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Biomedical subjects

R Davies

Publications and source records attributed to R Davies.

At least 19 recordsLinked to original sources
PubMed1992

Simulation model for planning renal services in a district health authority.

OBJECTIVE: To investigate the use of a computer simulation model in planning and budgeting for renal replacement services. SETTING: Regional renal unit. RESULTS: The simulation provided projections that accurately reflected the actual numbers of people maintained on different forms of renal replacement therapy in previous years. Projections up to the end of the century showed that with no change in the demand for the service the total number of people on the renal replacement programme would increase by 40%. Increasing the uptake of new patients from 40 per million to 55 per million would mean an increase of 66% in patient numbers over the same period. Similarly, at present day prices the cost of providing the service would rise by 31% with no change in demand and by twice this with the greater uptake of new patients. Increasing the number of transplant operations was shown to offer little prospect of a reduction in these costs. CONCLUSION: The simulation program could be used by individual renal units to evaluate different treatment policies and to budget for resource use. Even at current demand levels resource requirements for renal replacement therapy will continue to grow until after the end of the century.

Budgets↗
PubMed1992

A phenotypically and karyotypically stable human thyroid epithelial line conditionally immortalized by SV40 large T antigen.

Primary cultures of normal human neonatal thyroid follicular cells were transfected with a plasmid expressing a temperature-sensitive (tsA58) mutant of SV40 large T antigen. An epithelial cell line, designated B-thy-ts.1, was obtained which showed tight temperature-dependent growth. In sharp contrast to previous such lines, which were derived from adult thyroid, B-thy-ts.1 has retained a well-differentiated phenotype as reflected in its morphology and cytokeratin expression pattern. In addition to phenotypic stability the line also displays an unusually stable karyotype, lacking the usual clastogenic effects of SV40, which we speculate to result from a greater DNA repair capacity of its cell of origin. B-thy-ts.1 should be a particularly useful tool with which to study the effects of activated oncogenes on epithelial growth and differentiation.

Antigens, Polyomavirus Transforming↗
PubMed1992

Ethinyl estradiol-induced cell proliferation in rat liver. Involvement of specific populations of hepatocytes.

Hepatocyte proliferation was analyzed in vivo during the time course of continuous administration to rats of the liver tumor promoter ethinyl estradiol (EE) at 10 p.p.m. in the diet. EE-induced acute liver hyperplasia was detected in male and female Sprague-Dawley rats as an increased mitotic index of hepatocytes after 2 days of treatment. 5'-Bromodeoxyuridine (BrdU) labeling showed that proliferating hepatocytes were randomly distributed throughout the hepatic lobule. Subsequently, and still during the first few days of continuous EE treatment, hepatocyte proliferation decreased to control levels, and a transient increase in the incidence of apoptosis in the liver was detected. Although consistent with the concept of liver growth regression after mitogen-induced hyperplasia, these results differ from others reported to date in that, in our experiments, the cessation of cell proliferation and the subsequent growth regression occurred without withdrawal of EE in our experiments. After returning to control levels, hepatocellular proliferation again increased between 3 and 6 months of chronic treatment and remained activated during the following months of continuous treatment, as seen by accumulative BrdU labeling. Proliferating hepatocytes were predominantly located in zone 2 of the hepatic lobule at this time, surrounding a periportal zone of vacuolated hepatocytes, which were also induced by the treatment. Moreover, hyperplasia of basophilic hepatocytes was also seen around some portal spaces. In another set of experiments, chronic EE-induced activation was characterized by flow cytometry on hepatocytes isolated from male Fischer rats. Ploidy analysis of hepatocyte cell suspensions showed that the normal polyploid pattern of hepatocytes was altered by EE, the proportion of diploid hepatocytes rising considerably. The results also showed that these diploid cells were the most susceptible hepatocyte population to EE-induced proliferation, as shown by a combination of BrdU labeling and cell sorting methods. In contrast to Sprague-Dawley rats, no vacuolated cells were found histologically in the livers of these animals and the proliferating hepatocytes were located adjacent to the portal areas. These results taken together support the existence of cell target populations in the liver responding to the effects of tumor promoters. The finding that a subpopulation of diploid hepatocytes was the liver cell class most susceptible to proliferation during chronic EE treatment may explain, at least in part, the behavior of EE as a tumor promoter in hepatocarcinogenesis.

Animals↗
PubMed1992

A longitudinal analysis of factors related to survival in old age.

Data from a longitudinal study of the elderly in rural North Wales are used in an exploratory study of the relationships between very broadly defined social circumstances and longevity. A statistical modeling approach is adopted and has some nonroutine features necessitated by missing data on dates of death. A variety of demographic, socioeconomic, social network, quality-of-life, dependence, and health variables are found, individually, to be related to survival. Multivariate analysis demonstrated that many of these relationships are spurious and, in particular, there is no prima facie evidence that survival is affected by social networks or quality-of-life factors. However, socioeconomic factors emerge as important for the old elderly.

Aged↗
PubMed1992

Comparison of methods for the determination of unbound triiodothyronine in pregnancy.

OBJECTIVE: To study the changes in unbound T3 concentration in the first trimester of pregnancy. DESIGN: We measured serum unbound T3 concentration before and after termination of pregnancy. PATIENTS: Twenty-six clinically euthyroid women. MEASUREMENTS: We used one non-analogue assay (Sclavo) and three analogue assays (Amersham, Becton Dickinson and Diagnostic Products Corporation). RESULTS: Regression analysis did not show any significant agreement between the analogue and non-analogue assays. After termination of pregnancy, unbound T3 concentration as measured by Sclavo and Amersham assays did not change whereas unbound T3 concentration increased and decreased as measured by Becton Dickinson and Diagnostic Products assays respectively. Changes were not directly related to albumin or thyroid binding globulin. CONCLUSION: We believe unbound T3 concentrations as measured by the analogue assays used in this study are due to a balance of errors and cannot be used to determine true physiological changes in pregnancy.

Abortion, Induced↗
PubMed1992

Thyrotoxicosis and hyperemesis gravidarum associated with a serum activity which stimulates human thyroid cells in vitro.

OBJECTIVE: To investigate in-vitro thyroid stimulatory activity in the serum of patients with hyperemesis gravidarum and thyrotoxicosis. DESIGN: Serum from hyperthyroid patients was incubated with cultures of human thyroid cells. Attempts were made to neutralize stimulatory activity with antisera to hCG. PATIENTS: Five patients presenting in early pregnancy with hyperemesis and thyrotoxicosis. MEASUREMENTS: Serum concentrations of thyroid hormones (total and free), TSH and hCG. Accumulation of extracellular cAMP in response to serum. RESULTS: All five patients had biochemical hyperthyroidism with no evidence of an underlying autoimmune disease. The mean cAMP accumulation over 4 hours with sera from 12 non-pregnant controls was 130.6 (121.8-142.8), from 12 pregnant controls 132.4 (118.1-143.8), compared with values of 144.7, 159.1, 166.2, 178.9 and 320.5 for the thyrotoxic patients. The stimulatory activity could not be neutralized by addition of anti-hCG or by depleting the sera of hCG. CONCLUSIONS: Thyrotoxicosis may present with hyperemesis in early pregnancy. Clinical and biochemical features may be masked by the pregnancy or by the intercurrent illness. The hypothesis that hCG is a thyroid stimulator in patients with hyperemesis gravidarum is not supported by the immuno-neutralization data in this study.

Cells, Cultured↗
PubMed1992

Limbal nodules in Sweet's syndrome.

Sweet's syndrome is acute febrile neutrophilic dermatosis. Conjunctivitis and episceritis have been described with it before. A case of Sweet's syndrome, described here, was found to have limbal nodules with histology similar to the skin lesions. This is the first report of this association.

Biopsy↗
PubMed1992

Human chorionic gonadotropin may not be responsible for thyroid-stimulating activity in normal pregnancy serum.

Although hCG can activate thyroid cells in culture there is considerable doubt as to whether it is responsible for the changes in thyroid function which occur during normal pregnancy. Thyroid-stimulating activity (TSA), measured using iodide uptake into FRTL-5 cells, was demonstrated in 32/51 (63%) first and 15/29 (52%) third trimester sera. Free T3 was increased (P less than 0.001) and TSH decreased (P less than 0.01) in first trimester. In the early pregnancy group there was a positive correlation between hCG and TSA (r = 0.594, P less than 0.001) and a negative correlation between hCG and TSH (r = -0.329, P less than 0.02). In third trimester hCG concentration was often below that required to produce TSA in vitro and TSA could not be neutralized by antibodies to hCG. There was no correlation between hCG and TSH or thyroid hormones in the third trimester. In 26 women TSA decreased in parallel with serum hCG concentration after termination of pregnancy (P less than 0.001). Free T3 also decreased (P less than 0.01) and TSH increased (P less than 0.05) after termination. TSA persisted in many patients even after hCG was either very low or undetectable. Purified hCG stimulated iodide uptake in a concentration-dependent manner. Stimulation of iodide uptake by TSH was inhibited by the simultaneous presence of low concentrations of hCG while activity was restored with high concentrations. hCG may contribute to the thyroid changes in early pregnancy. However the poor correlation between TSA and thyroid tests suggests that other factors may be involved. The partial agonist activity of hCG may account for some of the inconsistencies observed but TSA in serum from late pregnancy or after termination of pregnancy is almost certainly due to another hormone or growth factor.

Adult↗
PubMed1992

Release of interleukin-6 by human thyroid epithelial cells immortalized by simian virus 40 DNA transfection.

Interleukin-6 (IL-6) has actions on a variety of endocrine tissues. The cytokine is secreted by cells of the anterior pituitary and endocrine pancreas and has recently been shown to be produced by cultures of thyroid epithelial cells. In this study we have examined some of the factors which regulate IL-6 release from an immortalized human thyroid line (HTori3). IL-6 release over 24 h was stimulated by TSH (5000 microU/ml), by forskolin (0.01 mmol/l), by fetal calf serum (1-20%) and by epidermal growth factor (20 ng/ml). Stimulation was also apparent with gamma-interferon and with tumour necrosis factor at concentrations known to enhance class II major histocompatibility antigen expression by thyroid epithelium. The most potent factor tested was interleukin-1 (IL-1), which controls IL-6 release from other cell types. Threefold stimulation was found with 1 U/ml rising to 350-fold with 1000 U/ml. The effect of IL-1 took 2 h to develop and was blocked by cycloheximide (100 mumol/l). Stimulation was not markedly inhibited by pertussis toxin. Many of the actions of IL-1 are mediated by prostaglandin E2 (PGE2). At concentrations as low as 30 nmol/l, PGE2 stimulated IL-6 release but the maximum stimulation obtained with PGE2 was only threefold. The effect of IL-1 was not inhibited by indomethacin. These data provide further evidence that IL-6 is produced by human thyrocytes. The effect of IL-1 has not been demonstrated previously. Stimulation of IL-6 release by IL-1 did not appear to be mediated by prostaglandin.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗
PubMed1991

Challenges to equity in health and health care: a Zimbabwean case study.

The current economic crisis in Africa has posed a serious challenge to policies of comprehensive and equitable health care. This paper examines the extent to which the Zimbabwe government has achieved the policy of "Equity in Health" it adopted at independence in 1980, that is provision of health care according to need. The paper identifies groups with the highest level of health needs in terms of both health status and economic factors which increase the risk of ill health. It describes a series of changes within the health sector in support of resource redistribution towards health needs, including a shift in the budget allocation towards preventive care, expansion of rural infrastructures, increased coverage of primary health care, introduction of free health services for those earning below Z$150 a month in 1980, increased manpower deployment in the public sector and the reorientation of medical training towards the health needs of the majority. The implementation of equity policies in health have however been challenged by several trends and features of the health care system, these becoming more pronounced in the economic stagnation period after 1983. These include the reduction in allocations to local authorities, increasing the pressure for fees, the static nominal level of the free health care limit despite inflation, the continued concentration of financial, higher cost manpower and other resources within urban, central and private sector health care and the lack of effective functioning of the referral system, with high cost central quaternary facilities being used as primary or secondary level care by nearby urban residents. While primary health care expansion has clearly been one of the success stories of Zimbabwe's health care post 1980, the paper notes plateauing coverage, with evidence of lack of coverage in more high risk, socio-economically marginal communities. Measures to address these continuing inequalities are discussed. Their implementation is seen to be dependent on increasing the capacity and organisation of the poor to more strongly influence policy and resource distribution in the health sector.

Financial Management↗
PubMed1990

Interactions of pancreatic secretory trypsin inhibitor in small intestinal juice: its hydrolysis and protection by intraluminal factors.

It has been proposed that modulation of cholecystokinin (CCK) release by proteinases, proteinase inhibitors and protein is mediated by a pancreatic secretory trypsin inhibitor (PSTI), also called monitor peptide, in the rat. When human [125I]-PSTI was incubated with fasting small bowel juice or activated pancreatic juice greater than 88% of tracer eluted from gel chromatography in the characteristic position of hydrolysed PSTI. However, when the small bowel juice had been pre-incubated with soybean trypsin inhibitor 3 g/l, casein 5 g/l or lactalbumin 30 g/l, the hydrolysis of PSTI diminished so that 95%, 32%, and 33% respectively, now eluted in the characteristic position of free (i.e. intact and not bound to an enzyme) PSTI. When [125I]-PSTI was incubated with pure trypsin, chymotrypsin, elastase or enterokinase greater than 95% of tracer eluted in the position of PSTI-enzyme complex. Incubation of PSTI with trypsin plus one other enzyme was required to produce hydrolysis. The degree of protection of PSTI from hydrolysis in duodenal juice produced by these substances correlates with their affects on CCK release. Our findings support the hypothesis that PSTIs mediate the modulation of CCK release by intraluminal proteinases, proteinase inhibitors and proteins.

Body Fluids↗
PubMed1990

The preparation of highly enriched fractions of binucleated rat hepatocytes by centrifugal elutriation and flow cytometry.

A procedure is described for the isolation of highly enriched fractions of binucleated hepatocytes from rat liver. Liver cells isolated by EGTA and collagenase perfusion were initially subjected to centrifugal elutriation and second to flow cytometry coupled with Hoechst 33342 staining. The elutriation step yielded hepatocyte fractions which contained almost entirely mononuclear diploid cells and fractions enriched in binucleate hepatocytes. The fractions with the highest proportion of binucleated hepatocytes contained between 50 and 56% of these cells. Subsequent flow cytometric cell sorting yielded fractions which contained greater than 80% binucleated cells. These cells were viable in culture as demonstrated by the immunohistochemical detection of bromodeoxyuridine incorporation.

Aneuploidy↗
PubMed1990

Sensitivity of the cell cycle to TGF beta 1 does not correlate with transformation of a rat liver epithelial cell line.

The effects of TGF beta 1 on cell cycle events in a rat liver derived epithelial cell line (BL9) and in two in vitro transformants of this line were studied by flow cytometry. Using either ethidium bromide staining or the incorporation of bromodeoxyuridine to evaluate DNA synthesis it was shown that TGF beta 1 prevented the entry of G0/G1 phase BL9 cells into S phase. TGF beta 1 did not exert its inhibitory effect(s) on DNA synthesis by the modulation of early events in the cell cycle. The tumorigenic transformed BL9 cell lines gave contrasting responses to the effects of TGF beta 1. DNA synthesis in a BL9 cell line derived by transfection with an active N-ras oncogene was unaffected by TFG beta 1 and thus appeared refractory to its growth controlling effects. On the other hand cells from a BL9 cell line derived by in vitro transformation with activated aflatoxin B1 retained their sensitivity to the effects of TGF beta 1. Thus the loss of the inhibitory effect of TGF beta 1 on DNA synthesis is not obligatory for the malignant transformation of rat liver epithelial cells.

Animals↗
PubMed1990

A new polymorphic locus, D7S411, isolated by cloning from preparative pulse-field gels is close to the mutation causing cystic fibrosis.

The mutation causing cystic fibrosis (CF) has been localized to the DNA sequence of 700 kb bounded by the loci identified by the markers pMP6d-9 (D7S399) and pJ3.11 (D7S8). A 560-kb fragment obtained after SacII digestion of DNA from a cell line containing this region of human chromosome 7 in a mouse background was separated using pulse-field gel electrophoresis and isolated from the gel. The DNA was digested with BamHI prior to cloning into lambda EMBL3. Approximately 0.1% of the resulting clones contained human repetitive sequences, and 24 such recombinants were studied. Of these, 23 are on chromosome 7; 8 clones were duplicated, and of the 15 different recombinants, 7 are between MET and INT1L1, and a further 7 are between INT1L1 and pMP6d-9, leaving a single marker, pG2, which is between pMP6d-9 and pJ3.11. pG2 recognizes an RFLP with XbaI. A cosmid walk from pG2 has generated a further marker, H80, which recognizes an RFLP with PstI. This new locus (D7S411) divides the remaining region between the CF flanking markers, thereby making it more accessible to fine pulse-field mapping and allowing the precise localization of further clones to this region. Although it is not possible to position the CF locus unequivocally with respect to D7S411, both polymorphic markers at this locus exhibit low but significant linkage disequilibrium with CF, placing the emphasis for the search for the gene on the D7S399 to D7S411 interval of 250 kb.

Blotting, Southern↗