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1.
Arch Orthop Trauma Surg ; 136(2): 233-9, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26476719

ABSTRACT

BACKGROUND: Rotator cuff tear is a leading etiology of shoulder pain and disability. Surgical treatment is indicated in patients with persistent pain who fail a trial of non-surgical treatment. Pain reduction following rotator cuff repair, particularly within the first 24-48 h, is a major concern to both doctors and patients. This study aimed to compare the postoperative antinociceptive additive effects of pre-incisional intra-articular (IA) ketamine when combined with morphine with two times the dose of morphine or saline. METHODS: In this prospective, randomized, double blind, controlled trial patients undergoing arthroscopic rotator cuff tear repair (ARCR) under general anesthesia were enrolled. Patients were randomly assigned to one of the three intervention groups. Twenty minutes prior to incision, morphine (20 mg/10 ml), ketamine (50 mg + morphine 10 mg/10 ml), or saline (0.9 % 10 ml) (n = 15/group), were administered to all patients. First 24 h postoperative analgesia consisted of intravenous patient controlled analgesia (IV-PCA) morphine and oral rescue paracetamol 1000 mg or oxycodone 5 mg. 24-h, 2-week and 3-month patient rated pain numeric rating scale (NRS) and analgesics consumption were documented. RESULTS: Patients' demographic and perioperative data were similar among all groups. The 24-h and the 2-week NRSs were significantly (p < 0.05) lower in both treatment groups compared to placebo, but were not significantly different between the two intervention groups. PCA-morphine and oral analgesics were consumed similarly among the groups throughout the study phases. CONCLUSIONS: Pre-incisional intra-articular morphine reduced pain in the first 2 weeks after arthroscopic rotator cuff repair. Further research is warranted to elucidate the optimal timing and dosing of IA ketamine and morphine for postoperative analgesic effects.


Subject(s)
Analgesics/therapeutic use , Arthroscopy , Ketamine/therapeutic use , Morphine/therapeutic use , Pain, Postoperative/prevention & control , Rotator Cuff/surgery , Analgesia, Patient-Controlled , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Injections, Intra-Articular , Male , Middle Aged , Pain Measurement , Preoperative Care , Prospective Studies
2.
J Vasc Surg ; 34(1): 41-6, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11436073

ABSTRACT

OBJECTIVE: Rupture of abdominal aortic aneurysms (AAAs) remains lethal. In a report of patients treated in the 1980s, we recommended aggressive management. Our continued experience prompted us to reevaluate this policy. METHODS: We reviewed clinical variables affecting outcome, morbidity, mortality, and trends in mortality of all patients managed at our institution with ruptured AAAs between January 2, 1980, and November 30, 1998. RESULTS: The study group included 413 consecutive patients, 339 men and 74 women. The mean age was 74.3 years (range, 49-96); 116 (28%) patients were older than 80 years. AAA was diagnosed before rupture in 119 (29%) patients. Eighty (19%) patients had preoperative cardiac arrest. Twenty-nine (7%) patients died before operation; 65 (17%) died during the operation. The surgical mortality rate (30-day) was 37%; the overall mortality rate was 45% and was higher in women (68%) than in men (40%) (P <.001). Advanced age, APACHE (Acute Physiology and Chronic Health Evaluation) II score, initial hematocrit, and preoperative cardiac arrest were associated multivariately with 30-day mortality rates by means of stepwise logistic regression (P <.05). Twelve (23%) of 53 patients with cardiac arrest survived the operation. Logistic regression, adjusted for age, sex, and APACHE II score, demonstrated a decrease in overall and 30-day mortality rates (P <.001) over 18 years. The mean overall mortality rate was 51% from 1980 to 1984 and 42% from 1994 to 1998. CONCLUSIONS: The mortality rate of ruptured AAAs remains excessive, despite improvement over 18 years. Patients older than 80 years with shock or cardiac arrest have the highest mortality rate and should be evaluated for possible endovascular treatment. Because the diagnosis of AAA was unknown in more than 70% of patients, screening of the high-risk population and elective repair are recommended.


Subject(s)
Aortic Aneurysm, Abdominal/mortality , Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/mortality , Aortic Rupture/surgery , APACHE , Aged , Aged, 80 and over , Female , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies
3.
J Foot Ankle Surg ; 40(2): 113-5, 2001.
Article in English | MEDLINE | ID: mdl-11324668

ABSTRACT

Knee dislocation is defined as a radiographically confirmed total loss of the tibiofemoral articulation. This rare injury is believed to be the result of a high-impact trauma. Knee dislocations are classified according the direction of tibial displacement with respect to the femur. Subtalar dislocation is the simultaneous dislocation of the distal articulations of the talus at both the talocalcaneal and talonavicular joints. These injuries are also quite rare and are mostly (80%-85%) classified as medial subtalar dislocations with the calcaneus lying medially, the head of the talus being prominent dorsolaterally and the navicular located medial and dorsal to the talar head. The authors report the case of an elderly patient who suffered ipsilateral anterior dislocation of his left knee and medial subtalar dislocation of his left foot. The authors believe this to be the first presentation in the English literature of an ipsilateral combination of these two injuries on the same limb.


Subject(s)
Joint Dislocations/complications , Knee Injuries/complications , Subtalar Joint/injuries , Aged , Aged, 80 and over , Foot Injuries/complications , Foot Injuries/therapy , Humans , Joint Dislocations/therapy , Knee Injuries/therapy , Male , Talus , Terminology as Topic , Tibia
4.
Surg Laparosc Endosc Percutan Tech ; 10(5): 296-301, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11083212

ABSTRACT

Laparoscopic resections of colon cancer may affect survival. To address the effects of pneumoperitoneum on tumor cell biology, we developed an experimental model. Mice were injected with colonic tumor cells. Local and systemic effects of pneumoperitoneum were evaluated. Treated mice were randomly assigned to a control group, an open cecectomy group, or a laparoscopic-simulated cecectomy group. When a tumor inoculum was injected into the peritoneal cavity, the frequency of tumors was not significantly different for mice in the laparoscopic-simulated and open cecectomy groups (60% vs 62%, respectively). There was no significant difference in survival time between the laparoscopic-simulated and open cecectomy groups, with median survivals of 24 days versus 22 days, respectively. Finally, when tumor cells were injected subcutaneously, the frequency of tumor nodules and the size and weight of tumors were not different between the two surgical groups. Laparoscopic-simulated cecectomy does not appear to adversely effect local factors or favorably affect systemic factors influencing tumor growth or survival.


Subject(s)
Adenocarcinoma/surgery , Colonic Neoplasms/surgery , Neoplasm Seeding , Pneumoperitoneum, Artificial , Animals , Disease Models, Animal , Mice , Mice, Inbred BALB C , Pneumoperitoneum, Artificial/adverse effects , Random Allocation , Tumor Cells, Cultured
5.
J Vasc Surg ; 31(6): 1193-205, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10842157

ABSTRACT

PURPOSE: Thrombolysis protects the structural and functional integrity of vein wall in an experimental model of acute deep venous thrombosis (DVT) immediately after treatment, but late sequelae have not been studied. We designed experiments to compare the effects of thrombolysis and surgical thrombectomy at 4 weeks after the treatment of DVT. METHODS: DVT was produced bilaterally in male mongrel dogs by proximal and distal femoral vein ligation. Five dogs underwent sham operation. After 48 hours, the ligatures were removed, and the thrombosis was treated with either Fogarty balloon catheter thrombectomy (shear force, 60 g; n = 6) or catheter-directed urokinase infusion (4000 U/min for 90 minutes; n = 6). At 4 weeks, patency and valvular competence were determined by duplex ultrasound scanning. Thrombogenicity was studied by the measurement of radiolabeled fibrin and platelet deposition. Veins were explanted and prepared for histologic examination, scanning electron microscopy, and functional studies in organ chambers. RESULTS: All veins were patent at 1 month. Recanalized thrombus was observed histologically in four (66%) thrombectomized veins, one (17%) thrombolyzed vein, and none of the sham-operated veins (P =.04). Scanning electron microscopy demonstrated similar luminal endothelial cell loss (11%-25%) in all three groups. Platelet and fibrin depositions were not different among groups. Valvular incompetence (reflux duration, >0.5 sec) did not differ significantly in the groups (thrombectomized veins, 2 of 12 (17%); thrombolyzed veins, 0 of 12 (0%); P = NS). In organ chamber studies, endothelium-dependent relaxations to calcium ionophore, but not adenosine diphosphate, were inhibited by an antagonist of nitric oxide production after thrombectomy (P <.05, thrombectomy vs sham- and thrombolysis-treated veins). All veins relaxed to exogenous nitric oxide. CONCLUSION: Both thrombectomy and thrombolysis restored patency and achieved similar valvular competence. Surgical thrombectomy, however, resulted in more residual thrombus and contributed to changes in endothelium-mediated relaxations at 4 weeks. Thrombolysis maintained both structural integrity and endothelial function.


Subject(s)
Femoral Vein/drug effects , Thrombolytic Therapy , Vasomotor System/drug effects , Venous Thrombosis/drug therapy , Adenosine Diphosphate/pharmacology , Analysis of Variance , Animals , Calcimycin/pharmacology , Catheterization , Dogs , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Femoral Vein/diagnostic imaging , Femoral Vein/pathology , Femoral Vein/physiopathology , Femoral Vein/surgery , Fibrin/analysis , Ionophores/pharmacology , Ligation , Male , Microscopy, Electron, Scanning , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/pharmacology , Plasminogen Activators/therapeutic use , Platelet Adhesiveness , Thrombectomy , Treatment Outcome , Ultrasonography, Doppler, Duplex , Urokinase-Type Plasminogen Activator/therapeutic use , Vascular Patency/physiology , Vasodilator Agents/pharmacology , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/surgery
6.
Stroke ; 31(4): 968-75, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10754007

ABSTRACT

BACKGROUND AND PURPOSE: Hypercholesterolemia is associated with abnormal endothelium-dependent vasorelaxation due to decreased nitric oxide bioavailability. Our aim was to examine the effect of adenovirus-mediated gene transfer of endothelial nitric oxide synthase (eNOS) to the hypercholesterolemic rabbit carotid artery in vivo. In addition, we examined whether adenovirus-mediated gene transfer was associated with vascular dysfunction. METHODS: Rabbits were fed a 1% cholesterol diet for 4 weeks followed by a 0.5% cholesterol diet for 6 weeks. Vascular reactivity was assessed in nontransduced carotid arteries from chow- and cholesterol-fed animals. In addition, carotid arteries were surgically isolated, and 2 separate doses of adenoviral vectors encoding eNOS or beta-galactosidase (AdbetaGal) on the contralateral side were delivered to the lumen (1x10(10) and 5x10(10) pfu/mL). RESULTS: Abnormal acetylcholine-mediated endothelium-dependent vasorelaxation was detected in the carotid artery from cholesterol-fed animals, whereas responses to calcium ionophore A23187 and diethylamine NONOate were normal. Vascular reactivity was similar in nontransduced and AdbetaGal-transduced hypercholesterolemic vessels. In vessels transduced with eNOS, transgene expression was demonstrated by immunostaining in both the endothelium and the adventitia and by Western blot analysis. High-dose but not low-dose eNOS gene transfer enhanced endothelium-dependent relaxation in vessels from cholesterol-fed rabbits. CONCLUSIONS: Adenovirus-mediated gene transfer of eNOS to carotid arteries of cholesterol-fed animals improves endothelium-dependent relaxation when an optimal viral titer is administered.


Subject(s)
Endothelium, Vascular/physiopathology , Gene Transfer Techniques , Hypercholesterolemia/physiopathology , Hypercholesterolemia/therapy , Nitric Oxide Synthase/genetics , Vasodilation , Animals , Carotid Arteries/pathology , Carotid Arteries/physiopathology , Hypercholesterolemia/metabolism , Hypercholesterolemia/pathology , Lipids/blood , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type III , Rabbits , Tissue Distribution , Vasomotor System/physiopathology , beta-Galactosidase/genetics , beta-Galactosidase/metabolism
7.
Orthopedics ; 22(11): 1029-33, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10580821

ABSTRACT

This article evaluates imaging of the scapula and scapulothoracic joint in patients with snapping scapula syndrome. Between 1990 and 1996, a total of 20 patients (10 men and 10 women) with snapping scapula syndrome were evaluated. Diagnosis was based on patient complaints and physical examination findings. There were 26 affected scapulae (6 patients had bilateral presentation). Imaging of the scapula included plain radiography, computed tomography (CT), and 3-dimensional computed tomography (3-D CT) reconstruction. Plain radiography revealed bony incongruity between the anterior aspect of the scapula and the chest wall in 7 scapulae, CT revealed such incongruity in 19 scapulae, and 3-D CT revealed incongruity in all 26 scapulae. Treatment was conservative, consisting of nonsteroidal anti-inflammatory drugs, a physiotherapy program, and subscapular injection of a local anesthetic and steroids. In 5 patients who responded poorly to conservative treatment, the region responsible for the snapping was resected. Pain relief and resolution of the snapping were complete following surgery in 4 patients, while pain and crepitation persisted in the fifth. Three-dimensional CT is recommended as the main imaging modality in the evaluation of any patient with snapping scapula syndrome who is a candidate for surgical intervention.


Subject(s)
Scapula/physiopathology , Shoulder Dislocation/diagnostic imaging , Shoulder Joint/physiopathology , Tomography, X-Ray Computed , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthralgia/etiology , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Scapula/surgery , Shoulder Dislocation/therapy , Shoulder Joint/diagnostic imaging , Tomography, X-Ray Computed/methods
8.
Anticancer Res ; 19(1A): 175-9, 1999.
Article in English | MEDLINE | ID: mdl-10226540

ABSTRACT

BACKGROUND: The association of TN expression, tumour grading and expression of commonly used histopathologic prognostic factors (p53 and estrogen receptor) was examined in 62 cases of invasive ductal carcinoma of the breast. MATERIAL AND METHODS: Following histological grading immunohistochemical reactions were undertaken on routine histopathologic samples and the results semiquantitatively evaluated. RESULTS: Strong TN expression was found in close proximity of the neoplastic epithelial cells in each case, but not in other areas of the stroma. In 10 (16%) cases TN expression was detected to the neoplastic epithelial cells as well. There was no statistically significant difference in the extent of stromal TN immunoreaction between tumours of different grades. A significant difference was found in p53 and estrogen receptor immunoreactions by tumour grade (p = 0.05). TN immunoreaction in the stroma did not correlate with the nuclear expression of p53, Ki-67 and estrogen receptor in the tumour cells. CONCLUSIONS: TN immunoreactivity does not seem to correlate with currently used prognostic factors. The increased expression of stromal TN in invasive breast ductal carcinomas is an other indicator of possible role played by the extracelular matrix components in cancer development.


Subject(s)
Breast Neoplasms/chemistry , Carcinoma, Ductal, Breast/chemistry , Tenascin/analysis , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Female , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Receptors, Estrogen/analysis , Tenascin/immunology , Tumor Suppressor Protein p53/analysis
9.
J Vasc Res ; 36(6): 437-44; discussion 532-4, 1999.
Article in English | MEDLINE | ID: mdl-10629419

ABSTRACT

L-arginine (L-Arg) may be limiting for inducible nitric oxide synthase (NOS) activity and under certain circumstances, such as increased concentrations of a NOS inhibitor, may also be limiting for endothelial NOS activity. It is unknown if L-Arg is limiting for recombinant eNOS activity in the vascular wall after adenoviral mediated gene transfer. Our aim was to examine, if L-Arg is limiting for recombinant eNOS activity in the normal or atherosclerotic vessel wall. Rings of rabbit aorta from chow or cholesterol fed animals were transduced with adenovirus vector encoding eNOS (AdeNOS) or beta-galactosidase (AdbetaGal). After 24 h, transgene expression was confirmed and vasomotor studies were performed in the absence or presence of L-Arg. During maximal contractions to phenylephrine (10(-5) M), L-Arg (3 mM) was added to the organ chamber for 30 min. Subsequently, relaxations to acetylcholine during half-maximal contractions were obtained. In the chow- and cholesterol-fed animals, relaxations were significantly enhanced in the NOS and NOS + L-Arg groups compared to the betaGal and betaGal + L-Arg groups. There was no difference between NOS and NOS + L-Arg or betaGal and betaGal + L-Arg rings from chow- or cholesterol-fed animals. While gene transfer of eNOS enhances endothelium-dependent vasorelaxation in the normal and atherosclerotic vessel wall, L-arginine is not limiting for recombinant eNOS activity.


Subject(s)
Arginine/pharmacology , Endothelium, Vascular/enzymology , Nitric Oxide Synthase/metabolism , Nitric Oxide/biosynthesis , Animals , Aorta , Blotting, Western , Immunohistochemistry , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Rabbits , Recombinant Proteins/metabolism , Staining and Labeling , beta-Galactosidase/analysis
10.
Nutr Metab Cardiovasc Dis ; 9(5): 220-7, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10656168

ABSTRACT

BACKGROUND AND AIM: The present work is a chapter in an investigation directed by the World Health Organization on the Pathobiological Determinants of Atherosclerosis In Youth (WHO-PBDAY). Our aim was to study the development of atherosclerotic lesions in a young population. METHODS AND RESULTS: Samples of left anterior descending coronary artery (LDC) and thoracic (TA) and abdominal aorta (AA) from five Collaborating Centres (Budapest/Hungary, Havana/Cuba, Heidelberg/Germany, Mexico City/Mexico, Peradeniya/Sri Lanka) of 214 subjects who died aged 15 and 34 were analysed at the Budapest Reference Centre. Slides stained with haematoxylin-eosin and with stains for extracellular matrix were quantitatively and qualitatively evaluated. Mean intima/media (I/M) ratio and the prevalence of type III-IV lesions (preatheroma; atheroma; calcified and fibrous atheroma) were determined and compared in different risk factor (high blood pressure, smoking) groups. High I/M ratio was found in the LDC and type III-IV lesions were frequently found both in the LDC and in the AA. I/M ratio and the occurrence of type III-IV lesions increased in all arteries by age. Atherosclerotic lesions in men were more severe, particularly in the LDC. Geographic origin had a limited effect on the histologic lesion parameters. Appearance of type III-IV lesions was associated with substantially different extracellular matrix changes. Myoelastic layer formation was found in each artery in both early and type III-IV lesions. Hypertension was associated with higher prevalence of type III-IV lesions in all arteries, in particular, in the TA; smoking showed a significant effect on the AA only. CONCLUSIONS: Atherosclerotic lesions were found in many of these young subjects. The effect of hypertension and smoking on their development suggests that control of risk factors, beginning in early adolescence, could help to prevent cardiovascular diseases.


Subject(s)
Aorta, Abdominal/pathology , Aorta, Thoracic/pathology , Arteriosclerosis/epidemiology , Arteriosclerosis/pathology , Coronary Vessels/pathology , Adolescent , Adult , Age Factors , Arteriosclerosis/etiology , Arteriosclerosis/prevention & control , Female , Global Health , Histocytochemistry , Humans , Hypertension/complications , Male , Prevalence , Risk Factors , Severity of Illness Index , Sex Factors , Smoking/adverse effects , World Health Organization
11.
Atherosclerosis ; 141(2): 265-71, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9862175

ABSTRACT

Cholesterol feeding results in impaired endothelium dependent vasorelaxation. The role of nitric oxide in this process is unclear. The aim of this study was to evaluate the role of nitric oxide in cholesterol-induced vasomotor dysfunction by examining the effect of overexpression of eNOS in the hypercholesterolemic rabbit aorta on vascular reactivity. Vascular rings from the thoracic aorta of hypercholesterolemic rabbits were exposed ex vivo either to an adenoviral vector encoding endothelial nitric oxide synthase (AdeNOS) or Escherichia coli beta Galactosidase (AdbetaGal). Transgene expression was examined by histochemistry for beta galactosidase, immunohistochemistry for eNOS and cyclic GMP measurements and vasomotor studies were performed. Transgene expression was found to localize to the endothelium and adventitia. cGMP levels were significantly greater in AdeNOS compared to AdbetaGal transduced rings. Acetylcholine mediated relaxation was significantly impaired in cholesterol fed rabbits and was markedly improved by overexpression of eNOS. These results suggest that reduced NO bioavailability observed in cholesterol-induced vascular dysfunction can be partially overcome by eNOS gene transfer.


Subject(s)
Acetylcholine/pharmacology , Aorta, Thoracic/physiopathology , Arteriosclerosis/physiopathology , Endothelium, Vascular/enzymology , Gene Transfer Techniques , Nitric Oxide Synthase/genetics , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Adenoviridae , Animals , Aorta, Thoracic/metabolism , Arteriosclerosis/metabolism , Cyclic GMP/metabolism , Escherichia coli , Genetic Vectors , In Vitro Techniques , Nitric Oxide/physiology , Nitric Oxide Synthase/metabolism , Rabbits , beta-Galactosidase/genetics , beta-Galactosidase/metabolism
12.
J Vasc Surg ; 28(5): 787-99, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9808845

ABSTRACT

PURPOSE: The experiments were designed to compare the effects of thrombolytic therapy (TL) and balloon-catheter thrombectomy (TX) on valvular competence, thrombogenicity, venous wall morphology, and function after acute deep venous thrombosis (DVT) in canine veins. METHODS: The femoral veins of male mongrel dogs were ligated proximally and distally for 48 hours to induce DVT. The thrombosed veins were treated with either TL (n = 5) or TX (n = 9), or no treatment was rendered (n = 6). Sham-operated dogs were used as controls. TL was performed with catheter-directed infusion of urokinase at 4000 U/min for 90 minutes. Three hours after the treatment, the valvular competence was determined with duplex scanning, thrombogenicity determined with deposition of radio-labeled platelet and fibrin, and function determined with response to contractile and relaxing agonists in organ chambers. The structural integrity of the endothelial layer was assessed by means of scanning electron microscopy. RESULTS: The removal or lysis of the thrombus was successful in all cases. The valvular competence did not differ among the groups. The platelet deposition was the highest after TX (P <.05), and the fibrin deposition was not significantly different among the groups. In the organ chamber experiments, relaxations to adenosine diphosphate and nitric oxide were reduced after TX (P <.05). The contractions to serotonin were enhanced after TX. Scanning electron microscopy results showed a comparable (51% to 75%) endothelial loss with either treatment. CONCLUSIONS: After experimental acute DVT, the TL and the TX at 3 hours had similar effects on the valvular competence and the endothelial morphology. However, the TL reduced thrombogenicity, which is consistent with the preserved endothelial responses to platelet products. These data suggest that TL may preserve vein function after DVT and may reduce the long-term potential for recurrent DVT and post-thrombotic syndrome.


Subject(s)
Endothelium, Vascular/pathology , Muscle, Smooth, Vascular/physiopathology , Thrombectomy , Thrombolytic Therapy , Venous Thrombosis/drug therapy , Venous Thrombosis/surgery , Animals , Catheterization , Dogs , Femoral Vein , Ligation , Male , Thrombectomy/methods , Venous Thrombosis/physiopathology
13.
Arterioscler Thromb Vasc Biol ; 18(7): 1157-63, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9672077

ABSTRACT

Macrophage colony stimulating factor (MCSF) is believed to play a key role in one of the earliest events in atherosclerosis, ie, monocyte to macrophage differentiation in the arterial intima. The aim of this study was to examine the biological effects of vascular wall expression of MCSF. A recombinant adenovirus vector encoding human MCSF (AdMCSF) was generated by standard techniques of homologous recombination in 293 cells. The rabbit carotid artery was transduced with AdMCSF. As negative controls, carotid arteries were transduced with either an adenoviral vector encoding beta-galactosidase, an adenoviral vector encoding apolipoprotein E, or diluent alone. Intima-media thickness ratio was calculated 5 and 21 days after transduction. The cell type present in intimal infiltrates was analyzed by immunohistochemistry. MCSF expression was demonstrated in the vessel wall of AdMCSF-transduced vessels by reverse transcription-polymerase chain reaction and immunofluorescence. In contrast to control vessels, adenovirus-mediated MCSF expression was associated with an intimal cellular infiltrate consisting of smooth muscle cells and small numbers of macrophages. Whereas the intima-media thickness ratio was greater in AdMCSF-transduced vessels at 5 days, this difference was no longer statistically significant at 21 days. These results suggest that MCSF may play a role in recruitment of monocytes and macrophages to the vessel wall and may contribute to smooth muscle cell proliferation and migration.


Subject(s)
Adenoviridae/genetics , Carotid Arteries/metabolism , Gene Expression , Gene Transfer Techniques , Macrophage Colony-Stimulating Factor/genetics , Animals , Fluorescent Antibody Technique, Indirect , Genetic Vectors , Humans , Immunohistochemistry , Macrophage Colony-Stimulating Factor/analysis , Polymerase Chain Reaction , RNA-Directed DNA Polymerase , Rabbits , Tissue Distribution , beta-Galactosidase/analysis , beta-Galactosidase/genetics
14.
Int Angiol ; 17(4): 282-6, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10204663

ABSTRACT

BACKGROUND: The aim of this study was to compare the histomorphologic appearance of atherosclerosis in amputated legs of diabetic and non-diabetic patients. METHODS: Twenty-eight legs amputated below the knee for chronic ischaemia were studied. Fourteen legs were amputated in patients with diabetes (10 Type II, 4 nonclassified) and 14 in non-diabetics. The mean age of patients at the time of the amputation was 63.3 years in diabetics and 63.9 years in non-diabetics. Samples were taken from the main arteries at the following levels: the midleg, 5 cm above the ankle, 3 cm below the ankle and 10 cm below the ankle. Cross-sections of the arteries were examined with light microscopy and the severity of the occlusive disease determined using morphometric analysis. Medial calcification and chronic inflammation were assessed semiquantitatively. RESULTS: Arteries at 5 cm above the ankle were more severely stenotic in diabetics than in non-diabetics (p<0.05). In both diabetics and non-diabetics the posterior tibial and plantar arteries appeared to be the most stenotic. Medial calcification tended to be more prominent in diabetics than in non-diabetics. Chronic inflammation in the arterial wall occurred at the same degree in diabetics and non-diabetics. In non-diabetics chronic inflammation was more severe in the posterior tibial and plantar arteries than in the anterior tibial and dorsalis pedis arteries (p<0.04). Chronic arterial inflammation correlated with the severity of chronic arterial occlusive disease (p<0.0002). CONCLUSIONS: In diabetics occlusive disease in amputated legs is more severe in arteries above the ankle than in non-diabetics. However, no difference was demonstrated in this series in arteries of the ankle and foot. Diabetics are likely to have more medial calcification in the arteries than non-diabetics. Chronic inflammation in the arterial wall is associated with more severe stenosis.


Subject(s)
Arteriosclerosis/pathology , Diabetes Mellitus, Type 2/pathology , Diabetic Angiopathies/pathology , Ischemia/pathology , Leg/blood supply , Amputation, Surgical , Humans , Middle Aged
15.
Hypertension ; 30(3 Pt 1): 314-20, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9314410

ABSTRACT

We tested the effects of overexpression of the endothelial nitric oxide synthase (eNOS) gene in the normal arterial wall by adenoviral-mediated gene transfer. Rabbit carotid arteries were surgically isolated and exposed to adenoviral vectors encoding eNOS (AdeNOS) or beta-galactosidase (Ad betaGal) on the contralateral side. Vector solutions at a concentration of 1 x 10(10) plaque forming units/mL were instilled for 20 minutes before restoration of flow. Arteries were harvested 4 days later for immunostaining, measurement of cGMP, and vasomotor studies. Endothelium-specific gene transfer was confirmed by staining for beta-galactosidase in the Ad betaGal arteries. Immunostaining of en face endothelial cell imprints from AdeNOS-transduced arteries with a monoclonal antibody to eNOS showed increased immunoreactivity. Basal cGMP levels were significantly greater in the AdeNOS-transduced arteries (18.4+/-4.6 versus 4.2+/-0.5 pmol/mg protein; P<.05). Contractions to phenylephrine were significantly reduced in the AdeNOS-transduced arteries (area under curve, 106+/-5 versus 119+/-7; P<.05), but in the presence of the eNOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA, 3 x 10(-4) mol/L), there was no difference between the two (area under curve, 148+/-5 versus 153+/-6; P=NS). Relaxations to acetylcholine obtained during submaximal contractions to phenylephrine were significantly enhanced in the AdeNOS-transduced arteries (EC50, 7.45+/-0.05 versus 7.23+/-0.03; P<.05). We conclude that overexpression of eNOS in the endothelium results in diminished contractile responses, as well as enhanced endothelium-dependent relaxations. These findings imply a possible role for vascular eNOS gene transfer in the treatment of vasospasm and endothelial dysfunction.


Subject(s)
Carotid Arteries/physiology , Endothelium, Vascular/enzymology , Endothelium, Vascular/physiology , Gene Transfer Techniques , Nitric Oxide Synthase/genetics , Vasodilation/physiology , Animals , Cyclic GMP/metabolism , Male , Phenylephrine/pharmacology , Potassium Chloride/pharmacology , Rabbits , Recombinant Proteins , Vasoconstriction , Vasoconstrictor Agents/pharmacology
16.
Circulation ; 96(7): 2254-61, 1997 Oct 07.
Article in English | MEDLINE | ID: mdl-9337198

ABSTRACT

BACKGROUND: Adventitial gene transfer may serve as a tool to study vascular biology and may have therapeutic potential. We investigated the hypothesis that adenovirus-mediated transfer of the gene for endothelial nitric oxide synthase (eNOS) to the adventitia would alter vascular reactivity. METHODS AND RESULTS: Rabbit carotid arteries were surgically isolated and adenoviral vectors encoding eNOS (AdeNOS) or beta-galactosidase instilled into the periarterial sheath at a concentration of 1 x 10(10) pfu/mL. Arteries were harvested 4 days later for immunostaining, NOS enzymatic assay, measurement of cGMP, and vasomotor studies. Transgene expression in the adventitia was confirmed by histochemistry for beta-galactosidase and immunostaining for eNOS with a monoclonal antibody. Calcium-dependent NOS enzymatic activity and cGMP levels were significantly greater in the AdeNOS-transduced arteries. Maximal contractions to phenylephrine (10(-5) mol/L) were diminished in the AdeNOS-transduced arteries (4.6+/-0.2 versus 5.6+/-0.2 g; P<.05), but in the presence of the eNOS inhibitor N(G)-monomethyl-L-argininc (3x10(-4) mol/L) there was no difference between the two groups (7.1+/-0.2 versus 7.5+/-0.3 g; P=NS). Relaxations to calcium ionophore obtained during submaximal contractions to phenylephrine were significantly enhanced in the AdeNOS-transduced arteries (-log EC50, 7.77+/-0.08 versus 7.45+/-0.07; P<.02). CONCLUSIONS: We conclude that eNOS gene transfer to the adventitia alters vascular reactivity, as demonstrated by diminished contractile responses to phenylephrine and enhanced relaxations to calcium ionophore. This may represent a therapeutic strategy for vascular diseases characterized by decreased bioavailability of NO.


Subject(s)
Carotid Arteries/physiology , Endothelium, Vascular/enzymology , Gene Transfer Techniques , Nitric Oxide Synthase/biosynthesis , 1-Methyl-3-isobutylxanthine/pharmacology , Analysis of Variance , Animals , Calcimycin/pharmacology , Calcium/metabolism , Carotid Arteries/drug effects , Cattle , Cloning, Molecular , Cyclic GMP/metabolism , Cytomegalovirus , Genetic Vectors , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , Nitric Oxide Synthase/metabolism , Nitroprusside/pharmacology , Phenylephrine/pharmacology , Rabbits , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/metabolism , beta-Galactosidase/biosynthesis , omega-N-Methylarginine/pharmacology
18.
Am J Physiol ; 271(6 Pt 2): H2238-45, 1996 Dec.
Article in English | MEDLINE | ID: mdl-8997279

ABSTRACT

The vascular effects of somatostatin (ST) and its mechanism of action are not well understood. In the present study, we investigated the direct effects of ST on the vascular tone of rat saphenous artery and vein using videomicroangiometry in situ. ST was administered either in superfusion or in infusion. We found opposite effects in arteries and veins: ST (10(-12)-10(-7) M) dilated the artery (outer diameter increased from 533 +/- 28 to 600 +/- 29 microns, administered in superfusion) and contracted the vein (from 709 +/- 26 to 640 +/- 26 microns and from 775 +/- 30 to 708 +/- 60 microns in superfusion and infusion, respectively). These effects of ST were completely abolished after deendothelization (air bolus maintained for 6 min in vessel lumen) and after local infusion of NG-nitro-L-arginine (L-NNA; 10(-4) M), a nitric oxide (NO) synthesis inhibitor. An NO-dependent basal vasodilator tone in the rat saphenous vein responsible for 10.9 +/- 0.3% of the total vessel diameter was found. After ST administration the venous diameter reduction was similar to that measured after deendothelization or L-NNA. We conclude that ST in situ induces NO release from endothelial cells of rat saphenous artery causing vasodilation, whereas, in contrast, it inhibits the basal NO-dependent vasodilator tone of the saphenous vein inducing vasoconstriction.


Subject(s)
Nitric Oxide/physiology , Saphenous Vein/drug effects , Somatostatin/pharmacology , Thigh/blood supply , Animals , Arteries/drug effects , Endothelium, Vascular/physiology , Enzyme Inhibitors/pharmacology , Female , Male , Nitric Oxide/antagonists & inhibitors , Nitroarginine/pharmacology , Rats , Rats, Sprague-Dawley , Vasoconstriction , Vasodilation
19.
J Vasc Surg ; 24(5): 793-9, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8918326

ABSTRACT

PURPOSE: To study the hemodynamic effects of an arteriovenous fistula (AVF) used as an adjunct to venous reconstructions and to determine the optimal size for such a fistula. METHODS: A model of limb circulation with an AVF (in vitro system) was constructed with silicon elastic tubes and 40% glycerin solution as the fluid medium. Pulsatile arterial flow and venous return was maintained with a roller pump and a centrifugal assist device. Flows and pressures were measured for three different fistula diameters (3, 4, and 5 mm). A canine model of venous hypertension with outflow obstruction was constructed in 15 adult mongrel dogs. After 7 to 13 days an externally supported 8-mm expanded polytetrafluoroethylene femorocaval graft was implanted with a distal AVF (3 mm, n = 5; 4 mm, n = 5; 5 mm, n = 5). Arterial and venous flows and venous pressures were measured proximal and distal to the fistula before and after exercise. RESULTS: In the in vitro system, flows through the venous graft increased with increasing fistula size, but venous return decreased progressively, increasing the distal venous pressure. In the canine model, flow in the venous graft increased with each AVF (p < 0.01). Only the 3-mm AVF resulted in decreased distal femoral vein pressure (p < 0.01), orthograde flow, and improved venous return with exercise. CONCLUSION: AVFs increased flow through the femorocaval grafts, yet they impeded venous return. The ideal AVF-to-graft ratio used in our study was 0.375, because it increased graft flow, permitted forward flow in the femoral vein while reducing pressure, and improved venous return with exercise.


Subject(s)
Arteriovenous Shunt, Surgical , Extremities/blood supply , Femoral Artery/physiology , Femoral Vein/physiology , Vena Cava, Inferior/physiology , Animals , Chronic Disease , Disease Models, Animal , Dogs , Electric Stimulation , Femoral Artery/surgery , Femoral Vein/surgery , Humans , Hypertension/physiopathology , Models, Anatomic , Pulsatile Flow , Random Allocation , Regional Blood Flow , Veins , Vena Cava, Inferior/surgery
20.
J Vasc Surg ; 24(5): 800-8, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8918327

ABSTRACT

PURPOSE: This study was undertaken to define the surgical anatomy of the medial perforating veins (PVs) of the leg and to provide information on how to gain access to all medial PVs from the superficial posterior compartment during a subfascial endoscopic procedure. METHODS: The venous anatomy of 40 limbs (from 23 cadavers) were studied. Medial PVs located between the ankle and the tibial tuberosity were dissected. None of the subjects had pathologic evidence of venous disease. Each PV's type (direct or indirect), size (< 1 mm, 1 to 2 mm, > 2 mm), location (distances from ankle [D1], and tibia [D2]), and accessibility from the superficial posterior compartment were recorded. RESULTS: Five hundred fifty-two PVs were identified (mean, 13.8; range, 7 to 22). Two hundred eighty-seven PVs (52%) directly connected the superficial with the deep systems, 228 (41%) were indirect muscle perforators, and 37 PVs (7%) were undetermined. One hundred thirty-seven PVs (25%) were > 2 mm. Sixty-three percent of PVs were accessible from the superficial posterior compartment. In the distal half of the leg, two groups of direct PVs could be identified (Cockett II: D1, 7 to 9 cm; Cockett III: D1, 10 to 12 cm). In the proximal half of the leg, paratibial direct PVs (D2 < or = 1 cm) were found clustered in three groups (D1, 18 to 22 cm; D1, 23 to 27 cm; D1, 28 to 32 cm). CONCLUSIONS: Our study confirmed the presence of the Cockett II and III PVs and three groups of proximal paratibial PVs, including the "24-cm" perforators. Two thirds of the medial direct PVs are accessible for endoscopic division from the superficial posterior compartment. To divide paratibial PVs, however, incision of the paratibial deep fascia is frequently required.


Subject(s)
Endoscopy/methods , Fasciotomy , Leg/blood supply , Veins/surgery , Cadaver , Corrosion Casting , Fascia/anatomy & histology , Female , Humans , Male , Middle Aged , Veins/anatomy & histology
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