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R Harris

Publications and source records attributed to R Harris.

At least 55 records · Page 3Linked to original sources
PubMed2000

Prenatal genotyping for the RhD blood group antigen: considerations in developing an accurate test.

Experience performing prenatal genotyping for RHD has shown that consideration must be given to developing a molecular test capable of detecting recombination/gene conversion events involving the RHD and RHCE genes that can lead to erroneous results. Out of 50 prenatal RHD tests performed over the past 5 years, four samples were encountered that gave false-positive results. In only one of the tests, incorrect results were issued to the physician. In the other three instances, the erroneous nature of the test results was revealed through the analysis of multiple regions of the RHD gene and, more importantly, because the mother, and sometimes the father, were tested in parallel with the fetus. In an extension of the observations obtained from the prenatal testing program, a large panel of RhD-negative blood donors were subjected to molecular analysis of the RHD gene. Of 1,183 donors screened, 187 were found to phenotype as RhD negative. Of the 187 donors confirmed RhD negative serologically, 22 (11.8%) were found to retain remnants of the RHD gene that, depending upon the characteristics of the molecular assay performed, could lead to a false-positive result in a genotyping assay. On the basis of the experience presented here, it is recommended that any molecular RHD assay include an analysis of multiple areas of the RHD gene so as to allow for the detection of recombination/gene conversion events between the RHD and RHCE genes. Moreover, it is strongly recommended that the mother (at a minimum) and father be subjected to molecular analysis simultaneously with the fetus to confirm that the known phenotypes of the parent(s) are consistent with their respective genotypes.

Exons↗
PubMed2000

Does the absorbable fibrin adhesive bandage facilitate partial nephrectomy?

PURPOSE: To evaluate the ability of the absorbable fibrin adhesive bandage (AFAB), a prototype product comprising lyophilized fibrinogen and thrombin on a VicrylTM mesh backing, to seal the collecting system and control bleeding after partial nephrectomy. MATERIALS AND METHODS: Growing female pigs (n = 18) underwent left nephrectomy and a 40% (by length) right lower pole partial nephrectomy. One of three treatments was immediately applied: Conventional-closure of the collecting system, ligation of visible segmental vessels, application of SurgicelTM with bolstering sutures to the renal capsule; AFAB-application of up to two 4 x 4-inch AFABs held under pressure for 60 seconds; Placebo-application of a hemostatically inert VicrylTM bandage, visually identical to the AFAB. Blood loss and ischemic and total operative times were recorded, and abdominal computerized tomography (CT) was performed on postoperative day 6. Animals were sacrificed at 6 weeks to evaluate the remaining renal mass histologically. RESULTS: Compared with conventional therapy, use of the AFAB resulted in significantly less bleeding (13 versus 68 ml., p <0.001) and lower operative (7.2 versus 16.3 minutes, p <0.001) and ischemic times (3.4 versus 7.8 minutes, p <0.001). Estimated blood loss in the placebo bandage group was dramatically higher (357 ml., p <0.001). Postoperative CT and histological sectioning suggested that the AFAB produces a stable, durable clot and that healing is at least as successful as with conventional treatment. CONCLUSION: Use of the AFAB facilitated performance of partial nephrectomy by reducing blood loss and ischemic and total operative times. The AFAB appears equivalent to conventional surgery in its ability to seal the collecting system.

Absorbable Implants↗
PubMed2000

Quantification of human immunodeficiency virus type 1 p24 antigen and antibody rivals human immunodeficiency virus type 1 RNA and CD4+ enumeration for prognosis. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

BACKGROUND: The sensitivity, specificity and positive predictive value of baseline serum concentrations of HIV-1 immune complex-dissociated (ICD) p24 antigen for predicting disease progression and mortality were assessed and compared with results obtained for HIV-1 ICD p24 antigen with HIV-1 p24 antibody and for HIV-1 RNA with CD4+ lymphocyte percent. METHODS: Data from HIV-infected children enrolled in a North American clinical trial (National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial) were analyzed. Disease progression was defined as growth failure, CD4+ lymphocyte percent decline to <15% after study entry or development of an AIDS-defining opportunistic infection. RESULTS: Baseline samples were available for ICD p24 antigen testing (median concentration, 319 pg/ml; range, <50 to 15,640) in 240 children. The combination of detectable ICD p24 antigen and low p24 antibody was more sensitive but less specific than the combination of high HIV-1 RNA and low CD4+ lymphocyte percent in predicting disease progression and mortality. Using receiver operating characteristic curves, the specificity of ICD p24 antigen with p24 antibody for classifying children's disease progression or mortality was as great as, or greater than, HIV-1 RNA with CD4+ lymphocyte percent at points on the curve corresponding to higher sensitivity. CONCLUSIONS: The use of ICD p24 antigen with p24 antibody to identify children at high risk of disease progression or mortality could be a viable alternative to the more expensive and technically difficult HIV-1 RNA and CD4+ lymphocyte assays in resource-poor settings, including developing countries where the majority of children with HIV-1 infection reside.

CD4 Lymphocyte Count↗
PubMed2000

Disease management for diabetes mellitus: impact on hemoglobin A1c.

OBJECTIVE: To describe outcomes associated with a health maintenance organization (HMO)-sponsored disease management program for diabetes. STUDY DESIGN: Descriptive study that compared outcomes of patients with diabetes before and after entry into a disease management program. PATIENTS AND METHODS: The study was conducted in a mixed-model HMO with 275,000 members. The disease management program included a Steering Committee, clinical guidelines, primary care site-based diabetes education, coverage of glucose meters and strips, simplified outcomes reporting, and support of clinical leadership. Data were obtained for 5332 continuously enrolled patients who voluntarily entered the disease management program; 3291 patients (61.7%) received 3 months or more of follow-up, and 663 (12.4%) received 1 year or more of follow-up. The primary outcomes were change from baseline of mean hemoglobin A1c (HbA1c) and medication use after 3 months and 1 year of follow-up. RESULTS: The mean baseline HbA1c for all program participants was 8.51% (standard deviation [SD] = 1.86%). At 3 months of follow-up, the mean HbA1c value for 2794 of 3291 participants (84.0%) had decreased to 7.41% (SD = 1.33%; P = .0001). At 1 year of follow-up, the HbA1c value, available for 605 of 663 patients (91.3%), had decreased from a mean baseline value of 8.76% (SD = 1.87%) to 7.41% (SD = 1.24%; P = .0001). Among 663 patients with 1 year of follow-up, insulin use increased from 30.0% to 31.6%, and sulfonylurea use decreased from 40.7% to 33.8%. Troglitazone and metformin use increased from 7.7% and 23.8%, respectively, to 16.4% and 28.8%, respectively. CONCLUSIONS: Our data suggest that a multifaceted disease management program for diabetes can result in significant short-term improvements in glycemic control in the managed care setting. While the improvement in the HbA1c was accompanied by an increase in the use of insulin, troglitazone, and metformin, we suggest the influence of disease management on glycemic control among our participants was significant and should be considered in future studies in this area.

Adolescent↗
PubMed1999

Plant diversity and productivity experiments in european grasslands

At eight European field sites, the impact of loss of plant diversity on primary productivity was simulated by synthesizing grassland communities with different numbers of plant species. Results differed in detail at each location, but there was an overall log-linear reduction of average aboveground biomass with loss of species. For a given number of species, communities with fewer functional groups were less productive. These diversity effects occurred along with differences associated with species composition and geographic location. Niche complementarity and positive species interactions appear to play a role in generating diversity-productivity relationships within sites in addition to sampling from the species pool.

Journal Article↗
PubMed1999

Impediments to writing do-not-resuscitate orders.

BACKGROUND: Physicians are frequently unaware of their patients' desires regarding end-of-life care. Consequently, opportunities to implement do-not-resuscitate (DNR) orders are often missed. OBJECTIVE: To determine the reasons attending physicians do not write DNR orders when patients face increased mortality. METHODS: Over 4 months, the medical records of all inpatients on the General Medicine Service were reviewed at the time of discharge to identify patients with conditions predicting increased mortality. These cases were presented to a 5-member panel who decided if a DNR order was indicated. Reasons for missing DNR orders were discussed with the attending physicians. RESULTS: Of 613 consecutive admissions, the panel identified 149 patients (24%) for whom DNR orders were indicated. In 88 (59%) of these, DNR orders were absent. The lack of a DNR order did not correlate with age (P = .95), sex (P = .61), or race (P = .80). The attending physicians' explanations for not writing DNR orders in these 88 cases included the belief that the patient was not in imminent danger of death (n = 49 [56%]), the belief that the primary physician should discuss DNR issues (n = 43 [49%]), and the lack of an appropriate opportunity to discuss end-of-life issues (n = 38 [43%]). In 11 (12%) of the 88 cases, patients or their families did not accept the recommendation for a DNR order. No physicians expressed concerns regarding the morality of DNR orders, discomfort discussing end-of-life issues, or the threat of litigation as reasons for not writing a DNR order. CONCLUSIONS: Limitations in the extent and depth of the physician-patient relationship appear to be the most frequent impediments to writing DNR orders in our institution.

Adult↗
PubMed1999

The rational clinical examination. Does this patient have breast cancer? The screening clinical breast examination: should it be done? How?

CONTEXT: The clinical breast examination (CBE) is widely recommended and practiced as a tool for breast cancer screening; however, its effectiveness is dependent on its precision and accuracy. OBJECTIVE: To collect evidence on the effectiveness of CBE in screening for breast cancer and information on the best technique to use. DATA SOURCES: We searched the English-language literature using the MEDLINE database (1966-1997) and manual review of all reference lists, as well as contacting investigators of several published studies for clarifications and unpublished data. STUDY SELECTION AND DATA EXTRACTION: To study CBE effectiveness, we included all controlled trials and case-control studies in which CBE was at least part of the screening modality; for technique, we included both clinical studies and those that used silicone breast models. All 3 authors reviewed and agreed on the studies selected for inclusion in the pooled analyses. DATA SYNTHESIS: Randomized clinical trials demonstrated reduced breast cancer mortality rates among women screened by both CBE and mammography. Evidence of CBE's independent contribution was less direct; CBE alone detected between 3% and 45% of breast cancers found that screening mammography missed. The precision of CBE was difficult to determine because of the lack of consistent and standardized examination techniques. Studies on CBE precision reported fair agreement (kappa = 0.22-0.59). Pooling trial data, we estimated CBE sensitivity at 54% and specificity at 94%. The likelihood ratio of a positive CBE result is 10.6 (95% confidence interval [CI], 5.8-19.2), while the likelihood ratio of a negative test result is 0.47 (95% CI, 0.40-0.56). Longer duration of CBE and a higher number of specific techniques used were associated with greater accuracy. The preferred technique for CBE includes proper positioning of the patient, thoroughness of search, use of a vertical-strip search pattern, proper position and movement of the fingers, and a CBE duration of at least 3 minutes per breast. The value of inspection is unproved. Professional and lay examiners improved their sensitivity on silicone breast models after being taught this technique. CONCLUSIONS: Indirect evidence supports the effectiveness of CBE in screening for breast cancer. Although the screening clinical examination by itself does not rule out disease, the high specificity of certain abnormal findings greatly increases the probability of breast cancer.

Adult↗
PubMed1999

Peptides, antibodies, and FRET on beads in flow cytometry: A model system using fluoresceinated and biotinylated beta-endorphin.

BACKGROUND: Particulate surfaces such as beads are routinely used as platforms for molecular assembly for fundamental and practical applications in flow cytometry. Molecular assembly is transduced as the direct analysis of fluorescence, or as a result of fluorescence resonance energy transfer. Binding of fluorescent ligands to beads sometimes alters their emission yield relative to the unbound ligands. Characterizing the physical basis of factors that regulate the fluorescence yield of bound fluorophores (on beads) is a necessary step toward their rational use as mediators of numerous fluorescence based applications. METHODS: We have examined the binding between two biotinylated and fluoresceinated beta-endorphin peptides and commercial streptavidin beads using flow cytometric analysis. We have analyzed the assembly between a specific monoclonal antibody and an endorphin peptide in solution using resonance energy transfer and compared the results on beads in flow cytometry using steady-state and time-resolved fluorescence. RESULTS: We have defined conditions for binding biotinylated and fluoresceinated endorphin peptides to beads. These measurements suggest that the peptide structure can influence both the intensity of fluorescence and the mode of peptide binding on the bead surface. We have defined conditions for binding antibody to the bead using biotinylated protein A. We compared and contrasted the interactions between the fluoresceinated endorphin peptide and the rhodamine- labeled antibody. In solution we measure a K(d) of <38 nM by resonance energy transfer and on beads 22 nM. DISCUSSION: Some issues important to the modular assembly of a fluorescence resonance energy transfer (FRET) based sensing scheme have been resolved. The affinity of peptides used herein is a function of their solubility in water, and the emission intensity of the bound species depends on the separation distance between the fluorescein and the biotin moiety. This is due to the quasi-specific quenching interaction between the fluorescein and a proximal binding pocket of streptavidin. Detection of antibodies in solution and on beads either by FRET or capture of fluorescent ligands by dark antibodies subsequently enables the determination of K(d) values, which indicate agreement between solution and flow cytometric determinations.

Antibodies↗
PubMed1999

Activity of doxorubicin covalently bound to a novel human serum albumin microcapsule.

UNLABELLED: Doxorubicin is widely used in the treatment of human malignancies, however is associated with significant cardiac, bone marrow and gastro-intestinal toxicity. Delivery systems may ameliorate this toxicity and increase treatment specificity by increasing the proportion of drug delivered to sites of disease. We have developed a novel preparation of doxorubicin (Dox) covalently linked to a heat stabilised human serum albumin microparticle (HSAM) carrier (median particle diameter of 4 microm) and assessed its activity in 4 malignant cell lines. MATERIALS AND METHODS: Doxorubicin microcapsules were compared with free doxorubicin in the rat carcinoma cell line, WRC256, and the human lines, OVCAR3, MCF7 and the Dox resistant MCF7/Dox, using a cell counting technique. IC50 were calculated from regression analysis of the resulting survival curves. Endocytosis of the microcapsules by cells in culture was observed. The rate of microcapsule uptake was assessed using dual wavelength filtered fluorescence microscopy and flow cytometry. RESULTS: The mean IC50 following incubation with the Dox microcapsules was around 5 times greater than Dox for WRC256 (p < 0.001), MCF7 (p < 0.01) and for OVCAR3 (p < 0.01). MCF7/Dox was significantly more sensitive to Dox microcapsules than free Dox (p = 0.034). A negative correlation between the rate of microcapsule uptake and the IC50 values for each cell line in culture exists (r = -0.96, p = 0.04). CONCLUSIONS: We conclude that: 1) Doxorubicin microcapsules retain activity in vitro and appear to overcome p-glycoprotein mediated Dox resistance. 2) The observed activity of Dox microcapsules correlates with the rate of particle uptake. Further studies in animal tumour models are in progress.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Fibrinogen-coated albumin microcapsules reduce bleeding in severely thrombocytopenic rabbits.

Severe thrombocytopenia frequently occurs in patients receiving chemotherapy and in patients with autoimmune disorders. Thrombocytopenia is associated with bleeding, which may be serious and life threatening. Current treatment strategies for thrombocytopenia may require transfusion of allogeneic platelets, which is associated with serious drawbacks. These include the occurrence of anti-platelet antibodies, which may result in refractoriness to further platelet transfusions, and the potential risk of transfer of blood-borne diseases. Therefore, we have recently developed a platelet substitute product (Synthocytes), which is composed of human albumin microcapsules with fibrinogen immobilized on their surface. Here we show that the intravenous administration of these microcapsules not only corrects the prolonged bleeding time in rabbits rendered thrombocytopenic either by anti-platelet antibodies or by chemotherapy, but also reduces bleeding from surgical wounds inflicted in the abdominal skin and musculature. No potential systemic prothrombotic effect of the microcapsules was observed in a model of rabbit venous thrombosis. As for the mechanism of action, experiments with normal and thrombocytopenic human blood in an endothelial cell matrix-coated perfusion chamber demonstrated an interaction between the fibrinogen-coated albumin microcapsules and native platelets. It was shown that the fibrinogen-coated albumin microcapsules could facilitate platelet adhesion to endothelial cell matrix and correct the impaired formation of platelet aggregates in relatively platelet-poor blood. This study indicates that fibrinogen-coated albumin microcapsules can act to improve primary hemostasis under thrombocytopenic conditions and may eventually be a promising agent for prophylaxis and treatment of bleeding in patients with severe thrombocytopenia.

Albumins↗
PubMed1999

Patient preferences for colon cancer screening.

OBJECTIVE: To measure patient preferences for four different screening strategies: annual fecal occult blood testing (FOBT) alone; flexible sigmoidoscopy (FSIG) every 5 years alone; both annual FOBT and FSIG every 5 years; or no screening. DESIGN: Survey. SETTING: University internal medicine clinic. PATIENTS: Convenience sample of 146 adults (aged 50-75 years) with no previous history of colon cancer. INTERVENTION: Three-part educational program on colon cancer screening administered verbally by trained research assistants. MEASUREMENTS AND MAIN RESULTS: Patient preferences for screening were measured at three points: after descriptive information about colon cancer and screening options (testing procedure information); after information about test performance but with no out-of-pocket costs (test performance information); and finally with hypothetical out-of-pocket costs (cost information). After only descriptive test information, the most popular strategies were FOBT alone (45%) or both tests (38%). Fewer patients preferred FSIG alone (13%). After information about test performance, more subjects preferred both tests (47%), and fewer subjects preferred FOBT alone (36%) (p =.12). With hypothetical out-of-pocket costs, the proportion preferring FOBT alone increased to 53%, while those preferring both tests decreased to 31% (p <.001). Less than 5% of patients preferred no screening. CONCLUSIONS: Patient preferences for colon cancer screening were modestly sensitive to information about test performance and strongly sensitive to out-of-pocket costs. The heterogeneity of patients' preferences for how to be screened supports informed shared decision making as a possible means of improving colon cancer screening.

Aged↗
PubMed1999

The 'easy street' myth: self harm among aboriginal and non-aboriginal female sole parents in urban state housing.

OBJECTIVE: To test the hypothesis that, controlling for socio-demographic factors, destructive behaviour among Aboriginal and non-Aboriginal female sole parents will not be significantly different. METHOD: This study took place among an urban population of sole parents in Adelaide, South Australia, living in government housing. Two sample subsets were made up of 52 Aboriginal and 45 non-Aboriginal mothers from similar postcodes. Trained interviewers administered a questionnaire which, in addition to basic demographic data, elicited information concerning finance, housing, upbringing, experience of abuse and police interaction. The major issue of concern in the study was suicide attempt. RESULTS: 1-in-3 of the whole sample, 2-in-5 of the non-Aboriginal and 1-in-4 of the Aboriginal subset had attempted suicide at least once and half more than once. Statistical differences among 'attempters' vs. 'non-attempters', irrespective of ethnicity, included increased familial alcohol abuse, physical and sexual abuse, economic difficulty, poor self esteem and perceived discriminatory treatment by welfare agencies and, in the case of Aboriginals, by police. CONCLUSION: The social environment is critical to understanding destructive behaviour, including self-harm, regardless of culture or ethnicity. The data show that suicide attempts among female sole parents in State-housing is one of the few health indices for which Aboriginal statistics are less than for non-Aboriginals. IMPLICATIONS: It is evident that class, rather than ethnicity, better explains self-harm in this urban population. It is suggested that reluctance to access services, especially in times of crisis, relates in part to perceptions of care services and that, for Aboriginals, the value of culturally appropriate community-run services have specific public health and policy implications.

Adult↗
PubMed1999

National Confidential Enquiry into counselling for genetic disorders by non-geneticists: general recommendations and specific standards for improving care.

OBJECTIVES: To assess genetic counselling by non-geneticists and to improve clinical practice. DESIGN: National retrospective review of casenotes. SETTING: Antenatal, paediatric, medical, and surgical units. SAMPLE: 1293 genetic events were identified, involving potentially avoidable cases of Down's syndrome, neural tube defect, cystic fibrosis, beta thalassaemia major and late onset medullary carcinoma of the thyroid (multiple endocrine neoplasia). Notes were available for review in 888 (69%) of these cases. OUTCOMES: Documented counselling, offers of relevant genetic screening and prenatal diagnosis. RESULTS: Clinical audit was frustrated by poor quality hospital records lacking evidence of counselling. Non-geneticist clinicians concentrate on the management of disease, and may overlook the need for counselling and recording data which patients will later need for decisions about reproduction or disease prevention. Counselling, screening and prenatal diagnosis were sometimes impossible because of late booking in pregnancy, or because of delayed diagnosis of an earlier affected child with cystic fibrosis. There are marked regional inequalities of access to genetic services, particularly for minority ethnic groups with increased risks of thalassaemia. Although patients were selected for this enquiry because they had known high risks of genetic disorders, on average less than half were referred to medical geneticists. General recommendations relevant for improvement of care for patients and families with medical genetic needs and those specific for each disorder are given. CONCLUSIONS: Assessment of the quality of genetic care becomes increasingly important as genetic counselling spreads beyond the narrow confines of specialist genetic services. Even though the events studied in this enquiry largely occurred between 1991 and 1995, there is little reason to believe that clinicians in general have become markedly better trained in medical genetics. The General Medical Council and Medical Royal Colleges should urgently consider the need for a national policy for improving undergraduate and postgraduate medical, nursing and midwifery education in genetics. Commissioners of clinical services should require that genetic management be at least as well-documented as surgical operations, drug records and informed consent, perhaps by using a nationally agreed pro-forma for prenatal diagnosis. Regular audit of counselling provided by non-geneticists is necessary to confirm that clinical improvements are occurring and standards are being met. The Confidential Enquiry provides data for a systematic approach to clinical governance of genetics in all specialities. This sets the scene for multi-speciality NHS genetic services capable of giving patients greater consistency both in access and in quality.

Clinical Competence↗
PubMed1999

Resting sestamibi imaging for the prognosis of low-risk chest pain.

OBJECTIVE: To assess the prognostic value of resting Tc-99m sestamibi scanning for adverse cardiac events (ACEs) in ED chest pain patients with a low probability of acute cardiac ischemia (ACI). METHODS: Sixty-nine consenting, hemodynamically stable patients with chest pain and a nondiagnostic electrocardiogram received an injection of 25 mCi of sestamibi during or within two hours of active pain. Scans were interpreted locally by a nuclear cardiologist or radiologist. Interrater reliability was assessed. ACEs of myocardial infarction (MI), death, or revascularization were assessed during the index hospitalization and over a one-year follow-up period. RESULTS: For ACEs, rest scanning with sestamibi had a sensitivity of 71% (95% CI = 0.33 to 0.97), a specificity of 92% (95% CI = 0.82 to 0.97), and an accuracy of 90% (95% CI = 0.87 to 0.99). The positive predictive value was 50% (95% CI = 0.19 to 0.82) and the negative predictive value was 97% (95% CI = 0.87 to 0.98). Sestamibi scanning was highly discriminating, with 62% of patients with positive scans but only 3% with negative scans having ACEs (p<0.001, log rank test). CONCLUSION: In patients with low-risk chest pain, sestamibi scanning has good specificity and moderate sensitivity for ACEs over a 12-month period.

Chest Pain↗