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Biomedical subjects

J MacDonald

Publications and source records attributed to J MacDonald.

At least 19 recordsLinked to original sources
PubMed2006

Day case transradial coronary angioplasty: a four-year single-center experience.

We examined the safety and feasibility of elective outpatient transradial coronary angioplasty (PCI). Four hundred and forty two patients underwent procedures over a 4-year period. Over 95% had an excellent angiographic result and 85% were discharged the same day. Radial access was successful in 417 (94%) patients. There were no major vascular complications. One patient died of a subacute stent thrombosis. Outpatient transradial PCI is safe and feasible for the majority of elective PCI cases.

Aged↗
PubMed2004

Revision of vagal nerve stimulator electrodes: technical approach.

BACKGROUND: As the number of implanted vagal nerve stimulators grows, the need for removal or revision of the devices will become more frequent. Our purpose was to demonstrate the feasibility of complete removal of the vagal nerve stimulator electrode using microsurgical technique. METHODS: . Operative databases at the University of Utah (1995 through 2002), Westchester Medical Center (1995 through 2001), and University of Arizona Health Sciences Center (1995 through 1999) were retrospectively reviewed. Patients who had undergone removal or revision of a previously placed vagal nerve stimulator electrode were identified. Patients who had a vagal nerve stimulator device removed but had the lead trimmed and incompletely removed were excluded. FINDINGS: Seven patients underwent complete removal of the lead. Microsurgical dissection allowed removal of the helical electrode from the vagus nerve without apparent physiological consequences. Four patients had a new electrode placed just proximal to the original lead site. The operative procedure required an additional 30 minutes to complete compared with initial device placement. The four patients who underwent replacement of the electrode demonstrated normal device function and lead resistance at the time of postoperative follow-up. Each experienced a return to prior stimulation response and seizure control. CONCLUSIONS: This series suggests that the electrode can be removed from the vagus nerve and repositioned without significant consequence in most cases.

Adult↗
PubMed2004

In vitro generation and stability of the lactokinin beta-lactoglobulin fragment (142-148).

The objectives of this study were to investigate the generation of beta-lactoglobulin fragment (142-148) (beta-LG f(142-148) during the hydrolysis of whey proteins, and the in vitro stability of this fragment upon incubation with gastrointestinal and serum proteinases and peptidases. An enzyme immunoassay (EIA) protocol was developed for the quantification of beta-LG f(142-148) in whey protein hydrolysates and in human blood serum. The minimum detection limit was 3 ng/mL. The level of the peptide in whey protein hydrolysates was influenced by the degree of hydrolysis (DH). As expected, highest levels of this peptide were found in hydrolysates generated with trypsin. Sequential incubation of hydrolysates at different DH values with pepsin and Corolase PP, to simulate gastrointestinal digestion, generally resulted in the degradation of beta-LG f(142-148) as determined by EIA. Reversed-phase HPLC and angiotensin-I-converting enzyme (ACE) activity assays demonstrated that synthetic beta-LG f(142-148) was rapidly degraded upon incubation with human serum. Furthermore, beta-LG f(142-148) could not be detected by EIA in the sera of 2 human volunteers following its oral ingestion or in sera from these volunteers subsequently spiked with beta-LG f(142-148). These in vitro results indicate that beta-LG f(142-148) is probably not sufficiently stable to gastrointestinal and serum proteinases and peptidases to act as an hypotensive agent in humans following oral ingestion. The in vitro methodology described herein has general application in evaluating the hypotensive potential of food protein-derived ACE inhibitory peptides.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Agricultural environmental management; case studies from theory to practice.

Six farms were examined, each from a different sector of Scottish agriculture. Surveys were carried out to identify both diffuse pollution risks and options for habitat conservation and enhancement. Financial data were also gathered to determine the current sources of farm income, both from sale of produce and from grants. Whole farm plans were produced aimed at bringing about reductions in diffuse pollution to water, soil and air and also habitat improvements. The assembled information was used to devise a possible agri-environment grant scheme to aid the implementation of the whole farm plans.

Agriculture↗
PubMed2003

Elevated anticardiolipin antibodies in acute liver failure.

Antibodies to cardiolipin (aCLA), a phospholipid primarily localized in inner mitochondrial membranes, were transiently elevated (P<0.01) when mice were exposed to an industrial surfactant and then infected with influenza B virus, a model of acute liver failure (ALF). Children with ALF also had elevated levels of aCLA.

Animals↗
PubMed2003

A lay person versus a trained endoscopist: can the preop endoscopy simulator detect a difference?

The purpose of this study was to establish construct validation of a flexible sigmoidoscopy simulator by comparing training-level grouped subjects. These included clerical staff (n = 10), residents (n = 19), and experts (n = 5). Each participant performed 3 scopes. The ANOVA group-based results for trainer-measured variables are shown in Table 1. These results demonstrate that the flexible sigmoidoscopy simulator distinguished the trained from the untrained and the resident from the expert. Although there was no statistically significant differences between the senior residents and the experts, the expert commonly outperformed the residents. Establishing the transferability of simulator training to real life is next. If the transfer of skill can be established, it may give rise to a new skills training approach.

Administrative Personnel↗
PubMed2003

Use of glazes on porcelain from near ground zero to measure Hiroshima neutron fluence.

Several porcelain samples from almost directly beneath the atomic explosion at Hiroshima on 6 August 1945, have been scanned for induced fission tracks, produced mostly by the thermal neutrons from the bomb due to interactions with trace uranium in their glass coatings. The ability to use porcelain opens a new and abundant material for retrospective dosimetry. Four different samples had thermal neutron fluences in 1945 of 1.0, 3.8, 4.1, and 8.9 x 10(12) cm(-2). The different values are not caused by track fading, but are likely to result from differing shielding at different nearby positions. Assuming that the three highest fluences, which have overlapping uncertainties, are at locations of minimum shielding, the statistically weighted thermal fluence in the air at ground level and ground zero was 4.8 x 10(12) cm(-2) with a statistical uncertainty of 15%. This value lies between the calculated value of 6.5 x 10(12) given in DS86 and the 3.7 x 10(12) inferred from induced radionuclides by Hoshi et al. (1998).

Calibration↗
PubMed2002

Calibration of radioactive contamination monitors for practical use in hospitals.

Quantitative assessment of radioactive contamination is a desirable aim in any department using radionuclides. Guidance is available for calibration of contamination monitors with sealed reference sources but the calibrations obtained in this way are of limited practical use. In this work, we examined methods for calibration using radionuclides used in the hospital workplace. Calibration factors (s-1 per Bq.cm-2) were obtained for 99mTc, 131I, 90Y and 89Sr for three types of monitor for a range of contamination areas, and minimum detectable activities were calculated. Of the three detectors evaluated, the Berthold LB122/LB6357F proved the most sensitive for all radionuclides tested. The effect of contamination area was found to be significant; calibration factors for a particular monitor varied by up to a factor of 4 with contamination area, which has important implications, for example in the estimation of skin doses. User departments need to be aware of this variation and how to correct for it.

Calibration↗
PubMed2001

Effects of Stachybotrys chartarum on surfactant convertase activity in juvenile mice.

We have shown recently that alveolar type II cells are sensitive to exposure to Stachybotrys chartarum spores, both in vitro and in an in vivo juvenile mouse model. In mice, this sensitivity is manifest in part as a significant increase in the newly secreted, biologically active, heavy aggregate form of alveolar surfactant (H) and the accumulation of the lighter, "metabolically used", biologically inactive alveolar surfactant forms (L(vivo)) in the interalveolar space. Conversion of the heavy, surface-active alveolar surfactant to the light metabolically used, nonsurface active forms is believed to involve the activity of an enzyme, namely convertase, which is thought to be derived from lamellar bodies (LB) in alveolar type II cells. The purpose of this study was to evaluate the effects of S. chartarum spores on mouse H and LB convertase activity by measuring their rates of conversion to L(vivo) using the in vitro surface area cycling technique. It was determined whether there were concurrent changes in the protein and phospholipid concentrations of the raw bronchoalveolar lavage fluid (RL) and LB fractions that could be correlated with changes in convertase activity. Conversions of H to L(vivo) in untreated control mice and saline-, isosatratoxin F-, and Cladosporium cladosporioides-exposed mice were not significantly different (p > 0.05). However, conversion from H to L(vivo) in the mice exposed to S. chartarum spores was significantly higher than all other treatment groups (p < 0.001). LB to L(vivo) conversions in untreated and saline-exposed mice were not significantly different, although they were significantly higher than the H to L(vivo) conversions in these two animal treatment groups (p < 0.005), which supports the position that LB is a source of convertase activity in animals. LB to L(vivo) conversion from C. cladosporioides-, isosatrotoxin F-, and S. chartarum-exposed mice were all significantly depressed (p < 0.003) compared to the LB to L(vivo) conversion values obtained from untreated and saline-exposed mice. Protein concentrations in RL, H, L(vivo), and LB from mice exposed to S. chartarum spores were significantly elevated compared to those from the other treatment groups (p < 0.001). Protein concentration in H isolated from C. cladosporioides-exposed mice was also significantly elevated above untreated and saline control animal levels. Phospholipid concentrations in H isolated from S. chartarum-exposed mice were significantly elevated compared to those from other treatment groups, while LB phospholipid concentrations were significantly increased compared to saline and untreated control animal groups. These results show that S. chartarum spores significantly alter convertase activity in both the H and LB surfactant fractions in juvenile mice and that these changes can be related to changes in protein and phospholipid concentrations in alveolar lavage fractions. As surfactant promotes lung stability by reducing the surface tension of the air-alveolar interface, these results further support our position that inhalation exposure to S. chartarum spores in exposed individuals may lead to altered surfactant metabolism, and possibly to lung dysfunction through diminished alveolar surfactant surface tension attributes, and lung stability.

Animals↗
PubMed2001

Endothelium-derived hyperpolarizing factor : identification and mechanisms of action in human subcutaneous resistance arteries.

BACKGROUND: Both a vascular endothelial cytochrome P450 (CYP450) product of arachidonic acid metabolism and the potassium ion (K(+)) have been identified as endothelium-derived hyperpolarizing factors (EDHFs) in animal vascular tissues. We studied the relative importance of EDHF, nitric oxide (NO), and prostacyclin (PGI(2)) as vasodilators in human subcutaneous arteries. We also examined the mechanisms underlying the vasodilator action of EDHF to elucidate its identity. METHODS AND RESULTS: Subcutaneous resistance arteries were obtained from 41 healthy volunteers. The contribution of EDHF to the vasodilation induced by acetylcholine was assessed by inhibiting production of NO, PGI(2), and membrane hyperpolarization. The mechanisms underlying the relaxation evoked by K(+) and EDHF were elucidated. EDHF was found to account for approximately 80% of acetylcholine-mediated vasorelaxation. Its action was insensitive to the combination of barium and ouabain, whereas barium and ouabain reversed K(+)-mediated vasorelaxation. EDHF-mediated vasorelaxation, however, was sensitive to the phospholipase A(2) inhibitor oleyloxyethyl phosphorylcholine and the CYP450 inhibitor ketoconazole. CONCLUSIONS: EDHF is the major contributor to endothelium-dependent vasorelaxation in human subcutaneous resistance arteries. A product of phospholipase A(2)/CYP450-dependent metabolism of arachidonic acid and not K(+) is the likely identity of EDHF in human subcutaneous resistance arteries.

Acetylcholine↗
PubMed2001

Phase I clinical and pharmacokinetic trial of irofulven.

PURPOSE: To evaluate the clinical tolerability of a new schedule of 6-hydroxymethylacylfulvene (irofulven, MGI 114, HMAF, NSC 683863), a semisynthetic sesquiterpene derived from the cytotoxic mushroom metabolite illudin S. Irofulven has been shown to induce DNA damage and apoptosis in vitro and has shown activity in a number of human tumor xenograft models. A number of drug-resistant cell lines including those that express the mdr phenotype, retain sensitivity to irofulven. METHODS: We conducted a phase I trial of irofulven given as an intravenous infusion (30 min) on a daily x5 schedule every 28 days. A total of ten patients were enrolled and treated at three dose levels, 6, 8, and 11 mg/m2 per day. RESULTS: Irofulven reached steady-state concentrations during the 30-min infusions with biexponential kinetics. Irofulven disappeared rapidly from plasma and was detectable for only 15-30 min after the end of the infusion. The mean half-life was 4.91 min and the mean clearance was 4.57 l/mm per m2. Peak plasma concentrations of irofulven of approximately 300 ng/ml were achieved. Pharmacokinetic parameters did not differ significantly from day 1 to day 5. Irofulven was highly emetogenic. Other prominent toxicities included anorexia and fatigue. One case of delayed-onset metabolic acidosis possibly secondary to irofulven was observed. No other renal or metabolic toxicity was encountered. One patient experienced a late-onset grade 3 extravasation skin injury thought to be secondary to extravasation of irofulven. Minimal marrow suppression was observed. No objective tumor responses were observed. CONCLUSIONS: The recommended phase II dose on this schedule is 6 mg/m2.

Acidosis↗
PubMed2001

Signalling mechanisms underlying the myogenic response in human subcutaneous resistance arteries.

OBJECTIVE: In this study we have examined for the first time the signal transduction mechanisms involved in the generation of pressure-dependent myogenic tone in human small resistance arteries from the subcutaneous vascular bed. METHODS: Myogenic responses and the subcellular mechanisms involved in the generation of this response were studied on a pressure myograph. RESULTS AND CONCLUSION: Human subcutaneous resistance arteries constricted 14.1+/-1.1% in response to an increases in intraluminal pressure from 40 to 80 mmHg and a further 3.5+/-1.7% in response to the 80-120-mmHg pressure step. Ca(2+) depletion or nifedipine abolished this response, whereas BAY K 8644 increased this response to 20.6+/-2.1% (P<0.05, response vs. control). The phospholipase C inhibitor U-73122 reduced the myogenic response to 2.5+/-1.0% at 80 mmHg (P<0.01, response vs. control) and abolished it at 120 mmHg. Diacylglycerol lipase inhibition with RHC-80267 abolished all myogenic responses to pressure. The protein kinase C (PKC) activator phorbol 12,13-dibutyrate increased the maximal myogenic response to 20.9+/-1.8% (P<0.05, response vs. control), whereas the PKC inhibitor calphostin C abolished myogenic responses. These data show that the generation of pressure-dependent myogenic tone in human subcutaneous arteries is dependent on Ca(2+) influx via voltage operated Ca(2+) channels (VOCCs) and a concomitant requirement for the activation of phospholipase C (PLC), diacylglycerol, and PKC.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2001

Analysis of pulmonary surfactant by Fourier-transform infrared spectroscopy following exposure to Stachybotrys chartarum (atra) spores.

Lung cells are among the first tissues of the body to be exposed to air-borne environmental contaminants. Consequently the function of these cells may be altered before other cells are affected. As gas exchange takes place in the lungs, changes in cellular function may have serious implications for the processes of oxygen uptake and carbon dioxide elimination. In order for these processes to occur, the lung must maintain a high degree of expandability. This latter function is accomplished in part by the pulmonary surfactant which is synthesized and released by alveolar type II cells. Earlier studies have shown that exposure to gas phase materials such as smoke or organic solvents can alter the composition and function of the surfactant. The present study examines the ability of highly toxigenic mold spores to alter surfactant composition. Stachybotrys chartarum spores suspended in saline were instilled into mouse trachea as described earlier. After 24 h, the lungs were lavaged and the different processing stages of surfactant isolated by repeated centrifugation. Intracellular surfactant was isolated from the homogenized lung tissue by centrifugation on a discontinuous sucrose gradient. Samples were extracted into chloroform-methanol, dried and analyzed by Fourier-Transform infrared spectroscopy (FTIR). Exposure to S. chartarum induced an overall reduction of phospholipid among the three surfactant subfractions. The intermediate and spent surfactant fractions in particular were reduced to about half of the values observed in the saline-treated group. The relative distribution of phospholipid was also altered by spore exposure. Within the intracellular surfactant pool, higher levels of phospholipid were detected after spore exposure. In addition, changes were observed in the nature of the phospholipids. In particular strong intramolecular hydrogen bonding, together with other changes, suggested that spore exposure was associated with absence of an acyl chain esterified on the glycerol backbone, resulting in elevated levels of lysophospholipid in the samples. This study shows that mold spores and their products induce changes in regulation of both secretion and synthesis of surfactant, as well as alterations in the pattern of phospholipid targeting to the pulmonary surfactant pools.

Animals↗
PubMed2001

Neonatal mouse model: review of methods and results.

The neonatal mouse model, in various forms, has been used experimentally since 1959 and a large number of chemicals have been tested. The neonatal model is known to be very sensitive for the detection of carcinogens that operate via a genotoxic mode of action. In contrast, it is known not to respond to chemicals that act via epigenetic mechanisms, commonly observed in the two-year carcinogenicity studies. As such, the model has a high sensitivity and specificity in its response. Dose selection for the neonatal model is based on the maximum tolerated or feasible dose. Traditionally, compounds have been tested via the IP route of administration in this model. In some cases, this has limited the amount of material that can be administered because of the low dosing volumes (10 to 20 microL) that can be administered IP. For the ILSI project, the neonatal model was adapted for oral administration, which has the advantages of being the same route for which most pharmaceuticals are administered. In addition, a 10-fold increase in the volume of administration (100 to 200 microL) and the ability to dose drugs in suspension, permits much higher doses to be used as compared to the IP route of administration. The spontaneous tumors in the neonatal model occurred mainly in the liver of male mice and lung of male and female mice with a few tumors observed in the Harderian gland. The positive control, DEN produced a robust, uniform, and reproducible tumor response with the target organs essentially limited to liver and lung. A total of 13 compounds out of the 21 ILSI ACT compounds were evaluated in the neonatal model involving 18 studies with duplicate studies for some compounds. The genotoxic carcinogens including those used as positive controls were clearly positive (cyclophosphamide, diethylnitrosamine, 6-nitrochrysene). The non-genotoxic rodent carcinogens were clearly negative (chlorpromazine, sulfisoxazole, sulfamethoxazole, clofibrate, DEHP, haloperidol, metaproteranol, and phenobarbital). The non-genotoxic human carcinogen (cyclosporin) was clearly negative. The two other human carcinogens phenacetin and DES were negative and interestingly estradiol was negative in one of the two oral studies, but was clearly positive in the other. Considering the mode of action for three of the human carcinogens (DES, cyclosporin and phenacetin), which were negative in this model, the mode of action in humans is likely to be epigenetic. Overall, for the 3 clearly genotoxic chemicals, all were positive. For the 9 clearly non-genotoxic chemicals, all 9 were negative. The two human carcinogens for which genotoxicity may or may not play a role (DES and phenacetin) were negative and estradiol was positive in I of the two oral studies. Overall, the extensive database for compounds tested in the neonatal mouse model would support its use as an alternative model for the assessment of the carcinogenic potential of a chemical. The model responds to chemicals that act via a genotoxic mode of action that represent a greater concern for human cancer risk.

Administration, Oral↗
PubMed2001

Personal radon dosimetry from eyeglass lenses.

Eyeglass lenses are commonly composed of allyl-diglycol carbonate (CR-39), an alpha-particle detecting plastic, thus making such lenses personal radon dosemeters. Samples of such lenses have been obtained, etched to reveal that radon and radon progeny alpha tracks can be seen in abundance, and sensitivities have been calibrated in radon chambers as a primary calibration, and with a uranium-based source of alpha particles as a convenient secondary standard. With one exception natural, environmental (fossil) track densities ranged from less than 3,000 to nearly 70,000 per cm2 for eyeglasses that had been worn for various times from one to nearly five years. Average radon concentrations to which those wearers were exposed are inferred to be in the range 14 to 130 Bq x m(-3) (0.4 to 3.5 pCi x l(-1)). A protocol for consistent, meaningful readout is derived and used. In the exceptional case the fossil track density was 1,780,000 cm(-2) and the inferred (24 h) average radon concentration was 6500 Bq x m(-3) (175 pCi x l(-1)) for a worker at an inactive uranium mine that is used for therapy.

Eyeglasses↗
PubMed2001

Alternative models for carcinogenicity testing.

The International Conference on Harmonisation Expert Working Group on Safety suggested that under certain circumstances, data from alternative assays could be used in safety evaluation in place of a second bioassay. Several alternatives were discussed. Six of these models were evaluated in a collaborative effort under the auspices of the Health and Environmental Sciences Institute (HESI) branch of the International Life Sciences Institute (ILSI). Standard protocols, pathology review, and statistical evaluations were developed. Twenty-one chemicals were evaluated, including genotoxic, nongenotoxic, carcinogenic, and noncarcinogenic chemicals. The models that were evaluated included the p53(+/-) heterozygous knockout mouse, the rasH2 transgenic mouse, the TgAC transgenic mouse (dermal and oral administration), the homozygous XPA knockout and the XPA/p53 knockout mouse models. Also evaluated were the neonatal mouse models and the Syrian Hamster Embryo (SHE) transformation assay. The results of this comprehensive study suggest that some of these models might be useful in hazard identification if used in conjunction with information from other sources in a weight of evidence, integrated analysis approach to risk assessment.

Animals↗
PubMed2001

Dealing with emergencies in rural areas of Europe: proceedings from WONCA Europe 2000.

On 4 July 2000, two workshops on handling emergencies in rural areas of Europe were held at the WONCA (World Organisation of National Colleges and Academies of Family Medicine/General Practice) conference in Vienna under the auspices of EURIPA (European Rural and Isolated Practitioners' Association). Papers submitted covered varying patterns of service provision and examples of short intensive training for emergencies at resident and general practitioner levels. Ways of collecting data routinely for accident prevention were also discussed. The workshops concluded that there was a need for more research in the application of emergency skills, that lack of confidence in dealing with emergencies may contribute to recruitment problems, and that further work towards a document detailing training requirements for emergencies was needed. This will be developed at a EURIPA workshop at WONCA in Tampere, June 2001.

Accident Prevention↗