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Biomedical subjects

Gorav Ailawadi

Publications and source records attributed to Gorav Ailawadi.

At least 19 recordsLinked to original sources
PubMed2006

The nitric oxide donor DETA-NONOate decreases matrix metalloproteinase-9 expression and activity in rat aortic smooth muscle and abdominal aortic explants.

Our objective was to examine the role of an exogenous nitric oxide (NO) donor, DETA-NONOate (DETA), on matrix metalloproteinase (MMP)-9, MMP-2, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 expression and activity in interleukin (IL)-1beta-induced rat aortic smooth muscle cells (RA-SMCs) and rat aortic explants (RAEs). RA-SMCs were incubated with IL-1beta (2 ng/ml), an inflammatory cytokine known to induce MMP-9 expression, and increasing concentrations of DETA (0, 1.0, 10, 100 microM; n = 3/group) for 48 hr. RAEs were incubated with IL-1beta (2 ng/mL) and increasing concentrations of DETA (0, 5.0, 50, 100, and 500 microM; n = 3/group) for 48 hr. Media were collected and assayed for NO(x) by the Griess reaction and MMP-9 activity by zymography. Messenger RNA (mRNA) was extracted from cells and analyzed for MMP-9, MMP-2, and TIMP-1 expression levels by quantitative real-time reverse-transcriptase polymerase chain reaction. All statistical analyses were performed by analysis of variance. In RA-SMCs and RAEs, DETA administration resulted in a dose-dependent increase in media NOx concentration (RA-SCM p < 0.01, RAE p < 0.01) and a concurrent decrease in both MMP-9 expression (RASMC p = 0.01, RAE p = 0.01) and activity (RASMC p = 0.04, RAE p = 0.006). There were no significant differences seen in MMP-2 and TIMP-1 expression or activity in response to DETA exposure. DETA decreased IL-1beta-induced MMP-9 expression and activity in both RA-SMCs and RAEs in a dose-dependent fashion. In addition, DETA administration had no effect on MMP-2 or TIMP-1 expression or activity in vitro. These data suggest that NO donors may be beneficial in decreasing MMP-9 levels and might serve to inhibit MMP-9-dependent vessel wall remodeling seen during abdominal aortic aneurysm formation.

Animals↗
PubMed2006

Clinical experience with radiotracer-guided thoracoscopic biopsy of small, indeterminate lung nodules.

BACKGROUND: Although computed tomography lung-screening programs report a 31% to 51% incidence of subcentimeter pulmonary nodules, 85% are too small to biopsy or interrogate with positron emission spectroscopy scans. We developed a technique using transthoracic percutaneous radiotracer injection with thoracoscopic radioprobe localization and excision for small pulmonary nodules. This report describes our series of the first 46 patients evaluated with this technique. METHODS: Forty-six patients (79% smokers; 52% males; median age, 64 years) were evaluated. Patient selection was based on the surgeon's anticipated difficulty in thoracoscopically locating small nodules because of lesion size or location. Computed tomographic-guided injection of radiotracer solution was made into or adjacent to the nodule the day of surgery. Intraoperative gamma probe localization, followed by thoracoscopic excision of the lesion, was subsequently performed. RESULTS: Median nodule size was 9 mm (range, 3 to 22 mm), and median depth was 5 mm (range, 0 to 50 mm). Forty-four (96%) of the lesions were successfully localized and excised. Median time from injection to surgery was 270 minutes. Failures were the result of inadvertent pleural or chest wall radiotracer placement. Forty-six percent (21 of 46) of the lesions were malignant, of which 71% (15 of 21) were primary lung cancers. Patients with lung cancer underwent lobectomy or segmentectomy. Fourteen of 15 were stage IA, whereas 1 was stage IIIB (6 mm primary with 4 mm intralobar metastasis). Complications were three pneumothoraces at the time of radiotracer injection. CONCLUSIONS: Computed tomography-guided radiotracer localization of small pulmonary nodules combined with thoracoscopic excisional biopsy is feasible and safe. This technique successfully localized and excised the nodule in 96% of cases.

Biopsy↗
PubMed2006

A biologic basis for asymmetric growth in descending thoracic aortic aneurysms: a role for matrix metalloproteinase 9 and 2.

OBJECTIVE: This study was undertaken to define matrix metalloproteinase (MMP) expression in the anterior and posterior wall of descending thoracic aortic aneurysms (TAAs) and correlate it with specific computed tomography (CT) image sites within the descending thoracic aorta. METHODS: Serial CT images of patients with TAAs were compared with age- and gender-matched normal descending thoracic aortas at levels T4-T12. The mean circumference of the TAAs was 153 mm (n = 12) and 148 mm (n = 11) at T8 and T10, respectively, compared with 75 mm (n = 12) and 75 mm (n = 10) in controls (P < .001). Aortic tissue was collected from a separate set of eight patients undergoing descending TAA resection (processed < or =12 hours of excision) and six cadavers (processed < or =24 hours of death). Tissue collected between the intercostals arteries was defined as posterior wall, and directly opposite was the anterior wall. MMP-9 and MMP-2 messenger RNA (mRNA) extracted from aortic tissue was analyzed by quantitative real time polymerase chain reaction (PCR) and normalized to beta-actin. Immunohistochemistry was performed for MMP-9 and MMP-2. CT aortic measurements and MMP expression were compared by t tests and analysis of variance, respectively. RESULTS: The ratio of arc distance between the intercostals on the posterior wall to total aortic circumference was 0.14 in healthy controls compared with 0.08 in TAAs at vertebral level T8 (P = .001). At T10, the ratio was 0.15 in healthy controls compared with 0.11 in TAAs (P = .001). MMP-9 expression in TAAs was 4.3-fold higher in the anterior wall compared with the posterior wall (P = .03). Conversely, MMP-2 expression in TAAs was 3.2-fold higher in the posterior wall compared with the anterior wall (P = .008). MMP expression was not detected in control cadaver aortas. CONCLUSION: Anterior walls of expanding TAAs grow at a greater rate than the posterior wall, as determined from the lower ratio of intercostal arc distance to total circumference in TAAs. Differential MMP expression appears to be a biologic marker for asymmetric growth in the TAA wall. CLINICAL RELEVANCE: The pathogenesis of thoracic aortic aneurysms (TAAs) is poorly understood. Multiple lines of evidence suggest that matrix metalloproteinases (MMPs), a family of enzymes, are important in aneurysm development. Earlier experiments documented a regional variation of MMP-9 in stimulated rodent aortas, with production greater in the abdominal aorta compared with the thoracic aorta. The present study extends that observation and documents asymmetric aneurysm development in the TAA wall, with increased anterior wall growth in correlation to increased MMP-9 production. An improved understanding of the mechanisms by which MMP production is regulated is critical.

Aortic Aneurysm, Thoracic↗
PubMed2005

Neutrophil depletion inhibits experimental abdominal aortic aneurysm formation.

BACKGROUND: Neutrophils may be an important source of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two matrix-degrading enzymes thought to be critical in the formation of an abdominal aortic aneurysm (AAA). The purpose of this investigation was to test the hypothesis that neutrophil depletion would limit experimental AAA formation by altering one or both of these enzymes. METHODS AND RESULTS: Control, rabbit serum-treated (RS; n=27) or anti-neutrophil-antibody-treated (anti-PMN; n=25) C57BL/6 mice underwent aortic elastase perfusion to induce experimental aneurysms. Anti-PMN-treated mice became neutropenic (mean, 349 cells/microL), experiencing an 84% decrease in the circulating absolute neutrophil count (P<0.001) before elastase perfusion. Fourteen days after elastase perfusion, control mice exhibited a mean aortic diameter (AD) increase of 104+/-14% (P<0.0001), and 67% developed AAAs, whereas anti-PMN-treated mice exhibited a mean AD increase of 42+/-33%, with 8% developing AAAs. The control group also had increased tissue neutrophils (20.3 versus 8.6 cells per 5 high-powered fields [HPFs]; P=0.02) and macrophages (6.1 versus 2.1 cells per 5 HPFs, P=0.005) as compared with anti-PMN-treated mice. There were no differences in monocyte chemotactic protein-1 or macrophage inflammatory protein-1alpha chemokine levels between groups by enzyme-linked immunosorbent assay. Neutrophil collagenase (MMP-8) expression was detected only in the 14-day control mice, with increased MMP-8 protein levels by Western blotting (P=0.017), and MMP-8-positive neutrophils were seen almost exclusively in this group. Conversely, there were no statistical differences in MMP-2 or MMP-9 mRNA expression, protein levels, enzyme activity, or immunostaining patterns between groups. When C57BL/6 wild-type (n=15) and MMP-8-deficient mice (n=17) were subjected to elastase perfusion, however, ADs at 14 days were no different in size (134+/-7.9% versus 154+/-9.9%; P=0.603), which suggests that MMP-8 serves only as a marker for the presence of neutrophils and is not critical for AAA formation. CONCLUSIONS: Circulating neutrophils are an important initial component of experimental AAA formation. Neutrophil depletion inhibits AAA development through a non-MMP-2/9-mediated mechanism associated with attenuated inflammatory cell recruitment.

Animals↗
PubMed2005

Gender differences in rat aortic smooth muscle cell matrix metalloproteinase-9.

BACKGROUND: A predilection exists for men to develop abdominal aortic aneurysms (AAAs), but the reasons for this gender predisposition are not known. Matrix metalloproteinase-9 (MMP-9) has been implicated in both human and experimental AAAs. This investigation tested the hypothesis that male and female gender differences exist in the production of MMP-9 by rat aortic smooth muscle cells (RASMCs). STUDY DESIGN: In the first set of experiments, cultured male and female RASMCs were stimulated with interleukin-1 beta (IL-1beta) at 2 ng/mL. Messenger RNA was extracted from the RASMCs and gene expression of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1), an MMP-9 inhibitor, was measured by quantitative real-time polymerase chain reaction. Cell culture media were collected for measurement of MMP-9 protein levels and MMP-9 activity by Western blotting and gelatin zymography, respectively. In the second set of experiments, male RASMCs were treated with 17-beta-estradiol (10(-10) to 10(-6) mol/L) and MMP-9 activity was measured. In the third set of experiments, male rats were pretreated with estradiol, and MMP-9 activity was measured in the media from explanted aortas. RESULTS: MMP-9 gene expression was 10-fold higher in male versus female RASMCs (p=0.003). MMP-9 protein levels (p=0.005) and gelatinolytic activities (p=0.01) were also greater in male than female RASMCs. TIMP-1 expression was fourfold higher in male versus female RASMCs (p<0.001). Estradiol-treated male RASMCs did not exhibit a decrease in MMP-9 activity. But aortic explants from male rats pretreated with 17-beta-estradiol had 60% less MMP-9 activity than explants from male controls (p=0.03). CONCLUSIONS: MMP-9 and TIMP-1 are greater in male than in female RASMCs. These findings support the tenet that gender-related differences in MMP-9 may contribute to AAA formation.

Animals↗
PubMed2005

Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic aneurysms.

BACKGROUND: Selective estrogen receptor modulators (SERMs), similar to estrogens, possess vasoprotective effects by reducing release of reactive oxygen species. Little is known about the potential effects of SERMs on the pathogenesis of abdominal aortic aneurysms (AAAs). This study's objective was to investigate the growth of experimental AAAs in the setting of the SERM tamoxifen. METHODS: In the first set of experiments, adult male rats underwent subcutaneous tamoxifen pellet (delivering 10 mg/kg/day) implantation (n = 14) or sham operation (n = 16). Seven days later, all animals underwent pancreatic elastase perfusion of the abdominal aorta. Aortic diameters were determined at that time, and aortas were harvested 7 and 14 days after elastase perfusion for immunohistochemistry, real-time polymerase chain reaction, Western blot analysis, and zymography. In the second set of experiments, a direct irreversible catalase inhibitor, 3-amino-1,2,4-triazole (AT), was administered intraperitoneally (1 mg/kg) daily to tamoxifen-treated (n = 6) and control rats (n = 6), starting on day 7 after elastase perfusion. Aortic diameters were measured on day 14. In a third set of experiments, rats were perfused with catalase (150 mg/kg) after the elastase (n = 5), followed by daily intravenous injections of catalase (150 mg/kg/day) administered for 10 days. A control group of rats (n = 7) received 0.9% NaCl instead of catalase. RESULTS: Mean AAA diameters were approximately 50% smaller in tamoxifen-treated rats compared with sham rats 14 days after elastase perfusion (P = .002). The tamoxifen-treated group's aortas had a five-fold increase in catalase mRNA expression (P = .02) on day 7 and an eight-fold increase in catalase protein on day 14 (P = .04). Matrix metalloprotroteinase-9 activity was 2.4-fold higher (P = .01) on day 7 in the aortas of the controls compared to the tamoxifen-treated group's aortas. Tamoxifen-treated rats had approximately 40% fewer aortic polymorphonuclear neutrophils compared to controls on day 7 (P = .05). Administration of the direct catalase inhibitor AT to tamoxifen-treated rats partially reversed the aneurysm inhibitory effect of tamoxifen by nearly 30% (P = .02). In contrast, catalase administration inhibited AAA formation by 44% (P = .002). CONCLUSIONS: The selective estrogen receptor modulator tamoxifen inhibits the development of AAAs in male rats in association with an up-regulation of catalase and inhibition of aortic wall neutrophil infiltration.

Amitrole↗
PubMed2004

Gender differences in experimental aortic aneurysm formation.

OBJECTIVE: It is hypothesized that a male predominance, similar to that in humans, persists in a rodent model of experimental abdominal aortic aneurysm (AAA) via alterations in matrix metalloproteinases (MMPs). METHODS AND RESULTS: Group I experiments were as follows: elastase perfusion of the infrarenal aorta was performed in male (M) and female (F) rats. At 14 days, aortas were harvested for immunohistochemistry, real-time polymerase chain reaction (PCR), and zymography. Group II experiments were the following: abdominal aorta was transplanted from F or M donors into F or M recipients. At 14 days, rodents that had undergone transplantation underwent elastase perfusion. In group III, male rats were given estradiol or sham 5 days before elastase perfusion. In group I, M rats had larger AAAs with higher frequency than did F rats. M rat aortas had more significant macrophage infiltrates and increased matrix metalloproteinase (MMP)-9 production and activity. In group II, M-to-M aortic transplants uniformly developed aneurysms after elastase perfusion, whereas F-to-F aortic transplants remained resistant to aneurysm formation. F aortas transplanted into M recipients, however, lost aneurysm resistance. In group III, estradiol-treated rats demonstrated smaller aneurysms and less macrophage infiltrate and MMP-9 compared with M controls after elastase. CONCLUSIONS: These data provide evidence of gender-related differences in AAA development, which may reflect an estrogen-mediated reduction in macrophage MMP-9 production.

Animals↗
PubMed2004

Attending, house officer, and medical student perceptions about teaching in the third-year medical school general surgery clerkship.

BACKGROUND: There has been declining interest in surgery among medical students and one reason might be the third-year clerkship experience. The aim of this study was to clarify the perceptions and expectations of attendings, residents, and medical students on the clerkship experience. STUDY DESIGN: A survey was distributed to all general surgery attendings, the entire general surgery house staff, and an entire third year medical school class inclusive of the 2001-2002 academic year at a single institution. Statistic analysis consisted of chi-square and Kruskal-Wallis-ANOVA on ranks with Dunn's test for multiple comparisons. A p < 0.05 was significant. RESULTS: Responses were obtained from 59 attending surgeons (50%), 38 surgical residents (32%), and 107 medical students (66%). Of this student cohort, 35% were planning to choose a surgical specialty as a career. Agreement was high among faculty, students, and residents about factors considered important in evaluation, expectations of skills, and level of skills needed before the clerkship. Medical students desired more hours of instruction, believed they performed fewer procedures per week, and thought that feedback was poor compared with the opinions of faculty and residents (p < 0.002). Nearly 50% of medical students believed they were an inconvenience to the service; 30% of house officers and 27% of faculty (p < 0.001) believed this also. Almost all faculty and residents, however, wanted medical students on the service (> 95%). Faculty believed residents did a better job teaching than either the students or residents themselves did (p < 0.001), and students thought that residents were the primary source of education in patient care. CONCLUSIONS: Considerable differences exist between faculty, surgical resident, and medical student perceptions and expectations of medical student education. Structured direct faculty contact, definition of medical student roles on the surgical team, and more consistent feedback can be rapidly improved.

Attitude of Health Personnel↗
PubMed2004

Common celiacomesenteric trunk: aneurysmal and occlusive disease.

Eighteen patients (14 men, 4 women), ages 24 to 77 years, with a common celiacomesenteric trunk (CMT) were treated between 1965 and 2004 at the University of Michigan. Four patients had CMT aneurysmal or occlusive disease that led to operative treatment. Pertinent arteriographic findings in these 4 patients included a CMT aneurysm (n = 2), an occluded proximal CMT (n = 1), and a type III aortic dissection that was compressing the CMT (n = 1). Therapy in these 4 patients included placement of a polytetrafluoroethylene bypass graft from the supraceliac aorta to the CMT (n = 2) or a Dacron bypass graft from a thoracoabdominal bypass to the CMT (n = 1), and endovascular fenestration of the septum between the true and false lumens of an aortic dissection at the level of the CMT (n = 1).

Adult↗
PubMed2004

Early MT-1 MMP expression following elastase exposure is associated with increased cleaved MMP-2 activity in experimental rodent aortic aneurysms.

OBJECTIVE: The objective of this study was to determine the significance of membrane type 1 matrix metalloproteinase (MT1-MMP) activation of MMP-2 in experimental abdominal aortic aneurysms. METHODS: Rat aortas were perfused with either saline as a control or elastase, and harvested on 2, 4, or 7 days after perfusion (n = 5 per treatment group/day). Aortic MT1-MMP and MMP-2 expression and protein were determined by real time polymerase chain reaction and Western blotting, respectively. Aortic explants were used to measure MMP-2 activity by zymography. Rat aortic smooth muscle cells in vitro were exposed to increasing doses of elastase and analyzed for MT-1 MMP expression. RESULTS: Aneurysms formed in 80% of the elastase-perfused aortas at 7 days, whereas none formed in the saline-perfused aortas. Significantly increased MT1-MMP expression was observed only on day 4, when levels were 6.5-fold higher in elastase-perfused aortas compared with saline-perfused aortas (P < .01). By day 7, MT1-MMP protein was present only in the elastase-perfused aortas (P = .02). By immunohistochemistry, MT1-MMP was detectable only in the elastase-perfused group at day 7. Cleaved MMP-2 activity (P = .045) was increased in elastase-perfused aortas compared with saline perfused aortas at day 7. In rat aortic smooth muscle cells, MT-1 MMP expression increased in response to elastase (P = .02). CONCLUSION: The rodent aortic aneurysm model exhibits upregulation of MT1-MMP expression and protein with subsequent increased conversion of MMP-2 from the latent to the cleaved form.

Animals↗
PubMed2004

Increased MMP-9 expression and activity by aortic smooth muscle cells after nitric oxide synthase inhibition is associated with increased nuclear factor-kappaB and activator protein-1 activity.

OBJECTIVE: To determine the mechanism underlying increased expression and activity of matrix metalloproteinase 9 (MMP-9) by rat aortic smooth muscle cells (RA-SMC) after inhibition of inducible nitric oxide synthase (iNOS). METHODS AND RESULTS: Treatment of interleukin-1beta-stimulated RA-SMC with aminoguanidine led to an increase of 96% in MMP-9 activity (P = 0.003) by gelatin zymography, a 40% increase in pro-MMP-9 protein (P = 0.018) by Western blot, and a 155% increase in MMP-9 mRNA (P = 0.06) by reverse transcription polymerase chain reaction. Aminoguanidine also caused a 26% decrease in cytosolic IkappaB levels (P = 0.014) by Western blot, as well as a 97% increase in nuclear factor-kappaB binding and a 216% increase in activator protein-1 binding as measured by electrophoretic mobility shift assay. No significant changes were noted in MMP-2 or TIMP-1 expression, protein levels, or activity after aminoguanidine administration. CONCLUSIONS: MMP-9 expression and activity is increased in cytokine stimulated RA-SMCs after iNOS inhibition, coincident with activation of the nuclear factor-kappaB and activator protein-1 pathways. We speculate that local derangements in iNOS may favor MMP-9-dependent vessel wall damage in vivo via an inflammatory cascade mechanism.

Animals↗
PubMed2003

Ultrasound measurement of aortic diameters in rodent models of aneurysm disease.

BACKGROUND: This investigation was undertaken to evaluate transabdominal ultrasound (US) measurements of aortic diameters in rats and mice as a complementary method to video microscopy (VM), the current standard for assessing the diameter of rodent aortas. METHODS: Aortic diameters were measured in 64 rats (n = 132 sets) and 12 mice (n = 36 sets) following experimental induction of aortic aneurysms. Diameters were measured at the renal vein, midinfrarenal aorta, and aortic bifurcation. RESULTS: In the rat, anteroposterior (AP) US measurements were closely correlated with transverse VM measurements, with correlation coefficients ranging from 0.66 to 0.77 (P < 0.0001) for axial US images and 0.58 to 0.63 (P < 0.0001) for sagittal US images. In the mouse, significant correlation coefficients were 0.57 (P < 0.001) near the renal vein and 0.44 (P = 0.007) at the midinfrarenal aorta. Aortic diameters increased significantly with increasing animal age and weight (R = 0.40, P = 0.003 at the renal vein, R = 0.29, P = 0.04 in the midinfrarenal aorta, and R = 0.39, P = 0.004 at the aortic bifurcation), suggesting that weight matched rodents must be used to define aortic dimensions in treatment groups as opposed to repeated comparisons with baseline measurements in a growing rat. CONCLUSION: Noninvasive aortic US measurements throughout the course of a rodent study of aneurysmal disease provide a practical alternative to VM for the repeated determinations of aortic diameters.

Animals↗
PubMed2003

National variation in operative mortality rates for esophageal resection and the need for quality improvement.

HYPOTHESIS: Operative mortality rates for esophageal resection vary across hospital volume groups in a nationally representative sample of hospitals. DESIGN: Cross-sectional study of all adult patients in the Nationwide Inpatient Sample who underwent esophageal resection from 1995 through 1999 (N = 3023). Operative mortality was determined for hospital volume quartiles (low, <3 per year; medium, 3-5 per year; high, 6-16 per year; very high, >16 per year). Multiple logistic regression of in-hospital mortality was used for case-mix adjusted analyses. SETTING: Hospitals performing at least 1 esophageal resection from 1995 through 1999 in the Nationwide Inpatient Sample. PATIENTS: Patients having esophageal resection from 1995 through 1999 in the Nationwide Inpatient Sample. RESULTS: Overall mortality was 8.2% and varied 3-fold from 11.8% to 3.7% across hospital volume groups (P<.001). In the case-mix-adjusted multivariate analysis, having surgery at a low-volume hospital (odds ratio, 2.9; 95% confidence interval, 1.7-4.9; P<.001) or medium-volume hospital (odds ratio, 2.4; 95% confidence interval, 1.4-4.3; P =.002) was associated with an increased risk of mortality compared with the reference group of very high-volume hospitals. The effect of volume on mortality was significant for both malignant and benign disease. Given the absolute risk difference of 8.1% between very high- and low-volume hospitals, only 12 patients would need to be referred to prevent 1 death after esophageal resection. CONCLUSIONS: The operative mortality rate for esophageal resection varies across hospitals in the United States. To improve the quality of care and reduce operative mortality rates for patients in need of esophageal surgery, patients should either be referred to higher-volume hospitals, or quality improvement should be directed at lower-volume hospitals.

Aged↗
PubMed2003

101 laparoscopic splenectomies for the treatment of benign and malignant hematologic disorders.

BACKGROUND: Laparoscopic splenectomy (LS) is the surgical approach of choice for patients with hematologic disorders requiring splenectomy. Patients with idiopathic thrombocytopenic purpura (ITP) have normal to slightly enlarged spleens and benefit the most from LS. METHODS: We reviewed the perioperative outcomes in 101 patients who underwent LS between May 1996 and December 2002. Patients were divided into three groups--ITP, other benign, and malignant hematologic disorders--and compared. RESULTS: The ITP patients (n = 48) had significantly smaller spleens and operative times compared with the other groups. Splenomegaly in the other benign (n = 23) and malignant hematologic disorders (n = 30) groups was responsible for higher open conversion rates and greater need for hand-assisted laparoscopic splenectomy (HALS). CONCLUSIONS: Laparoscopic splenectomy and HALS can be performed with good results for benign and malignant hematologic disorders. The benefits of HALS are similar to LS, so there should be a low threshold for HALS in patients with large spleens.

Case-Control Studies↗
PubMed2003

A nonintrinsic regional basis for increased infrarenal aortic MMP-9 expression and activity.

OBJECTIVE: This investigation was undertaken to determine whether intrinsic or regional factors at different anatomic sites of the aorta affect expression and activity of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). METHODS: Aortas from Sprague-Dawley rats (n = 22) were divided into arch, descending thoracic, and infrarenal abdominal segments. Specimens were stimulated with interleukin-1beta (IL-1beta) (2 ng/mL) for 72 hours. In separate experiments, syngeneic aortic segments were transplanted from the thoracic or abdominal aortas of donor rats into the infrarenal aortic position of recipient rats (n = 12 each). At 4 weeks, aortas from rats who had received transplants were harvested, sectioned into arch, thoracic, and transplanted thoracic or transplanted abdominal segments, and stimulated with IL-1beta. Reverse transcriptase polymerase chain reaction, zymography, and reverse zymography were performed to assess MMP-9, MMP-2, and TIMP-1 in all aortic segments. Differences were assessed with analysis of variance (ANOVA) and post-hoc Tukey test. RESULTS: In control rats, abdominal segments had significantly higher MMP-9 expression compared with arch and thoracic segments (P <.002). Total MMP-9 activity was also higher in abdominal segments (P <.02). In rats who received transplants, transplanted thoracic (P <.004) and transplanted abdominal (P <.05) segments demonstrated upregulation of MMP-9 expression, compared with control arch and thoracic segments. Zymography documented increased total MMP-9 activity in transplanted thoracic (P <.03) and transplanted abdominal (P <.04) segments versus arch and thoracic segments. No significant difference in MMP-9 expression was found between control abdominal, transplanted thoracic, or transplanted abdominal segments. No significant differences in MMP-2 or TIMP-1 expression or activity were demonstrated in either control or transplanted segments. CONCLUSIONS: These data demonstrate that variations in aortic MMP-9 expression and activity result from regional factors affecting the aorta rather than intrinsic aortic wall differences. Increases in abdominal aortic MMP-9 may contribute to the predilection for aneurysm to develop in the infrarenal aorta.

Actins↗
PubMed2003

Gadolinium as a nonnephrotoxic contrast agent for catheter-based arteriographic evaluation of renal arteries in patients with azotemia.

OBJECTIVE: This study was undertaken to determine the effect of gadolinium arteriography on renal function and its diagnostic accuracy in patients with azotemia with suspected renovascular disease. METHODS: Catheter-based digital subtraction arteriographic studies with gadolinium as the contrast agent were performed on 25 occasions in 21 consecutive patients with azotemia to evaluate renal arterial circulation. Gadolinium (gadodiamide, 287 mg/mL) was the only contrast used in these studies. Quantities of gadolinium administered ranged from 40 to 264 mL (mean +/- standard deviation, 124 +/- 74 mL). Serial determinations of renal function were performed in all patients. Arteriography was undertaken 20 times after prior renal revascularizations: seven times as a routine postoperative follow-up study, nine for increasing azotemia, three for worsening hypertension, and once for evaluation of a known renal artery stenosis in patient with an abdominal aortic aneurysm. Three additional arteriograms were performed as part of an evaluation for suspected renovascular hypertension. The two remaining arteriograms were performed in patients with known aortic aneurysms in whom renal artery stenosis was suspected. RESULTS: No adverse changes in renal function followed gadolinium arteriography. Prearteriography serum creatinine values ranged from 1.6 to 9.1 mg/dL (3.0 +/- 1.4 mg/dL), compared with postangiography values that ranged from 1.2 to 8.4 mg/dL (2.9 +/- 1.3 mg/dL). Comparable blood urea nitrogen values ranged from 23 to 71 mg/dL (40.1 +/- 13.5 mg/dL) before arteriography and from 21 to 68 mg/dL (36.5 +/- 13.3 mg/dL) after arteriography. All 38 renal arteries evaluated were adequately imaged. First-order and second-order branchings were well visualized on selective renal studies. Twenty-one renal arteries showed no abnormalities, including six of seven reconstructed arteries subjected to early postoperative evaluation. Twelve renal arteries manifested significant disease, including seven with stenoses and five that had become occluded. Among five additional renal arteries studied, two exhibited obstructing thrombus, two had dissections, and one had a kinked aortorenal bypass graft. CONCLUSION: Catheter-based arteriography in patients with azotemia with gadolinium as a contrast agent is a safe and effective means to evaluate the renal arterial circulation. The preferential use of gadolinium in lieu of nephrotoxic iodinated contrast agents for catheter-based arteriography in patients with azotemia is supported by this experience.

Adult↗
PubMed2003

Endovascular treatment of aortic aneurysms in patients with renal transplants.

Endovascular treatment of an abdominal aortic aneurysm was undertaken in two orthotopic renal transplant recipients with US Food and Drug Administration-approved aortic stents without specific measures taken to protect the transplanted kidney. Renal function remained unchanged in both patients. Follow-up imaging studies showed successful aneurysm exclusion. Endovascular abdominal aortic aneurysm treatment in renal transplant recipients does not appear to place the transplanted kidney at undue ischemic risk and may be the preferred approach in select patients.

Aged↗