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L C Brown

Publications and source records attributed to L C Brown.

At least 19 recordsLinked to original sources
PubMed2004

Genetic approach to the role of cysteine proteases in the expansion of abdominal aortic aneurysms.

BACKGROUND: The elastinolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage. Cystatin C, an inhibitor of these enzymes, is expressed in arterial smooth muscle cells; an imbalance in cystatin C has been implicated in the aortic wall degeneration observed in abdominal aortic aneurysms (AAAs). The aim of the study was to investigate the impact of a polymorphism in the signal peptide of the cystatin C gene on the growth of small AAAs. METHODS: Some 424 patients with a small AAA (4.0-5.5 cm) were monitored for AAA growth by ultrasonography and provided a DNA sample for analysis of the + 148 G > A polymorphism in the cystatin C signal peptide and the-82 G > C polymorphism in the gene promoter. The median length of follow-up was 2.8 years and AAA growth rates were calculated by linear regression analysis. RESULTS: For patients of + 148 GG (n = 263), GA (n = 147) and AA (n = 20) genotypes, the mean(s.d.) AAA growth rates were 0.37(0.29), 0.37(0.23) and 0.30(0.26) cm, and initial diameters were 4.58(0.35), 4.58(0.35) and 4.62(0.36) cm, respectively. Patients of + 148 AA genotype had a slower aneurysm growth rate (unadjusted P = 0.058; after adjustment for age, sex, initial AAA diameter and smoking, P = 0.027). There also was a trend for the rare homozygotes of the-82 C allele to have slower AAA growth (adjusted P = 0.055). Smoking history had a stronger association with aneurysm growth (P = 0.003). CONCLUSION: There was a weak association between variation in the cystatin C gene and AAA growth. Medical strategies to limit AAA growth might include the inhibition of cysteine proteases.

Aged↗
PubMed2004

The UK Endovascular Aneurysm Repair (EVAR) trials: design, methodology and progress.

OBJECTIVES: The endovascular aneurysm repair (EVAR) trials aim to assess the efficacy of EVAR in the treatment of AAA in terms of mortality, quality of life, durability and cost-effectiveness. DESIGN: Male and female patients aged at least 60 years with an AAA diameter measuring at least 5.5 cm on a computed tomography (CT) scan are assessed for anatomical suitability for EVAR. Suitable patients are offered entry either into EVAR Trial 1 if they are considered fit for conventional open repair or EVAR Trial 2 if they are considered unfit. EVAR 1 randomly allocates patients to EVAR or open repair and EVAR 2 randomly allocates patients to EVAR with best medical treatment or best medical treatment alone. Target recruitment for EVAR Trials 1 and 2 is 900 and 280 patients, respectively. PROGRESS: Recruitment began in September 1999 and there are currently 40 UK centres participating in the trials. Monthly targets are being exceeded in EVAR Trial 1 with 1037 patients randomised by October 2003. EVAR Trial 2 is also meeting monthly targets with a total of 319 patients randomised. When recruitment closes in December 2003 patients will need to be followed for at least 1 year from their operation. Publication of full results for both trials is expected in mid 2005.

Aortic Aneurysm, Abdominal↗
PubMed2002

Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms.

BACKGROUND: Two clinical trials, one British and one American, have shown that early, prophylactic elective surgery does not improve five-year survival among patients with small abdominal aortic aneurysms. We report long-term outcomes in the United Kingdom Small Aneurysm Trial. METHODS: We randomly assigned 1090 patients, 60 to 76 years of age, with small abdominal aortic aneurysms (diameter, 4.0 to 5.5 cm) to one of two groups: 563 were assigned to undergo early elective surgery, and 527 were assigned to undergo surveillance by ultrasonography. Patients were followed in the trial until June 1998 and thereafter until August 2001; the mean duration of follow-up was 8 years (range, 6 to 10). RESULTS: The mean duration of survival was 6.5 years among patients in the surveillance group, as compared with 6.7 years among patients in the early-surgery group (P=0.29). The adjusted hazard ratio for death from any cause in the early-surgery group as compared with the surveillance group was 0.83 (95 percent confidence interval, 0.69 to 1.00; P=0.05). The 30-day operative mortality in the early-surgery group (5.5 percent) led to an early disadvantage in terms of survival. The survival curves crossed at three years, and at eight years, mortality in the early-surgery group was 7.2 percentage points lower than that in the surveillance group (P=0.03). There was no evidence that age, sex, or the initial size of the aneurysm modified the hazard ratio or that delayed surgery in the surveillance group increased 30-day postoperative mortality. Death was attributable to a ruptured aneurysm in 19 of the 411 men who died (5 percent) and in 12 of the 85 women who died (14 percent) (P=0.001). The rate of early cessation of smoking was higher in the early-surgery group than in the surveillance group. CONCLUSIONS: Among patients with a small abdominal aortic aneurysm, we found no long-term difference in mean survival between the early-surgery and surveillance groups, although after eight years, total mortality was lower in the early-surgery group. This difference may be attributed in part to beneficial changes in lifestyle adopted by members of the early-surgery group.

Age Factors↗
PubMed2001

Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature. In explant culture, aneurysm biopsies secrete large amounts of interleukin-6 (IL-6), and among aneurysm patients, the circulating concentration of IL-6 appears to be increased. METHODS AND RESULTS: We investigated, in 19 patients, whether aneurysm wall was an important source of circulating IL-6. We also tested the hypotheses, in 466 patients with a small aneurysm, that (1) high concentrations of circulating IL-6 signaled rapid aneurysm growth and (2) the -174 G-->C polymorphism in the IL-6 promoter predicted survival. For 19 patients with large or inflammatory aneurysms, the concentration of IL-6 was higher in the iliac arteries than the brachial arteries (median difference 26.5 pg/mL, this difference increasing with aneurysm diameter, P=0.01). In 466 patients with small aneurysms, the frequency of the -174 C allele (0.40) was similar to that in a normal healthy population. Patients of GG genotype had lower plasma concentrations of IL-6 than patients of GC and CC genotypes (medians 1.9, 4.8, and 15.6 pg/mL, respectively, Kruskal-Wallis P=0.047). Cardiovascular and all-cause mortalities were lower for patients of GG genotype than for patients of GC and CC genotype: hazard ratios 0.32 (95% CI 0.12 to 0.93), P=0.036, and 0.51 (95% CI 0.25 to 1.00), P=0.05, respectively. There was no association between plasma IL-6 or IL-6 genotype and aneurysm growth. CONCLUSIONS: Aortic aneurysms appear to be an important source of circulating IL-6, the concentration being influenced by genotype. For patients with small aneurysms, the -174 G-->C IL-6 genotype predicts future cardiovascular mortality.

Aged↗
PubMed2000

Descriptive epidemiology of de novo acute leukaemia in the Sultanate of Oman.

A hospital-based epidemiological study of de novo acute leukaemia was carried out in the Sultanate of Oman, a sparsely populated Arabian Gulf country which has undergone rapid and dramatic socio-economic changes recently. A total of 65/99 Omanis (66%) were diagnosed as acute lymphoblastic leukaemia (ALL) and 34/99 (34%) as acute myeloid leukaemia (AML). Trends and peak values in age-specific incidence rates for ALL are generally in line with those of Western countries. The proportion of T-ALL cases is however higher than that in Caucasian populations but lower than in many non-white populations. AML frequency particularly in childhood is similar to that observed in many African countries.

Acute Disease↗
PubMed2000

Percutaneous fibrin sheath stripping versus transcatheter urokinase infusion for malfunctioning well-positioned tunneled central venous dialysis catheters: a prospective, randomized trial.

PURPOSE: To compare central dialysis catheter patency rates after stripping procedures with those after urokinase (UK) infusion. MATERIALS AND METHODS: Fifty-seven tunneled catheters with either (i) flow rates less than 250 mL/min and established baseline flow rates > or = 300 mL/min or (ii) flow rates 50 mL/min less than higher established baseline flows were prospectively randomized to undergo stripping procedures (n = 28) or UK infusion (n = 29) at 30,000 U/h via each port concurrently, for a total 250,000 U. Success and patency were determined by dialysis at normal flow rates (> or = 300 mL/min) or at the previously established higher baseline rate. Flow rates were monitored weekly. Primary patency ended with catheter malfunction or removal. Kaplan-Meier survival analysis was used to construct survival curves. RESULTS: In the stripping group, initial clinical success was 89% (25 of 28). The 15-, 30-, and 45-day primary patency rates were 75% (n = 20), 52% (n = 13), and 35% (n = 8), respectively. The median duration of additional function was 32 days (95% CI: 18-48 d). In the UK group, initial clinical success was 97% (28 of 29). The 15-, 30-, and 45-day primary patency rates were 86% (n = 21), 63% (n = 13), and 48% (n = 9), respectively. The median duration of additional patency was 42 days (95% CI: 22-153 d). The Wilcoxon test for equality detected no significant difference in the survival curves for the two treatment groups (P = .236). CONCLUSION: There is no significant difference in time to primary patency between the two methods. Both allow temporary catheter salvage in most patients.

Adult↗
PubMed1999

Inhibition of prostaglandin E2 synthesis in abdominal aortic aneurysms: implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms.

BACKGROUND: There is no treatment proven to limit the growth of abdominal aortic aneurysms, in which the histological hallmarks include inflammation and medial atrophy, with apoptosis of smooth muscle cells and destruction of elastin. METHODS AND RESULTS: Aneurysm biopsies were used for explant cultures, the preparation of smooth muscle cell cultures, and isolation of macrophages. Tissue macrophages stained strongly for cyclooxygenase 2. Prostaglandin E2 (PGE2) concentrations in aneurysm tissue homogenates, conditioned medium from explants, and isolated macrophages were 49+/-22 ng/g, 319+/-38 ng/mL, and 22+/-21 ng/mL, respectively. PGE2 inhibited DNA synthesis and proliferation in normal aortic smooth muscle cells (IC50, 23.2+/-3.8 and 23.6+/-4.5 ng/mL, respectively). In smooth muscle cells derived from aneurysmal aorta, PGE2 also caused cell death, with generation of oligonucleosomes. Conditioned medium from the mixed smooth muscle and monocyte cultures derived from explants also had potent growth-inhibitory effects, and fractionation of this medium showed that the growth-inhibitory molecule(s) coeluted with PGE2. In explants, indomethacin 10 micromol/L or mefenamic acid 10 micromol/L abolished PGE2 secretion and significantly reduced IL-1beta and IL-6 secretion. In a separate case-control study, the expansion of abdominal aortic aneurysms was compared in 15 patients taking nonsteroidal anti-inflammatory drugs and 63 control subjects; median growth rates were 1.5 and 3.2 mm/y, respectively, P=0.001. CONCLUSIONS: The adverse effects of PGE2 on aortic smooth muscle cell viability and cytokine secretion in vitro and the apparent effect of anti-inflammatory drugs to lower aneurysm growth rates suggest that selective inhibition of PGE2 synthesis could be an effective treatment to curtail aneurysm expansion.

Adolescent↗
PubMed1999

Risk factors for aneurysm rupture in patients kept under ultrasound surveillance. UK Small Aneurysm Trial Participants.

OBJECTIVE: To investigate risk factors associated with aneurysm rupture using patients randomized into the U.K. Small Aneurysm Trial (n = 1090) or monitored for aneurysm growth in the associated study (n = 1167). SUMMARY BACKGROUND DATA: The U.K. Small Aneurysm Trial has shown that ultrasound surveillance is a safe management option for patients with small abdominal aortic aneurysms (4.0 to 5.5 cm in diameter), with an annual rupture rate of 1%. METHODS: In the cohort of 2257 patients (79% male), aged 59 to 77 years, 103 instances of abdominal aortic aneurysm rupture were identified during the 7-year period of follow-up (1991-1998). Almost all patients (98%) had initial aneurysm diameters in the range of 3 to 6 cm, and the majority of ruptures (76%) occurred in patients with aneurysms > or =5 cm in diameter. Kaplan-Meier survival and Cox regression analysis were used to identify baseline risk factors associated with aneurysm rupture. RESULTS: After 3 years, the annual rate of aneurysm rupture was 2.2% (95% confidence interval 1.7 to 2.8). The risk of rupture was independently and significantly associated with female sex (p < 0.001), larger initial aneurysm diameter (p < 0.001), lower FEV1 (p = 0.004), current smoking (p = 0.01), and higher mean blood pressure (p = 0.01). Age, body mass index, serum cholesterol concentration, and ankle/brachial pressure index were not associated with an increased risk of aneurysm rupture. CONCLUSIONS: Within this cohort of patients, women had a threefold higher risk of aneurysm rupture than men. Effective control of blood pressure and cessation of smoking are likely to diminish the risk of rupture.

Aged↗
PubMed1999

Et Tu, Counselor: may an in-house attorney file a qui tam action against the attorney's employer?

Most corporations probably do not consider their in-house counsel to be potential qui tam threats. That may be a naive assumption. Case law provides an illustrative view of the legal ramifications involved when an attorney brings a qui tam suit. In general, there is no prohibition on attorneys who wish to bring these actions. Nevertheless, a corporation can take preventive steps to eliminate the likelihood of attorney qui tam actions. In addition, the corporation can take advantage of state professional ethics laws to mount a defensive action against the attorney who files any such action.

Confidentiality↗
PubMed1995

Special report on patient care. The new federal patient-dumping regulations: some commonly asked questions and answers.

Until both providers and government surveyors become more familiar with the new EMTALA regulations, there will be an uncomfortable period of adjustment, and perhaps some turmoil as well, particularly regarding the new requirement that facilities who receive suspicious transfers report those transfers to HCFA. Providers should carefully examine their internal policies on discharge and transfer of emergency patients to assure that those policies are consistent with the new regulations. Particular attention should be given to inservice training for medical and support personnel in the emergency department, because they must precisely comply with the law and their errors can subject the hospital to costly investigations and potential fines of $50,000 for each violation.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1995

As outcomes measurement and management become widespread, providers should beware of legal pitfalls.

Until new statutes and court decisions clarify the law applicable to outcomes research, providers will continue to face new questions. In the meantime, paying careful attention to satisfying the requirements of existing laws protecting peer review information will put providers in the best position to minimize their exposure. Providers should review their current outcomes measurement and management systems to ensure that (1) they are structured to take full advantage of the confidentiality protections available under state law, and (2) appropriate access to outcomes data for those who need it is clearly provided for in the relevant documentation.

Confidentiality↗
PubMed1995

The Delta Dental case: "Fair procedure" comes to managed care. Delta Dental Plan of California v. Banasky.

All providers contemplating managed care contracts, both individual and institutional, should carefully review the health plans' internal administrative review and dispute resolution procedures before making their decisions, especially if the contracts will represent significant income for the provider. While there may be judicial recourse in California and in other states that adopt the holding in Delta Dental, in other states providers may well be held to the health plans' internal administrative decisions as a matter of contractual agreement. Health plans should also review their own policies and procedures for adequacy under applicable state law. The health care community will not know the full extent of Delta Dental's implications until later cases area decided, but for now it seems certain that another wave of change in this area is just beginning.

California↗
PubMed1994

Reversibility of tachyphylaxis to C5A in guinea pig tissues, perfused human placental lobule, and umbilical artery.

The spasmogenic effect of C5a is mediated by histamine and/or eicosanoids. Tachyphylaxis to this effect of C5a occurs rapidly, but the spasmogenic effects of C5a on a guinea pig lung parenchymal strips, field-stimulated ventricular papillary muscle, and human umbilical artery were completely restored by a 1-h period of drug-free rest, whereas that of guinea pig ileum was not. Perfusion of the isolated human placental lobule with C5a caused a transient pressor response that was largely abolished by indomethacin (5 microM), indicating mediation by cyclooxygenase metabolites. This pressor response to C5a was also completely restored following a 1-h rest period. The results show that tissue rest reverses tachyphylaxis to the spasmogenic effects of C5a in tissues where the response is mediated by cyclooxygenase metabolites. Where the response is mediated by histamine released by mast cells, restoration does not occur, presumably because of the catastrophic nature of mast cell degranulation. Histamine released in guinea pig papillary muscle by C5a may be from non-mast-cell sources.

Animals↗