accurately because of left upper joint metallic holder artifacts. In second patient the liver injury was accurately diagnosed, but there were visualization problems caused by the massive retroperitoneal hematoma from right adrenal gland injury. The investigation showed that sensitivity of CT scan data was 98%, specificity-97% and accuracy rate-98%. All above mentioned clearly states the importance of MDCT in the emergency department. MDCT ensures precise diagnosis in maximally short period of time and thereby helps to choose proper treatment and decreases post-traumatic complications.


Subject(s)
Abdominal Injuries/diagnostic imaging , Tomography, Spiral Computed , Abdominal Injuries/surgery , Adolescent , Adult , Aged , Female , Humans , Kidney/diagnostic imaging , Kidney/injuries , Liver/diagnostic imaging , Liver/injuries , Male , Middle Aged , Spleen/diagnostic imaging , Spleen/injuries , Thoracic Injuries/diagnostic imaging , Young Adult
3.
Kardiologiia ; 50(3): 65-70, 2010.
Article in Russian | MEDLINE | ID: mdl-20459408

ABSTRACT

With the aim of studying clinical profiles of hereditary cases of hypertrophic cardiomyopathy (HCMP) we examined 64 patients with HCMP of both sexes (mean age 43.8+/-11.7 years). Genealogy of 40 patients (62.5%) revealed no cases of the disease among first degree relatives. They were defined as sporadic forms of HCMP. Genealogical screening revealed 22 patients (37.5%) with familial forms of HCMP. In 8 cases study of genealogy of probands detected 16 more patients. Results of assessment of familial history, ECG and echocardiographic investigations reflected degree of thickening of interventricular septum, asymmetric character of distribution of hypertrophy in the myocardium, and cases of sudden deaths in first degree relatives as possible hereditary signs in familial HCMP determining variations of clinical phenotype of the disease through interrelated disturbances of contractile and electrical myocardial functions.


Subject(s)
Cardiomyopathy, Hypertrophic, Familial/genetics , Genetic Predisposition to Disease , Adult , Cardiomyopathy, Hypertrophic, Familial/diagnosis , Cardiomyopathy, Hypertrophic, Familial/epidemiology , Death, Sudden, Cardiac/epidemiology , Echocardiography , Electrocardiography , Female , Genotype , Georgia (Republic)/epidemiology , Humans , Incidence , Male , Pedigree , Survival Rate
4.
Georgian Med News ; (174): 10-3, 2009 Sep.
Article in Russian | MEDLINE | ID: mdl-19801721

ABSTRACT

The goal of our study was to ascertain the role and place of helical CT for preoperative diagnosis of acute appendicitis. Our study relied upon the results of helical CT scans of 60 patients, which were diagnosed probable acute appendicitis based upon clinical signs. Of these 60 patients 49 (81,6%) were female, 11 (18,4%) male. For all patients laboratory studies of blood were made, 31 patients were examined by ultrasonography. Among this group the diagnosis of acute appendicitis was verified by CT scan in 41 patients. In the case of 5 patients the scan was equivocal because of smaller amount of omentum; in this subgroup of 5 patients (5% overall) three were given radiocontrast dye, and two (3,3% overall) were not. In 11 (18,3%) cases the diagnosis of acute appendicitis was not verified, and in three cases the diagnosis was incorrect. According to data of our study and intraoperative data analysis, sensitivity of this method approaches 93% and the specificity - 92%, and overall diagnostic accuracy 93%. Helical CT may be stated as diagnostic method of choice in the diagnosis of acute appendicitis. It is helpful in clinical decision making, and reducing the amount of false appendectomies.


Subject(s)
Appendicitis/diagnostic imaging , Tomography, Spiral Computed , Adolescent , Adult , Appendicitis/pathology , Appendicitis/surgery , Female , Humans , In Vitro Techniques , Male , Young Adult
5.
Georgian Med News ; (168): 7-10, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19359710

ABSTRACT

Natural Orifice Transluminal Endoscopic Surgery is a new method of mini invasive surgery, which involves passing surgical instruments, and a tiny camera, through a natural orifice, such as the mouth, vagina, urethra or rectum, what provides the access to the desired organ. The procedure is approved due to its benefits - less pain, quicker recoveries, fewer complications and no scar - as it lets us avoid major incisions through the skin, muscle and nerves of the abdomen. Besides that the transluminal access is considered to be the most safe and feasible for clinical application. Here are discussed the two operations of Transvaginal Appendectomy performed in Caucasus - Academician N. Kipshidze University Hospital in Tbilisi. The first patient - a 28-year woman, weight - 72 kg, height - 180 cm, married, has one child - was submitted to the hospital with anamnesis of 48 hours acute appendicitis, typical clinical semiotics and laboratory records. In the second case the patient was a 22-year old woman, height - 170 cm, weight - 68 kg, married, with 2 children. She was hospitalized with 24 hours acute appendicitis anamnesis and typical clinical semiotics and laboratory records. Both operations were performed under general anesthesia, using Karl Storz GmbH & Co. equipment. The duration of the first procedure was 76 minutes and the second operation lasted for 88 minutes. The operations were made without any technical difficulties or complications. None of the patients had the need of non-narcotic analgesia during the post-operational period. No gynecological or surgical problems or any complications were detected during the observation period. The patients had superior postoperative evolution, so the stationary stay made up 36 hours after the first operation and 30 hours after the second. Essentially NOTES is a new trend in endoscopic surgery - the non-scar surgery with major advantages compared to the conventional - the NOTES takes endoscopic surgery one step further in terms of reducing pain and avoiding long hospitalization and is much more effective. The doctors hope to have more developed and flexible endoscopic surgical tools as they are planning to perform more complicated procedures in the future. Taking in consideration the appropriate experience of the operator the procedure is safe, more physiological and precise. Natural-orifice surgery becomes more familiar and as more procedures are successfully performed, the acceptance of it will grow. We consider NOTES is a challenge in surgery and in the nearest future in case of suitable technical support it will replace not only conventional medicine but laparoscopic too.


Subject(s)
Appendectomy/methods , Cicatrix/prevention & control , Adult , Female , Humans , Vagina , Young Adult
6.
Georgian Med News ; (166): 13-7, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19202210

ABSTRACT

Retrospectively review of long-term outcome of balloon angioplasty (TBA) in the treatment of native dialysis A-V fistulae stenosis was conducted. From February 2008 to January 2009, seven hemodialysis patients (5 women and 2 men; mean age 46.4 years) were treated for stenosis of the A-V fistula at the venous outflow tract. Angioplasty was performed with the use of high-pressure balloons. Percutaneous transluminal angioplasty was used. There were no any complications during and after procedure. In 4 cases residual stenosis did not exceed 10% and in 3 cases 30%. After 3 month the improvement rate was 85%. Two patients required surgical treatment. None of the patients displayed any major complications from the procedure. This study confirms the efficacy of PTA in the treatment of vascular access stenosis. Elevated dialysis blood line pressure can be the first sign of fistula stenosis. Although our series is small, we have nevertheless demonstrated that the concerted efforts of nephrologists, interventional radiologists, and surgeons are the key to maintaining and prolonging vascular access survival in this group of patients.


Subject(s)
Angioplasty, Balloon/methods , Angioscopy/methods , Brachiocephalic Veins , Graft Occlusion, Vascular/therapy , Renal Dialysis/adverse effects , Adult , Aged , Arteriovenous Shunt, Surgical/adverse effects , Catheters, Indwelling/adverse effects , Female , Follow-Up Studies , Graft Occlusion, Vascular/diagnosis , Graft Occlusion, Vascular/etiology , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Phlebography , Retrospective Studies , Treatment Outcome , Ultrasonography, Doppler , Young Adult
7.
Georgian Med News ; (162): 51-3, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18830031

ABSTRACT

Cardiogenic shock remains unsolved problem in modern Cardiology. Despite some achievements, in-hospital mortality rate still varies between 52-70%. In era of new developments in the field of circulatory assist devices IABP still remains the main supportive method for patients with shock. The most powerful predictors of hospital survival among shock patients are percutaneous revascularization with stenting and use of Intra-Aortic Balloon Counterpulsation (IABP). As we have experienced: inability to establish circulatory assistance can be fatal even with "open coronaries". Here we want to represent three cases of treatment of patients with ST Elevation Acute Myocardial Infarction complicated with cardiogenic shock.


Subject(s)
Angioplasty, Balloon/methods , Myocardial Infarction/drug therapy , Myocardial Infarction/surgery , Shock, Cardiogenic/drug therapy , Shock, Cardiogenic/surgery , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/therapeutic use , Carbazoles/therapeutic use , Carvedilol , Clopidogrel , Combined Modality Therapy , Coronary Angiography , Drug Therapy, Combination , Electrocardiography , Female , Humans , Male , Myocardial Infarction/diagnosis , Platelet Aggregation Inhibitors/therapeutic use , Propanolamines/therapeutic use , Shock, Cardiogenic/diagnosis , Stents , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic use , Vasodilator Agents/therapeutic use
8.
Adv Gerontol ; 18: 66-70, 2006.
Article in Russian | MEDLINE | ID: mdl-16676800

ABSTRACT

Systolic arterial pressure rises uninterruptedly with age and it appears as a strong independent risk-factor of cardiovascular, cerebral and renal complications. A combined using Norvasc and Egilok gives stable hypotensive effect, provides regression of left ventricular hyper-trophy with improvement parameters of systolic and diastolic function, which is vitally important for researched contingent of patients. A combined using small therapy doses of drugs protects geriatric patients against side effects.


Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Heart Ventricles/drug effects , Hypertension/drug therapy , Ventricular Function, Left/drug effects , Aged , Aged, 80 and over , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Drug Therapy, Combination , Echocardiography , Electrocardiography , Female , Heart Ventricles/diagnostic imaging , Humans , Hypertension/diagnostic imaging , Hypertension/physiopathology , Male , Middle Aged
9.
Georgian Med News ; (130): 57-61, 2006 Jan.
Article in Russian | MEDLINE | ID: mdl-16510914

ABSTRACT

It is known that the atrial fibrillation is a sorrow "privilege" of the senile groups of people. The aim of the given paper was to study the reasons of atrial fibrillation arising in old (60-74 years) and senile (75-89 years) patients and possibility of prevention paroxysms of atrial fibrillation and its complications with help of prolonged selective beta-blocker egilok retard pro daily doses 50-100 mg. The results which were received after the examination and treatment of 147 patients who were under stationary and dispensary treatment at the Research Institute of Experimental and Clinical therapy for 12 months. We have achieved full absence of paroxysmal atrial fibrillation in 89.8% patients (132 patients). The use of egilok retard gives stable hypotensive effect in old and senile patients, provides the regression of the left ventricular hypertrophy with improvement of its parameters and diastolic function, which is especially important for the studied contingent of the patients.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Atrial Fibrillation/prevention & control , Tachycardia, Paroxysmal/prevention & control , Aged , Aged, 80 and over , Atrial Fibrillation/physiopathology , Follow-Up Studies , Heart Rate/drug effects , Humans , Middle Aged , Myocardial Contraction/drug effects , Tachycardia, Paroxysmal/physiopathology , Treatment Outcome
10.
Georgian Med News ; (119): 9-13, 2005 Feb.
Article in Russian | MEDLINE | ID: mdl-15834171

ABSTRACT

The goal of this research was to study influence of the MS on the electrophysiological parameters of the heart conduction system. The research involved 32 patients suffering from heart arrhythmias (18 females and 14 males, average age 52,8-/+12,9). The patients were categorized into 2 groups. Group I included 15 patients (9 females and 6 males, average age 47,5-/+8,9) suffering from heart arrhythmias and with signs of MS. Group I was subdivided into 2 subgroups: I subgroup--10 patients without diabetes, and II subgroup 5 patients with type II diabetes. Group II comprised of 17 patients (8 females and 9 males, average age 57,4-/+11,9) with arrhythmias without any signs of MS. The refractoriness dispersion between the right atrium (RA) and the left atrium (LA) caused by the MS, directly provokes development of atrial fibrillation and type II (atypical) atrial flutter. In cases of metabolic syndrome and "slow-fast" type of PRAVNT caused by the metabolic failures, the prolongation of the antegrade effective refractory period (ERP) of the slow AV nodal pathways and the retrograde ERP of the fast AV nodal pathways provoked prolongation of the tachycardia cycle and, consequently, reduction of the heart rate during paroxysms of tachycardia. Metabolic failures produce direct effect upon the sinus node function, causing suppression of its function as the SNSS develops, which requires implantation of pacemaker. The research results for metabolic syndrome and AV blockage cases demonstrated that the latter was always of a distal type, which was caused by a direct effect of metabolic failures upon the electrophysiology of the atrioventricular junction.


Subject(s)
Arrhythmias, Cardiac/etiology , Diabetes Mellitus, Type 2/complications , Metabolic Syndrome/complications , Adult , Arrhythmias, Cardiac/surgery , Atrial Fibrillation/etiology , Atrial Fibrillation/physiopathology , Atrial Fibrillation/surgery , Atrial Flutter/etiology , Atrial Flutter/physiopathology , Atrial Flutter/surgery , Catheter Ablation , Echocardiography , Electrocardiography , Female , Humans , Male , Middle Aged , Tachycardia, Paroxysmal/etiology , Tachycardia, Paroxysmal/physiopathology , Treatment Outcome
11.
Adv Gerontol ; 14: 66-9, 2004.
Article in Russian | MEDLINE | ID: mdl-15559501

ABSTRACT

Arterial hypertension is a leading pathology in the elderly. This pathology become extremely important in a spread atherosclerotic process commonly observed in the geriatric patients. While the aspects of left ventricle in arterial hypertensive patients are rather well known, this pathology needs further investigations connected with the studies on age-related changes in cardiovascular system. Particular attention should be paid to a symptomatic of "hypertensive heart" in the elderly patients.


Subject(s)
Hypertension/complications , Hypertrophy, Left Ventricular/etiology , Aged , Aged, 80 and over , Female , Humans , Hypertension/diagnosis , Hypertrophy, Left Ventricular/physiopathology , Male , Middle Aged
13.
Int Angiol ; 22(4): 349-55, 2003 Dec.
Article in English | MEDLINE | ID: mdl-15153818

ABSTRACT

AIM: The aim of this paper is to assess the feasibility and efficacy of fibrin in inducing neovascularization as an angiogenic substance and/or carrier for vascular endothelial growth factor (VEGF) in patients with limb ischemia. METHODS: Twenty-three patients with limb ischemia and referred for below the knee amputations were randomized for treatment: group 1, 7 patients received only a saline injection; group 2, 9 received intramuscular injection of fibrin and group 3, 7 received the fibrin composition with deferoxamine and added VEGF(165). The fibrin meshwork was introduced into the popliteal area of the diseased limbs using a dual syringe system (1 contained thrombin solution [1 mg, 5000 U] and 1 contained fibrinogen [1 mg, Baxter Hyland Immuno] solution). In group 3, Deferoxamine (100 microg) and 500 microg of VEGF(165) were added to the fibrinogen solution. RESULTS: In the control group 5 patients had undergone below the knee amputation at the 3-6 month follow-up. Only 1 patient from Group 2 had below the knee amputation 5 months following Fibrin only administration. Clinical improvement was noted in all 8 patients following fibrin administration and in all 7 patients injected with the fibrin meshwork, deferoxamine and VEGF combination. CONCLUSION: IM injection of fibrin is safe and appears to be an efficient method to treat limb ischemia. These findings indicate that use of fibrin may be a novel and simple method for inducing therapeutic angiogenesis.


Subject(s)
Deferoxamine/administration & dosage , Fibrin/administration & dosage , Fibrinogen/administration & dosage , Ischemia/therapy , Vascular Endothelial Growth Factors/administration & dosage , Adult , Drug Therapy, Combination , Feasibility Studies , Humans , Injections, Intramuscular , Male , Middle Aged , Neovascularization, Physiologic/drug effects , Pilot Projects
14.
J Clin Laser Med Surg ; 19(5): 261-5, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11710621

ABSTRACT

BACKGROUND: It is believed that restenosis following coronary interventions is the result of endothelial denudation that leads to thrombus formation, vascular remodeling, and smooth muscle cell proliferation. Low-power red laser light (LPRLL) irradiation enhances endothelial cell growth in vitro and in vivo, and reduces restenosis in animal models. The present study investigated the optimal dose of intravascular LPRLL therapy in the prevention of in-stent stenosis in a porcine coronary stent model. METHODS AND RESULTS: Selected right coronary artery segments were pretreated with a LPRLL balloon, delivering a dose of 0 mW during 1 min (group 1, n = 10), 50 mW during 1 min (group II, n = 10), or 100 mW during 1 min (group III, n = 10) before stenting. Quantitative coronary analysis of the stented vessel was performed before stenting, immediately after stenting, and at 6 weeks follow-up. The pigs were sacrificed, and histologic and morphometric analyses were conducted. At 6 weeks, minimal luminal stent diameter was significantly narrower in the control group compared to the 50-mW dose group (p < 0.05). These results were confirmed by morphometric analysis. Neointimal area was also significantly decreased in the 50-mW dose group. CONCLUSIONS: Intravascular LPRLL contributes to reduction of angiographic in-stent restenosis and neointimal hyperplasia in this animal model. The optimal dose using the LPRLL balloon system seems to be approximately 5 mW delivered during 1 min.


Subject(s)
Coronary Restenosis/prevention & control , Endothelium, Vascular/radiation effects , Low-Level Light Therapy , Stents , Animals , Dose-Response Relationship, Radiation , Models, Animal , Swine
15.
Circulation ; 104(15): 1850-5, 2001 Oct 09.
Article in English | MEDLINE | ID: mdl-11591625

ABSTRACT

BACKGROUND: Neointimal hyperplasia after PTCA is an important component of restenosis. METHODS AND RESULTS: Cultures of rabbit endothelial cells and smooth muscle cells (SMCs) were irradiated with different doses of nonablative infrared (1064-nm) radiation. Normalized viability index detected with nondestructive Alamar Blue assay and direct cell count were studied. Our experiments demonstrated dose-dependent cytostatic or cytotoxic effects of laser irradiation. We also evaluated the long-term effect of endoluminal nonablative infrared laser irradiation on neointimal hyperplasia in a rabbit balloon injury model. PTCA of both iliac arteries of 23 New Zealand White rabbits was performed. One iliac artery was subjected to intra-arterial subablative infrared irradiation via a diffuse tip fiber. The contralateral vessel served as control. The diet was supplemented with 0.25% cholesterol and 2% peanut oil for 10 days before and 60 days after PTCA. Morphometry after 60 days showed that intimal areas were 0.76+/-0.18 and 1.85+/-0.30 mm(2) in the laser and control arteries, respectively (P=2.2x10(-11)). CONCLUSIONS: We conclude that nonablative infrared laser inhibited neointimal hyperplasia after PTCA in cholesterol-fed rabbits for up to 60 days.


Subject(s)
Angioplasty, Balloon, Coronary/adverse effects , Endothelium, Vascular/radiation effects , Hyperplasia/prevention & control , Infrared Rays/therapeutic use , Muscle, Smooth, Vascular/radiation effects , Tunica Intima/radiation effects , Animals , Catheterization/instrumentation , Cell Count , Cell Division/radiation effects , Cell Survival/radiation effects , Cells, Cultured , Disease Models, Animal , Dose-Response Relationship, Radiation , Endothelium, Vascular/cytology , Fiber Optic Technology/instrumentation , Hyperplasia/etiology , Hyperplasia/pathology , Iliac Artery/pathology , Iliac Artery/radiation effects , Iliac Artery/surgery , Laser Therapy , Muscle, Smooth, Vascular/cytology , Rabbits , Treatment Outcome , Tunica Intima/injuries
16.
Catheter Cardiovasc Interv ; 54(2): 247-56, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11590694

ABSTRACT

Myointimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA) is a key component of the process of restenosis. The c-myc is a critical cell-cycle division protein involved in the formation of neointima. We evaluated the long-term impact of local delivery of c-myc neutrally charged antisense oligonucleotides (Resten-NG) on myointimal hyperplasia after PTCA in a rabbit model. PTCA was performed in the iliac arteries of 25 New Zealand white rabbits, using a Transport catheter at 8 atm for 30 sec, three times; 500 microg Resten-NG (n = 11) or saline (n = 14) was delivered to the PTCA site at 2 atm with the outer balloon for 2 min. The diet was supplemented with 0.25% cholesterol for 10 days before and 60 days after PTCA. Angiography was performed at harvest, and vessels were fixed in formalin, processed, and stained with hematoxylin and eosin (H&E) and Movat. Quantitative angiography showed that local delivery of antisense c-myc at PTCA reduced late luminal loss from 1.8 +/- 0.30 mm in control animals to 0.90 +/- 0.30 mm in the treatment group (P = 0.001). Histological analysis by planimetry showed that intimal areas were 1.67 +/- 0.44 mm(2) and 0.82 +/- 0.32 mm(2) in the control and antisense delivery groups, respectively (P < 0.05). We conclude that local delivery of Resten-NG inhibited myointimal hyperplasia after PTCA in cholesterol-fed rabbits for up to 60 days.


Subject(s)
Angioplasty, Balloon, Coronary/adverse effects , Drug Delivery Systems , Genes, myc/physiology , Iliac Artery/injuries , Oligonucleotides, Antisense/administration & dosage , Oligonucleotides, Antisense/metabolism , Tunica Intima/metabolism , Tunica Intima/pathology , Animals , Blotting, Western , Cell Culture Techniques , Constriction, Pathologic/metabolism , Disease Models, Animal , Hyperplasia/metabolism , Iliac Artery/metabolism , Iliac Artery/pathology , Muscle, Smooth, Vascular/metabolism , Rabbits , Time Factors , Tunica Intima/injuries
19.
Curr Opin Mol Ther ; 3(3): 265-77, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11497351

ABSTRACT

One of the potential clinical applications of antisense therapy is the prevention or treatment of restenosis following coronary interventions. Inhibition of several cellular proto-oncogenes have been shown to inhibit smooth muscle cell proliferation in vitro and to reduce neointimal thickening in vivo. The clinical applicability of antisense technology, however, remains limited due to a relative lack of specificity, slow uptake across the cell membrane and rapid intracellular degradation of the oligonucleotide. The one study in humans with c-myc antisense yielded a negative result with respect to restenosis after stent implantation. Recent studies have introduced phosphorothioate morpholino oligomers (PMO), which represent an unusual DNA chemistry with a six-membered morpholino ring instead of a deoxyribose sugar. In addition, the charged phosphodiester internucleotide linkage is replaced by an uncharged phosphorothioate. The PMOs are resistant to serum nucleases found in serum and exhibit a high degree of specificity and efficacy in both in vitro and cell-free translation studies. In vivo studies in four different animal models of restenosis demonstrated significant reduction of myointimal response. The combination of enhanced efficacy and greater specificity introduced by the PMO chemistry led us to re-examine the potential efficacy of a neutrally charged c-myc antisense approach for the prevention of restenosis. Clinical studies are underway to investigate safety and efficacy of local delivery of this latest generation of antisense to reduce restenosis after coronary stenting.


Subject(s)
Coronary Restenosis/prevention & control , Genetic Therapy , Morpholines/therapeutic use , Oligonucleotides, Antisense/therapeutic use , Thionucleotides/therapeutic use , Animals , Coronary Restenosis/drug therapy , Coronary Restenosis/pathology , Coronary Restenosis/physiopathology , Disease Models, Animal , Genes, myc , Humans , Iliac Artery/drug effects , Iliac Artery/pathology , Morpholines/pharmacokinetics , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/pathology , Muscle, Smooth, Vascular/physiology , Oligonucleotides, Antisense/genetics , Oligonucleotides, Antisense/pharmacokinetics , Randomized Controlled Trials as Topic , Stents , Thionucleotides/genetics , Thionucleotides/pharmacology
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