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Biomedical subjects

S A Clarke

Publications and source records attributed to S A Clarke.

14 recordsLinked to original sources
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↗
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↗
PubMed1975

Hexamethylmelamine-induced regression of human lung tumors growing in immune deprived mice.

Hexamethylmelamine is known to be effective in humans in the treatment of certain malignant tumors, especially bronchial carcinoma. It is, however, quite inactive against a number of animal tumors, making difficult a study of its mechanism of action in experimental systems. In a reexamination of the effects of hexamethylmelamine, two tumors were found to be very sensitive, namely, a mouse plasma cell tumor (PC6) and a human bronchial carcinoma (P246) growing in immune deprived mice. Both tumors undergo a significant and almost complete regression, even when well established, and hence may serve as model systems for the study of the mechanism of action of hexamethylmelamine.

Animals↗
PubMedDate not supplied

Chemotherapy of human tumors in T-lymphocyte-deficient mice.

Human lung, ovarian, colonic, and renal carcinomas have been grown in mice artificially deprived of T-lymphocytes. All grew slowly and were shown to have a human karyotype even after several transplant generations. Their responses to chemotherapy were similar to the expected clinical response with the important exception of hexamethylmelamine which caused complete regression of two lung carcinomas (even when weighing up to 2.5 g at the start of treatment) and a renal carcinoma, while completely inhibiting the growth of an ovarian carcinoma and another lung carcinoma. Measurement of plasma carcinoembryonic antigen levels proved to be of value in assessing drug efficacy.

Altretamine↗