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Biomedical subjects

P Livingston

Publications and source records attributed to P Livingston.

16 recordsLinked to original sources

How acceptable is a referral and telephone-based outcall programme for men diagnosed with cancer? A feasibility study.

The objective of this study was to determine the feasibility and acceptability of a referral and outcall programme from a telephone-based information and support service, for men newly diagnosed with colorectal or prostate cancer. A block randomized controlled trial was performed involving 100 newly diagnosed colorectal and prostate cancer patients. Patients were referred to the Cancer Information Support Service (CISS) through clinicians at diagnosis. Clinicians were randomized into one of three conditions. Active referral 1: specialist referral with four CISS outcalls: (1)<or=1 week of diagnosis; (2) at 6 weeks; (3) 3 months; and (4) 6 months post diagnosis. Active referral 2: specialist referral with one CISS outcall<or=1 week of diagnosis. Passive referral: specialist recommended patient contacts CISS, but contact at the patient's initiative. Patients completed research questionnaires at study entry (before CISS contact), then 4 and 7 months post diagnosis. Overall, 96% of participants reported a positive experience with the referral process; 87% reported they were not concerned about receiving the calls; and 84% indicated the timing of the calls was helpful. In conclusion, the referral and outcall programme was achievable and acceptable for men newly diagnosed with colorectal or prostate cancer.

Adult↗

Quality of care for women presenting with benign breast conditions.

The aim of the study was to investigate the management of women with benign breast problems. A consecutive sample of women (n = 194) was assessed who presented to public or private sector providers. The main reasons for referral were breast lumps (62%); 56% of women who attended the public sector did not receive any recommendation compared to 40% who attended the private sector and clinical/general practitioner reviews were recommended to more women in the private sector (54%). Reasons for the discrepancy between public and private patients require further investigation.

Australia↗

Do women have equitable access to quality breast prosthesis services?

Although up to 90% of women who have had a mastectomy use breast prostheses, significant gaps exist around current breast prosthesis services for Australian women. These gaps include the timeliness and quality of information provision, the disparity in financial assistance, and the lack of knowledge regarding the determinants of what constitutes a "quality" breast prosthesis. Revised policy initiatives are central to addressing these gaps to ensure equitable access to quality breast prosthesis services.

Australia↗

Specificity analysis of sera from breast cancer patients vaccinated with MUC1-KLH plus QS-21.

The mucin MUC1 is expressed on breast cancers in an underglycosylated form compared to normal tissues and is therefore a potential target for cancer immunotherapy. MUC1 contains multiple tandem repeats of the 20 amino acid (aa) peptide (VTSAPDTRPAPGSTAPPAHG). The APDTRPA epitope is particularly immunogenic since it is recognized by a variety of murine monoclonal antibodies and by some sera and cytotoxic T-cells from unimmunized patients with epithelial cancers. We have prepared a 30 aa peptide (C)VTSAPDTRPAPGSTAPPAHGVTSAPDTRPA with cysteine at the N-terminal end, and used the cysteine for chemical conjugation to keyhole limpet haemocyanin (KLH). Six breast cancer patients immunized with this conjugate plus the immunological adjuvant QS-21 have all produced high titre (by ELISA) IgG and IgM antibodies against the 30 aa MUC1 peptide, but these sera reacted moderately, or not at all, with MUC1-positive tumour cells. To understand this specificity better, we prepared a series of smaller peptides to determine the epitopes recognized by these immune sera in inhibition assays. Only peptides containing APDTRPA at the C-terminal end were able to completely inhibit ELISA reactivity for the full 30 aa peptide. No sera were completely inhibited by APDTR, APDTRP, PDTRPA or any other peptides that did not contain the full APDTRPA epitope. Remarkably, sera from all six patients recognized this same epitope and were completely inhibited by only this epitope. The specificity of these sera (1) primarily for C-terminal APDTRPA, and the absence of this epitope at the C-terminal end of any tumour mucins, and (2) the N-terminal APDTRPA alanine, which is normally buried in the beta turn MUC1 assumes in its secondary structure may explain the moderate to weak reactivity of these high titer sera against MUC1-positive tumour cells.

Amino Acid Sequence↗

A strategy for involving general practitioners in smoking control.

OBJECTIVE: In 1991, the Victorian Smoking and Health Program introduced a simple intervention strategy for general practitioners that could be integrated conveniently and inexpensively into the routine care of patients who smoke. The aim of this study was to determine whether there had been a change over time in whether or not GPs advised their patients not to smoke. METHOD: The extent to which smokers remembered GPs talking to them about smoking was assessed in population-based surveys of adults in Victoria in 1990 (prior to the implementation of the intervention) and in 1992, 1994 and 1996. RESULTS: Over time there was a significant increase in the proportion of smokers who reported that their GP had provided them with help or information to stop smoking (chi 2 = 17.58, p < 0.001). In 1996, 9% of smokers said their doctor had advised them to contact Quit. CONCLUSION: Levels of recalled advice and provision of information regarding smoking cessation have increased by 10% over the past six years. However, nearly half the smokers in this study reported that they had been given inappropriate advice or no advice at all. IMPLICATIONS: A brief intervention by GPs, supplemented by appropriate referrals, has the potential to assist significant numbers of smokers to quit and may be more practical for GPs who are unable to personally provide all of the support smokers may need to quit.

Chi-Square Distribution↗

FC-2.15, a monoclonal antibody active against human breast cancer, specifically recognizes Lewis(x) hapten.

FC-2.15 is a murine IgM monoclonal antibody that recognizes breast and colon human carcinomas, chronic myeloid leukemias, Sternberg cells of Hodgkin's lymphoma and some normal cells, such as peripheral polymorphonuclear granulocytes. It has been previously demonstrated that FC-2.15 recognizes the carbohydrate moiety of different glycoproteins. FC-2.15 is able to mediate the in vitro lysis of Ag-2.15+ cells by human complement. In a phase I clinical trial, FC-2.15 induced antitumor responses and reversible neutropenia was its main toxicity. In this work, analysis of epitope specificity has demonstrated that FC-2.15 specifically recognizes terminally exposed Lewis(x) trisaccharide but not sialyl-Lewis(x), Lewis(a), trifucosylated Lewis(y), blood-group antigens A and B, globo H and gangliosides. In polymorphonuclear granulocytes (PMN), myeloid leukemic cells and colon carcinoma T84 cells, Lewis(x) was found to be almost exclusively N-linked to the protein core, whereas in breast carcinoma MCF-7 cells, Lewis(x) appeared to be mostly O-linked. Treatment with neuraminidase increased detection by FC-2.15 in normal PMN, myeloid leukemia cells and T84 cells but not in MCF-7 cells.

Animals↗

Ganglioside vaccines with emphasis on GM2.

Gangliosides are neuraminic acid-containing glycosphingolipids that are anchored into the cell membrane lipid bilayer by lipophilic ceramide chains. They are overexpressed on tissues of neuroectodermal origin, and particularly in tumors such as melanomas, sarcomas, neuroblastomas, astrocytomas, and small cell lung cancers. Both active and passive immunotherapy trials have identified gangliosides as uniquely effective targets for antibody mediated melanoma immunotherapy. Induction of antibodies against GM2 by vaccination has correlated with an improved prognosis in American Joint Committee on Cancer (AJCC) stage III melanoma patients and vaccines containing GM2 chemically conjugated to keyhole limpet hemocyanin (KLH; GM2-KLH) plus the immunologic adjuvant QS-21 have proven to be consistently immunogenic. Phase III trials with this vaccine are ongoing in patients with melanoma in the United States, Canada, Europe, Australia, and New Zealand. GD2, fucosylated GMI, and GD3-KLH conjugates plus QS-21 are also consistently immunogenic, inducing IgM and IgG antibodies in the majority of patients. Polyvalent ganglioside-KLH conjugate plus QS-21 vaccines should be available in early 1999 for testing in phase II and III clinical trials.

Adjuvants, Immunologic↗

Tumor cell reactivity mediated by IgM antibodies in sera from melanoma patients vaccinated with GM2 ganglioside covalently linked to KLH is increased by IgG antibodies.

Natural IgM antibodies against the melanoma cell-surface ganglioside GM2, and IgM antibodies induced by vaccination with GM2 adherent to bacillus Calmette-Guerin, have been correlated with increased disease-free and overall survival in melanoma patients in previous phase I and II clinical trials. A vaccine containing GM2 covalently attached to keyhole limpet hemocyanin (KLH) plus the immunological adjuvant QS-21 now induces higher-titer, longer-lasting IgM antibodies against GM2 and has recently entered phase III clinical trials. For the first time this new vaccine also induces IgG antibodies against GM2 in the majority of immunized patients. With regard to immunity against bacteria, IgM antibodies have been described to be 1000-fold more effective than IgG antibodies at opsonification, complement-mediated cytotoxicity and protection from bacterial challenge. Though IgG antibodies have the theoretical advantage of being able to mediate antibody-directed cell-mediated cytotoxicity (ADCC), they may inhibit complement mediated IgM effector mechanisms against melanoma cells. Our goal was to confirm the functional characteristics of the anti-GM2 IgM and IgG antibodies induced by vaccination and to determine the impact that IgG antibodies might have on IgM antibody reactivity with GM2-positive tumor cells. Post-immunization sera from seven immunized patients were separated by size-exclusion chromatography into IgM and IgG fractions and a variety of serological assays were performed with the individual fractions and their combinations. Assays identifying specific IgM or IgG reactivity demonstrated partial inhibition by the opposite fraction. However, when the endpoint was complement-mediated lysis or overall antibody binding, which may more faithfully predict in vivo complement-mediated opsonification and lysis, the combinations of IgM and IgG fractions consistently demonstrated higher reactivity than either fraction alone. In addition, ADCC was induced in all seven patients. The results were the same whether the sera were obtained after 2 months or 2 years of immunizations. These findings suggest that IgG antibodies induced by the GM2-KLH plus QS-21 vaccine will not inhibit and should further augment the clinical impact of induced IgM antibodies.

Antibodies, Neoplasm↗

Antibody response to immunization with ganglioside GD3 and GD3 congeners (lactones, amide and gangliosidol) in patients with malignant melanoma.

GD3 is the ganglioside most abundantly expressed on the cell surface of human melanoma, and treatment with a murine MAb recognizing GD3 has induced major responses in a small proportion of patients with melanoma. We have therefore attempted to induce production of GD3 antibodies in melanoma patients by active immunization. We found, however, that vaccination with GD3-expressing melanoma cells or purified GD3 does not result in antibody production. We describe here attempts to overcome the poor immunogenicity of GD3 in patients with melanoma by chemical modification. GD3 lactones, GD3 amide and GD3 gangliosidol were synthesized, and the humoral immune response to these derivatives was analyzed. Immunization of melanoma patients with these GD3 derivatives resulted in production of IgM antibodies and, in the case of GD3 amide, also of IgG antibodies. The antibodies to the GD3 derivatives did not cross-react with GD3. This is in contrast to observations in the mouse, where GD3 lactone I induced antibodies that showed cross-reactivity with GD3. Thus, the human immune response was specifically directed toward the modified epitope, rather than to the native structure.

Amides↗

Lack of circulating thyroid stimulating immunoglobulins in cats with hyperthyroidism.

Although feline hyperthyroidism has become a commonly diagnosed disorder of older cats, the underlying etiology remains unknown. Pathological findings of adenomatous hyperplasia involving both thyroid lobes in most hyperthyroid cats suggests the possibility that feline hyperthyroidism may be similar to human Graves' disease, which results from high circulating levels of thyroid stimulating immunoglobulins (TSIs). To exclude high circulating levels of TSIs as the cause of feline hyperthyroidism, we measured intracellular concentrations of cyclic adenosine monophosphate (cAMP) in functioning rat thyroid cells (FRTL-5) incubated with IgG extracted from hyperthyroid cat serum. Since TSIs stimulate thyroid hormone secretion through activation of cAMP, their presence can be evidenced in vitro by generation of high cAMP concentrations in cultured thyroid cells. No significant difference was found in intracellular cAMP concentrations in FRTL-5 cells incubated with IgG from normal versus hyperthyroid cats. In contrast, IgG from a human patient with Graves' disease caused substantially more cAMP generation than either normal human IgG or IgG from the cats of this study. These results indicate that feline hyperthyroidism does not result from high circulating concentrations of TSI and, in that respect, is not analogous to Graves' disease.

Animals↗

Knowledge, attitudes and experience associated with testing for prostate cancer: a comparison between male doctors and men in the community.

BACKGROUND: Debate about testing for prostate cancer using prostate-specific antigen (PSA) and digital rectal examination (DRE) continues. The evidence of benefit from screening for prostate cancer using PSA tests is inconclusive, and it is unclear how PSA can be used most effectively in the detection of prostate cancer. Given the lack of consensus, it is important that consumers understand the issues in a way that will permit them to decide whether or not to have a test and, if symptomatic, how their condition is managed. AIMS: To compare prostate cancer knowledge, attitudes and testing experiences reported by male doctors and men in the community, despite the lack of evidence of a benefit. METHODS: The primary method for ascertaining the attitudes of male doctors (MD) was a telephone survey, with some doctors electing to complete a written survey. Each MD was selected, at random, from a register of male practitioners aged > or = 49 years of age. A total of 266 MD participated in the survey. The community sample (CS) was accessed using a telephone survey. Five hundred male Victorian residents aged > or = 49 years of age participated in the study. RESULTS: Knowledge - Overall, 55% of the CS indicated correctly that prostate disease is sometimes cancer, compared to 83% of MD. Attitudes - Fifty-five per cent of MD believed men should be tested for prostate disease at least every 2 years, compared to 68% of men in the CS. Testing experience - Forty-five per cent of MD had been tested for prostate cancer in the past, and 92% of those tests were reported as negative. In the CS, 56% had been tested for prostate cancer in the past, and 78% of the results were reported as negative. The significant independent predictors of having had a prostate test among MD were: (i) age (> or = 60 years; odds ratio (OR): 1.59; 95% confidence intervals (CI): 1.30-1.88) and (ii) positive attitudes towards regular testing for prostate cancer (OR: 2.27; 95% CI: 1.98-2.56). The significant independent predictors for the CS were: (i) age (> or = 60 years; OR: 1.65; 95% CI: 1.40-1.89), (ii) being married (OR: 1.30; 95% CI: 1.00-1.60), (iii) knowledge that prostate disease was sometimes cancer (OR: 1.46; 95% CI: 1.26-1.66) and (iv) positive attitudes towards regular testing for prostate cancer (OR: 2.12; 95% CI: 1.90-2.34). CONCLUSIONS: The results highlight that testing for prostate cancer is widespread in the community and in the medical profession. Further research should be undertaken to identify how to help men make fully informed decisions about prostate cancer testing.

Aged↗