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Biomedical subjects

G Charnley

Publications and source records attributed to G Charnley.

At least 19 recordsLinked to original sources
PubMed2005

Human exposure to dioxins from food, 1999-2002.

In response to aggressive attempts to control dioxin emissions over the last 35 years, human exposures to dioxins from the environment have declined significantly. The primary source of human exposure to dioxins at present is food. The sources of dioxins in food are not well understood and are probably varied. Data on the levels of dioxins measured in various foods for samples collected from 2000 to 2002 have recently been released by the US Food and Drug Administration as part of its Total Diet Study. Data on samples collected in 1999, and released in 2002, are also available. Based on those data and on the US Department of Agriculture's most recent food consumption survey (1994-1996 & 1998 Continuing Survey of Food Intakes by Individuals), estimates of dioxin intake for the total US population and for three age groups of children were obtained. Results show that the most recent mean dietary exposures for all groups are below 2 pg TEQ/kg BW/day, the tolerable daily intake established for dioxins by the World Health Organization. Between 1999 and 2002 mean dioxin intakes from food appear to have decreased, but when estimates are adjusted based on a standardized limit of detection and evaluating only those {congenerxfood} combinations common to all 4 years, no trend is apparent. When dioxin concentrations below the limit of detection are represented by one-half the limit, approximately 5% of the intake estimates for 2-year-olds and 1% of the intake estimates for 6-year-olds exceed the tolerable daily intake by about 10%, although such upper-percentile estimates should not be equated with excess risk. When non-detectable dioxin values are set to zero (i.e., when only dioxin values actually measured are used), only 1% of intake estimates exceed the tolerable daily intake for 2-year-olds. As expected, about 50% of daily dietary dioxin intake by the total US population is attributable to meat and dairy products, based on the same food group classifications used by the National Academy of Sciences' Committee on the Implications of Dioxin in the Food Supply. This information may be useful for targeting future risk management activities.

Adolescent↗
PubMed2001

Partial resurfacing arthroplasty of the femoral head in avascular necrosis. Methods, indications, and results.

The current study reports results using a partial surface replacement for osteonecrosis of the femoral head. The surgical technique, implant design, and instrumentation cause minor soft tissue disruption and require little bony resection. Thirty-seven prostheses were placed in 33 patients during the past 7 years. The mean age of the patients was 43 years (range, 24-59 years), and the preoperative Ficat classification was Stage III in 26 hips, Stage IV in 10, and Stage II in one hip. For the surviving prostheses, the mean followup was 49 months (range, 24-89 months). Of the 28 surviving implants, 24 continue to function well and the patients have excellent or good hip scores according to the Merle d'Aubigne system. There were nine failures, mainly attributable to the extension of the osteonecrosis. In comparison with alternative techniques, the operative surgery for partial surface replacement is straightforward, requiring little preoperative planning and immediate weightbearing postoperatively. Should failure occur, little bone stock loss is incurred and revision to a total hip replacement is as simple as primary hip arthroplasty.

Adult↗
PubMed2001

Children's health, susceptibility, and regulatory approaches to reducing risks from chemical carcinogens.

Risk-based regulation of chemical exposures from the environment generally relies on assumptions about the extent of people's susceptibility to chemically induced diseases. Those assumptions are intended to be health-protective; that is, they err on the side of overstating susceptibility. Recent concern about children's special susceptibilities has led to proposals that would make risk-based regulations one-tenth more stringent, unless data are available to refute the assumption that children are more susceptible than adults. In this paper we highlight some of the questions that should be addressed in the context of risk assessment to determine whether such increased stringency would accomplish the desired result of improving children's health. In particular, characterizing benefits of greater stringency requires more information about dose-response relationships than is currently available. Lowering regulatory levels has attendant costs but may not achieve benefits, for example, if the previous level were already below an actual or practical threshold. Without an ability to understand the potential benefit (or lack thereof) of the additional stringency, an appropriate consideration of benefits and costs is not possible.

Adult↗
PubMed1999

Preliminary results of partial surface replacement of the femoral head in osteonecrosis.

We report our initial results using a partial surface replacement for osteonecrosis of the femoral head. We believe the prosthesis has the most minimalist design that has been reported either in Europe or North America. The surgical technique, implant design, and instrumentation cause minor soft tissue disruption and require little bony resection. We report the results of our first 25 prostheses performed over the past 5 years in 19 patients. The mean age was 42.5 years, (range, 24-59 years), with a preoperative Ficat classification of 15 hips, stage III; 9 hips, stage IV; and I hip, stage II. For the surviving prostheses, mean follow-up was 43 months, (range, 20-60 months). Of these 19 surviving implants, 15 continue to function well with excellent or good hip scores according to the Merle d'Aubigne system. We have had 6 failures: 1 owing to technical error, 4 owing to local tissue factors, and 1 owing to a progression of the osteonecrosis. The parameters for the use of this prosthesis are defined with our increasing experience, and the prosthesis is compared with other prosthetic implants available. In comparison with alternative techniques, the operative surgery is straightforward requiring little preoperative planning; immediate weight bearing is allowed postoperatively. Should failure occur, little bone stock loss is incurred, and revision to a total hip replacement is as simple as primary hip arthroplasty.

Adult↗
PubMed1998

A public health context for residual risk assessment and risk management under the clean air act.

The 1990 amendments to the Clean Air Act required the EPA to institute new pollution control technology requirements for industrial sources of air pollution. In part because agreement could not be reached on the best way for the EPA to determine whether any significant risks to human health will remain after the technology controls are in place, the amendments also created a Commission on Risk Assessment and Risk Management and gave the commission a broad mandate to review and make recommendations concerning risk assessment and risk management in federal regulatory programs. In its March 1997 final report to Congress and the administration, the commission recommended a tiered approach to assessing such residual risks. That approach included the idea that when decisions about managing residual risks are made, emissions should be evaluated in the context of other sources of air pollution. Evaluating risks in their larger contexts is consistent with what the commission called a public health approach to environmental risk management. This paper describes the public health approach and how it applies to evaluating residual risks under the Clean Air Act.

Air Pollution↗
PubMed1996

Excision of heterotopic ossification around the knee following brain injury.

We present the results of five patients who underwent resection of heterotopic ossification around the knee following traumatic brain injury. All the patients had improved function and no pain at a minimum of 1 year follow up, irrespective of their preoperative neurological status. Our philosophy for such surgery is outlined and, although the surgical goals may seem small, the outcome for any individual patient may be considerable.

Adult↗
PubMed1996

Articulated radial head replacement and elbow release for post head-injury heterotopic ossification.

This is a case report of the release of an elbow ankylosed by post-head-injury heterotopic ossification. An extensive bony resection and soft-tissue release was required. At surgery a pathological, osteoporotic fracture of the radial head was found that could not be preserved and thus was removed. In its place an articulated "floating radial head prosthesis" was used that allowed immediate rehabilitation and avoided the need for temporary joint distraction or stabilization. The initial excellent function achieved has been maintained, at a > 3-year follow-up and without the complications experienced with silicone radial head prostheses.

Adult↗
PubMed1996

A floating prosthesis for radial-head fractures.

We report our experience over seven years with a floating radial-head prosthesis for acute fractures of the radial head and the complications which may result from such injury. The prosthesis has an integrated articulation which allows change of position during movement of the elbow. We present the results in 12 patients with a minimum follow-up of two years. Five prostheses had been implanted shortly after injury with an average follow-up of 49 months and seven for the treatment of sequelae with an average follow-up of 43 months. All prostheses have performed well with an improved functional score (modified from Broberg and Morrey 1986). We have not experienced any of the complications previously reported with silicone radial-head replacement. Our initial results suggest that the prosthesis may be suitable for the early or delayed treatment of Mason type-III fractures and more complex injuries involving the radial head.

Adolescent↗
PubMed1987

Gastric carcinogenesis: a model for the identification of risk factors.

In a series of extensive studies on gastric carcinogenesis, we have used Sprague-Dawley rats to examine the morphologic, histochemical, and biochemical effects of risk and protective factors on N-methyl-N'-nitro-N-nitroso guanidine (MNNG)-induced tumors in an attempt to link early observations with the end-point lesion, gastric cancer. We have observed that the putative risk factors sodium chloride (NaCl); a mixture of bile acids; aspirin; alcohol; and nitrite enhance MNNG-induced neoplasia of the gastric mucosa. On the other hand butylated hydroxyanisol (BHA), Se and difluromethylornithine (DFMO) were protective and inhibited the induction of gastric mucosal neoplasia. In most cases, early changes detected by a number of criteria correlated with the end-point, gastric neoplasia. This model appears to be useful in screening and evaluating chemicals for risk for or protection against gastric cancer.

Animals↗
PubMed1987

Biologically motivated cancer risk models.

A two-stage dose response model is proposed for use in cancer risk assessment. The model assumes that transformation probabilities and cellular dynamics are exposure- and time-dependent.

Animals↗
PubMed1985

Carcinogenicity in rats of the nitrosated bile acid conjugates N-nitrosoglycocholic acid and N-nitrosotaurocholic acid.

Two nitrosated bile acid conjugates, N-nitrosoglycocholic acid and N-nitrosotaurocholic acid, were examined for carcinogenicity in a 2-year study with male Fischer rats using a 6-week p.o. dosing protocol with a total of 300 mg compound/rat. Both compounds were approximately equally carcinogenic and induced significant levels of hepatocellular carcinoma in 54 to 70% of the animals at risk. Gastric tumors of the glandular and aglandular stomach were observed in 12 to 13% of the treated rats. Although the incidence was not significant, these levels were much higher than those in historic controls. Malignant liver and gastric tumors were not detected in vehicle control rats. Alkaline phosphatase-positive foci, putative early mucosal alterations which may precede neoplasia, were found in approximately 35% of the glandular stomachs of compound-treated rats but not in those of control rats.

Alkaline Phosphatase↗
PubMed1985

Flow cytometric analysis of the effect of sodium chloride on gastric cancer risk in the rat.

Dietary sodium chloride has been identified, both experimentally and epidemiologically, as a risk factor for gastric cancer. In order to elucidate the manner in which salt increases gastric tumor incidence in N-methyl-N'-nitro-N-nitrosoguanidine-treated animals, flow cytometric cell cycle analyses were performed on rats which had been treated with 1 ml of a solution of saturated NaCl by gavage and sacrificed 0, 1, 6, 12, 24, or 48 h after treatment. The gastric antra were excised, disaggregated, and stained with propidium iodide for cell cycle analysis. Results showed that there is a reduction in cell yield at early time points due to the toxicity of NaCl, followed by a net increase in the number of cells in the S phase of the cell cycle at 24 h. Treatment of rats with NaCl 24 h prior to a dose of 10 micrograms of 3H-labeled N-methyl-N'-nitro-N-nitrosoguanidine did not lead to an increase in alkylation of DNA isolated from mucosal cells. Therefore, the hypothesis that salt enhances gastric cancer risk from N-methyl-N'-nitro-N-nitrosoguanidine by disruption of the "mucosal barrier" leading to an increased effective dose to target cells is not supported by the results of these experiments. Several studies have shown that cells in S phase are the most susceptible to mutagenesis and that increasing the number of cycling cells in a target organ will increase tumor incidence (e.g., partial hepatectomy). Thus it is possible that NaCl increases gastric cancer risk through the mitogenesis which results from the damage caused to the mucosa by this agent.

Animals↗
PubMed1981

Urinary excretion of dimethylnitrosamine: a quantitative relationship between dose and urinary excretion.

The urinary excretion of dimethylnitrosamine (DMN) was studied in male Sprague-Dawley rats. Animals were given DMN (3, 5, 10, 20, 30 and 50 mg/kg body weight, i.p.) or [3H]DMN (0.1, 1 and 3 mg; 8.7, 1.5 and 0.28 mCi/kg body weight, respectively, i.p.) diluted with sterile 0.9% NaCl. Urine was collected for 24 h after dosing. DMN was quantitated by gas chromatography using a Thermal Energy Analyzer as detector and [3H]DMN by liquid scintillation counting after purification by high pressure liquid chromatography. Multiple regression analysis programs were used to evaluate the fit of the data to a variety of models relating excretion to dose. All models which gave an acceptable fit including a term for dose squared. The models are discussed in terms of the relationship between urinary excretion and blood clearance of DMN.

Animals↗