Citations

Abstract One hundred and ninety patients with Clostridium difficile toxin-associated colitis (CTAC) or pseudomembranous colitis (PMC) were identified, from microbiology records, disease index and proctoscopy service records, and studied retrospectively. CTAC was associated with cephalosporin antibiotic administration in 70 per cent of the patients. CTAC developed postoperatively in 108 patients after all types of surgery with no preponderance for abdominal surgery. Identification of cytotoxin in stool samples was the primary diagnostic test in 81 per cent of patients but cytotoxin was isolated in 98 per cent of all patients. Pseudomembranes visible on proctoscopy established the diagnosis in 19 per cent of patients and were more commonly seen in severe colitis (71 per cent) than in mild colitis (23 per cent). CTAC responded similarly to oral vancomycin and metronidazole with a relapse rate of 20–23 per cent, respectively. With its association with cephalosporin administration, CTAC is likely to occur with increasing frequency in surgical practice. Oral metronidazole is an effective, cheap, alternative to vancomycin therapy.

AbstractThe aim was to determine whether changes in enteric bacteriology, absorption, morphology, and emptying occur after ileal pouch–anal anastomosis for ulcerative colitis, and to relate any changes to the clinical result. Twenty patients were studied 26 ± 2 months (mean ± s.e.m.) after operation. Eight patients had a good result, six a poor result, and six a history of recurrent pouch ileitis. Anaerobic and aerobic overgrowth occurred in the jejunum of patients with a poor result, but not in those with a good result or with pouch ileitis. In contrast, ileal pouch bacterial overgrowth occurred in all patients regardless of the clinical result. Patients with jejunal overgrowth had increased 24 h stool volume and stool nitrogen, but other patients did not. The larger the stool volume, the greater the anaerobic overgrowth. Pouch biopsies showed chronic inflammation in all patients, while 45 per cent had colonic metaplasia. Neither the inflammation nor the metaplasia correlated with the clinical result, nor did the clinical result correlate with the efficiency of pouch emptying. In conclusion, jejunal bacterial overgrowth after ileal pouch–anal anastomosis was associated with an increased stool output, azotorrhoea, and a poor clinical result. A distinguishing bacterial, absorptive, morphological, or emptying abnormality was not found in patients with a history of recurrent pouch ileitis.

Abstract Aberrant patterns of pre-mRNA processing are typical of human malignancies, yet the mechanisms responsible for these changes remain undefined. We have recently shown overexpression of a core splice regulatory protein, serine-arginine protein kinase 1 (SRPK1), in dysplastic and neoplastic pancreatic ductular cells. In the present study, we have established that SRPK1 levels are similarly up-regulated in breast and colonic tumors where its expression increases coordinately with tumor grade. Targeting SRPK1 for inhibition using small interfering RNA in breast and colonic tumor cell lines in vitro resulted in both increased apoptotic potential and enhanced cell killing after treatment with gemcitabine and cisplatin. Recent reports have described multifaceted interactions between the mitogen-activated protein kinase (MAPK) and AKT signaling networks and the splice regulatory machinery. Consequently, we have shown that targeted inhibition of SRPK1 in tumor cells results in reduced phosphorylation of MAPK3, MAPK1, and AKT. Alterations in the splice pattern and resulting expression of MAPK kinase are implicated in mediating the antitumoral effects resulting from SRPK1 down-regulation. The up-regulation of SRPK1 in multiple cancers and its ability to regulate multiple relevant signaling pathways provide support for developing agents to inhibit this kinase for possible broad application to treat epithelial cancers. [Cancer Res 2007;67(5):2072–80]

AbstractThe aim of this retrospective study was to determine the outcome of patients with a dysfunctional pelvic ileal reservoir in whom disconnection of an ileal pouch-anal anastomosis (IPAA), pouch revision and reanastomosis had been carried out. There were 23 patients (15 women). At the revision operation functional problems were found to be due to a long efferent spout (nine patients), sepsis and/or fistula (four), a redundant blind limb (three), a twisted pouch (three), anastomotic problems (three) or no reservoir (one). The pouch was salvaged in 16 patients and a new pouch was constructed in seven. The pouch-anal anastomosis was resutured in 22 patients and stapled in one. Postoperative complications (all minor) occurred in six patients. Two patients underwent two revisions of IPAA. At a median follow-up of 5 (range 1–10) years, 11 patients reported good to excellent function, five reported fair function and one reported recurrent pouchitis. Revision surgery was unsuccessful in six of 23 patients (three had gross incontinence, two excessive bowel movements and one Crohn's disease), and they subsequently underwent pouch excision. It is concluded that revision of an ileal reservoir and IPAA can be undertaken safely with good results in carefully selected patients.

To determine if dehydroepiandrosterone (DHEA) replacement improves insulin secretion, insulin action, and/or postprandial glucose metabolism, 112 elderly subjects with relative DHEA deficiency ingested a labeled mixed meal and underwent a frequently sampled intravenous glucose tolerance test before and after 2 years of either DHEA or placebo. Despite restoring DHEA sulphate concentrations to values observed in young men and women, the changes over time in fasting and postprandial glucose concentrations, meal appearance, glucose disposal, and endogenous glucose production were identical to those observed after 2 years of placebo. The change over time in postmeal and intravenous glucose tolerance test insulin and C-peptide concentrations did not differ in men treated with DHEA or placebo. In contrast, postmeal and intravenous glucose tolerance test change over time in insulin and C-peptide concentrations were greater (P < 0.05) in women after DHEA than after placebo. However, since DHEA tended to decrease insulin action, the change over time in disposition indexes did not differ between DHEA- and placebo-treated women, indicating that the slight increase in insulin secretion was a compensatory response to a slight decrease in insulin action. We conclude that 2 years of replacement of DHEA in elderly men and women does not improve insulin secretion, insulin action, or the pattern of postprandial glucose metabolism.

We have recently commissioned a temporary radiation therapy facility that is novel in two aspects: it was constructed using modular components, and the LINAC was installed in one of the modular sections before it was lifted into position. Additional steel and granular fill was added to the modular sections on‐site during construction. The building will be disassembled and removed when no longer needed. This paper describes the radiation shielding specifications and survey of the facility, as well as the ramifications for acceptance testing occasioned by the novel installation procedure. The LINAC is a Varian 21EX operating at 6 MV and 18 MV. The radiation levels outside the vault satisfied the design criteria, and no anomalous leakage was detected along the joints of the modular structure. At 18 MV and 600 monitor units (MU) per minute, the radiation level outside the primary barrier walls was of photons; there were no detectable neutrons. Outside the direct‐shielded door, the levels were of photons and of neutrons. The isocentricity of the accelerator met the acceptance criteria and was not affected by its preinstallation into an integrated baseframe and subsequent transport to the building site.PACS numbers: 87.52.Df, 87.52.Ga

Despite advances in imaging, understanding the underlying pathways, and clinical translation of animal models of disease there remains an urgent need for therapies that reduce brain damage after stroke and promote functional recovery in patients. Blocking oxidant radicals, reducing matrix metalloproteinase-induced neuronal damage, and use of stem cell therapy have been proposed and tested individually in prior studies. Here we provide a comprehensive integrative management approach to reducing damage and promoting recovery by combining biological therapies targeting these areas. In a rat model of transient cerebral ischemia (middle cerebral artery occlusion) gene delivery vectors were used to overexpress tissue inhibitor of matrix metalloproteinase 1 and 2 (TIMP1 and TIMP2) 3 days before ischemia. After occlusion, autologous bone marrow cells alone or in combination with agents to improve NO bioavailability were administered intraarterially. When infarct size, BrdU incorporation, and motor function recovery were determined in the treatment groups the largest beneficial effect was seen in rats receiving the triple combined therapy, surpassing effects of single or double therapies. Our study highlights the utility of combined drug, gene, and cell therapy in the treatment of stroke.

Increasing application of expensive medical technologies, including joint replacement, is of concern in the current economic climate. Successful upper limb joint replacements (ULJRs) are being performed, but few detailed data about their utilization are available. To explore the resource implications of such surgery, the utilization of total shoulder replacement (TSR), total elbow replacement (TER) and total wrist replacement (TWR) were examined from the time these procedures first became available at the Mayo Clinic up to 1990. The age- and sex-adjusted utilization rate for TSR among Olmsted County, Minnesota, residents was 1.8 per 100000 person-years (p-y), 0.8 per 100000 p-y for TER and 1.1 per 100000 p-y for TWR. Overall utilization of primary ULJR among Olmsted County residents during the 19-year study period was 3.8 per 100000 p-y. The commonest indication for TSR was osteoarthritis (46 per cent) and for TER and TWR was rheumatoid arthritis (50 and 81 per cent respectively). There was no consistent trend in the utilization of these procedures among Olmsted County residents, but the number of referral patients receiving a ULJR at the Mayo Clinic increased steadily during the study period. The Mayo Clinic experience suggests an increasing demand for ULJR, particularly TSR and TER. With continued advances in, and diffusion of, the technology this demand may increase further.

AbstractMutations in the BRCA2 gene have been implicated in pancreatic cancer susceptibility through studies of high-risk breast and ovarian cancer families. To determine the contribution of mutations in BRCA2 to familial pancreatic cancer, we screened affected probands from 151 high-risk families identified through pancreatic cancer clinics for germ-line BRCA2 mutations. Of these families, 118 had two or more first- and second-degree relatives with pancreatic cancer, and an additional 33 had two or more affected second-degree relatives. The average age of onset for pancreatic cancer was 62.8 years. Five BRCA2 truncating mutations were identified, three in families with two or more first- and second-degree relatives with pancreatic cancer. Three of the families with mutations had a history of breast cancer but not ovarian cancer. Four of five families with mutations were identified through probands with early-onset (<55 years) pancreatic cancer. The results of this study were combined with those from a BRCA2 mutation study of 29 other families from the same Johns Hopkins University National Familial Pancreatic Tumor Registry to estimate the frequency of BRCA2 mutations. A total of 10 carriers from 180 families were identified, suggesting that BRCA2 mutations account for 6% of moderate and high-risk pancreatic cancer families. (Cancer Epidemiol Biomarkers Prev 2007;16(2):342–6)