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Biomedical subjects

A Harris

Publications and source records attributed to A Harris.

At least 73 records · Page 4Linked to original sources
PubMed2001

Delta4, an endothelial specific notch ligand expressed at sites of physiological and tumor angiogenesis.

Delta-Notch signalling regulates cell-fate choices in a variety of tissues during development. We report the expression of Delta4 (D14) in arterial endothelium during mouse embryogenesis and in the endothelium of tumor blood vessels. The expression of D14 in the mouse begins at 8 dpc in the dorsal aortae, umbilical artery and the heart. Subsequent expression is restricted to smaller vessels and capillaries and is reduced in most adult tissues. However, it is high in the vasculature of xenograft human tumors in the mouse, in endogenous human tumors and is regulated by hypoxia. These data implicate D14 and the Notch signalling pathway in angiogenesis and suggest possible new targets for antiangiogenic tumor therapy.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Baastrup's disease correlating with diffuse lumbar paraspinal atrophy: a case report.

Baastrup's disease ("kissing spine") is an x-ray finding that has been considered a possible cause of low back pain (LBP) since the 1930s. Its etiology is unknown, and there are no reports of muscle or soft tissue changes associated with it. This case report concerns a 57-year-old man with chronic LBP, stiffness, and indurated skin over the back. He had classic sclerotic changes between the spinous processes on x-ray, which is consistent with Baastrup's disease. Computed tomography (CT) and electromyography were performed. CT showed profound fatty replacement of the paraspinal musculature. An electromyography report showed severe isolated paraspinal denervation. This case suggests that diffuse fatty replacement of the paraspinal muscles, perhaps due to a compartment syndrome or other vascular event, may have a role in the pathogenesis of Baastrup's disease.

Diagnosis, Differential↗
PubMed2001

[Beyond "successful aging: Rembrandt in his self-portraits].

The process of aging has been generally associated with cognitive dedine. However, some complex cognitive abilities, such as wisdom and judgement, have been suggested to improve with age. In the current study, the development of an advanced artistic ability is examined over the life span of Rembrandt H. van Rijn. Analysis of the paintings revealed the development of an old-age-style in the last portrait, characterised by uniformity of texture, facture, and lighting. The self-portrait painted in the last year of Rembrandt's life reflects a high degree of integration of artistic skill and experience gathered in the course of life, and hence reflects features of wisdom in the sence suggested by Baltes. The development of a mature "late" style can help to characterise the emergence of qualitatively different and advanced cognitive abilities in old age.

Aging↗
PubMed2001

Effect of brimonidine tartrate on ocular hemodynamics in healthy volunteers.

While alpha2-adrenergic agonists, such as brimonidine tartrate, significantly reduce the intraocular pressure (IOP), the presence of vasoconstrictor postsynaptic alpha2 receptors on vascular smooth muscle raise the possibility that brimonidine could potentially compromise ocular blood flow. Consequently, the ocular hemodynamic effects of brimonidine were studied in normal subjects. Twelve healthy volunteers were included in this prospective, double-masked, placebo controlled, crossover-designed clinical trial. They received either brimonidine tartrate 0.2% or placebo b.i.d. for 2 weeks. Goldmann tonometry and color Doppler imaging (CDI) were performed at baseline, at 2 hr, 1 week, and 2 weeks after the treatment. Fundus angiography using a scanning laser ophthalmoscope was performed at baseline and 2 weeks after treatment to determine retinal arteriovenous passage time. Brimonidine lowered IOP at 2 hr, 1 week, and 2 weeks (p = 0.058, p = 0.031, and p = 0.022, respectively). Brimonidine did not affect the retrobulbar arterial velocities measured by CDI, nor retinal arteriovenous passage time. In conclusion, two-week treatment with brimonidine reduces IOP and does not reduce the bulk retinal or retrobulbar arterial perfusion in young healthy volunteers.

Administration, Topical↗
PubMed2001

In vivo glycosylation of mucin tandem repeats.

The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease.

Amino Acid Sequence↗
PubMed2001

Intraocular pressure and photorefractive keratectomy: a comparison of three different tonometers.

PURPOSE: To evaluate the intraocular pressure (IOP) with three different instruments, Goldmann applanation tonometer (GAT), noncontact tonometer, and Tono-Pen after photorefractive keratectomy (PRK) for myopia. METHODS: A prospective case series study to evaluate preoperative and postoperative IOP measurements of 149 eyes at 12 months. We performed GAT, noncontact tonometry, Tono-Pen central, and Tono-Pen temporal periphery measurements. We also performed measurements of the central corneal thickness (CCT) by ultrasonic pachymetry and keratometry. Pre-operative IOP reading served as control for all studies. RESULTS: After PRK, IOP reading was significantly reduced in the treated eyes when compared with the control measurements (11.87+/-1.73 vs. 13.37+/-1.52 mm Hg, p<0.0001 with GAT; 12.07+/-1.6 vs. 13.51+/-1.59 mm Hg, p<0.0001 with noncontact tonometer; 12.18+/-1.6 vs. 13.48+/-1.55 mm Hg, p<0.0001 with Tono-Pen central; 13.48+/-1.65 vs. 13.71+/-1.56 Hg, p<0.0104 with Tono-Pen temporal periphery). There was also a significant correlation between IOP reading changes measured by GAT, noncontact tonometer, Tono-Pen central, and change of CCT and between reduction of IOP reading and keratometry (r2>0.39, p<0.0001 for each). The correlation between IOP reading change by Tono-Pen temporal periphery and CCT was also significant but r2 value was only 0.034. Tono-Pen temporal periphery postoperative IOP measurements had the best correlation with preoperative GAT IOP (r2 = 0.57, p<0.0001). CONCLUSIONS: PRK reduced IOP reading as measured by GAT, noncontact tonometer, and Tono-Pen central; less so when measured by Tono-Pen temporal periphery. Early detection of glaucoma and IOP follow-up in glaucoma patients may be done best by peripheral Tono-Pen measurements over the nonablated cornea.

Adult↗
PubMed2001

The impact of glaucoma medication on parameters of ocular perfusion.

Whereas intraocular pressure is considered a major risk factor in glaucoma, growing evidence now indicates that ocular ischemia plays a major role too. By virtue of this and because many existing medications are able to interact with vasculature, altering ocular blood flow, it is essential that current and future medications for glaucoma be evaluated for their effect on ocular circulation. The authors review published papers examining the effect of topical and some systemic medications on ocular blood flow, focusing mostly on data from the human eye. The authors provide a comprehensive review on the effect of subclasses of medications (eg, carbonic anhydrase inhibitors, beta-blockers, alpha-adrenergic agonists, and prostaglandin analogues on optic nerve head, and on retinal, choroidal, and retrobulbar circulation. The various claims for enhancements or reduction of ocular circulation within each class of medication are reviewed and evaluated.

Adrenergic alpha-Agonists↗
PubMed2001

Economics, competition and the regulation of public health risks.

OBJECTIVE: The efficiency of regulation of public health risks has been questioned on the grounds that the costs of regulation may outweigh the benefits. There are strong arguments that risk management is best left to the market place, where individual consumers can make the trade-off between risk and the forgone benefits of reduced consumption of hazardous products. The paper reviews the economic arguments for the regulation of health risks and the use of safety standards. RESULTS: There are five key arguments for regulation of public health risks. Consumers misperceive the hazards of products and therefore take more risks than they would if fully informed. The provision of information has certain public goods characteristics (it is non-rival). There may be economies of scale in collecting, providing and disseminating information that is costly to acquire. The private decision maker may not be the person bearing the whole risk, exposing others to risk e.g. children. If public policy has chosen to provide public finance for health care it may be efficient to discourage risk taking by individuals even if that risk taking is optimal from the individual's perspective. CONCLUSION: There are arguments for public intervention to reduce private health risks and regulation of risk is a legitimate tool to achieve the socially optimal level of risk in certain circumstances. Private subjective assessment of risk may not capture the full social benefits of risk reduction. Regulation by safety standards however may fail to capture the full range of concerns about risk, including avoiding catastrophe, taking personal control of risk, and a distrust of expert opinion.

Australia↗
PubMed2001

An economic evaluation of universal infant vaccination against hepatitis B virus using a combination vaccine (Hib-HepB): a decision analytic approach to cost effectiveness.

OBJECTIVE: To evaluate the health impact and cost effectiveness of two infant vaccination strategies for protection against hepatitis B virus (HBV) infection in the Australian population. Vaccinating only high-risk infants, assuming 65% compliance, was compared with universal vaccination of infants using a combination Hib-HepB vaccine, with 87.4% compliance. METHOD: A Markov model simulated the natural history of HBV infection and disease in an Australian birth cohort. The cohort was divided into those at high risk of infection (infants born into high-risk families) and low-risk infants. Clinical and epidemiological data used were obtained from published reports and a survey of clinical experts. The model included the health costs associated with acute and chronic HBV infection, and the sequelae of chronic HBV infection. RESULTS: The model predicted that universal hepatitis B vaccination of an Australian birth cohort (260,000 births) would result in a 77% reduction in cases of HBV infection. The incremental cost per life year gained was $11,862, which is low compared with many other health care interventions. With no discounting of costs or consequences, universal vaccination with the combination vaccine was predicted to save lives and reduce costs. CONCLUSION: There is no socially accepted threshold value for cost per life year gained to guide decisions about funding Australian health care interventions. Nevertheless, based on these results, universal hepatitis B vaccination of Australian infants using a combination Hib-HepB vaccine would almost certainly be regarded as a worthwhile investment of public funds.

Australia↗
PubMed2001

Risk factors for emergence of resistance to broad-spectrum cephalosporins among Enterobacter spp.

Among 477 patients with susceptible Enterobacter spp., 49 subsequently harbored third-generation cephalosporin-resistant Enterobacter spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk [OR] = 2.3, P = 0.01); quinolone therapy was protective (OR = 0.4, P = 0.03). There were trends toward decreased risk for resistance among patients receiving broad-spectrum cephalosporins and either aminoglycosides or imipenem. Of the patients receiving broad-spectrum cephalosporins, 19% developed resistance.

Bacteremia↗
PubMed2001

New neuroretinal rim blood flow evaluation method combining Heidelberg retina flowmetry and tomography.

AIM: Accurate Heidelberg retina flowmeter (HRF) measurements require correct manual setting of the HRF photodetector sensitivity. The neuroretinal rim produces a weak signal relative to the peripapillary retina. A newly developed HRF alignment and sensitivity protocol, capable of accurate rim measurement, was investigated. METHODS: 18 eyes of nine healthy volunteers were examined by HRF. Three images of each eye were taken using three different imaging methods. Method 1: a conventional image (optic nerve head centred image with photodetector sensitivity optimised for the strong signal from the peripapillary retina); method 2: the setting of method 1 with photodetector sensitivity optimised for the weak signal from the rim; and method 3: the setting of method 2 with the temporal rim margin tangent to the lateral image border to remove the overpowering signal from the temporal peripapillary retina. The neuroretinal rim was defined by the Heidelberg retina tomograph (HRT). Blood flow and reflectivity values (DC component) in the rim area were compared for the three methods using pointwise analysis. Coefficients of variation of repeated measurements in 12 subjects have been calculated for method 3. RESULTS: The neuroretinal rim area measured by method 1 had a significantly lower brightness compared with method 2 and 3 (p=0.0002 and p=0.0002, respectively). Method 2 provided proper sensitivity for the weak signals of the rim area based on rim tissue DC values; however, this sensitivity setting was too high for the strong signal from the peripapillary retina. Method 3 avoided the strong peripapillary signal with the proper signal from the rim and provided significantly higher flow values of the rim area at 75 and 90 percentile pixels (p=0.0065 and p=0.0038 respectively) compared with method 2. Interobserver repeatability ranged from 16.85% to 21.96% for the different parameters. CONCLUSIONS: Method 3 provides an accurate and reproducible flow measurement of the neuroretinal rim area through proper sensitivity for the weak rim signal, alignment, and removal of the strong temporal signal from the image. This new method is recommended to improve accuracy of blood flow measurement in the neuroretinal rim.

Adolescent↗
PubMed2001

Infectious aneurysm clipping by an MRI/MRA wand-guided protocol. A case report and technical note.

Infectious aneurysms are potentially deadly sequelae of multiple etiologies, typically associated with subacute bacterial endocarditis (SBE). Since these aneurysms tend to be distal, there are no consistent landmarks by which to localize them, in contrast to more typical aneurysms that occur on the circle of Willis or proximal, large cerebral vessel bifurcations. In addition, they tend to be extremely friable and may be obscured by blood if intracranial hemorrhage (ICH) has already occurred. These factors make clipping these aneurysms technically difficult, and searching for easily ruptured aneurysms without standard landmarks adds risk to the procedure. In this report, we describe the case of a 9-year-old boy with SBE and subsequent ICH secondary to a mycotic aneurysm. This aneurysm was localized to within millimeters by the MRI protocol described herein. The aneurysm was excised and the patient recovered without incident. Thus, MRI/MRA-guided frameless stereotaxy may be useful for localizing distal mycotic aneurysms, improving patient outcome by decreasing morbidity and mortality.

Aneurysm, Infected↗
PubMed2001

The 3120 +1G-->A splicing mutation in CFTR is common in Brazilian cystic fibrosis patients.

Cystic fibrosis patients from Rio de Janeiro, Brazil, were screened for mutations in exons 11 and 16 of the cystic fibrosis transmembrane conductance regulator gene (CFTR) by a nonradioactive single-stranded conformational polymorphism (SSCP) analysis technique. This procedure was used to evaluate the undefined mutations in one or both alleles of 64 cystic fibrosis patients. Unusual SSCP profiles were investigated further by sequence analysis. Two patients were shown to carry the G542X mutation (exon 11) and five had the splicing mutation 3120+1G-->A(intron 16), one of them being homozygous for the mutation. This is the first report of the 3120+ IG-->A mutation in Brazil. where it appears to be a frequent disease-associated molecular alteration in the CFTR gene.

Brazil↗
PubMed2001

Cost-effectiveness analysis and the consistency of decision making: evidence from pharmaceutical reimbursement in australia (1991 to 1996).

OBJECTIVE: The principle aim of this study was to generate a league table of drugs considered by the Australian Pharmaceutical Benefits Advisory Committee (PBAC) for reimbursement. The table was used to test the hypothesis that decisions made by the PBAC are consistent with the maxim of economic efficiency. In addition, we explored whether the past decisions by the PBAC revealed a threshold incremental cost-effectiveness ratio beyond which the PBAC is not prepared to recommend reimbursement of a drug. METHODS: All 355 submissions made to the PBAC between January 1991 and June 1996 were reviewed. Submissions using cost per life-year gained (26 submissions) or the cost per quality adjusted life-year (QALY) gained (9 submissions) were ranked in a league table and compared with advice given by the PBAC about that drug. The confidentiality restrictions for the submissions require that the individual drug details cannot be revealed in this article. RESULTS: There was a statistically significant difference between the cost per life-year gained for drugs that were recommended for listing and those that were not, suggesting that the PBAC has been broadly consistent with the use of economic efficiency as a criterion for decision making. We did not find an explicit threshold beyond which the PBAC was unwilling to pay for additional life years gained. However, between 1992 and 1996 the PBAC appears to have been unlikely to recommend a drug for listing if the additional cost per life-year exceeded 76 000 Australian dollars [$AU] (1998/1999 values) and was unlikely to reject a drug for which the additional cost per life-year gained was less than $AU42 000. The cost-effectiveness ratio was not the only factor determining the reimbursement decision. CONCLUSIONS: The results of this preliminary study indicate that decisions to recommend a drug for listing by the PBAC in the last few years have, by and large, been consistent with the notion of economic efficiency.

Australia↗
PubMed2001

Translabial sonography of vaginal fibroids: report of 2 cases and review of the literature.

OBJECTIVE: To determine the role of translabial sonography in the diagnosis of vaginal fibroids. METHODS: Two women with vaginal masses of undetermined origin were examined by various imaging procedures, including translabial sonography. RESULTS: Initial examinations, which included transabdominal sonography, cystoscopy, and cystourethrography, yielded inconclusive findings. Translabial sonography, however, suggested isolated vaginal leiomyomas in both patients, and in both the diagnosis was confirmed histologically after surgery. CONCLUSIONS: Translabial sonography should be considered as an adjunct to transabdominal and transvaginal sonography for patients with suspected vaginal fibroids.

Adult↗