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Biomedical subjects

G Sinclair

Publications and source records attributed to G Sinclair.

At least 19 recordsLinked to original sources
PubMed2005

What factors influence survival in patients with unresected synchronous liver metastases after resection of colorectal cancer?

OBJECTIVE: The aim of this study was to determine whether the survival of patients with untreated synchronous liver metastases after resection of a colorectal cancer was associated with any features of the primary tumour. METHODS: Information for 398 consecutive patients with unresected liver metastases in the period 1971-2001 was examined by multivariate survival analysis. RESULTS: Of 19 clinical and pathological variables considered, survival was independently associated only with residual tumour in a line of resection (hazard ratio (HR) 1.95), venous invasion (HR 1.87), right colonic tumour (HR 1.68), lymph node metastasis (HR 1.54), and extra-hepatic metastasis (HR 1.16); 8.3% of patients had none of these adverse features. Their 2-year overall survival rate was 39.2%, compared with only 16.5% (P < 0.001) in those with one or more adverse features. CONCLUSIONS: These findings may assist in selecting patients most likely to benefit from treatment of hepatic metastases and in counselling patients and their relatives.

Aged↗
PubMed2004

Three-dimensional optical trapping of partially silvered silica microparticles.

We demonstrate three-dimensional trapping of micrometer-diameter silica particles, partially coated with silver, within conventional optical tweezers. Although metallic particles are usually repelled from the beam focus by the scattering force, we show that transparent spheres partially coated with silver can be trapped with efficiencies comparable with dielectric particles. The trapping characteristics of these particles are examined as a function of metallic coverage, and the application of these particles to surface-enhanced resonance Raman scattering is investigated.

Coated Materials, Biocompatible↗
PubMed2004

Adverse histopathological findings as a guide to patient management after curative resection of node-positive colonic cancer.

BACKGROUND: The aim of this study was to identify patient and tumour characteristics that might assist in developing an improved approach to patient selection for chemotherapy after resection of clinicopathological stage C colonic cancer. METHODS: Clinical, pathological and follow-up data have been collected prospectively for all patients undergoing resection for colorectal cancer at Concord Hospital since 1971. From an initial 2980 patients, after exclusions 378 remained who had a potentially curative operation for colonic cancer with nodal metastases and did not receive adjuvant chemotherapy. Associations between several pathological features and survival were examined by proportional hazards regression. RESULTS: In a multivariate model, both overall and colonic cancer-specific survival rates were negatively associated with serosal surface involvement, apical node metastasis, high histological grade and venous invasion. The survival of patients with stage C disease who had none of these adverse features was not significantly different from that of patients with stage B lesions. However, survival diminished significantly when one or more of the adverse features were present. CONCLUSION: Patients with a stage C tumour but with none of the identified adverse features experience relatively good survival and are unlikely to benefit from adjuvant chemotherapy. In this series such patients accounted for 40.5 per cent of patients with stage C disease.

Aged↗
PubMed2004

Changes in serum concentrations of methylmalonic acid and vitamin B12 in cobalt-supplemented ewes and their lambs on two cobalt-deficient properties.

AIM: To determine concurrent changes in serum methylmalonic acid (MMA) and vitamin B12 concentrations of ewes and their lambs on cobalt-deficient properties, subsequent to cobalt supplementation. METHODS: Three experiments were carried out on two farms. Groups of ewes (n=25-50) were either supplemented with cobalt bullets during late pregnancy, 23-47 days before the mean lambing date, or left unsupplemented. In two experiments, lambs from within each group were supplemented directly by vitamin B12 injection at 3-weekly intervals from birth, and in the third experiment by injection with micro-encapsulated vitamin B12 at tailing and 3 months later. Pasture samples were obtained for analysis of cobalt content at each sampling time. Blood samples were obtained and liveweight recorded from ewes and lambs at approximately monthly intervals. On one farm (two experiments), liver and milk samples were obtained from ewes and liver samples from lambs. RESULTS: Serum vitamin B12 concentrations in unsupplemented ewes fell below 250 pmol/L during early lactation in all experiments and mean concentrations as low as 100 pmol/L were recorded. MMA concentration was maintained below 2 micromol/L in serum from supplemented ewes but increased to mean concentrations ranging from 7 to 14 micromol/L at the nadir of serum vitamin B12 concentration during peak lactation. A significant liveweight response to supplementation was recorded in ewes on one property, and the vitamin B12 concentration in the ewes' milk and in the livers of their lambs more than doubled. No liveweight-gain response to supplementation was observed in lambs on this property. Mean serum MMA concentrations in lambs ranged from <2 in supplemented, to 19.2 micromol/L in unsupplemented lambs, and the latter had concurrent serum vitamin B12 concentrations of >300 pmol/L. Pasture cobalt concentration was lowest at 0.04-0.09 microg/kg dry matter (DM) on the property on which responses in lambs occurred but considerably higher (>0.09 microg/kg DM) on the property on which responses in ewes occurred. On the second property, serum vitamin B12 concentrations in lambs at tailing were extremely low (100 pmol/L), irrespective of supplementation of dams with cobalt. Mean serum MMA concentration was increased to 20 and 42 micromol/L in lambs from supplemented and non-supplemented ewes, respectively. Weight-gain response to direct supplementation of lambs with vitamin B12 occurred during suckling in the latter, but not the former. Lambs from ewes supplemented with vitamin B12 showed a much bigger increase in serum vitamin B12 concentrations a month after supplementation than did lambs from unsupplemented ewes (+1,400 pmol/L vs + 650 pmol/L). CONCLUSIONS: Serum MMA concentration gave a more precise indication of responsiveness to vitamin B12 or cobalt supplementation than serum vitamin B12 concentrations in ewes and lambs. Neither very low serum vitamin B12 nor elevated MMA concentrations were necessarily indicative of responsiveness to supplementation in suckling lambs, but the latter gave an early indication of impending responsiveness. Supplementation of the ewe with a cobalt bullet appeared to protect the growth performance of the lamb for 90 days and influence the subsequent serum vitamin B12 response in the lamb to vitamin B12 supplementation. CLINICAL SIGNIFICANCE: Supplementing ewes with cobalt bullets in late pregnancy can improve the vitamin B12 status of their lambs, and modify their response to vitamin B12 supplementation.

Journal Article↗
PubMed2004

Concurrent changes in serum vitamin B12 and methylmalonic acid during cobalt or vitamin B12 supplementation of lambs while suckling and after weaning on properties in the South Island of New Zealand considered to be cobalt-deficient.

AIM: To compare serum analyses of vitamin B12 and methylmalonic acid (MMA) as indices of cobalt/vitamin B12 deficiency in lambs around weaning. METHODS: Lambs on five properties, considered to be cobalt- deficient, were supplemented with either cobalt bullets, or short- or long-acting vitamin B12 preparations. Blood samples, and in some cases liver biopsies, and liveweights were obtained at monthly intervals. Serum samples were assayed for vitamin B12 and MMA and liver for vitamin B12 concentrations. Pasture cobalt concentrations were measured on three of the properties. RESULTS: Pasture cobalt concentrations were generally maintained below 0.07 microg/g dry matter (DM) on the properties sampled. Growth responses to supplementation were observed on only 2/5 properties, despite serum vitamin B12 concentrations being within the currently used 'marginal' reference range (336-499 pmol/L) for at least 3 months on all properties and in the deficient reference range (0-335 pmol/L) for at least 2 months on all farms except one. Serum MMA concentrations in supplemented lambs were <2 micromol/L, except in those animals sampled 1 month after receiving treatment with a short-acting vitamin B12 injection. Serum MMA concentrations in unsupplemented animals on properties on which no growth response to supplementation occurred generally reached peak levels of between 4 and 7 micromol/L at the nadir of serum vitamin B12 concentration. When a growth response was observed, differences in weight gain between supplemented and unsupplemented lambs occurred as mean serum MMA concentrations increased from 9 to 14 micromol/L. On one property where supplementation commenced before weaning, normal growth rates were maintained despite serum vitamin B12 concentrations of 140 pmol/L and serum MMA concentrations in excess of 40 micromol/L serum. CONCLUSIONS: The possibility that current serum vitamin B12 references ranges for diagnosis of cobalt deficiency are set too high and lead to over-diagnosis of responsiveness to cobalt/ vitamin B12 supplementation is discussed. The suggestion is made that serum MMA concentrations in excess of 9-14 micromol/L will provide a more reliable diagnostic test for cobalt deficiency. However, there was sufficient variation between properties in the relationships between cobalt concentrations of pasture and serum vitamin B12 or MMA concentrations to require more rigorous testing of the reliability of using serum MMA concentration for this purpose. The possibility that differences in rumen fermentation and therefore propionate and vitamin B12 production could be involved is discussed. The measurement of serum MMA and vitamin B12 appears to be of little value whilst the lamb is still suckling. CLINICAL SIGNIFICANCE: Serum MMA concentration may offer advantages over serum vitamin B12 concentrations in the diagnosis of a cobalt/vitamin B12 responsiveness in weaned lambs.

Journal Article↗
PubMed2003

Anastomotic leakage after curative anterior resection results in a higher prevalence of local recurrence.

BACKGROUND: The aim of this study was to determine whether leakage from a colorectal anastomosis following potentially curative anterior resection for rectal cancer is an independent risk factor for local recurrence. METHODS: The study included all patients who had a potentially curative anterior resection with anastomosis for adenocarcinoma of the rectum between 1971 and 1991 at Concord Hospital. The data were collected prospectively, with complete follow-up for at least 5 years. The Kaplan-Meier method was used to compare time to recurrence between strata of categorical variables. Proportional hazards regression was used in multivariate modelling. RESULTS: There were 403 patients in the study. After adjustment for lymph node metastases, the distal resection margin of resection, non-total anatomical dissection of the rectum and the level of anastomosis, multivariate analysis identified a significant association between anastomotic leakage and local recurrence (hazard ratio 3.8, 95 per cent confidence interval 1.8 to 7.9). CONCLUSION: Leakage following a colorectal anastomosis after potentially curative resection for adenocarcinoma of the rectum is an independent predictor of local recurrence.

Adenocarcinoma↗
PubMed2002

Combined endoscopic laser and radiotherapy palliation of advanced rectal cancer.

BACKGROUND: In the palliative treatment of patients with advanced, inoperable rectal cancer, combined endoscopic laser and radiotherapy have been claimed to be more effective than laser therapy alone. The number of laser treatments, laser energy used, relapse rate, treatment of relapse, morbidity and survival in consecutive patients who were treated either by laser therapy alone or laser plus radiotherapy was compared. METHODS: Prospective data were analysed with regard to number of treatments, laser energy used, relapse rate, morbidity and survival for 56 consecutive patients. RESULTS: The crude relapse rate was significantly higher in the laser only group than in the laser plus radiotherapy group (58 and 15%, respectively; P = 0.002). There was no difference between the groups in the median total number of laser treatments or the mean total laser energy used. In patients experiencing a relapse, there was no difference in the median number of relapses, the number of laser treatments post-relapse or the total energy used post-relapse. Survival did not differ between the groups and there were no treatment-related deaths. CONCLUSIONS: These findings demonstrate a clear reduction in relapse after using combined laser and radiotherapy to palliate patients with advanced rectal cancer with no appreciable additional morbidity and have encouraged continuing use of this treatment.

Aged↗
PubMed2001

Heterologous expression and characterization of a rare Gaucher disease mutation (c.481C > T) from a Canadian aboriginal population using archival tissue samples.

Gaucher disease is an inherited sphingolipidosis resulting from deleterious mutations in the glucocerebrosidase gene. Through direct sequence analysis of genomic DNA from whole blood, fibroblast cultures, and formalin-fixed archival tissue samples, we have identified a rare homozygous C > T transition at cDNA nucleotide 481 of the glucocerebrosidase gene that results in a proline to serine amino acid substitution (p.P122S) in an aboriginal family of Cree descent in northern Alberta, Canada. A 13-month-old boy (JB) presented with severe visceral Gaucher disease and was treated with enzyme replacement. Currently, at 11 years he is developmentally delayed, with oculomotor apraxia. A cousin (MS) had previously died at age 7 from complications of severe Gaucher disease, before enzyme replacement therapy was available. She was also developmentally delayed. Heterologous expression of this allele using a baculovirus expression system revealed 19.2% of normal enzyme activity on the artificial substrate 4-methylumbelliferyl beta-d-glucopyranoside (4MUGP). Genotype/phenotype correlation is complicated by incomplete clinical details, enzyme replacement therapy, and the difficulty in excluding other genetic and environmental causes of developmental delay. However the development of oculomotor apraxia in JB suggests a Type 3 Gaucher phenotype. The only previous report of this mutation was also from a member of the Cree Nation, who has had a rather similar clinical course. A protocol is described for the isolation of genomic DNA from formalin-fixed bone marrow aspirate archival specimens obtained from the deceased for subsequent PCR-based sequence analysis and mutation detection. This technique will be applicable to the screening of this and other populations for the frequency of known Gaucher mutations where traditional DNA sources are unavailable.

Adolescent↗
PubMed2001

Development and validation of a self-completed HIV symptom index.

Traditional, open-ended provider questions regarding patient symptoms are insensitive. Better methods are needed to measure symptoms for clinical management, patient-oriented research, and adverse drug-event reporting. Our objective was to develop and initially validate a brief, self-reported HIV symptom index tailored to patients exposed to multidrug antiretroviral therapies and protease inhibitors, and to compare the new index to existing symptom measures. The research design was a multistage design including quantitative review of existing literature, qualitative and quantitative analyses of pilot data, and quantitative analyses of a prospective sample. Statistical analyses include frequencies, chi-square tests for significance, linear and logistic regression. The subjects were from a multisite convenience sample (n = 73) within the AIDS Clinical Trials Group and a prospective sample from the Cleveland Veterans Affairs Medical Center (n = 115). Measures were patient-reported symptoms and health-related quality of life, physician-assessed disease severity, CD4 cell count, and HIV-1 RNA viral quantification. A 20-item, self-completed HIV symptom index was developed based upon prior reports of symptom frequency and bother and expert opinion. When compared with prior measures the index included more frequent and bothersome symptoms, yet was easier to use (self-report rather than provider interview). The index required less than 5 minutes to complete, achieved excellent completion rates, and was thought comprehensive and comprehensible in a convenience sample. It was further tested in a prospective sample of patients and demonstrated strong associations with physical and mental health summary scores and with disease severity. These associations were independent of CD4 cell count and HIV-1 RNA viral quantification. This 20-item HIV symptom index has demonstrated construct validity, and offers a simple and rational approach to measuring HIV symptoms for clinical management, patient-oriented research, and adverse drug reporting.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Patient- and provider-reported adherence: toward a clinically useful approach to measuring antiretroviral adherence.

We seek to develop a clinically useful measure of antiretroviral medication adherence. Because there is no gold standard for adherence, we will assess the clinical validity of patient- and provider-reported adherence by the strength of their expected associations with current viral load, depressive symptoms, alcohol and illicit drug use, and homelessness. The Veterans Aging Cohort 3 Site Study (VACS 3) is a multisite study of 881 patients at Cleveland, Houston, and Manhattan Veterans Affairs health care systems. Data was collected on adherence using patient report and provider assessment; depressive symptoms using the Center for Epidemiological Studies Depression (CESD) and provider assessment; alcohol use using the Alcohol Use Disorders Identification Test (AUDIT) and provider assessment; and homelessness using patient report only. Viral load was collected from electronic laboratory data. Although agreement between providers and patients about the patient's adherence was not better than chance (61%; weighted kappa =.07), both patient and provider-reported adherence were related to viral load (P <.001), current alcohol use (P <.01), current drug use (P <.01), and depressive symptoms (P <.001). Patient-reported adherence was also associated with homelessness (P <.05). In multivariate regression models, provider assessment of adherence demonstrated independent associations with viral load (P <.001), current alcohol use (P <.001), current drug use (P <.001), and depressive symptoms (P <.001) after adjustment for the patient's report of adherence (also significantly associated). The consistent and largely independent association between patient and provider reported adherence and a range of variables previously shown to be associated with adherence suggests that patient- and provider-reported adherence independently measure actual adherence. Future work will explore how patient- and provider-reported adherence might best be combined, and whether the measure may be further enhanced with pharmacy refill data.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Endoscopic laser stricturotomy and balloon dilatation for benign colorectal strictures.

BACKGROUND: A fibrous stricture may develop at the site of a colorectal anastomosis or as a complication following abdominal aortic surgery. A major resection may be necessary if the stricture cannot be released. The authors' experience with endoscopic stricturotomy using neodymium:yttrium-aluminium-garnet laser, together with balloon dilatation, as a conservative method of treating such strictures, is reported here. METHODS: The case notes of all patients referred for laser treatment of benign distal large bowel strictures at Concord Hospital were reviewed. RESULTS: Ten patients had endoscopic laser treatment combined with endoscopic balloon dilatation between October 1991 and July 1999. An anastomotic stricture had developed in eight patients and two patients had a fibrous stricture of the upper rectum after abdominal aortic aneurysm surgery. Nine of the 10 patients had their stricture treated successfully without complication or recurrence (median follow up 82 months; range: 14-104 months). The remaining patient re-presented with a large bowel obstruction at the site of his stricture 6 years following initial treatment. CONCLUSION: A protocol combining laser stricturotomy with balloon dilatation appears to be a safe and effective treatment of such strictures.

Adult↗
PubMed2000

The A-X of Atridox.

Explore the source record for details and available documents.

Administration, Topical↗
PubMed1999

Local recurrence after curative excision of the rectum for cancer without adjuvant therapy: role of total anatomical dissection.

BACKGROUND: The wide variability of reported local recurrence rates after curative resection of rectal cancer without adjuvant therapy may be a consequence of many different factors. However, few studies have investigated the potential effects of such factors on local recurrence by multivariate analysis. The present study examined clinical and tumour characteristics, operation type and operative technique as potential predictors of local recurrence in patients treated by surgery alone. METHODS: Prospective data were analysed by bivariate and multivariate methods including actuarial survival and proportional hazards regression. RESULTS: Local recurrence (pelvic or pelvic and systemic) was diagnosed in 59 of 596 patients. The 5-year actuarial local recurrence rate was 11.1 (95 per cent confidence interval 8.7-14.3) per cent. Independent predictive factors for local recurrence were: positive nodes (hazard ratio (HR) 5.5, P < 0.01); distal margin of 1 cm or less (HR 3.8, P < 0.01); venous invasion (HR 2.0, P = 0.02) and total anatomical dissection of the rectum (HR 2.0, P = 0.01). There was no difference in local recurrence between patients who had the mesorectum divided and those in whom it was totally excised. CONCLUSION: Nodal involvement is the most potent predictor of local recurrence. In patients in whom total anatomical dissection is performed, total mesorectal excision confers no additional protection against local recurrence.

Aged↗
PubMed1999

[Management of colorectal cancer in Australian hospitals. Twenty four years' experience].

This study analyses time trends in clinical features tumour pathology and treatment outcomes of patients with colorectal cancer (CRC) treated by surgery alone during the period 1971 to 1994 in a large Australian tertiary referral centre. Throughout this period, both surgical technique and pathology reporting were standardized and a specialized unit of colon and rectal surgery was established in 1980. Improvement in overall survival during this 24 year period reflects changes in tumour stage with an increasing proportion of stage A tumours, declining proportions of stage D tumours, and some improvement in survival for stages B and C colon cancer only.

Adult↗
PubMed1998

A novel complex allele and two new point mutations in type 2 (acute neuronopathic) Gaucher disease.

Gaucher disease, the most prevalent inherited sphingolipidosis, is characterized by lipid laden histiocytes in the spleen, liver and bone marrow sinusoids of affected individuals. It results from deleterious mutations in the functional gene of glucocerebrosidase (acid beta-glucosidase, EC. 3.2.1.45) and is transmitted as an autosomal recessive trait. Three clinical forms of Gaucher disease have been described: Type 1 non-neuronopathic, type 2 acute neuronopathic, and type 3 subacute neuronopathic. In this report, we describe the identification and characterization of three novel mutations from two patients who died with type 2 Gaucher disease. Two heterozygous missense point mutations, one at cDNA nucleotide 238A (E41L) and the other at cDNA nucleotide 508T (R131C) were identified, both in the context of a cDNA nucleotide 1448C (L444P) mutation in the second allele. One of these L444P mutations was identified as a novel complex allele resulting from a crossover involving the glucocerebrosidase functional gene and pseudogene beginning between genomic nucleotides 5689 and 5723 and extending through the rest of the coding sequence. Based on the recent identification and sequence analysis of the metaxin gene and pseudogene contiguous with the glucocerebrosidase pseudogene and functional gene respectively, we have developed a PCR-based method for the analysis of the origin and extent of this recombination.

Adult↗
PubMed1998

Quality of life in patients undergoing treatment for chronic radiation-induced rectal bleeding.

BACKGROUND: Laser and formalin therapy have recently been shown to be safe methods of haemostasis in patients with chronic radiation-induced rectal bleeding (CRRB). The effectiveness of this treatment in terms of improved quality of life remains to be determined. The aim of this study was to develop a questionnaire measure of self-perceived quality of life in patients with CRRB. METHODS: A self-completed Rectal Bleeding Quality of Life Scale (RBQOLS) based on the social and emotional problems experienced by patients with CRRB was developed using standard psychometric methods. Before laser and formalin therapy, 34 consecutive patients completed the questionnaire which was repeated 1 month after treatment and again 5 months later. The validity of the scale was assessed in relation to patient response to treatment. RESULTS: The RBQOLS had high reliability (alpha=0.89) and its concurrent validity was confirmed by a significant association with the pretreatment severity of CRRB assessed endoscopically. The mean RBQOLS score increased from 102 (95 per cent confidence interval 90-114) before treatment to 126 (111-141) after treatment (t=3.1, 33 d.f., P=0.004) and 136 (122-151) at follow-up attesting to its predictive validity. CONCLUSION: The RBQOLS is a reliable and valid device for assessing quality of life of patients with this uncommon, previously intractable and potentially life threatening complication of radiotherapy.

Aged↗