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Biomedical subjects

A Harris

Publications and source records attributed to A Harris.

At least 181 records · Page 10Linked to original sources
PubMed1998

Localization of expression of human beta defensin-1 in the pancreas and kidney.

Defensins are antimicrobial peptides which play a key role in innate immunity. High levels of human beta defensin-1 (hBD-1) have previously been detected in the kidney and pancreas, but the cell-specific location of hBD-1 mRNA has not been determined. The expression of hBD-1 mRNA has been examined in fetal and adult pancreas and kidney by mRNA in situ hybridization. In fetal pancreas, hBD-1 expression was detected in the developing acini and in adult pancreas in the acini, but not in the pancreatic ducts. In both fetal and adult kidney, hBD-1 expression was detected in the collecting ducts and in the loops of Henle in adult kidney. Expression of hBD-1 mRNA in the pancreas and kidney from early development and in the acini of the adult pancreas, rather than in the pancreatic ducts, may indicate that in these tissues, hBD-1 fulfils physiological functions in addition to host defence.

Adult↗
PubMed1998

Resource costing for multinational neurologic clinical trials: methods and results.

We present the results of a multinational resource costing study for a prospective economic evaluation of a new medical technology for treatment of subarachnoid hemorrhage within a clinical trial. The study describes a framework for the collection and analysis of international resource cost data that can contribute to a consistent and accurate intercountry estimation of cost. Of the 15 countries that participated in the clinical trial, we collected cost information in the following seven: Australia, France, Germany, the UK, Italy, Spain, and Sweden. The collection of cost data in these countries was structured through the use of worksheets to provide accurate and efficient cost reporting. We converted total average costs to average variable costs and then aggregated the data to develop study unit costs. When unit costs were unavailable, we developed an index table, based on a market-basket approach, to estimate unit costs. To estimate the cost of a given procedure, the market-basket estimation process required that cost information be available for at least one country. When cost information was unavailable in all countries for a given procedure, we estimated costs using a method based on physician-work and practice-expense resource-based relative value units. Finally, we converted study unit costs to a common currency using purchasing power parity measures. Through this costing exercise we developed a set of unit costs for patient services and per diem hospital services. We conclude by discussing the implications of our costing exercise and suggest guidelines to facilitate more effective multinational costing exercises.

Australia↗
PubMed1998

Calcium-activated chloride conductance in a pancreatic adenocarcinoma cell line of ductal origin (HPAF) and in freshly isolated human pancreatic duct cells.

Using the whole-cell patch-clamp technique, a calcium-activated chloride conductance (CACC) could be elicited in HPAF cells by addition of 1 microM ionomycin to the bath solution (66 +/- 22 pA/pF;Vm + 60 mV) or by addition of 1 microM calcium to the pipette solution (136 +/- 17 pA/pF; Vm + 60 mV). Both conductances had similar biophysical characteristics, including time-dependent inactivation at hyperpolarising potentials and a linear/slightly outwardly rectifying current/voltage (I/V) curve with a reversal potential (Erev) close to the calculated chloride equilibrium potential. The anion permeability sequence obtained from shifts in Erev was I > Br >/= Cl. 4,4'-Diisothiocyanatostilbene disulphonic acid (DIDS, 500 microM) caused a 13% inhibition of the current (Vm + 60 mV) while 100 microM glibenclamide, 30 nM TS-TM-calix[4]arene and 10 microM tamoxifen, all chloride channel blockers, had no marked effects (8%, -6% and -2% inhibition respectively). Niflumic acid (100 microM) caused a voltage-dependent inhibition of the current of 48% and 17% (Vm +/- 60 mV, respectively). In freshly isolated human pancreatic duct cells (PDCs) a CACC was elicited with 1 microM calcium in the pipette solution (260 +/- 62 pA/pF; Vm + 60 mV). The presence of this CACC in human PDCs could provide a possible therapeutic pathway for treatment of pancreatic insufficiency of the human pancreas in cystic fibrosis.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

A novel type of internal barium block of a maxi-K+ channel from human vas deferens epithelial cells.

We have recently shown that a maxi-K+ channel from vas deferens epithelial cells contains two Ba2+-binding sites accessible from the external side: a "flickering" site located deep in the channel pore and a "slow" site located close to the extracellular mouth of the channel. Using the patch-clamp technique, we have now studied the effect of internal Ba2+ on this channel. Cytoplasmic Ba2+ produced a voltage- and concentration-dependent "slow" type of block with a dissociation constant of approximately 100 microM. However, based on its voltage dependence and sensitivity to K+ concentration, this block was clearly different from the external "slow" Ba2+ block previously described. Kinetic analysis also revealed a novel "fast flickering" block restricted to channel bursts, with an unblocking rate of approximately 310 s(-1), some 10-fold faster than the external "flickering" block. Taken together, these results show that this channel contains multiple Ba2+-binding sites within the conduction pore. We have incorporated this information into a new model of Ba2+ block, a novel feature of which is that internal "slow" block results from the binding of at least two Ba2+ ions. Our results suggest that current models for Ba2+ block of maxi-K+ channels need to be revised.

Barium↗
PubMed1998

Insulin-like growth factors in human breast cancer.

IGF1 and IGF2 are circulating peptide hormones and locally-acting growth factors with both paracrine and autocrine functions. IGF1 and IGF2 signal through a common tyrosine kinase receptor, the insulin-like growth factor 1 receptor (IGF1R), and have mitogenic, cell survival, and insulin-like actions that are essential for embryogenesis, post-natal growth physiology, and breast development. The activities of IGF1 and 2 are tightly-regulated by a network of binding proteins and targeted degradation mechanisms. This complex regulatory system is disrupted in breast cancer, leading to excess IGF1R signaling. Evidence for this statement includes: a) breast cancers are infiltrated with IGF2 expressing stromal cells; b) mannose 6-phosphate/IGF2 receptor (M6P/IGF2R) is mutated in breast cancer, leading to loss of IGF2 degradation; c) IGF1R is overexpressed by malignant breast epithelial cells, and in some cases IGF1R is amplified; and d) complex changes in IGF binding protein expression occur during breast cancer progression which most likely also affect IGF1 and 2 signaling. The clinical importance of these epigenetic and genetic changes has recently been stressed by the finding that IGF1R signaling alters the apoptotic response of breast cancer cells to genotoxic stress and, in addition, IGF1R activation sensitizes cells to estrogen by inducing phosphorylation of the estrogen receptor. As a consequence of these findings, we propose that IGF analysis of breast cancer samples should shift from prognostic studies to an evaluation of IGF ligands, receptors, and binding proteins as resistance/sensitivity markers for radiation, chemotherapy, and endocrine therapy.

Apoptosis↗
PubMed1998

Ocular haemodynamics in glaucoma associated with high myopia.

The ocular blood flow of a group of high myopic and glaucomatous eyes has been investigated by means of the Color Doppler Imaging (CDI) technique, comparing the results with those of some very myopic eyes without glaucoma, some non-myopic glaucomatous eyes and with a control group. The Ophthalmic Artery (OA), the Short Posterior Ciliary Arteries (SPCAs) and the Central Retinal Artery (CRA) were considered. For every vessel, peak systolic velocity (SV), end-diastolic velocity (DV) and the Pourcelot Resistivity Index were studied. The statistical analysis was performed by means of t-test according to Bonferroni procedure for multiple comparisons. The authors registered in the group of eyes with glaucoma associated with very severe myopia some abnormalities of the OA blood flow systolic velocity which might be interpreted as a vascular risk factor for the pathogenesis of the glaucomatous optic neuropathy; these abnormalities are more severe in glaucoma patients with high myopia than in an age-matched group of glaucoma patients without myopia.

Adult↗
PubMed1998

Cholelithiasis and dietary risk factors: an epidemiologic investigation in Vidauban, Southeast France. General Practitioner's Group of Vidauban.

Dietary risk factors have been implicated in the development of cholelithiasis. The aim of this study was to determine in a homogeneous French population whether a particular type of diet may be lithogenic. Seventy-six subjects over 30 years of age (26 men, 50 women) with cholelithiasis detected by ultrasound were selected from a population sample of 830 subjects by drawing lots using the polling list. These were matched by 76 control subjects without cholelithiasis randomly selected from the same population. Univariate analysis was significant for a high calorie diet >2500 kcal/day (OR = 3.62, P = 0.0065), a diet rich in carbohydrates with a consumption > or = 55 g/day (OR = 2.98, P = 0.0067), and a diet rich in total lipids (OR = 4.97, P = 0.023) or saturated fatty acids (OR = 3.06, P = 0.0146). An alcohol consumption equivalent to 20-40 g/day was protective (P = 0.018). Multivariate analysis confirmed these results. Our study suggests that a change in dietary habits by limiting excess calories, saturated fats and carbohydrates could reduce the incidence of cholelithiasis.

Adult↗
PubMed1998

The acute effect of topical beta-adrenoreceptor blocking agents on retinal and optic nerve head circulation.

PURPOSE: Topical beta-blockers are the most common treatment for ocular hypertension in glaucoma, but their ocular hemodynamic effects are not well known. We investigated the acute effects of betaxolol (beta-1 selective antagonist), levobunolol (non-selective antagonist with active polar metabolite), and timolol (non-selective antagonist) on retinal and superficial optic nerve head circulation. METHODS: Intraocular pressure (IOP), heart rate, blood pressure, and retinal circulation were evaluated in 12 healthy subjects (6F/6M; mean age=24+/-2 years) before and two hours after instillation of each drug on separate occasions at least two weeks apart. Macular capillary blood velocity (MCBV), epipapillary blood velocities (EBV), arteriovenous passage (AVP) times, and arterial and venous diameters were measured by digital image analysis of scanning laser fluorescein angiograms. RESULTS: All drugs significantly (p<0.05) reduced IOP. There was no significant effect on blood pressure or calculated ocular perfusion pressure. Only levobunolol significantly lowered heart rate (p<0.05). Each drug produced a significant (p<0.01) decrease in AVP time of approximately 25%. MCBV was significantly (p<0.01) increased by approximately 20% in all three conditions; each drug also produced significant (p<0.01) increases in EBV. Arterial and venous diameters remained unaffected. CONCLUSION: All three drugs, despite different beta-adrenergic properties, increased blood velocities in retinal and epipapillary capillaries. These changes, occurring as they do in concert with decreased retinal arteriovenous passage time at constant retinal arterial and venous diameter, may indicate improved retinal perfusion after drug treatment. Improved circulation, if it indeed occurs, in tandem with reduced IOP, might explain in part the beneficial effect of beta-adrenoreceptor blocking agents in glaucomatous patients.

Administration, Topical↗
PubMed1998

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene.

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

Antigens, CD↗
PubMed1998

Legionella bozemanii pneumonia in three patients with AIDS.

Legionella bozemanii is known to cause pneumonia often in immunocompromised hosts. To our knowledge, we describe the first three cases of L. bozemanii pneumonia in patients with AIDS. At the time of presentation, these patients had varied histories, physical findings, and radiological findings. All three patients had a uniformly excellent response to treatment despite receiving different antibiotic regimens. The cases illustrate the need for thorough diagnostic workups and prompt institution of antibiotic therapy when clinical suspicion for L. bozemanii infection is high.

AIDS-Related Opportunistic Infections↗
PubMed1998

Current regimens for treatment of Helicobacter pylori infection.

The aim of treatment of Helicobacter pylori is eradication of the bacterium from the foregut. Treatment is difficult because of the bacterium's habitat and acquired resistance to commonly used antibiotics. Dual therapy, the 2 week combination of omeprazole or ranitidine bismuth citrate and either amoxycillin or clarithromycin, eradicates H. pylori in 50-80% of patients. Classical triple therapy is commonly associated with side effects, is highly dependent on patient's compliance, and is significantly less effective in the presence of metronidazole-resistant strains of H. pylori, where eradication may be 50%. One week, twice daily, proton pump inhibitor (PPI)-based triple therapy regimens eradicate about 90% of H. pylori and are associated with mild side effects. Second line regimens include 7 days treatment with omeprazole and 3 times daily amoxycillin and metronidazole or a PPI-based quadruple therapy regimen. In some cases, the bacterium defeats all attempts at eradication.

Amoxicillin↗
PubMed1998

Perioperative cost-finding analysis of the routine use of intraoperative forced-air warming during general anesthesia.

BACKGROUND: Despite the well-documented ability of forced-air warming (FAW) to maintain normothermia, it is unclear whether this technique results in a net increase or decrease in costs. The authors did a prospective cost-finding study comparing FAW with routine thermal care in patients at low risk for perioperative complications who were undergoing general anesthesia. METHODS: After institutional review board approval was received, 100 patients were studied who were having elective surgery scheduled for more than 2 h during general endotracheal anesthesia. Patients were randomly assigned to one of two groups: FAW or routine thermal care. All patients received a standardized anesthetic. Anesthesia providers were blinded to core temperatures and the use of FAW. Primary outcomes were those associated with perioperative costs. RESULTS: The time from completion of surgical dressing until tracheal extubation was significantly reduced in the FAW group (10 +/- 1 min compared with 14 +/- 1 min; mean +/- SEM; P < 0.01). There was no demonstrable difference in attainment of postanesthesia care unit discharge criteria between the two groups, although the FAW group used one less cotton blanket there. The net savings related to the use of the FAW depends on the percentage of the intraoperative costs that are fixed rather than variable ($15 additional for FAW if all costs are fixed compared with $29 savings if all costs were variable). CONCLUSIONS: Routine intraoperative FAW significantly reduced time until extubation and use of cotton blankets in the postanesthesia care unit. These results suggest that the influence of FAW on net total perioperative costs depends on patient and surgical characteristics and institutional factors related to cost accounting.

Adolescent↗
PubMed1998

Heidelberg retinal flowmetry: factors affecting blood flow measurement.

AIMS: To evaluate factors affecting Heidelberg retinal flowmeter (HRF) measurements of retinal and optic nerve head blood flow in human subjects. METHODS: The angle of incidence between laser beam and fundus, and camera distance from the eye, were evaluated for their effect upon measures of blood volume, velocity, and flow in a single 100 x 100 x 400 microns volume of temporal peripapillary retinal tissue in normal volunteers. Both intra and intersession reproducibility of these measures were studied. Intersession data were obtained by taking one image per week for 4 weeks. Finally, the intersession haemodynamic data were examined in the entire image (640 x 2560 x 400 microns), using histograms of pixel by pixel blood flow. RESULTS: Measures of blood volume, velocity, and flow from a single anatomical site were unaffected by laser beam to fundus angle of incidence (n = 12). As camera distance from the eye was increased (from 2 to 5 to 7 cm), flow measurements showed increasing individual changes, despite unaltered measured vessel lengths and constant overall mean flow (n = 14). The coefficient of variation for two intersession images of optic nerve head blood flow averaged 7% (n = 20); in contrast, the 4 week intersession coefficient of variation averaged 30% (n = 15). Intersession reproducibility was increased by using flow histograms from the entire image: the coefficients of variation averaged 16% for total flow and 17% for flow in the pixel of median flow. CONCLUSION: HRF measures of flow are independent of the laser beam to fundus angle of the incidence and dependent upon camera distance from the eye. Intersession reproducibility is best using pixel by pixel analysis of the entire image.

Blood Flow Velocity↗
PubMed1998

Effects of short term increase of intraocular pressure on optic disc cupping.

AIMS: To evaluate the effect of acute elevation of intraocular pressure (IOP) on optic disc cupping. METHODS: 10 emmetropic and 10 myopic volunteers were included in this study. The cup area (CA) and cup volume (CV) of the optic disc were determined with the Heidelberg retina tomograph (HRT). After baseline determinations, a suction cup was used to increase the intraocular pressure (IOP) to 20-25 mm Hg above the baseline and HRT images were obtained. RESULTS: Baseline IOP was 13.5 (SD 1.3) nim Hg and 12.6 (2.6) mm Hg in the emmetropic and myopic groups, respectively. The IOP was elevated to 35.4 (3.3) mm Hg and 34.4 (2.5) mm Hg in the emmetropic and myopic groups, respectively. When compared with their baseline values, the cupping variables (CA and CV) were significantly increased (p < 0.05) during the suction treatment in both emmetropic and myopic subjects. CONCLUSION: There was a significant enlargement in the optic disc cupping during the artificial increment of intraocular pressure in both emmetropic and myopic eyes. In non-glaucomatous eyes the optic nerve head has a partially dynamic topography dependent upon the level of IOP.

Adult↗