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Biomedical subjects

C E Evans

Publications and source records attributed to C E Evans.

At least 37 records · Page 2Linked to original sources

Casting the screening net: separating big fish from little fish.

Screening tests are a rapidly growing part of medical practice. If we are going to make the best use of resources, screening tests need to be considered in terms of effectiveness, efficiency and equity. We present a framework as a way to think about screening programmes. The framework expands on existing literature that recognizes two categories of screening: universal and opportunistic. By adding the dimension of 'selectivity', we identify four categories of screening: active non-selective (universal or mass screening), active selective, opportunistic non-selective and opportunistic selective. We illustrate the framework by categorizing screening recommendations for high serum cholesterol levels. We conclude there is no one ideal strategy for screening that simultaneously satisfies criteria of effectiveness, efficiency and equity. However, our framework allows a systematic consideration and balancing of these objectives in the development and assessment of screening programs. In this way, it may assist decision-makers by making this trade-off more explicit.

Canada↗

The effect of dietary sodium on calcium metabolism in premenopausal and postmenopausal women.

OBJECTIVE: To investigate the effects of high and low sodium diets on urinary calcium, bone turnover and calcium absorption in pre and postmenopausal women. DESIGN: Experimental, prospective and longitudinal study. SETTING: Samples were taken at the hospital and the diets were followed at home. SUBJECTS: Volunteers were recruited from the hospital and were either hospital staff or post-graduate students. No volunteers failed to complete the study but one was omitted from analysis due to lack of compliance. INTERVENTIONS: Eleven healthy premenopausal women aged 22-47 y and 11 healthy postmenopausal women ages 45-70 y followed a high (300 mmol/d) and a low (50 mmol/d) sodium diet for one week each. On the 7th day of each diet, blood and urine samples were taken. RESULTS: On the high sodium diet 24 h urinary sodium and calcium values relative to creatinine were significantly higher for all subjects (P < 0.05). Postmenopausal women on the high sodium diet had biochemical evidence of increased bone resorption in relation to the low sodium diet. However in premenopausal women there was no such change. Calcium absorption did not change significantly in either group. CONCLUSIONS: It appears that postmenopausal, but not premenopausal, women respond to a high sodium diet by an increase in bone resorption which may lead to reduced bone density. SPONSORSHIP: Arthritis and Rheumatism Council Project Grant R44.

Absorption↗

A comparison of techniques to assess skin blanching following the topical application of glucocorticoids.

Glucocorticoid-induced dermal blanching provides a useful research tool to study steroid potency and sensitivity. Conventional measurement of the intensity of blanching relies on subjective assessment by a trained observer using a visual score. Several objective techniques have recently been reported to detect skin blanching, but their sensitivity has not been compared previously with subjective visual recordings. In this report we aimed to establish whether objective methods offer sufficient sensitivity to be employed in epidemiological studies of glucocorticoid responsiveness. In healthy subjects we applied beclomethasone dipropionate at three concentrations (1, 10 and 100 micrograms/ml) under an occluded dressing overnight. The following morning we measured blanching using a visual score, laser Doppler velocimetry with the MBF 3D monitor (Moor Instruments Ltd, U.K.) and a perfusion imager (Lisca, Sweden), and reflectance spectrophotometry with the Dia-Stron 'erythemameter'. Using the visual score, blanching was detected at all concentrations of steroid. Neither laser Doppler instrument detected vasoconstriction at any concentration. By contrast, the reflectance spectrophotometer successfully recorded blanching at 10 and 100 micrograms/ml, but not at 1 microgram/ml. We conclude that laser Doppler instruments, including the novel scanning perfusion imager, do not detect glucocorticoid-induced skin blanching, perhaps because it reflects venular rather than arteriolar vasoconstriction. By contrast, the Dia-Stron reflectance spectrophotometer has sufficient sensitivity to be used as an alternative to visual assessment in epidemiological studies of human glucocorticoid-induced dermal blanching.

Administration, Topical↗

Modulation of cell phenotype in human osteoblast-like cells by the simian virus 40.

At present, the majority of in vitro research into bone metabolism is performed on either primary cultures of bone or osteosarcoma lines. A better model of the behaviour of normal bone cells would be a cell line derived from normal, adult bone that retained osteoblast-like characteristics. We infected a culture of bone cells from adult humans with simian virus 1613, a variant of the simian virus 40, and obtained 12 clones of variable morphology. The clones were maintained in culture for as long as 6 months. Population doubling times, synthesis of alkaline phosphatase and osteocalcin, secretion of mineral, morphology, and ability to withstand freezing were examined. SV/EC cell morphology varied from the polygonal, osteoblast-like to the bipolar, fibroblast-like. Population doubling times ranged from 0.55 to 2.8 days (compared with 3.9 days for the nontransformed human osteoblast-like cells). Synthesis of alkaline phosphatase varied but was less than that by the human osteoblast-like cells. With the exception of clone 11, all of the transformed clones synthesised mineral in vitro under mineralising conditions. Four clones showed increased synthesis of alkaline phosphatase and increased population doubling times after passaging. All of the clones were successfully frozen and thawed, but, unlike normal human osteoblast-like cells, none responded to stimulation with parathyroid hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

The osteogenic potential of rib autografts can be preserved in culture.

STUDY DESIGN: This was an experimental study to compare various methods of storing rib autograft between stages of spinal surgery. OBJECTIVE: The authors' goal was to determine the optimum conditions for storing bone graft, while preserving its osteogenic potential. SUMMARY OF BACKGROUND DATA: It never has been demonstrated that osteoblastic function can be preserved after bone graft is stored. Other researchers have shown preservation of cellular function, but not its nature. METHODS: Excised rib was stored in one of several ways: in culture medium at -196 C, 4 C, or 37 C, or in saline at 4 C for 2 weeks and then cultured at 37 C. Any cells produced were characterized using standard techniques. RESULTS: Bone stored at 37 C and -196 C retained its osteogenic potential. Bone stored at 4 C in saline did not. Bone stored at 4 C in culture medium was intermediate in its preservation of osteogenic capacity. CONCLUSIONS: Bone stored under suitable conditions retains osteogenic potential, and when reimplanted will add osteogenic cells to the fusion mass.

Adolescent↗

Effects of two novel bisphosphonates on bone cells in vitro.

Bisphosphonates are now widely used in the treatment of bone diseases, particularly where there is uncontrolled bone resorption, as they are known to be potent inhibitors of osteoclasis. It is still unclear whether the bisphosphonates act by inhibiting osteoclast maturation or by blocking the mechanism of bone resorption, and little is known of their effects on osteoblasts. Recent studies with 3-amino-1, hydroxypropylidene-1,1-bisphosphonic acid (APD) in the treatment of osteolytic metastases in breast cancer have suggested that APD may affect osteoblasts directly. We have now investigated the effects of two novel bisphosphonates, CGP 47072 and CGP 42446A on osteoclastogenesis in fetal rat calvariae cultured on collagen gels and on human osteoblasts (hOB) cultured as explants from bone taken from patients at surgery. We also compared the action of these new bisphosphonates with that of APD, which at concentrations of 2.5 x 10(-6) M to 2.5 x 10(-10) M inhibited osteoclast recruitment, even when this was stimulated by conditioned medium from MCF7 breast cancer cells. This bisphosphonate was particularly potent if cultured with calvaria taken at 19 days gestation, when more immature osteoclast precursors are present. If calvariae from 20 days gestation were used, which contain more mature cells, it produced less inhibition. In contrast, CGP 42446A (2.5 x 10(-6) M to 2.5 x 10(-8) M) was more effective in inhibiting osteoclast maturation in calvariae from 20 days gestation than in those from 19 days. CGP 47072 had a similar pattern of effects but was less potent than either of the other two compounds. APD or CGP 42446A at 10(-5) M significantly inhibited hOB numbers and DNA synthesis, but lower concentrations had little effect. CGP 47072 did not inhibit human osteoblast replication. It is unlikely that these effects are due to calcium chelation, as none of these compounds mimicked results obtained with EDTA, which was effective only at 2.5 x 10(-6) M in reducing osteoclast size and 10(-4) M in human osteoblast cultures. These results demonstrate that all three bisphosphonates are able to inhibit osteoclast formation at low concentrations. APD may be able to influence less mature osteoclast precursors and CGP 42446A and CGP 47072 may exert their effects on the fusion of more mature precursor cells on the bone surface. At these concentrations, however, there is little or no effect on osteoblasts.

Animals↗

Report of the Canadian Hypertension Society Consensus Conference: 2. Diagnosis of hypertension in adults.

OBJECTIVE: To update recommendations for the diagnosis of mild hypertension in adults and to assess the role of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring. DATA SOURCES: Literature reviews of previous consensus conferences were updated with searches of MEDLINE for the period Jan. 1, 1988, to Nov. 15, 1991, and supplemented by reference lists and personal files. STUDY SELECTION: Panel members selected relevant articles and rated them according to methodologic criteria. DATA EXTRACTION: The data extracted concerned the measurement of blood pressure, the diagnosis of hypertension, the treatment of mild hypertension, and the reliability and validity of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring in the diagnosis of mild hypertension. The recommendations made were graded according to the level of evidence available, circulated to many experts and approved at a consensus conference. MAIN RESULTS: Previous recommendations for the accurate measurement of blood pressure remain mostly unchanged. Antihypertensive treatment should be prescribed for patients (including the elderly) with an average diastolic blood pressure of at least 100 mm Hg, for those with isolated systolic hypertension (systolic blood pressure of at least 160 mm Hg and diastolic blood pressure of less than 90 mm Hg) and for patients with a diastolic blood pressure of 90 to 99 mm Hg and target-organ damage. Clinical judgement is required in treating patients with a diastolic blood pressure of 90 to 99 mm Hg without target-organ damage, and individual risk for cardiovascular disease must be taken into account. There is insufficient evidence to warrant the routine use of echocardiography, self-measurement of blood pressure or ambulatory blood pressure monitoring in diagnosis. CONCLUSIONS: Recent high-quality evidence supports several new recommendations for the diagnosis of mild hypertension in adults. Additional research is needed to determine the role of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring.

Adult↗

Myeloma affects both the growth and function of human osteoblast-like cells.

Myeloma behaves differently to other osteolytic tumours which metastasize to bone, in that the latter usually provoke reactive bone formation in the host bone. A previous study showed that a myeloma cell line (GM1500) secreted an osteoblast-inhibiting factor(s). The present study was undertaken to determine whether other myeloma cells also secreted a factor(s) which inhibited both cell proliferation and DNA synthesis of osteoblast-like cells and whether the myeloma also affected the function of osteoblasts. The results showed that a second cell line (Karpas 707) as well as myeloma tissue taken from two patients had a similar effect. The myeloma cells did not affect total collagen or protein synthesis, and did not affect the overall degree of mineralization. A biphasic effect was seen on alkaline phosphatase activity. Thus, although the proliferation of the pre-osteoblast was affected, the synthetic functions of the osteoblasts were not.

Alkaline Phosphatase↗

The effects of heating and devitrification on the structure and biological activity of aluminosilicate refractory ceramic fibres.

Three grades of ceramic fibre have been examined for their composition, structures and biological effect in several in vitro assay systems. The fibres were examined in the 'as-manufactured' state and after heating at 1200 and 1400 degrees C. Devitrification of the fibres at 1200 degrees C probably gave mullite crystals on the surface and caused the formation of the high-temperature form of cristobalite and, in zirconia grade fibres, the high-temperature, tetragonal form of zirconia as well. Further heating changed surface structure and led to zircon production in the zirconia fibres. Heating reduced the affinity of the fibres for the surface of V79-4 cells and lowered fibre toxicity toward these cells and towards macrophage-like cells. These changes in toxicity were not due to a reduction in the fibrous nature of the materials although they did become more brittle and powders prepared from them contained more isometric particles than those from as-manufactured materials. This suggests that the devitrification occurring during the use of these materials in high-temperature environments will not necessarily enhance their adverse biological activities despite the production of one phase of crystalline silica.

Aluminum Silicates↗

Factors affecting the interaction of asbestos fibres with mammalian cells: a study using cells in suspension.

One of the earliest events in pathogenesis by mineral fibres must be an interaction between fibre and cell surfaces. Using a simple technique in which cells in suspension were incubated with fibres and adhesion monitored by separation on a density gradient it has been shown that such interactions occur through two distinct mechanisms. The first, a charge-mediated effect, occurs with positively charged fibres such as chrysotile asbestos. The second, with amphibole or glassy fibres, is mediated by fibronectin which first binds to the fibre. The bound protein then attaches to RGD receptors on the cell surface; calcium and magnesium ions are necessary for optimal adhesion. The RGD receptors bind to a tripeptide region on the protein and small peptides containing the RGD sequence block fibre-cell interaction. If the surface silanol groups on the fibre were chemically coupled to trialkylsilyl groups then interaction was slowed.

Amino Acid Sequence↗

Breast carcinomas synthesize factors which influence osteoblast-like cells independently of osteoclasts in vitro.

Bone metastases in breast cancer may be osteolytic, osteosclerotic, or a mixture of the two. Although stimulation of bone resorption by breast cancer cells has attracted some interest, the formation of osteosclerotic secondary tumours and the influence of human mammary carcinoma cells on osteoblasts (bone forming cells), both important in understanding breast cancer--bone interactions, have been largely neglected. We therefore examined the effects of conditioned medium (CM) from two cultured human breast cancer cell lines (MCF7 and ZR-75) and from primary cultures of breast carcinomas from two patients, on osteoblasts and recruitment of bone-resorbing cells (osteoclasts) in vitro. Osteoblast-like cells (BDC) were cultured from human trabecular bone explants. Osteoclast maturation was studied in fetal rat calvaria cultured on collagen gels. CM from the MCF-7 line and cells derived from one patient each inhibited BDC DNA synthesis, but stimulated osteoclast recruitment. In contrast, CM from the second patient's cells or ZR-75 enhanced DNA synthesis in BDC, but blocked osteoclast maturation. This suggests that human breast carcinomas secrete soluble factors which influence both osteoclasts and osteoblasts. A further unexpected implication is that mammary carcinoma cells may cause local osteosclerosis by directly stimulating osteoblasts, rather than through raised bone turnover in metastases.

Animals↗

Effect of donor age on the growth in vitro of cells obtained from human trabecular bone.

The proliferation of human bone-derived cells (BDCs) was assessed in vitro, using [3H]thymidine incorporation and cell counting in a haemacytometer. The cells were cultured from human trabecular bone from 87 patients aged 2-88 years. The in vitro growth of these cells was unaffected by the chronological age of the donor. However, the cell number at confluence was shown to decrease with increasing donor age, this trend being most marked after 60 years of age. Other assays of the metabolic efficiency of the BDCs, namely, total protein, osteocalcin, and alkaline phosphatase synthesis, did not show any change with increasing donor age. These results suggest that while the ability of individual cells to divide and to perform specific synthetic activities is unimpaired with increasing age, other subtler changes may occur, leading to a decrease in the bone's osteogenic capacity.

Adolescent↗

Interaction of amosite and surface-modified amosite with a V79-4 (Chinese hamster lung) cell line.

We have been examining a number of chemically modified mineral fibers, derived from amosite asbestos, by in vitro methods to clarify the role of the fiber surface in determining biological activity. The various fibers have identical size distributions but differ in their affinities for components of the cell membrane. They were treated with boiling toluene or chemically modified by treatment with alkyldimethylchlorosilanes (R = C8, C18) that react with free-surface hydroxyl groups to form the corresponding siloxanes. Fibers in MEM supplemented with 15% fetal calf serum were added to a suspension of V79-4 cells labeled with tritiated thymidine and the mixture was incubated. Aliquots of this mixture were spun down on a density gradient to determine the degree of cell-fiber interaction. At 37 degrees C native amosite (UICC standard) stuck to cells within 15 min of incubation, and the amount of sticking was maximum within 70 min. Decreasing the temperature decreased the amount of sticking, and at 20 degrees C no sticking was observable. The chemically modified amosite and the amosite treated with boiling toluene did not stick to the cells even after 70 min. Soaking the toluene-treated amosite with aqueous solutions at room temperature for 48 hr produced a material that had the same sticking properties as the original untreated fiber. These results indicate that the silanol content, and possibly the degree of hydration of the fiber surface, is important for a fiber to stick to a cell surface.

Animals↗

Does myeloma secrete an osteoblast inhibiting factor?

Unlike most other tumours, myeloma causes bone destruction without an osteoblastic reaction; we tried to assess whether myeloma secretes a humoral factor that inhibits osteoblasts. Human bone-derived cells were either co-cultured with myeloma cells, or cultured in medium conditioned by myeloma cells. Bone-derived cell growth was measured by cell counts and by uptake of tritiated thymidine (3H-Tdr); growth was inhibited when cultured in medium conditioned by myeloma cells and some inhibition was seen when the bone-derived cells were co-cultured with myeloma cells. The inhibiting effect was dose-dependent and also dependent upon the density of the myeloma cells conditioning the medium. The results of our study suggest that myeloma secretes an osteoblast inhibiting factor of less than 50,000 Dalton molecular weight.

Cell Count↗

Home blood pressure-measuring devices: a comparative study of accuracy.

Self monitoring of blood pressure by hypertensive patients has been shown to be of value and is increasingly popular. However, the accuracy and ease of use of at least some of the equipment for home use is questionable. We tested 23 pairs of home blood pressure devices, using static methods, trained observers with volunteer subjects and hypertensive patients. Eleven (48%) of the 23 pairs of devices tested were found inconsistent with their duplicate and failed the standards for automated devices of the Association for the Advancement of Medical Instrumentation. Several of the devices, all sold for home use by lay people, contained no instructions whatsoever and even patients using those machines with instructions required further training in blood pressure measurement. While home blood pressure monitoring is useful in certain circumstances, care must be taken in the choice of device, and training is required for all devices.

Blood Pressure Determination↗