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Biomedical subjects

J McCartney

Publications and source records attributed to J McCartney.

17 recordsLinked to original sources
PubMed2004

The thickness of the temporal squama and its implication for transcranial sonography.

BACKGROUND AND PURPOSE: The difficult transtemporal ultrasound window is a relatively frequent occurrence. The authors assessed if the thickness of the temporal bone squama as measured in the "bone window" of the head computerized tomography (CT) scan can predict the transtemporal acoustic window. METHODS: The authors retrospectively reviewed the head CTs on their bone window setting of patients in which nonimaging transcranial Dopplers (TCDs) had been performed. The thickness of the temporal squama in its thinnest portion was measured. The temporal TCD windows were graded in three classes: class 1 as good, class 2 when only a partial study is possible, and class 3 as an impossible ultrasonic window. In a case-control design, for every patient with any class 2 and 3 TCD temporal window, a patient with a class 1 window was randomly included from the same time period. RESULTS: Fifty-five temporal bones (56%) were class 1, 17 (17%) were class 2, and 27 (27%) were class 3. Bone thicknesses (in mm, mean +/- SD) were greater in those with poorer windows: class 1 = 2.67 +/- 0.70, class 2 = 4.06 +/- 0.56, and class 3 = 5.04 +/- 1.06, P < or = .0001 by Cusick's nonparametric test of trend. Temporal squama thickness of > or = 5 mm portends 86% sensitivity, 90% specificity, 70% positive predictive value, and a positive likelihood ratio of 8.6 for a class 3 transtemporal ultrasound window. CONCLUSION: Measurement of temporal bone thickness on the bone window setting of the head CT scan may be useful in identifying patients who are poor candidates for transcranial ultrasound.

Adolescent↗
PubMed2001

Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep.

The efficacy of osteogenic protein-1 (OP-1; BMP-7) in regeneration of articular cartilage was examined by creating knee chondral defects in sheep. With a specially designed instrument in both knees, two 10 mm (diameter) chondral defects were created: one in the trochlea and the other on the femoral condyle. The recombinant BMP was delivered via an extra-articulary positioned mini-osmotic pump, which was fixed to the femoral diaphysis above the knee joint, and connected by a polyethylene tubing to the articular space. Prior to use, the compatibility of OP-1 with mini-osmotic pumps was tested in vitro by measuring aggregation/precipitation and modification of the released protein by size exclusion and reversed phase HPLC. The average amount of aggregation was 15% and about 5% of OP-1 was modified. However, the biological activity of OP-1 released from pumps over a period of 2 weeks at 37 degrees C was equal to ROS cell assay OP-1 standard. Following surgery, a total of 55 microg (low dose) or 170 microg (high dose) OP-1 in acetate buffer (pH 4.5) was slowly released from the pump over a period of 2 weeks. The pumps connected to control knees were filled with acetate buffer as a vehicle. Twelve animals were operated, six of which were treated with the low OP-1 dose, and six with the high OP-1 dose. Three sheep of each group were killed either at 3 or 6 months following surgery, based on arthroscopical evaluation. The chondral defects in the control knees remained empty during the observation period. At 3 months following surgery, defects treated with both OP-1 doses were filled with connective tissue and cartilage. At 6 months following surgery, both doses of OP-1 stimulated regeneration in treated knees. The boundaries between new and old cartilage were well fused and mechanically resisted animals' weight bearing. The regenerated cartilage was rich in proteoglycans and type II collagen, as demonstrated by toluidine blue staining and immunohistochemistry. No signs of endochondral bone formation above the bony tidemark were observed. We suggest that a recombinant bone morphogenctic protein stimulates ingrowth of mesenchymal cells into the chondral defects which then transform into newly formed articular cartilage-like tissue.

Alkaline Phosphatase↗
PubMed2000

Human articular chondrocytes express osteogenic protein-1.

This study demonstrates for the first time that human articular chondrocytes express osteogenic protein-1 (OP-1). OP-1 was originally purified from bone matrix and was shown to induce cartilage and bone formation. Both OP-1 protein and message were present in human normal and osteoarthritic (OA) cartilages. OP-1 mRNA was upregulated in OA cartilage compared with normal adult tissues. However, the level of mature OP-1 protein in the same OA tissues was downregulated, whereas the pro-OP-1 remained high. Moreover, these two forms of OP-1 were localized in an inverted manner. Mature OP-1 was primarily detected in the superficial layer, whereas the pro-form was mostly in the deep layer of cartilage. The presence of pro- and mature OP-1 in extracts of normal and OA cartilages was confirmed by Western blotting. These findings imply that articular chondrocytes continue to express and synthesize OP-1 throughout adulthood. The observed patterns of the distribution of pro- and mature OP-1 also suggest differences in the processing of this molecule by normal and OA chondrocytes and by the cells in the superficial and deep layers. Distinct distribution of OP-1 and its potential activation in deep zones and regions of cloning in OA cartilages may provide clues to the potential involvement of endogenous OP-1 in repair mechanisms. (J Histochem Cytochem 48:239-250, 2000)

Adolescent↗
PubMed1999

Reflections on volatile substance dependency treatment. Negotiating the boundary between inner and outer reality.

A brief review of the causal and treatment literature relating to volatile substance dependency suggests the interaction between individual and system requires careful attention and understanding. A model is tentatively and provisionally adumbrated to help clarify the main factors involved from a dynamic biopsychosocial perspective. Ego boundary disturbances emerge from and reciprocally influence behaviour and social interactions. These disturbances can be avoided temporarily, although inevitably deepened in the long-term, by substance dependence. Two case examples, selected because they differ in many respects, including relative treatment effectiveness, illustrate this integrative perspective. The discussion focuses on explaining the differing outcomes in terms of the extent to which the inner-outer boundary is open to modification and how far it can be successfully negotiated and clarified. A major factor in differentiating between inside and outside is thought to be causal perceptions or "attributions." Successful differentiation tends to facilitate change, as opposed to reinforcing maladaptive homeostasis. Key issues for therapists overlap with addictions treatment in general, including emotional blocks or barriers in patients, difficulty engaging systems in a strategic manner, and countertransference problems. It is argued that these difficulties in therapy might respond to integrative psychotherapeutic responses, provided the differences in perspective are sufficiently understood.

Administration, Inhalation↗
PubMed1998

Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis.

Cartilage-derived morphogenetic proteins-1 and -2 (CDMP-1 and CDMP-2) are members of the bone morphogenetic protein (BMP) family, which play important roles in embryonic skeletal development. We studied the biological activities of recombinant CDMP-1 and CDMP-2 in chondrogenic and osteogenic differentiation and investigated their binding properties to type I and type II serine/threonine kinase receptors. In vivo, CDMP-1 and CDMP-2 were capable of inducing dose-dependently de novo cartilage and bone formation in an ectopic implantation assay. In vitro studies using primary chondrocyte cultures showed that both CDMP-1 and CDMP-2 stimulated equally de novo synthesis of proteoglycan aggrecan in a concentration-dependent manner. This activity was equipotent when compared with osteogenic protein-1 (OP-1). In contrast, CDMPs were less stimulatory than OP-1 in osteogenic differentiation as evaluated by alkaline phosphatase activity and expression levels of bone markers in ATDC5, ROB-C26, and MC3T3-E1 cells. CDMP-2 was the least osteogenic in these assays. Receptor binding studies of CDMP-1 and CDMP-2 revealed that both have affinity for the BMP receptor type IB (BMPR-IB) and BMPR-II, and weakly for BMPR-IA. Moreover, using a promoter/reporter construct, transcriptional activation signal was transduced by BMPR-IB in the presence of BMPR-II upon CDMP-1 and CDMP-2 binding. Our data show that distinct members of the BMP family differentially regulate the progression in the osteogenic lineage, and this may be due to their selective affinity for specific receptor complexes.

Aggrecans↗
PubMed1997

Between knowledge and desire: perceptions of decision-making in the addictive behaviors.

Behavioral change in the addictions is often conceptualized in terms of decision-making. It is argued that there are various problems and ambiguities inherent in the experimental research approach. An exploratory study across a range of dependencies (smoking, excessive gambling, drinking, and eating) is reported. The main aim is to examine personal accounts and views of the decision-making process instead of looking at this indirectly. Qualitative and quantitative evidence from a clinical and general population sample supports the perceived importance of decision-making across the dependencies studied. Such a process is thought to facilitate action and commitment. Firmness of decision in the clinical sample is significantly related to confidence in maintaining change. However, choices or decisions often involve relatively unsystematic processing. Blocks to implementation include unpleasant affect. The importance of understanding the link between affect and decision is emphasized as this is thought to be one of the critical determinants of successful change, yet is rarely explicitly studied. The discussion elaborates on possible ways of integrating decision-making with current clinical practice.

Adolescent↗
PubMed1995

Addictive behaviors: relationship factors and their perceived influence on change.

An empirical study of a British clinical population is reported, in which the influence of relationships on confidence in maintaining change across a number of addictive behaviors was investigated. The hypothesis was that the perceived quality of relationships would be correlated with a client's confidence in sustaining abstinence or change. It was also thought that qualitative data would help clarify some of the underlying processes mediating such a link if it were established. The results largely supported the predictions, although relationship difficulties were significantly more common in gamblers and alcoholics compared with smokers and overeaters. The discussion develops the view that the notion of emotional disclosure and system theory's emphasis on circular causality are particularly useful concepts in making sense of the data.

Alcoholism↗
PubMed1993

Medical applications of single-chain antibodies.

A single-chain antibody or single-chain Fv (sFv) incorporates the complete antibody binding site in a single polypeptide chain of minimal size, with an approximate molecular weight of 26,000. In antibodies, the antigen combining site is part of the Fv region, which is composed of the VH and VL variable domains on separate heavy and light chains. Efforts over nearly two decades have indicated that Fv fragments can only rarely be prepared from IgG and IgA antibodies by proteolytic dissection. Beginning in 1988, single-chain analogues of Fv fragments and their fusion proteins have been reliably generated by antibody engineering methods. The first step involves obtaining the genes encoding VH and VL domains with desired binding properties; these V genes may be isolated from a specific hybridoma cell line, selected from a combinatorial V-gene library, or made by V gene synthesis. The single-chain Fv is formed by connecting the component V genes with an oligonucleotide that encodes an appropriately designed linker peptide, such as (Gly4-Ser)3. The linker bridges the C-terminus of the first V region and N-terminus of the second, ordered as either VH-linker-VL or VL-linker-VH. In principle, the sFv binding site can faithfully replicate both the affinity and specificity of its parent antibody combining site, as demonstrated in our model studies with the 26-10 anti-digoxin sFv. Furthermore, the sFv remains stable at low concentrations that promote VH and VL dissociation from the Fv heterodimer, resulting in loss of Fv binding. Intravenously administered sFv proteins exhibit accelerated biodistribution and exceptionally fast clearance compared to IgG or Fab. These pharmacokinetic properties allow rapid imaging by sFv, which therefore may be labeled with a short-lived isotope such as Tc-99m. Expression of a single gene product from fused sFv and effector genes facilitates immunotargeting of the effector protein, as shown for single-chain Fv toxin fusion proteins.

Amino Acid Sequence↗
PubMed1992

Systems analysis of a drug dependency service in London: St George's Hospital.

Elements of a systems approach to analysing service delivery are outlined. A specific example--St George's Hospital Addiction Behaviour Department--is detailed. Dynamics of the system--from the client's perspective and the workers viewpoint--demonstrate some of the ways in which emotional conflict surrounding the task is handled. The conclusions focus on what might constitute adaptive resolution of systems dilemmas as well as highlighting the public-health concerns relating to AIDS which, we argue, compromise the primary task of an addiction service at the present time.

Acquired Immunodeficiency Syndrome↗
PubMed1981

The perception of drinking roles by recovering problem drinkers.

The perception of and attitude to drinking patterns in recovering problem drinkers (N = 29) is analysed, utilizing a similar methodology to that of Richard & Burley (1978). Fault is found, however, in the latter study both in a failure to define variables and in the authors' statistical handling of the results. In the present study, it was found that controlled drinking is only seen as close to the problem drinker's concept of himself when it entails reasonably high levels of consumption. The importance of this finding for therapy is outlined. The possible negative effects of role conflict are mentioned. It is also found that problem drinkers perceive themselves as having quite different characteristics from those they themselves attribute to alcoholics. This finding is interpreted in terms of the fundamental attribution error (Jones & Nisbett, 1972).

Adult↗
PubMed1979

Boerhaave syndrome.

Explore the source record for details and available documents.

Aortic Dissection↗
PubMed1976

The effect of dopamine on renal microcirculation in hemorrhagic shock in dogs.

Dopamine, a naturally occuring catecholamine, was infused at the rate of 6 micrograms per kilogram per minute on an hemorrhagic shock model in dogs. Urinary output was continuously recorded, with arterial pressure being maintained at 50 millimeters of mercury. At the termination of the experiment, the dogs were sacrificed, and renal microcirculation was studied by an angiomicrohistologic technique. There was a dramatic increase in urinary output following the infusion of dopamine. Results of the microcirculatory study of the renal vasculature showed markedly increased cortical perfusion and dilation of vessels, particularly at a level of afferent arterioles; however, findings on efferent arterioles were inconsistent. Also, changes in the microvasculature of the medulla were less striking than those of the cortex following the administration of dopamine.

Animals↗
PubMedDate not supplied

Antigen recognition and targeted delivery by the single-chain Fv.

The single-chain Fv (sFv) has proven attractive for immuno-targeting, both alone and as a targeting element within sFv fusion proteins. This chapter summarizes the features of sFv proteins that have sparked this interest, starting with the conservation of Fv architecture that makes general sFv design practical. The length and composition of linkers used to bridge V domains are discussed based on the sFv literature; special emphasis is given to the (Gly4Ser)3 15-residue linker that has proven of broad utility for constructing Fv regions of antibodies and other members of the immunoglobulin superfamily. The refolding properties of sFv proteins are summarized and examples given from our laboratory. Spontaneous refolding from the fully reduced and denatured state, typified by 26-10 sFv, is contrasted with disulfide-restricted refolding, exemplified by MOPC 315 and R11D10 sFv proteins, which recover antigen binding only if their disulfides have been oxidized prior to removal of denaturant. The medical value of sFv proteins hinges on their reliability in antigen recognition and rapidity in targeted delivery. Detailed analysis of specificity and affinity of antigen binding by the 26-10 antidigoxin sFv has demonstrated very high fidelity to the binding properties of the parent 26-10 sFv. These results gave confidence to the pursuit of more complex biomedical applications of these proteins, which is indicated by our work with the R11D10 sFv for the imaging of myocardial infarctions. Diagnostic imaging and therapeutic immunotargeting by sFv present significant opportunities, particularly as a result of their pharmacokinetic properties. Intravenously administered sFv offers much faster clearance than conventional Fab fragments or intact immunoglobulin with minimal background binding.

Amino Acid Sequence↗
PubMedDate not supplied

Understanding and helping the children of problem drinkers: a systems-psychodynamic perspective.

A brief overview of some of the psychological sequelae associated with parental alcohol abuse emphasises the variety of coping mechanisms utilised by children. In order to understand the experience from the child's perspective and assess possible effects on development, a psychodynamic-systems model is introduced. In-depth case material is then presented which attempts to utilise the proposed theoretical integration. The paper concludes with a discussion of some of the possible implications of the psychodynamic-system viewpoint for effective treatment.

Adolescent↗