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Biomedical subjects

S Nicholson

Publications and source records attributed to S Nicholson.

At least 19 recordsLinked to original sources
PubMed1992

Prevalence of hepatitis C antibodies in patients with clotting disorders in Victoria. Relationship with other blood borne viruses and liver disease.

OBJECTIVE: To elucidate the seroepidemiology of hepatitis C in patients with clotting disorders in comparison with other blood borne infections; to examine the effects of hepatitis C on liver function; and to assess the effectiveness of current screening and inactivation procedures used in preventing the transmission of blood borne viruses by clotting factor preparations. DESIGN: A retrospective analysis of the prevalence of antibodies to hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) by means of commercially available enzyme immunoassays (for antibodies to HCV and HIV) or radioimmunoassays (for HBV antibodies and surface antigen). An analysis was made of serum transaminase levels where such information was available and this was correlated with HCV status. PATIENTS AND SETTING: Panels of sera were collected from adults and children with clotting disorders attending two Melbourne haemophilia treatment centres in 1973 (n = 33), 1980 (n = 33), 1984-1985 (n = 111) and 1987-1990 (n = 217) and tested for antibodies to HCV, HBV and HIV. RESULTS: The prevalence of antibodies to HCV in the four panels tested was 45%, 74%, 75% and 76%, and the prevalence of markers of infection with HBV was 66%, 74%, 62% and 65% respectively. No antibodies to HIV were found in sera in Panels I and II but the prevalence in Panels III and IV was 23% and 36% respectively. In subjects in whom liver function test results were available, there was a significant association between the presence of antibodies to HCV and raised transaminase levels. Since heat inactivation of clotting factors was commenced in Australia in 1984, no new cases of transmission of HIV by clotting factors has been detected, but transmission of HCV in 19 subjects and HBV in one subject could not be excluded. CONCLUSIONS: Hepatitis C infection in haemophiliacs has been a very frequent event, and the presence of antibodies to HCV is associated with an increased incidence of raised transaminase levels. Screening and heat inactivation of clotting factors has prevented further HIV transmission, but exposure to HBV and HCV has not been eliminated.

Adolescent↗
PubMed1992

The development of hepatitis C antibody shortly after acute icteric non-A non-B hepatitis.

OBJECTIVE: To determine the relationship between the development of hepatitis C antibody (anti-HCV) and the clinical symptoms in acute hepatitis C. DESIGN: Retrospective analysis of sera from patients with acute non-A non-B hepatitis. SETTING AND PATIENTS: Patients admitted to Fairfield Hospital with the diagnosis of acute non-A non-B hepatitis between 1979 and 1989. Inclusion criteria included a typical clinical illness, accompanied by an alanine aminotransferase level of more than 2.5 times the upper limit of normal (normal, less than or equal to 40 U/L) and negative serological test results for acute hepatitis A and B. MAIN OUTCOME MEASURE: Time to develop anti-HCV after the onset of symptoms in patients with acute hepatitis C. RESULTS: Seroconversion was demonstrated in 26 of the 128 patients who fulfilled the inclusion criteria. In these patients, antibody was detected between one week and 32 weeks after the onset of dark urine; more than half the patients (54%) had seroconverted by four weeks and a third (34%) developed antibodies within two weeks. Of 20 patients who had sera collected within four weeks of the onset of dark urine, 14 (70%) had developed antibody. CONCLUSION: These results suggest that in patients with community-acquired hepatitis C, seroconversion occurs significantly earlier than is observed in patients who have been infected by blood transfusion. Sera taken shortly after the onset of symptomatic hepatitis C may be useful in the diagnosis of this condition.

Acute Disease↗
PubMed1992

Studies on the immediate and delayed leucocytosis elicited by brief (30-min) strenuous exercise.

Eight healthy male volunteers exercised for two 30-min sessions starting 3 h apart on an electronically braked cycle ergometer at a work load (mean 155.9 W, SD 33.4 W) which required an oxygen consumption that was 70% of their maximal rate of oxygen uptake. Venous blood samples were taken through an indwelling cannula over a period of 6 h beginning shortly before the first bout of exercise and were analysed for routine haematological parameters and for lactate, noradrenaline, adrenaline and cortisol. Both bouts of exercise induced an immediate leucocytosis due to rises in lymphocytes and neutrophils but only the first exercise bout induced a substantial delayed neutrophilia. In at least five subjects, changes in lymphocyte and platelet numbers were correlated (Spearman's rank procedure, P less than 0.05) with simultaneous changes in the plasma concentrations of lactate, noradrenaline and adrenaline over the 6-h period studied. Increases in the plasma concentration of cortisol due to exercise correlated positively with the percentage changes in neutrophil numbers at 3 h and 6 h. These results are consistent with the suggestion that the immediate and delayed leucocytosis induced by exercise are mediated respectively by catecholamine and by cortisol.

Adult↗
PubMed1992

Fat-suppression magnetic resonance imaging in the preoperative localization of parathyroid adenomas.

Prospective localization of parathyroid adenomas was attempted in 16 patients with hyperparathyroidism prior to surgery. All patients had magnetic resonance imaging (MRI) using T1-weighted spin-echo (SE) sequences and a fat-suppression sequence, the short-tau inversion recovery (STIR) sequence. Correlation with the results of surgery yielded an overall sensitivity of 71% and a specificity of 94%. Performance was good in patients with previous surgery and with ectopic tumours. We believe that fat-suppression MRI is a valuable technique in the preoperative localization of parathyroid adenomas in patients with hyperparathyroidism.

Adenoma↗
PubMed1992

Relationship between c-erbB-2 protein product expression and response to endocrine therapy in advanced breast cancer.

Of 221 patients with breast cancer of known epidermal growth factor receptor (EGFR) and oestrogen receptor (ER) status, 99 had developed recurrences during the period of follow-up (range 3-60 months, median 24 months). Of these, 72 received endocrine therapy as first-line treatment for relapse. Immunohistochemical assessment of c-erbB-2 protein product expression was made using paraffin-embedded tumour tissue from 65 of these 72 patients. Including patients whose disease remained stable for more than 6 months with those showing an objective response (CR or PR for more than 3 months), only one (7%) of 14 c-erbB-2 positive tumours responded to endocrine manipulation compared with 19 (37%) of 51 c-erbB-2 negative tumours (P less than 0.05). Coexpression of c-erbB-2 reduced the response rate of ER positive patients from 48% to 20% and of ER negative cases from 27% to 0% (P less than 0.01). EGFR and c-erbB-2 protein appeared to have additive effects in reducing the likelihood of response, and none of eight patients with EGFR positive, c-erbB-2 positive tumours derived benefit from endocrine therapy. The results of this study suggest that c-erbB-2 protein overexpression, a marker of poor prognosis in breast cancer, is associated with a lack of response to endocrine therapy on relapse, and particularly in combination with EGFR may be useful in directing therapeutic choices.

Adult↗
PubMed1992

Epidermal growth factor receptor and other oncogenes as prognostic markers.

Analysis of epidermal growth factor receptor (EGFr) and estrogen receptor (ER) was performed on tumor samples from 231 patients with operable breast cancer followed for up to 6 years after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) had tumors greater than 10 fmol/mg of 125I-EGF binding (EGFr+) and 47% (109) had cystolic ER concentration greater than 5 fmol/mg (ER+), with a marked inverse relationship between EGFr and ER (P less than .00001). EGFr was second only to axillary-node status as a prognostic marker for all patients in terms of both relapse-free and overall survival in univariate analysis (P less than .001, log-rank EGFr + v EGFr-). For patients with histologically negative axillary nodes, EGFr was superior to ER in predicting relapse and survival (P less than .01 and P less than .005, respectively, compared to P less than .1 and P less than .1, log-rank). In a multivariate (Cox model) analysis, only EGFr--out of EGFr, ER, size, and grade--was predictive for either relapse-free or overall survival for patients with node-negative disease (P = .052 and P = .026, respectively). One hundred eighty-seven case patients in the series were assessed for neu expression immunochemically, and 31 were positive. There was a highly significant increased risk of relapse and death in the positive group. In patients with otherwise good prognostic markers (ER+, node-negative, well-differentiated tumors), neu expression predicted for significantly worsened overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗
PubMed1991

Hepatitis C antibody testing: problems associated with non-specific binding.

The prevalence of antibodies to hepatitis C virus (anti-HCV) was measured in a number of groups known to be at increased risk of blood-borne viral infections, using an enzyme-linked immunosorbent assay (EIA) based on a nonstructural peptide generated by recombinant DNA technology. The assay was repeatably reactive in 75.6% of men with haemophilia, 61.9% of intravenous drug users, 34.1% of homosexual men who were regular attenders at a gay sauna and 30.8% of prisoners. A lower reactivity was detected in sera collected from female prostitutes (10.4%), patients undergoing maintenance haemodialysis (5.9%), or renal transplantation (6.9%) and patients attending a sexually transmitted diseases clinic (6.2%). We also measured reactivity among inmates of a large institution for the mentally handicapped in which hepatitis B is known to be endemic, and in panels of sera which had been stored for 25-35 years. The test was positive in 41.1% of mentally handicapped patients with Down's syndrome and 7% of subjects with other forms of mental retardation. Similarly some 23% and 20% of sera collected in 1954 and 1964 from patients with a variety of illnesses were found to be reactive. As most diagnostic assays suffer from some degree of non-specificity and confirmatory tests for the anti-HCV assay were not initially available in Australia, we analysed the distribution of optical density (OD) values in the different groups, in an attempt to obtain an insight into the specificity of the results being obtained. Whereas the ODs of sera collected from patients with haemophilia and IVDU had a bimodal pattern, with two well separated sets of results on either side of the cut-off.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Viral↗
PubMed1991

pNR-2/pS2 immunohistochemical staining in breast cancer: correlation with prognostic factors and endocrine response.

Expression of the oestrogen-regulated pNR-2/pS2 protein has been studied in paraffin sections of a series of 172 primary breast cancers using an immunohistochemical technique. Positive staining of tumour cells was found in 117 tumours (68%): most of these tumours contained only a small proportion of positive cells. pNR-2 immunohistochemical staining correlated positively and significantly with the presence of oestrogen receptor. Mean percentages of pNR-2 positive cells were lower in tumours from postmenopausal women. Smaller, better differentiated tumours were significantly more likely to stain positively for pNR-2. The percentages of pNR-2 positive tumour cells in primary tumours and synchronously excised lymph node metastases were very similar. pNR-2 expression showed an unexpected positive association with lymph node metastasis. We were unable to find any significant association between pNR-2 immunohistochemical staining and either time to relapse or overall survival. There was a significant association between pNR-2 expression in primary tumours and response to endocrine therapy on relapse: positive pNR-2 immunohistochemical staining in primary tumours is predictive of response to hormonal therapy on relapse.

Aminoglutethimide↗
PubMed1991

Epidermal growth factor receptor (EGFr); results of a 6 year follow-up study in operable breast cancer with emphasis on the node negative subgroup.

More accurate criteria are required for the selection of patients with node-negative breast cancer for systemic adjuvant therapy. Expression of epidermal growth factor receptor (EGFr) has been shown previously to be inversely related to oestrogen receptor (ER) in patients with operable breast cancer and to be associated with a poorer prognosis. Analysis of EGFr and ER was performed on tumour samples from 231 patients with operable breast cancer followed for up to 6 years after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) had tumours with greater than 10 fmol mg-1 I125-EGF binding (EGFr+) and 47% (109) and cystolic ER concentrations greater than 5 fmol mg-1 (ER+), with a marked inverse relationship between EGFr and ER (P less than 0.00001). In a univariate analysis EGFr was second only to axillary node status as a prognostic marker for all patients both in terms of relapse-free and overall survival (P less than 0.001, log rank). For patients with histologically negative axillary nodes EGFr was superior to ER in predicting relapse and survival (P less than 0.01 and P less than 0.005 respectively compared to P less than 0.1 and P less than 0.1, log rank). In a multivariate (Cox model) analysis only EGFr, out of EGFr, ER, size and grade, was predictive for either relapse-free or overall survival for patients with node-negative disease (P = 0.05 and P = 0.026 respectively). EGFr has been shown to be a marker of poor prognosis for patients with node-negative breast cancer. Since patients with EGFr+ tumours are unlikely to respond to hormone therapy it may be possible to select them for trials of systemic adjuvant chemotherapy.

Breast Neoplasms↗
PubMed1991

Brief exercise induces an immediate and a delayed leucocytosis.

Haematological profiles were measured: (1) before and for 5 h 30 min after 30 min sports (squash, swimming, jogging); and (2) before, during and for 2 h 30 min after 30 min cycle ergometry at workloads which required rates of oxygen consumption that were between 48% and 84% of maximal. In both instances exercise induced an immediate leucocytosis (owing to rises in both neutrophils and lymphocytes) which subsided rapidly at the finish of exercise and was followed by a delayed neutrophilia of greater magnitude which peaked at approximately 3 h after the start of exercise. Changes in plasma catecholamines and cortisol recorded during and after exercise (cycle ergometry only) support the hypothesis that the immediate leucocytosis during brief exercise is attributable to elevated catecholamine levels, whereas the delayed neutrophilia is due to raised cortisol levels.

Adult↗
PubMed1991

The varicose vein waiting list: results of a validation exercise.

A lengthening waiting list for treatment of varicose veins in a busy teaching hospital prompted a careful review. Patients were sent a detailed questionnaire which addressed current symptoms, progression of the complaint and the desire for surgical treatment. Of 519 patients on the waiting list, replies were received from 471 (91%). Forty-eight patients could not be traced after two questionnaires had been sent and enquiries made with their last known local GP. A further 87 (17%) patients were removed from the waiting list because they no longer desired treatment or had had treatment in the private sector. The remaining 384 patients were sent appointments for specially organised Saturday morning assessment clinics attended by consultants and senior registrars. Eighty patients failed to attend without giving a reason and were removed from the waiting list. Of 304 patients reviewed, surgical treatment was considered necessary for 219, of whom 182 were suitable for day-case surgery, leaving only 37 patients of the original 519 who required inpatient surgical care. This study has shown how careful assessment and the increased provision of day-case facilities can relieve pressure on inpatient care.

Adult↗
PubMed1991

Testing of saliva for antibodies to HIV-1.

To determine whether saliva is a potentially useful sample for screening for HIV infection when serum is not obtainable, saliva and serum samples from 50 HIV-infected and 50 uninfected subjects were tested for antibody to HIV-1 (anti-HIV-1) using a second-generation enzyme-linked immunosorbent assay (ELISA; Abbott) and prototype antibody-capture ELISA (Wellcome). Of saliva specimens from HIV-infected people, six gave negative results on the Abbott and one on the Wellcome assays; all specimens from uninfected people were negative by both assays. Sensitivity for the Abbott assay was therefore 88.0% [95% confidence interval (Cl) 76.2-94.4%], an unacceptable level for screening purposes. Sensitivity for the Wellcome assay was 98% (95% Cl 89.5-99.6%), a more satisfactory level for population screening. Further validation of this technique is necessary, and of methods for collection of saliva specimens in particular.

AIDS Serodiagnosis↗
PubMed1990

Epidermal growth factor receptor (EGFr) as a marker for poor prognosis in node-negative breast cancer patients: neu and tamoxifen failure.

Analysis of EGFr and ER was performed on tumour samples from 231 patients with operable breast cancer followed for up to 6 yr after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) had tumours greater than 10 fmol/mg 125I-EGF binding (EGFr+) and 47% (109) had cystolic ER concentration greater than 5 fmol/mg (ER+), with a marked inverse relationship between EGFr and ER (P less than 0.00001). EGFr was second only to axillary node status as a prognostic marker for all patients both in terms of relapse-free and overall survival (P less than 0.001, logrank EGFr+ vs EGFr-). For patients with histologically negative axillary nodes EGFr was superior to ER in predicting relapse and survival (P less than 0.01 and P less than 0.005, respectively, compared to P less than 0.1 and P less than 0.1, logrank). In a multivariate (Cox model) analysis only EGFr, out of EGFr, ER, size and grade, was predictive for either relapse-free or overall survival for patients with node-negative disease (P = 0.052 and P = 0.026, respectively). The correlation of neu expression with response to tamoxifen in patients with recurrent disease was assessed immunochemically. Response rate was reduced in the presence of neu from 50 to 17% for ER+ cases and from 26 to 0% for ER- cases.

Biomarkers, Tumor↗
PubMed1990

Epidemiology and hepatitis C virus in Victoria.

Parenterally transmitted non-A, non-B (NANB) hepatitis virus or hepatitis C virus is a common cause of both acute and chronic hepatitis. Using a recently developed enzyme-linked immunosorbent assay we looked at the prevalence of antibodies to hepatis C virus (anti-HCV) in a number of groups. People with haemophilia (75.6%) and intravenous drug users (61.9%) had the highest prevalence, while homosexual men attending a sauna (34.1%) and prisoners (30.8%) had a moderately high prevalence of anti-HCV. A lower prevalence of antibody was detected in female prostitutes (10.4%), institutionalised mentally retarded subjects (9.5%), homosexual men requesting human immunodeficiency virus (HIV) testing through their local doctor (8.8%), dialysis patients (5.9%), renal transplant patients (6.9%), and patients referred from a sexually transmitted diseases clinic (6.2%). The lowest prevalence of anti-HCV was recorded in women attending a provincial hospital for antenatal care (0.4%). The predominance of anti-HCV in groups of people exposed to blood-borne and sexually transmitted infections suggests that these routes may be primarily involved in the spread of hepatitis C virus infection.

Adult↗
PubMed1990

Expression of the neuron-specific glycoprotein GP50 by granule cell cultures.

The expression and properties of the neuron-specific glycoprotein, GP50, by neonatal rat granule cells grown in primary tissue culture were studied using the monoclonal antibody MabSM-GP50. GP50 was expressed by granule cells in culture but not by astrocytes or PC12 cells that had been induced to differentiate with nerve growth factor. Immunocytochemical staining of granule cell cultures demonstrated that immunoreactivity was concentrated in the cell body. Although the amount of GP50 increased slowly throughout the culture period the maximum level of expression in vitro was markedly lower than that observed in cerebellum of the comparable age. Radiolabelling of cell surface proteins by lactoperoxidase-catalyzed iodination demonstrated that GP50 was expressed on the surface of granule cells. Following phase-partitioning of granule cells in the presence of Triton X-114, 75% of GP50 was found to be present in the detergent phase, indicating that it is an integral membrane protein. Sucrose density gradient centrifugation of Triton X-100 extracts of granule cells resolved GP50 into two components with sedimentation coefficients of 3.6S and 7.3S. The 3.6S species (Mr 42,000 Da) accounted for greater than 80% of the total, indicating that GP50 is present predominantly in a monomeric form within the membrane. These properties are similar to those of GP50 expressed in P12 cerebellum but contrast with the behavior of GP50 from mature brain, in which the 7.3S, hydrophilic form is the predominant species. The results suggest that the mature expression of GP50 may be dependent upon the histotypic pattern of development which occurs in vivo.

Animals↗