Biomedical subjects

G R Seabrook

Publications and source records attributed to G R Seabrook.

At least 37 records · Page 2Linked to original sources

PubMed2000

All-trans-retinoic acid decreases vein graft intimal hyperplasia and matrix metalloproteinase activity in vivo.

BACKGROUND: Development of vein graft intimal hyperplasia has been associated with increased activity of matrix metalloproteinases (MMPs). All-trans-retinoic acid (atRA) decreases expression and activity of MMPs in tissue culture and has decreased intimal hyperplasia following arterial balloon catheter injury. We examined the effect of oral administration of atRA on intimal hyperplasia and MMP expression in an animal model of vein bypass grafting. MATERIALS AND METHODS: Interposition jugular vein bypass grafts were placed in the carotid artery of New Zealand white rabbits. Animals received either atRA (10 mg/kg/day) or vehicle (corn oil) for a period of 2 weeks. Retinoic acid serum levels were determined by HPLC. Intimal and medial areas were measured using morphometric analysis of perfusion-fixed vein graft specimens, and intimal thickness was calculated using circumferential measurements. Expression of MMP-2, MMP-9, and TIMP-1 in vein grafts and unoperated control veins was determined using Northern analysis, and proteolytic activity was determined using substrate gel zymography. RESULTS: Animals treated with atRA had significantly elevated serum levels of this compound and its metabolites. A decrease in intimal to medial ratio was noted after 28 days in vein grafts from treated animals (0.63 vs 0.88, P < 0.01), and a decrease in calculated intimal thickness was noted at 7 and 28 days. Expression of MMP-2 was decreased in treated animals 7 days following surgery, and expression of both MMP-2 and MMP-9 was decreased at 28 days. A decrease in proteolytic activity was noted on zymography at 68 kDa, 7 and 28 days following surgery in vein grafts from animals treated with atRA, corresponding with a decrease in the active form of MMP-2. Increased expression of TIMP-1 was noted in vein grafts from both the treated and the control groups, 7 and 28 days following graft placement. CONCLUSIONS: Oral administration of all-trans-retinoic acid resulted in decreased intimal hyperplasia in an animal model of vein bypass grafting. This was associated with decreased expression and activity of MMP-2 in treated animals.

Animals↗

PubMed2000

Functional characterization of bradykinin analogues on recombinant human bradykinin B(1) and B(2) receptors.

We have examined the activity of a range of kinins on recombinant human bradykinin receptors, using a high throughput functional assay which measures intracellular Ca(2+) responses. The most potent agonist for Chinese hamster ovary (CHO) cells stably expressing recombinant human bradykinin B(1) receptors were Des-Arg(9)-bradykinin (EC(50)=7.9 nM) and Des-Arg(10)-kallidin (EC(50)=8.6 nM), while the most potent agonist for CHO cells expressing human bradykinin B(2) receptors was bradykinin (EC(50)=2.0 nM). These findings confirm the validity of the recombinant system and the microtitre plate imaging-based characterization system when compared to known agonist properties of the native receptors. The concentration-response relationship for bradykinin at bradykinin B(2) receptors was potently inhibited by [D-Arg(0),Hyp(3), beta-(2-thienyl)-Ala(5),D-Tic(7),Oic(8)]-bradykinin (Hoe140) (IC(50)=71 nM), which was 500-fold more potent against the B(2)-expressing cells than the B(1) cells. Bradykinin B(1) receptor-mediated responses activated by Des-Arg(10)-kallidin were fully antagonized by Des-Arg(9)-[Leu(8)]bradykinin (IC(50)=59 nM), Des-Arg(10)-Hoe140 (IC(50)=211 nM) and most potently by Lys-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-D-Igl-Oic (B9858) (IC(50)=14 nM), none of which displayed any activity against the bradykinin B(2) receptor cell line up to 3 microM. None of the antagonists displayed partial agonism activity in these cell lines. All bradykinin B(1) and B(2) receptor antagonists tested acted in an apparently non-competitive manner that is likely to be due in part to their kinetics and to the nature of the functional assay used.

Animals↗

PubMed2000

Mobilisation of intracellular Ca2+ by mGluR5 metabotropic glutamate receptor activation in neonatal rat cultured dorsal root ganglia neurones.

The ability of metabotropic glutamate receptor activation to mobilise intracellular calcium was investigated in cultured dorsal root ganglion (DRG) neurones from neonatal rats using the calcium sensitive fluorescent dye Fura-2. L-glutamate (10 microM) caused sustained and oscillatory increases in intracellular calcium concentration ([Ca2+]i) in a subpopulation of cultured DRG neurones. The oscillatory responses were not blocked by combined application of the ionotropic glutamate receptor antagonists MK 801 (2 microM) and CNQX (20 microM). Oscillations in [Ca2+]i were also observed following application of the nonselective metabotropic glutamate receptor (mGluR) agonist, trans-(1S,3R)-1-aminocyclopentane-1S, 3R-dicarboxylic acid (1S,3R)-ACPD, 20 microM) and the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 500 microM). These responses were blocked by the selective Group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) (100 microM) and Ca2+ release channel inhibitors ryanodine (100 microM) and dantrolene (10 microM). The predominantly Group II agonist (2S,2'R,3'R)-2-(2'3'-dicarboxy-cyclopropyl)glycine (DCG-IV, 100 microM) failed to produce Ca2+ transients alone but suppressed responses to CHPG. Reverse transcriptase PCR techniques, using primers specific to Group I mGluRs, revealed the presence of mGluR5 but not mGluR1 mRNA in these cells. Therefore, glutamate can cause a slowly activating and reversible mobilisation of [Ca2+]i in sensory neurones by activation of ionotropic receptors, and can induce oscillatory calcium transients by selectively activating metabotropic glutamate receptors that are likely to be of the mGluR5 subtype.

Animals↗

PubMed2000

Intraoperative carotid evaluation.

HYPOTHESIS: Intraoperative duplex scanning can identify technical defects and increase the quality of carotid artery repair. DESIGN: We evaluated 100 consecutive carotid operations in 96 patients (60 men and 36 women) from 1995 to 1998. Spectral-derived peak systolic flow velocities (PSV) were graded (PSV < 100 cm/s, normal laminar flow; PSV 100-150 cm/s, mild or moderate flow disturbance; PSV > 150 cm/s, severe flow disturbance). Prospective criteria for intraoperative revision included PSV greater than 150 cm/s, spectral broadening, and B-mode imaging of intimal flaps or intraluminal debris. Preoperative, intraoperative, and 6-week follow-up duplex scan results were analyzed. SETTING: All patients were evaluated and treated at a single academic institution. INTERVENTIONS: All procedures were performed with the patient under general endotracheal anesthesia; 86% underwent shunting and 70% underwent patching. MAIN OUTCOME MEASURE: Number and type of revisions, patency of repair, residual and recurrent stenosis, and ipsilateral neurologic events. RESULTS: There were 33 intraoperative duplex studies with abnormal findings. Seven involved the common carotid artery and resulted in intraoperative revision of 5 intimal flaps at the site of the proximal clamp. In 11 patients, incomplete eversion endarterectomy resulted in elevated distal intimal flaps in the external carotid artery that were repaired through a separate arteriotomy. There were 15 abnormalities in the internal carotid artery prompting 5 revisions. Five studies with PSV of 100 to 150 cm/s had no defects on B-mode imaging and were observed without treatment. Five false-positive studies were attributed to increased flow velocity due to contralateral occlusive discase. At 6 weeks' follow-up, 4 of 5 repaired common carotid arteries were normal on duplex scan and 1 had a mild residual stenosis. Ten of the 11 external carotid repairs were patent and 1 was occluded. Four of the 5 internal carotid artery repairs were normal on postoperative evaluation and 1 had a mild residual stenosis. Of the 10 abnormal internal carotid arteries that were observed, 9 were normal on postoperative duplex and 1 had a mild residual stenosis. One perioperative stroke occurred in a patient with a normal, patent carotid repair. CONCLUSIONS: Intraoperative duplex evaluation of carotid reconstruction is an efficient, sensitive tool that can detect technical lesions that will jeopardize surgical reconstruction. Interpretive judgment is required because all flow disturbances do not dictate surgical intervention. This technique enables the surgeon to maximize the quality of the arterial reconstruction during carotid artery surgery.

Aged↗

PubMed2000

Metalloproteinase levels are decreased in symptomatic carotid plaques.

BACKGROUND: Matrix metalloproteinase enzymes (MMP) have been identified in carotid atherosclerotic plaques, but their role in the development of clinical symptoms remains ill defined. We correlated the activity and levels of metalloproteinase enzymes and their inhibitors in human carotid plaques to ischemic neurologic events. METHODS: Carotid plaques were collected at the time of endarterectomy from 23 patients with carotid stenosis. Sixteen patients were asymptomatic and 7 patients had symptoms of stroke or transient ischemic attack within 6 weeks of surgery. Protein was extracted from the plaques, proteolytic activity was determined by gelatin zymography, and pro-MMP and tissue inhibitor of metalloproteinase (TIMP) enzyme content were measured by ELISA assay. Macrophage accumulation in the plaque was determined using immunohistochemistry. RESULTS: Plaques from symptomatic patients had decreased proteolytic activity on substrate gel zymography at the 62- and 92-kDa regions (corresponding to active MMP-2 and pro-MMP-9). A decrease in pro-MMP-9 (8.21 +/- 2.35 vs 17.42 +/- 3.14 ng, P < 0. 05) and an increase in TIMP-2 protein (12.62 +/- 0.58 vs 10.56 +/- 0. 77 ng, P < 0.05) were noted on ELISA in plaques from symptomatic patients. No difference was noted in macrophage accumulation in the plaques between the two groups. CONCLUSIONS: Plaques from patients who present with ischemic neurologic symptoms have decreased proteolytic activity associated with decreased pro-MMP-9 and increased TIMP-2 protein levels. These data suggest that metalloproteinase enzymes are not responsible for plaque instability in the carotid circulation and may in fact promote plaque stability.

Aged↗

PubMed2000

All-trans-retinoic acid decreases cell proliferation and increases apoptosis in an animal model of vein bypass grafting.

BACKGROUND: We have previously demonstrated a decrease in intimal hyperplasia in vein bypass grafts from animals treated with all-trans-retinoic acid (atRA). The purpose of this study was to examine the effect of atRA on proliferation and apoptosis rates in healing vein bypass grafts. METHODS: Interposition jugular vein bypass grafts were placed in the carotid artery of 30 New Zealand white rabbits. Animals received either atRA (10 mg/kg/d) or vehicle (corn oil) for a period of 2 weeks. Animals were killed at 3, 7, or 28 days after graft placement after having received 3 doses of 5-bromo-2'-¿Deoxyuridine (BRDU, 35 Mg/KG). Animals Were Perfusion Fixed, And Vein Grafts Were Prepared For Immunohistochemistry By Using Antibodies To Brdu, Proliferating Cell Nuclear Antigen, And Bcl-XL. Apoptosis Was Measured By Using The Tunel Assay. Histologic Sections Were Analyzed By A Pathologist Blinded To The Study, And An Index Of Positively Stained Cells Was Generated For Each Layer Of The Vein Graft Wall. RESULTS: All-trans-retinoic acid reduced the proliferation index in the neointima of vein grafts during the first week after surgery. Apoptotic rates were higher in the intima of vein grafts from animals treated with atRA, which could not be explained by changes in bcl-xl expression. No differences were noted in the media or adventitia between the groups. CONCLUSIONS: atRA decreased cell proliferation and increased apoptosis in the intima of healing vein bypass grafts. These effects contribute to decreased intimal hyperplasia, which has been previously noted.

Anastomosis, Surgical↗

PubMed1999

Ascorbic acid prevents cigarette smoke injury to endothelium-dependent arterial relaxation.

BACKGROUND: Arterial endothelium-dependent acetylcholine relaxation is impaired by smoking, and this injury may be mediated by oxygen free radicals. The purpose of this study was to examine the effect of ascorbic acid (AA) treatment on this injury. MATERIALS AND METHODS: New Zealand White rabbits (n = 6, each group) were placed in a 240-ft3 airflow chamber for 3 h per day, 5 days per week over an 8-week period. Animals were divided into four groups and fed rabbit chow and water or rabbit chow and AA (250 ml/kg)-supplemented water. The control-smoke rabbit group and the ascorbic acid-smoke rabbit group were exposed to mainstream cigarette smoke from a robotic smoke generator for the 3-h period, while the control-no smoke rabbit group and ascorbic acid-no smoke rabbit group were similarly placed in the chamber without smoke. At the end of 8 weeks, rabbits were sacrificed and segments of their superficial femoral arteries were suspended from tension transducers and the maximal contraction was determined. The remaining rings were contracted to 50% of the maximum and relaxation was determined by adding acetylcholine. Groups were compared using one-way ANOVA. RESULTS: Rings from control-smoke (5.13 +/- 0.21 g) and AA-smoke rabbits (6. 24 +/- 0.46 g) exhibited increased mean contraction to KCl (P < 0. 05) compared to control-no smoke rabbits (3.86 +/- 0.40 g). Acetylcholine-dependent relaxation was significantly reduced in the rings from the control-smoke rabbits compared to control-no smoke rabbits (acetylcholine, 5 x 10(-7) M: 24.7 +/- 2.7% versus 55.3 +/- 8.0%; acetylcholine, 7 x 10(-7) M: 27.5 +/- 2.3% versus 56.3 +/- 9. 2%). The AA-smoke group (acetylcholine, 5 x 10(-7) M: 61.8 +/- 12. 4%; 7 x 10(-7) M: 67.9 +/- 11.4%) had significantly increased relaxation compared to the control-smoke group (P < 0.05). There was no statistical difference in the mean percentage ring relaxation between the control-no smoke, AA-no smoke, and AA-smoke groups. CONCLUSIONS: Ascorbic acid protected the artery from cigarette smoke-induced endothelial injury.

Animals↗

PubMed1999

Cigarette smoke impairs endothelium-dependent relaxation in rabbit superficial femoral veins.

BACKGROUND: The use of autogenous vein for arterial reconstruction provides the optimal conduit for limb salvage. Cigarette smoking is a risk factor for vascular disease and may adversely affect graft patency and limb preservation rates of extremities reconstructed with autogenous vein. This study was performed in order to determine the effects of cigarette smoke on venous endothelium-dependent relaxation which is mediated by nitric oxide. MATERIALS AND METHODS: New Zealand white rabbits were exposed to cigarette smoke in a 240-ft3 air-flow chamber for 3 h per day, 5 days per week, for 8 weeks. A control group was treated similarly without infusion of smoke into the chamber. Elevated serum cotinine and carboxyhemoglobin levels comparable to those of chronic smokers were observed in the experimental group. After 8 weeks, the superficial femoral veins were explanted, cut into 3-mm segments, and studied in organ chambers. RESULTS: No difference in contractile response to KCl (80 mM) (control, 0.10 +/- 0.06; smoke, 0.17 +/- 0.04) or norepinephrine (EC50) (control, 0.78 +/- 0.18; smoke, 0.87 +/- 0.11) was seen. A significant decrease in relaxation was noted with all doses of acetylcholine (M) (control, 10(-8) - 50.35 +/- 8.37, 3 x 10(-8) - 71.20 +/- 9.05, 10(-7) - 88.32 +/- 13.72, 3 x 10(-7) - 92. 86 +/- 13.69; and smoke, 10(-8) - 8.25 +/- 1.83*, 3 x 10(-8) - 19.11 +/- 5.11*, 10(-7) - 31.84 +/- 7.90*, 3 x 10(-7) - 39.74 +/- 8.65*; *P < 0.05). Both control and smoke veins relaxed completely with sodium nitroprusside. CONCLUSIONS: Superficial femoral veins, when exposed to cigarette smoke, demonstrated a significant decrease in endothelium-dependent relaxation in response to acetylcholine without smooth muscle injury. This loss of vasomotor tone could be detrimental over time in veins which have been placed as arterial conduits.

Acetylcholine↗

PubMed1999

cGMP is decreased after acute ischemia in chronically ischemic canine limbs.

BACKGROUND: A chronic partially ischemic state may alter the skeletal muscle response to acute ischemia and free radical formation. METHODS: In order to investigate this hypothesis, a chronic ischemic state was established by ligating the right femoral artery of four mongrel dogs. ABIs were decreased from 1.05 +/- 0.25 preligation to 0.54 +/- 0.14 at 6 weeks (P = 0.04). At the end of 8 weeks, the hindlimb was subjected to 3 h of acute ischemia by clamping the iliac artery. The clamp was then released for 2 h of reperfusion. Plasma samples from the right iliac vein were taken during the ischemia-reperfusion period for analysis of cGMP. Tibialis anterior biopsies for Western analysis of eNOS and iNOS were taken upon completion of reperfusion. Comparisons to control dogs subjected to the acute ischemia and reperfusion without prior femoral artery ligation were made. RESULTS: cGMP levels were increased in the controls at 3 h of ischemia (3539 +/- 350) and 2 h of reperfusion (2880 +/- 269). The chronic ischemia group did not develop a corresponding increase in cGMP at 3 h of ischemia (2762 +/- 251) or after 2 h of reperfusion (2102 +/- 130). Western analysis of eNOS and iNOS revealed similar levels in both groups. Analysis of eNOS revealed 0.6429 +/- 0.086 and 0.5916 +/- 0.072 (densitometric units +/- SEM) for study and control dogs, respectively. Analysis of iNOS revealed 0.3401 +/- 0.067 and 0.2475 +/- 0.066 for study and control dogs, respectively. CONCLUSION: Previous ligation of the femoral artery resulting in chronic partial ischemia in this model demonstrated no increase in cGMP following acute ischemia that was not accompanied by a change in eNOS or iNOS levels. Nitric oxide activity is reflected by cGMP levels, which may increase in response to free radicals in the acute setting of complete ischemia.

Acute Disease↗

PubMed1999

Cholesterol, but not cigarette smoke, decreases rabbit carotid artery relaxation.

The purpose of this study was to determine the physiologic effects of cigarette smoke exposure and dietary cholesterol on the availability of nitric oxide in carotid vascular rings. New Zealand white rabbits were placed in an airflow chamber for 3 hr/day over an 8-week period and were exposed to smoke from 600 cigarettes/per day added to the chamber inflow by a robotic smoke generator. New Zealand white rabbits, made hypercholesterolemic, and one group fed a normal diet, were similarly placed in the chamber without exposure to cigarette smoke. In those exposed groups, serum cotinine and cholesterol levels were consistently elevated. After the 8-week period, the carotid arteries were harvested. The vessels were cut into 3-mm rings which were suspended from pressure transducers. The rings were contracted with potassium chloride (KCl) to determine vessel integrity. One ring from each carotid was maximally contracted with 1 x 10(-3) molar norepinephrine (NE) while the experimental ring was contracted to 50% of maximum. Relaxation of the rings was achieved by adding incremental doses of acetylcholine. Our results showed that endothelial dysfunction, as measured by acetylcholine-mediated vasorelaxation, occurs in the rabbit carotid artery when exposed to high dietary cholesterol. Cigarette exposure alone in this particular vessel did not result in significant alteration in acetylcholine-mediated vasorelaxation.

Acetylcholine↗

PubMed1999

Endovascular therapy of iliac arteries: routine application of intraluminal stents does not improve clinical patency.

Our objective in this study was to review our experience with endovascular therapy of iliac artery occlusive disease over the past decade, and to compare the results of angioplasty alone with the addition of endovascular stents to these procedures. This report details a retrospective analysis of clinical data on 141 consecutive patients with iliac artery occlusive disease, treated by balloon angioplasty alone, or with the addition of intraluminal stents. The procedures analyzed included 58 common iliac artery interventions (26 angioplasties and 32 stent insertions) and 83 external iliac artery procedures (43 angioplasties and 40 stent insertions). Early and continued success, and their components, are reported and compared according to published standards. While endovascular therapy of iliac artery occlusive disease is effective in relieving symptoms, clinical patency rates are lower than those reported for direct reconstruction. Primary stent placement has not enhanced clinical patency in the iliac arteries, and the selective insertion of these devices for more complicated angioplasty procedures seems warranted.

Adult↗

PubMed1999

Airborne particulates in the OR environment.

Intraoperative sampling of airborne particulates is rarely performed in the OR environment because of technical difficulties associated with sampling methodologies and because of the common belief that airborne contamination is infrequently associated with surgical site infections (SSIs). In this study, investigators recovered non-viable (i.e., lint) and viable (i.e., microorganisms) particulates during vascular surgery using a personal cascade impactor sampling device. The predominant nonviable particulates recovered during intraoperative sampling were wood pulp fibers from disposable gowns and drapes. Several potential nosocomial pathogens (e.g., Staphylococcus aureus, Staphylococcus epidermidis) and other drug-resistant isolates frequently were recovered from an area adjacent to the surgical field. The widespread presence of airborne particulates during surgery suggests that further studies are warranted to assess the role these particles may play in the development of SSIs or in dissemination of nosocomial pathogens within the OR and hospital environment.

Air Microbiology↗

PubMed1999

Transgenic animals relevant to Alzheimer's disease.

This article reviews the functional studies that have been carried out on transgenic and knockout animals that are relevant to Alzheimer's disease (AD). The discussion focuses upon the functional characterisation of these strains, particularly upon factors that affect synaptic processes that are thought to contribute to memory formation, including hippocampal long-term potentiation. We examine the use of transgenes associated with amyloid precursor protein and presenilin-1, their mutations linked to early onset familial AD, and the recent attempts to establish double transgenic strains that have an AD-like pathology which occurs with a more rapid onset. The development of new transgenic strains relevant to Alzheimer's disease has rapidly outpaced their characterisation for functional deficits in synaptic plasticity. To date most studies have focused on those transgenes linked to the minority of familial early onset rather than late-onset sporadic AD cases, and have focused on those changes linked to the induction of the early-phase of hippocampal long-term potentiation. Future studies will need to address the question of whether the development of AD pathology can be reversed or at least halted and this will be aided by the use of conditional transgenics in which genes linked to AD can either be switched on or off later in development. Furthermore, it remains to be resolved whether the deficits in synaptic function are specific to the hippocampus and whether deficits affect late-phase long-term potentiation. Nonetheless, the recent advances in genome sciences and the development of transgenic technology have provided a unique opportunity to study how genes associated with human cognitive dysfunction alter synaptic transmission between neurones in the mammalian brain.

Alzheimer Disease↗

PubMed1999

Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein.

Abnormal processing of amyloid precursor protein (APP), in particular the generation of beta-amyloid (Abeta) peptides, has been implicated in the pathogenesis of Alzheimer's disease. This study examined the consequences of deleting the APP gene on hippocampal synaptic plasticity, and upon the biophysical properties of morphologically identified neurones in APP-null mice. The hippocampus of APP-null mice had a characteristic increase in gliosis throughout the CA1 region and a disruption of staining for the dendritic marker MAP2 and the presynaptic marker synaptophysin. The disruption of MAP2 staining was associated with a significant reduction in overall dendritic length and projection depth of biocytin labeled CA1 neurones. In two groups of APP-null mice that were examined at 8-12 months, and 20-24 months of age, there was an impairment in the formation of long-term potentiation (LTP) in the CA1 region compared to isogenic age matched controls. This LTP deficit was not associated with an alteration in the amplitude of EPSPs at low stimulus frequencies (0.033 Hz) or facilitation during a 100 Hz stimulus train, but was associated with a reduction in post-tetanic potentiation. Paired-pulse depression of GABA-mediated inhibitory post-synaptic currents was also attenuated in APP-null mice. These data demonstrate that the impaired synaptic plasticity in APP deficient mice is associated with abnormal neuronal morphology and synaptic function within the hippocampus.

Aging↗

PubMed1999

Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein.

Mutations in the beta-amyloid precursor protein are strongly associated with some cases of familial Alzheimer's disease. The normal physiological role of beta-amyloid precursor protein in the brain was evaluated in a cross-sectional analysis of mice deficient in beta-amyloid precursor protein. Compared with wild-type control mice the beta-amyloid precursor protein-null mice developed age-dependent deficits in cognitive function and also had impairments in long-term potentiation. In addition, the brains of the beta-amyloid precursor protein-null mice had marked reactive gliosis in many areas, especially in the cortex and hippocampus. A subpopulation of mice (n = 15) died prematurely (between three and 18 months of age). Analysis of another six mice from the same population that were showing weight loss and hypolocomotor activity exhibited a marked reactive gliosis as detected by immunoreactivity for glial fibrillary acidic protein and a profound loss of immunoreactivities for the presynaptic terminal vesicle marker proteins synaptophysin and synapsin and the dendritic marker microtubule-associated protein-2 in many brain areas, but most predominantly in the cortex and hippocampus. These results suggest that normal beta-amyloid precursor protein may serve an essential role in the maintenance of synaptic function during ageing. A compromise of this function of the beta-amyloid precursor protein may contribute to the progression of the memory decline and the neurodegenerative changes seen in Alzheimer's disease.

Aging↗

PubMed1999

Women have increased risk of perioperative myocardial infarction and higher long-term mortality rates after lower extremity arterial bypass grafting.

PURPOSE: The purpose of this study was to determine the effect of gender on the immediate and long-term postoperative morbidity, mortality, and patency rates for infrainguinal autogenous vein bypass grafts. METHODS: Data were abstracted for consecutive patients who were followed in a prospective surveillance protocol after undergoing infrainguinal autogenous vein bypass grafting during the years 1988 to 1994. There were 165 grafts constructed in 148 patients (101 in 87 men, and 64 in 61 women). Gender differences were analyzed with Student t test or chi2 test for risk factors, indications for reconstruction, and complications. The patency rates and the long-term survival rates were compared by means of life-table analysis. Eagle criteria and long-term survival rates were compared with multivariate analysis. RESULTS: The mean follow-up period was 36 months (39 months for men, and 32 months for women), with a range of 6 to 123 months for the total follow-up period. The two groups did not differ in age at the time of operation (66.6 +/- 1.2 years for men, and 66.7 +/- 1.5 years for women) or in history of diabetes (48% for men, and 56% for women). The risks were similar for hypertension (48% for men vs 45% women), preoperative myocardial infarction (23% for men vs 26% for women), and previous coronary artery bypass grafting (9% for men vs 8% for women). The thallium stress scintigraphy results showed a diagnosis of proportionately more preoperative defects in men (reversible, 34% vs 18%, P <.05; overall, 75% vs 43%, P <.05). The 30-day limb loss rates (0.9% for men, and 0% for women) and mortality rates (2.2% for men, and 5% for women) were similar. Women had statistically more perioperative myocardial infarctions than did men (6 of 61, 9.8% vs 2 of 101, 2%; P <.05), as was documented with electrocardiography and cardiac isoenzymes. Two of these women died within a 30-day postoperative period. The 3-year primary patency rate was 85% for the men and 88% for the women, and the primary assisted patency rate was 97% for the men and 97% for the women. The secondary patency rate was 98% for the men and 97% for the women. The limb salvage rate was slightly higher for the men than for the women (93% vs 87%), although this was not statistically significant. The 5-year survival rate for women was statistically less than for men, with life-table analysis (58% for men vs 42% for women; P <.05). CONCLUSION: After distal bypass grafting, men and women have similar rates of patency and limb salvage, but women have a higher incidence rate of perioperative myocardial infarction and a decreased 5-year survival rate. These data suggest that women have unrecognized cardiac disease that affects them adversely in the perioperative period and the long term when compared with men who undergo the same operation.

Aged↗

PubMed1999

Health-related quality of life and functional outcome following arterial reconstruction for limb salvage.

Vascular surgery outcomes have traditionally been measured by limb salvage and graft patency. However, as health care resources are rationed, the patient's functional outcome and quality of life will require assessment. The in situ saphenous vein graft has proven successful in achieving long-term limb salvage for patients with critical ischemia, with the expectation of preserving a life-style and sense of well-being that would be lost with limb amputation. This study was conducted to measure functional capacity and quality of life in these patients. Seventy patients with successful in situ saphenous vein bypass grafts constructed for limb-threatening ischemia, followed for a mean of 45.6 months in a surveillance program with normal graft flow characteristics, were compared with a group of age and gender-matched controls with normal limb pressures and no history of vascular occlusive disease. A questionnaire was designed from standardized health status scales and administered to the two groups to assess symptoms, health perceptions, physical functioning and life quality. When comparing the groups of revascularized and control patients, symptoms and perceptions about their health were similar. However, the revascularized patients had significantly decreased functional capacity in their ability to walk various distances (P< or =0.005), perform household tasks (P< or =0.001) and bathe (P< or =0.001). The patient group with vascular grafts functioned as well as the controls only in activities of dressing and using the toilet. Indicators of life quality that rate independence and mobility, including the ability to procure groceries (P< or = 0.001), prepare meals (P< or =0.005) participate in social activities (P< or =0.001) and drive an automobile (P< or =0.01), were also significantly limited in the patients with successful vascular reconstructions. Although achieving long-term limb salvage and graft patency, the patients in this group of successful vascular reconstructions retain functional disabilities that require significant care. Despite these physical handicaps, these patients have a remarkably similar sense of well-being and lack of somatic complaints compared with the control group. This medical outcome study identifies the functional capacity and lifetime needs for vascular surgery patients that will provide useful data for those responsible for allocating health care resources.

Activities of Daily Living↗

PubMed1999

Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry.

PURPOSE: To evaluate catheter-directed thrombolysis for treatment of symptomatic lower extremity deep venous thrombosis (DVT). MATERIALS AND METHODS: From a registry of patients (n = 473) with symptomatic lower limb DVT, results of 312 urokinase infusions in 303 limbs of 287 patients (137 male and 150 female patients; mean age, 47.5 years) were analyzed. DVT symptoms were acute (< or = 10 days) in 188 (66%) patients, chronic (> 10 days) in 45 (16%), and acute and chronic in 54 (19%). A history of DVT existed in 90 (31%). Lysis grades were calculated by using venographic results. RESULTS: Iliofemoral DVT (n = 221 [71%]) and femoral-popliteal DVT (n = 79 [25%]) were treated with urokinase infusions (mean, 7.8 million i.u.) for a mean of 53.4 hours. After thrombolysis, 99 iliac and five femoral vein lesions were treated with stents. Grade III (complete) lysis was achieved in 96 (31%) infusions; grade II (50%-99% lysis), in 162 (52%); and grade I (< 50% lysis), in 54 (17%). For acute thrombosis, grade III lysis occurred in 34% of cases of acute and in 19% of cases of chronic DVT (P < .01). Major bleeding complications occurred in 54 (11%) patients, most often at the puncture site. Six patients (1%) developed pulmonary emboli. Two deaths (< 1%) were attributed to pulmonary embolism and intracranial hemorrhage. At 1 year, the primary patency rate was 60%. Lysis grade was predictive of 1-year patency rate (grade III, 79%; grade II, 58%; grade I, 32%; P < .001). CONCLUSION: Catheter-directed thrombolysis is safe and effective. These data can guide patient selection for this therapeutic technique.

Female↗