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Biomedical subjects

A Forbes

Publications and source records attributed to A Forbes.

At least 37 records · Page 2Linked to original sources
PubMed2005

Feasibility of RNA collection for micro-array gene expression analysis in the treatment of cervical carcinoma: a scientific correlate of RTOG C-0128.

PURPOSE: To determine the feasibility of RNA collection in a multi-institutional cooperative group setting to be utilized for micro-array gene expression analysis, and to describe the methodology. METHODS: RTOG C0128, a phase I-II, protocol was designed to look at the safety and efficacy of external beam radiation therapy to 45 Gy with concomitant 5-FU and cisplatin chemotherapy, brachytherapy to deliver 85 Gy to point A, and Celecoxib at 400 mg twice daily for 1 year. Patients had the option of participating in a tissue collection portion of the protocol to be utilized for micro-array gene expression analysis before treatment and at the time of the first implant. RNA quality was determined by two parameters: the absorbance ratio at 260 nm/280 nm, and by the ratio of the integrated peak of 28S RNA to 18S RNA after gel electrophoresis. RESULTS: From August 2001 to March 2004, 84 patients were accrued to the trial, and tissue was obtained prior to initiation of therapy on 34 patients (40%). FIGO stages for the patients who provided tissue were IB (23%), II (57%), and IIIA-IVA (20%). Additionally, biopsies were obtained at the time of the first implant from 22 of the accrued patients making paired samples available on 26% for RNA extraction and micro-array gene expression analysis. The mean +/- SEM amount of tissue obtained pretreatment was 97 +/- 13 mg compared with 51 +/- 8 mg for tissue obtained at the time of the first implant (P = 0.009). The mean total RNA extracted from the samples prior to treatment was 119 +/- 19 microg versus 35 +/- 6 microg at the time of the first procedure (P = 0.001). The RNA quality was assessed via the absorbance ratio at 260 nm divided by 280 nm. The mean values pretreatment and at first implant were 1.87 +/- 0.07 versus 1.66 +/- 0.11, respectively (P = 0.002); however, the integrated peak of 28S RNA to 18S RNA after gel electrophoresis was not significantly different (P = 0.26). CONCLUSIONS: RNA extraction for gene expression analysis can be successfully performed in the multi-institutional cooperative group setting. Fresh tissue samples were obtained on 40% of accrued patients prior to treatment. The amount of biopsy material and the quantity of RNA extracted were greater prior to treatment compared with the first implant. The quality of RNA was superior prior to treatment as measured by the ratio of absorbance at 260/280 nm. These results indicate that gene expression analysis is feasible in the cooperative group setting utilizing amplification techniques for the RNA. Hopefully, this will allow for improvement in prognosis, therapeutic development, and correlation with acute and late toxicities in patients with cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Dreaming during anaesthesia in patients at high risk of awareness.

Dreaming during anaesthesia is commonly reported but remains poorly understood. In this study, adult surgical patients at high risk of awareness were randomly assigned to receive bispectral index (BIS)-guided anaesthesia or routine care, and were interviewed about dreaming three times postoperatively. Dreaming patients (n = 134) were compared with all other patients who were interviewed at least once (n = 2251). Intraoperative dreaming was reported by 4.2%, 3.9% and 3.4% of patients at 2-4 h, 24-36 h and 30 days after surgery, respectively. Fewer BIS-monitored patients reported intra-operative dreaming at 2-4 h than control patients (2.7% vs. 5.7%; p = 0.004). Reports of dreaming were similar in the two groups at 24-36 h and 30 days. Dreaming patients were younger (p = 0.001); healthier (p < 0.001) and more likely to be women (p < 0.001), and were less satisfied with anaesthetic care (p = 0.004) than other patients.

Adult↗
PubMed2005

A general autoimmunity gene (PTPN22) is not associated with inflammatory bowel disease in a British population.

A single-nucleotide polymorphism (C1858T) causing an amino acid substitution (R620W) in the lymphoid protein tyrosine phosphatase gene PTPN22 has been implicated in type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, juvenile idiopathic arthritis and Hashimoto's thyroiditis, thus revealing a general role for this gene in autoimmune disease. We investigated the association of the C1858T variant in an additional autoimmune disease population by performing a case-control study of 514 British individuals with inflammatory bowel disease (IBD) [294 with Crohn's disease (CD) and 220 with ulcerative colitis (UC)] and 374 normal controls. No significant differences in genotype or allele frequencies were observed between IBD, CD or UC and controls, indicating that PTPN22 does not influence risk of IBD.

Amino Acid Substitution↗
PubMed2005

Recovery from bispectral index-guided anaesthesia in a large randomized controlled trial of patients at high risk of awareness.

Electroencephalographic monitors of anaesthetic depth are reported to assist anaesthetists in reducing recovery times. We explored the effect of bispectral index (BIS) monitoring on recovery times in a double-blind, randomized controlled trial of 2,463 patients at high risk of awareness. Patients were randomized to BIS-guided anaesthesia or routine care. In the BIS group, anaesthesia was adjusted to maintain a BIS value of 40-60 from the commencement of laryngoscopy to the start of wound closure, and 55-70 during wound closure. In the routine care group, anaesthesia was adjusted according to traditional clinical signs. In multivariate models, BIS monitoring, female gender, lower American Society of Anesthesiologists' physical status and shorter duration of anaesthesia predicted faster time to eye-opening after anaesthesia, and faster time to post-anaesthesia care unit discharge. BIS monitoring did not affect times to tracheal extubation among patients admitted to the intensive care unit. We conclude that BIS monitoring has statistically significant, but clinically modest, effects on recovery times in high risk surgical patients.

Adult↗
PubMed2004

Effectiveness of intermediate care in nursing-led in-patient units.

BACKGROUND: The Nursing led inpatient Unit (NLU) is one of a range of services that have been considered in order to manage more successfully the transition between hospital and home for patients with extended recovery times. OBJECTIVES: To determine whether nursing-led inpatient units are effective in preparing patients for discharge from hospital compared to usual inpatient care. SEARCH STRATEGY: We searched The Cochrane Library, the Specialized Register of the Cochrane Effective Practice and Organisation of Care (EPOC) group, MEDLINE, CINAHL, EMBASE, BNI and HMIC databases. Citation searches were undertaken on the science and social science citation indices. Authors were contacted to identify additional data. SELECTION CRITERIA: Controlled trials and interrupted time series designs that compared the NLU to usual inpatient care managed by doctors. Patients over 18 years of age following an acute hospital admission for a physical health condition. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Ten random or quasi-random controlled trials reported on a total of 1896 patients. There was no statistically significant effect on inpatient mortality ( OR 1.10, 95% CI 0.56 to 2.16) or mortality to longest follow up (OR 0.92, 95% CI 0.65 to 1.29) but higher qaulity studies showed a larger non-significant increase in inpatient mortality (OR 1.52, 95% CI 0.86 to 2.68). Discharge to institutional care was reduced for the NLU (OR 0.44 95% CI 0.22 to 0.89) and functional status at discharge increased (SMD 0.37, 95% CI 0.20 to 0.54) but there was a near significant increase in inpatient stay (WMD 5.13 days 95% CI -0.5 days to 10.76 days). Early readmissions were reduced (OR 0.52 95% CI 0.34 to 0.80). One study compared a NLU for the chronically critically ill with ICU care. Mortality (OR 0.62 95% CI 0.35 to 1.10) and length of inpatient stay differ did not differ (WMD 2 days, 95% CI 10.96 to -6.96 days). Early readmissions were reduced (OR 0.33 95% CI 0.12 to 0.94). Costs of care on the NLU were higher for UK studies but lower for US based studies. REVIEWERS' CONCLUSIONS: There is some evidence that patients discharged from a NLU are better prepared for discharge but it is unclear if this is simply a product of an increased length of inpatient stay. No statistically significant adverse effects were noted but the possibility of increased early mortality cannot be discounted. More research is needed.

Health Care Costs↗
PubMed2004

The effects of withdrawing tegaserod treatment in comparison with continuous treatment in irritable bowel syndrome patients with abdominal pain/discomfort, bloating and constipation: a clinical study.

BACKGROUND: The post-withdrawal characteristics of tegaserod treatment in patients with irritable bowel syndrome with constipation remain undefined. AIM: To evaluate the effects of continuous tegaserod treatment, versus intermittent or withdrawal of treatment in patients with irritable bowel syndrome with constipation. METHODS: In a randomized, open-label trial, all patients initially received tegaserod 6 mg b.d. Responders were randomized to continue or withdraw from treatment for 8 weeks and symptom recurrence was assessed. Tegaserod was re-introduced in withdrawal patients who experienced symptom recurrence, allowing an assessment of intermittent treatment. Two separate analyses assessed the effects of intermittent and withdrawal of treatment on symptom recurrence. RESULTS: Five hundred irritable bowel syndrome with constipation patients initially received tegaserod; 410 completed treatment. Time to symptom recurrence was shorter in withdrawal patients than those maintained on tegaserod. Significantly more patients maintained on tegaserod had not experienced symptom recurrence by week 8, compared with intermittent (86.5% vs. 58.1%, respectively) or withdrawal of treatment (69.2% vs. 11.3%, respectively) (P < 0.0001 for both). Significant treatment effects were observed for bloating (P < 0.01) and abdominal pain/discomfort (P < 0.02). Most adverse events were mild to moderate. CONCLUSIONS: Irritable bowel syndrome with constipation patients who receive continuous or intermittent tegaserod are less likely to experience symptom recurrence than patients withdrawn from treatment.

Abdominal Pain↗
PubMed2004

Bispectral index monitoring to prevent awareness during anaesthesia: the B-Aware randomised controlled trial.

BACKGROUND: Awareness is an uncommon complication of anaesthesia, affecting 0.1-0.2% of all surgical patients. Bispectral index (BIS) monitoring measures the depth of anaesthesia and facilitates anaesthetic titration. In this trial we determined whether BIS-guided anaesthesia reduced the incidence of awareness during surgery in adults. METHODS: We did a prospective, randomised, double-blind, multicentre trial. Adult patients at high risk of awareness were randomly allocated to BIS-guided anaesthesia or routine care. Patients were assessed by a blinded observer for awareness at 2-6 h, 24-36 h, and 30 days after surgery. An independent committee, blinded to group identity, assessed every report of awareness. The primary outcome measure was confirmed awareness under anaesthesia at any time. FINDINGS: Of 2463 eligible and consenting patients, 1225 were assigned to the BIS group and 1238 to the routine care group. There were two reports of awareness in the BIS-guided group and 11 reports in the routine care group (p=0.022). BIS-guided anaesthesia reduced the risk of awareness by 82% (95% CI 17-98%). INTERPRETATION: BIS-guided anaesthesia reduces the risk of awareness in at-risk adult surgical patients undergoing relaxant general anaesthesia. With a cost of routine BIS monitoring at US16 dollars per use in Australia and a number needed to treat of 138, the cost of preventing one case of awareness in high-risk patients is about 2200 dollars.

Anesthesia Recovery Period↗
PubMed2004

Rate of cartilage loss at two years predicts subsequent total knee arthroplasty: a prospective study.

OBJECTIVE: To determine whether cartilage volume loss is an independent predictor of knee replacement. DESIGN: Prospective community based, four year prospective cohort study. METHODS: 123 subjects with mild to moderate symptomatic radiographic knee osteoarthritis were recruited by either advertising, the Victorian branch of the Arthritis Foundation of Australia, treating general practitioners, orthopaedic surgeons, or rheumatologists; 113 completed the study. Magnetic resonance imaging was carried out at baseline and at 2 years on the symptomatic knee. Rate of change in tibial cartilage volume was calculated. Subjects were then followed up at year 4 to determine whether they had undergone a knee replacement. RESULTS: The rate of tibial cartilage loss over two years was an independent predictor of knee replacement at four years. For every 1% increase in the rate of tibial cartilage loss there was a 20% increase risk of undergoing a knee replacement at four years (95% confidence interval, 10% to 30%). Those in the highest tertile of tibial cartilage loss had 7.1 (1.4 to 36.5) higher odds of undergoing a knee replacement than those in the lowest tertile. WOMAC score at baseline, female sex, and tibial bone size (but not age and radiographic score) were also predictors of knee replacement. CONCLUSIONS: The data suggest that treatment targeted at reducing the rate of knee cartilage loss in subjects with symptomatic osteoarthritis may delay knee replacement. This has important implications in terms of prevention and therapeutic interventions in osteoarthritis.

Aged↗
PubMed2004

Low molecular weight heparin (tinzaparin) vs. placebo in the treatment of mild to moderately active ulcerative colitis.

BACKGROUND: Heparin has anti-inflammatory and immunomodulatory activity which may be of therapeutic benefit in the treatment of ulcerative colitis. AIM: To test whether low molecular weight heparin, given subcutaneously, would provide a significant therapeutic response compared with placebo in the treatment of mild to moderate ulcerative colitis. STUDY DESIGN: A prospective, double-blind, randomized, placebo-controlled, multi-centre trial comparing tinzaparin 175 anti-Xa IU/kg/day (innohep, LEO Pharma) subcutaneously for 14 days followed by tinzaparin 4500 anti-Xa IU/day subcutaneously for 28 days with placebo, administered subcutaneously once daily for up to 42 days. The primary outcome measure was the mean change in colitis activity from baseline to the end of study treatment assessed by the sum of scores of stool frequency, rectal bleeding, sigmoidoscopic appearance and histology. Secondary outcome measures included changes in individual activity indices and laboratory parameters. Patients were assessed at weekly intervals for 6 weeks and within 1 week of completing treatment. RESULTS: One hundred patients with active ulcerative colitis (up to six bloody stools per day, no fever, no tachycardia or systemic disturbances) were randomized. Forty-eight received tinzaparin and 52 received placebo. The difference in the mean percentage change in colitis activity from baseline to end of treatment (tinzaparin-placebo) was not statistically significant (P = 0.84). There was no difference between tinzaparin and placebo in any secondary outcome measure. One major bleed (rectal), occurred in a patient receiving placebo. CONCLUSION: This is the largest trial to date of heparin in ulcerative colitis. The results show no benefit of low molecular weight heparin over placebo in mild to moderately active ulcerative colitis.

Adolescent↗
PubMed2004

An 11-year experience of enterocutaneous fistula.

BACKGROUND: Enterocutaneous fistula has traditionally been associated with substantial morbidity and mortality, related to fluid, electrolyte and metabolic disturbance, sepsis and malnutrition. METHODS: A retrospective review of enterocutaneous fistula in 277 consecutive patients treated over an 11-year period in a major tertiary referral centre was undertaken to evaluate current management practice and outcome. RESULTS: Most fistulas occurred secondary to abdominal surgery, and a high proportion (52.7 per cent) occurred in association with inflammatory bowel disease. A low rate of spontaneous healing was observed (19.9 per cent). The healing rate after definitive fistula surgery was 82.0 per cent, although more than one attempt was required to achieve surgical closure in some patients. Definitive fistula resection resulted in a mortality rate of 3.0 per cent. In addition, one patient died after laparotomy for intra-abdominal sepsis and an additional 24 patients died from complications of fistulation, giving an overall fistula-related mortality rate of 10.8 per cent. CONCLUSION: Early recognition and control of sepsis, management of fluid and electrolyte imbalances, meticulous wound care and nutritional support appear to reduce the mortality rate, and allow spontaneous fistula closure in some patients. Definitive surgical management is performed only after restitution of normal physiology, usually after at least 6 months.

Adolescent↗
PubMed2004

Direct observation of the asphaltene structure in paving-grade bitumen using confocal laser-scanning microscopy.

The structure of the asphaltene phase in the bitumen is believed to have a significant effect on its rheological properties. It has traditionally been difficult to observe the asphaltene phase in unaltered samples of bitumen. The maltenes are thought to form a continuous phase in which the asphaltenes are 'dispersed'. In this study, confocal laser-scanning microscopy (CLSM) operating in fluorescence mode was used to examine the structure of paving-grade Safaniya and San Joaquin bitumen. The asphaltene fraction fluoresces in the 515-545 nm wavelength range when irradiated with light with a wavelength of 488 nm. The major advantages of CLSM are that the bitumen sample requires little pretreatment or preparation that may affect the original dispersion of asphaltenes and the bitumen is observed at ambient temperature and pressure. This reduces the possibility of producing images that are not representative of the original material. CLSM was able to show the distribution of maltene and asphaltene components in bitumen. The asphaltene aggregates in the bitumen were observed to be 2-7 micro m in size and formed a dispersed 'sol' structure in the continuous maltene matrix rather than a network 'gel' structure. Surprisingly, the structure and fluorescence of the asphaltene phase does not appear to alter radically upon oxidative ageing. The structure of the asphaltene phase of an AR4000 San Joaquin bitumen was found to be more homogeneous than that of Safaniya bitumen, illustrating the range of structures that can be observed in bitumens by this method.

Journal Article↗
PubMed2004

Good practices that address continuity during transition from child to adult care: synthesis of the evidence.

BACKGROUND: Effective transition to adult services is required by an increasing number of children with ongoing needs. AIM: To identify practices that promote continuity at transition between child and adult services. METHODS: Systematic examination of the evidence from two search strategies yielding 5319 items. RESULTS: Only three of the 126 appraised items had strong external validity. A large range of different practices, which focused on the service, the young person and the family, were identified. Practices within the service addressed structural, process and outcome components. CONCLUSION: Four transition models are proposed for testing.

Adolescent↗
PubMed2004

Arthrographic joint distension with saline and steroid improves function and reduces pain in patients with painful stiff shoulder: results of a randomised, double blind, placebo controlled trial.

OBJECTIVE: To determine whether arthrographic distension with a mixture of saline and steroid, in patients with painful stiff shoulder for at least 3 months, is better than placebo in improving function, pain, and range of motion at 3, 6, and 12 weeks. METHODS: A randomised, placebo controlled trial with participant and outcome assessor blinding in which shoulder joint distension with normal saline and corticosteroid was compared with placebo (arthrogram). Outcome measures, assessed at 3, 6, and 12 weeks, included a shoulder-specific disability measure (SPADI), a patient preference measure (Problem Elicitation Technique (PET)), pain, and range of active motion. RESULTS: From 96 potential participants, 48 were recruited. Four withdrew from the placebo group after the 3 week assessment and three subsequently received arthrographic distension with saline and steroid. At 3 weeks, significantly greater improvement in SPADI (p = 0.005), PET, overall pain, active total shoulder abduction, and hand behind back was found in participants in the joint distension and steroid group than in the placebo group. At 6 weeks the results of the intention to treat analysis favoured joint distension, although the between-group differences were only significant for improvement in PET (difference in mean change in PET between groups = 45.9 (95% CI 3.2 to 88.7). Excluding the four withdrawals, the between-group differences for the disability and pain measures significantly favoured distension over placebo. At 12 weeks, both the intention to treat analysis and an analysis excluding the four withdrawals demonstrated a significantly greater improvement in PET score for the distension group. CONCLUSIONS: Short term efficacy of arthrographic distension with normal saline and corticosteroid over placebo was demonstrated in patients with painful stiff shoulder.

Anti-Inflammatory Agents↗
PubMed2004

Short course prednisolone for adhesive capsulitis (frozen shoulder or stiff painful shoulder): a randomised, double blind, placebo controlled trial.

OBJECTIVE: To determine whether a short course of prednisolone is superior to placebo for improving pain, function, and range of motion in adhesive capsulitis. DESIGN: Double blind, randomised, placebo controlled trial. SETTING: Community based rheumatology practice in Australia. PARTICIPANTS: 50 participants (24 active, 26 placebo); 46 completed the 12 week protocol. Entry criteria were age > or =18 years, pain and stiffness in predominantly one shoulder for > or =3 weeks, and restriction of passive motion by >30 degrees in two or more planes. INTERVENTIONS: 30 mg oral prednisolone/day for three weeks or placebo. MAIN OUTCOME MEASURES: Overall, night, and activity related pain, SPADI, Croft shoulder disability questionnaire, DASH, HAQ, SF-36, participant rated improvement, and range of active motion measured at baseline and at 3, 6, and 12 weeks. RESULTS: At 3 weeks, there was greater improvement in overall pain in the prednisolone group than in the placebo group (mean (SD) change from baseline, 4.1 (2.3) v 1.4 (2.3); adjusted difference in mean change between the two groups, 2.4 (95% CI, 1.1 to 3.8)). There was also greater improvement in disability, range of active motion, and participant rated improvement (marked or moderate overall improvement in 22/23 v 11/23; RR = 2 (1.3 to 3.1), p = 0.001). At 6 weeks the analysis favoured the prednisolone group for most outcomes but none of the differences was significant. At 12 weeks, the analysis tended to favour the placebo group. CONCLUSIONS: A three week course of 30 mg prednisolone daily is of significant short term benefit in adhesive capsulitis but benefits are not maintained beyond six weeks.

Anti-Inflammatory Agents↗
PubMed2004

Pancolonic indigo carmine dye spraying for the detection of dysplasia in ulcerative colitis.

BACKGROUND AND AIMS: Colonoscopic surveillance for cancer in longstanding extensive ulcerative colitis relies heavily on non-targeted mucosal biopsies. Chromoendoscopy can aid detection of subtle mucosal abnormalities. We hypothesised that routine pancolonic indigo carmine dye spraying would improve the macroscopic detection of dysplasia and reduce the dependence on non-targeted biopsies. PATIENTS AND METHODS: One hundred patients with longstanding extensive ulcerative colitis attending for colonoscopic surveillance underwent "back to back" colonoscopies. During the first examination, visible abnormalities were biopsied, and quadrantic non-targeted biopsies were taken every 10 cm. Pancolonic indigo carmine (0.1%) was used during the second colonoscopic examination, and any additional visible abnormalities were biopsied. RESULTS: Median extubation times for the first and second colonoscopies were 11 and 10 minutes, respectively. The non-targeted biopsy protocol detected no dysplasia in 2904 biopsies. Forty three mucosal abnormalities (20 patients) were detected during the pre-dye spray colonoscopy of which two (two patients) were dysplastic: both were considered to be dysplasia associated lesions/masses. A total of 114 additional abnormalities (55 patients) were detected following dye spraying, of which seven (five patients) were dysplastic: all were considered to be adenomas. There was a strong trend towards statistically increased dysplasia detection following dye spraying (p = 0.06, paired exact test). The targeted biopsy protocol detected dysplasia in significantly more patients than the non-targeted protocol (p = 0.02, paired exact test). CONCLUSIONS: No dysplasia was detected in 2904 non-targeted biopsies. In comparison, a targeted biopsy protocol with pancolonic chromoendoscopy required fewer biopsies (157) yet detected nine dysplastic lesions, seven of which were only visible after indigo carmine application. Careful mucosal examination aided by pancolonic chromoendoscopy and targeted biopsies of suspicious lesions may be a more effective surveillance methodology than taking multiple non-targeted biopsies.

Adult↗