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Biomedical subjects

A M Graham

Publications and source records attributed to A M Graham.

At least 19 recordsLinked to original sources
PubMed2000

alpha-melanocyte-stimulating hormone modulates nitric oxide production in melanocytes.

We have previously observed that melanocytes produce nitric oxide in response to ultraviolet radiation and lipopolysaccharide and in this study have examined how these responses are affected by alpha-melanocyte-stimulating hormone. Nitric oxide production by cultured cells was measured electrochemically in real time using an ISO-nitric oxide sensor probe. B16 mouse melanoma cells released nitric oxide in response to lipopolysaccharide and the effects were enhanced in cells that had been grown in the presence of 10-11-10-9 M alpha-melanocyte-stimulating hormone prior to stimulation. At concentrations in excess of 10-9 M alpha-melanocyte-stimulating hormone decreased nitric oxide production. Preincubation with lipopolysaccharide, a well-known inducer of inducible nitric oxide synthase, also increased nitric oxide production but this response was reduced by alpha-melanocyte-stimulating hormone. alpha-Melanocyte-stimulating hormone also increased the levels of nitric oxide produced in response to ultraviolet radiation (20-100 mJ per cm2) in B16 cells. The same effect was seen in human melanocytes and as this was inhibited by aminoguanidine would appear to involve an induction of inducible nitric oxide synthase. Reverse transcription-polymerase chain reaction showed that melanocytic cells express inducible nitric oxide synthase mRNA. Western blotting analysis and immunocytochemistry confirmed the presence of inducible nitric oxide synthase protein in B16 cells and FM55 human melanoma cells and that the levels were increased in response to alpha-melanocyte-stimulating hormone. alpha-Melanocyte-stimulating hormone, however, decreased inducible nitric oxide synthase protein expression, which occurred in response to lipopolysaccharide. These results suggest that alpha-melanocyte-stimulating hormone regulates nitric oxide production in melanocytic cells by modulating the induction of inducible nitric oxide synthase. Additional experiments showed that nitric oxide increased melanin production by B16 cells and human melanocytes. This is in keeping with a melanogenic role for nitric oxide but whether its production by melanocytes in response to alpha-melanocyte-stimulating hormone is associated with such a role or whether it has some other significance relating to melanocyte differentiation or in mediating immunomodulatory actions of alpha-melanocyte-stimulating hormone remains to be seen.

Adolescent↗
PubMed2000

Predictors of health after revascularization for extremity ischemia.

BACKGROUND: To assess the impact of surgical revascularization for lower extremity ischemia, we determined (with the use of the SF-36 health survey) the functional health status of patients who underwent either inflow or outflow procedures. METHODS: The SF-36 survey was given prospectively to 104 patients before operation and at intervals ranging from 10 days to 1 year after operation from January 1998 to July 1999. To determine whether revascularization was associated with improved patient health status, mean scores were compared before and after operation by univariate and multivariate analysis. To identify the factors that influenced patient health status, we performed multiple regression analysis to test the hypothesis that outcome is affected by age, gender, time since procedure, diabetes, indication, and inflow versus outflow procedure. RESULTS: There was a significant decrease in the general health score of patients before outflow bypass as compared with inflow procedure (45.3 +/- 5.3 versus 32.1 +/- 3.3 [mean +/- SEM]; P <.05). After the procedure, only those patients who had undergone inflow procedures had improved outcome scores. Diabetes, outflow procedures, limb salvage as indication, and time since operation were determined by multiple regression affecting outcome scores to be significant factors. CONCLUSIONS: The SF-36 health survey demonstrated that diabetes, procedure type, indication, and time after procedure significantly affected the functional outcome for patients who were treated surgically for lower extremity ischemia. Despite successful revascularization, significant deficits in functional health remain in patients with lower extremity ischemia.

Aged↗
PubMed1999

Endovascular management of ureteroarterial fistula.

Ureteroarterial fistulas, although rare, appear to be increasing in frequency. Because open surgical repair may be difficult and associated with significant risk for complications, endovascular intervention may provide an attractive treatment alternative. We review the diagnosis and management of a ureteroarterial fistula and iliac pseudoaneurysm that presented with massive hematuria during ureteral stent removal. The patient was treated by means of the percutaneous embolization of the right hypogastric artery and placement of an expanded polytetrafluoroethylene stent-graft. Endovascular stent-graft placement may serve as a safe and practical alternative in the treatment of these patients, whose cases are challenging.

Angiography, Digital Subtraction↗
PubMed1998

Intrahepatic proliferation of 'naive' and 'memory' T cells during liver allograft rejection: primary immune response within the allograft.

Liver allograft rejection is mediated by a primary response of T lymphocytes, followed by infiltration of the graft with a mixed inflammatory reaction. Using single and double label immunocytochemistry, we examined the proliferation index and the phenotype of leukocytes on liver biopsies from 10 patients with acute rejection before and after treatment with i.v. steroids, 10 patients with chronic rejection, 10 patients without rejection posttransplant, and 15 nongrafted, nonimmunosuppressed patients. Proliferation of mononuclear leukocytes (assessed by expression of Ki-67, a nuclear antigen associated with the cell cycle) inside the allograft was a prominent feature of acute and chronic rejection and was down-regulated by steroid treatment. Leukocytes in cell cycle were located predominantly in the portal tracts at the site of the inflammatory infiltrate. The majority of 'naive' (CD45RA+) and 'memory' (CD45RO+) CD4+ T lymphocytes were also periportally distributed. In contrast, CD8+ T lymphocytes, CD57+ natural killer cells, and CD68+ macrophages were located intraparenchymally throughout the liver lobules, whereas CD20+ B lymphocytes were only present in some of the portal tracts. Predominantly CD4+ and occasionally CD8+ lymphocytes were proliferating (assessed by double staining). The proliferating CD4+ cells were of both naive (CD4+, CD45RA+) and memory (CD4+, CD45RO+) phenotypes. To our knowledge, this is the first description of proliferating naive T lymphocytes in situ in liver allografts. These findings suggest that there may be a primary immune response generated within the allograft as well as in draining lymphatic tissue. This implicates not only intrahepatic proliferation of T lymphocytes as a prominent feature of rejection, but also suggests that the liver has a special immunological status comparable to that of lymphatic tissue.

Adult↗
PubMed1998

Bile duct cells in primary biliary cirrhosis are 'primed' for apoptosis.

OBJECTIVE: Primary biliary cirrhosis (PBC) is characterized by progressive, immune-mediated destruction of bile ducts (<75 microm diameter) and secondary changes related to cholestasis which may involve apoptosis. In this study we sought to examine the protein expression of genes involved in apoptosis in biliary epithelium of PBC cases. DESIGN: In order to investigate the susceptibility of biliary epithelial cells to apoptosis and their ability to proliferate, we examined the expression of a number of apoptosis related proteins in early and late stage PBC and histologically normal liver control tissue using immunohistochemistry. METHODS: Liver biopsies from 15 early (stages I and II) and 14 late (stages III and IV) cases of PBC and 15 normal cases were examined immunohistochemically for expression of p53, CD95/Fas, bax, bcl-x, bcl-2 and the proliferation marker Ki-67. RESULTS: CD95/Fas, bax and bcl-x were identified in biliary epithelium in 8/15, 11/15 and 8/15 normal biopsies. Weak expression of bcl-2 was found, but p53 was not identified. In cases of PBC surviving bile ducts showed strong bax and bcl-x expression. Inflammatory infiltrates were strongly bcl-2 positive. In cases showing a marked ductular reaction there was increased reactivity for bax and bcl-x in ductules. No change in CD95/Fas or p53 expression was seen. An increase in Ki-67 positive biliary epithelial cells was seen in PBC cases, indicating cell cycle activity. CONCLUSIONS: Bile duct epithelium constitutively expresses several genes involved in the execution of apoptosis but these cells also retain the ability to proliferate.

Apoptosis↗
PubMed1998

Development of wall surface tangent DPIV measurement techniques for arterial branch models.

Experimental techniques for measuring unsteady flow in a glass arterial bifurcation model have been developed to aid in quantifying three-dimensional wall shear fluctuations associated with arterial disease. The unique feature of the current technique is the use of a "curved" laser sheet, which was everywhere tangent to the inner wall of a daughter tube in an arterial bifurcation model. Surface tangent velocity vector field measurements were made to demonstrate the potential of this technique. Ensemble-averaged data showing weak secondary flows as well as statistical distributions of flow angles are presented. Measurements of this type may be used to estimate mean and instantaneous wall shear magnitude and direction, data that are necessary for understanding the importance of circumferential motions on arterial disease.

Arterioles↗
PubMed1998

Elective aortic surgery with minimal banked blood.

It has been a historical supposition that aortic surgery, even in an elective setting, has been associated with the transfusion of large amounts of blood products. We feel that this assumption is now dated, and in fact far fewer patients now receive allogenic blood products. To assess this assumption, we carried out a retrospective chart review of all patients who underwent elective aortic surgery over an 18-month period from April 1994 to October 1995. Factors analyzed included type of procedure, blood loss, amount of Cell Saver blood replaced, need for autologous blood transfusion, and need for allogenic blood transfusion. Sixty-seven patients underwent elective aortic surgery with either an aortic tube graft (23), an aortobiiliac graft (25), or an aortobifemoral graft (19). The male:female ratio was 48:19, with a mean age of 67 years (range, 42-85 years). Mortality and morbidity were 4.4 per cent and 8.9 per cent, respectively. The average blood loss per patient was 770 cc. Cell saver was used in 65 patients, with the average amount of blood returned being 542 cc. Overall, 73 per cent of patients did not require allogenic blood transfusion, and 58 per cent did not need any type of transfusion. Of those who stored autologous blood prior to operation, none required allogenic blood perioperatively. With the new advances in autologous blood transfusion both by predeposit and salvage transfusion, we have greatly reduced the need for transfusion of allogenic blood products in patients undergoing major aortic surgery. This is reassuring, and although increasing short-term cost, will reduce the morbidity-infectious, noninfectious, and immunologic-associated in prior decades with allogenic blood transfusions. We strongly recommend the use of Cell Saver techniques, and also, where possible, patients should be encouraged to donate their own blood prior to major aortic procedures for future transfusion.

Adult↗
PubMed1998

Flow modulates endothelial regulation of smooth muscle cell proliferation: a new model.

BACKGROUND: With a co-culture model, we have previously demonstrated that endothelial cells (ECs) exert regulatory control over smooth muscle cell (SMC) behavior. ECs appeared to stimulate SMC proliferation in static culture. This study was performed to test the hypothesis that the EC stimulation of SMC proliferation was effected by shear stress. METHODS: Bovine SMCs were cultured on a thin semipermeable membrane either alone or opposite ECs in co-culture (SMC/EC). A novel parallel-plate flow device was developed and used for exposing the EC side of the co-culture to shear stress. EC and SMC proliferation rates were determined after 24 hours' exposure to 0, 1, or 10 dynes/cm2 of shear stress. RESULTS: SMC proliferation decreased significantly from 362 +/- 65 cpm/microgram DNA (control, mean +/- SEM) to 68 +/- 43 cpm/microgram (1 dyne/cm2) and 99 +/- 18 cpm/microgram (10 dynes/cm2)(P < .05). EC proliferation after flow decreased as compared with no-flow controls 71 +/- 15 cpm/micrograms DNA (control, mean +/- SEM) to 29 +/- 5 cpm/microgram (1 dyne/cm2) and 21 +/- 4 cpm/microgram (10 dynes/cm2)(P < .05). CONCLUSIONS: In a model designed to study SMC/EC interactions in a flow environment, it was seen that EC exposure to shear stress alters the growth characteristics of SMCs. This suggests that hemodynamic mechanical forces may be sufficient to alter the EC regulation of SMC behavior.

Animals↗
PubMed1997

Efficacy of prophylactic vena cava filters in high-risk trauma patients.

Severely injured trauma patients are at increased risk of pulmonary embolism (PE). Certain injuries may preclude the use of standard prophylactic measures, and even when used, these measures may be ineffective in the trauma population. We defined a group of trauma patients who are at statistically elevated risk of venous thromboembolic events. We then adopted an aggressive approach to the placement of prophylactic inferior vena cava (IVC) filters in these high-risk patients. Between January 1994 and January 1996 we treated 250 trauma patients who met our high-risk criteria. Prophylactic IVC filters were placed in 99 of these patients, and 151 received deep venous thrombosis prophylaxis with either heparin, sequential compression stockings, or a combination of these modalities. High-risk patients did not receive filters if they were unlikely to survive or showed rapid clinical improvement and were felt to not remain at high risk. The incidence of pulmonary embolism in this high-risk population was 1.6%. This is a significant reduction (p = 0.045, Fisher exact test) from the 4.8% incidence of PE in high-risk historical control patients with similar injury profiles. No patient with a prophylactic IVC filter suffered a clinically evident PE and there were no complications associated with placement of these filters. We conclude that the placement of prophylactic IVC filters in high-risk trauma patients is a safe and effective method of reducing the incidence of pulmonary embolism.

Adult↗
PubMed1997

The utility of dobutamine echocardiography in preoperative evaluation for elective aortic surgery.

BACKGROUND: Preoperative cardiac evaluations have been advocated prior to major vascular procedures to reduce the incidence of postoperative cardiac complications. This study was undertaken to evaluate the efficacy and predictive value of routine dobutamine echocardiography (DE) in the screening of patients undergoing elective aortic surgery. METHODS: Dobutamine echocardiography was performed preoperatively on all patients having elective aortic procedures by our university surgical group from June 1995 to August 1996. The cardiac morbidity and mortality from this group were compared with that of a similar group undergoing elective aortic procedures from June 1993 to May 1995 with no dobutamine echocardiography (NDE). RESULTS: Although there was no statistically significant difference in either overall mortality (4.4% in NDE vs. 2.3% in DE) or cardiac mortality (2.9% in NDE vs. 0% in DE) between the two groups, cardiac events occurred only in those patients with previous coronary artery disease. In addition, dobutamine echocardiography had a negative predictive value of 97% CONCLUSIONS: Although routine screening is not necessary, selective screening of patients using dobutamine stress echocardiography is justified because of its high negative predictive value.

Adrenergic beta-Agonists↗
PubMed1995

Symptomatic subclavian steal syndrome four decades after operation for dysphagia lusoria.

Congenital abnormalities of the aortic arch may lead to signs and symptoms of tracheal and esophageal obstruction secondary to a restrictive vascular ring. There are many case reports and monographs concerning the surgical management of dysphagia lusoria. This case provides the first example of long-term follow-up of surgical intervention for relief of dysphagia lusoria. A 45-year-old laborer presented with a several year history of episodic bilateral blindness and a more recent onset of "drop attacks." Notably this patient had presented at the age of 18 months with difficulty breathing and eating since birth. The patient also had frequent upper respiratory infections and episodes of pneumonia. Workup revealed a right-sided aortic arch with a left ligamentum arteriosum. When he was first seen in our clinic, history and physical examination revealed claudication and diminished pulses in the left upper extremity. Arteriography and duplex studies confirmed reversal of flow in the patient's left vertebral artery. The arteriogram demonstrated the presence of a right-sided aortic arch and descending aorta along with the proximal stump of the previously ligated left subclavian artery. He underwent left carotid to left axillary artery bypass for the treatment of symptomatic subclavian steal syndrome. His symptoms have resolved with return of antegrade vertebral flow and the presence of normal pulses in the left arm. Congenital aortic abnormalities that lead to tracheal and esophageal compromise are numerous and varied. Surgical management requires a thorough understanding of the person's anatomy and preoperative planning. The life expectancy of patients with dysphagia lusoria necessitates consideration of the long-term consequences of surgical intervention.

Aorta, Thoracic↗
PubMed1995

Antiphospholipid antibodies lead to increased risk in cardiovascular surgery.

BACKGROUND: Antiphospholipid (APL) antibodies are a heterogenous group of antibodies that have been associated with an increase in bleeding complications and a marked increase in thrombotic events, both of which result in significant patient morbidity and mortality. PATIENTS AND METHODS: A retrospective analysis of patients identified to be positive for APL via a university thrombosis registry who had cardiovascular surgery between 1989 and 1994. RESULTS: Seventy-one patients positive for APL antibodies were identified. Of those patients, 19 had cardiovascular surgical procedures (11 women and 8 men, mean age 58.4 years, range 38 to 78). A total of 48 cardiovascular surgical procedures (mean 2.5 procedures/patient) were performed in the 19 patients. These procedures included 13 lower-extremity reconstructions, 11 upper-extremity reconstructions/fistulas, 8 cardiac valve replacements, 5 coronary artery bypass procedures, 5 major amputations, 4 infrarenal aortic reconstructions, and 2 carotid endarterectomies. Sixteen of the 19 patients (84.2%) suffered major postoperative complications. These included 16 thrombosed grafts, 5 strokes, 5 major bleeding events, 2 pulmonary emboli, and 2 myocardial infarctions. Ultimately, 12 of the 19 patients (63.2%) died of complications related to surgery. CONCLUSIONS: This series of patients confirms that patients with circulating APL antibodies are prone to excessive postoperative morbidity and mortality after cardiovascular surgical procedures. The presence of APL antibodies may be a maker of increased risk of complications after cardiovascular surgery.

Adult↗
PubMed1995

Carotid artery duplex scanning in preoperative assessment for coronary artery revascularization: the association between peripheral vascular disease, carotid artery stenosis, and stroke.

PURPOSE: The purpose of this study was to identify high-risk populations for severe carotid artery disease (SCD) and neurologic events (NE) after nonemergency isolated coronary artery bypass graft procedures (CABG). METHODS: Between February 1989 and July 1992, 387 patients underwent preoperative carotid artery duplex scanning as part of a preoperative assessment for nonemergency cardiac procedures. Of these patients, 376 had isolated CABG, and 11 had combined carotid endarterectomy (CEA) and CABG. Patient demographics, risk factors, and preoperative neurologic symptoms were recorded and analyzed. Severe carotid artery disease was defined as a 80% or greater stenosis of either internal carotid artery by carotid artery duplex scanning. Patients were evaluated for neurologic events (cerebrovascular accident, transient ischemic attack, amaurosis fugax, or reversible ischemic neurologic deficits) during the in-hospital postoperative period. RESULTS: The prevalence of SCD was 8.5% (33 patients). The 33 patients with SCD were significantly older (65.6 +/- 6.5 years vs 62.5 +/- 10.4 years, p = 0.02), had previous CEA (27.3% vs 2.0%, p = 0.00001), had preoperative neurologic symptoms (21.2% vs 5.9%, p = 0.002), and had peripheral vascular disease (PVD) (63.6% vs 16.9%, p = 0.00001). The sensitivity of PVD for SCD is 63.6% (n = 21/33) (specificity 83.1%, positive predictive value 25.9%, negative predictive value 96.1%). In patients undergoing CABG alone, those who had postoperative NE were older (69.6 +/- 6.7 years vs 62.5 +/- 10.3 years, p = 0.036) and more likely to have PVD (50% vs 19.7%, p = 0.034), SCD (40% vs 4.9%, p = 0.001) and previous CEA (40% vs 2.7%, p = 0.0002). The incidence of postoperative NE in patients with SCD was 18.2% vs 1.7% in patients without SCD (p = 0.001). The sensitivity of SCD for NE was 40% (n = 4/10) (specificity 95.1%, positive predictive value 18.2%, negative predictive value 98.3%). CONCLUSIONS: PVD may be helpful to identify patients at high risk for severe carotid artery stenosis. Postoperative NE in patients with CABG are associated with increasing age, carotid artery stenosis greater than 80%, previous CEA, and PVD.

Adult↗
PubMed1995

Enhanced revascularisation after angiogenic stimulation in a rabbit model of bilateral limb ischaemia.

OBJECTIVE: We previously demonstrated stimulation of collateral vessel formation in a rabbit model of unilateral limb ischaemia after administration of endothelial cell growth factor (ECGF). To distinguish clearly the effects of ischaemia alone from those of ischaemia combined with angiogenic stimulation in the same animal, a model of bilateral hindlimb ischaemia was used to evaluate further the angiogenic effect of ECGF. DESIGN: Ischaemia was produced in both hindlimbs of 11 rabbits by femoral artery excision. Beginning 10 days later, ECGF (8 mg in 3 ml of saline) was injected in one hindlimb while 3 ml of saline alone was injected in the other every other day for a total of five doses. OUTCOME MEASURES: Calf systolic blood pressure was measured in both limbs on postoperative days, 10, 30, and 50. On day 50, collateral formation was quantitated angiographically, and muscle samples were obtained for quantitation of capillary density and histologic studies. RESULTS: The mean calf systolic blood pressure in the both hindlimbs was similar on day 10 (36.9 +/- 2.3 versus 38.1 +/- 2.9 mmHg) but was significantly higher in the ECGF-treated limb on day 30 (68.9 +/- 3.1 versus 45.0 +/- 2.9 mmHg) and day 50 (83.0 +/- 3.0 versus 57.0 +/- 1.7; p < 0.0001 for both comparisons). On day 50, collateral vessels were significantly more numerous in the ECGF-treated limb (17.2 +/- 1.6 versus 11.0 +/- 0.8; p < 0.0006), as were capillaries (225.9 +/- 11.4 versus 159.6 +/- 12.9 per mm2; p < 0.002). CONCLUSION: Local administration of ECGF enhanced collateral development leading to significantly improved perfusion in the treated as compared with the untreated limb in the same animal. Exogenous administration of an angiogenic mitogen can upregulate the normal collateral response to ischaemia and may be useful in treating severe limb ischaemia.

Angiography↗