Reasons that some screening programmes fail to control cervical cancer.
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Biomedical subjects
Publications and source records attributed to J Chamberlain.
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Plasma levels of N-carboxy-3-morpholinosydnonimine ethyl ester (molsidomine, Corvaton) and its pharmacologically active metabolite 3-morpholinosydnonimine (SIN-1) were measured in six healthy male and female volunteers after single intravenous and oral dosing of 4 mg molsidomine. Additionally indocyanine green and phenazone (antipyrine) clearances were determined to estimate hepatic blood flow and metabolic liver function in each subject. The pharmacokinetic parameters of molsidomine were similar to already published data in healthy volunteers and patients. The plasma level of SIN-1 formed was always lower than the molsidomine level but obviously reflects the corresponding molsidomine concentration time course in plasma. Indocyanine green plasma clearance was reduced by 15%. after intravenous dosing of 4 mg molsidomine. There was no clear-cut relationship between the plasma clearances of molsidomine and phenazone in these subjects with normal metabolic liver function.
Cystic adventitial arterial disease (CAAD) is usually situated in the popliteal artery and is a well recognized cause of intermittent claudication in otherwise healthy, young, non-smokers. Three cases of CAAD have recently been encountered, involving the popliteal artery in two patients and the common femoral in one. Two of these patients were hypertensive smokers in their sixth decades and only one was an otherwise healthy non-smoker, but all three had a characteristically rapid onset of symptoms. All had angiographic appearances suggestive of CAAD, confirmed by ultrasound and CAT scanning in one patient. Two were treated by resection of the affected artery and a replacement graft, both with excellent results. One popliteal lesion was bypassed with a vein graft which occluded after 3 months. CAAD may occur more commonly than generally realized. It can present in patients whose condition suggests an atheromatous cause for their symptoms. Since good results can be expected from appropriate surgical treatment in most cases, CAAD should be considered in the diagnosis of all patients with claudication, particularly when the onset has been rapid.
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It has been suggested that sodium pertechnetate 99mTc millimicrospheres can be used to measure Kupffer-cell function. We studied animals and humans to show whether the clearance and catabolism of 99mTc-labelled millimicrospheres can be used as a measure of Kupffer-cell function. Comparison with albumin 125I-microaggregates clearance of human serum albumin failed to demonstrate that they can be used for this purpose. We suggest that their blood clearance is mainly an expression of liver blood flow.
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This paper describes an analysis of the social, psychological and demographic factors associated with attendance/non-attendance at a clinic providing mammography and an examination carried out by medically-trained staff. Six hundred and fifty-four women aged 45-64 were interviewed approx. 1 month before they received an invitation to attend for breast screening. Seventy-two percent of these women subsequently attended the clinic. In all 30 different variables were measured. The attender could best be characterised as someone who previously used other types of preventive health service, felt vulnerable to breast cancer and saw breast screening as being beneficial. The implications of these and other findings are discussed.
A workshop of the Project on Evaluation of Screening Programmes of the International Union against Cancer (UICC) was held in Lyon, France. on November 20-22, 1984. The focus of the workshop was on screening for gynaecological cancer, especially for cancer of the cervix uteri. This report summarizes the presentations, conclusions and recommendations from the workshop.
The kinetics of a sustained-release formulation of pentoxifylline were compared with those of a capsule and an intravenous infusion. Ten healthy subjects received each of the oral pentoxifylline formulations (400 mg) three times a day for 9 days in a random crossover fashion. Pentoxifylline (200 mg) was also given intravenously on a separate day. After intravenous pentoxifylline, plasma levels declined in a biphasic manner, with a terminal t1/2 of 1.63 +/- 0.8 hr. Plasma clearance was 1333 +/- 481 ml/min and the volume of distribution was 168 +/- 82.3 l. Cumulation of pentoxifylline in plasma after repeated dosing was minimal. Plasma levels of the active 5-hydroxylated metabolite were generally higher than those of the parent drug after both routes of administration. Urinary excretion of two acid metabolites after oral and intravenous dosing indicated almost complete absorption of drug-related substances from both of the oral formulations, although bioavailability averaged 20% to 30%.
Screening healthy women in order to detect the earliest signs of breast cancer may offer a possibility of curing many breast cancer patients who would be incurable if left until they developed symptoms. However, the natural history of breast cancer is very variable, probably indicating a wide spectrum of different growth rates of the tumour. Therefore it cannot necessarily be assumed that cancers detected by screening at an apparently early stage will behave in the same way as symptomatic cancers at that stage. To prove that screening enables cancer to be cured one needs to compare the number of deaths in a group of women who have been offered screening with those in a comparable group who have not. Unlike the situation in clinical trials of different treatments, comparison of the survival of screen-detected cancers with symptom-detected cancers is inadequate proof, because of selection bias, lead-time bias and length-bias. One randomized controlled trial of screening for breast cancer has so far been published and this shows that women in the group who were offered screening suffered one third fewer deaths from breast cancer than women in the control group, the difference persisting for up to 14 years from the first screening invitation. Further trials are now under way in Canada and various European countries, hoping to confirm this finding and to explore various other issues. Of the screening test methods currently available mammography seems the most sensitive and specific and its radiation hazard is now of almost negligible proportions provided that regular careful monitoring of the equipment is carried out. However it may have the disadvantage of overdiagnosing cases of borderline non-invasive neoplasia which might not progress to invasive cancer within the woman's lifetime. Clinical examination of the breasts is a less satisfactory test in older women but it may be useful in premenopausal women in whom mammography is less sensitive. The validity of self-examination of the breasts by women themselves is still largely unknown, but it is unlikely that compliance with regular breast self-examination will be as high as women's acceptance of screening. Further research is required into the optimal frequency of screening and into its cost-effectiveness.
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In 12 healthy male volunteers, molsidomine 1, 2 and 4 mg i.v. increased resting heart rate and decreased systolic blood pressure, the latter still being affected after 8 hours. After single oral doses of 1 and 2 mg, systolic pressure tended to be reduced for 90 minutes and exercise heart rate tended to be increased. After oral treatment with 2 mg molsidomine three times daily for 1 week, the pharmacokinetic parameters and the effects on heart rate and blood pressure after the final dose were not different from those after the first dose. The terminal half-life was independent of dose and route of administration. Clearance and distribution volume were not dose-dependent. The bioavailability of a 2 mg oral dose of molsidomine was 44%. Inter-individual variation in heart rate, blood pressure and pharmacokinetics was observed.
Concentrations of sodium (Na), phosphorus (P), sulphur (S), chlorine (Cl) and potassium (K) and their variations during brain development were measured in freeze-dried thick sections from rat brain (16-20 micron). Sprague-Dawley rats were bred and the day of finding vaginal spermatozoa was considered as day zero of pregnancy. On days 12E, 13E, 14E, 16E, 19E, 21E (embryonic) and postnatal day one whole embryos or fetal heads were rapidly frozen in liquid Freon 22 cooled with liquid nitrogen (-180 degrees C), sectioned in a cryostat (-20 to -40 degrees C), and processed for X-ray microanalysis on pure carbon plates. Concentrations of Na and Cl differed in the cells of the cerebral cortex, ependyma, choroid plexus and cerebral spinal fluid (CSF). During cerebral development, Na and Cl concentrations appeared to be correlated, while K was more related to P. S was low and unchanged in all compartments during development and was thus considered as an internal control. K was inversely related to Na and Cl fluctuations within the choroid plexus epithelia. Sharp phase changes of elemental composition appeared in all tissues at specific growth stages, e.g. days 14E and 19E. These results demonstrate rhythmic changes in the inorganic components of developing rat brain cells and fluid environment presumably reflecting physiological fluctuations and cell cycle phenomena. Such changes may also be related directly or indirectly to known 'growth phase changes' in the developing rat.
Using the health belief model as an organizing frame-work, variables were examined that might predict attendance at a class teaching breast self-examination. The results show that various health belief dimensions are among the best predictors although other strong predictors are identified and some modifications to the health belief model are proposed.
In a screening service for breast cancer the results of routine repeat tests of women will contribute more than the results of their initial tests. A comparison of first and subsequent screens in a group of high risk women suggests that the sensitivity of screening declines between first and subsequent visits, whereas its specificity improves. Despite improved specificity, the ratio of benign biopsies to cancer was worse at repeated screening (21 to 1) than at first screening (6 to 1). This was because between first and subsequent screens the yield of cancers fell to a greater extent than the yield of benign disease. The patients with breast cancer diagnosed during this study were remarkable for their good prognosis, 92% being still alive and 86% free from recurrence at their last follow up, the follow up intervals ranging from four to eight years.