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Biomedical subjects

S A Clarke

Publications and source records attributed to S A Clarke.

At least 19 recordsLinked to original sources
PubMed2006

Healing of an ulnar defect using a proprietary TCP bone graft substitute, JAX, in association with autologous osteogenic cells and growth factors.

Currently, available synthetic bone substitutes have adequate osteoconductive properties but have little or no osteoinductivity. Recent research has focused on using osteogenic growth factors or cells to provide this. JAX is a beta tricalcium phosphate bone graft substitute that has a novel shape and interlocking design. This study investigated delivery methods and the use of autologous cell therapy to enhance healing of a bone defect using JAX as a scaffold. Bone marrow was harvested from 24 New Zealand White rabbits. The mononuclear cell fraction was isolated and culture expanded. Bilateral 1.5 cm defects in the ulna were filled with: Group 1: JAX alone, Group 2: JAX plus 1x10(7) autologous BMSCs injected at the time of surgery, Group 3: JAX plus 8x10(6) autologous BMSCs cultured on granules for 14 days prior to surgery, Group 4: JAX plus fresh bone marrow (BMA), Group 5: cortical autograft, Group 6: JAX plus 2.5 microg VEGF. Radiographs demonstrated that there was more new bone in the BMA and VEGF groups compared to JAX alone. Groups containing autologous BMSCs were only slightly better than JAX alone in the amount of bone in the defect but did improve bridging of the osteotomy. Histomorphometry identified a significant increase in bone volume in the BMA group compared to JAX alone. BMA and VEGF enhanced healing of bone defects whereas expanded BMSCs provided little advantage over scaffold alone. There was no difference between delivery methods of autologous BMSCs. These observations suggest that the provision of osteogenic cells alone is insufficient to enhance bone healing and that additional factors are required to initiate this process in vivo.

Animals↗
PubMed2006

The effects of growth hormone treatment on health-related quality of life in children.

BACKGROUND/AIMS: The effects of growth hormone deficiency (GHD) on linear growth in children are well documented, but there is less convincing evidence regarding the impact on health-related quality of life (QOL). We examined QOL in children aged 8-16 years with acquired GHD following treatment for malignancy (AGHD) or idiopathic GHD (IGHD) on commencing growth hormone treatment (GHT) over 6 months. We adopted a longitudinal design involving consecutive patients and their families attending clinic over an 18-month period. Mothers and children were invited to complete questionnaires before GHT (T1) and 6 months later (T2). METHODS: Mothers of 22 children (AGHD n = 14; IGHD n = 8) completed standardized measures of child QOL and behaviour. Children completed parallel measures of QOL, short-term memory tasks and fitness either in clinic or at the family home. RESULTS: For children with AGHD, QOL was significantly below population norms at T1 and improved over time. For children diagnosed with IGHD, QOL at T1 was below, but comparable with population norms. QOL improved over time, though not significantly. CONCLUSION: GHT is potentially valuable for improving QOL in children, especially in cases of AGHD. We conclude that benefits of GHT for QOL need to be evaluated independent of different diagnostic groups.

Adolescent↗
PubMed2005

Somatostatin for intractable postoperative chylothorax in a premature infant.

A premature infant of 31 weeks' gestation underwent repair of an oesophageal atresia, distal tracheo-oesophageal fistula and anal stenosis. A lymphatic leak was noted at the time of surgery. Chylous drainage persisted and an intravenous infusion of somatostatin was begun. The volume of chyle drained fell dramatically within the first 24 h and was negligible by the 5th day of treatment. No reaccumulation of the chylothorax was seen after the cessation of somatostatin. To our knowledge this is the youngest reported child in whom somatostatin has been used successfully in treating a postoperative chylothorax.

Chylothorax↗
PubMed2004

The effect of osteogenic growth factors on bone growth into a ceramic filled defect around an implant.

Currently available synthetic bone substitutes perform poorly compared to autograft. It is hoped that by adding osteogenic growth factors to the materials, new bone formation could be increased and the clinical outcome improved. In this study, IGF-1, bFGF and TGFbeta1, alone and in combination, were absorbed onto a carrier of beta-tricalcium phosphate (betaTCP) and implanted into a defect around a hydroxyapatite-coated, stainless steel implant in the proximal tibia of rat in a model of revision arthroplasty. Animals were sacrificed at 6 and 26 weeks for routine histology and histomorphometry and mechanical push out tests. The results show that only bFGF had a significant effect on ceramic resorption. The groups that received bFGF and bFGF in combination with TGFbeta1 had smaller and fewer betaTCP particles remaining in the defect at 6 and 26 weeks. No growth factor combination significantly enhanced new bone formation or the mechanical strength of the implant. These results indicate that, of the growth factors tested, only bFGF had any beneficial effect on the host response to the implant, perhaps by delaying osteoblast differentiation and thereby prolonging osteoclast access to the ceramic.

Animals↗
PubMed2004

Bone growth into a ceramic-filled defect around an implant. The response to transforming growth factor beta1.

Synthetic bone substitutes provide an alternative to autograft but do not give equivalent clinical results. Their performance may be enhanced by adding osteogenic growth factors. In this study, TGFbeta1 was absorbed on to a carrier of beta tricalcium phosphate and Gelfoam and used to fill a defect around a tibial implant in a rat model of revision arthoplasty. We added 0.0, 0.02 microg, 0.1 microg or 1.0 microg of TGFbeta1 to the carrier and then implanted it around an hydroxyapatite-coated stainless-steel pin in the proximal tibia of rats. The tibiae were harvested at three, six or 26 weeks and the amount of bone formation and ceramic resorption were assessed. TGFbeta1 had no effect on the amount of bone in the defect, the amount of fluorescent label incorporated or the rate of mineral apposition. The growth factor did not significantly affect the amount of betaTCP remaining in the tissue at any of the time points.

Animals↗
PubMed2003

Isolation of monocytes from human peripheral blood using immuno-affinity expanded-bed adsorption.

A novel technique for the separation of monocytes from human peripheral blood preparations has been developed. The technique is based on the use of expanded-bed adsorption and a solid perfluorocarbon derivatized with avidin or streptavidin for the indirect positive or negative capture of cells labeled with biotinylated monoclonal antibodies. The perfluorocarbon support was prepared and characterized and the contactor design and operating conditions, that enable cells to be selectively isolated, were investigated. Experiments consisted of applying an immunolabeled pulse of 1 x 10(8) peripheral blood mononuclear cells (PBMCs), isolated by density gradient centrifugation, directly onto a refrigerated expanded bed. The major cell types remaining were T-lymphocytes, B-lymphocytes, and monocytes. Monocytes could be positively adsorbed, following labeling with anti-CD14 mAb, with a clearance of up to 89% and a depletion factor of 7.6. They could also be "eluted" using mechanical shear, with a 77% yield of the applied cells at a purity of 90% and >/= 65% viability. Negative isolation of monocytes, following labeling of the other cells present with anti-CD2, CD7, CD16, CD19, and CD56 mAbs, resulted in lymphocyte depletions of up to 81% with a monocyte enrichment factor of 3.8 and purity of 71%. The monocyte viability in the flowthrough was assessed to be > 95%. This combination of expanded-bed adsorption and fluidizable affinity supports shows significant potential for the intensification of cell separations.

Cell Separation↗
PubMed2003

The response of macrophages to particles of resorbable polymers and their degradation products.

Alpha polyesters such as poly(L-lactide) and poly(glycolide) are biodegradable materials used in fracture fixation and they need to be assessed for problems associated with their degradation products. This study has compared cell responses to low molecular weight poly(L-lactide) particles, lactate monomer, poly(glycolide) particles and glycolic acid at cytotoxic and sub-cytotoxic concentrations. Murine macrophages were cultured in vitro and the release of lactate dehydrogenase (LDH), prostaglandin E(2) (PGE(2) and interleukin-1 alpha IL-1alpha was measured following the addition of particles or monomer. Experiments revealed that both the poly(L-lactide) and poly(glycolide) particles gave rise to dose dependent increases in LDH release and an increase in IL-1alpha and PGE(2) release. Comparisons of the poly(L-lactide) particles to the poly(glycolide) particles did not reveal any differences in their stimulation of LDH, IL-1alpha and PGE(2) release. The lactate and glycolate monomers did not increase PGE(2) or IL-1alpha release above control levels. There was no difference in biocompatibility between the poly(L-lactide) and poly(glycolide) degradation products both in particulate and monomeric form.

Journal Article↗
PubMed2002

Testing bone substitutes in a small animal model of revision arthroplasty.

This study evaluated a modification of the rat-pin model to enable testing of bone substitute materials. The model was characterized using the ceramic, beta-tricalcium phosphate (betaTCP) as a filler. A 1 mm wide, 3.6 mm deep defect was created around a stainless steel (SS) implant in the proximal tibia of a rat. This defect was filled with a ceramic powder. Large particles (90-312microm) of betaTCP were mixed with Gelfoam to form a paste which was then molded around the proximal end of either an uncoated SS pin or a pin coated with hydroxyapatite (HA). The pin with its ceramic collar was then implanted into the proximal tibia of 16 male Sprague Dawley rats. Two animals with coated implants and two with uncoated implants were sacrificed at 3, 6, 14 and 26 weeks. Longitudinal sections of each tibia were stained with toluidine blue and labeled for tartrate resistant acid phosphatase (TRAP). There was initial fibrous tissue interposition around the implants which was completely remodeled around the HA coated pins but which persisted in apposition to the SS pins. The remodeling process peaked at 3 weeks around the HA coated pins and at 6 weeks around the uncoated implants. There was little remodeling around either implant by 26 weeks. There was considerable residual betaTCP present which was well tolerated as the particles were often encased in bone. The model has several characteristics of revision arthroplasty and the results demonstrate the suitability of this model for testing bone substitutes.

Journal Article↗
PubMed2001

Integrin expression at the bone/biomaterial interface.

The aim of this study was to visualize integrin expression by cells in interface tissue in relation to their ligands. Tissue samples were obtained from 25 patients undergoing revision of aseptically loose total joint replacements. Serial sections were immunolabeled for the integrins alpha(2)beta(1), alpha(v)beta(3), alpha(4)beta(1), alpha(L)beta(2) (CD11a), alpha(M)beta(2) (CD11b), and alpha(X)beta(2) (CD11c), and the ligands fibronectin, laminin, vitronectin, intercellular adhesion molecule-1, and vascular adhesion molecule-1. Most cells were found to express alpha(2)beta(1), most macrophages and giant cells expressed CD11b, and the majority of CD11a was found on perivascular T lymphocytes. From the small amount of alpha(4)beta(1) and vascular adhesion molecule-1 expression in the interface tissue and the combination of CD11a, CD11b, and intercellular adhesion molecule-1 expression, it would seem that macrophages use beta(2) integrins to transmigrate.

Aged↗
PubMed2001

Percutaneous transfemoral testicular vein embolisation in the treatment of childhood varicocoele.

BACKGROUND: Controversy surrounds the early treatment of childhood varicocoele and its role in the prevention of testicular atrophy and male infertility. Various techniques exist, all with varying degrees of success. OBJECTIVES: To show that percutaneous transfemoral testicular vein embolisation is an effective alternative when compared to the conventional open surgical approach. MATERIALS AND METHODS: A retrospective review examining 48 boys (aged 9-18 years; mean 13.2 years) who were treated with transcatheter testicular vein embolisation between 1985 and 1999. Follow-up took the form of out-patient clinical assessment and a telephone questionnaire. Patients were graded as 'good', 'moderate' or 'poor', according to various criteria. RESULTS: Of the 48 patients, 43 (90%) had satisfactory embolisations. Thirty-eight (88 %) had a 'good' clinical outcome at follow-up. There were five technical failures due to a combination of abnormal venous anatomy and severe venospasm. CONCLUSIONS: We believe that where the expertise necessary for testicular embolisation is available, it should be offered as the intervention of first choice. Surgery should be reserved for the rare cases where embolisation is not possible or when recurrence has occurred.

Adolescent↗
PubMed2001

Correlation of synovial fluid cytokine levels with histological and clinical parameters of primary and revision total hip and total knee replacements.

We retrieved synovial tissue and fluid samples from patients undergoing primary total hip replacement (THR) (n 15), revision of aseptically loose THR (n 12), primary total knee replacement (TKR) (n 13) and revision of aseptically loose TKR (n 6). Several histological parameters were assessed on a relative scale of 14. Primary TJRs were clinically evaluated for degree of osteoarthrosis. Revision TJRs were assessed for migration of the implant, gross loosening and the degree of radiolucency. Cytokine levels in synovial fluid were determined with ELISA. All cytokines were significantly higher in revision TJRs than in primary replacements, as were the degree of macrophage and giant cell infiltration. We found no relationship between any clinical variable and the levels of any cytokine, but migration of the implant was related to the presence of PE debris. A significant correlation was seen between the presence of macrophages and the levels of IL-1beta, IL-8 and IL-10, but not IL-6. No differences were noted between hips and knees for any of the variables, except in the levels of IL-6, where higher levels were found in THRs. These results suggest a unique role for IL-6 that requires further investigation.

Adult↗
PubMed2001

Mortality in rheumatoid arthritis: relationship to single and composite measures of disease activity.

BACKGROUND: Rheumatoid arthritis (RA) is a heterogeneous disease characterized by a variable course of remissions and relapses. Single measures of disease activity at only one point in time may not reflect the overall control of disease activity. OBJECTIVE: The aim was to determine (i) the predictive value of 20 baseline demographic and disease variables on mortality, and (ii) the relationship between serial measures of the Stoke index (SI; a validated index of disease activity in RA) and mortality in RA. METHODS: Mortality in 309 RA patients followed up for a median of 14 yr was analysed retrospectively. The standardized mortality ratio (SMR) was calculated for all causes of death. The predictive values of baseline and time-integrated variables were assessed using multivariate Cox proportional hazards regression analysis. RESULTS: The SMR was 1.65. At baseline, only nodules, erosions, RA latex titre, white cell count and globulin level were predictive of mortality after correction for age, sex and disease duration. Using a stepwise Cox proportional hazards regression model, the most powerful predictors of mortality were age, nodules and RA latex titre. Individual measures of disease activity and the SI at baseline were not predictive of mortality. However, the mean level of the SI over 12 months was related to mortality (P=0.039). CONCLUSIONS: At baseline, the demographic and disease variables most significantly related to mortality in RA are age, nodules and RA latex titre. Individual measures of disease activity at a single point in time are poor predictors of mortality in RA. However, measurement of the mean level of disease activity over time using the composite SI has a significant relationship with mortality. A high level of sustained inflammation appears to be an important predictor of premature death.

Adult↗
PubMed1996

Working with noncompliant and abusive dialysis patients: practical strategies based on ethics and the law.

The patient population in dialysis facilities today reflects common societal problems such as human immunodeficiency virus infection, illicit drug use, distrust of and disrespect for authority, and a propensity toward violence. An increase in calls from dialysis units for guidance in dealing with noncompliant and abusive patients prompted ESRD Network 5 to examine this problem and develop an educational program, "Working with Noncompliant and Abusive Patients." This article provides an overview of the ESRD Network 5 study of the ethical, legal, psychosocial, and administrative aspects of this problem, presents practical strategies for working with such patients, and demonstrates the application of these strategies in three cases. It emphasizes the importance for dialysis units of four elements in the successful treatment of such patients: instruction for all levels of dialysis staff; a team approach; written policies; and patient education at the time of admission about these policies, including the consequences of verbal and physical abuse and the circumstances under which patients will be discharged from the dialysis unit.

Aggression↗
PubMed1991

Somatosensory evoked potentials in intracranial hypertension: analysis of the effects of hypoxia.

The loss of somatosensory evoked potentials (SSEP's) was investigated in a feline model of intracranial hypertension. Threshold values of cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) required for maintenance of SSEP's are defined using a mathematical model. The model describes loss of amplitude of SSEP's using the form of a dose-response curve. Amplitude of the SSEP's declined to 50% of control values at a CBF of 15 ml/100 gm/min and a CPP of 20 mm Hg in the normoxic animal; in the presence of mild hypoxia (8 to 9 kPa), a significant increase in these values to 18 ml/100 gm/min and 32 mm Hg, respectively, occurred. No reliable changes in latency or central conduction time were demonstrated. It is concluded that given adequate oxygenation, evoked electrical activity is lost at too low a level of CPP for this parameter to be useful in clinical monitoring. However, even mild hypoxia, when combined with intracranial hypertension, produces a major risk to neuronal integrity.

Animals↗
PubMed1983

Hematoma-induced febrile response in the pediatric patient.

Frequently there is a temperature elevation in children following operative procedures or trauma involving the long bones. A combined clinical and laboratory study investigated the possibility that this was secondary to blood resorption. A clinical study was conducted by reviewing the records of all children admitted to the hospital over a 10-year period with closed femoral or tibial fractures. All these patients demonstrated a temperature elevation to at least 101 degrees F. In the laboratory study, rabbits of different ages were bled, and this blood was reinjected into their quadriceps muscle to create hematomas. Control rabbits were hemorrhaged and either were not reinjected with their blood or were injected intramuscularly with lactated Ringer's solution. Those rabbits that received the intramuscular blood injections developed significant temperature elevations, and the younger the rabbit the more pronounced the temperature rise.

Adolescent↗
PubMed1982

An examination of autonomic nervous function in genetically diabetic mice.

1 This study was designed to determine whether the autonomic innervation of the heart and vas deferens in genetically diabetic mice exhibited dysfunction similar to those seen in chemically diabetic animals and diabetic patients. 2 Diabetic mutant mice (outcrossed from the C57 BL/KS db/db strain) were compared with their non-diabetic litter-mates at age 20 to 22 weeks. Right and left atria and vasa deferentia were removed from freshly killed animals and subjected to nerve stimulation and treatment with noradrenaline (NA) or acetylcholine (ACh) in organ baths. 3 Right atria from diabetic animals were less responsive to noradrenergic nerve stimulation than control preparations but there was no such difference between the noradrenergic responses of left atria from the two groups of mice. Both atria were hypersensitive to exogenous NA. 4 Atria from diabetic mice responded to cholinergic nerve stimulation and exogenous ACh in a fashion similar to those of non-diabetic mice. Likewise in the responses of vasa deferentia to nerve stimulation were similar in the two groups. These findings are indicative of some autonomic nervous dysfunction characteristic, to an extent, of diabetes mellitus.

Animals↗
PubMed1982

The regrowth of right atrial noradrenergic nerves after 6-hydroxydopamine in genetically diabetic mice; effects of insulin treatment.

1 This study examined the rate of repletion of right atrial noradrenaline levels after a single dose (100 mg/kg i.p.) of 6-hydroxydopamine (6-OH Da) in diabetic and non-diabetic mice of the C57 BL/KS db/db strain. 2 In mice which received no 6-OH Da there was no significant difference, in endogenous noradrenaline levels, between diabetic and non-diabetic animals. The depletion of noradrenaline 24 h after 6-OHDa was slightly more profound in the diabetic mice than in non-diabetic controls. Thereafter the rate of repletion of noradrenaline was more rapid in the diabetic group. 3 The normal noradrenaline content was reinstated in diabetic mice between 7 and 10 days after 6-OHDa. In the non-diabetic group levels similar to those found in untreated mie were not reinstated until 14 days after 6-OHDa. 4 Ten days after 6-OHDa right atria from diabetic mice were markedly more responsive to stimulation of the intramural noradrenergic nerves than were preparations from non-diabetic mice. 5 A group of diabetic mice was treated with insulin (10 m Units/g daily) for 6 weeks. The right atria from these animals, examined 10 days after 6-OHDa, were similar in their responses to noradrenergic nerve stimulation to the preparations from the non-diabetic mice. 6 All these groups of atria gave similar responses to exogenous noradrenaline. These findings indicate that regrowth of noradrenergic terminals after 6-OHDa was more rapid in diabetic mice than in either insulin-treated diabetic mice or non-diabetic mice.

Animals↗