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Biomedical subjects

C Barnes

Publications and source records attributed to C Barnes.

At least 19 recordsLinked to original sources

Developing indicators for the Medicare Quality Indicator System (MQIS): challenges and lessons learned.

BACKGROUND: The Medicare Quality Indicator System (MQIS), initiated in 1993, was intended to form the basis for the Health Care Financing Administration's (HCFA's; Washington, DC) hospital-based quality measurement system. The MEDSTAT Group (Washington, DC) established quality indicator development methods for five clinical conditions, including early-stage breast cancer, diabetes mellitus, and upper gastrointestinal and lower intestinal bleeding. DEVELOPMENT OF QUALITY INDICATORS: Five national expert panels were convened to identify scientifically based hospital processes of care related to positive patient outcomes, as described in research studies and/or broadly accepted by the medical and allied health professions as indicators of high-quality care. LESSONS AND CHALLENGES: One of the most important lessons learned was the need for a narrow clinical focus for each quality indicator module. If the focus was adequately narrowed, all other tasks could be accomplished more efficiently and less ambiguously. Also, selection of the expert panel chair should occur early because of the chair's pivotal contributions to the clinical focus selection, literature review, and development of draft quality indicators. Perhaps the most starting finding and biggest challenge was the paucity of scientifically sound literature to support the clinical topics; except for the breast cancer studies, most of the available literature was categorized as flawed to some degree. A critical challenge for development of quality indicators is to translate what has been learned from the best scientific efficacy studies into indicators of effective rather than efficacious care. CONCLUSIONS: In choosing quality indicators, disease incidence and potential for quality improvement are important parameters. Although the former is relatively easy to define, the latter is not.

Breast Neoplasms

Plasminogen activator inhibitor type 2 in breast cancer.

The serine protease urokinase plasminogen activator (uPA) is causally involved in cancer invasion and metastasis. Activity of this protease in vivo is controlled principally by two inhibitors, one of which is plasminogen activator inhibitor type 2 (PAI-2). In this study, we show that PAI-2 levels were significantly higher in primary breast carcinomas (n = 152) than benign breast tumours (n = 18). In the primary cancers, PAI-2 levels correlated weakly but significantly with those of uPA and PAI-1, but not with tissue type plasminogen activator (tPA) or uPA receptor (uPAR) levels. Using Northern blotting, mRNA for PAI-2 was found in 28.6% of 49 primary breast cancers. In contrast to findings at the protein level, PAI-2 mRNA levels failed to correlate with those for uPA or PAI-1. After immunocytochemistry with primary cancers, PAI-2 was detected predominantly in the malignant cells of primary carcinomas but was also present in stromal cells. Using the median value as a cut-off point, PAI-2 showed no significant relationship with either disease-free interval or overall survival. However, using an optimum cut-off value, patients with low levels of PAI-2 had a worse outcome than those with a high level. We conclude that, unlike PAI-1, high levels of PAI-2 may be a favourable prognostic marker in breast cancer.

Age Factors

The role and practice of the genetic nurse: report of the AGNC Working Party.

The role of the genetic nurse has evolved historically with the emergence of clinical genetics in the field of health care. During 1994, a Practice Working Party was convened by the Genetic Nurses and Social Workers Association in response to discussion about the role of the nurse within and between regional genetics centres. The Working Party conducted a study of the current nursing practice and attitudes of nurses and clinicians to the nursing role, as a basis for future discussion and planning for educational needs. This paper describes the role of the genetic nurse within the United Kingdom and offers suggestions for assessment of competency. Strong themes emerging from respondents' comments include the need and desire for multi-professional team work, and it is apparent that most respondents felt the families' needs would best be served by a skilful combination of medical and nursing input, rather than adherence to traditional roles.

Genetic Counseling

Narp, a novel member of the pentraxin family, promotes neurite outgrowth and is dynamically regulated by neuronal activity.

Stimulus-linked RNA and protein synthesis is required for establishment of long-term neuroplasticity. To identify molecular mechanisms underlying long-term neuroplasticity, we have used differential cDNA techniques to clone a novel immediate-early gene (IEG) that is rapidly induced in neurons of the hippocampus and cortex by physiological synaptic activity. Analysis of the deduced amino acid sequence indicates homology to members of the pentraxin family of secreted lectins that include C-reactive protein and serum amyloid P component. Regions of homology include an 8 amino acid "pentraxin signature" sequence and a characteristic pentraxin calcium-binding domain. We have termed this gene and the encoded protein Narp (from neuronal activity-regulated pentraxin). Biochemical analyses confirm the presence of a functional signal sequence, and Narp is secreted by transfected COS-1 cells in culture. Additionally, Narp binds to agar matrix in a calcium-dependent manner consistent with the lectin properties of the pentraxin family. When cocultured with Narp-secreting COS-1 cells, neurons of cortical explants exhibit enhanced growth of neuronal dendritic processes. Neurite outgrowth-promoting activity is also observed using partially purified Narp and can be specifically immunodepleted, demonstrating that Narp is the active principle. Narp is fully active at a concentration of approximately 40 ng/ml, indicating a potency similar to known peptide growth factors. Because Narp is rapidly regulated by neuronal activity, its lectin and growth-promoting activities are likely to play role in the modification of cellular properties that underlie long-term plasticity.

Amino Acid Sequence

Early clinical experience with the Multi-Link coronary stent.

The Multi-Link coronary stent (Advanced Cardiovascular Systems, Santa Clara, CA) is a balloon expandable stent carved from a stainless steel cylinder and is composed of 12 corrugated rings connected by multiple links. This design gives the stent great flexibility and conformity as well as radial strength. For the 3 month period from November 1995 to January 1996, all patients undergoing stent implantation in our institution were treated with this device, except for vessels smaller than 2.7 mm or larger than 3.7 mm in diameter, left main disease, or those who could not tolerate anticoagulation therapy. Forty patients, with a total of 42 arteries or 44 lesions, were treated with 56 stents, or 1.33 stents per artery. Clinical presentation included stable angina in 13 (32.5%), unstable angina in 24 (60%), acute myocardial infarction in 2 (5%), of whom 1 was in cardiogenic shock, and atypical symptoms with an abnormal thallium stress test in 1 (2.5%). According to the American College of Cardiology/ American Heart Association (ACC/AHA) classification, 8 lesions (18%) were type A, 14 (32%) type B1, 11 (25%) type B2, and 11 (25%) type C. Forty-three lesions (97.7%) were de novo and 1 (2.3%) restenotic. Stent delivery was successful in all patients. Complications included 1 balloon rupture at 7 atm but without sequelae, and 2 patients in whom the coronary guide wire became kinked and locked inside the catheter shaft of the stent delivery system but stent delivery was eventually successful. Mean diameter stenosis was reduced from 76 +/- 13% presenting to 2 +/- 9% poststenting and minimal lumen diameter increased from 0.87 +/- 0.38 to 2.82 +/- 0.34 mm. There were no acute-subacute stent thromboses, bleeding/vascular complications, or major cardiac events such as myocardial infarction, coronary artery bypass surgery, or death during a follow-up period of 2-5 months (mean 3.6 months). In conclusion, our early clinical experience with the Multi-Link stent is very encouraging, with a very high rate of successful delivery and minimal complications.

Adult

Male/female comparison of morphine effect on food intake--relation to anorexia nervosa.

We have proposed that endogenous opioids play a critical role in the etiology of anorexia nervosa by mediating an auto-addiction. A biological predisposition may result from an atypical endogenous opioid system. Morphine activation of the system increases food intake in most species, including normal humans and rats, but decreases food intake in mice. The atypical opioid system in mice may be representative of that in anorexia nervosa patients, causing the biological predisposition. Anorexia nervosa is 10 times more prevalent in females than males. In the context of this auto-addiction opioid model, it was interesting to determine if the effects of morphine on food intake were markedly different between the two sexes. Full dose-response curves were done of the effects of morphine on food intake in males and females in both rats and mice, representing the typical and atypical responses, respectively. Differences between the sexes were not found to explain the marked prevalence of anorexia nervosa for females. The marked preference is probably at some other step.

Animals

Evaluation of four bioaerosol samplers in the outdoor environment.

INTRODUCTION: A comparative evaluation of four air samplers was performed using bioaerosol collection in the outdoor environment. METHODS: Test samplers used included a Rotorod, a Kramer-Collins suction trap, an all-glass impinger (AGI-30), and a high-volume cyclonic liquid impinger (SpinCon). All samples were analyzed microscopically for spores and pollen. The two collectors providing a liquid sample (AGI-30 and SpinCon) also were analyzed for specific allergen content by enzyme-linked immunoassay. RESULTS: The SpinCon collected a larger number of spores than the other devices. The number of spores collected by this unit per volume of air sampled was comparable to the AGI-30. The Rotorod and Kramer-Collins collected a lower number of spores per unit of air but collected a larger number of pollen grains per volume sampled. Alternaria allergens Alt a I and GP70 were collected by both liquid impingers; however, the SpinCon collected more Alt a I and the AGI-30 collected more GP70. CONCLUSIONS: The SpinCon is a device that is capable of efficiently sampling a high volume of air and concentrating it in a form that can be analyzed for the presence of spores and fungal allergens. It is less useful for collecting intact pollen grains. Pollen allergen quantitation has not yet been performed on the SpinCon effluent.

Aerosols

Multidrug resistance in ocular melanoma.

AIMS/BACKGROUND: Metastatic disease in patients with ocular melanoma is resistant to chemotherapy. One of the main mechanisms of modulating multidrug resistance is the expression of the multidrug resistance gene 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of this study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or enucleation. METHODS: Twelve recent ocular melanomas were received fresh, snap frozen and cryostat sections of tumour were analysed for expression of MDR1 by immunohistochemistry using a well characterised monoclonal antibody to MDR1. Tumour explants were established in short term tissue culture from four tumours and cell blocks were examined by immunohistochemistry. RESULTS: MDR1 expression was present in five of 12 ocular melanomas. Upregulation of protein expression was found in four cell lines established in short term culture from tumour explants. A recurrent tumour, initially treated by local excision and radioactive plaque, showed overexpression of MDR1 mRNA. CONCLUSIONS: These results suggest that significant level of MDR1 may be intrinsically present in ocular melanomas before exposure to drugs involved in multidrug resistance, and indicate the possible importance of MDR1 in modulating chemoresistance in ocular melanoma. Chemosensitisation may be of potential value in planning adjuvant chemotherapy for patients with metastatic disease.

ATP Binding Cassette Transporter, Subfamily B, Mem

Validation of the International Study Group criteria for Behçet's disease.

The International Study Group (ISG) for Behçet's disease proposed new international criteria for Behçet's disease in 1990. The aim of this study was to assess the performance of these criteria in new patient groups. Sensitivity was determined in 300 patients with Behçet's disease from seven countries, and specificity in a group of 62 control patients from China. The ISG criteria performed well compared to the other criteria sets in current use.

Behcet Syndrome

Genital tract function in men with Noonan syndrome.

In order to study the pattern of male fertility in Noonan syndrome, and its potential implications for genetic counselling, the genital tract function was studied in 11 adult males with Noonan syndrome. Bilateral testicular maldescent occurred in six. The mean testicular volume was 21 (SD 4) ml. The stretched flaccid penile length was 11.4 (SD 1.2) cm. Puberty was delayed in three. Four of the men had fathered children. The LH and testosterone levels were essentially normal in all men, while the FSH levels were grossly raised in the group with testicular maldescent, with the exception of one man. Semen samples were obtained from five men, and azoospermia or oligozoospermia was present in four of them. Sexual function is not affected in men with Noonan syndrome, but the onset of sexual activity was delayed in men with late onset of puberty. Bilateral testicular maldescent appears to be the main factor contributing to impairment of fertility in men with Noonan syndrome.

Adolescent

Identification and localization of the GM1 ganglioside in the cochlea using thin-layer chromatography and cholera toxin.

Using high-performance thin-layer chromatography, we identified GM1, GM3, GD3, GD1a, GT1b, GQ1b, and other gangliosides in chinchilla cochlea and cerebellum. GM1 was also identified on chromatograms with the B-subunit of cholera toxin (BCT). BCT was also used to determine the distribution of GM1 in fixed and unfixed tissues from cochlea, cerebellum, and sciatic nerve. Positive control tissues showed expected labeling of GM1 by BCT. Negative controls showed expected suppression of BCT binding to GM1 after GM1 extraction and GM1 absorption. In the cochlea, GM1 appeared abundant in plasma membranes of most epithelial cells lining the endolymphatic surface of the scala media, including the interdental, inner supporting, pillar, Deiters, Hensen, Claudius, Boettcher, spiral prominence, and external sulcus. GM1 appeared less abundant in cells of the stria vascularis, Reissner's membrane, and in nerve fibers. In hair cells, the stereocilia appeared to contain GM1; however, the endolymphatic surface of the cuticular plate and the body of the outer hair cells appeared to contain little GM1. In addition, the tectorial membrane, connective tissue of the spiral limbus, and amorphous layer of the basilar membrane also appeared to contain little GM1. Enzymatic degradation of glycoproteins and transformation of polysialogangliosides to GM1 increased the reactivity of BCT to cochlear GM1. This further supported the presence of GM1 and other gangliosides in the cochlea. Although the functional significance of GM1 and other gangliosides in the cochlea is not yet known, they are likely to play important roles in membrane function.

Animals

Premedication reduces the incidence of systemic reactions during inhalant rush immunotherapy with mixtures of allergenic extracts.

BACKGROUND: Rush immunotherapy, while having many potential benefits, is associated with an increased incidence of systemic reactions. OBJECTIVE: To determine whether pretreatment with medications reduces the rate of systemic reactions during rush immunotherapy and to identify predictors of such reactions if possible. METHODS: We conducted a double-blind, placebo-controlled study of 22 allergic children ages 6 to 18 years who received rush immunotherapy. Active treatment consisted of a combination of H1 and H2 histamine antagonists and a corticosteroid in gelatin capsules given prior to administration of rush immunotherapy whereas placebo patients received lactose. Rush immunotherapy consisted of eight injections of increasing doses of a mixture of allergens to which each patient was skin-reactive over 1 1/2 days. Serial skin tests and peak expiratory flow rate measurements were performed during the procedure. Following the initial series of injections, patients were followed for 8 weeks and had blood drawn at 2-week intervals for measurements of specific IgG and IgE. RESULTS: Systemic reactions were observed in 3 (27%) active and 8 (73%) placebo patients (Fisher's exact test: P = .047). The mean time for systemic reactions was 63 minutes after a previous injection. The most common dose causing a systemic reaction was 0.3 mL of 1:1000 (wt/vol). The best predictors of development of a systemic reaction were degrees of skin sensitivity to the extract before and after premedication. Local reactions were not associated with subsequent systemic reactions. Specific IgG rose by 2 weeks while specific IgE did not change significantly during the 8-week follow-up period. Pretreatment did not change the number of systemic reactions seen with subsequent injections. CONCLUSIONS: Premedication significantly reduces the incidence of systemic reactions during rush immunotherapy and is therefore recommended. Degree of skin sensitivity to the injected extract may eventually prove to be a clinically useful predictor for the development of systemic reactions.

Adolescent

Apolipoprotein B mRNA editing in vitro is a zinc-dependent process.

Apolipoprotein B mRNA editing involves the conversion of a cytidine at nucleotide 6666 to a uridine, thereby creating a translational stop codon from a glutamine codon. Recent evidence suggest that a cytidine deaminase is responsible for catalyzing the C to U conversion. All known nucleotide deaminases require zinc as part of their catalytic domain. Utilizing the selective chelator for zinc, 1,10-penanthroline, we demonstrate that in vitro editing activity in rat liver extracts is zinc dependent. These data, taken together with recent reports, strongly support a role for a cytidine deaminase and nucleotide conversion as the catalytic mechanism for apoB mRNA editing.

Animals

Grief and mid-trimester fetal loss.

Fetal loss through miscarriage or termination of pregnancy for genetic reasons often provokes the grief of bereavement. This is not fully understood, and the extent of the distress is often underestimated by professionals and family alike. We have examined elements of the normal bereavement process and have found that they may occur in specific and accentuated forms in mid-trimester fetal loss. We discuss our findings in the light of the attachment theory--a psychodynamic model for understanding grief reactions.

Abortion, Therapeutic

Selection of representative Alternaria strain groups on the basis of morphology, enzyme profile, and allergen content.

In an attempt to identify representative strains, 12 strains of Alternaria alternata were contributed by four different research groups. Each was grown on two types of solid media and characterized with descriptions of pigmentation and morphology. Enzyme profiles were determined on both the cellular antigen and the culture filtrate material with use of a commercial kit. Concentrations of a previously described Alt a 1 and a 70 kd allergen, GP70, were measured by a two-antibody "sandwich" ELISA. Allergenic proteins were visualized by IgE immunoblots. With use of these criteria, four separate strains were identified that might serve as representative of Alternaria for further research.

Alkaline Phosphatase

The effect of time and extraction buffers on residual protein and allergen content of extracts derived from four strains of Alternaria.

BACKGROUND: A series of studies was performed to identify optimal elution conditions for production of desired Alternaria allergens with simultaneous reduction of undesired ones. METHODS: Proteins and allergens from four strains of Alternaria extracted for differing time intervals and in different buffers were analyzed by one- and two-dimensional electrophoresis, as well as by immunoglobulin E enzyme-linked immunosorbent assay inhibition and immunoblotting. RESULTS: The amount of protein and carbohydrate released varied with each time interval but was consistent between buffers. Extracts from longer time intervals tended to contain more carbohydrate. Electrophoresis of the four strains demonstrated many similar proteins; however, the concentrations of these proteins showed considerable interstrain difference. Comparison of extraction times for single strains by immunoblotting showed that certain allergens are preferentially released during specific time intervals. Some allergens were seen to be most prevalent in a 24-hour extract, whereas others were most prevalent in a 1-hour extract. Two-dimensional electrophoresis resolved bands into discrete spots. The major shared elements of the four strains could be easily identified. The appearance and disappearance of individual protein elements with time was seen. CONCLUSIONS: Elution conditions have a significant impact on quantities of specific glycoproteins contained in extracts of Alternaria and must be controlled and optimized when such extracts are produced for allergen purification.

Allergens

A double monoclonal antibody assay for the Alternaria allergen GP70.

A double monoclonal antibody-based assay for the 70-kD Alternaria allergen GP70 is described. The assay is sensitive to GP70 concentrations as low as 0.2 microgram/mL and is highly specific for this allergen. The glycoprotein detected by this assay is shown to bind to human IgE from Alternaria-sensitive patients, proving that it is an allergen. Two of three commercial Alternaria preparations tested contained no detectable GP70. Several related fungi were shown to contain detectable concentrations of GP70, but the most abundant source was a commercial preparation of house dust. Further measurement of GP70 in biologic materials should increase our knowledge of the distribution and importance of this Alternaria allergen in the environment and in the development of allergic diseases.

Allergens