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Biomedical subjects

P Carey

Publications and source records attributed to P Carey.

At least 19 recordsLinked to original sources

Cancer education and the primary school teacher in England and Wales.

Many adult behaviors and attitudes develop in early childhood. There is a growing acceptance of the need for health education of children of primary school age. Cancer is an important topic within health education, and this study was designed to assess the level of cancer education in schools. Data were collected from a randomly selected sample of over 1,000 teachers of children in primary school years 3-6 (ages 7-11 years). Cancer had been taught about by 18% of the sample, and their pupils' ages had no significant effect on whether they had taught about cancer. Cancer was most often taught about in response to a real-life situation, and the majority of the teachers did not use cancer education resources to help them. The study sought to ascertain why so many teachers had taught about cancer. It appears that concerns over their own lack of personal knowledge, and a perceived lack of resources, were the most common reasons. The young age of the pupils was also a deterrent to cancer education, especially among the teachers of the younger pupils. The results indicate various interventions that may increase the level of primary-school-based cancer education. These include improving teachers' awareness of cancer education issues and providing appropriate cancer education resources.

Attitude to Health

Is health locus of control related to health education activity.

Analysis of responses of 1922 teachers indicated that Multidimensional Health Locus of Control scale was a suitable instrument for assessing their health beliefs. The results suggest that health belief is not linked to whether teachers teach about cancer and, by implication, health generally.

Adolescent

Effect of atrial natriuretic hormone on vasopressin and thirst response to osmotic stimulation in human subjects.

To evaluate the effect of systemically administered atrial natriuretic hormone (ANH) on osmotically induced secretion of arginine vasopressin (AVP) and thirst sensation, 11 healthy men, aged 18 to 28 years, were studied on four occasions. The intravenous infusions of placebo (P) or one of three doses of ser-tyr28 human ANH (0.6 [LD], 1.8 [MD], and 5.4 [HD] pmol/kg/min) were given in random order over 2 hours. During the second hour, subjects also received a 5% saline (HS) infusion (0.1 ml/kg/min). The baseline parameters were similar on each of the study days. Plasma ANH levels increased approximately twofold, eightfold, and 25-fold during LD, MD, and HD infusions, respectively. HS infusion caused increases in serum sodium level (5 to 7 mEq/L) and osmolality (14 to 15 mOsm/L) (p < 0.001). During HS infusion on P day, ANH levels almost doubled (p < 0.001). AVP levels remained stable during the first hour of ANH infusions. An addition of HS caused a significant increase in AVP levels (p < 0.001). The magnitude of this increase was similar on each of the study days. Similarly, thirst perception increased significantly (p < 0.01) and to the same extent during HS infusion on all study days. Both AVP levels and thirst showed a very good correlation with serum osmolality on each of the study days, and there were no significant differences between any of the slopes or intercepts. We conclude that short-term elevation of plasma ANH levels up to 25-fold affects neither the osmotically stimulated secretion of AVP nor thirst perception.

Adult

Autologous bone marrow transplantation in poor-risk high-grade non-Hodgkin's lymphoma in first complete remission. Newcastle and Northern Lymphoma Group.

We report the safety and efficacy of autologous bone marrow transplantation (ABMT) in 30 patients with high-grade non-Hodgkin's lymphoma (NHL) in first complete remission (CR1) following remission induction chemotherapy. Two patients relapsed prior to ABMT. All patients were conditioned with high-dose melphalan. In Addition, ten received fractionated total body irradiation, one hemi-body irradiation and four high-dose etoposide. Unmanipulated non-cryopreserved autologous marrow was reinfused within 56 h of harvesting. Engraftment occurred in all patients with a median of 11 days of neutropenia (< 0.5 x 10(9) l-1), a median requirement for platelet transfusion of 3 days and packed red cell transfusion of 2 units, with a median hospital stay of 18 days post transplant. There was no procedure-related mortality and only minor morbidity was observed. Two patients relapsed at 1 and 2 months post transplantation, and one patient died of carcinoma of the lung 33 months after transplantation. The remaining 25 patients remain alive, well and in CR1 with a median follow-up of 44 months. The event-free survival at 3 years for all patients considered for ABMT was 83%. We conclude that ABMT for high-grade NHL in CR1 with non-cryopreserved marrow results in rapid haematological recovery without growth factor support. It is safe and is associated with high survival when used as consolidation of CR in high-risk patients.

Adolescent

Zidovudine phosphorylation in HIV-infected patients and seronegative volunteers.

OBJECTIVES AND DESIGN: Measurement of phosphorylated zidovudine (ZDV) inside infected cells is more likely to provide satisfactory dose response relationships than serum concentrations. This study provides information on ZDV phosphorylation in HIV-seronegative volunteers (n = 5) and in patients with HIV infection (n = 12). METHODS: Intracellular ZDV phosphate metabolites were measured in peripheral blood mononuclear cells isolated from whole blood by density cushion centrifugation. Cells were washed and extracted overnight with 60% methanol prior to analysis by high performance liquid chromatography. Fractions eluted from the column corresponding to ZDV, ZDV monophosphate (ZDV-MP), ZDV diphosphate (ZDV-DP) and ZDV triphosphate (ZDV-TP) were collected, hydrolysed by acid phosphatase and ZDV levels quantified by radioimmunoassay. RESULTS: The area under the plasma ZDV concentration-time curve (AUC0-6 h) was similar in seronegative volunteers and patients [mean +/- SD, 4.64 +/- 2.50 versus 5.56 +/- 2.67 mumoles/l h; 95% confidence interval (CI), -4.39-2.23; P = 0.646, Mann-Whitney U test]. However, ZDV phosphorylation was greater in patients, with the AUC0-6 h for total phosphate metabolites being 5.91 +/- 3.42 pmoles/10(6) cells h compared with seronegative volunteers (0.66 +/- 0.48 pmoles/10(6) cells h; 95% CI, -8.35 to -2.32; P = 0.0003). The concentration of ZDV-TP was similar in both groups, the increase in total phosphates in patients being due primarily to ZDV-MP. ZDV-MP AUC0-6 h and total ZDV phosphate AUC0-6 h were closely correlated (r2 = 0.94). The relationship between total ZDV phosphate AUC0-6 h and the CD4 count demonstrates that patients with a count < 100 x 10(6)/l have much higher ZDV phosphate levels, predominantly ZDV-MP. CONCLUSION: ZDV is phosphorylated to a greater extent in patients than in healthy volunteers. The increased ZDV-MP in patients with low CD4 counts may explain the well known occurrence of increased ZDV toxicity in patients with more advanced disease. The ability to measure ZDV phosphorylated metabolites (without the administration of radiolabelled nucleoside) represents a significant advance in our understanding of the clinical pharmacology of the drug.

Acquired Immunodeficiency Syndrome

Continuous-infusion 5-fluorouracil combined with doxorubicin and cyclophosphamide: feasibility study.

Previous studies have demonstrated continuous-infusion 5-fluorouracil (CI 5-FU) to be an active single-agent treatment for breast cancer without significant myelotoxicity. These qualities made CI 5-FU an attractive agent for combination with other effective but myelosuppressive agents. In this study we attempted to determine the maximal doses of CI 5-FU that could be added to a combination of agents known to be dose limited by myelotoxicity, doxorubicin 50 mg/m2 day 2 and cyclophosphamide 150 mg/m2 days 3-12 of a 28-day cycle. Patients who received doxorubicin and cyclophosphamide alone developed significant myelotoxicity but did not develop stomatitis. The addition of 5-7 days of CI 5-FU at 200-300 mg/m2 was associated more closely with increased stomatitis (P = .11) than with increased granulocytopenia (P = .57). The stomatitis observed for low doses of CI 5-FU given with doxorubicin and cyclophosphamide would not have been expected for these low doses of CI 5-FU given as a single agent. We conclude that the addition of CI 5-FU to myelotoxic doses of doxorubicin and cyclophosphamide is not a promising therapeutic strategy for significantly increasing the effectiveness of this combination of agents.

Adenocarcinoma

Teachers' attitudes to cancer education: a discussion in the light of a recent English survey.

Various attempts have been made at encouraging cancer education in British schools, and while some have had limited success, there is still a reluctance amongst teachers to adopt this subject in the classroom. The study discussed in this paper was an attempt to ascertain the current status of cancer education in English secondary education. Over 1,200 English secondary (11-16 years olds) schools took part and the data were collected between February and June 1990. Although there is evidence to suggest an element of self-selection, results from this sample indicate a growing commitment and enthusiasm for cancer education, in comparison to previous, similar studies. Over half the teachers had taught about cancer and 68.8% rated it an important health education topic. However, cancer did rate lowest out of a variety of health issues. Several reasons for this are discussed and all appear to relate to teachers' negative attitudes toward cancer, apparently based on preconception and misinformation. These must be overcome if cancer education is to achieve its true potential in English schools.

Adolescent

Cost-effectiveness of epoetin alfa therapy for anemia of end-stage renal disease.

The cost-effectiveness of epoetin alfa therapy for anemia in 20 patients with end-stage renal disease was retrospectively studied. Ten patients on continuous ambulatory peritoneal dialysis (CAPD) were given subcutaneous epoetin alfa as part of a multicenter, protocol-controlled study of the efficacy of epoetin alfa. Ten patients on in-center hemodialysis were given intravenous epoetin alfa as part of their routine clinical care. Change in hematocrit was used as the measure of effectiveness of epoetin alfa. Medication, laboratory, and transfusion costs were monitored for the six months preceding the initiation of epoetin alfa and the first six months of treatment. The cost of therapy increased for all patients by an average of $2722 +/- 1118; transfusion costs decreased, whereas medication and laboratory costs increased. Laboratory costs were significantly greater in CAPD patients than in hemodialysis patients during epoetin alfa therapy; no significant differences in medication costs or transfusion costs were noted between the groups. The mean increase in hematocrit for all patients was 7.4 volume percent. Following the initial change in hematocrit, further therapeutic response did not appear to be determined by increasing expenditures. Epoetin alfa was shown to be effective in treating anemia in patients with end-stage renal disease, but it was associated with higher costs of therapy.

Adult

Parents' knowledge of neonatal screening and response to false-positive cystic fibrosis testing.

Neonatal screening for cystic fibrosis (CF) has become feasible through analyzing dried blood specimens for immunoreactive trypsinogen (IRT), but the benefits and risks of such a screening program remain to be delineated. This study, a survey of the parents of 104 Wisconsin infants with false-positive IRT tests, showed parents had knowledge deficits about neonatal screening in general, misconceptions about test results, and high levels of anxiety. Parenting behaviors were reportedly unchanged during the usual 3-day waiting period between the news of the abnormal screening test and the diagnostic sweat test. Most, but not all, parents were relieved by negative sweat test results subsequent to the abnormal IRT test. Factors associated with continued parental concern included having less than a high school education and/or having an infant with low Apgar scores. Additionally, those contacted by telephone were more likely to have misinformation and lingering concerns about the presence of CF in their child.

Anxiety

Nutritional assessment of infants with cystic fibrosis diagnosed through screening.

Presymptomatic infants diagnosed through neonatal screening for cystic fibrosis can have biochemical evidence of malnutrition. With aggressive dietary management and treatment with pancreatic enzymes, normal biochemical indices of nutrition can be achieved at 12 months of life in most cases. Males with cystic fibrosis appear to be more at risk than females for abnormal growth and biochemical indices of nutrition in the first year of life. This may be related to the observed decrease in fat intake when compared to females. Males, especially, should be carefully observed for development of nutritional abnormalities based on this data. Careful attention should be paid to vitamin E and essential fatty acid status in all CF infants. The numbers in this study are small and the long-term consequences of early nutritional intervention await the conclusion of the randomized, controlled study on-going in Wisconsin.

Cystic Fibrosis

Design issues for a breast cancer chemoprevention trial.

A design to evaluate the efficacy of tamoxifen as a chemopreventive agent for breast cancer in healthy, high-risk women is proposed. Factors to be considered include basic incidence rates in the general population, definition of high risk, screening efforts, sample size, and compliance to protocol. Assuming a breast cancer incidence of 3/1,000/year in women 50-59 years old with a first degree relative with breast cancer, we estimate that approximately 16,000 subjects would need to be randomized into a tamoxifen-placebo controlled trial to detect a 50% reduction in incidence. This assumes a 5% (two-sided) significance level and 90% power. Such a trial would need to be multicentered and might cost $64 million over a 5-year period.

Breast Neoplasms

Long-term survival of patients treated with combination chemotherapy for metastatic breast cancer.

Long-term survival of patients with metastatic breast cancer treated on two prospective stratified randomised trials has been analysed. Patients on study B122 received either cyclophosphamide, methotrexate and 5-fluorouracil (CMF) or cyclophosphamide, doxorubicin and 5-fluorouracil (CAF). On study B141 patients received CAF or mitolactol (dibromodulcitol), doxorubicin and vincristine alternating after every three cycles with three cycles of CMF (DAV/CMF). Long-term follow-up of 172 patients showed no significant survival difference (in multivariate regression models) for treatment with either CMF vs. CAF or CAF vs. DAV/CMF. The difference in median survival times between CMF and CAF showed a trend in favour of CAF. Advances in the management of metastatic breast cancer in postmenopausal women obtained by doxorubicin regimens have had a small but measurable impact on survival, but known patient discriminants were not overridden by the treatment regimens investigated in these studies.

Antineoplastic Combined Chemotherapy Protocols

Stability of buffered lidocaine and epinephrine used for local anesthesia.

Buffered lidocaine has been recently recommended for local anesthesia, as there is less pain on injection of the buffered solution. Reduced pain on injection of lidocaine and epinephrine buffered to a neutral pH was confirmed in 20 subjects (P less than .01). Concentrations of buffered lidocaine and epinephrine were performed in order to evaluate their stability. Buffered lidocaine dropped to 66.1% of initial concentrations after 4 weeks when stored at 25 degrees C. Buffered epinephrine fell to 1.34% of its initial concentration under similar conditions. Buffered lidocaine and epinephrine maintained 94.54% and 82.04%, respectively, of their initial concentrations after 4 weeks when refrigerated at 0-4 degrees C. Both lidocaine and epinephrine maintained greater than 90% concentration 2 weeks after buffering when stored at 0-4 degrees C. This permits batch buffering of lidocaine with epinephrine and storage for periods up to 2 weeks when properly refrigerated.

Anesthesia, Local

Cytogenetic analysis of a granulocytic sarcoma in a patient without systemic leukaemia.

Granulocytic sarcoma is a rare complication of leukaemia. Occasionally it presents before the development of systemic leukaemia when diagnosis may be difficult. A case of granulocytic sarcoma occurring in a patient with no overt evidence of leukaemia, but in whom cytogenetic analysis of the bone marrow showed a clonal t(12;13) translocation, is reported. Cytogenetic analysis of tissues in this disease may indicate evidence of systemic disease before overt morphological changes.

Bone Marrow

Demonstration of direct involvement of cytokines in graft-versus-host reactions using an in vitro human skin explant model.

A human skin explant model was used to investigate the role of cytokines in graft-versus-host reactions (GVHR). Responder cells from HLA mismatched mixed lymphocyte cultures (MLC) produced GVHR (Grades I-III) in skin explant assays. Cell-free supernatants from these experiments also induced similar histopathological changes in the skin. The greatest degree of correlation between the GVHR observed with responder cells and the supernatant was shown with CD4 enriched MLC (p less than 0.001). Supernatants were assayed for tumour necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma) and CD4 enriched MLC populations produced high levels of these cytokines. These results correlated with the grade of GVHR observed in skin explant assays. The GVHR produced by the supernatant alone could be inhibited by both anti-IFN gamma and anti-TNF alpha polyclonal antibodies. The results suggest that TNF alpha and IFN gamma are directly involved in tissue damage during graft-versus-host disease in allogeneic transplant in man.

Cytokines

Remodeling of the aorta after successful balloon coarctation angioplasty.

The purpose of this study was to examine whether remodeling of the aorta takes place after successful balloon angioplasty of aortic coarctation. During the 35 month period ending in December 1987, 30 children, aged 14 days to 13 years, underwent balloon angioplasty of unoperated aortic coarctation, with a resultant reduction in mean coarctation gradient from 44 +/- 20 to 10 +/- 8 mm Hg (p less than 0.001). On the basis of results of 6 to 30 months' follow-up catheterization data in 20 children, the patients were classified into group A (13 patients with good results; gradient less than or equal to 20 mm Hg and no recoarctation on angiography) and group B (7 patients with fair or poor results; gradient greater than 20 mm Hg with or without recoarctation on angiography). Measurements of the aorta at five sites (the ascending aorta, isthmus, coarcted segment and descending aorta distal to the coarctation and at the level of the diaphragm) were made in two angiographic views, corrected for magnification and averaged. A standardized diameter of the aorta at the five locations was calculated for each case before angioplasty and at follow-up study, and variance of the diameter was then determined. The variance of standardized aortic measures (0.233 versus 0.287) was similar (p greater than 0.05) in both groups before angioplasty, whereas at follow-up study (0.057 versus 0.129) they were different (p = 0.01). There was a greater percent improvement at follow-up study (0.233 versus 0.057) in the group with good results than in the group with fair or poor results (0.287 versus 0.129).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Improvement of platelet counts in steroid-unresponsive idiopathic immune thrombocytopenic purpura after short-course therapy with recombinant alpha 2b interferon.

In 13 patients with severe steroid-refractory idiopathic immune thrombocytopenia (ITP), a short course of recombinant alpha 2b interferon (IFN), given at a dose of 3 MU for 12 doses, caused a significant increase in platelet count in 11 patients. The rise in platelet count occurred following completion of the short course of IFN in 10 patients and occurred during therapy in one patient. Three patients showed an increase to normal platelet counts within 14 days of discontinuing the drug, eight showed a partial response, with a platelet count increase from 30 to 100 x 10(9)/L, and two patients showed minimal response. One complete responder relapsed at 5 months from initial response, and a further course of alpha 2b IFN caused a second prompt response with a rise of platelet count to supranormal levels. Short-course alpha 2b IFN can be recommended as a therapy for severe ITP. Responses are seen in splenectomized and nonsplenectomized subjects, and thrombocytopenia is not exacerbated during treatment.

Autoimmune Diseases