Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An enzyme-linked immunosorbent spot (ELISPOT) assay for interferon gamma production has been used to analyze specific T cell responses to a Flu 9-mer peptide, and a 9-mer peptide of carcinoembryonic antigen (CEA). Assays were performed on peripheral blood mononuclear cells (PBMC) of HLA-A2-positive patients with CEA-expressing carcinomas, both before and after vaccination with CEA-based vaccines, and from HLA-A2-positive healthy blood donors. The ELISPOT assay utilized aliquots of frozen PBMC, and assays were performed after 24 h in culture with peptide to rule out any artifacts due to long-term in vitro stimulation cycles. An internal standard was used for each assay to define reproducibility of the assay, and all samples from a given patient (pre- and post-vaccination, with both the Flu and CEA peptides) were analyzed simultaneously. The results indicated a trend towards healthy blood donors having higher levels of Flu-specific T cell precursors than do colon carcinoma patients, but these results were not statistically significant (P = 0.06). On the other hand, slightly higher CEA-specific T cell responses were observed in cancer patients with CEA-expressing carcinomas than in healthy blood donors. PBMC from two CEA-based vaccine clinical trials were analyzed for T cell responses to the same CEA peptide and to the Flu control peptide. The first trial consisted of three monthly vaccinations of CEA peptide (designated PPP) in adjuvant. The second trial consisted of cohorts receiving three monthly vaccinations of avipox-CEA recombinant (designated AAA) or cohorts receiving a primary vaccination with recombinant vaccinia-CEA followed by two monthly vaccinations with avipox-CEA (designated VAA). Few, if any, CEA-specific T cell responses were seen in the PPP vaccinations, while the majority of patients receiving the poxvirus CEA recombinants demonstrated increases in CEA-specific T cell responses and no increases in Flu-specific responses. CEA-specific IgG responses were also demonstrated in patients following recombinant CEA poxvirus vaccinations. Statistical analyses of the T cell responses to the same CEA peptide demonstrated a P value of 0.028 for the recombinant poxvirus vaccines, as compared with the peptide vaccine. There were no differences seen (P = 0.37) in Flu-specific responses after these two types of CEA vaccination. These results thus provide the first evidence that poxvirus recombinant-based vaccines are more potent in the initiation of tumor-antigen-specific T cell responses than vaccines employing peptide in adjuvant, when assays are conducted in an identical manner, and in defining responses to the same peptide. These results also demonstrate for the first time that an ELISPOT assay, performed over a 24-h period and without in vitro sensitization, can be successfully used to monitor immune responses to a tumor-associated antigen in cancer patients.
Cancer Immunol Immunother 2000 Dec
PMID:The use of a rapid ELISPOT assay to analyze peptide-specific immune responses in carcinoma patients to peptide vs. recombinant poxvirus vaccines. 1112 22

Prospective studies evaluating risk factors for abdominal aortic aneurysm are few. We studied the association of life-style factors with risk for abdominal aortic aneurysm among 29,133 male smokers 50-69 years of age, participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. During a mean follow-up of 5.8 years, 181 were diagnosed with ruptured abdominal aortic aneurysm or nonruptured abdominal aortic aneurysm plus aneurysmectomy. Risk for abdominal aortic aneurysm was positively associated with age [relative risk (RR) = 4.56, 95% confidence interval (CI) = 2.42-8.61 for > 65 vs < or = 55 years], smoking years (RR = 2.25, 95% CI = 1.33-3.81 for > 40 vs < or = 32 years), systolic blood pressure (RR = 1.92, 95% CI = 1.13-3.25 for > 160 vs < or = 130 mmHg), diastolic blood pressure (RR = 1.80, 95% CI = 1.05-3.08 for > 100 vs < or = 85 mmHg), and serum total cholesterol (RR = 1.85, 95% CI = 1.09-3.12 for > 6.5 vs < or = 5.0 mmol/liter). High-density lipoprotein cholesterol showed a strong inverse association with risk for aortic aneurysm (RR = 0.16, 95% CI = 0.08-0.32 for > 1.5 vs < or = 0.9 mmol/liter). High energy intake was associated with lower risk for aortic aneurysm (RR = 0.59, 95% CI = 0.38-0.94 for the highest quartile vs the lowest), whereas no associations with nutrients were evident. We conclude that classical risk factors for atherosclerotic diseases seem to be important in pathogenesis of large abdominal aortic aneurysms.
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PMID:Life-style factors and risk for abdominal aortic aneurysm in a cohort of Finnish male smokers. 1167 8

Antioxidants may retard atherogenesis and limit inflammatory processes involved in aneurysm formation. We evaluated effects of alpha-tocopherol and beta-carotene supplementation on incidence of large abdominal aortic aneurysm (AAA) in a randomised, double-blind, placebo-controlled trial. Subjects (n=29133) were 50-69-years-old male smokers, participants in the Finnish alpha-Tocopherol, beta-Carotene Cancer Prevention (ATBC) Study. They were randomised to receive either 50 mg/day of alpha-tocopherol, or 20 mg/day of beta-carotene, or both, or placebo in a 2x2 design. Incidence of AAA was evaluated from mortality and hospital registers. During 5.8 years of follow-up, 181 men were diagnosed with either ruptured AAA (n=77) or nonruptured large AAA treated with aneurysmectomy (n=104). Relative risk (RR) for AAA was 0.83 (95% confidence interval [CI] 0.62-1.11) among men receiving alpha-tocopherol compared with those who did not, and 0.93 (95% CI 0.69-1.24) among men receiving beta-carotene compared with those who did not. A modest though nonsignificant decrease in risk for nonruptured AAA was observed among alpha-tocopherol supplemented men (RR 0.71, 95% CI 0.48-1.04) compared with men not receiving alpha-tocopherol. For beta-carotene, RR for nonruptured AAA was 0.86 (95% CI 0.59-1.27) compared with men not receiving beta-carotene. Neither antioxidant affected risk for ruptured AAA. In conclusion, long-term supplementation with alpha-tocopherol or beta-carotene had no preventive effect on large AAA among male smokers.
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PMID:Alpha-tocopherol (vitamin E) and beta-carotene supplementation does not affect the risk for large abdominal aortic aneurysm in a controlled trial. 1142 17

The management of concomitant abdominal aortic aneurysm and intra-abdominal malignancies is still disputed; whether to treat the lesions simultaneously or as staged procedures being the main controversy. Abdominal aortic aneurysm associated with renal carcinoma is rare and combined aneurysm repair and nephrectomy appears to be the treatment of choice in selected patients. We report a case where the surgical management of simultaneously occurring abdominal aortic aneurysm and renal carcinoma was complicated by the presence of a duplicated inferior vena cava. The rationale for the treatment of this patient and the technical difficulties of the surgical procedure are discussed and a review of the literature to date is reported.
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PMID:Management of synchronous abdominal aortic aneurysm and renal carcinoma associated with duplication of the inferior vena cava. 1156 1

PTEN, a tumor suppressor gene, has been found to be inactivated by structural abnormalities or epigenetic changes in several types of human cancers. Recently, several studies have also suggested the possibility that the PTEN gene is a target of genomic instability in human cancers displaying microsatellite instability (MSI). To investigate the role of PTEN in human oral squamous cell carcinomas, we screened the entire coding region sequences and examined the expression of the PTEN gene in 81 oral cancers displaying microsatellite stability (MSS) and 5 oral cancers displaying MSI. Mutation of the PTEN gene was identified in one MSS cancer (1/81; 1.2%) and three MSI cancers (3/5; 60%). The MSS cancer harbored a missense mutation from Ala (GCA) to Val (GTA) at codon 137. Of the MSI cancers containing the PTEN mutation, case 36 had a missense mutation from Lys (AAA) to Glu (GAA) at codon 254, case 43 contained a frameshift mutation (one A deletion) in a 6 bp poly(A) tract affecting codon 265-267, and case 64 harbored two missense mutations from Val (GTG) to Ala (GCG) at codon 222, and from Gly (GGA) to Arg (AGA) at codon 230 indicating biallelic mutation of PTEN. Genomic deletion of exon 5, resulting in loss of PTEN mRNA, was observed in two MSS cancers. In spite of an intact PTEN gene, one MSS and one MSI cancer lacked PTEN mRNA. These findings suggest that the inactivation of PTEN by either mutation or loss of transcript plays a role in the pathogenesis of some oral cancers (8/86; 9.3%). Furthermore, inactivation of PTEN was far more frequent in MSI oral cancers (4/5; 80%) than in MSS oral cancers (4/81; 4.9%).
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PMID:Inactivation of the PTEN gene by mutation, exonic deletion, and loss of transcript in human oral squamous cell carcinomas. 1237 Jul 46

Background. Studies of medical admissions have questioned the validity of using claims data to adjust for preexisting medical conditions (comorbidities), but the impact of using comorbidities from claims data to risk-adjust mortality rates for high-risk surgery is not well characterized. The purpose of this study was to evaluate the relationship between comorbidities and mortality in administrative data in surgical populations and identify better risk-adjustment methods. Methods. Using the national Medicare database (1994-1997), we identified admissions for elective abdominal aortic aneurysm repair (140,577) and pancreaticoduodenectomy (10,530). We calculated the relative risk of mortality (adjusted for age, sex, race, and admission acuity) for 5 chronic conditions that are known (from clinical series) to increase the risk of postoperative mortality and are commonly used in claims-based risk-adjustment models. To explore the potential value of alternative risk-adjustment strategies, we examined relationships between surgical mortality and comorbidities using diagnosis codes identified from previous admissions. Results. Overall, in-hospital mortality for elective abdominal aortic aneurysm (AAA) repair and pancreaticoduodenectomy were 5.1% and 10.4%, respectively. For both procedures, 3 of the 5 comorbidities were associated with decreased risk of mortality: prior myocardial infarction (MI) [RR = 0.38; 95% confidence interval (CI), 0.33-0.43 for AAA; RR = 0.38; 95% CI, 0.21-0.69 for pancreaticoduodenectomy), malignancy (RR = 0.67; 95% CI, 0.59-0.76 for AAA; RR = 0.74; 95% CI, 0.45-1.21 for pancreaticoduodenectomy], and diabetes (RR = 0.76; 95% CI, 0.64-0.84 for AAA; RR = 0.59; 95% CI, 0.49-0.69 for pancreaticoduodenectomy). Using comorbidities identified from prior admissions increased the mortality risk estimates for prior MI (RR = 1.22; 95% CI, 1.08-1.38 for AAA; RR = 0.80; 95% CI, 0.49-1.30 for pancreaticoduodenectomy) and diabetes (RR = 1.41; 95% CI, 1.25-1.59 for AAA; RR = 0.94; 95% CI, 0.78-1.14 for pancreaticoduodenectomy). Conclusions. Because comorbidities coded on the index admission appear protective, incorporating them in risk-adjustment models for studies comparing surgical performance may penalize providers for taking care of sicker patients. When available, comorbidity information from prior hospitalizations may be more useful for risk adjustment.
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PMID:Adjusting surgical mortality rates for patient comorbidities: more harm than good? 1246 61

Renal transplant recipients are at increased risk of malignancy and infection. We present the case of a 72-year-old-man with recurrent bladder carcinoma, abdominal aortic aneurysm repair, and end-stage renal failure due to renovascular disease. He received a cadaveric renal allograft into his left iliac fossa, was given cyclosporin A, azathioprine, and prednisolone triple therapy immunosuppression, and had no rejection episodes. He presented four years post-transplantation with a two-year history of intermittent sweats and fevers. Previous episodes had been investigated with no firm diagnosis made. This time he had right iliac fossa pain of three weeks' duration. Examination revealed a tender mass. Investigations showed unchanged graft function, but elevated inflammatory indices. Ultrasonography and computed tomography detailed an infiltrating mass associated with the sigmoid colon, which colonoscopy failed to visualise. At laparotomy a 6-cm tumor was removed, with adherent sigmoid colon and bladder dome. Macroscopically the mass was an abscess, and microscopy found acute and chronic inflammatory giant cells and fibrillary masses suggestive of actinomycosis, with no malignancy. The patient recovered uneventfully on antibiotics. At six months' follow-up, examination, inflammatory markers, and radiographic imaging showed no evidence of recurrence. Twelve months later the patient died of rupture of his proximal abdominal aorta. There was no evidence of recurrence at postmortem examination. We conclude with a brief review of actinomycosis in transplant recipients.
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PMID:An unusual abdominal mass in a renal transplant recipient. 1253 66

Abdominal aortic aneurysm repair in patients undergoing chronic hemodialysis presents several surgical difficulties due to tissue fragility, accelerated atherosclerosis, and calcification of the aorta. In addition to these surgical procedure-related problems, anemia, electrolyte abnormalities, bleeding tendency, and susceptibility to infection were also critical issues in perioperative management. The aim of this study was to examine the surgical outcome of abdominal aortic aneurysm repair in patients undergoing chronic hemodialysis. Between January 1988 and August 2001, six patients undergoing chronic hemodialysis underwent repair of an abdominal aortic aneurysm. There were five males and one female, and the mean age was 65 years. Two of the six patients had bilateral common iliac artery aneurysms in addition to the abdominal aortic aneurysm. At the time of abdominal aortic aneurysm repair, the duration of hemodialysis had ranged from 3 to 109 months, with a mean of 34 months. All patients underwent hemodialysis on the day prior to the abdominal aortic aneurysm repair operation. The first postoperative hemodialysis was scheduled to be performed on the day after operation or later. The mean duration of operation was 291 min. Blood transfusion was required in all patients. The first postoperative hemodialysis was performed between the first and third postoperative days. Postoperative complications were: ileus in one, and atrial fibrillation and blue toe syndrome just after operation in one. There was no hospital death. The follow-up period was 56 months. One patient died of lingual cancer at 102 months after operation. Five patients are alive. Abdominal aortic aneurysm repair can be done in patients on chronic hemodialysis with an acceptable early and long-term outcome.
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PMID:Surgical outcome of abdominal aortic aneurysm repair in patients undergoing chronic hemodialysis. 1264 75

Treatment options for crescentic glomerulonephritis include the use of steroids, cytotoxic therapy, and, in severe cases, intravenous immunoglobulins and plasmapheresis. Injury and lysis of capillary glomerular basement membrane, which is made up of type IV collagen, laminin, fibronectin, and proteoglycans, by serine proteinases and matrix metalloproteinases (MMPs) likely is an important participant in the pathogenesis of crescentic glomerulonephritis. Tetracycline derivatives inhibit not only the activity of MMPs, but also their production, and have been investigated for the treatment of disorders in which the MMP system becomes amplified, such as degenerative osteoarthritis, periodontitis, cancer, and abdominal aortic aneurysm. We report an interesting case of crescentic glomerulonephritis in a young man who was treated with cyclophosphamide and prednisone. The patient developed steroid-induced acne that was treated with long-term oral doxycycline therapy. During the period the patient was administered doxycycline, proteinuria decreased by 70% and recurred when doxycycline was stopped. To our knowledge, this is the first report of possible benefits of a metalloproteinase inhibitor (doxycycline) in glomerulonephritis in humans. Future studies are urgently required to explore the option of metalloproteinase inhibitors in the treatment of proliferative glomerulonephritis.
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PMID:Doxycycline decreases proteinuria in glomerulonephritis. 1290 Aug 22

We report a novel nucleolar interaction between the AAA ATPase p97/VCP and the Werner protein (WRNp), a member of the RecQ helicase family. p97/VCP mediates several important cellular functions in eucaryotic cells, including membrane fusion of the endoplasmic reticulum and Golgi and ubiquitin-dependent protein degradation. Mutations in the WRN gene cause Werner syndrome, a genetic disorder characterized by premature onset of aging symptoms, a higher incidence of cancer, and a high susceptibility to DNA damage caused by topoisomerase inhibitors. We observed that both WRNp and valosin-containing protein (VCP) were present in the nucleoplasm and in nucleolar foci in mammalian cells and that WRNp and p97/VCP physically interacted in the nucleoli. Importantly, the nucleolar WRNp/VCP complex was dissociated by treatment with camptothecin, an inhibitor of topoisomerase I, whereas other WRNp-associated protein complexes, such as WRNp/Ku 80, were not dissociated by this drug. Because WRN syndrome cells are sensitive to topoisomerase inhibitors, these observations suggest that the VCP/WRNp interaction plays an important role in WRN biology. We propose a novel role for VCP in the DNA damage response pathway through modulation of WRNp availability.
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PMID:DNA damage modulates nucleolar interaction of the Werner protein with the AAA ATPase p97/VCP. 1293 74


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