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R S McLeod

Publications and source records attributed to R S McLeod.

At least 19 recordsLinked to original sources
PubMed1998

Intracellular translocation and stability of apolipoprotein B are inversely proportional to the length of the nascent polypeptide.

We have studied the relationship between the length of apolipoprotein B (apoB) and its intracellular translocation and stability using McArdle RH7777 (McA-RH7777) cells expressing recombinant human apoB variants, ranging in size from B15 to B100. The translocational status of apoB was assessed based on trypsin sensitivity of apoB using isolated microsomes as well as permeabilized cells. In isolated microsomes, shorter apoB variants (</=B48) were 75-100% resistant to exogenous trypsin digestion, whereas apoB variants larger than B48 were less than 40% trypsin-resistant. Experiments with hepatic microsomes isolated from rat or transgenic mice expressing human B48 and B100 also confirmed the high trypsin accessibility of B100 compared with B48. In permeabilized cells, apoB variants shorter than B48 were relatively resistant to exogenous trypsin (percentage of trypsin-resistant apoB greater than 70%) in contrast to recombinant human B72 and B100, which were only 55 and 42% trypsin-resistant, respectively. The trypsin sensitivity of human B100 was comparable with that of endogenous rat B100 in McA-RH7777 cells as well as endogenous B100 in HepG2 cells (percentages of trypsin-resistant cells were as follows: for human B100 construct, 42 +/- 7.5%; for endogenous McA-RH7777 B100, 52 +/- 2.9%; and for endogenous HepG2 B100, 46 +/- 6.3%). Overall, an inverse correlation between the length of apoB and its resistance to exogenous trypsin was evident irrespective of the model system examined. An inverse relationship was also observed between the size of apoB and its co-translational resistance to proteasomal degradation. Truncated apoB constructs were relatively insensitive to proteasome inhibition by MG132 co-translationally (during the pulse) compared with the full-length B100, which was highly sensitive (apoB recovered in the presence of MG132 as a percentage of control was as follows: B15, 127%; B29, 94%; B48, 110%; B72, 140%; B100, 282%). Post-translationally (over a 2-h chase), a similar inverse relationship was found, with B100 being the least stable in comparison with truncated apoB variants. In summary, as the size of the nascent apoB chain increases, there appears to be a greater cytosolic exposure of the polypeptide, leading to a higher sensitivity to proteasomal degradation.

Animals↗
PubMed1998

Mutation at the processing site of chicken low density lipoprotein receptor-related protein impairs efficient endoplasmic reticulum exit, but proteolytic cleavage is not essential for its endocytic functions.

The low density lipoprotein receptor-related protein (LRP) is synthesized as a proreceptor that undergoes post-translational proteolytic processing, yielding a noncovalently associated alphabeta dimer as the mature LRP. We tested the role of processing by creating a mutant in which the P1 residue (Arg3942) of the consensus site for furin cleavage (Arg-Asn-Arg-Arg3942 downward arrow) was replaced with Ser in chicken LRP. Transfection of the mutant LRP (designated LRP-RS) into a Chinese hamster ovary cell line lacking endogenous LRP resulted in expression of the unprocessed full-length proreceptor. Comparison of cell lines stably expressing either the wild-type LRP (LRP-wt) or the unprocessed LRP-RS showed that at comparable expression levels, both receptors restored the sensitivity of cellular protein synthesis to Pseudomonas exotoxin A (IC50 = 25 ng/ml). Subcellular fractionation and neuraminidase treatment showed that both LRP forms were transported to the plasma membrane. In addition, LRP-RS exhibited kinetics of binding, endocytosis, and degradation of methylamine-activated alpha2-macroglobulin that were identical to those of LRP-wt. The internalization rate constant was similar for LRP-wt (Ke = 0.259 min-1) and mutant LRP-RS (Ke = 0.252 min-1), suggesting that it takes about 4 min for the entire surface LRP pool to be internalized. Sorting of LRP from the endosomal compartment to lysosomes or recycling to the plasma membrane were also unaltered in mutant LRP-RS. Pulse-chase analysis showed that the lack of processing of LRP had no effect on the stability of its post-endoplasmic reticulum form or on the rate of its intracellular transit from the endoplasmic reticulum to the Golgi apparatus. However, the exit of mutant LRP from the endoplasmic reticulum was retarded by the Arg3942-to-Ser substitution, as evidenced by prolonged retention within the endoplasmic reticulum (t1/2 = 4 h for LRP-wt and t1/2 > 13 h for LRP-RS).

Animals↗
PubMed1998

Surgery and the randomised controlled trial: past, present and future.

Randomised controlled trials (RCTs), with their prospective definition of methods and outcome measures, double-blind assessment of outcomes and unbiased selection of subjects and controls, provide the best possible evidence for deciding the value of a medical or surgical intervention. Few surgical studies are designed as RCTs, and those that are should be of a higher quality. The lack of good surgical RCTs may be a result of surgeons lacking the necessary training, expertise and desire to perform RCTs, inadequate funding from granting agencies, difficulties in securing patient consent or a lack of sufficient patient numbers. If an RCT is not feasible for a particular study, then alternative research designs, such as prospective matched-pair trials, may need to be better developed and used. If RCTs can be performed, other strategies to increase the number and quality of RCTs may be needed: Education of surgeons in clinical research methods Improved funding of surgical RCTs Compulsory evaluation of new techniques and technology before their general adoption is permitted.

Evidence-Based Medicine↗
PubMed1998

Functional expression of the chicken low density lipoprotein receptor-related protein in a mutant chinese hamster ovary cell line restores toxicity of Pseudomonas exotoxin A and degradation of alpha2-macroglobulin.

The low density lipoprotein receptor-related protein (LRP) is responsible for the clearance of several physiological ligands including a complex of proteinase and alpha2-macroglobulin (alpha2M) and for the entrance of Pseudomonas exotoxin A (PEA) into cells. We have prepared expression plasmids for the full-length chicken LRP (designated LRP100) and two intermediates encoding 25 and 67% of the receptor (designated LRP25 and LRP67, respectively) using overlapping cDNA fragments. LRP25 and LRP67 encode the N-terminal 22 and 64%, respectively, of LRP100 plus the transmembrane and intracellular domains. Transient transfection of these plasmids into COS-7 cells yielded recombinant proteins of expected molecular mass and immunoreactivity. However, LRP100 was incompletely processed into alpha- (515-kDa) and beta- (85-kDa) chains and was poorly transported from the endoplasmic reticulum to the Golgi compartment. Stable transformants of LRP100, LRP67, and LRP25 were generated in a mutant Chinese hamster ovary cell line that lacked expression of endogenous LRP and was resistant to PEA. All forms of recombinant LRP proteins were transported from the endoplasmic reticulum to the Golgi apparatus in Chinese hamster ovary cells as shown by their sensitivity to endoglycosidase H and resistance to neuraminidase. Cell surface iodination and subcellular fractionation studies indicated that all three LRP variants were expressed on the plasma membrane. Furthermore, expression of the three LRP variants restored, to various degrees, sensitivity to PEA and the ability to degrade methylamine-activated alpha2M (alpha2M*). These data suggest that deletion of large internal portions of LRP, including the processing site, does not prevent transport of LRP to the plasma membrane, nor does it abolish the interaction of LRP with alpha2M* or PEA. This LRP expression system may allow for the characterization of domains within LRP responsible for its multifunctionality.

ADP Ribose Transferases↗
PubMed1998

Handsewn vs. stapled anastomoses in colon and rectal surgery: a meta-analysis.

PURPOSE: Trials comparing handsewn with stapled anastomoses in colon and rectal surgery have not found statistical differences. Despite this, authors have differed in their conclusions as to which technique is superior. To help determine whether differences in patient outcomes are present, a meta-analysis of all trials was performed. METHOD: A meta-analysis of all randomized, controlled trials assessing handsewn and stapled colon and rectal anastomoses was done using a fixed-effects model. Outcome variables were mortality, technical problems, leak rates, wound infections, strictures, and cancer recurrence. Outcomes were assessed for all anastomoses involving the colon and for the subset of colorectal anastomoses. RESULTS: Thirteen distinct trials met the inclusion criteria. Intraoperative technical problems were more likely to occur with stapled than with handsewn anastomoses for all anastomoses (P < 0.0001) and for colorectal anastomoses (P < 0.001). Strictures were also more common following stapled anastomoses (P = 0.015 for all anastomoses; P = 0.028 for colorectal anastomoses). All other outcome measures, including mortality, clinical and radiologic leak rates, and local cancer recurrence rates showed no difference between groups. CONCLUSION: Although intraoperative technical problems and postoperative strictures were more common with stapled anastomoses, other outcome measures showed no difference between groups. Thus, both techniques are effective, and the choice may be based on personal preference.

Anastomosis, Surgical↗
PubMed1998

Quality of life of patients with inflammatory bowel disease after surgery.

Quality of life is an important outcome measure following surgery for ulcerative colitis. Quality of life incorporates not only the physical or functional outcome; it also considers the emotional and social well-being of patients. Quality of life may be measured using disease-specific or generic quality of life measures or by utility measurement. Although the pelvic pouch procedure is preferred by most patients, there are data to suggest that the quality of life is excellent irrespective of the procedure, possibly because physical well-being is improved and is the main determinant of outcome. Those who have a pelvic pouch may be less restricted in some activities. Compared to medically treated patients, quality of life is usually superior in surgical patients, although it varies depending on the activity of the disease and the surgical outcome. Despite more publications on this topic in recent years, there is a need for further studies comparing quality of life in patients receiving medical and surgical treatment as well as assessing outcome following the various surgical procedures.

Humans↗
PubMed1998

Reliability of a Crohn's disease clinical classification scheme based on disease behavior.

Classification of Crohn's disease (CD) by disease behavior--either inflammatory (INF), fibrostenotic (FS), or fistulizing/perforating (FP)--has been proposed as a means of assisting management decisions and predicting outcomes for subgroup analysis in clinical trials and for making phenotype/genotype associations in molecular genetic studies. Accurate and reproducible classification of CD patient subgroups is of paramount importance in such studies but to be useful, the classification scheme must have good interrater agreement. We sought to assess the interrater agreement associated with the disease-behavior classification scheme of CD. Twelve patients with CD were randomly selected from a database of 964 patients with CD undergoing medical or surgical treatment or both. Clinical details of the 12 cases, along with their radiographs and surgical and pathological reports, were presented to a panel of 20 experts who were asked to classify each case based on the patient's overall disease course (scenario A) and as if the patient were being entered into a clinical trial on that day (scenario B). Calculations of strength of interrater agreement were made and were expressed as the kappa statistic (kappa), with kappa < 0.2 = poor strength of agreement; kappa 0.21 - 0.4 = fair; kappa 0.41 - 0.6 = moderate; kappa 0.61 - 0.8 = good; and kappa 0.81 - 1.0 = very good. Five panel participants did not complete the study, and three clinical vignettes were excluded because of incomplete scoring, leaving a total of 15 panel experts assessing nine cases. Overall interrater agreement was only fair with kappa = 0.353 for scenario A and kappa = 0.291 for scenario B. Interrater agreement was less when only the most straightforward case in each disease category was evaluated. Classification of CD by pattern of disease behavior yields only fair interrater agreement. This raises concerns regarding its applicability, particularly in ongoing studies of genotype/phenotype associations. Further refinement of disease subtypes and clear operational definitions are required.

Adult↗
PubMed1998

Sequences within the amino terminus of ApoB100 mediate its noncovalent association with apo(a).

Although sequences within the C terminus of apolipoprotein B (apoB) have been implicated in the formation of covalent lipoprotein(a) [Lp(a)] particles, sequences in apoB that mediate initial noncovalent interaction with apo(a) remain to be characterized. To address this question, we have used an affinity chromatography method in which 2 recombinant forms of apo(a) [r-apo(a); either a 17-kringle form (17K) or a derivative containing apo(a) kringle IV types 5-8] have been immobilized onto Sepharose beads. Conditioned media from rat hepatoma (McA-RH7777) cell lines stably expressing various carboxyl-terminally truncated forms of human apoB (ranging from full-length apoB to apoB15) were applied to the r-apo(a) affinity columns; the columns were subsequently washed and eluted with epsilon-aminocaproic acid (epsilon-ACA). Specific binding was quantified by Western blot analysis of column fractions. Of the apoB truncations examined, apoB94, apoB42, apoB37, and apoB29 exhibited complete specific binding to 17K r-apo(a). Only approximately 50% binding was observed for apoB18, whereas essentially no detectable binding was observed with apoB15. In all cases, similar results were obtained when the r-apo(a) kringle IV types 5-8-Sepharose column was used. Additionally, substitution of proline for epsilon-ACA as the eluent resulted in similar column profiles with either r-apo(a) affinity column. We also demonstrated that apoB48 present in chylomicrons bound completely to the 17K column in an epsilon-ACA-dependent manner. Taken together, these results represent the first demonstration that N-terminal sequences in apoB between amino acid residues 680 (apoB15) and 781 (apoB18) are essential for noncovalent association with apo(a) and that these sequences interact with domain(s) present within apo(a) kringle IV types 5-8.

Amino Acid Sequence↗
PubMed1998

Surgical management of acquired rectourethral fistula, emphasizing the posterior approach.

Rectourethral fistula is an uncommon surgical entity having a variety of congenital and acquired causes. Although several surgical approaches have been proposed in the literature, successful repair is often difficult. The 2 patients described had rectourethral fistulas after radical prostatectomy. One patient failed previous transabdominal and perineal repairs. The authors propose a 3-step approach to management of acquired rectourethral fistulas. A diverting transverse colostomy with insertion of a suprapubic or indwelling silicone rubber Foley catheter for 3 to 6 months will allow for a decrease in the inflammatory response surrounding the involved area and possible spontaneous closure. If spontaneous closure does not occur within this time, the fistula should be closed operatively through a posterior approach (modified York-Mason procedure). This approach provides excellent exposure and allows the suture lines to be offset, which in turn allows for better healing, present a minimal risk of impotence or incontinence and allows for complete separation of urinary and fecal streams. The third step involves closure of the colostomy followed by removal of the Foley or suprapubic catheter if there is no recurrence. Timing of this step is crucial and should be individualized according to the postoperative course.

Aged↗
PubMed1997

Normal activity of microsomal triglyceride transfer protein is required for the oleate-induced secretion of very low density lipoproteins containing apolipoprotein B from McA-RH7777 cells.

The requirement of the activity of microsomal triglyceride transfer protein (MTP) for very low density lipoprotein (VLDL) secretion was determined using McA-RH7777 cells stably transfected with human apoB48 (hB48). Secretion of VLDL containing hB48 (hB48-VLDL) by the transfected cells was induced by exogenous oleate (0.4 mM), and oleate-dependent VLDL secretion was selectively inhibited by brefeldin A (0.2 microg/ml). Two protocols were used to determine the effect of MTP inhibition on VLDL secretion. In the first protocol, cell protein and lipid were labeled with radioactive amino acids and oleate prior to MTP inhibition (using 5 microM of the photoaffinity inhibitor BMS-192951 to reduce MTP activity by 65-70%), and secretion of prelabeled apoB and triacylglycerol (TG) associated with lipoproteins was monitored during oleate-supplemented chase. In control cells, a 6-fold increase in incorporation of prelabeled TG into hB48-VLDL was observed after oleate supplement, while incorporation of prelabeled TG into VLDL containing endogenous rat apoB100 (rB100-VLDL) was unaffected. Inhibition of MTP activity abolished the oleate-induced utilization of prelabeled TG (by 80%) and hB48 (by 70%) for hB48-VLDL secretion but decreased utilization of pre-existing TG (by <25%) and B100 (by 45%) for rB100-VLDL secretion to a lesser extent. Inhibition of MTP did not affect incorporation of prelabeled TG or hB48 into high density lipoproteins containing hB48 (hB48-HDL). In the second protocol, MTP was inactivated prior to metabolic labeling of protein and lipid, and secretion of newly labeled apoB and TG as lipoproteins was monitored after oleate supplement. Under this condition, MTP inhibition decreased incorporation of newly labeled TG (by 80%) and hB48 (80%) into hB48-VLDL but did not affect their incorporation into hB48-HDL. Additionally, MTP inhibition decreased incorporation of newly labeled TG (by 50%) and rB100 (by 90%) into rB100-VLDL. Thus, normal activity of MTP is required for the oleate-induced secretion of hB48-VLDL from McA-RH7777 cells.

Animals↗
PubMed1997

Risk factors for pelvic pouch failure.

PURPOSE: This study was designed to identify factors associated with pelvic pouch failure. METHOD: A retrospective review of patients undergoing the pelvic pouch procedure with a minimum of 30 months follow-up was conducted. RESULTS: A total of 551 patients had pelvic pouch procedures from 1981 to 1992. Forty-nine patients (8.8 percent) have undergone pouch excision, and 9 (1.6 percent) have been defunctioned, for 58 (10.5 percent) patients with pouch failure. Cause of failure was leakage from the ileoanal anastomosis (IAA) in 21 (39 percent) patients, poor functional results in 13 (23 percent), pouchitis in 7 (12 percent), pouch leakage in 7 (12 percent), perianal disease in 7 (12 percent), and miscellaneous in 3 (5.2 percent). Nine of 22 patients (41 percent) had pouch failure during the first two years, with 2 of 147 patients (1 percent) having failure during the last two years of the study. The 58 patients whose pouches failed (Group 1) were compared with the 493 patients whose pouches did not fail (Group 2). Handsewn IAA (P < 0.001), tension on the IAA (P < 0.001), use of a defunctioning ileostomy (P < 0.01), a diagnosis of Crohn's disease (P < 0.001), and a leak from the pouch (P < 0.001) or the IAA (P < 0.001) were associated with pouch failure. Pouchitis was not a risk factor. CONCLUSION: The majority of pouch failures were caused by leaks at the IAA. Although the leak rate remained stable, leaks following a stapled anastomosis seemed to have a better prognosis than leaks following a handsewn anastomosis. Experience with the pouch procedure and the management of complications likely plays an important role in decreasing the risk of pouch failure.

Adult↗
PubMed1997

Preliminary report on the Mount Sinai Hospital Inflammatory Bowel Disease Genetics Project.

BACKGROUND: Although the etiology of inflammatory bowel disease (IBD) is unknown, there is increasing evidence that genetic predisposition plays a major etiologic role. To provide the framework for gene identification using a positional cloning approach, ascertainment of families with multiple affected members and careful documentation of pedigrees are essential. OBJECTIVE: To report the initial findings of the IBD Genetics Project of the Mount Sinai Hospital IBD Research Unit. METHODS: All records of patients with ulcerative colitis and Crohn's disease followed at the Mount Sinai Hospital IBD Unit were reviewed. A questionnaire was sent to all patients to ascertain those with a family history of IBD. Patients with a presumed family history were contacted by a research assistant, and after confirmation of diagnosis, relevant clinical information, pedigrees, and consent to contact family members were obtained. Blood for DNA and cell line preparation were collected from affected and nonaffected family members. RESULTS: Of 2,504 patients registered in the IBD database, 231 (9.2 percent) were found to have an affected family member: 96 of 964 (10 percent) with Crohn's disease (CD) and 135 of 1,540 (8.8 percent) with ulcerative colitis (UC). A mean of 2.4 family members were affected. In families in which the proband had CD, 82.3 percent had only two affected family members, 78.1 percent had only family members affected with CD, and 82.3 percent had only first-degree family members affected. In families in which the proband had UC, 70.4 percent had only two affected family members, 71.1 percent had only family members affected with UC, and 65.2 percent had only first-degree family members affected. In the 231 families, there were 103 sibling pairs: 46 percent with CD, 28 percent with UC, and 26 percent with CD/UC. CONCLUSION: These data suggest that approximately 10 percent of IBD patients have affected family members, with the rate being similar in UC and CD. Future research is directed to genome scanning and linkage analysis in this cohort of patients.

Colitis, Ulcerative↗
PubMed1997

Outcome of the pelvic pouch procedure in patients with prior perianal disease.

PURPOSE: There is concern that patients with presumed ulcerative colitis and significant perianal disease may in fact have Crohn's disease. Moreover, prior perianal disease may be an independent factor for poor outcome of the pelvic pouch. The aim of this study was to evaluate the effect of prior perianal disease on pelvic pouch outcome. METHODS: Between 1982 and 1994, 52 of 753 patients (6.9 percent) who had a pelvic pouch procedure were prospectively identified as having perianal disease. Outcome of the pelvic pouch of these 52 patients (Group I) were compared with the outcome of 701 pelvic pouch patients with no prior perianal disease (Group II). The perianal diseases identified in Group I were fissure-in-ano (17), perianal abscesses (13), fistula-in-ano (7), rectovaginal fistula (3), and significant hemorrhoids/skin tags (25). Eleven patients (21 percent) had more than one type of perianal disease. Twenty-seven patients (52 percent) required a total of 33 perianal operations for the different anal pathologies. RESULTS: Both groups were comparable for the following characteristics: age at time of pelvic pouch procedure, pathology (ulcerative colitis or indeterminate colitis), design of pouch, and type of ileoanal anastomosis (handsewn or stapled). An ileoanal anastomosis leak developed in 21 percent of patients (n = 11) in Group I vs. 11.4 percent (n = 80) in Group II (P < 0.05). Perianal postoperative complications occurred in 11.5 percent of patients (n = 6) in Group I vs. 1.7 percent (n = 12) in Group II (P < 0.05). Total pouch failure rate was not significantly different between the two groups (11.5 vs. 7.6 percent; P > 0.05). Crohn's disease was subsequently diagnosed in 1.9 vs. 2.7 percent (P > 0.05). Subgroup analysis of Group I patients showed no significant difference in outcome according to type of perianal lesion or a history of perianal surgery. CONCLUSION: Prior perianal disease significantly increases the risk of developing an ileoanal anastomotic leak and postoperative perianal complications. However, a pelvic pouch procedure may be an acceptable surgical alternative for selected ulcerative colitis patients with prior perianal disease because the overall pouch failure rate is not significantly increased.

Adult↗
PubMed1997

Risk and significance of endoscopic/radiological evidence of recurrent Crohn's disease.

BACKGROUND & AIMS: The aim of this study was to determine the risk of endoscopic/radiological recurrence of Crohn's disease postoperatively and the long-term outcome. METHODS: A randomized placebo-controlled trial was performed to determine the effectiveness of mesalamine in preventing recurrent Crohn's disease postoperatively. Patients in the control group were examined endoscopically/radiologically before entry into and annually during the trial. Findings were classified as minimal or severe. RESULTS: There were 76 patients (49 men and 37 women; mean age, 37.1 +/- 13.2 years). Fifty (61.7%) had terminal ileal resections. Overall, 55 endoscopic/radiological recurrences were observed in 51 patients (67.1%). Expressed actuarially, the recurrence rate was 27.5% at 1 year (95% confidence interval [CI], 15.8%-37.6%), 60.8% at 2 years (95% CI, 46%-71.3%), and 77.3% at 3 years (95% CI, 62.7%-86.3%). Nineteen (37%) were symptomatic and 12 (24%) were initially asymptomatic but later became symptomatic (mean, 13.0 +/- 8.8 months), whereas 20 (39%) remained asymptomatic (mean, 16.9 +/- 17.4 months). Patients with severe endoscopic/radiological disease were significantly more likely to be or become symptomatic than those with minimal disease (23 of 32 vs. 8 of 19, respectively; P = 0.0437). CONCLUSIONS: This study suggests that postoperative endoscopic/radiological recurrences occur later than previously reported. Furthermore, many of these patients, especially with minimal disease, will remain asymptomatic.

Actuarial Analysis↗
PubMed1997

Comparison of hemorrhoidal treatments: a meta-analysis.

OBJECTIVE: To determine whether any method of hemorrhoid therapy has been shown to be superior in randomized trials. METHOD: A meta-analysis of all randomized controlled trials assessing two or more treatment modalities for symptomatic hemorrhoids. MAIN OUTCOME MEASURES: Response to therapy, the need for further therapy, complications and pain. RESULTS: Eighteen trials were available for analysis. Hemorrhoidectomy was found to be significantly more effective than manual dilatation of the anus (p = 0.0017) and associated with less need for further therapy (p = 0.034), no significant difference in complications (p = 0.60) but more pain (p < 0.001). Patients who underwent hemorrhoidectomy had a better response to treatment than did patients who were treated with rubber-band ligation (p = 0.001), although complications were greater (p = 0.02), as was pain (p < 0.0001). Rubber-band ligation was better than sclerotherapy in response to treatment for all hemorrhoids (p = 0.005) and for hemorrhoids stratified by grade (grades 1 and 2, p = 0.007, grade 3, p = 0.042), with no difference in the complication rate (p = 0.35). Patients treated with sclerotherapy (p = 0.031) or infrared coagulation (p = 0.0014) were more likely to require further therapy than those treated with rubber-band ligation, although pain was greater after rubber-band ligation (p = 0.03 for sclerotherapy, p < 0.0001 for infrared coagulation). CONCLUSIONS: Rubber-band ligation is recommended as the initial mode of therapy for grades 1 to 3 hemorrhoids. Although hemorrhoidectomy showed better response, it is associated with more complications and pain than rubber-band ligation. Thus, it should be reserved for patients whose hemorrhoids fail to respond to rubber-band ligation.

Diathermy↗
PubMed1997

Symposium on rectal cancer: 2. Local recurrence after surgery for rectal cancer.

Local recurrence is a serious complication in patients with rectal cancer because of the frequency with which it occurs, its impact on quality of life and the fact that treatment is rarely successful. Although local recurrence rates varying from 4% to 51% have been reported, recent series have reported rates of less than 10%. Various factors may affect the rate of local recurrence, including the stage and location of the tumour. Other prognostic factors may be of importance, but it is controversial whether they are independent risk factors. Finally, there is mounting evidence that the local recurrence rate varies with the surgeon. Whether this is due to the surgical technique or surgical expertise is not clear, but randomized controlled trials addressing the issue of extent of resection are indicated in order to optimize surgical results.

Humans↗
PubMed1997

Intracellular degradation of newly synthesized apolipoprotein B.

Intracellular degradation of newly synthesized apolipoprotein (apo) B can occur at every stage of the secretory pathway, from the protein translation, polypeptide translocation across the membrane of endoplasmic reticulum (ER), to vesicular transport. The prevalence of apoB degradation at each stage varies in different hepatic cell systems examined. Proteolysis of nascent apoB can be catalyzed by the ubiquitin-proteasome system in the cytosol, and probably by unidentified ER resident proteases as well. Cytosolic and ER lumenal molecular chaperones that facilitate apoB translocation and folding may also assist in the degradation of misfolded apoB proteins. Factors affecting the synthesis and mobilization of lipids during lipoprotein assembly exert important regulatory effects on apoB degradation in trans, and specific hydrophobic amino acid sequence elements within the apoB-100 molecule may play roles in apoB degradation in cis. This review summarizes the current understanding of the cellular and molecular mechanisms responsible for intracellular degradation of apoB in hepatocytes. The emphasis centers primarily on the topology of apoB with respect to the ER membrane during and after apoB translation and its relationship to proteolytic mechanisms potentially involved in apoB degradation.

Animals↗