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Biomedical subjects

D Parkin

Publications and source records attributed to D Parkin.

At least 19 recordsLinked to original sources

DNA fingerprinting of benign and malignant breast lesions.

Paired blood and breast tissue samples from 96 patients undergoing surgical excision of a breast lesion were subjected to DNA fingerprint analysis using the minisatellite probes 33.6 and 33.15. The 'fingerprints' of the blood and breast DNA were compared. DNA fingerprint changes seen were classified as band additions, band deletions or changes in band intensity. Significantly more DNA fingerprint changes were seen in malignant than in benign lesions (probe 33.6, P<0.01; probe 33.15, P=0.01; both probes, P = 0.04). The frequency of the changes detected in the breast cancers was unrelated to tumour grade or the presence of invasion. DNA ploidy was measured in 70 of the breast carcinomas. DNA fingerprint changes were seen in 41 of these, but flow cytometry detected aneuploidy in only 29 tumours (P=0.04). The DNA fingerprinting technique is unlikely to be useful in differentiating between benign and malignant breast lesions as changes were detected in one of the fibroadenomas studied. However, it may be a useful technique in screening tumour DNA for abnormalities suitable for more detailed analysis.

Breast Diseases

Mature results of a randomized trial of two doses of cisplatin for the treatment of ovarian cancer. Scottish Gynecology Cancer Trials Group.

PURPOSE: In 1992, we reported the first results of a randomized study in ovarian cancer, comprising two doses of cisplatin and indicated a significant difference (P = .0008) in median survival. Four years later, we now describe the results of this trial. PATIENTS AND METHODS: After a median follow-up of 4 years and 9 months, 115 of 159 cases of advanced ovarian cancer, originally randomized to receive six cycles of cyclophosphamide 750 mg/m2 and either a high dose (HD) of 100 mg/m2 cisplatin or a low dose (LD) of 50 mg/m2 (LD) cisplatin, have now died. RESULTS: The overall survival for HD and LD patients is 32.4% and 26.6%, respectively, and the overall relative death rate is 0.68 (P = .043). This represents a reduction in overall benefit with longer follow-up compared with the first 2 years (relative death rate of 0.52). Toxicity, particularly neurotoxicity, is still evident in the fourth year (10/31 on HD compared with 1/24 on LD). CONCLUSION: Our recommended dose of cisplatin in combination schedule is therefore 75 mg/m2, representing the optimal balance between efficacy and toxicity.

Antineoplastic Combined Chemotherapy Protocols

Incomplete excision of CIN in conization: further excision or conservative management?

The aim of this study was to investigate the experience of the further management in 112 cases with histological diagnosis of incomplete excision of CIN in cone biopsy. Two groups of women were studied. The women in the first group (n = 78) had a second excision while the women in the second group (n = 34) underwent conservative management with cytology and colposcopy. The histologic, cytologic and colposcopic findings in the women of both groups were compared. From the first group 38% had a second cone, 62% an hysterectomy; in 5 cases the second cone was followed by hysterectomy and the histology was negative in 75% and 65%, respectively. No indication of residual disease was found within 2-10 years of follow-up in any of the women in the second group. According to our study and being aware of the natural history of CIN, we can conclude that the decision for further excision should not be based exclusively on the histology report of involved margins, but should only be taken after careful cytological and colposcopic selection of the cases.

Adult

Lanterns in the jungle: is the NHS driven by the wrong kind of efficiency?

The performance of the National Health Service is assessed in part by an Efficiency Index (EI) which is applied to the service as a whole as well as to individual health authorities. The EI relates increases in the amount of patient care activity to increases in total expenditure. The index can give a misleading impression of performance, creates perverse incentives and is at odds with the overall strategy of the health service which is to place greater emphasis on the promotion of health and to provide more care in primary and community-based settings. The philosophy, validity and appropriateness of the EI are discussed.

Community Health Services

Hyperviscosity syndrome in disseminated breast adenocarcinoma.

Circulation within the bloodstream of mucin derived from mucin-producing adenocarcinomas has been documented infrequently but has been associated with vascular occlusion, organ infarction, and hyperviscosity. The nature of the mucin and the therapeutic role of plasmapheresis in this condition has not been reported. A 64-yr-old female, who had undergone a mastectomy 3 yrs previously for an infiltrating mucinous breast adenocarcinoma, presented with dementia. A blood film showed marked rouleaux and a bluish background. No abnormal bands were detected on plasma protein electrophoresis. Blood, serum and plasma viscosity were above the range of readability of the viscometer. A bone marrow biopsy showed replacement with tumor similar to the original. Repeated plasmaphereses substantially reduced viscosity and temporarily improved her mental state. Post mortem revealed numerous infarcts with eosinophilic mucoid material in the lumen of many small vessels. That the offending plasma constituent was a sialomucin was suggested by mucin stains of the tumor and peripheral blood, a plasma sialic acid level 10 x normal and a substantial fall in viscosity after in vitro treatment of plasma with neuraminidase.

Adenocarcinoma, Mucinous

An evaluation of ambulatory visit groups in rheumatology out-patients.

The development of case mix measures for National Health Service (NHS) care has become of great importance recently. Much effort has been put into devising measures for in-patient care, but measures for ambulatory (outpatient, day care and primary care) visits are less developed. Ambulatory Visit Groups (AVGs) is an American system devised to aggregate ambulatory visits into iso-resource groups. However, some assumptions made in the construction of the AVG system may not hold for the UK health service, including the use of consultation time as a proxy for the total resource use associated with the out-patient attendance. To test AVGs in the UK context, a three-month prospective study of rheumatology out-patient attendances at two hospitals in Newcastle upon Tyne assembled a database of 3393 'visits', together with resource use data. The AVGs derived from these were analysed to evaluate the homogeneity of the groups with respect to consultation resource use, and the degree to which consultation time can be considered a proxy for resource use in this setting. Consultation time distributions were markedly skewed, and required log transformation before analysis. Variation in log consultation time was found to depend as much on the clinician as on the AVG, and the two were observed to interact. Resource use distributions were also skewed, and were similarly transformed for analysis. Non-parametric analysis of variance showed resource use to be significantly associated with AVG, but the amount of variation associated with the AVG appeared to be small and inconsistent.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care

Econometric analyses of national health expenditures: can positive economics help to answer normative questions?

The size of national health care expenditure is an important research and policy issue. This paper reviews theoretical and empirical analyses of an implied optimal size for a health sector. Various economic theories are explicitly or implicitly invoked, but none is fully satisfactory. Theory provides, at best, a loose justification for empirical specifications of health sector behaviour. Nevertheless, this has a large and growing empirical research industry. The complexity of the issues provides an excuse for reliance on empirical analyses using ad hoc models. The paper analyses aggregate time-series data, using the cointegration approach, on health, health care expenditures and national income. Only one national model met both statistical criteria and showed a significant relationship: between potential life years lost and health care expenditure in the UK. The case for any general relationships remains unproven. There is no objective scientific method to determine optimal health expenditure, nor should we expect one. However, positive analyses can help with normative questions. A better understanding of health expenditure determination would arise from better specification of the relationships, perhaps by analysis at a lower level of aggregation.

Bias

The effects of leukaemia inhibitory factor on platelet function.

Leukaemia inhibitory factor (LIF) is able to promote megakaryocytopoiesis in vitro and elevate platelet counts in vivo, and is a potential new therapeutic agent for the treatment of thrombocytopenia. To determine whether platelets released under conditions of LIF-stimulated megakaryocytopoiesis have intact function, we compared aggregation responses of platelets from mice with constitutively elevated LIF levels (FD/LIF mice) and mice injected with recombinant murine LIF (rmLIF mice) with their respective control mice. We report that ex vivo platelet aggregability and thromboxane B2 release were intact in the LIF-treated mice, and were significantly enhanced in some situations. LIF-treated mice also had significantly increased platelet counts (FD/LIF mice: 1302 +/- 173 x 10(9)/l compared to 1012 +/- 99 x 10(9)/l for FD mice; rmLIF mice: 1460 +/- 193 x 10(9)/l compared to 985 +/- 67 x 10(9)/l for FCS/NS mice), increased platelet volumes and elevated plasma fibrinogen and calcium levels. The platelet hyperreactivity seen in the LIF-treated mice is likely to reflect the larger platelet volumes and/or the effect of plasma components such as fibrinogen, elevated levels of which were due to the concomitant action of LIF as a stimulant of acute phase protein synthesis.

Animals

Linkage studies with 17q and 18q markers in a breast/ovarian cancer family.

Genes on chromosomes 17q and 18q have been shown to code for putative tumor suppressors. By a combination of allele-loss studies on sporadic ovarian carcinomas and linkage analysis on a breast/ovarian cancer family, we have investigated the involvement of such genes in these diseases. Allele loss occurred in sporadic tumors from both chromosome 17p, in 18/26 (69%) cases, and chromosome 17q, in 15/22 (68%) cases. In the three familial tumors studied, allele loss also occurred on chromosome 17 (in 2/3 cases for 17p markers and in 2/2 cases for a 17q allele). Allele loss on chromosome 18q, at the DCC (deleted in colorectal carcinomas) locus, was not as common (6/16 cases [38%]) in sporadic ovarian tumors but had occurred in all three familial tumors. The results of linkage analysis on the breast/ovarian cancer family suggested linkage between the disease locus and 17q markers, with a maximum lod score of 1.507 obtained with Mfd188 (D17S579) polymorphism at 5% recombination. The maximum lod score for DCC was 0.323 at 0.1% recombination. In this family our results are consistent with a predisposing gene for breast/ovarian cancer being located at chromosome 17q21.

Adult

Cancer mortality among Polish migrants to France.

Cancer risk in the Polish-born population of France has been compared to that in Poland and in native French subjects (born in France), using mortality data from the period 1979-1985. The Polish-born community in France is a long-established one--most migration occurred during the 1920s--so that for many cancer sites the cancer pattern is closer to that of French natives than that in Poland (eg oral cavity, oesophagus, large bowel, gall bladder, uterus, leukaemia). Polish migrants, however, retain their characteristically high rates of cancer of the stomach and lung (in men), and low rates of breast and prostate cancer. The Polish-born community has a characteristic pattern of residence (living mainly in the Nord and the Pas-de-Calais) and occupational status (a higher proportion of 'workers' than the French-born); these are important confounding factors which can mask the true differences in risk for several sites (larynx, oesophagus, large bowel) if no adjustment is made during analysis.

Adolescent

Cancer in Italian migrants.

Migration of Italians to other parts of the world has a long history and has involved very large numbers of individuals. The study of the health consequences of this migration is made possible by the availability of statistics on mortality and morbidity, both in Italy and in the host countries, and of social and economic information on the various Italian communities abroad. The results of the major studies are reviewed, comparing the rates in immigrants with those in the host countries and in Italy. The differences in cancer rates between Italian and local-born populations--for stomach cancer in both sexes, and for cancer of the colon, lung, and breast in females, and for prostate cancer--are consistent with the direction of differences between rates in Italy and those in the host countries. For colon and rectum cancer in males, there are unexpected findings in most of the United States' studies. Analysis by duration of residence shows changes in the risk for several sites in males, but not in females, according to length of stay in the host country. This finding possibly reflects greater stability of habits and lifestyle in females compared to males.

Australia

Case mix measures for ambulatory care.

Resource management in Ambulatory Care is recognized as an increasingly important area for development by many countries, and there has been much interest in the part that Case Mix Measures (CMMs) can play in this. There are a number of possible approaches to case mix, and several measures already exist. However, these are at present mainly still at the development stage and all are North American in origin. This paper reviews the role and state of the art of ambulatory CMMs and reports on an initial evaluation of the Ambulatory Visit Group (AVG) methodology using European data. Although the AVG grouper works under limited conditions, important questions remain concerning its validity and usefulness.

Ambulatory Care

Blood coagulation profile in long-term hormone replacement therapy with mestranol.

The coagulation profile of oophorectomised women on long-term (15 yr) hormone replacement therapy with mestranol (30 micrograms/day) is compared to that of women on long-term placebo. Analysis of these data showed no significant difference in prothrombin time, partial thromboplastin time or in anti-thrombin III level in these groups.

Adult

A radioimmunoassay for metoclopramide.

A radioimmunoassay for the anti-emetic drug, metoclopramide, in the pmol range was developed. The immunogen was prepared by photolytic coupling of metoclopramide to bovine serum albumin. A crosslinking reagent, N-hydroxy-succinimidyl-4-azidobenzoate, was first reacted with serum albumin through nucleophilic substitution. Ultraviolet irradiation (lambda greater than 300 nm) of the photoactive serum albumin conjugate in the presence of metoclopramide resulted in covalent attachment of the drug to the protein. An 125I-labelled metoclopramide derivative was prepared by diazotisation of the aromatic amine group and substitution of the resultant diazo group with 125I-. Binding data of the antibody with radioiodinated metoclopramide gave a linear Scatchard plot indicative of a homogeneous antibody population. A dissociation constant of 3 X 10(-11) mol/l was calculated for the antigen-antibody interaction. The antibodies showed negligible cross-reactivity with lignocaine which is structurally closely related to metoclopramide.

Albumins