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Biomedical subjects

M J Solomon

Publications and source records attributed to M J Solomon.

At least 73 records · Page 4Linked to original sources
PubMed1996

Laparoscopic rectopexy using mesh fixation with a spiked chromium staple.

UNLABELLED: Abdominal rectopexy for patients with rectal prolapse is well suited for performance laparoscopically because no resection or anastomosis is necessary, with potential benefits being a decrease in postoperative pain, better cosmesis, and an earlier return to normal activity. PURPOSE: Objectives of this study were to determine the feasibility of laparoscopic abdominal rectopexy using a solitary spiked chromium staple to fix the mesh to the sacrum and to compare initial results with consecutive previous abdominal rectopexies (historical control study). METHODS: Duration of operation (anesthetic plus surgery), the day a solid diet was first tolerated, day of discharge, and patient morphine requirements in the first 48 hours were documented prospectively for the laparoscopic group and retrospectively from medical records for an open abdominal rectopexy group. RESULTS: Laparoscopic rectopexy group had lower morphine requirements when using patient-controlled analgesia (mean, 38.2 vs. 100.6 mg; P < 0.02), an earlier tolerance of solid diet (mean, 2.7 vs. 5.8 days; P < 0.001), and an earlier discharge from the hospital (mean, 6.3 vs. 11.0 days; P < 0.01). Operating time was longer for the laparoscopic group (mean, 198 vs. 130 minutes; P < 0.001). CONCLUSIONS: Laparoscopic rectopexy is feasible, may have benefits in reducing postoperative pain, and may aid earlier return to normal diet and activity. Given the inherent bias of a historical control study, a randomized controlled study has commenced to confirm these results.

Adult↗
PubMed1996

Fistulae and abscesses in symptomatic perianal Crohn's disease.

Perianal disease occurs in up to 90% of patients with Crohn's disease [1-4]. Many of these patients have only mild symptoms or are asymptomatic and thus require no intervention. Clinical features are variable and include hypertrophic skin tags, ulceration, perianal abscess and fistulae, anal canal ulcers, fissures, induration and stenosis. Perianal abscess and fistula often occur simultaneously and are usually symptomatic. Symptoms range from pain, discharge, bleeding, to gross faecal incontinence with restriction of lifestyle and sexual activity. There is little uniformity amongst clinicians in the investigation and management of perianal Crohn's disease [5]. This is due, in part, to the variability in both frequency and severity of attacks and to spontaneous remissions and exacerbations of perianal disease. Secondly, assessment of severity of illness and the response to treatment is difficult to objectively quantitative. Improvement in quality of life is the aim of therapy not cure of perianal disease. Investigative modalities for perianal Crohn's are changing due to the limitations of conventional fistulography, CT scanning and clinical evaluation. MRI scanning has been introduced more recently, however, requires an endorectal coil to obtain good anatomical visualisation and has limited availability [6-12]. Endorectal ultrasonography has been shown to detect more abscesses and fistula in Crohn's patients than clinical examination, proctosigmoidoscopy and CT scanning, better delineation of fistulous tracts than fistulography and has the ability to change the clinical management of referring physicians [13-16]. Most fistulae are not explored surgically and therefore the documentation of fistulae in symptomatic Crohn's disease has been limited and are usually classified only as high or low [4]. Park's has pointed out this terminology for cryptoglandular disease is "... an ambiguous one" and hence developed a more precise nomenclature [17]. The objective of this study was to document prospectively by transanorectal ultrasonography fistulae and abscesses in symptomatic perianal Crohn's disease and to classify them according to Park's nomenclature and determine the incidence of these at the time of referral for a new exacerbation of the disease. Anal wall thickness was measured prospectively by ultrasonography as it has been shown to be increased in patients with perianal Crohn's disease and may reflect disease activity [13, 18].

Abscess↗
PubMed1996

Postpartum avulsion of the terminal ileal wall in Crohn's disease.

A case of acute perforation of the terminal ileum induced by avulsion of the bowel wall in a segment of acutely inflamed Crohn's disease is presented. This case is unusual in that the avulsion developed after delivery following the rapid retraction of the uterus which had been compressing a small localized perforation and abscess. A review of the literature has failed to demonstrate a similar case report.

Adult↗
PubMed1995

Long-term results of anterior resection using the double-stapling technique.

PURPOSE: This study was designed to determine the anastomotic leak rate, local recurrence rate, and survival of patients undergoing anterior resection with the double-stapling technique for rectal cancer. METHODS: Between 1981 and 1992, 189 patients underwent a curative (166) or palliative (23) anterior resection using the double-stapling technique. A chart review was performed, and follow-up information was obtained from the patient or family physician. Follow-up was complete in 186 patients (98 percent). RESULTS: There were five (2.6 percent) stapler-related complications, of which two patients required a defunctioning colostomy. Postoperative mortality was 1.6 percent, and clinical leak rate was 7.3 percent. Clinical leak rate was significantly higher in patients with lesions in the lower third (20 percent) compared with those in the middle and upper thirds (9 and 1 percent, respectively; P < 0.05). After a mean follow-up of 32 +/- 29 months, local recurrence rate was 9.1 percent but was significantly higher in patients more than 65 years old (14 vs. 1 percent; P < 0.005) and in patients with resection margins less than 2.0 cm (17 vs. 5.5 percent; P < 0.05). Five-year survival was 78 percent. CONCLUSIONS: Anterior resection performed with the double-stapling technique has an acceptable clinical leak rate, local recurrence rate, and survival rate. However, the clinical leak rate appears to be increased in patients with low tumors and, therefore, a defunctioning colostomy should be considered. Resection margins of more than 2 cm are necessary.

Adult↗
PubMed1995

Assessment of peripouch inflammation after ileoanal anastomosis using endoluminal ultrasonography.

PURPOSE: This study was designed to assess the impact of endoluminal transpouch ultrasonography in the investigation and management of inflammatory complications of pelvic pouches and to compare endoluminal transpouch ultrasonography to pouchography and computerized axial tomograph scanning. METHODS: A prospective evaluation was made of the presentation, investigation, treatment, and clinical outcome of 16 patients referred for endoluminal transpouch ultrasonography with dysfunctional pelvic pouches and no evidence of pouchitis on endoscopy. RESULTS: There were 5 normal and 11 abnormal examinations. Six patients had peripouch inflammatory phlegmons, four patients had peripouch abscesses, and one patient had a rectovaginal fistula. A total of nine patients had anastomotic leaks detected. Two patients had abscesses drained under ultrasound guidance and a pigtail catheter left in situ. Pouchography detected only 3 of 8 (38 percent) anastomotic leaks detected by endoluminal transpouch ultrasonography. Computerized axial tomograph scan detected 2 of 5 (40 percent) peripouch abscesses or phlegmon detected by endoluminal transpouch ultrasonography. Patients with peripouch sepsis had significantly thicker anal wall thickness (23.8 vs. 16.8 mm; P < 0.02) and external sphincter thickness (9.1 vs. 7.3 mm; P < 0.05) than pouches with no sepsis. CONCLUSIONS: Endoluminal transpouch ultrasonography appears to detect anastomotic leaks and peripouch sepsis and may guide the initial management of patients with dysfunctional pelvic pouches and an inconclusive clinical and endoscopic examination.

Abscess↗
PubMed1995

Should we be performing more randomized controlled trials evaluating surgical operations?

BACKGROUND: The objective of this study was, first to determine what proportion of clinical treatment evaluation questions involving surgical operations could be answered by a randomized controlled trial (RCT). Second, for those questions not amenable to a RCT, to determine the problems that potentially preclude the initiation of RCT in an ideal clinical research setting. METHODS: A sample of treatment evaluation questions involving a surgical procedure was obtained by a computerized search of the surgical literature. Problems precluding a RCT were defined. Their face validity and interobserver and intraobserver reliability were assessed. By use of these criteria, the sample questions were evaluated to determine whether a RCT could be performed and, if not, the predominant reasons precluding RCT of surgical procedures. RESULTS: Only 38.8% of treatment evaluation questions could have been answered by a RCT in an ideal clinical research setting. Patient preference was the most common precluding problem encountered (40% of all problems). The principal precluding problem was patient preference in 23.1%, an uncommon condition in 24.2%, and lack of community (clinical) equipoise in 10%. Methodologic issues (1.2%) and surgical preference (2.3%) were infrequent precluding problems. Questions evaluating therapy for malignant disease, comparing surgical with nonsurgical therapies, and where survival was the primary outcome were more likely to have problems precluding RCT. CONCLUSIONS: In the ideal situation RCT can be performed to evaluate only 40% of treatment questions involving surgical procedures. Patient preferences, uncommon conditions, and lack of surgical community equipoise appear to be the most common reasons precluding the of RCT of surgical operations.

Humans↗
PubMed1995

KIN28 encodes a C-terminal domain kinase that controls mRNA transcription in Saccharomyces cerevisiae but lacks cyclin-dependent kinase-activating kinase (CAK) activity.

The Saccharomyces cerevisiae gene KIN28 is a member of the cyclin-dependent kinase (CDK) family. The Kin28 protein shares extensive sequence identity with the vertebrate CDK-activating kinase MO15 (Cdk7), which phosphorylates CDKs in vitro on a critical threonine residue. Kin28 and MO15 have recently been found to copurify with the transcription factor IIH (TFIIH) holoenzyme of yeast and human cells, respectively. Although TFIIH is capable of phosphorylating the C-terminal domain (CTD) of RNA polymerase II, it has been unclear whether Kin28 is the physiologically relevant CTD kinase or what role CTD phosphorylation plays in transcription. In this study, we used a thermosensitive allele of KIN28 and a hemagglutinin epitope-tagged Kin28 protein to investigate Kin28 function in transcription and in the cell cycle. We show that Kin28 acts as a positive regulator of mRNA transcription in vivo and possesses CTD kinase activity in vitro. However, Kin28 neither regulates the phosphorylation state of the yeast cell cycle CDK, Cdc28, nor possesses CDK-activating kinase activity in vitro. We conclude that Kin28 is a strong candidate for the physiological CTD kinase of S. cerevisiae and that Kin28 function is required for mRNA transcription.

Base Sequence↗
PubMed1995

Anal wall thickness under normal and inflammatory conditions of the anorectum as determined by endoluminal ultrasonography.

OBJECTIVES: To determine the normal dimensions of the anal wall and if there were detectable differences in inflammatory disorders. METHODS: A cross-sectional survey was performed on all patients referred to a university anorectal ultrasound clinic who had either perianal Crohn's disease (17 patients), ileoanal pouches (15 patients), perianal fistula (15 patients), or previous radiation to the rectum (5 patients). Results were compared to 40 normal controls. Anal wall thickness (AWT), mucosa, submucosa, internal sphincter thickness (MSIT), and external sphincter thickness (EST) were measured or calculated. Intra- and interobserver reliability was assessed. RESULTS: The mean AWT was 14.8 mm (95% CI: 14.0-15.6), mean EST was 8.3 mm (95% CI: 7.6-9.0), and the mean MSIT was 6.5 mm (95% CI: 5.8-7.2) in the control subjects. Measurements did not differ significantly with sex or with an increase in age. Patients with perianal Crohn's disease, ileoanal pouches with septic complications, and previous local radiotherapy had significant increases in anal wall thickness. In Crohn's disease, the significant increase was in MSIT, whereas, in the pouch patients, the increase was in the EST. Reliability studies demonstrated a learning curve with experience and a better correlation with determination of AWT than MSIT. CONCLUSIONS: Patients with anorectal inflammatory conditions have increased thickness in anal wall dimensions.

Aged↗
PubMed1994

Periodic health examination, 1994 update: 2. Screening strategies for colorectal cancer. Canadian Task Force on the Periodic Health Examination.

OBJECTIVE: To make recommendations on the effectiveness of screening for colorectal cancer in asymptomatic patients over 40 years of age. OPTIONS: Multiphase screening that begins with test for fecal occult blood, uniphase screening with sigmoidoscopy and uniphase screening with colonoscopy. Options included screening repeated at different intervals and different procedures for patients with selected risk factors. OUTCOMES: Rates of death, death from cancer and cancer detection; compliance, feasibility and accuracy of each manoeuvre. EVIDENCE: A MEDLINE search for articles published between January 1966 and June 1993 with the use of MeSH terms "screening" and "colorectal neoplasia," a check with the reference sections of review articles published before June 1993 and a survey of content experts. Articles were weighted according to the Canadian Task Force on the Periodic Health Examination levels of evidence. VALUES: The highest value was assigned to manoeuvres that lowered the rate of death from cancer and had a low rate of false-positive results and acceptable cost and compliance. Recommendations were determined by consensus of the authors, members of the task force and colorectal cancer experts. BENEFITS, HARMS AND COSTS: There is evidence that annual fecal occult blood testing with the use of the rehydrated Hemoccult test has a small but significant benefit in lowering the rate of death from cancer after more than 10 years of screening; however, the high rate of false-positive results (9.8%) and the poor sensitivity of annual (49%) and biennial (38%) screening make this a poor method for detecting colorectal cancer. There is fair evidence that screening with sigmoidoscopy may improve survival rates; however, this may be due to volunteer bias. The high cost of and poor compliance with colonoscopic screening make this an unfeasible strategy.

Adult↗
PubMed1994

Reliability and validity studies of endoluminal ultrasonography for anorectal disorders.

PURPOSE: Endoluminal ultrasonography (ELUS) is accurate in the assessment of penetration through the rectal wall by carcinoma. Clinical studies were performed to determine the reliability and validity of ELUS. METHODS: The interobserver reliability among four observers with varying experience with ELUS was determined for staging the penetration of rectal cancer through the rectal wall. The ability of ELUS to change the clinical management of the referring clinician (comprehensiveness) was assessed on all referrals over a six-month period. RESULTS: The reliability of ELUS for staging rectal cancer demonstrated only fair to moderate correlation (weighted kappa range, 0.22-0.47). The accuracy of ELUS compared with surgical pathology demonstrated a learning curve proportional to the experience of the observer. In 45 percent of referrals, ELUS changed the clinical management of patients and in 76 percent of referrals the clinician's confidence in the diagnosis and management of patients was altered. ELUS was more likely to change the management of patients with pelvic pouch sepsis (70 percent) and early neoplastic lesions (57 percent) than in more advanced neoplastic lesions (40 percent), perianal Crohn's disease (40 percent), complex noninflammatory bowel disease sepsis (33 percent), and incontinence (31 percent). CONCLUSIONS: ELUS has the ability to change the clinical management of a variety of anorectal conditions. However, for neoplasia the interobserver reliability is only moderate and a learning curve exists.

Adenocarcinoma↗
PubMed1994

The function(s) of CAK, the p34cdc2-activating kinase.

The protein kinase p34cdc2 plays a central role in controlling the G2 to mitosis transition in all eukaryotic cells. It is regulated by protein-protein association and by multiple phosphorylations; one of these phosphorylations is absolutely required for activity. Until recently, the molecular identity of the protein kinase that phosphorylates this site was unknown. The subunits of this enzyme have been identified recently as p40MO15, the catalytic subunit, and cyclin H, a regulatory subunit. Similarities between this kinase and the p34cdc2 family of protein kinases suggest how p40MO15 itself may be regulated.

Amino Acid Sequence↗
PubMed1994

Does intraoperative hepatic ultrasonography change surgical decision making during liver resection?

BACKGROUND: Intraoperative hepatic ultrasonography (IOUS) has been used to accurately identify and localize hepatic tumors as an adjunct to hepatic resection and for the detection of occult liver metastases during primary resection of other gastrointestinal carcinomas. The face validity of IOUS to identify more lesions than conventional diagnostic modalities and the content validity of IOUS to change the planned surgical management has been assessed in a blinded, prospective manner. METHODS: Sixty-two patients were studied at two institutions by one surgeon. IOUS was compared with computed tomography (CT) angioportography in 30 patients undergoing planned hepatic resection (19 metastatic, 11 primary) and with conventional hepatic ultrasonography (+/- venous enhanced CT scan) in 32 patients undergoing primary excision of gastrointestinal carcinomas. RESULTS: Twenty of the 30 hepatic resections (67%) were changed or guided by IOUS as determined by the operating surgeon at the completion of the laparotomy. IOUS detected 26 more metastases (44%) in 10 of 19 patients (1 to 5 per patient). Two patients had preoperatively suspected metastases refuted by IOUS-guided biopsy. Eight of the 11 patients (73%) undergoing resection of primary carcinoma of the liver had the planned procedure changed or guided by IOUS. This included four hepatocellular carcinomas with more extensive involvement at the confluence of the hepatic veins and the inferior vena cava, necessitating resection with the aid of total vascular isolation. In 32 patients undergoing primary resection of gastrointestinal carcinomas, 5 patients (16%) had the stage of disease altered by IOUS when compared with conventional ultrasound (+/- venous enhanced CT scan). CONCLUSIONS: The validity of IOUS is good. IOUS guided the intraoperative surgical management of two thirds of the patients undergoing hepatic resection when compared with CT angioportography. Intraoperative hepatic ultrasonography using a reproducible systematic approach can change the clinical management of patients undergoing hepatic resection for malignancy.

Algorithms↗
PubMed1994

p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest.

Cell-cell contact and TGF-beta can arrest the cell cycle in G1. Mv1Lu mink epithelial cells arrested by either mechanism are incapable of assembling active complexes containing the G1 cyclin, cyclin E, and its catalytic subunit, Cdk2. These growth inhibitory signals block Cdk2 activation by raising the threshold level of cyclin E necessary to activate Cdk2. In arrested cells the threshold is set higher than physiological cyclin E levels and is determined by an inhibitor that binds to cyclin E-Cdk2 complexes. A 27-kD protein that binds to and prevents the activation of cyclin E-Cdk2 complexes can be purified from arrested cells but not from proliferating cells, using cyclin E-Cdk2 affinity chromatography. p27 is present in proliferating cells, but it is sequestered and unavailable to interact with cyclin E-Cdk2 complexes. Cyclin D2-Cdk4 complexes bind competitively to and down-regulate the activity of p27 and may thereby act in a pathway that reverses Cdk2 inhibition and enables G1 progression.

Animals↗
PubMed1994

Inactivation of a Cdk2 inhibitor during interleukin 2-induced proliferation of human T lymphocytes.

Peripheral blood T lymphocytes require two sequential mitogenic signals to reenter the cell cycle from their natural, quiescent state. One signal is provided by stimulation of the T-cell antigen receptor, and this induces the synthesis of both cyclins and cyclin-dependent kinases (CDKs) that are necessary for progression through G1. Antigen receptor stimulation alone, however, is insufficient to promote activation of G1 cyclin-Cdk2 complexes. This is because quiescent lymphocytes contain an inhibitor of Cdk2 that binds directly to this kinase and prevents its activation by cyclins. The second mitogenic signal, which can be provided by the cytokine interleukin 2, leads to inactivation of this inhibitor, thereby allowing Cdk2 activation and progression into S phase. Enrichment of the Cdk2 inhibitor from G1 lymphocytes by cyclin-CDK affinity chromatography indicates that it may be p27Kip1. These observations show how sequentially acting mitogenic signals can combine to promote activation of cell cycle proteins and thereby cause cell proliferation to start. CDK inhibitors have been shown previously to be induced by signals that negatively regulate cell proliferation. Our new observations show that similar proteins are down-regulated by positively acting signals, such as interleukin 2. This finding suggests that both positive and negative growth signals converge on common targets which are regulators of G1 cyclin-CDK complexes. Inactivation of G1 cyclin-CDK inhibitors by mitogenic growth factors may be one biochemical pathway underlying cell cycle commitment at the restriction point in G1.

Adult↗
PubMed1994

Randomized controlled trials in surgery.

BACKGROUND: The objective was to determine the number of randomized controlled trials (RCT) performed by surgeons, published in surgical journals, or comprising a surgical arm and to assess their characteristics and overall quality. METHODS: RCT in general surgery (including gastrointestinal, breast, surgical oncology, vascular, critical care, and trauma) published in 1990 were retrieved by MEDLINE and analyzed to determine the funding agency, type of therapy, area of surgery, journal published, country of origin, number of centers, and whether a surgeon was the principal author. The completeness of the MEDLINE search was compared to a manual search of the literature. All RCT were assessed with Chalmers' qualitative score. RESULTS: MEDLINE retrieved 202 surgical RCT (46% of those retrieved by a manual search) with a mean score of 0.40 +/- 0.13. However, surgical RCT were performed by surgeons in only one third of trials, compared surgical therapies in only one quarter of trials, and were published in surgical journals in less than one third of trials. Only 22% of surgical RCT were funded by peer reviewed granting agencies. The strongest variables determining the quality of surgical RCT were the type of therapy tested (p = 0.0001), the type of journal published (p = 0.006), and the area of general surgery (p = 0.007). CONCLUSIONS: Although surgical RCT are being performed, there are a relatively low proportion and standard of RCT performed by surgeons as the principal author, published in surgical journals, and comparing surgical therapies. This may reflect a lack of expertise by surgeons in clinical trials, lack of funding for surgical trials, methodologic problems peculiar to surgical trials, or a need for adoption of other research designs to assess surgical therapies.

Authorship↗
PubMed1993

CAK, the p34cdc2 activating kinase, contains a protein identical or closely related to p40MO15.

The mitotic inducer p34cdc2 requires association with a cyclin and phosphorylation on Thr161 for its activity as a protein kinase. CAK, the p34cdc2 activating kinase, was previously identified as an enzyme necessary for this activating phosphorylation. We confirm here that CAK is a protein kinase and describe its purification over 13,000-fold from Xenopus egg extracts. We further show that CAK contains a protein identical or closely related to the previously identified Xenopus MO15 gene: p40MO15 copurifies with CAK, and an antiserum to p40MO15 specifically depletes cAK activity. CAK appears to be the only protein in Xenopus egg extracts that can activate complexes of either p34cdc2 or the closely related protein kinase, p33cdk2, with either cyclin A or cyclin B. The sequence similarity between p40MO15 and p34cdc2, and the approximately 200 kDa size of CAK, suggest that p40MO15 may itself be regulated by subunit association and by protein phosphorylations.

Amino Acid Sequence↗