Biomedical subjects

A J Fitzgerald

Publications and source records attributed to A J Fitzgerald.

At least 19 recordsLinked to original sources

PubMed2005

Trial of trefoil factor 3 enemas, in combination with oral 5-aminosalicylic acid, for the treatment of mild-to-moderate left-sided ulcerative colitis.

BACKGROUND: Current treatment of ulcerative colitis is imperfect. Trefoil peptides are known to stimulate repair in many models of injury, including animal models of colitis. AIM: To assess the efficacy of trefoil factor family-3 enema treatment in a clinical trial. METHODS: A total of 16 patients with mild-to-moderate left sided ulcerative colitis were recruited into a double-blind randomized placebo-controlled study. Patients taking steroids or with proctitis only were excluded. Patients received 75 mL enemas containing either human recombinant trefoil factor family-3 (10 mg/mL) or saline alone once a day for 14 days. All patients also received an oral dose-increment of 1.2 g of mesalazine daily above their normal usage. Patients were assessed at 0, 2, 4 and 12 weeks. Remission was defined as Ulcerative Colitis Disease Activity Index of 0 or 1 with no blood in stool. Individual clinical improvement was defined as a Ulcerative Colitis Disease Activity Index reduction of >3. Data was analysed using chi-square test and anova. RESULTS: Median Ulcerative Colitis Disease Activity Index at entry were 8.5 (trefoil factor family-3 group) and 8 (placebo group). Analysed on an intention-to-treat basis, only one patient went into remission (in trefoil factor family-3 group at day 28). Clinical improvement was seen in two trefoil factor family-3 and three placebo patients on day 14 and two patients in each group on day 28. CONCLUSION: Increasing the dose of 5-aminosalicylic acid was moderately effective in reducing the Ulcerative Colitis Disease Activity Index but was insufficient to induce remission. Trefoil factor family-3 enemas were well-tolerated but did not provide additional benefit above that of adding additional 5-aminosalicylic acid alone.

Administration, Oral↗

PubMed2005

Reparative properties of a commercial fish protein hydrolysate preparation.

BACKGROUND: A partially hydrolysed and dried product of pacific whiting fish is currently marketed as a health food supplement to support "intestinal health". However, there has been only limited scientific study regarding its true biological activity. AIMS: We therefore tested its efficacy in a variety of models of epithelial injury and repair. METHODS: Effects on proliferation were determined using [(3)H] thymidine incorporation into epithelial rat intestinal RIE-1 and human colonic HT29 cells. Effects on restitution (cell migration) were analysed using wounded HT29 monolayers and its ability to influence gastric injury analysed using a rat indomethacin restraint model. Partial characterisation of bioactive agents was performed using mass spectroscopy, high pressure liquid chromatography, and gas chromatography. RESULTS: Both cell proliferation and cell migration were increased by about threefold when added at 1 mg/ml (p<0.01). Gastric injury was reduced by 59% when gavaged at 25 mg/ml (p<0.05), results similar to using the potent cytoprotective agent epidermal growth factor at 12.5 mug/ml. The vast majority of biological activity was soluble in ethanol, with glutamine in its single, di-, and tripeptide forms probably accounting for approximately 40% of the total bioactivity seen. Fatty acid constituents may also have contributed to cell migratory activity. CONCLUSIONS: Fish protein hydrolysate possesses biological activity when analysed in a variety of models of injury and repair and could provide a novel inexpensive approach for the prevention and treatment of the injurious effects of non-steroidal anti-inflammatory drugs and other ulcerative conditions of the bowel. Further studies appear justified.

Animals↗

PubMed2004

In vivo study of human skin using pulsed terahertz radiation.

Studies in terahertz (THz) imaging have revealed a significant difference between skin cancer (basal cell carcinoma) and healthy tissue. Since water has strong absorptions at THz frequencies and tumours tend to have different water content from normal tissue, a likely contrast mechanism is variation in water content. Thus, we have previously devised a finite difference time-domain (FDTD) model which is able to closely simulate the interaction of THz radiation with water. In this work we investigate the interaction of THz radiation with normal human skin on the forearm and palm of the hand in vivo. We conduct the first ever systematic in vivo study of the response of THz radiation to normal skin. We take in vivo reflection measurements of normal skin on the forearm and palm of the hand of 20 volunteers. We compare individual examples of THz responses with the mean response for the areas of skin under investigation. Using the in vivo data, we demonstrate that the FDTD model can be applied to biological tissue. In particular, we successfully simulate the interaction of THz radiation with the volar forearm. Understanding the interaction of THz radiation with normal skin will form a step towards developing improved imaging algorithms for diagnostic detection of skin cancer and other tissue disorders using THz radiation.

Algorithms↗

PubMed2004

Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo.

BACKGROUND: Terahertz radiation lies between the infrared and microwave regions of the electromagnetic spectrum and can be used to excite large amplitude vibrational modes of molecules and probe the weak interactions between them. Terahertz pulsed imaging (TPI) is a noninvasive imaging technique that utilises this radiation. OBJECTIVES: To determine whether TPI could differentiate between basal cell carcinoma (BCC) and normal tissue and to test whether it can help facilitate delineation of tumour margins prior to surgery. METHODS: A portable TPI system was used in the clinic to image 18 BCCs ex vivo and five in vivo. RESULTS: The diseased tissue showed a change in terahertz properties compared with normal tissue, manifested through a broadening of the reflected terahertz pulse. Regions of disease identified in the terahertz image correlated well with histology. CONCLUSIONS: This study has confirmed the potential of TPI to identify the extent of BCC in vivo and to delineate tumour margins. Further clinical study of TPI as a surgical tool is now required.

Aged↗

PubMed2003

Effect of epidermal growth factor administration on intestinal cell proliferation, crypt fission and polyp formation in multiple intestinal neoplasia (Min) mice.

Recombinant epidermal growth factor (EGF) may be useful to treat severe ulcerative gastrointestinal injury. There is concern, however, that systemic use of this potent mitogen might increase tumour development and/or progression in susceptible subjects. We therefore examined the effect of chronic administration of systemic EGF to multiple intestinal neoplasia (Min ) mice, who have a genetic defect in the adenomatous polyposis coli (APC) gene, leading to increased polyp development. Min mice (n =26) and wild-type littermates (n =26) received saline or EGF (223 microg of EGF/kg per day) for 4 weeks using subcutaneous osmotic mini-pumps. Cell proliferation and crypt fission were analysed using microdissection techniques and the number and size of polyps in the small and large intestines were determined. EGF increased wet weight and crypt cell proliferation rate by approx. 20% (all P <0.01 compared with the relevant control) in the small intestine and colon of both control and Min mice. In both groups, EGF reduced the colonic fission index by approx. 40% (P <0.01), but did not affect crypt fission in the small intestine. In Min mice, administration of EGF did not increase numbers of polyps or degree of dysplasia, but resulted in a 40% increase in the polyp size in the proximal intestine (P <0.02), but not in the remainder of the small intestine or colon. No polyps were found in control mice given EGF. EGF did not initiate polyp formation in control or Min mice. However, as polyp size is an important determinant for subsequent risk of malignant change in human colon cancer, further studies appear justified.

Adenomatous Polyposis Coli↗

PubMed2002

Evaluation of image quality in terahertz pulsed imaging using test objects.

As with other imaging modalities, the performance of terahertz (THz) imaging systems is limited by factors of spatial resolution, contrast and noise. The purpose of this paper is to introduce test objects and image analysis methods to evaluate and compare THz image quality in a quantitative and objective way, so that alternative terahertz imaging system configurations and acquisition techniques can be compared, and the range of image parameters can be assessed. Two test objects were designed and manufactured, one to determine the modulation transfer functions (MTF) and the other to derive image signal to noise ratio (SNR) at a range of contrasts. As expected the higher THz frequencies had larger MTFs, and better spatial resolution as determined by the spatial frequency at which the MTF dropped below the 20% threshold. Image SNR was compared for time domain and frequency domain image parameters and time delay based images consistently demonstrated higher SNR than intensity based parameters such as relative transmittance because the latter are more strongly affected by the sources of noise in the THz system such as laser fluctuations and detector shot noise.

Diagnostic Imaging↗

PubMed2002

Wavelet compression in medical terahertz pulsed imaging.

This paper concerns the robustness of discrete wavelet transform (DWT) compression in terahertz pulsed imaging (TPI). TPI datasets consist of terahertz time-domain series which are sampled at each 'pixel' of the image, leading to file sizes which are typically of the order of several megabytes (MB) per image. This makes efficient compression highly desirable for both transmission and storage. However, since the data may be required for diagnostic purposes it is essential that no relevant information is lost or artefacts introduced. We show that for a nylon step wedge the estimates of refractive index and absorption coefficients are not significantly altered when the terahertz data are reconstructed from only 20% of DWT coefficients.

Algorithms↗

PubMed2002

An introduction to medical imaging with coherent terahertz frequency radiation.

Methods have recently been developed that make use of electromagnetic radiation at terahertz (THz) frequencies, the region of the spectrum between millimetre wavelengths and the infrared, for imaging purposes. Radiation at these wavelengths is non-ionizing and subject to far less Rayleigh scatter than visible or infrared wavelengths, making it suitable for medical applications. This paper introduces THz pulsed imaging and discusses its potential for in vivo medical applications in comparison with existing modalities.

Alginates↗

PubMed2002

Lectins can reverse the distal intestinal atrophy associated with elemental diets in mice.

BACKGROUND: Elemental diets cause intestinal atrophy and reduced intestinal integrity, which can lead to significant increases in intestinal permeability and bacterial translocation. Recently, several lectins have been shown to have trophic effects on the intestine. AIMS: We examined the effects of concanavalin-A and phytohaemagglutinin on cell proliferation and crypt fission throughout the intestine of mice fed on elemental diets. METHODS: Mice were randomized to chow fed, elemental diet, elemental diet plus concanavalin-A and elemental diet plus phytohaemagglutinin groups. Cell proliferation and crypt fission were estimated in microdissected crypts. Plasma gastrin and enteroglucagon levels were measured by radioimmunoassay. RESULTS: Elemental diet feeding significantly decreased cell proliferation and crypt fission of the middle and distal small intestine and throughout the colon. Phytohaemagglutinin significantly increased the weight of the intestine, but concanavalin-A had little effect. Cell proliferation in the small intestine was significantly increased by both lectins. However, in the stomach and colon, only phytohaemagglutinin increased proliferation. Crypt fission in the colon was dramatically increased by phytohaemagglutinin. Phytohaemagglutinin increased the plasma gastrin level, but not the enteroglucagon level. CONCLUSIONS: Lectins have significant trophic effects on the small intestine and colon of mice fed elemental diets, and these actions vary between different sites in the gastrointestinal tract.

Animals↗

PubMed2002

A comparison of techniques to optimize measurement of voltage changes in electrical impedance tomography by minimizing phase shift errors.

In electrical impedance tomography, errors due to stray capacitance may be reduced by optimization of the reference phase of the demodulator. Two possible methods, maximization of the demodulator output and minimization of reciprocity error have been assessed, applied to each electrode combination individually, or to all combinations as a whole. Using an EIT system with a single impedance measuring circuit and multiplexer to address the 16 electrodes, the methods were tested on resistor-capacitor networks, saline-filled tanks and humans during variation of the saline concentration of a constant fluid volume in the stomach. Optimization of each channel individually gave less error, particularly on humans, and maximization of the output of the demodulator was more robust. This method is, therefore, recommended to optimize systems and reduce systematic errors with similar EIT systems.

Artifacts↗

PubMed2001

Comparison of the effects of concanavalin-A and epidermal growth factor on epithelial cell proliferation in the rat intestine.

BACKGROUND: Concanavalin-A, the lectin present in Jack beans, binds to mannose- and glucose-containing residues and can interact with the epidermal growth factor receptor and moderate cell proliferation in vitro. AIM: To compare the actions of concanavalin-A and epidermal growth factor on the gastrointestinal tract in vivo. METHODS: Rats maintained on total parenteral nutrition were given intragastric concanavalin-A, intravenous epidermal growth factor or concanavalin-A and epidermal growth factor. Cell proliferation and crypt fission were assayed in 'micro-dissected' crypts. RESULTS: Concanavalin-A and epidermal growth factor both significantly elevated proliferation in the small intestine and colon. No significant interaction between the effects of these two agents was seen, except in the mid small intestine where there was a synergistic interaction. Concanavalin-A had no effect on crypt branching. Epidermal growth factor significantly reduced branching in the distal small intestine and mid colon. CONCLUSION: The effects of the two agents appeared to be separate, except in the mid small intestine where they were additive. This is in marked contrast with the actions reported in vitro, where concanavalin-A is a powerful inhibitor of epidermal growth factor-induced cell proliferation. Concanavalin-A thus has potential for enhancing the functions of the small intestine.

Animals↗

PubMed2001

Glicentin, an active enteroglucagon, has a significant trophic role on the small intestine but not on the colon in the rat.

BACKGROUND: Many experiments have indicated that the gut glucagons (enteroglucagons) are associated with cell proliferation in the small intestine. However, recent studies have failed to show trophic effects of glicentin (enteroglucagon) on the intestine. AIMS: To examine the effects of glicentin on intestinal proliferation in vivo in the rat. METHODS: Rats were established on total parenteral nutrition for 6 days. Four experimental groups were given daily doses of 1, 4, 20 and 80 microg/rat of glicentin via the jugular vein. Rats fed by total parenteral nutrition and rats fed chow ad libitum were used as controls. Tissues taken from the duodenum, jejunum, ileum and colon were fixed in Carnoy's fluid and microdissected to determine the metaphase arrest scores and crypt fission ratios. RESULTS: The mean metaphase arrest scores per crypt of the small intestine were significantly increased in the rats given 4, 20 and 80 microg of glicentin. These responses were dose-dependent, and were most prominent in the ileum. Crypt fission of the ileum was significantly decreased in the 20 and 80 microg glicentin groups. Glicentin had no effects on proliferation or fission in the colon. CONCLUSIONS: Glicentin is trophic to the rat small intestine, but not the colon.

Animals↗

PubMed2001

Breast cancer screening education: comparing outcome skills of nurse practitioner students and medical residents.

BACKGROUND: Nurse practitioner students, along with all primary care trainees, need breast cancer screening education. The purpose of the study was to compare the performances of nurse practitioner students and medical residents before and after receiving training. METHODS AND RESULTS: In a pretest/posttest design, 51 nurse practitioner students and 47 medical residents received training either from a standardized patient or from a lecture/demonstration class. Before training and 1 year after, participants took the written test and had their skills evaluated by a standardized patient. There were no significant differences between the nurse practitioner students and the medical residents in the mean scores on the written pretest or on the written posttest with both groups improving their scores. The nurse practitioner students had significantly higher scores on the practicum posttest (P <.05). CONCLUSIONS: Nurse practitioner students perform well in learning breast cancer screening. More than one method of teaching is effective.

Breast Neoplasms↗

PubMed2001

Breast cancer screening for primary care trainees: comparison of two teaching methods.

BACKGROUND: This study compared the efficacies of two methods of teaching breast cancer screening to primary care trainees. METHODS: Fifty-one nurse-practitioner students were assigned by class section and 47 medical residents by practice site to receive a lecture-demonstration class or individual/small-group instruction from a standardized patient. Prior to instruction and one year later, participants took a written test to assess knowledge and standardized patients evaluated their skills. RESULTS: Overall, the participants improved their breast cancer screening skills. CONCLUSION: The standardized patient teaching method was of greater benefit to the nurse-practitioner students.

Breast Neoplasms↗

PubMed2001

The interaction between Terahertz radiation and biological tissue.

Terahertz (THz) radiation occupies that region of the electromagnetic (EM) spectrum between approximately 0.3 and 20 THz. Recent advances in methods of producing THz radiation have stimulated interest in studying the interaction between radiation and biological molecules and tissue. Given that the photon energies associated with this region of the spectrum are 2.0 x 10(-22) to 1.3 x 10(-20) J, an analysis of the interactions requires an understanding of the permittivity and conductivity of the medium (which describe the bulk motions of the molecules) and the possible transitions between the molecular energy levels. This paper reviews current understanding of the interactions between THz radiation and biological molecules, cells and tissues. At frequencies below approximately 6 THz. the interaction may be understood as a classical EM wave interaction (using the parameters of permittivity and conductivity), whereas at higher frequencies. transitions between different molecular vibrational and rotational energy levels become increasingly important and are more readily understood using a quantum-mechanical framework. The latter is of particular interest in using THz to probe transitions between different vibrational modes of deoxyribonucleic acid. Much additional experimental work is required in order to fully understand the interactions between THz radiation and biological molecules and tissue.

Amino Acids↗

PubMed2000

Systemic effect of peanut agglutinin following intravenous infusion into rats.

BACKGROUND: Ingested peanut agglutinin stimulates colonic proliferation in humans. In rats, ingested peanut agglutinin stimulates hormone release and proliferation in the small and large intestines. Peanut agglutinin is absorbed into the circulation but little is known about the systemic effect of this lectin. Therefore, we studied the effect of intravenous peanut agglutinin on hormone release and intestinal growth. METHOD: Six rats per group received peanut agglutinin infusion at 0, 2, 20 or 200 microg/rat/day for 6 days via the right jugular vein. Organ weights were measured, pancreatic enzymes, DNA, RNA and protein levels were analysed. Plasma hormones were measured by radioimmunoassay. All tissues were examined histologically. Small intestinal and colonic proliferation rates were estimated by metaphase arrest. RESULTS: High-dose peanut agglutinin significantly reduced the wet weight of the stomach by 7% (P < 0.05) and large intestine by 10% (P < 0.05). Peanut agglutinin dose-dependently released enteroglucagon; low-, medium- and high-dose by 64%, 126% (P < 0.01) and 180% (P < 0.01), respectively, and glucagon-like peptide-1 by 127% (P < 0.01), 169% (P < 0.01) and 315% (P < 0.001), respectively. Peanut agglutinin had no effect on cholesystokinin, gastrin or insulin levels. Peanut agglutinin, low-, medium- and high-dose stimulated proliferation in the mid colon by 42% (P < 0.01), 30% and 38%, respectively. Only high-dose peanut agglutinin stimulated proliferation in the distal colon by 54% (P < 0.01). No histological changes were evident in any tissue. CONCLUSION: Intravenous peanut agglutinin released hormones and stimulated colonic proliferation. Proliferation of the small intestine seen after ingestion of peanut agglutinin in previous studies appears to require luminal contact between enterocytes and the lectin. Possible clinical applications include reversal of atrophy during total parenteral nutrition, anastomotic healing after surgery and restoration of mucosa integrity in colitis.

Animals↗

PubMed2000

Glucagon-like peptide-2 increases sucrase-isomaltase but not caudal-related homeobox protein-2 gene expression.

To determine the effect of glucagon-like peptide-2 (GLP-2) on sucrase-isomaltase and caudal-related homeobox protein-2 (Cdx-2) gene expression, male Wistar rats were divided into total parenteral nutrition (TPN)-fed and GLP-2-treated, TPN-fed groups. TPN was given via a jugular line, inserted under anesthesia, for 7 days. The treatment group received 40 microg/day of GLP-2 intravenously with the TPN diet. The small intestine and colon were weighed and measured. Tissue was obtained from the jejunum, terminal ileum, and midcolon. RNA analysis, morphometry, and microdissection were performed. The weight of the small intestine of GLP-2-treated rats was greater than that of TPN-fed rats (P < 0.001). GLP-2 increased the mean metaphase arrests/crypt in both the jejunum and ileum (P < 0.001). Ileal expression of sucrase-isomaltase was increased by 1. 6-fold (P < 0.05). Jejunal expression was increased by a similar amount, although not significantly (P = 0.08). There was no change in Cdx-2 gene expression. Thus GLP-2 can maintain small intestinal morphology and function, but effects on gene expression are not mediated by gross changes in the level of the mRNA for the homeobox protein Cdx-2.

Animals↗

PubMed1997

Extraction of electrical characteristics from pixels of multifrequency EIT images.

Computer modelling has shown that electrical characteristics of individual pixels may be extracted from within multiple-frequency electrical impedance tomography (MFEIT) images formed using a reference data set obtained from a purely resistive, homogeneous medium. In some applications it is desirable to extract the electrical characteristics of individual pixels from images where a purely resistive, homogeneous reference data set is not available. One such application of the technique of MFEIT is to allow the acquisition of in vivo images using reference data sets obtained from a non-homogeneous medium with a reactive component. However, the reactive component of the reference data set introduces difficulties with the extraction of the true electrical characteristics from the image pixels. This study was a preliminary investigation of a technique to extract electrical parameters from multifrequency images when the reference data set has a reactive component. Unlike the situation in which a homogeneous, resistive data set is available, it is not possible to obtain the impedance and phase information directly from the image pixel values of the MFEIT images data set, as the phase of the reactive reference is not known. The method reported here to extract the electrical characteristics (the Cole-Cole plot) initially assumes that this phase angle is zero. With this assumption, an impedance spectrum can be directly extracted from the image set. To obtain the true Cole-Cole plot a correction must be applied to account for the inherent rotation of the extracted impedance spectrum about the origin, which is a result of the assumption. This work shows that the angle of rotation associated with the reactive component of the reference data set may be determined using a priori knowledge of the distribution of frequencies of the Cole-Cole plot. Using this angle of rotation, the true Cole-Cole plot can be obtained from the impedance spectrum extracted from the MFEIT image data set. The method was investigated using simulated data, both with and without noise, and also for image data obtained in vitro. The in vitro studies involved 32 logarithmically spaced frequencies from 4 kHz up to 1 MHz and demonstrated that differences between the true characteristics and those of the impedance spectrum were reduced significantly after application of the correction technique. The differences between the extracted parameters and the true values prior to correction were in the range from 16% to 70%. Following application of the correction technique the differences were reduced to less than 5%. The parameters obtained from the Cole-Cole plot may be useful as a characterization of the nature and health of the imaged tissues.

Biometry↗