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Biomedical subjects

G A Murrell

Publications and source records attributed to G A Murrell.

At least 19 recordsLinked to original sources

The Achilles Functional Index.

The literature regarding the management of spontaneous rupture of the Achilles tendon is controversial and confusing. The relative infrequency of the condition in any one center prohibits the completion of well-designed clinical studies. Many of the disputes could be addressed and innovations tested if an appropriate animal model were available. We present a method for evaluating Achilles tendon function from measurements of the prints, preserved in bromphenol-blue-impregnated photocopying paper, of the hindfeet of walking rats. The stimulus for this study was derived from de Medinaceli's method for assessing the functional condition of rat sciatic nerves (de Medinaceli L, Freed WJ, Wyatt RJ: An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp Neurol 77:634-643, 1982). Four variables were measured from these walking tracks, and comparisons between the damaged (experimental) and intact (normal) side were converted to proportional deficits. The relative contribution of each parameter to the overall deficit was determined by multiple linear regression analysis, and the variables were weighted accordingly to obtain an "Achilles Functional Index" (AFI). A sham operation produced no functional deficit, whereas animals subjected to a 0.5-cm midsubstance Achilles tendon defect demonstrated a markedly impaired AFI. Animals with repaired transected Achilles tendons also demonstrated a significant, but less severely impaired AFI. The functional deficit in this repair group returned to control values by postoperative day 15, whereas animals with a defect remained impaired at day 15. Furthermore, an excellent correlation was found between the functional recovery and biomechanical properties (ultimate failure load) of the healing tendon (r = 0.94; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Achilles Tendon

The functional recovery of peripheral nerves following defined acute crush injuries.

This study evaluates the effect of crushing load on functional recovery of the sciatic nerve. Male Sprague-Dawley rats were divided into five groups: sham operation, resected sciatic nerve, and 100 g (13 mm Hg/mm2), 500 g (50 mm Hg/mm2), and 15,000 g (1,000 mm Hg/mm2) of sciatic crush load (groups 1-5). In groups 3-5, a 5-mm segment of sciatic nerve was crushed for 10 min using a specially designed crushing device. Motor functional recovery was assessed from hind-limb walking tracks by calculating a sciatic functional index. There was no detectable functional deficit in the group receiving sham operations, while the resected sciatic nerve group exhibited complete dysfunction for the full duration of the experiment. All groups subjected to crush exhibited an initial deficit that gradually recovered to normal by day 14 (100-g crush), day 39 (500-g crush), and day 53 (15,000-g crush). Histological changes were also related to the initial crushing load and the length of the recovery period. Results indicate that the crushing device described is able to administer an adjustable, defined crush injury to the rat sciatic nerve, and that the functional deficit resulting from such an injury can be easily monitored with a sciatic functional index. The rate of recovery of crushed nerves was directly related to the initial load. All crushed nerves recovered in this experiment, even after the application of a 15,000-g load for 10 min.

Animals

The informed consent treatment report.

A brief history of informed consent and introduction of the "Informed Consent Treatment Report" (ICTR) is presented. The ICTR is a document developed in 1984 that combines the requirements of informed consent and the elements of good treatment planning and presentation to achieved improved patient and practice management. An outline of the parts and sections of the ICTR is included as a guide for preparing an informed consent and treatment planning document.

Dental Records

Scientific comment. Basic science of Dupuytren's disease.

At a cellular level, the major phenomenon in Dupuytren's contracture is an increase in proliferating fibroblasts, rather than an alteration in the type of fibroblasts. The collagen and glycosaminoglycan changes observed in the tissues of Dupuytren's contracture are likely to be secondary to changes in fibroblast density. Oxygen free radicals released from narrowed microvessels and from the fibroblasts themselves may play a role in stimulating fibroblast proliferation. Messina's experiments with continuous distraction and the success of limited fasciotomy indicate a role for physical forces in the pathogenesis of Dupuytren's contracture. The mechanism whereby physical events stimulate biochemical changes are undetermined, but preliminary investigations suggest that electrical fields and ion channels may be important. The future of Dupuytren's contracture rests with the delineation of these chemical and physical processes and their application and rigorous testing in the clinical setting.

Cell Division

An insight into Dupuytren's contracture.

Dupuytren's contracture is a deforming, fibrotic condition of the palmar fascia which has confounded clinicians and scientists since the early descriptions by Guillaume Dupuytren in 1831. It predominantly affects elderly, male caucasians, has a hereditary predisposition and has strong associations with diabetes, alcohol consumption, cigarette smoking and HIV infection. The major morphological features are an increase in fibroblasts, particularly around narrowed fibroblasts; a finding consistent with localised ischaemia. During ischaemia, adenosine triphosphate (ATP) is converted to hypoxanthine and xanthine, and endothelial xanthine dehydrogenase to xanthine oxidase (alcohol also mediates this change, a finding of particular relevance given the association of Dupuytren's contracture with alcohol intake). Xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and uric acid with the release of superoxide free radicals (O2-), hydrogen peroxide (H2O2) and hydroxyl radicals (OH.). These free radicals are highly reactive, with half-lives in the order of milliseconds and are toxic in high concentrations. A potential for free radical generation in Dupuytren's contracture was elicited by finding a sixfold increase in hypoxanthine concentrations in Dupuytren's contracture compared with control palmar fascia. In vitro studies affirmed the toxic effects of oxygen free radicals to Dupuytren's contracture fibroblasts, but also showed that, at lower concentrations (concentrations similar to those likely to occur in Dupuytren's contracture), free radicals had a stimulatory effect on fibroblast proliferation. Cultured fibroblasts were found to release their own O2-. These endogenously released free radicals were also found to be important in fibroblast proliferation. The collagen changes of Dupuytren's contracture were examined. The results established that fibroblast origin was unimportant, but that inhibition of type I collagen production at high fibroblast density accounted for the increase in type III/I collagen ratios observed by previous investigators. These biochemical and morphological observations throw new light on Dupuytren's contracture. They suggest that age, genetic and environmental factors may contribute to micro vessel narrowing with consequent localised ischaemia and free radical generation. Endothelial xanthine oxidase derived free radicals may both damage the surrounding stroma and stimulate fibroblasts to proliferate. Proliferating fibroblasts lay down and contract collagen in lines of stress.Progressive fibroblast proliferation and deposition of collagen is likely to encourage further microvessel narrowing with a positive feedback effect consistent with the progressive nature of the condition.

Capillaries

The collagen changes of Dupuytren's contracture.

In Dupuytren's contracture there is an increase in the ratio of type III to type I collagen. The objective of this study was to determine if fibroblasts from patients with Dupuytren's contracture have an intrinsic aberration in collagen production or whether local factors govern the collagen changes in Dupuytren's contracture. Using a new collagen micro-method, we found that fibroblasts cultured from palmar fascia affected by Dupuytren's contracture produced similar collagen to fibroblasts derived from the palmar fascia of age- and sex-matched patients with carpal tunnel syndrome. Furthermore, the collagen changes of Dupuytren's contracture could be reproduced in all cell lines by increasing fibroblast density. At high fibroblast density, type I collagen production was inhibited: a finding that could account for the increased types III/I collagen ratio in Dupuytren's contracture. These results suggest that a genetic defect in collagen production is unlikely and that the important phenomenon is an increase in fibroblast density.

Collagen

The role of the fibroblast in Dupuytren's contracture.

Ultrastructural, immunohistochemical, and biochemical studies to date show that the fibroblast in Dupuytren's contracture is identical to palmar fascia fibroblasts in patients unaffected by Dupuytren's contracture, and to all other fibroblasts. The major difference relating to fibroblasts is that in Dupuytren's contracture there are more of them, and they are clustered around narrowed microvessels. It is probable that these two phenomena are linked because recent studies indicate a greater potential for ischemia-induced oxygen free radical generation in Dupuytren's contracture, and because oxygen free radicals in these concentrations can stimulate fibroblast proliferation. The major source of oxygen free radicals is likely to be from microvascular endothelial xanthine oxidase-catalyzed reactions. These observations also account for many of the epidemiologic associations of Dupuytren's contracture, because (1) age, race, and diabetes are associated with microvessel narrowing and (2) age, diabetes, alcohol consumption, HIV infection, cigarette smoking, and trauma are associated with increased free radical generation. Nonsteroidal anti-inflammatory drugs and allopurinol are two agents that decrease oxygen free radical release and may inhibit or prevent Dupuytren's contracture.

Collagen

Modulation of fibroblast proliferation by oxygen free radicals.

The major unexplained phenomenon in fibrotic conditions is an increase in replicating fibroblasts. In this report we present evidence that oxygen free radicals can both stimulate and inhibit proliferation of cultured human fibroblasts, and that fibroblasts themselves release superoxide (O2.-) free radicals. Fibroblasts released O2.- in concentrations which stimulated proliferation, a finding confirmed by a dose-dependent inhibition of proliferation by free radical scavengers. Oxygen free radicals released by a host of agents may thus provide a very fast, specific and sensitive trigger for fibroblast proliferation. Prolonged stimulation may result in fibrosis, and agents which inhibit free radical release may have a role in the prevention of fibrosis.

Cell Division

Cell-controlling factors in Dupuytren's contracture.

The search for the causative factors in Dupuytren's disease has historically progressed form gross anatomical dissection, through microscopical tissue studies, to the biochemistry of the collagen produced. But these elements are merely the end products of cellular activity - not revealing the factors responsible for the changes in cellular activity. Recent biochemical investigations suggest that a number of conditions including localized microvascular ischemia and high alcohol concentrations transform the "benign" xanthine dehydrogenase of endothelial cells to the oxygen-free radical-releasing xanthine oxidase. Oxygen-free radicals are highly reactive species with half-lives in the order of milliseconds capable of both damaging the surrounding peri-microvasculature and stimulating fibroblast proliferation. It is this stimulation of fibroblast proliferation in the palmar fascia that is the key event in the pathogenesis of Dupuytren's contracture.

Dupuytren Contracture

Aetiology of Dupuytren's contracture.

Dupuytren's contracture is a fascinating, deforming, fibrotic condition of the palmar fascia which has confounded clinicians and scientists for centuries. The aim of this paper is to place in perspective the longstanding associations of age, sex, race, hereditary factors, diabetes and alcohol consumption with the more recent novel investigations at the cellular level. In concert, the findings indicate that a number of factors may lead to the narrowing of palmar fascia microvessels, with localized ischaemia and oxygen free radical release. Oxygen free radicals are likely to damage the surrounding stroma, and stimulate fibroblast proliferation. Proliferating fibroblasts lay down collagen and contract in the lines of stress. The process is likely to encourage further microvessel ischaemia with a positive feedback effect that is consistent with the progressive nature of the condition.

Dupuytren Contracture

Dupuytren's contracture. Fine structure in relation to aetiology.

The fine structure of palmar fascia from patients with Dupuytren's contracture (DC) was compared with that from patients with carpal tunnel syndrome (CTS). In contrast to previous assumptions, the ultrastructure of fibroblasts both in vivo and in vitro from DC and CTS appeared identical, indicating that myofibroblasts are not specific to DC. The major differences between DC and CTS were: 1) a sixfold and fortyfold increase in fibroblast density in cord and nodular areas of DC compared with CTS; 2) a more disorganised pattern of collagen fibrils in DC; and 3) markedly narrowed microvessels surrounded by thickened, laminated basal laminae and proliferating fibroblasts in DC compared with CTS. To account for these morphological changes a hypothesis is presented which proposes that oxygen-free radicals cause pericytic necrosis and fibroblastic proliferation. This hypothesis provides a potential avenue for therapy of DC and other fibrotic conditions.

Aged

Complete denture esthetics.

Complete denture esthetics can no longer be considered solely a function of tooth selection and arrangement or the colors and contours of the denture bases. Denture esthetics must also include the entire face in which the expressions of inner feelings, personality, comfort, image, well-being, and perceptions of past dental experiences are all very evident. These hard and soft components all contribute to the complete denture esthetic result; they are inseparable and should be given every consideration when developing a successful complete denture esthetic restoration. Both the patient and the dentist must understand this interrelationship for optimal success.

Denture Design

Video-assisted prosthodontics.

An 8 mm camcorder was used to produce and replay video tape recordings of patient consultations, diagnosis, and treatment. The benefits of this modality were presented and discussed.

Consumer Behavior

Esthetics and the edentulous patient.

Most individuals undergo some degree of psychological shock, depression, and loss of self-esteem after the loss of their teeth. Optimum success in the treatment of the edentulous patient can no longer be limited to the proper fit, function, speech, selection, and arrangement of teeth. In addition, today's dentists must use treatment strategies that include proper psychological management, caring, and recognition of the importance of the patient's perception of what is personally esthetic. This article addresses the esthetic considerations of this restorative challenge.

Consumer Behavior

Free radicals and Dupuytren's contracture.

The concentration of substrate expressed as hypoxanthine capable of reacting with xanthine oxidase to release superoxide free radicals (O2-) was measured in control and Dupuytren's contracture palmar fascia. In Dupuytren's contracture palmar fascia the concentration of hypoxanthine was six times that of control and was greatest in "nodular" areas. Xanthine oxidase activity was also detected in Dupuytren's contracture palmar fascia. These results suggest a greater potential for hypoxanthine-xanthine oxidase generated oxygen free radical formation in Dupuytren's contracture than in control palmar fascia. Production of free radicals may be an important factor in the pathogenesis of Dupuytren's contracture. The benefit of allopurinol in the management of Dupuytren's contracture and other fibrotic conditions may thus be explained, as allopurinol binds to xanthine oxidase and prevents release of free radicals.

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