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Biomedical subjects

P Ford

Publications and source records attributed to P Ford.

At least 37 records · Page 2Linked to original sources

Evaluation of a training and diagnostic ultrasound service for general practitioners using narrowband ISDN.

We carried out a four-month pilot study of telemedicine for the delivery of training and diagnostic ultrasound services for general practitioners (GPs). Two health centres and a district general hospital were linked using ISDN (128 kbit/s) and PC-based videoconferencing units. Sixteen videoconferencing sessions were conducted, with 64 patients scanned over the ISDN link for a range of clinical conditions. Nine cases of pathology were demonstrated and confirmed by a consultant radiologist. A total of 229 images were transmitted using the store-and-forward facility, of which 194 (85%) images were of diagnostic quality and 35 (15%) were regarded as non-diagnostic. Allowing for sampling error, we would expect 79-89% of stored images to provide diagnostic information at a 95% confidence level. A total of 115 store-and-forward images (SAFI) were randomly selected and compared with hard-copy images (HCI) for technical quality. There was a significant difference in the quality of images. The results show that SAFI are far superior to HCI, traditionally used by clinicians for making primary diagnosis and that the superior quality of the SAFI improved diagnostic accuracy. This pilot study showed a high degree of confidence in videoconferencing for training GPs to carry out ultrasound clinics, enhancing their ability to make accurate diagnoses, and providing them with immediate access the second and higher opinion.

Education, Medical, Continuing↗

Reconstitution of a regulated transepithelial water pathway in cells transfected with AQP2 and an AQP1/AQP2 hybrid containing the AQP2-C terminus.

Transepithelial water permeability was measured in LLC-PK1 cells stably transfected with aquaporins (AQPs): AQP1, AQP2, and a chimera of AQP1 and AQP2 containing 41 amino acids of the C-terminus of AQP2. Transepithelial water fluxes (Jw) were not previously reported in cells transfected with aquaporins. Jw were now recorded each minute using a specially developed experimental device. A significant increase in Posm after forskolin (FK) plus vasopressin (VP) was found in AQP2 transfected cells (39.9 +/- 8.2 vs. 12.5 +/- 3.3 cm.sec-1.10(-3)), but not in cells transfected with AQP1 (15.3 +/- 3.6 vs. 13.4 +/- 3.6 cm.sec-1.10(-3)). In the case of the AQP1/2 cells (chimera) the FK plus VP induced Posm was smaller than in AQP2 cells but significantly higher than in mock cells at rest (18.1 +/- 4.8 vs. 6.7 +/- 1.0 cm.sec-1.10(-3)). The increases in Posm values were not paralleled by increases in 14C-Mannitol permeability. HgCl2 inhibited the hydrosmotic response to FK plus VP in AQP2 transfected epithelia. Results were comparable to those observed, in parallel experiments, in a native ADH-sensitive water channel containing epithelial barrier (the toad urinary bladder). Electron microscopy showed confluent LLC-PK1 cells with microvilli at the mucosal border. The presence of spherical or elongated intracellular vacuoles was observed in AQP2 transfected cells, specially after FK plus VP stimulus and under an osmotic gradient. These results demonstrate regulated transepithelial water permeability in epithelial cells transfected with AQP2.

Animals↗

Suicide in urban New South Wales, Australia 1985-1994: socio-economic and migrant interactions.

Variation of suicide with socio-economic status (SES) in urban NSW (Australia) during 1985-1994, by sex and country or region of birth, was examined using Poisson regression analysis of vital statistics and population data (age >¿ approximately 15 yr). Quintiles of SES were defined by municipality of residence and comparisons of suicide by SES were adjusted for age and country (or region) of birth (COB), and examined by COB. Risk of suicide in females was 28% that of males for all adults and 21% for youth (age 15-24 yr). Suicide risk was lower in males from southern Europe, Middle East and Asia, and higher in northern and eastern European males, compared to the Australian-born. Risks for suicide increased significantly with decreasing SES in males, but not in females. The relationship of male suicide and SES was stronger when controlled for COB. For males, the relative risk of suicide, adjusted for age and COB, was 66% higher in the lowest SES quintile compared to the highest quintile. and 39% higher for youth (age 15-24 yr). For male suicide, the population attributable fraction for SES (less than the highest quintile) was 27%. Analysis of SES differentials in male suicide according to COB indicated a significant inverse suicide gradient in relation to SES for the Australian-born and those born in New Zealand and the United Kingdom or Eire, but not in non-English speaking COB groups, except for Asia. For Australian-born males, suicide risk was 71% higher in the lowest SES group (compared to the highest), adjusted for age. These findings indicate that SES plays an important role in male suicide rates among the Australian-born and migrants from English-speaking countries and Asia, and among youth; but not in female suicide, nor suicide in most non-English speaking migrant groups. Reduction in SES differentials through economic and social policies may reduce male suicide in lower SES groups and should be seen to be at least as important as individual level interventions.

Adolescent↗

In vitro evaluation of complex carbohydrate denture adhesive formulations.

OBJECTIVE: Acemannan, a complex mannose carbohydrate derived from the aloe vera plant, has an inherent stickiness/viscosity. Prototype Acemannan denture adhesive formulations were evaluated for pH changes, cytotoxicity to human gingival fibroblasts and adhesive strength in both dry and wet conditions. METHOD AND MATERIALS: The denture adhesive formulations consisted of five combinations of Acemannan with varying concentrations of preservatives and two other formulations without preservatives. The pH of each formulation was measured over 24 hours. Assessment of cytotoxicity was accomplished using the in vitro, tetrazolium-based colorimetric assay on cultures of human gingival fibroblasts after exposure to the adhesive formulations for up to 24 hours. The adhesive strength was evaluated with a universal testing machine under initial dry conditions and after immersion in a constant-temperature water bath for up to 20 minutes. RESULTS: Formulations 1 and 2 achieved and maintained pH values above 6.0 (the critical pH for hydroxyapatite dissolution) approximately 6 hours into the study. None of the prototypes demonstrated an initial pH above the critical pH. Formulations 1, 2, 3, and 5 exhibited significant cytotoxicity to human gingival fibroblasts over 24 hours. Formulations 4, 20:1, and 150:1 demonstrated minimal cytotoxicity. Formulation 1 exhibited the poorest adhesive strength, while the most viscous formulation (prototype 150:1) was by far the best performer. Generally, adhesive bond strengths for all prototypes were quite high and relatively stable over time in a wet environment. CONCLUSION: To achieve the ideal adhesive in terms of strength, pH, and cytotoxicity, Acemannan formulation 150:1 should be adjusted to contain the preservative concentration of formulation 4 and have an initial pH value of 6.0 or higher.

Adhesiveness↗

Biophysical properties of epithelial water channels.

The biophysical models describing the structure of water pores or channels have evolved, during the last forty years, from a pure 'black box' approach to a molecular based proposal. The initial 'sieving pore' in which water and other molecules were moving together was replaced by a more restrictive model, where water is moving alone in a 'single file' mode. Aquaporins discovery and cloning [G.M. Preston, T.P. Carroll, W.B. Guggino, P. Agre, Science 256 (1992) 365] leaded to the 'hour-glass model' and other alternative proposals, combining information coming from molecular biology experiments and two dimensional crystallography. Concerning water transfers in epithelial barriers the problem is quite complex, because there are at least two alternative pathways: paracellular and transcellular and three different driving forces: hydrostatic pressure, osmotic pressure or 'transport coupled' movements. In the case of ADH-sensitive epithelia it is more or less accepted that regulated water channels (AQP2), that can be inserted in the apical membrane, coexist with basolateral resident water channels (AQP3). The mechanism underlying the so-called 'transport associated water transfer' is still controversial. From the classical standing gradient model to the ion-water co-transport, different hypothesis are under consideration. Coming back to hormonal regulations, other than the well-known regulation by neuro-hypophysis peptides, a steroid second messenger, progesterone, has been recently proposed [P. Ford, G. Amodeo, C. Capurro, C. Ibarra, R. Dorr, P. Ripoche, M. Parisi, Am. J. Physiol. 270 (1996) F880].

Journal Article↗

The clinical value of serum ferritin tests in endurance athletes.

OBJECTIVE: It is common practice to measure serum ferritin levels in endurance athletes because of the belief that low iron stores may compromise performance. The direct relationship between endurance performance and iron deficiency anemia is well known, but there are theoretical reasons to believe that endurance performance may be adversely affected by low iron stores even in the absence of frank anemia. The purpose of this article is to provide a critical review of the scientific evidence relating low iron stores to endurance performance. DATA SOURCES: Medline was searched using MeSH for articles related to ferritin and endurance published since 1985. Additional references were reviewed from the bibliographies of the retrieved articles. STUDY SELECTION: All clinical study designs were reviewed as well as relevant animal studies. Conclusions regarding endurance performance in humans were limited to data from clinical studies. DATA EXTRACTION AND SYNTHESIS: In reviewing the literature, the relative strengths of the study designs were examined carefully. Particular attention of the effectiveness of each study in isolating ferritin as the key independent variable. Dependent measures of endurance capacity were also evaluated. MAIN RESULTS: Eight studies isolated serum ferritin as the experimental variable. Only one study reported a significant improvement in endurance performance (time to exhaustion) in subjects with low ferritin levels treated with oral iron, but this finding may have been magnified by an unexplained decrease in time to exhaustion in the control group. Iron dosages differed in the studies reviewed. Two additional studies that reported increases in performance parameters following increases in ferritin were confounded by concomitant increases in hemoglobin levels. CONCLUSIONS: Iron supplementation can raise serum ferritin levels, but increases in ferritin concentration, unaccompanied by increases in hemoglobin concentration, have not been shown to increase endurance performance. Of concern to the clinician is that athletes with low ferritin levels but hemoglobin in the low-normal range may have iron deficiency anemia responsive to iron supplementation. Low ferritin with hemoglobin in the mid- to upper normal range is at best a relative indication for iron supplementation: low ferritin with hemoglobin in the low normal range is a stronger, yet still relative, indication for iron supplementation in athletes.

Anemia, Iron-Deficiency↗

Effect of cyclosporin A on the expression of tissue kallikrein, kininogen, and bradykinin receptor in rat.

The tissue kallikrein-kinin system is involved in vasodilation and blood pressure regulation. In the present study, we investigated the effects of chronic cyclosporin A (CsA) administration on blood pressure and the expression of tissue kallikrein, kininogen, and bradykinin receptor in normotensive Wistar rats. Chronic administration of CsA significantly increased systolic blood pressure compared with control rats (n = 6, P < 0.01), although body weight was significantly lower than control rats (n = 6, P < 0.01). The development of hypertension was accompanied by the altered expression of kallikrein-kinin system components. Immunoreactive renal kallikrein and urinary excretion of tissue kallikrein levels were increased by chronic administration of CsA (n = 5 or 6, P < 0.05). Levels of N-tosyl-L-phenylalanine chloromethyl ketone-trypsin and kallikrein-releasable kininogens in sera increased in response to chronic CsA treatment (n = 5 or 6, P < 0.05). Chronic CsA treatment significantly increased renal kallikrein, bradykinin B2 receptor, and hepatic kininogen mRNA levels. The increased levels of tissue kallikrein-kinin system components were accompanied by significant increases in 24-h urine excretion and water intake after chronic CsA treatment (n = 5, P < 0.05). These results suggest that enhanced activity of the tissue kallikrein-kinin system may compensate for the CsA-induced vasoconstriction and hypertension.

Animals↗

Involvement of activator protein-1 and nuclear factor-kappaB transcription factors in the control of the DT-diaphorase expression induced by mitomycin C treatment.

The antitumor antibiotic mitomycin C is activated by several bioreductive enzymes, including DT-diaphorase. In HT29 cells, mitomycin C treatment results in the induction of DT-diaphorase as reflected in elevated steady state DT-diaphorase mRNA levels. An increase in the transcriptional rate was demonstrated by nuclear run-on assay. To investigate the molecular basis of the change in transcriptional activity caused by mitomycin C treatment, electrophoretic mobility shift assays were used to demonstrate the induction of nuclear factor binding to elements in the 5' flanking region of the DT-diaphorase gene. Treatment of HT29 cells with mitomycin C resulted in the dose-dependent induction of binding activity directed to the activator protein-1 (AP-1) binding element with a time course similar to that of mRNA elevation. Supershift assays using specific antibodies to Jun and Fos demonstrated the participation of both proteins in the binding activities generated. A binding activity for the nuclear factor-kappaB (NF-kappaB) site was induced with a similar time course. Both competitor and supershift experiments indicated that a heterodimer of the NF-kappaB proteins p50 and p65 was contained in the bound complex. To further investigate the functional consequences of such binding, we transfected HT29 cells with a plasmid containing 3 kb of the DT-diaphorase 5' region upstream of a reporter gene, chloramphenicol acetyltransferase. Treatment with mitomycin C resulted in a 5.5-fold increase in the expression of a chloramphenicol acetyltransferase construct containing 3 kb of DT-diaphorase promoter sequence. Using a series of deletion mutations based on this full-length construct, we found that two regions of the DT-diaphorase promoter region, positions -346 to -588 (containing the AP-1 element) and positions -785 to -890 (containing the NF-kappaB element) are required for the full expression of the mitomycin C response. The specific involvement of these binding elements was confirmed using mutational analysis. The results demonstrate that mutation of either element alone or of both diminishes the response, indicating an additive interaction between the elements at a minimum. However, inducibility characterizes a promoter fragment as small as 78 base-pairs from the transcription start site. Treatment of cells with mitomycin C induced binding to a 38-base-pair region (-40 to -78) devoid of known transcription factor binding elements. These data suggest that mitomycin C induces the overexpression of DT-diaphorase through a mechanism involving both the AP-1 and NF-kappaB response elements and that inducibility depends on a novel factor binding element.

DNA Mutational Analysis↗

Developing outcome indicators in continuing care: part 2.

In their follow-up to last week's article which described the development of outcome indicators for nursing older people in continuing care settings, the authors describe in detail the process of indicator development. Referring to theoretical models, they provide a practical example of how a nurse could use one of his or her experiences from nursing to illustrate the distinct value of patient interventions provided by a registered practitioner.

Aged↗

Developing outcome indicators in continuing care: part 1.

In the first of two articles, the authors describe the development of outcome measures for nursing older people in a continuing care setting. They describe why such a process was initiated and the framework which guided the project, including current nursing and government policy and theories of knowledge and expert practice. The second article will appear next week.

Accidental Falls↗

Validation of a knowledge-based boundary detection algorithm: a multicenter study.

A completely operator-independent boundary detection algorithm for multigated blood pool (MGBP) studies has been evaluated at four medical centers. The knowledge-based boundary detector (KBBD) algorithm is nondeterministic, utilizing a priori domain knowledge in the form of rule sets for the localization of cardiac chambers and image features, providing a case-by-case method for the identification and boundary definition of the left ventricle (LV). The nondeterministic algorithm employs multiple processing pathways, where KBBD rules have been designed for conventional (CONV) imaging geometries (nominal 45 degrees LAO, nonzoom) as well as for highly zoomed and/or caudally tilted (ZOOM) studies. The resultant ejection fractions (LVEF) from the KBBD program have been compared with the standard LVEF calculations in 253 total cases in four institutions, 157 utilizing CONV geometry and 96 utilizing ZOOM geometries. The criteria for success was a KBBD boundary adequately defined over the LV as judged by an experienced observer, and the correlation of KBBD LVEFs to the standard calculation of LVEFs for the institution. The overall success rate for all institutions combined was 99.2%, with an overall correlation coefficient of r=0.95 (P<0.001). The individual success rates and EF correlations (r), for CONV and ZOOM geometers were: 98%, r=0.93 (CONV) and 100%, r=0.95 (ZOOM). The KBBD algorithm can be adapted to varying clinical situations, employing automatic processing using artificial intelligence, with performance close to that of a human operator.

Algorithms↗