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Biomedical subjects

C Cunningham

Publications and source records attributed to C Cunningham.

At least 91 records · Page 5Linked to original sources
PubMed1999

Rectal excision and colonic pouch-anal anastomosis for rectal cancer: oncologic results at five years.

PURPOSE: Preservation of the anal sphincter is now accepted as a primary aim in surgical treatment of rectal cancer. The use of colonic J-pouch-anal anastomosis after complete rectal excision is one method that permits retention of continence without compromising oncologic principles. This study aimed to assess carcinologic results of rectal excision followed by colonic J-pouch anal anastomosis, with particular reference to rate of locoregional recurrence. METHOD: From 1984 to 1990 complete rectal excision and colonic pouch-anal anastomosis were performed in 167 patients for cancer of the middle or low rectum. A total of 154 patients were followed for this study for a minimum of five years, with evaluation of the frequency of locoregional recurrence. RESULTS: Sixty-five patients died during the period of surveillance, giving a five-year survival rate of 68.8 percent. Twenty patients (13 percent) presented with locoregional recurrence at an average of 31 months after surgery. In 11 cases (7 percent) the local recurrence was not associated with metastatic disease, and six of these patients underwent further curative surgery. CONCLUSIONS: These results confirm that coloanal anastomosis after complete rectal excision is a valuable option in the surgical treatment of rectal cancer and is accompanied by a frequency of isolated locoregional recurrence of less than 7 percent, of which half underwent surgical resection with curative intent.

Anal Canal↗
PubMed1999

The cognitive and behavioural effects of clobazam and standard monotherapy are comparable. Canadian Study Group for Childhood Epilepsy.

PURPOSE: To compare the cognitive and behavioural effects of clobazam versus standard monotherapy in the treatment of childhood epilepsy. METHODS: A randomized, double-blind, prospective design was carried out at three Canadian pediatric epilepsy centres. This study was part of a larger multi-centre study on the efficacy of clobazam. Children with newly diagnosed epilepsy were assigned randomly to receive clobazam or carbamazepine. Children who had failed previous treatment with carbamazepine were assigned randomly to clobazam or phenytoin. Children who had failed on any other antiepileptic drug were assigned randomly to receive clobazam or carbamazepine. In a subset of patients neuropsychological assessments were carried out at 6 weeks and 12 months after initiation of medication. Intelligence, memory, attention, psychomotor speed, and impulsivity were assessed. RESULTS: There were no differences between the clobazam and standard monotherapy groups on any of the neuropsychological measures obtained at 6 weeks or 12 months. There was no evidence for a deterioration in performance for those children who remained on clobazam for the entire 12-month study period. CONCLUSION: The cognitive and behavioural effects of clobazam appear to be similar to those of standard monotherapy.

Adolescent↗
PubMed1999

The rainbow trout Oncorhynchus mykiss interleukin-1 beta gene has a differ organization to mammals and undergoes incomplete splicing.

The rainbow trout interleukin (IL)-1 beta gene consists of six exons/five introns, in contrast to mammals which have seven exons/six introns. The missing exon appears to be at the 5' end of the gene, probably equivalent to exon 1 or 2 of mammals. Fewer and smaller introns make the trout IL-1 beta only half the size of mammalian IL-1 beta genes. Highest homology (> 60% amino acid similarity) is seen between exon 5 of trout and exon 6 of mammals. Reverse transcription-PCR analysis revealed two additional incompletely spliced variants of the trout IL-1 beta gene, containing intron 5 or introns 4 and 5. All three transcripts are detectable in gill, kidney, liver and spleen tissue from bacterially challenged fish but only the fully spliced transcript is detectable in blood. Northern blot analysis revealed that the latter transcript is also induced following stimulation of kidney leucocytes with lipopolysaccharide for 4 h. A second inducible transcript is also detected but is larger (approximately 3 kb) than any of the above, suggesting that it could be from a second gene. Southern blot analysis also suggests at least two copies of the IL-1 beta gene or genes related to the 3' end of the IL-1 beta sequence, are present in trout.

Alternative Splicing↗
PubMed1999

Cloning and expression of single chain antibody fragments in Escherichia coli and Pichia pastoris.

The potential of recombinant antibody fragments is likely to be fulfilled only if they can be produced routinely at high concentrations. We have compared the ability of Escherichia coli and Pichia pastoris to produce functional recombinant single chain antibody (scAb) fragments. Two scAb fragments were expressed, an antihuman type V acid phosphatase (TRAP) and an anti-Pseudomonas aeruginosa lipoprotein I. We report here that, while expression from P. pastoris resulted in a significantly increased level of expression of the anti-TRAP scAb compared to E. coli, neither fragment was able to bind its target antigen as well as the bacterial product.

Acid Phosphatase↗
PubMed1999

The impact of re-engineering and other cost reduction strategies on the staff of a large teaching hospital: a longitudinal study.

OBJECTIVES: To examine changes over time in the hospital staff's perceptions of how rapid organizational change, caused by fiscal constraints imposed by governments, affects them, their work environment, and the quality of care and services that they provide. METHODS: A random sample of hospital employees (n = 900) of a large Ontario teaching hospital participated in a longitudinal study which involved surveys at 3 measurement periods over a 2-year period. The questionnaire used in this study included scales reflecting work environment, emotional distress, personal resources, spillover from work to home and vice versa, and perceptions regarding patient care and the hospital as an employer. RESULTS: Significant increases in depression, anxiety, emotional exhaustion, and job insecurity were seen among employees, particularly during the first year of the change process. By the end of the second year, employees reported deterioration in team work, increased unclarity of role, and increased use of distraction to cope. Job demands increased throughout the period whereas little change occurred in the employee's job influence or decision latitude. Overall, the work environment was negatively affected. Although patient care was unaffected in the first year, a significant decline in perceptions of patient care, attention to quality improvement, and overall quality of care were later seen. CONCLUSIONS: This study raises questions about whether hospital re-engineering and mergers will be able to achieve the cost reductions sought without sacrificing quality of work life. Along with the rapid change, there was increase in emotional distress among staff and a deterioration in their relationship with their employer.

Adaptation, Psychological↗
PubMed1999

Rethinking public health: new training for new times.

The new public health agenda will require major changes in the way health authorities, local authorities, Trusts and Primary Care Groups organise and manage their activities. The requirement is for inter-agency co-ordination and inter-professional and inter-sectoral working to a shared agenda, yet the human and resources development planning to achieve these goals has not been done. This paper summarises the key training issues and argues for a collaborative, decentralised and quality assured approach to multidisciplinary public health management education and training. Only with such a joined up human resources plan can Our Healthier Nation succeed where The Health of the Nation signally failed.

Health Planning↗
PubMed1999

Contribution of endoscopic retrograde pancreatography in management of complications following distal pancreatic trauma.

Pancreatic trauma is associated with high morbidity and mortality. Treatment of this condition is controversial. This retrospective study aimed to evaluate the management of distal pancreatic trauma and its complications, assessing the role of endoscopic retrograde cholangiopancreatography (ERCP). The clinical course and surgical management of 38 patients with distal pancreatic trauma were analyzed in a university hospital in Paris, France. Twenty-five patients were referred after initial treatment elsewhere. As initial treatment, patients underwent external drainage (n = 25), pancreatic resection (n = 6), laparotomy alone (n = 5), and no surgery (n = 2). Nineteen patients with pancreatic duct injury and no pancreatic resection developed fistulae (n = 14) or pseudocysts (n = 5). Only four of these patients recovered without a subsequent pancreatic resection or internal drainage procedure. In the absence of duct injury, patients recovered without the need for pancreatic resection. ERCP was performed in 16 cases and provided critical information on duct status influencing surgical management. We conclude that the presence of pancreatic trauma duct injury is a major determinant of complications and outcome after pancreatic trauma. It is optimally managed by pancreatic resection. ERCP is valuable in providing a definitive diagnosis of duct injury, thereby directing treatment.

Abdominal Injuries↗
PubMed1999

Determination of monoamine oxidase activity by HPLC with fluorimetric detection.

The aldehyde produced from the oxidative deamination of primary and secondary amines by the monoamine oxidases (EC 1.4.3.4; MAO) or the semicarbazide-sensitive amine oxidases (EC 1.4.3.6; SSAO) may be determined followed reaction at elevated temperatures with 2-diphenylacetyl-1,3-indandione-1-hydrazone (DIH), separation by high-performance chromatography liquid (C-8 column, eluting isocratically with acetonitrile, ammonium acetate, water) and fluorimetric detection (excitation and emission wavelengths 430 and 525 nm). The detection limits for benzaldehyde, p-hydroxybenzaldehyde and 2-phenylacetaldehyde were 125 nM, 150 and 62.3 nM, respectively. Thus the assay is appropriate for determination of amine oxidase activities towards benzylamine, 2-phenylethylamine and tyramine. The fluorescence of the DIH adduct with indole-3-aldehyde was strongly quenched, giving a relatively high detection limit (17.5 microM). The detection limit was lower (3.8 microM) when the absorbance at 430 nm was monitored. Enzyme activities determined by this procedure were shown to be linear with enzyme-protein concentration (rat liver mitochondria). The presence of 1-2 mM semicarbazide, necessary for determining MAO activities in samples also containing SSAO, did not adversely affect the derivatization reaction. The DIH-aldehyde adducts were sufficiently stable to permit their storage at low temperatures prior to assay. The product produced by reaction of 5-hydroxyindole acetaldehyde with DIH had no significant fluorescence and too low an absorbance at 430 nm to allow its determination for assay of activities towards 5-HT. This procedure can also measure succinic semialdehyde (detection limit 240 nM) and thus would be applicable to the determination of GABA transaminase activity.

Aldehydes↗
PubMed1999

Treatment of attention-deficit/hyperactivity disorder.

OBJECTIVES: To determine (a) the long-term and short-term effectiveness and safety of pharmacological and nonpharmacological interventions for attention-deficit/hyperactivity disorder (ADHD) in children and adults and (b) whether combined interventions are more effective than individual interventions. SEARCH STRATEGY: MEDLINE (from 1966), CINAHL (from 1982), HEALTHStar (from 1975), PsycINFO (from 1984), EMBASE (from 1984), and the Cochrane Library searches were completed in November 1997. Reference lists of eligible studies and files of members of the research team and partner organizations were also searched. SELECTION CRITERIA: Studies were selected if they focused on the treatment of ADHD in humans and were published in any language as a full report in peer-reviewed journals. Studies including conditions other than ADHD were reported if separate subgroup analyses for patients with ADHD were provided. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data for 41 variables on general characteristics, along with detailed information on interventions, outcomes, and tests. Differences were resolved by consensus or by a third researcher. Studies were not combined quantitatively because the quality of reporting was low and heterogeneity existed across outcome measures and tests. MAIN RESULTS: Seventy-eight studies (77 randomized controlled trials) met the inclusion criteria. Twenty-three studies compared drugs and showed few, if any, differences among methylphenidate (MPH), dextroamphetamine (DEX), and pemoline; studies comparing stimulants with tricyclic antidepressants (2) were inconclusive. Six studies compared drugs with nondrug interventions and showed consistently that stimulants, particularly MPH, may be more effective than nonpharmacological interventions. Twenty studies compared combination therapies with a stimulant or a nondrug intervention alone; no additional beneficial effects for combination therapies were shown. Nine studies compared tricyclic antidepressants with placebo and showed that desipramine may be more effective than placebo; no consistent effect was shown for imipramine. Fourteen studies (13 in school children and 1 in adults) evaluated long-term therapy (> or = 12 weeks) and showed a trend to general improvement regardless of treatment, but the length of followup was inadequate. MPH may reduce behavioral disturbance in children with ADHD while it is taken. Academic performance does not appear to be improved with stimulants. Twelve studies evaluated treatment in adults with ADHD. For MPH vs. placebo, the results were contradictory. Antidepressants may be effective in adults, but no beneficial effect was seen with pemoline, nicotine, or phenylalanine compared with placebo. Thirty-two reports (29 studies) evaluated adverse effects of drug therapy; many of the side effects associated with stimulant use appear to be relatively mild and of short duration and to respond to dosing or timing adjustments. Data are inadequate on the long-term effects and severity of adverse effects of most interventions. CONCLUSIONS: This report describes rigorous systematic reviews on the treatment of ADHD, ready for incorporation into evidence-based clinical practice guidelines or performance measures. The report also provides a detailed description of the many limitations of the evidence available and provides recommendations to fill existing knowledge gaps. Studies on ADHD have low reporting quality, methodological flaws, and heterogeneity across outcome measures and tests. A detailed description is included of the many limitations of the available evidence plus recommendations to fill existing knowledge gaps. Fulfilling such knowledge gaps will not be easy and will require genuine collaboration among decisionmakers.

Adrenergic Uptake Inhibitors↗
PubMed1998

Lymphocyte-specific protein 1 expression in eukaryotic cells reproduces the morphologic and motile abnormality of NAD 47/89 neutrophils.

Despite its name, the actin-binding protein lymphocyte-specific protein1 (LSP1) is found in all hematopoetic cells, and yet its role in cell function remains unclear. Recently, LSP1 was identified as the 47-kD protein overexpressed in the polymorphonuclear neutrophils of patients with a rare neutrophil disorder, neutrophil actin dysfunction with abnormalities of 47-kD and 89-kD proteins (NAD 47/89). These neutrophils are immotile, defective in actin polymerization in response to agonists, and display distinctive, fine, "hairlike" F-actin-rich projections on their cell surfaces. We now show that overexpression of LSP1 produces F-actin bundles that are likely responsible for the morphologic and motile abnormalities characteristic of the NAD 47/89 phenotype. Coincident with LSP1 overexpression, cells from each of several different eukaryotic lines, including a highly motile human melanoma line, develop hairlike surface projections that branch distinctively and contain F-actin and LSP1. The hairlike projections are supported at their core by thick actin bundles, composed of actin filaments of mixed polarity, which periodically anastomose to generate a branching structure. The motility of the melanoma cells is inhibited even at low levels of LSP1 expression. Therefore, these studies show that overexpression of LSP1 alone can recreate the morphologic and motile defects seen in NAD 47/89 and suggest that LSP1 is distinct from other known actin binding proteins in its effect on F-actin network structure.

Calcium-Binding Proteins↗
PubMed1998

Conversion of taurine into N-chlorotaurine (taurine chloramine) and sulphoacetaldehyde in response to oxidative stress.

N-Chlorotaurine (taurine chloramine), formed by treating taurine with hypochlorous acid, was shown to decompose to sulphoacetaldehyde with a first-order rate constant of 9.9+/-0.5 x 10(-4).h-1 at 37 degrees C in 0.1 M phosphate buffer, pH 7.4. Rat liver homogenates accelerated this decay in a process that was proportional to tissue-protein concentration and saturable, with maximum velocity (Vmax) and Km values of 0.28+/-0.01 nmol/min per mg of protein and 37+/-9 microM respectively. This activity was found to be lost on heat denaturation, but retained after dialysis. There was no detectable formation of sulphoacetaldehyde when taurine itself was incubated with the tissue homogenates under the same conditions. Activation of human neutrophils (1.67 x 10(6) cells/ml) with latex beads resulted in a respiratory burst of oxygen-radical production, the products of which were partially sequestered by 12.5 mM taurine. Under these conditions sulphoacetaldehyde was generated at a constant rate of 637+/-18 pmol/h per ml for over 7 h. A non-activated neutrophil suspension contained constant levels of 1.42+/-0.02 nmol/ml sulphoacetaldehyde, as did activated cells incubated in the absence of taurine, a basal level which may indicate a steady turnover of taurine in these cells. Such formation of chlorotaurine and its decay to the aldehyde may be the first steps in the metabolism of taurine to isethionate (2-hydroxyethanesulphonate) that has been demonstrated by various authors to occur in vivo.

Acetaldehyde↗
PubMed1998

Isolation of the first piscine transforming growth factor beta gene: analysis reveals tissue specific expression and a potential regulatory sequence in rainbow trout (Oncorhynchus mykiss).

The nucleotide sequence of a rainbow trout transforming growth factor beta (TGF-beta) peptide is presented, which translates into a 382 amino acid precursor molecule containing a 20 amino acid leader and a mature peptide of 112 amino acids. The mature peptide has nine conserved cysteines and a conserved proline (position 36) and glycine (position 46), all characteristics of TGF-beta superfamily molecules. Within the precursor region are three glycosylation sites, two in common with known TGF-beta s, an integrin binding site (RGD) and the tetrabasic peptide cleavage site (RKKR). The full 3' untranslated region (UTR) consists of 542 nucleotides with a polyadenylation signal 16 nucleotides upstream of the poly(A) tail. The 5' UTR contains an open reading frame with the potential to encode an eleven amino acid peptide, which may have significance for regulation of TGF-beta translation. A wide tissue distribution of TGF-beta message was detected by RT-PCR; in blood leukocytes, kidney macrophages, brain, gill, and spleen tissue but not liver. A phylogenetic tree reveals the trout TGF-beta sequence is most related to xenopus TGF-beta 5, with these sequences and that of chicken TGF-beta 4 grouping with mammalian TGF-beta 1 s. The impact of the trout sequence on current theories of TGF-beta isotype evolution is discussed.

Amino Acid Sequence↗
PubMed1998

Long-term functional outcome after low anterior resection: comparison of low colorectal anastomosis and colonic J-pouch-anal anastomosis.

OBJECTIVE: The purpose of this study was to compare long-term functional results of two methods of reconstruction after anterior rectal resection for cancer: low colorectal anastomosis and colonic J-pouch-anal anastomosis. SUMMARY BACKGROUND DATA: After anterior resection for mid or low rectal cancer, the decision to perform low colorectal or coloanal anastomosis is made intraoperatively, depending on the distance of the tumor from the anal verge. Functional results of these operations are considered to be similar one to two years after surgery. No study to date has compared long-term functional results after rectal excision followed by either low colorectal anastomosis or colonic J-pouch-anal anastomosis. METHODS: From 1987 to 1992, 173 patients underwent anterior resection for cancer located between 2 to 12 cm from the anal verge. All patients alive without recurrence were contacted by telephone interview for assessment of functional results. There were 47 patients with colonic J-pouch-anal anastomosis and 34 patients with low colorectal anastomosis. Minimum follow-up was three years for all patients (mean, 5 years). RESULTS: The two groups were well matched for gender, age, histologic stage, and use of adjuvant therapies. Patients with colonic J-pouch-anal anastomosis displayed significantly better function in terms of frequency of defecation (1.57+/-1 vs. 2.79+/-1; P=0.001) and presence of irregular transit or stool "clustering" (30 vs. 71 percent; P=0.003). Patients who underwent colonic J-pouch-anal anastomosis were significantly less likely to require constipating agents (4 vs. 21 percent; P=0.03) or need to follow a restricted diet (14 vs. 41 percent; P=0.01). Results concerning the need to defecate again within one hour and disruption of social or professional life as a consequence of surgery showed a tendency in favor of colonic J-pouch-anal anastomosis. CONCLUSION: Colonic J-pouch-anal anastomosis offers superior long-term function compared with low colorectal anastomosis after radical treatment of rectal cancer. Preservation of a short rectal segment followed by a straight colorectal anastomosis does not offer any clinical advantage over colonic J-pouch-anal anastomosis.

Aged↗
PubMed1998

Use of a jejunal pouch with ileal interposition in salvage surgery after restorative proctocolectomy.

PURPOSE: A novel technique is described for pouch reconstruction after failed restorative proctocolectomy and pouch excision. METHODS: Surgery was undertaken in two patients who had undergone restorative proctocolectomy with subsequent excision of the ileal J-pouch after necrosis. At revisional surgery it was technically impossible to form a pouch using the terminal ileum because of mesenteric shortening. A new 18-cm J-pouch was formed with a jejunal segment. After selective division of axial vessels, adequate length was obtained to allow formation of a jejunal-pouch-anal anastomosis. The small bowel distal to the pouch was interposed between the proximal jejunum and J-pouch and a defunctioning stoma was made. RESULTS: The postoperative course was uneventful in both cases. The functional results at 3 and 12 months after stoma closure were good, with five to seven bowel movements per day and complete continence. CONCLUSION: Shortening of the terminal ileal mesentery may preclude the formation of an ileal pouch in patients undergoing salvage surgery after failed restorative proctocolectomy. This novel technique of jejunal J-pouch formation and small-bowel interposition has value as an alternative to definitive ileostomy or Kock's pouch in such patients.

Adolescent↗
PubMed1998

Production of soluble single-chain T-cell receptor fragments in Escherichia coli trxB mutants.

Antibodies and T cell receptors (TCR) both belong to the immunoglobulin superfamily whose members are characterised by the possession of one or more immunoglobulin domains. The production of soluble single chain antibody fragments in Escherichia coli has, in recent years, become a routine laboratory procedure. In contrast, the production of T cell receptors in bacteria has remained problematic as the majority of the recombinant protein is insoluble. In this paper we show that single chain TCR produced in E. coli BL21 (DE3) and directed to the periplasm was also insoluble and that this was in part due to the failure of the cell protein processing machinery to cleave the pelB leader sequence. This problem was overcome by expressing the single chain TCR in the cytoplasm of E. coli which carry an inactive thioredoxin reductase gene. This strain allows the formation of disulphide bonds in the cell cytoplasm which we believe encourages the correct folding of the recombinant protein. We have constructed both a human and mouse single chain TCR in these bacteria and demonstrated using BIAcore technology that these molecules have folded in a conformation which allows their recognition by conformational specific ligands. In addition, we have used one of our soluble single chain TCR preparations to isolate a TCR specific Fab molecule from a phage antibody library.

Amino Acid Sequence↗
PubMed1998

Influence of a defunctioning stoma on leakage rates after low colorectal anastomosis and colonic J pouch-anal anastomosis.

BACKGROUND: Anal sphincter function is increasingly preserved following rectal excision for cancer and provides a better quality of life for patients than does a permanent colostomy. However, anastomotic complications may cause considerable morbidity and mortality. This retrospective study examined the incidence of anastomotic complications following two forms of reconstruction after resection for mid-rectal cancer: colonic pouch-anal anastomosis (CPAA) and low colorectal anastomosis (LCRA). METHODS: Some 258 consecutive patients with mid-rectal cancers between 6 and 11 cm from the anal verge underwent proctectomy with mesorectal excision and either CPAA or LCRA. The incidence of clinical and radiological leaks was determined in these patients who were considered in three groups: LCRA (defunctioning stoma), LCRA (no defunctioning stoma) and CPAA (all defunctioned). RESULTS: In the LCRA group without a defunctioning stoma, a clinical leak occurred in 17.0 per cent, compared with two of 30 in the LCRA group with a defunctioning stoma. In the CPAA group a clinical leak occurred in 4.9 per cent of patients, which was not significantly different from the rate in those with a defunctioned LCRA. Patients with a non-defunctioned LCRA were more likely to suffer a clinical anastomotic leak (P=0.01), peritonitis (P=0.001) and require unscheduled reoperation (P=0.006) than those with a defunctioned LCRA and/or CPAA. CONCLUSION: The use of a protective defunctioning stoma is advocated in conjunction with LCRAs.

Aged↗
PubMed1998

Identification of the UL4 protein of herpes simplex virus type 1.

Herpes simplex virus type 1 gene UL4 is predicted to encode a 199-amino-acid protein with a molecular mass of 21 5 kDa. We report here identification of this protein and its localization in the nuclei of infected cells. Antisera raised against oligopeptides corresponding to the C terminus of the predicted UL4 protein were used for identification of a 25 kDa protein as the product of the UL4 gene. This protein was not detected in cells infected with a UL4 defective mutant virus, but was synthesized by coupled in vitro transcription-translation of the UL4 gene. Synthesis of the 25 kDa protein was blocked by phosphonoacetic acid, an inhibitor of DNA synthesis, indicating that the UL4 gene is expressed with gamma kinetics. Subcellular fractionation showed the protein to be localized in the nucleus. It was not detected in virions or light particles.

Amino Acid Sequence↗