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Biomedical subjects

D M Wallace

Publications and source records attributed to D M Wallace.

At least 19 recordsLinked to original sources
PubMed2001

Minimally invasive vein harvest and wound healing using the SaphLITE Retractor System.

BACKGROUND: In response to reported wound complication rates of 19% to 43% for traditional saphenous vein harvest, several minimally invasive vein harvest (MIVH) techniques have been developed. The purpose of this investigation is to determine the effectiveness of one such MIVH technology, the Genzyme SaphLITE Retractor System (Genzyme Biosurgery, Cambridge, MA). METHODS: Since May 2000, saphenectomy was undertaken in 305 coronary artery bypass graft (CABG) patients using SaphLITE in a prospective, nonrandomized trial at three centers. Patients were assessed for wound healing (ASEPSIS tool) and incisional pain (numeric scale) through the postoperative visit. Harvest times, incision lengths, and vein lengths were recorded. RESULTS: ASEPSIS indicated satisfactory healing in 96.0%. Infection rate was 1.3% with four patients requiring antibiotics and debridement of one incision. Of hospitalized patients, 85.4% had no or minimal affected leg pain. Additional mean data include: harvest time 43.4 +/- 17.6 minutes, incision number 3.0 +/- 1.2, incision length 2.9 +/- 1.4 cm, and vein length 46.0 +/- 15.2 cm. CONCLUSIONS: SaphLITE provides an effective alternative to traditional saphenous vein harvest, with improved wound healing, decreased pain, and acceptable harvest times.

Adult↗
PubMed2001

A phase I-II study of synchronous chemoradiotherapy for poor prognosis locally advanced bladder cancer.

BACKGROUND: The management of locally advanced bladder cancer remains controversial with poor local control with radiotherapy alone. Synchronous chemotherapy regimens have yielded encouraging results in other primary sites. PATIENTS AND METHODS: Patients with T2-T4a N0/NX M0 bladder cancer were entered into this single centre phase I-II study. Patients received radiotherapy to 55 Gy in 20 fractions over four weeks. Concurrent chemotherapy was given with Mitomycin C 12 mg/m2 day 1 and 5-fluorouracil 500 mg/m2/24 hours weeks one and four of radiotherapy for five or seven days on each occasion. RESULTS: Thirty-one patients entered the trial from March 1998 to December 1999 (22: 5-day; 9: 7-day schedule). Median age was 68 (range 58-79) years, 23 males and 8 females. T2: 9 (29%); T3a: 4 (12%); T3b: 9 (29%); T4: 9 (29%); TCC grade 2: 8 (26%) and grade 3: 23 (74%); 14 of 31 had hydronephrosis. Ten of thirty-one had a GFR < 50 ml/min. Toxicity was mild to moderate with the five-day schedule. More severe toxicity was seen with the seven-day schedule: five of nine patients failed to complete planned therapy. Pathological complete response rate at three months was 74% (5-day regimen) and 50% (7-day regimen). Overall 12-month survival was 65%. CONCLUSION: Chemoradiotherapy with the five-day schedule is feasible with acceptable toxicity in poor prognosis patients. A randomised trial is being launched.

Aged↗
PubMed2001

cDNA array analysis of cag pathogenicity island-associated Helicobacter pylori epithelial cell response genes.

Helicobacter pylori strains containing the cag pathogenicity island (PAI) induce NF-kappaB activation and interleukin-8 secretion in gastric epithelial cells. The aim of this study was to investigate changes in epithelial gene expression induced by cag PAI-positive and -negative strains of H. pylori using high-density cDNA array hybridization technology. Radio-labeled cDNA prepared from H. pylori-infected Kato 3 gastric epithelial cells was hybridized to high-density cDNA arrays to identify changes in epithelial gene expression compared to noninfected controls. In vivo expression of selected, differentially expressed genes was examined by reverse transcription-PCR analysis of H. pylori-positive and -negative gastric mucosa. Screening of ca. 57,800 cDNAs identified 208 known genes and 48 novel genes and/or expressed sequence tags of unknown function to be differentially expressed in Kato 3 cells following H. pylori infection. Marked differences in gene expression profiles were observed following cag PAI-positive and cag PAI-negative infection with 15 novel cDNAs and 92 known genes being differentially expressed. H. pylori was found to change the expression of genes encoding growth factors and cytokine/chemokines and their receptors, apoptosis proteins, transcription factors and metalloprotease-disintegrin proteins (ADAMs), and tissue inhibitors of metalloproteinases. Gastric differential expression of selected known genes (amphiregulin and ADAM 10) and a novel gene (HPYR1) was confirmed in vivo in patients with H. pylori infection. Confirmation of the in vivo expression of selected genes demonstrates the usefulness of this approach for investigating pathogen-induced changes in host gene expression.

ADAM Proteins↗
PubMed2000

The role of apolipoprotein E in Alzheimer's disease: pharmacogenomic target selection.

The association of inheritance of different apolipoprotein E (APOE, gene; apoE, protein) alleles with the risk and rate of onset of Alzheimer's disease (AD) is now well established and widely confirmed. While there are now a collection of hypotheses concerning the specific relationship of APOE polymorphisms to various phenotypic manifestations of AD, no single compelling theory has been tested and universally accepted. The only clear fact emerging during the past 6 years is that differences in APOE genotype affect the average rate of disease onset as a predictable function of the inheritance of this polymorphic gene. Methods now exist to enable experimental designs to study the metabolic effects of inheriting different APOE alleles, addressing what differences that may be present for many years, perhaps over the entire lifetime, can lead to earlier or later manifestations of the disease and are therapeutically tractable. This review summarizes part of an experimental approach to identify biological pathways influenced by the different APOE polymorphisms that are relevant to the pathogenesis of AD.

Alleles↗
PubMed2000

Global analysis of transcription kinetics during competence development in Streptococcus pneumoniae using high density DNA arrays.

The kinetics of global changes in transcription patterns during competence development in Streptococcus pneumoniae was analysed with high-density arrays. Four thousand three hundred and one clones of a S. pneumoniae library, covering almost the entire genome, were amplified by PCR and gridded at high density onto nylon membranes. Competence was induced by the addition of CSP (competence stimulating peptide) to S. pneumoniae cultures grown to the early exponential phase. RNA was extracted from samples at 5 min intervals (for a period of 30 min) after the addition of CSP. Radiolabelled cDNA was generated from isolated total RNA by random priming and the probes were hybridized to identical high density arrays. Genes whose transcription was induced or repressed during competence were identified. Most of the genes previously known to be competence induced were detected together with several novel genes that all displayed the characteristic transient kinetics of competence-induced genes. Among the newly identified genes many have suggested functions compatible with roles in genetic transformation. Some of them may represent new members of the early or late competence regulons showing competence specific consensus sequences in their promoter regions. Northern experiments and mutational analysis were used to confirm some of the results.

Base Sequence↗
PubMed2000

Bcl-2 expression identifies patients with advanced bladder cancer treated by radiotherapy who benefit from neoadjuvant chemotherapy.

OBJECTIVE: To assess the prognostic significance of Bcl-2 expression on the clinical outcome after radiotherapy for muscle-invasive bladder cancer, and to determine if it is possible to identify a subgroup of patients to whom neoadjuvant chemotherapy can be targeted to improve survival. PATIENTS AND METHODS: Immunohistochemical staining for Bcl-2 and p53 was performed on the tumours of 51 patients with stage T2-T4a NXM0 transitional cell carcinoma of the bladder who had been included in a randomized clinical trial of radiotherapy with or without neoadjuvant cisplatin. The association between positive staining and salvage cystectomy rate and overall survival was examined, with a median follow-up of 12 years. RESULTS: Bcl-2 and p53 expression was positive in 31 (61%) and 39 (76%) of the tumours, with no association between either, or with tumour stage or grade. There was no difference according to Bcl-2 positivity in the salvage cystectomy rate (P = 0.83) or survival (P = 0.68) for the 51 patients as a whole, but Bcl-2-negative patients receiving neoadjuvant cisplatin had a significantly better prognosis, with a median survival of 72 months compared to 17 months in Bcl-2-positive patients, and a 5-year survival rate of 55% (P = 0.03). CONCLUSIONS: Quantifying Bcl-2 in patients undergoing radiotherapy for advanced bladder cancer identifies those who may benefit from neoadjuvant chemotherapy. Further studies of other members of the Bcl-2 family and other proteins controlling both cell proliferation and apoptosis are warranted, to define the roles and the interactions between them that may contribute to oncogenesis and resistance to standard treatments. This may allow the targeting of specific treatments to patients known to be sensitive to them, and aid the future development of novel therapies for bladder cancer.

Adult↗
PubMed2000

Warfarin is safe as secondary prophylaxis in patients with cancer and a previous episode of venous thrombosis.

The purpose of this study was to establish the safety and efficacy of sodium warfarin in the secondary prophylaxis of venous thrombosis in patients with cancer. This was an inception cohort study of patients enrolled in an anticoagulation clinic between July 1991 and October 1996. The rates of bleeding and recurrent thrombosis were evaluated in all the patients, and the results in patients with cancer (n = 104) were compared with those without cancer (n = 208). The rate of major hemorrhage was 0.4% and 0.3% per treatment month in the patients with cancer and those without cancer, respectively. The rates of recurrent thrombosis were 1.2% and 0.2% per treatment month in the patients with cancer compared with those without cancer, respectively. We conclude that warfarin is safe when used for the secondary prophylaxis of patients with cancer who have had a venous or arterial thrombosis, and the risk of major hemorrhage is not significantly different when compared with the risk in patients without cancer. The rate of recurrent thrombosis is approximately sixfold higher in patients with cancer being treated with warfarin for secondary prophylaxis of thrombosis compared with patients without cancer. Nonetheless, the rate of recurrent thrombosis is not overly excessive, and warfarin can be viewed as a relatively effective form of therapy for these patients.

Anticoagulants↗
PubMed2000

Long-term risk of salvage cystectomy after radiotherapy for muscle-invasive bladder cancer.

OBJECTIVES: To establish the long-term outcome for muscle-invasive transitional cell carcinoma of the bladder treated by radiotherapy with or without neoadjuvant cisplatin. METHODS: 159 patients with T2-T4a NX M0 bladder cancer were entered into a prospective randomized trial between June 1984 and June 1988. Follow-up was by 3-monthly cystoscopy in the first year, 6-monthly the next 2 years and yearly thereafter. Salvage surgery was performed at the discretion of the participating clinician. RESULTS: Minimum follow-up was 9 (median 11) years, at which time 29 patients (18%) remain alive. Median survival was 24 months with no difference between the treatment groups (chi(2) = 0.08, p = 0.77). Overall cystectomy rate was 24% (radiotherapy alone 20%, combined therapy 28%; p = 0.24). Median time to cystectomy from primary treatment was 12 months; range 56 days to 10 years. The risk of cystectomy was 11, 10 and 7% for the first, second and third years after radiotherapy respectively, and 8% in total after the third year. The proportion of patients alive in each successive year who had required a cystectomy was between 20 and 30% for 5 of the first 8 years after treatment. CONCLUSIONS: Salvage cystectomy is necessary in a quarter of patients after radiotherapy and this can be needed up to 10 years after treatment. During this time, multiple invasive procedures are likely to be performed, resulting in significant patient morbidity and cost. Patients should be fully counselled about the need for prolonged surveillance and the persisting risk of salvage surgery when deciding between primary cystectomy and radiotherapy.

Adult↗
PubMed1999

Identification of two novel diurnal genes by screening of a rat brain cDNA library.

While the hypothalamus is fundamental for sleep and circadian regulation, the molecular mechanism involved are poorly understood. We have used a differential gene expression technique to identify hypothalamic genes which have altered expression in rat sleep periods. Complex cDNA probes from rat hypothalami removed at Zeitgeber times 4 and 15 were hybridised to rat brain cDNA library girds. From 30 differentially expressed clones, six were further analysed and two were confirmed to exhibit increased expression at Zeitgeber time 4. A Northern blot hybridization of brain, heart, kidney, lung, testis and skin mRNA showed that both clones were brain specific. Therefore, we have identified two novel brain specific diurnally expressed hypothalamic genes. Both genes may have roles in sleep or circadian regulation.

Animals↗
PubMed1999

Phase II trial of radical surgery for locally advanced pelvic neoplasia.

BACKGROUND: Reported operative mortality and survival rates following total pelvic exenteration (TPE) for recurrent pelvic neoplasia are now as good as those for many primary treatments. The currently accepted primary treatments for these tumours are, however, still either radiotherapy alone or radiotherapy and chemotherapy. The primary aim of this study was to evaluate the safety and tolerability of TPE and secondarily to ascertain survival after TPE. METHODS: This was a phase II study of 50 patients with locally advanced pelvic tumours who underwent TPE. RESULTS: Thirty-two patients (64 per cent) underwent TPE for recurrent carcinoma of the cervix, seven (14 per cent) for rectal cancer, three (6 per cent) for vulval carcinoma, three (6 per cent) for vaginal carcinoma, two (4 per cent) for prostate cancer and three (6 per cent) for other tumours. The 30-day mortality rate was 8 per cent with an in-hospital mortality rate of 16 per cent. The crude morbidity rate was 62 per cent, with 23 patients (46 per cent) having grade III or IV toxicity. A complete response was achieved in 63 per cent and a partial response in 37 per cent of patients. The overall median survival time was 86 weeks; it was 111 weeks in patients in whom a complete response was achieved. CONCLUSION: The survival and operative mortality rates that are now attainable with TPE are comparable to those achieved with chemoradiotherapy in advanced pelvic neoplasia. TPE should no longer be reserved for salvage therapy and should perhaps be compared with chemoradiotherapy as first-line treatment in a phase III randomized trial in patients with these tumours.

Adult↗
PubMed1999

Patients' tolerance of transrectal ultrasound-guided prostatic biopsy: an audit of 104 cases.

OBJECTIVE: To determine the frequency and severity of complications following transrectal ultrasonography (TRUS) guided prostatic biopsy, and of pain during the procedure. PATIENTS AND METHODS: The study included 129 men undergoing TRUS-guided prostatic biopsy who were asked to complete a questionnaire about pain and complications one week after biopsy. RESULTS: Of the 104 men who completed the questionnaire, 24% found the procedure moderately to extremely painful and 19% felt that they had had significant complications afterward, the commonest of these being painful or difficult voiding (13%) and haematuria (11%). Systemic symptoms of fever or 'sweats' occurred in 6%, with a diagnosis of septicaemia in three men, despite antibiotic prophylaxis. However, acute urinary retention occurred in only one man. Of all patients, 20% saw their general practitioner within a week, all of whom were prescribed antibiotics in addition to those given prophylactically in hospital. CONCLUSION: TRUS-guided biopsy is often a painful experience for patients and is commonly associated with complications, particularly voiding difficulties. Of particular concern were the three patients with septicaemia, and that one in five men felt sufficiently unwell to visit their doctor within a week of the procedure.

Anti-Bacterial Agents↗
PubMed1999

CCR7 (EBI1) receptor down-regulation in asthma: differential gene expression in human CD4+ T lymphocytes.

Asthma is an inflammatory disorder, and the CD4+ T lymphocyte plays a key role in mediating the inflammatory response. We used a high-density grid, hybridization-based, differential gene expression technology to analyse molecular mechanisms underlying in vivo CD4+ T-cell activation in both steroid-resistant asthma (SRA) and steroid-sensitive asthma (SSA). Hybridization of radioactively-labelled first-strand cDNAs prepared from different biological samples, to identical high-density gridded arrays of PCR amplicons derived from cDNA clone inserts immobilized on nylon membranes, was compared by phosphorimaging. Hybridization data were captured and processed using image analysis software that can identify the location and signal intensity of each hybridized cDNA. This produces a hierarchy of signals of differing intensities between the two grids, representing differential gene expression in the two different RNA samples. CCR7 (EBI1), a lymphocyte-specific G-protein-coupled receptor, was down-regulated in the CD4+ T cells of SRA and SSA non-atopic, compared to non-asthmatic non-atopic individuals. This observation is intriguing given that CCR7 and its ligand EBI1-Ligand Chemokine (ELC), may play a role in the migration and homing of normal lymphocytes. Also, TNFR2 is up-regulated in both SSA non-atopic and SRA atopic as compared to non-asthmatic controls. LAMR1 is down-regulated in CD4+ T cells of SRA compared to non-asthmatic individuals, irrespective of their atopic status. These could be general phenomena resulting from cytokine release.

Adult↗
PubMed1998

Identification of two novel diurnal genes by screening of a rat brain cDNA library.

While the hypothalamus is fundamental for sleep and circadian regulation, the molecular mechanisms involved are poorly understood. We have used a differential gene expression technique to identify hypothalamic genes which have altered expression in rat sleep periods. Complex cDNA probes from rat hypothalami removed at Zeitgeber times 4 and 15 were hybridised to rat brain cDNA library girds. From 30 differentially expressed clones, six were further analysed and two were confirmed to exhibit increased expression at Zeitgeber time 4. A Northern blot hybridization of brain, heart, kidney, lung, testis and skin mRNA showed that both clones were brain specific. Therefore, we have identified two novel brain specific diurnally expressed hypothalamic genes. Both genes may have roles in sleep or circadian regulation.

Animals↗
PubMed1998

Occupational urothelial tumours: a regional case-control study.

OBJECTIVE: To investigate the role of occupational exposures in the risk of developing urothelial cancer. MATERIALS AND METHODS: Occupational histories, obtained using a self-administered questionnaire, for 803 patients with urothelial cancer (first diagnosed 1991-93) were compared with similar information for 2135 matched controls. Relative risks (RRs) were estimated using conditional logistic regression. Comparisons were also made with historical regional employment information available from the 1971 census. RESULTS: There were many statistically significant positive associations for urothelial cancer risks and ever being employed in specified occupations (with or without statistical adjustment for smoking status in 1991). Smoking-adjusted RRs of > 2.0 were obtained for seven occupations; manufacture of fire lighters/ patent fuels (RR 4.30, 95% confidence interval 0.78-23.79), rodent extermination (3.71, 1.20-11.48), manufacture of dyestuffs (2.61, 0.98-7.00), leather work (2.51, 1.44-4.35), cable manufacturing industry (2.46, 1.20-5.04), textile printing and dyeing (2.32, 0.98-5.45), and sewage works (2.19, 1.16-4.11). Analyses of the occupations followed in 1971 (thus allowing for 20-year latency) indicated an elevated RR for workers in the plastics industry (5.22, 1.57-17.36). CONCLUSIONS: The historical legacy of exposure to aromatic amines in the rubber, cable-making, dyestuffs and other industries remains. An important proportion of patients presenting with urothelial tumours are likely to have had occupational exposure to urothelial carcinogens. A review of occupational exposures in the contemporaneous plastic, textile and leather industries is warranted.

Adult↗
PubMed1997

Efficacy and safety of oral anticoagulation in patients with cancer.

The treatment of venous thrombosis in patients with cancer is a common clinical problem. It appears that long term oral anticoagulant therapy with coumadin does not carry a significantly increased risk of major bleeding compared with the risk in patients without cancer. However, the risk of recurrent thrombosis in these individuals appears to be higher than in those patients without cancer. Nevertheless, the treatment of most patients with cancer and venous thrombosis with standard anticoagulant therapy is reasonable. Prospective, randomized trials are required to determine the optimal therapy for these patients, and, in particular, those that have failed traditional anticoagulation.

Administration, Oral↗
PubMed1996

Case report: paravesical suture granuloma resembling bladder carcinoma on CT scanning.

Paravesical granuloma formation is a rare complication of inguinal herniorrhaphy. Infected non-absorbable suture material is the usual cause. We present a case of paravesical granuloma that was initially thought to be bladder carcinoma both clinically and on CT scanning. The patient presented with urinary symptoms. Repeated biopsies revealed only reactive changes with no evidence of malignancy. CT showed a mass which appeared to arise from the anterior aspect of the bladder with a central area of low attenuation. The diagnosis was established at cystoscopy with deep resection of the mass, when two retained silk stitches with surrounding pus and granulation tissue was found. The diagnosis of paravesical suture granuloma (PSG) should be considered in patients with suprapubic symptoms, no haematuria, an atypical mass and a history of herniorrhaphy, which may have been many years prior to the time of presentation.

Cystoscopy↗
PubMed1995

Slow N-acetylation genotype is a susceptibility factor in occupational and smoking related bladder cancer.

Bladder cancer is a common multifactorial disease and is known to be associated with occupational exposure to arylamines. Smoking is also a recognised contributory environmental cause. Occupational bladder cancer has previously been associated with slow acetylation by N-acetyltransferase (NAT) in humans in phenotyping studies, but more recently there has been some controversy regarding this issue. NAT is an enzymic activity involved in the metabolism of arylamines, and its 'classical' polymorphism is due to multiple alleles at the NAT2 locus. A genotyping approach has been used to investigate NAT2 type in a population of 189 Caucasian bladder cancer patients attending a clinic at a hospital in Birmingham. Genomic DNA was prepared from a blood sample donated by each of the patients and was used in the polymerase chain reaction with primers specific for all NAT2 alleles. Restriction fragment length polymorphism analysis was used to determine which alleles were present. Results have been compared to those from an age-matched non-malignant Caucasian control population (59 individuals) from the same region. Occupational and smoking history was determined by questionnaire and a significant excess of genotypic slow acetylators is found in those groups of bladder cancer patients exposed to arylamines as a result of their occupation or who are cigarette smokers. A higher proportion of slow acetylators is also found in those bladder cancer patients without identified exposure to arylamines when compared to the non-malignant controls. Slow NAT genotype is therefore a contributory risk factor in bladder carcinogenesis which acts through influencing individual response to environmental carcinogens.

Acetylation↗