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Biomedical subjects

R A Clark

Publications and source records attributed to R A Clark.

At least 109 records · Page 6Linked to original sources
PubMed1997

Determination of factors associated with condom use among women infected with human immunodeficiency virus.

To better understand potential barriers to condom use and the sexual behaviour of women infected with human immunodeficiency virus (HIV), an anonymous self-administered survey was performed on a convenience sample of 83 predominantly single HIV+ women. Most women had only one sexual partner who usually knew of the subject's serostatus. Only a minority of partners (26%) were known to also be HIV infected. Subjects were surprisingly more likely to use condoms with their main partner as opposed to other partners. Factors found to be associated with condom non-use included younger age, low education level, partner HIV+, history of a sexually transmitted disease (STD), and use of drugs or alcohol during sex. Although most subjects indicated the decision was mutual when deciding not to use a condom, 20% stated it a was a partner decision. Future intervention efforts should target these identified high-risk individuals and optimally involve the partners of HIV-infected women.

Adolescent↗
PubMed1997

Medical image databases for CAD applications in digital mammography: design issues.

The evaluation of algorithms' developed for computer assisted diagnosis in digital mammography requires image databases that allow relative comparisons and assessment of algorithms clinical value. A review of the literature indicates that there is no consensus on the guidelines of how databases should be established. Image selection is usually done based on subjective criteria or availability. The generation of common database(s) available to the research community makes relative evaluations of algorithms with similar properties easier. However, questions regarding the "right database size," the "right image resolution," and the "right contents" remain. In this paper, database issues are reviewed and discussed and possible remedies to the various problems are proposed.

Algorithms↗
PubMed1997

Location and stability of rectus muscle pulleys. Muscle paths as a function of gaze.

PURPOSE: The paths of the rectus extraocular muscles (EOMs) are constrained by pulleys, connective tissue sleeves mechanically coupled to the orbital walls. This study sought to investigate, using high-resolution magnetic resonance imaging (MRI), the location and stability of EOM pulleys in normal subjects and those with strabismus. METHODS: Multiple contiguous coronal MRI scans spanning the anterior-to-posterior extent of the orbit during primary gaze, upgaze, downgaze, adduction, and abduction were analyzed digitally to determine the paths of the rectus EOMs. Pulley locations were inferred from EOM paths. RESULTS: Data for 10 orbits of six normal subjects established the normal paths of the rectus extraocular muscles in primary gaze. Muscle paths in primary position were highly uniform across normal subjects. In secondary gaze positions, rectus muscle paths at the level of the pulleys exhibited small but consistent shifts, relative to the orbit, opposite the direction of gaze, consistent with the expected mechanical effects of the intermuscular connective tissue suspensions of the pulleys. Twelve orbits of seven subjects with strabismus showed, as a group, no significant difference from normal in rectus muscle paths in primary gaze and no significant difference from normal in changes of muscle paths in secondary gaze. Two subjects with incomitant strabismus wer found to have grossly abnormal rectus muscle paths in primary gaze, suggesting heterotopic pulleys. Computer simulations of these heterotopic pulley locations accounted for the observed patterns of incomitant strabismus in both. CONCLUSIONS: High-resolution MRI can determine the location and sideslip of rectus EOM pulleys. Pulley position is highly uniform across normal subjects, consistent with the notion that musculo-orbital tissue connections determine the pulling direction of the rectus EOMs. In normal subjects and subjects with strabismus, pulleys exhibit small shifts with eccentric gaze that are consistent with secondary intermuscular, but not musculo-global, mechanical couplings. Heterotopic pulley position is a potential cause of incomitant strabismus.

Adult↗
PubMed1997

The facilitator effect: results from a four-year follow-up of children with asthma.

BACKGROUND: A long-term evaluation of the process and outcomes of primary and secondary care is required to establish whether audit facilitators can improve the care of childhood asthma. AIM: To examine the long-term effect of an intervention by an audit facilitator on the management of children with asthma, and to investigate the implications for health service costs. METHOD: A 4-year follow up was conducted of an intervention and control group totalling 2557 children aged 1-15 years from 12 general practices in the Tayside region. Primary care consultations, prescriptions, hospital contacts and health service costs 1 year before and 3 years after a facilitator visited practices were recorded. The facilitator encouraged the diagnosis and treatment of childhood asthma in the intervention group. RESULTS: Favourable changes in consultation patterns, prescriptions and reduced hospital admissions seen during the intervention year did not persist in subsequent years. Two and three years after the facilitator visit the process and outcome of care was similar in both groups. The reduction in health service costs seen in the intervention group was equivalent to the cost of employing a facilitator. CONCLUSION: The effect of a facilitator lasts only for the period of intervention. Enthusiasts will say that improving patient care without increasing health service costs justifies the widespread deployment of facilitators. Others more interested in long-term outcomes may disagree.

Adolescent↗
PubMed1997

Does participation in distance learning and audit improve the care of patients with acute asthma attacks? The General Practitioners in Asthma Group.

OBJECTIVE: To test whether general practitioners who completed an audit cycle encompassing a data recording exercise, distance learning programme and personalized feedback changed their management of patients with acute asthma attacks. DESIGN, SETTING AND SUBJECTS: Practice and patient details from two national correspondence surveys of the management of acute asthma attacks in the United Kingdom in 1991-92 and 1992-93 were compared. Main outcome measures were use of nebulised bronchodilators, systemic steroids during an asthma attack, and increased use of prophylactic therapy after attacks. RESULTS: Ninety-one general practitioners completed an audit cycle and reported data on 782 patients with asthma attacks in 1991-92 and 669 in 1992-93. There were no significant changes in practice resources during this time. Management changed in line with recommended guidelines and audit feedback suggestions leading to more use of nebulised bronchodilators [272 (35%) before, 268 (40%) after, Odds Ratio (OR) 0.80, 95% Confidence Intervals (CI) 0.64-0.99], systemic steroids [563 (72%) before, 506 (76%) after, OR 0.83, CI 0.65-1.06], and 'step-up' in preventative therapy [402 (51%) before, 382 (57%) after, OR 0.79, CI 0.64-0.98]. CONCLUSION: General Practitioners who completed an audit cycle showed changes in the management of acute asthma attacks in line with guidelines which may have been caused by participation in distance learning and clinical audit. However, general practitioners motivated to change clinical management may be similarly motivated to take part in audit. Audit may be the catalyst for change rather than the cause of change.

Acute Disease↗
PubMed1996

Idiopathic genital ulcers in women infected with human immunodeficiency virus.

A national survey of investigators caring for human immunodeficiency virus (HIV)-infected women was undertaken to describe the clinical presentation of idiopathic genital ulcer disease. Patients with negative syphilis and herpes simplex testing and/or negative genital ulcer biopsy were included in this study. Study participants (n = 29) were generally severely immunocompromised (median CD4 cell count was 50/mm3, and 68% had an acquired immunodeficiency syndrome [AIDS]-defining opportunistic process). Thirty-seven percent had coexistent oral ulcers and 19% had their genital ulcer progress to fistula formation (four rectovaginal and one vaginal-perineal). There was generally a favorable response to topical, systemic, and intralesional steroid treatment. This study suggests that idiopathic or probable aphthous genital ulcers in women have similar clinical characteristics to aphthous oroesophageal ulcers. Although infrequent, these genital ulcers can cause severe morbidity. Further research is warranted to better define the pathophysiology and optimal management.

Adult↗
PubMed1996

Platelet-derived growth factor and inflammatory cytokines have differential effects on the expression of integrins alpha 1 beta 1 and alpha 5 beta 1 by human dermal fibroblasts in vitro.

Dermal fibroblasts are essential for the repair of cutaneous wounds. Fibroblasts presumably use cell surface receptors of the integrin family during migration into a wound from the adjacent uninjured tissue and for the subsequent matrix repairs. We have investigated the possible roles of platelet-derived growth factor and inflammatory cytokines in the regulation of integrin expression on wound fibroblasts using a porcine cutaneous wound model and cultured human cells. Tissue specimens collected from 4-day pig wounds were stained with antibodies specific for the alpha 1 and alpha 5 integrin subunits. Staining for alpha 1 was markedly decreased on fibroblasts adjacent to the wound and in the granulation tissue, while staining for alpha 5 was clearly enhanced in both locations. Normal adult human dermal fibroblasts in culture express the integrins alpha 1 beta 1, a collagen receptor, and alpha 5 beta 1 a fibronectin receptor. Quantitative flow cytometry was used to measure cell surface integrin expression after treatment with platelet-derived growth factor (PDGF)-AA, PDGF-AB, or PDGF BB. Each isoform of PDGF produced a significant decrease in the level of alpha 1 present on the cell surface and an increase in the level of alpha 5. Furthermore, PDGF-BB produced a corresponding decrease in alpha 1 mRNA and an increase in alpha 5 mRNA. In contrast, treatment with three inflammatory cytokines, IL-1 beta, TNF-alpha, and IFN-gamma, produced clear increases in the levels of alpha 1 and alpha 5 present on the cell surface. Our observations suggest that the differential effects of PDGF and inflammatory cytokines may be part of the mechanism regulating the expression of alpha 1 and alpha 5 integrins by dermal fibroblasts during wound repair.

Animals↗
PubMed1996

Clinical manifestations of infection with human immunodeficiency virus among adolescents in Louisiana.

PURPOSE: There is limited information regarding the clinical manifestations of human immunodeficiency virus (HIV) infection among adolescents. To better define the clinical presentation and course of HIV disease in this population, a retrospective review of all HIV-infected persons age 13-21 years at entry into a public, inner-city HIV outpatient clinic in New Orleans, Louisiana, was undertaken. RESULTS: A total of 141 adolescents were included in this study. The cohort was predominantly female (65%) and African-American (83%), and acquired HIV infection through sexual contact (89%). As many as 75% of the females and 48% of the males were diagnosed with at least one sexually transmitted disease (STD), respectively, and young African-American females with a CD4 cell count > 500/mm3 were at highest risk. The proportions of female adolescents having a gravida > or = 1 and 2 were 82% and 20%, respectively. A total of 55% of females were diagnosed with squamous intraepithelial lesions (SIL) at least once. Similar to adults, the majority of opportunistic processes occurred in adolescents with a CD4 cell count < 200/mm3. Known HIV-related symptoms (oral hairy leukoplakia, thrush, and zoster) were significantly predictive (p < .0001) for HIV disease progression. CONCLUSIONS: Although HIV-related symptoms and infections do not appear to be unique in the adolescent population, it is clear that STDs and pregnancies are common among female adolescents. Our results emphasize the need for aggressive STD and contraceptive protection counseling, and surveillance screening for STDs and cervical dysplasia.

AIDS-Related Opportunistic Infections↗
PubMed1996

Interpretation of calcifications in screen/film, digitized, and wavelet-enhanced monitor-displayed mammograms: a receiver operating characteristic study.

RATIONALE AND OBJECTIVES: The acceptance of filmless digital mammography is currently limited by digitization and display drawbacks, as well as bias toward hard-copy interpretation. In the current study, we evaluated a wavelet-based image enhancement method for the filmless interpretation of breast calcifications. METHODS: A set of 100 mammograms (58 with calcification clusters) was digitized at 105 microns and 4,096 gray levels per pixel and was processed with nonlinear filters and wavelets. Standard receiver operating characteristic analysis was performed by four radiologists, who independently read the films, the unprocessed digital images, and unprocessed and wavelet-enhanced digital images presented simultaneously. RESULTS: Statistical differences were observed between screen/film and unprocessed digitized mammography displayed on monitors. Differences were not significant when wavelet enhancement was included in the monitor display. Interobserver variation in the digitized reading was greater than in film reading, but the wavelet enhancement reduced the difference. CONCLUSION: Wavelet-enhanced digital mammograms may assist radiologists in diagnosing calcifications directly from computer monitors and may compensate for current technologic limitations. A study with a larger data-base is needed before this method is accepted for clinical use.

Breast Diseases↗
PubMed1996

Extracellular matrix alters PDGF regulation of fibroblast integrins.

Extracellular matrix (ECM) and growth factors are potent regulators of cell phenotype. These biological mediators of cellular responses are potentially interactive and as such could drive cells through progressive phenotypes to create new tissue as in morphogenesis and wound repair. In fact, ECM composition changes during tissue formation accompanied by alterations in cell growth and migration. How alterations in the ECM regulate cell activities is poorly defined. To address this question in wound repair, we cultured normal human dermal skin fibroblasts in relaxed collagen gels, fibronectin-rich cultures or stressed fibrin gels, and stressed collagen gels to model normal dermis, early wound provisional matrix, and late granulation tissue, respectively. Integrin subunits, alpha 2, alpha 3, and alpha 5, that define receptor specificity for collagen and provisional matrix, respectively, were measured at mRNA steady-state level before and after stimulation with platelet-derived growth factor-BB (PDGF-BB), a potent mitogen and chemoattractant for fibroblasts. Fibronectin-rich cultures and fibrin gels supported PDGF-BB induction of alpha 3 and alpha 5 mRNA. In contrast, both stressed and relaxed collagen attenuated these responses while promoting maximal alpha 2 mRNA expression. Posttranscriptional regulation was an important mechanism in this differential response. Together PDGF-BB and collagen gels promoted alpha 2, but not alpha 3 and alpha 5, mRNA stability. Conversely, when fibroblasts were in fibronectin-rich cultures, PDGF-BB promoted alpha 3 and alpha 5, but not alpha 2, mRNA stability. We suggest that ECM alterations during wound healing or any new tissue formation cause cells to respond differently to repeated growth factor stimuli. An ordered progression of cell phenotypes results, ultimately consummating tissue repair or morphogenesis.

Animals↗
PubMed1996

CD44 and hyaluronan-dependent rolling interactions of lymphocytes on tonsillar stroma.

Little is known about how lymphocytes migrate within secondary lymphoid organs. Stromal cells and their associated reticular fibers form a network of fibers that radiate from high endothelial venules to all areas of the lymph node and may provide a scaffold for lymphocyte migration. We studied interactions of lymphocytes with cultured human tonsillar stromal cells and their extracellular matrix using shear stress to distinguish transient interactions from firm adhesion. Tonsillar lymphocytes and SKW3 T lymphoma cells tethered and rolled on monolayers of cultured tonsillar stromal cells and their matrix. A significant proportion of these rolling interactions were independent of divalent cations and were mediated by CD44 binding to hyaluronan, as shown by inhibition with mAb to CD44, soluble hyaluronan, as hyaluronidase treatment of the substrate, and O-glycoprotease treatment of the rolling cells. O-glycoprotease treatment of the substrate also blocked binding completely to stromal matrix and partially to stromal monolayers. SKW3 cells tethered and rolled on plastic-immobilized hyaluronan, confirming the specificity of this interaction. By contrast, monolayers of resting or stimulated human umbilical vein endothelial cells failed to support CD44- and hyaluronan-dependent rolling. SKW3 cells added under flow conditions to frozen sections of human tonsil bound and rolled along reticular fibers in the presence of EDTA. Rolling was blocked by either CD44 mAb or hyaluronan. We propose that lymphocytes migrating through secondary lymphoid organs may use CD44 to bind to hyaluronan immobilized on stromal cells and reticular fibers.

Antigens, Surface↗
PubMed1996

PDGF induction of alpha 2 integrin gene expression is mediated by protein kinase C-zeta.

Platelet-derived growth factor (PDGF) stimulates fibroblasts to move over collagen and contract three-dimensional collagen gels, processes important in wound repair and fibrocontractive diseases. These processes depend on alpha 2 beta 1 integrin ligation of collagen and PDGF induces the expression of this integrin. Several lines of evidence presented here suggest that PKC-zeta plays a role in alpha 2 integrin gene expression. The induction was blocked by chemical inhibitors for protein tyrosine kinases (PTK), genistein, and protein kinase C (PKC), chelerythrine, and bisindolylmaleimide GF 109203X. Cells depleted of phorbol 12-myristate 13-acetate (PMA)-inducible PKCs by chronic treatment with PMA still demonstrated an alpha 2 response to PDGF indicating that a non-PMA-sensitive PKC isoform was required. PDGF induced kinase activity in PKC-zeta immunoprecipitates. Antisense oligonucleotides complementary to 5' end of PKC-zeta mRNA sequences blocked the PDGF-induced increase of alpha 2 mRNA levels up to 70%, indicating PKC-zeta, a non-PMA-sensitive PKC isoform, is a component of the PDGF stimulatory pathway for alpha 2 mRNA synthesis. A 961-base pair (bp) upstream region of alpha 2 gene/CAT construct transfected into human dermal fibroblasts was positively regulated by PDGF as judged by CAT enzymatic levels. Both PTK and PKC inhibitors blocked PDGF-stimulation of the alpha 2 promoter fragment/CAT construct, indicating that the phosphorylation requirement occurred at alpha 2 promoter-directed transcription level. Therefore, we propose that PDGF-stimulatory pathway of alpha 2 integrin gene expression involves multiple cellular protein kinases, one of which is PKC-zeta.

Adult↗
PubMed1996

Keratinocytes in human wounds express alpha v beta 6 integrin.

Cell adhesion receptors of the integrin family play a major role during re-epithelialization of human wounds. We have previously documented that the expression of alpha v family integrins is induced in keratinocytes of mucosal wounds [1]. In the present investigation, we extended these studies to determine whether alpha v beta 6 integrin is expressed during wound healing in humans. Mucosal and epidermal wound sections from 1- to 7-day-old wounds were used for immunolocalization of integrins and their putative ligands. In addition, freshly isolated epidermal keratinocytes were used to study integrin expression in vitro. Expression of alpha v beta 6 integrin appeared relatively late during mucosal and dermal wound healing. Maximal expression was seen in 7-day-old wounds in which epithelial sheets had fused and granulation tissue was present. Fibronectin and tenascin, both possible ligands for alpha v beta 6 integrin, were found concentrated underneath the basal epithelial cells expressing this receptor, and the maximal expression of tenascin coincided with that of alpha v beta 6 integrin. Freshly isolated epidermal keratinocytes did not stain for alpha v beta 6 integrin but began to express this integrin after subculturing. Our results suggest that the expression of alpha v beta 6 integrin, a putative binding integrin for fibronectin and tenascin, is induced in keratinocytes when epithelial sheets fuse during wound healing.

Antigens, Neoplasm↗
PubMed1996

Studies in vitro on the role of alpha v and beta 1 integrins in the adhesion of human dermal fibroblasts to provisional matrix proteins fibronectin, vitronectin, and fibrinogen.

Fibroblasts that migrate into a wound during the early stages of repair use cell surface integrins to interact with extracellular molecules as they move away from the interstitial matrix of normal tissue and into the provisional matrix of the wound. Therefore, to understand a critical phase of wound healing, it is necessary to understand the details of integrin involvement. Normal adult human dermal fibroblasts in culture express many receptors for the provisional matrix proteins fibronectin, vitronectin, and fibrinogen, including the integrins alpha 3 beta 1, alpha 4 beta 1, alpha 5 beta 1, alpha v beta 1, alpha v beta 3, and alpha v beta 5. We used quantitative flow cytometry to estimate the relative numbers of these receptors and immunoprecipitation to confirm the expression of alpha v beta 1. Adult human dermal fibroblasts primarily use beta 1 integrins, alpha 4 beta 1, alpha 5 beta 1, and possibly alpha v beta 1, for attachment to fibronectin. alpha v beta 3 and perhaps other integrins containing the alpha v subunit serve fibroblasts as secondary or auxiliary receptors for fibronectin. In contrast, these cells use alpha v integrins but probably not beta 1 integrins for attachment to vitronectin. alpha v beta 3 and alpha v beta 5 apparently act in concert to mediate attachment to vitronectin, and these two integrins may perform different functions during wound repair. Fibroblast adhesion to certain preparations of fibrinogen occurs, at least partially, through the small amount of fibronectin present in the preparations. Fibroblast attachment to fibrinogen purified free of fibronectin also occurs, and that was demonstrated with a sensitive new assay called electrical cell-substrate impedance sensing. Fibroblast attachment to pure fibrinogen can be inhibited by RGD peptide, suggesting that integrins are involved.

Adult↗
PubMed1996

Adrenal suppression with inhaled budesonide and fluticasone propionate given by large volume spacer to asthmatic children.

BACKGROUND: The aim of this study was to compare the systemic bioactivity of inhaled budesonide (B) and fluticasone propionate (F), each given by large volume spacer, on a microgram equivalent basis in asthmatic children. METHODS: Ten stable asthmatic children of mean age 11 years and forced expiratory volume in one second (FEV1) 81.6% predicted, who were receiving treatment with < or = 400 micrograms/day of inhaled corticosteroid, were studied in a placebo controlled single blind (investigator blind) randomised crossover design comparing single doses of inhaled budesonide and fluticasone propionate 400 micrograms, 800 micrograms, and 1250 micrograms. Doses were given at 20.00 hours with mouth rinsing and an overnight 12 hour urine sample was collected for estimation of free cortisol and creatinine excretion. RESULTS: The results of overnight 12 hour urinary cortisol output (nmol/12 hours) showed suppression with all doses of fluticasone propionate (as geometric means): F400 micrograms (11.99), F800 micrograms (6.49), F1250 micrograms (7.00) compared with placebo (24.43), whereas budesonide caused no suppression at any dose. A comparison of the drugs showed that there were differences at 800 micrograms and 1250 micrograms levels for urinary cortisol: B800 micrograms versus F800 micrograms (2.65-fold, 95% CI 1.26 to 5.58), B1250 micrograms versus F1250 micrograms (2.94-fold, 95% CI 1.67 to 5.15). The results for the cortisol/creatinine ratio were similar to that of urinary cortisol, with fluticasone causing suppression at all doses and with differences between the drugs at 800 micrograms and 1250 micrograms. CONCLUSIONS: Single doses of inhaled fluticasone produce greater systemic bioactivity than budesonide when given by large volume spacer on a microgram equivalent basis in asthmatic children. The systemic bioactivity of fluticasone, like budesonide, is due mainly to lung bioavailability.

Administration, Inhalation↗
PubMed1996

Contraceptive and sexually transmitted diseases protection among adult and adolescent women infected with human immunodeficiency virus.

The goal of this study was to describe contraceptive and sexually transmitted disease (STD) prevention practices in human immunodeficiency virus (HIV) infected adult and adolescent women, and to determine if hormonal contraception has unique adverse effects in this population. A retrospective review of 241 HIV-infected women age 15-45 years was performed. The associations between contraceptive methods and selected characteristics were determined by chi-square methods and logistic regression modelling. African American race (RR 8.6, 95% CI 3.3, 22.5), injection drug use history (RR 5.0, 95% CI 2.2, 11.2), age < 25 years (RR 1.9, 95% CI 1.1, 3.5) and progestin only contraceptive use (RR 3.0, 95% CI 1.4, 6.6) were significantly associated with incident STDs. The only potential adverse effect of hormonal contraception noted in this retrospective study was the significant association between STDs and progestin-only contraception. Prospective studies to better delineate the true association between STDs and progestin-only agents after adjustment for behaviour patterns are warranted.

Adolescent↗