Long-term function and manovolumetric characteristics after ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: Long-term pouch function and physiological characteristics after ileal pouch-anal anastomosis (IPAA) are poorly described. The aim of this study was to undertake a prospective investigation of long-term pouch function and manovolumetric characteristics. METHODS: Forty-two patients with a median follow-up of 16 years after IPAA were included. Function was assessed using a questionnaire and a score was calculated ranging from 0 to 15 (15 being the worst). Manovolumetry was performed and pouchitis recorded. A paired analysis was conducted, as the results were compared with previous data for each patient. RESULTS: The median functional score was 3.5 (range 0-10) at 2 years and 5 (range 1-11) at 16 years (P = 0.013). Resting anal canal pressures were higher (P < 0.001) and squeeze pressures lower (P = 0.008) at long-term follow-up. Ileal pouch volumes at distension pressures of 10, 20 and 40 cm H(2)O were diminished at 16 years (P < 0.001, P = 0.005 and P = 0.058 respectively). The volume and pressure for first sensation and urge to defaecate were reduced. Increased age correlated positively with a poor functional score. A history of pouchitis did not affect functional or physiological characteristics. CONCLUSION: Ileal pouch function declines in the long term. The reasons are unclear, but the ageing process may have an impact.

The place for colectomy and ileorectal anastomosis: a valid surgical option for ulcerative colitis?

BACKGROUND: Conflicting views regarding the use of ileorectal anastomosis (IRA) in ulcerative colitis (UC) exist and this controversy prompted us to review our experience, especially against the background of the current tendency to choose the ileal pouch-anal procedure (IPAA). METHODS: Thirty-two consecutive patients with IRA were studied. Complications, failure rate, reasons for failure and functional results were assessed. The median follow-up time was 3.5 years. RESULTS: The overall complication rate was 28%. The rectum was excised in 4 patients, indicating a failure rate of 12%. The mean daily evacuation frequency was 5.6. Despite urgency occurring in one-third of the patients, continence function was well preserved. CONCLUSIONS: Employed on a selective basis, IRA is a safe procedure with low mortality and morbidity and good prospects for success in many patients with UC. The patients must be prepared to submit to life-long rectoscopy surveillance.

Serum lipids, lipoprotein(a) level, and apolipoprotein(a) isoforms as prognostic markers in patients with coronary heart disease.

OBJECTIVE: Our objective was to study prognostic factors for death in patients with coronary heart disease (CHD), focusing on serum lipids and lipoproteins. DESIGN AND SUBJECTS: The study subjects were 964 patients with angina pectoris who underwent coronary angiography between 1985 and 1987. Follow-up, including survival and cause of death, was carried out in April 1998. RESULTS: A total of 363 patients died. Increasing age, diabetes and low levels of HDL cholesterol and of apolipoprotein (apo) AI were associated with increased risk of total mortality and cardiac mortality. In men, low levels of LDL cholesterol and of apoB were associated with increased risk of death, but not of cardiac death only; high levels of lipoprotein(a) [Lp(a)] were not associated with increased risk. In women, however, there was a trend towards increased risk with increasing Lp(a) levels (P = 0.054); the smallest isoform of apo(a) was associated with a twofold increase in risk. In women, but not in men, risk decreased with increasing molecular weight of the apo(a) isoforms. CONCLUSIONS: Amongst lipoprotein variables, low levels of HDL cholesterol and of apoAI and the presence of low-molecular weight isoforms of apo(a) are associated with increased risk of death in patients with CHD. Apo(a) isoforms and Lp(a) levels seem to be more important as risk factors amongst women. Low LDL cholesterol and apoB levels were associated with increased risk, but only in men. These findings demonstrate the importance of a gender-specific analysis of risk factors for CHD.

Proteoglycans contribution to association of Lp(a) and LDL with smooth muscle cell extracellular matrix.

Lp(a) interference with fibrinolysis could contribute to atherothrombosis. Additionally, accumulation of Lp(a) and LDLs, could lead to cholesterol deposition and foam cell formation in atherogenesis. The interactions between Lp(a) and LDL could cause their entrapment in the extracellular matrix of lesions. We found that association of Lp(a) with matrix secreted by cultured human arterial smooth muscle cells increased 2 to 3 times the subsequent specific binding of radioactive LDL. Chondroitin sulfate proteoglycans seem responsible for formation of the specific matrix-Lp(a) and matrix-LDL aggregates. The proteoglycans appeared also to participate in a cooperative increase of radioactive LDL binding to matrix pretreated with Lp(a). In the matrix preincubated with LDL, approximately 50% of the additional lipoprotein was bound by ionic interactions. In the matrix preincubated with Lp(a), 20% of the additional LDL was held by ionic bonds, and the rest was held by strong nonionic associations. Binding analysis in physiological solutions confirmed that chondroitin sulfate-rich proteoglycans from the smooth muscle cell matrix have a high affinity for Lp(a) and LDL. The results provide an explanation to the observed localization of Lp(a) and LDL in the extracellular matrix of arterial lesions and suggest a mechanism for their cooperative accumulation there.

N-acetylcysteine treatment lowers plasma homocysteine but not serum lipoprotein(a) levels.

High levels of lipoprotein(a) (Lp(a)) or homocysteine in plasma have both been associated with an increased risk for premature cardiovascular disease. For both components, the plasma levels are primarily genetically determined, and they have been very restintant to therapeutic approaches. It has been suggested that N-acetylcysteine (NAC) breaks disulphide bonds in Lp(a) as well as between homocysteine and plasma proteins. In the present study we analyze if this mechanism, in vivo, could be used to lower plasma concentrations of Lp(a) and homocysteine. Treatment with NAC and placebo was performed in a double blind cross over design with 2 weeks wash-out between treatments. Eleven subjects with high plasma Lp(a) (> 0.3 milligram) were recruited from the Lipid Clinic at Sahlgren's Hospital, Göteborg, Sweden. Main outcome measures were treatment effects on plasma Lp(a) and plasma amino thiols (homocysteine, cysteine and cysteinyl glycine). There was no significant effect on plasma Lp(a) levels. Plasma thiols were significantly reduced during treatment with NAC: homocysteine by 45% (P < 0.0001), cysteinyl glycine by 24% (P < 0.0001) and cysteine by 11% (P = 0.0002). The high dose of NAC was well tolerated. In conclusion NAC has no effect on plasma Lp(a) levels while the reduction in homocysteine is considerable and might be of clinical significance in cases with high plasma homocysteine levels.

Recombinant human insulin-like growth factor-I decreases serum lipoprotein(a) concentrations in normal adult men.

OBJECTIVE: Lipoprotein(a) is a lipoprotein fraction associated with atherosclerosis. The serum concentration of lipoprotein(a) has been shown to be mainly genetically determined but recently evidence for hormonal regulation has been presented. The aim of the present study was to investigate the effects of insulin-like growth factor-I on serum lipoproteins, especially lipoprotein(a). DESIGN: The effects of one week of IGF-I treatment were studied in an open trial. SUBJECTS: Ten healthy men, who participated in a pharmacokinetic study, were given recombinant human insulin-like growth factor-I (40 micrograms/kg/day) as daily subcutaneous injections. MEASUREMENTS: Serum samples for measurements of lipoproteins were taken after an overnight fast before and after 7 days of treatment. RESULTS: There was decrease in serum lipoprotein(a) concentration (18.5 +/- 5.5%) in nine of the subjects, and a slight increase in one of the subjects with the lowest concentrations. Also serum apolipoprotein (b) (6.3 +/- 2.2%), serum cholesterol (10.6 +/- 1.8%) and serum triglyceride (14.8 +/- 4.8%) concentrations decreased. An unexpected finding was that fasting serum glucose concentrations increased (13 +/- 4%). CONCLUSION: Insulin-like growth factor-I is involved in the regulation of lipoprotein(a) concentrations, which might have novel therapeutic implications.