Biomedical subjects

S MacDonald

Publications and source records attributed to S MacDonald.

At least 19 recordsLinked to original sources

PubMed2006

Survey of pigs' kidneys with lesions consistent with PMWS and PDNS and ochratoxicosis. Part 2: pathological and histological findings.

One thousand condemned pigs' kidneys were collected in February 2002 from two pig abattoirs in England to assess the lesions due to postweaning multisystemic wasting syndrome (pmws) and porcine dermatitis and nephropathy syndrome (pdns) and the possible contribution of ochratoxicosis; 174 of the kidneys were pale, 295 were swollen and 81 were abnormally firm with the gross appearance of fibrosis. The main macroscopic finding was the presence of multifocal pale cortical lesions, observed in 446 of the kidneys, and there were large cysts in 266 of them. Histopathological lesions of non-suppurative tubulointerstitial nephritis, with degeneration and fibrosis of renal tubules, were identified in 213 of 250 (85.2 per cent) of the kidneys examined. These lesions were consistent with those reported in cases of pmws and pdns. The tubular degeneration and fibrosis were also consistent with ochratoxicosis. A higher mean concentration of ochratoxin A was significantly (P=0.020) associated with the presence of multifocal pale cortical lesions consistent with ochratoxicosis, but a causal relationship was not confirmed because histochemistry was not used to detect ochratoxin in the lesions directly. There was no significant correlation between the microscopic lesions and the concentration of ochratoxin. The degenerative lesions may have been caused by previous exposure to ochratoxin that had subsequently been excreted, but the microscopic lesions also included non-suppurative interstitial nephritis, which was unlikely to have been caused by ochratoxicosis.

Abattoirs↗

PubMed2005

Exposure of garden birds to aflatoxins in Britain.

Aflatoxins are potent biological toxins that have been shown to exert a range of acute and chronic pathological effects. Multiple mortality events of waterfowl caused by acute aflatoxicosis have been documented in the USA. However, international concern has recently been expressed regarding the potential effects of chronic exposure of wildlife species to low levels of dietary aflatoxin. This study documents for the first time the presence of hepatic aflatoxin residues in British wild birds: two passerine species, the house sparrow (Passer domesticus) and greenfinch (Carduelis chloris). Further research is required to investigate the source of the dietary aflatoxins and their pathological significance, if any, for wild birds in Britain.

Aflatoxins↗

PubMed2005

Coronary artery bypass graft imaging using ECG-gated multislice computed tomography: comparison with catheter angiography.

AIM: To compare the value of multislice computerized tomography (MSCT) in imaging coronary artery bypass grafts (CABGs) by direct quantitative comparison with standard invasive angiography. METHODS: Using MSCT, 50 consecutive patients who had previously undergone CABG surgery and had recently undergone invasive angiography for recurrent angina pectoris, were studied further using MSCT after intravenous injection of non-ionic contrast agent; cardiac imaging was performed during a single breath-hold. Graft anatomy was quantified, using both quantitative coronary angiography (QCA) and MSCT, by different investigators blinded to each other. Reproducibility was quantified using the standard error of the measurement expressed as a percentage in log-transformed values (CV%) and intraclass correlation (ICC). RESULTS: All 150 grafts were imaged using MSCT; only 4 patent grafts were not imaged using selective angiography. Good agreement was achieved between MSCT and QCA on assessment of proximal anastomoses (CV% 25.2, ICC 0.84), mid-vessel luminal diameter (CV% 15.5, ICC 0.91) and aneurysmal dilations (CV% 14.3). Reasonable agreement was reached on assessment of distal anastomoses (CV% 26.7, ICC 0.66) and categorization of distal run-off (ICC 0.73). Good agreement was observed for stenoses of over 50% luminal loss (CV% 8.7, ICC 0.97) but agreement on assessment of less severe lesions was poor (CV% 208.7, ICC 0.51). CONCLUSION: This study demonstrates that CABGs can be quantitatively evaluated using MSCT, and that significant lesions present in all CABG segments can be reliably identified. Agreement between MSCT and QCA for lesions of less than 50% luminal loss was poor.

Aged↗

PubMed2005

Assessment of subtle cognitive-communication deficits following acquired brain injury: A normative study of the Functional Assessment of Verbal Reasoning and Executive Strategies (FAVRES).

PRIMARY OBJECTIVE: To present a new measure, the Functional Assessment of Verbal Reasoning and Executive Strategies (FAVRES), with evidence for its reliability and validity in a normative study. The FAVRES is designed to evaluate the subtle cognitive-communication deficits of individuals with ABI. METHODS AND PROCEDURES: The FAVRES consists of four complex, contextually rich, verbal reasoning tasks that simulate everyday situations and require processing of text and discourse. Scoring considers the time, accuracy and justification of reasoning responses. The FAVRES scores of 52 adults with ABI were compared to those of 101 adults without ABI. OUTCOMES: FAVRES scores clearly differentiated the performances of individuals with and without ABI. Individuals with ABI were slower and less accurate in reasoning and presented fewer adequate rationales for their decisions. Inter-rater reliability for scoring was acceptable. CONCLUSIONS: The FAVRES provides a reliable, functional and quantifiable measure of the cognitive-communication difficulties of individuals with ABI.

Adolescent↗

PubMed2004

Survey of ochratoxin A and deoxynivalenol in stored grains from the 1999 harvest in the UK.

Three hundred and twenty samples from the 1999 UK harvest comprising wheat (201 samples), barley (106) and oats (13) were analysed for ochratoxin A and deoxynivalenol. A small number of organic samples was also obtained. Samples were collected from farms, central stores, mills, maltings and ports from across the UK from February to April 2000. Ochratoxin A and deoxynivalenol analysis was by affinity column clean up and high-performance liquid chromatography with fluorescence and ultraviolet light detection, respectively, with limits of detection of 0.2 and 20 microg kg(-1). The survey found ochratoxin A at below 5 microg kg(-1) in 97% of the samples indicating satisfactory storage conditions. The remaining 3% of the samples contained ochratoxin A at levels between 5.2 and 231 microg kg(-1), but none of these samples was intended for human consumption. Deoxynivalenol was detected in 88% of all samples, with 83% below 100 microg kg(-1); the maximum level was 600 microg kg(-1). Twenty samples containing deoxynivalenol at or above 150 microg kg(-1) by high-performance liquid chromatography were all confirmed by gas chromatography/mass spectrometry. Nivalenol was also detected by gas chromatography/mass spectrometry at levels of 50 microg kg(-1) or higher in 18 of 20 samples where deoxynivalenol was confirmed.

Chromatography, High Pressure Liquid↗

PubMed2002

Experimental one year ochratoxin A toxicosis in pigs.

Mild mycotoxic nephropathy was induced in 6 pigs by a diet containing ochratoxin A at 800 ppb, several times higher than that naturally encountered in some feed for pig production in Bulgaria. The nephropathy was expressed only as slightly hypertrophied kidneys with a faintly mottled surface, discernible at the end of the experiment to a skilled observer but probably not recognisable in routine slaughterhouse processing. Histological examination showed two types of changes: degenerative - affecting epithelial cells in some proximal tubules of pigs after 6 months, and proliferative changes in the interstitium which predominated after 1 year of exposure to ochratoxin A. Telangiectasis and lymph stasis were rarely seen. The renal lesions were similar to those described for classical mycotoxic porcine nephropathy formerly encountered in Denmark, but they were rather different from the porcine nephropathy which occurs spontaneously in Bulgaria. Measurement of ochratoxin A in serum provided analytical values complementary to feed intake and with similar concentration values. It also showed both accumulation with time, from 3 months to 6 months (approximately 1 ppm), and a 2-fold range of values within a group eating from a common feed source, as in commercial pig production. Mild symptomatology in this long, single-mycotoxin experiment serves to lessen somewhat the current perception of the direct renal toxicity of ochratoxin A alone, though a role in multi-toxin contexts is unquestioned.

Animal Feed↗

PubMed2002

A capture-recapture model to estimate prevalence of children born in Scotland with developmental eye defects.

BACKGROUND: Microphthalmia, anophthalmia and coloboma (MAC) are closely related structural developmental eye defects that have caused public concern in the UK following media reports of apparent clusters of cases. An extensive search was carried out to identify potential cases, and diagnoses were confirmed by ophthalmological review. Despite this effort, it was recognised that some cases would remain unidentified. Capture-recapture methods could improve the accuracy of the study's birth prevalence estimate. METHODS: A register of all children born with the developmental eye defects of MAC in Scotland (1981-96) was compiled. This identified 188 cases from eight national ascertainment sources. The methods described by Hook and Regal were used to determine possible estimates for each source. A log-linear method of capture-recapture was used to fit a model to the number of children identified by the different combinations of the eight national sources, and the individual sources were included in the model as main effects. RESULTS: Maximum-likelihood estimates were calculated for tables of captured/not captured by one source versus any other source. The estimated number of unobserved cases for the most complete source, the register of congenital anomalies for Scotland, and the seven others combined is 78 (95% CI 53-115). Estimates calculated from two different log-linear models of the numbers of cases unobserved by all sources were 61 (95% CI 43-86) and 175 (95% CI 106-287). An external check with an independent congenital-anomalies register in one region, which is known to have high completeness, gave an estimate of 120. The study found a birth prevalence of MAC in Scotland of 1.9/10000, based on total live births during the study period. The capture-recapture analysis suggests that the true birth prevalence lies between 2.4/10 000 and 3.5/10000. DISCUSSION: Our experience shows that, even with multiple sources of ascertainment and considerable resources directed at case identification, a considerable level of under-ascertainment of congenital eye-anomalies still results, and suggests that the use of capture-recapture analysis would be a useful addition to congenital anomalies registers for needs assessment, disease-burden estimates and health-service planning.

Eye Abnormalities↗

PubMed2001

Orthotopic liver transplantation using low-dose tacrolimus and sirolimus.

Although sirolimus (SRL) binds the immunophilin FK506-binding protein-12 (FKBP-12) with greater avidity than tacrolimus (TAC), animal studies have shown that SRL and TAC act synergistically to prevent rejection. Dose-related toxicity is more often the cause of TAC discontinuation than rejection. We hypothesized that SRL would allow for a substantial reduction in the concomitant dose of TAC after liver transplantation to levels less than the threshold for toxicity. A series of 56 liver transplant recipients were administered a combination of SRL and TAC (target trough levels, 7 and 5 ng/mL, respectively). Planned weaning of steroids commenced after 3 months. Pharmacokinetic (PK) studies were undertaken. Patient and graft survival were 52 patients (93%) and 51 grafts (91%), with a follow-up of 23 months (range, 6 to 35 months). One episode (1.8%) of hepatic artery thrombosis was seen. The rate of acute cellular rejection was 14%. No extra treatment was administered in 3 of 8 patients, and the other 5 episodes responded to a single course of steroids. Cytomegalovirus infection occurred in 4 patients (7%). Renal function, glucose control, and lipid metabolism are near normal in 47 patients (84%) without additional medication. Steroid elimination is completed in 51 patients (91%). Bioavailability of SRL and TAC varied between transplant recipients, but trough levels strongly correlated with the area under the curve (r(2) = 0.82 and r(2) = 0.84, respectively). Simultaneous administration did not affect the PK profile of the drugs at this dose. The ratio of trough level to daily dose correlated between SRL and TAC. The synergistic effect seen in animal models also occurs in clinical liver transplant recipients on SRL-TAC combination immunosuppression. A low-dose combination of SRL and TAC should be compared with conventional immunosuppression in a multicenter, randomized, controlled trial.

Adolescent↗

PubMed2001

Assessment of dietary exposure to ochratoxin A in the UK using a duplicate diet approach and analysis of urine and plasma samples.

The approach to assess exposure to ochratoxin A from the diet by the analysis of human plasma and urine samples has been developed. Composite duplicate diet samples from 50 individuals and corresponding plasma and urine samples were obtained over 30 days. Samples were analysed using sensitive methods capable of measuring ochratoxin A at 0.001 ng g(-1) in food, 0.1 ng ml(-1) in plasma and 0.01 ng ml(-1) in urine. Analysis of the foods indicated ochratoxin A levels contributing to an average intake in the range 0.26-3.54 ng kg(-1) bw day(-1) over the 30 days. Ochratoxin A was found in all plasma samples and in 46 urine samples. The correlation between the plasma ochratoxin A levels and ochratoxin A consumption was not significant (95% confidence limit). However, a significant correlation was found between ochratoxin A consumption and the urine ochratoxin A concentration expressed as the total amount excreted. This new work offers the possibility of using ochratoxin A in urine as a simple and reliable biomarker to estimate exposure to this mycotoxin.

Adult↗

PubMed2001

Posterior-stabilized and cruciate-retaining total knee replacement: a randomized study.

A randomized controlled study was done to compare the clinical, radiographic, and quality of life outcomes between posterior-stabilized and cruciate-retaining primary total knee implants. One hundred forty-three patients were enrolled in the study. Patients ranged in age from 57 to 89 years, had a primary diagnosis of osteoarthritis, and an intact functioning posterior cruciate ligament. Patients were excluded if they had a flexion contracture greater than 15 degrees, a varus deformity greater than 20 degrees, or a valgus deformity greater than 15 degrees. Patients were randomized to one of two study groups, posterior-stabilized AMK total knee implants (76 patients) or cruciate-retaining AMK total knee implants (67 patients). One hundred eight patients have had a minimum 2-year followup including 57 patients in the posterior-stabilized group and 51 patients in the cruciate-retaining group. Seventy-three patients have had a minimum 3-year followup including 37 patients in the posterior stabilized group and 36 patients in the cruciate-retaining group. The overall total Knee Society clinical rating score at 2 years averaged 157.1 points in the posterior-stabilized group and 156.5 points in the cruciate-retaining group. At 3 years, the scores averaged 156.8 points in the posterior-stabilized group and 163.5 points in the cruciate-retaining group. The range of motion component of the Knee Society score averaged 113.6 degrees for the posterior-stabilized group and 108.5 degrees for the cruciate-retaining group at 2 years, and 108.3 degrees in the cruciate-retaining group and 108.5 degrees in the posterior-stabilized group. Based on the various parameters analyzed, there were no notable differences between the groups with a posterior-stabilized and a cruciate-retaining total knee implant at 2 years. This trend seemed to be the same at 3 years.

Aged↗

PubMed2001

Effect of postpyloric feeding on gastroesophageal regurgitation and pulmonary microaspiration: results of a randomized controlled trial.

OBJECTIVE: To determine the extent to which postpyloric feeding reduces gastroesophageal regurgitation and pulmonary microaspiration in critically ill patients. DESIGN: Randomized trial. SETTING: A medical/surgical intensive care unit at a tertiary care hospital. PARTICIPANTS: Intensive care unit patients were expected to remain ventilated >72 hrs. We excluded patients with esophageal, gastric, or small bowel surgery in the last week and patients with overt or clinically significant gastrointestinal bleeding. We studied 33 patients; 42.4% were female, mean age (sd) was 59.2 (+/- 16.8) yrs, and mean Acute Physiology and Chronic Health Evaluation II score was 22.5 (7.8). INTERVENTIONS: Patients were randomized to gastric or postpyloric enteral feeds. Technetium 99-sulphur colloid was added to the feeds for 6 hrs of each of the first 3 days on study. MEASUREMENTS AND RESULTS: We sampled the oropharynx and trachea hourly for the 6 hrs per day that patients received radioisotope-labeled enteral feeds, and the level of radioactivity in these specimens was measured. We defined an episode of gastroesophageal regurgitation and microaspiration as an increase in radioactivity >100 counts per minute/g. Patients fed into the stomach had more episodes of gastroesophageal regurgitation (39.8% vs. 24.9%, p =.04) and trended toward more microaspiration (7.5% vs. 3.9%, p =.22) compared with patients fed beyond the pylorus. When the logarithmic mean of the radioactivity count was compared across groups, there was a trend toward an increase in gastroesophageal regurgitation (3.7 vs. 2.9 counts/g, p =.22) and a trend toward increased microaspiration (1.9 vs. 1.4 counts/g, p =.09) in patients fed into the stomach. Patients who had gastroesophageal regurgitation were much more likely to aspirate than patients who did not have gastroesophageal regurgitation (odds ratio: 3.2; 95% confidence interval: 1.36, 7.77). CONCLUSIONS: Feeding beyond the pylorus is associated with a significant reduction in gastroesophageal regurgitation and a trend toward less microaspiration.

APACHE↗

PubMed2001

Total parenteral nutrition in the surgical patient: a meta-analysis.

OBJECTIVE: To examine the relationship between total parenteral nutrition(TPN) and complication and death rates in surgical patients. DATA SOURCES: A computer search of published research on MEDLINE, personal files and a review of relevant reference lists. STUDY SELECTION: A review of 237 titles, abstracts or papers. Primary studies were included if they were randomized clinical trials of surgical patients that evaluated the effect of TPN (compared to no TPN or standard care) on complication and death rates. Studies comparing TPN to enteral nutrition (EN) were excluded. DATA EXTRACTION: Relevant data were abstracted on the methodology and outcomes of primary studies. Data were independently abstracted in duplicate. DATA SYNTHESIS: There were 27 randomized trials in surgical patients that compared the use of TPN to standard care (usual oral diet plus intravenous dextrose). When the results of these trials were aggregated, there was no effect on mortality (risk ratio = 0.97, 95% confidence intervals, 0.76 to 1.24). There were fewer major complications in patients who received TPN, although there was significant heterogeneity in the overall estimate (risk ratio = 0.81, 95% CI, 0.65 to 1.01). Because of this significant heterogeneity, several a priori hypotheses were examined. Studies that included only malnourished patients demonstrated a trend to a reduction in complication rates but no difference in death rate when compared with studies of patients who were not malnourished. Studies published in 1988 or earlier and studies with a lower methods score were associated with a significant reduction in complication rates and a trend to a reduction in death rate when compared with studies published after 1988 and studies with a higher methods score. There was no difference in studies that provided lipids as a component of TPN when compared with studies that did not. Studies that initiated TPN preoperatively demonstrated a trend to a reduction in complication rates but no difference in death rate when compared with studies that initiated TPN postoperatively. CONCLUSIONS: TPN does not influence the death rate of surgical patients. It may reduce the complication rate, especially in malnourished patients, but study results are influenced by methodologic quality and year of publication.

Enteral Nutrition↗

PubMed2000

Coagulation factor content of cryoprecipitate prepared from methylene blue plus light virus-inactivated plasma.

Levels of factor VIII (FVIII) and fibrinogen were assessed in control cryoprecipitate and cryoprecipitate prepared in two centres from plasma subjected to methylene blue (MB) photochemical virus inactivation. The level of coagulation FVIII activity was reduced in plasma by approximately 30% after MB photoinactivation, with only 44% (centre A) and 31% (centre B) of units meeting the current UK specification of 0.7 iu/ml. A revised specification of 0.5 iu/ml is suggested. Losses of less than 11% were seen for von Willebrand factor (VWF)-related activities. Cryoprecipitate prepared from group O or group A MB-treated plasma contained 27-40% less FVIII than control units. This reflected the lower levels in MB-treated plasma. The concentrating power of the cryoprecipitation process was not reduced for FVIII or fibrinogen in MB-treated units. MB cryoprecipitate from centre A still met the UK guideline specification for FVIII and fibrinogen content, whereas at centre B only 62.5% of the group O cryoprecipitates contained > 70 iu FVIII/unit. This may reflect the lower product volume and lower FVIII content of group O plasma used at centre B and suggests that maintenance of total coagulation factor recovery in MB-treated cryoprecipitate will require the higher product volume.

Antigens↗

PubMed2000

In vitro properties of red cells prepared from half-strength citrate CPD/RAS-2 (Erythro-sol) donations in PL-146 plastic.

Whole blood donations were collected into 0.5CPD anticoagulant in PL-146 plastic. This was shown to improve the stability of plasma FVIII levels when compared with CPD. RAS-2 was used as additive and this improved the in vitro properties of the red cells, such that post processing 2,3-DPG levels were maintained for 21 days and ATP levels were maintained for 28 days. Whether or not such improvements in red cell properties yield a benefit in clinical use remains to be established.

Anticoagulants↗

PubMed2000

Association and linkage of atopic dermatitis with chromosome 13q12-14 and 5q31-33 markers.

Atopic dermatitis is a chronic inflammatory skin disease that affects 10-20% of the population. Linkage of atopy, asthma, allergic rhinitis, and total serum IgE levels to several different chromosomal regions have been described extensively, but little is known about the genetic control of atopic dermatitis. We tested for the association and linkage between atopic dermatitis and five chromosomal regions: 5q31-33, 6p21.3, 12q15-24.1, 13q12-31, and 14q11.2/14q32.1-32.3. Marker analysis was performed in two Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 non-atopic children from a German birth cohort study (MAS'90), parental DNA was tested in 77 of 192 children with atopic dermatitis; (ii) 40 Swedish families with at least one family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. Evidence for linkage and allelic association for atopic dermatitis was observed for markers on chromosome 13q12-14 and 5q31-33.

Child↗

PubMed2000

Cross-cultural and gender differences in childhood amnesia.

In two experiments, we examined cross-cultural and gender differences in adults' earliest memories. To do this, we asked male and female adults from three cultural backgrounds (New Zealand European, New Zealand Maori, and Asian) to describe and date their earliest personal memory. Consistent with past research, Asian adults reported significantly later memories than European adults, however this effect was due exclusively to the extremely late memories reported by Asian females. Maori adults, whose traditional culture includes a strong emphasis on the past, reported significantly earlier memories than adults from the other two cultural groups. Across all three cultures, the memories reported by women contained more information than the memories reported by men. These findings support the view that the age and content of our earliest memories are influenced by a wide range of factors including our culture and our gender. These factors must be incorporated into any comprehensive theory of autobiographical memory.

Adult↗

PubMed2000

Studies on the removal of abnormal prion protein by processes used in the manufacture of human plasma products.

BACKGROUND AND OBJECTIVES: To identify if any process steps used in plasma fractionation may have a capability of removing agents of human transmissible spongiform encephalopathy (TSE). MATERIALS AND METHODS: Sixteen fractionation steps were investigated separately by adding a preparation of hamster adapted scrapie 263K to the starting material at each process step and determining the distribution into resultant fractions of protease-K-resistant (abnormal) prion protein by Western blot analysis. RESULTS: A number of process operations were found to remove abnormal prion protein to the limit of detection of the assay. These were cold ethanol precipitation of fraction IV (log reduction, LR, >/=3.0) and a depth filtration (LR >/=4.9) in the albumin process; cold ethanol fraction I+III precipitation (LR >/=3.7) and a depth filtration (LR >/=2.8) in the immunoglobulin processes and adsorption with DEAE-Toyopearl 650M ion exchanger (LR >/=3.5) in the fibrinogen process. In addition, a substantial degree of removal of abnormal prion protein was observed across DEAE-Toyopearl 650M ion exchange (LR = 3.1) used in the preparation of factor-VIII concentrate; DEAE-cellulose ion exchange (LR = 3.0) and DEAE-sepharose ion exchange (LR = 3.0) used in the preparation of factor-IX concentrates and S-sepharose ion exchange (LR = 2.9) used in the preparation of thrombin. CONCLUSIONS: Plasma fractionation processes used in the manufacture of albumin, immunoglobulins, factor-VIII concentrate, factor-IX concentrates, fibrinogen and thrombin all contain steps which may be capable of removing causative agents of human TSEs.

Animals↗

PubMed1999

Development and testing of the Resistiveness to Care Scale.

A conceptual model and objective scale for measuring resistiveness to care in individuals with advanced dementia of the Alzheimer type (DAT) were empirically generated from the perspective of nursing staff caregivers and through observation of residents with DAT. The resistiveness to care scale (RTC-DAT) was judged to have content validity and reduced to 13 items. Quantifiable scoring procedures and methods for rating videotapes and conducting clinical observations were developed. The RTC-DAT was tested with 68 subjects at three sites. The RTC has a range of 0-156. Initial testing provided reliability estimates of .82-.87 for internal consistency and good to excellent kappas. Criterion-related validity with observed discomfort and construct validity by factor analysis support the RTC-DAT. Measurement issues and recommendations for use in research are discussed.

Activities of Daily Living↗