Persisting anorectal dysfunction after rectal cancer surgery.

AIM: Sphincter-saving rectal cancer management affects anorectal function. This study evaluated persisting anorectal dysfunction and its impact on patients' well-being. METHOD: Seventy-nine patients with a follow-up of 12-37 (median 22) months and 79 age- and sex-matched control subjects completed questionnaires. RESULTS: The median number of diurnal bowel movements was three in patients and one in controls (P < 0.0001). Nocturnal defaecation occurred in 53% of patients. The median Vaizey score was 8 in patients and 4 in controls (P < 0.0001). Urgency without incontinence was reported by 47% of patients and 49% of controls (P = 0.873), soiling by 28% of patients and 3% of controls (P < 0.0001), incontinence for flatus by 73% of patients and 49% of controls (P = 0.0019), and incontinence for solid stools by 16% of patients and 4% of controls (P = 0.0153). Incontinence of liquid stools occurred in 17 of 20 patients and in one of five controls who had liquid stools (P = 0.0123). Incontinence for gas, liquid or solid stool occurred once or more weekly in 47%, 19% and 6% of patients respectively. Evacuation difficulties were reported by 98% of patients, but also by 77% of controls. Neoadjuvant radio(chemo)therapy adversely affected defaecation frequency and continence. Incontinence was associated with severe discomfort in 50% of patients, severe anxiety in 40% and severe embarrassment in 48%. CONCLUSION: Anorectal dysfunction is a frequent problem after management of rectal cancer with an impact on the well-being of patients.

Treatment options to improve anorectal function following rectal resection: a systematic review.

AIM: Common problems after rectal resection are loose stools, faecal incontinence, increased frequency and evacuation difficulties, for which there are various therapeutic options. A systematic review was conducted to assess the outcome of treatment options aimed to improve anorectal function after rectal surgery. METHOD: Publications including a therapeutic approach to improve anorectal function after rectal surgery were searched using the following databases: MEDLINE, PubMed, EMBASE, Pedro, CINAHL, Web of Science, PsychInfo and the Cochrane Library. The focus was on outcome parameters of symptomatic improvement of faecal incontinence, evaluation of defaecation and quality of life. RESULTS: The degree of agreement on eligibility and methodological quality between reviewers calculated with kappa was 0.85. Fifteen studies were included. Treatment options included pelvic floor re-education (n=7), colonic irrigation (n=2) and sacral nerve stimulation (SNS) (n=6). Nine studies reported reduced incontinence scores and a decreased number of incontinent episodes. In 10 studies an improvement in resting and squeeze pressure was observed after treatment with pelvic floor re-education or SNS. Three studies reported improved quality of life after pelvic floor re-education. Significant improvement of the Fecal Incontinence Quality of Life Scale was found in three studies after SNS. CONCLUSION: Conservative therapies such as pelvic floor re-education and colonic irrigation can improve anorectal function. SNS might be an effective solution in selected patients. However, methodologically qualitative studies are limited and randomized controlled trials are needed to draw evidence-based conclusions.

Do posture and straining influence urinary-flow parameters in normal women?

The influence of posture of the pelvis and straining on urinary flow was investigated in 21 normal women, mainly physiotherapists, who were asked to urinate on an uro-flow chair at their usual time and frequency. Subjects were at random instructed to urinate in five different test situations: anteversion, anteversion with straining, retroversion, retroversion with straining, and forward bending without straining. The urinary-flow parameters investigated were volume, peak flow, time to peak, peak-to-end time, total time, and mean flow. The analysis was done by means of analysis of variance but only for micturition volumes >150 mL. The morphology of the urinary-flow curves was examined for the presence of irregularities and increasing (after top) or decreasing (for top) curve tops and after-dribbling. Results demonstrated no significant differences for peak flow, total time, and mean flow in the anteversion, retroversion, and the forward-bending position. This holds for test situations and re-test controls. However, straining increased the peak flow and mean flow rates in all positions and in all women, whereas it reduced the total voiding time. The voided volumes were lowest in anteversion. Irregularities were less frequent in the forward-bending position. It can be concluded that the forward-bending position is the most preferable urinating position to relax the pelvic floor muscles. Neurourol. Urodynam. 19:3-8, 2000.

Composition and structural and functional properties of discoidal and spherical phospholipid-apoE3 complexes.

To model the common structural unit in the system of reverse cholesterol transport, we studied the composition, structure, and physicochemical properties of complexes generated between dipalmitoylphosphatidylcholine (DPPC) or palmitoyllinoleoylphosphatidylcholine (PLPC) and apoE3 in the absence and in the presence of cholesterol (Chol); the data were compared with similar experiments using apoA-I, the major proteins of high-density lipoproteins. The conformation and organization of lipid-binding domains of apoE3 within the complexes were calculated by computer modeling. The transition temperatures of DPPC within discoidal complexes with mean diameters of 116 A (GGE) or 148 A (EM) were higher for complexes versus liposomes both in the absence and in the presence of Chol. Association of apoE3 with DPPC resulted in a more structured state of the apolipoprotein molecule versus the soluble apolipoprotein; this state was characterized by parallel orientation of alpha-helixes of apoE3 and DPPC acyl chains. Substrate efficiency of the apoE3-PLPC-Chol complexes in the lecithin-cholesterol acyltransferase (LCAT) reaction expressed as Vmax/Km was 0.5 mole cholesteryl esters/h per 1 microM. The transformation of discoidal apoE3-DPPC-Chol complexes into spherical particles was induced by LCAT and accumulation of cholesteryl esters was approximately 62% of the total cholesterol. Parallel orientation of phospholipid acyl chains with helical segments disappeared in these particles. Discoidal apoE3-DPPC complexes incorporated unesterified cholesterol released from Chol-loaded J774 macrophages. The data support the concept that association of apoE3 and apoA-I with phospholipids is qualitatively similar due to similar orientation of helical repeats in the C-terminal domains of apoE3 and apoA-I.

Structural and functional properties of apolipoprotein B in chemically modified low density lipoproteins.

The structural and compositional changes occurring during in vitro chemical modification of apolipoprotein B-100 (apo B), the apolipoprotein component of low density lipoproteins (LDL), were investigated in this study. The functional properties of chemically modified apo B and especially its potential to induce accumulation of cholesterol esters in macrophages were related to the structural changes of apo B. Acetylation, maleylation or malondialdehyde conjugation did not significantly affect the lipid composition of LDL. However, the unsaturated cholesteryl esters content, especially that of cholesteryl arachidonate was significantly decreased through Cu-oxidation. The number of reactive lysine residues in apo B was decreased by Cu-catalyzed LDL oxidation, acetylation, maleylation and by malondialdehyde conjugation. The number of free cysteines decreased from six in native apo B-100 to three in Cu-oxidized LDL. The tryptophan fluorescence intensity decreased most in malondialdehyde-conjugated LDL and in Cu-oxidized LDL, compared with acetylated and maleylated LDL. The secondary structure of native and chemically modified LDL was measured by attenuated total reflection infrared spectroscopy and by circular dichroism. No significant changes were observed in the secondary structure of any of the modified LDL. These data suggest that neither acetylation, malondialdehyde treatment or even Cu-oxidation substantially altered the secondary structure of apo B, in spite of significant modifications in the primary structure. Incubation of chemically modified LDL with J774 macrophages induced an accumulation of cellular cholesteryl esters and foam cell formation. The highest cholesterol accumulation was induced after malondialdehyde treatment of LDL. These data suggest that the cellular uptake and accumulation of modified LDL is not modulated by changes in the apo B structure. Rather it seems dependent upon the net charge of the apo B protein and probably involves the modification of critical lysine residues.

Diminished capacity to release metabolites of nitric oxide synthase in macrophages loaded with oxidized low-density lipoproteins.

Activation of J774-macrophages with lipopolysaccharide (LPS) or LPS and recombinant interferon-gamma (IFN-gamma) induced nitric oxide (NO) synthase activity, as measured by the production of nitrite and citrulline. NO synthase activity was suppressed by loading the cells with oxidatively modified low-density lipoprotein (ox-LDL) but not with acetylated LDL (ac-LDL), although the intracellular lipid accumulation was comparable. This suggests that the extent of activation of lipid-loaded macrophages may be influenced by the type of lipid.