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Biomedical subjects

T Graham

Publications and source records attributed to T Graham.

At least 19 recordsLinked to original sources

Use of in-stream reservoirs to reduce bacterial contamination of rural watersheds.

An investigation into bacterial water quality problems was conducted on an interconnected stream and irrigation system within the Oldman River Basin of southern Alberta, Canada. Levels of indicator bacteria, including fecal coliforms, generic Escherichia coli and fecal streptococci, were repeatedly measured in streams and irrigation return canals of this river basin during the summer of 2001. Bacterial-loading segments of the irrigation/stream system were identified through a comparison of indicator bacteria levels in pairs of upstream and downstream sites. Mann-Whitney U-tests indicated that reservoirs significantly reduced bacterial counts. A temporal comparison of E. coli counts and river discharges suggested that these indicator bacteria do not originate from within in-stream sediments. Site-specific as well as cumulative inputs from a variety of non-point sources are likely to be responsible for the high downstream levels of indicator bacteria in this water system. The use of management practices such as in-stream reservoirs may significantly reduce contamination, and increase the quality of limited rural water supplies to allow their reuse and safe discharge into downstream water sources. The identification of bacteria-loading river/canal segments could also be used to prioritize restoration projects.

Agriculture↗

Severe hypercholesterolemia mediated by lipoprotein X in patients with chronic graft-versus-host disease of the liver.

We describe a series of cases of extreme hypercholesterolemia mediated by lipoprotein X in patients with chronic graft-versus-host disease of the liver after an allogeneic bone marrow transplant. All of the patients presented with a total cholesterol in excess of 1000 mg/dl (25.9 mmol/l). At the time they were also noted to have pseudohyponatremia. Cholesterol appeared to be predominantly carried by lipoprotein X. Intrahepatic cholestasis leading to reflux of bile lipoproteins into the bloodstream and subsequent formation of protein X appears to be the mechanism underlying this phenomenon. Complications, including retinal cholesterol thromboembolism and cholesteroloma of the lung have been seen in the patient with the highest cholesterol levels. Severe hypercholesterolemia is an important, and likely more common than previously reported, long-term complication of allogeneic hematopoietic stem cell transplantation. It is important for clinicians to familiarize themselves with the diagnostic and therapeutic challenges this condition presents.

Adult↗

Germline truncating mutations in both MSH2 and BRCA2 in a single kindred.

There has been interest in the literature in the possible existence of a gene that predisposes to both breast cancer (BC) and colorectal cancer (CRC). We describe the detailed characterisation of one kindred, MON1080, with 10 cases of BC or CRC invasive cancer among 26 first-, second- or third-degree relatives. Linkage analysis suggested that a mutation was present in BRCA2. DNA sequencing from III: 22 (diagnosed with lobular BC) identified a BRCA2 exon 3 542G>T (L105X) mutation. Her sister (III: 25) had BC and endometrial cancer and carries the same mutation. Following immunohistochemical and microsatellite instability studies, mutation analysis by protein truncation test, cDNA sequencing and quantitative real-time PCR revealed a deletion of MSH2 exon 8 in III: 25, confirming her as a double heterozygote for truncating mutations in both BRCA2 and MSH2. The exon 8 deletion was identified as a 14.9 kb deletion occurring between two Alu sequences. The breakpoint lies within a sequence of 45 bp that is identical in both Alu sequences. In this large BC/CRC kindred, MON1080, disease-causing truncating mutations are present in both MSH2 and BRCA2. There appeared to be no increased susceptibility to the development of colorectal tumours in BRCA2 mutation carriers or to the development of breast tumours in MSH2 mutation carriers. Additionally, two double heterozygotes did not appear to have a different phenotype than would be expected from the presence of a mutation in each gene alone.

Adult↗

Evidence of avian pneumovirus spread beyond Minnesota among wild and domestic birds in central North America.

To detect avian pneumovirus (APV) in central North America, nasal turbinates or choanal deft tissues from domestic turkeys and wild birds were examined for the presence of APV RNA by reverse transcriptase-polymerase chain reaction (RT-PCR), whereas serum samples from domestic turkeys were analyzed for APV antibodies by enzyme-linked immunosorbent assay (ELISA). In 2002, the seroprevalence of disease in domestic turkeys in Minnesota remained high (42.3% of the flocks). In addition, there is evidence the disease has spread to turkey flocks in North Dakota (8.2%), South Dakota (7%), Iowa (10%), and Wisconsin (8.6%) as detected by RT-PCR and/or ELISA. House sparrows and ring-billed gulls sampled in Minnesota and snow geese from Saskatchewan, Canada, were found to harbor APV RNA. Sequence analysis of wild bird APV strains showed high amino acid sequence identity among wild bird isolates (<97%) and between wild bird and turkey viral isolates (93.2%-99.3%). This study demonstrated that APV infections were present in domestic turkey flocks and wild birds outside the state of Minnesota; however, the role of wild birds in spreading APV to domestic turkeys remains unclear.

Amino Acid Sequence↗

Reducing psychiatric stigma and discrimination--evaluating an educational intervention with the police force in England.

BACKGROUND: Across the world there are programmes challenging negative stereotypes of people with mental health problems and associated discriminatory behaviours, but the evidence base describing what works in practice is still underdeveloped. This paper evaluates the effectiveness of a mental health training intervention with the police force in England. METHOD: A total of 109 police officers attended training workshops and completed pre- and post-questionnaires detailing knowledge, attitudes and behavioural interventions. RESULTS: Mean attitude scores fell from 2.4 at baseline to 2.3 at follow-up (p < 0.0001) using a 5-point Likert scale. Five key message statements were assessed - 70 % of cases successfully reported more messages at follow-up as compared to baseline; however, the stereotype linking people with mental health problems with violent behaviour overall was not successfully challenged. Positive impacts on police work, particularly improvements in communication between officers and subjects, were reported by a third of cases. CONCLUSIONS: Short educational interventions can produce changes in participants' reported attitudes towards people with mental health problems, and can leave police officers feeling more informed and more confident to support people in mental distress.

Attitude to Health↗

The effect of diet fed to lambs on subsequent development of Trichostrongylus colubriformis larvae in vitro and on pasture.

Contrasting herbage diets were fed to lambs to evaluate their effect on subsequent development of Trichostrongylus colubriformis larvae in faeces and on pasture. The diets had either no condensed tannin (CT), lucerne (Medicago sativa cv. Otaio), white clover (Trifolium repens cv. Tahora), or had moderate to high concentrations of CT, sulla (Hedysarum coronarium cv. Grassland Aokau), Lotus corniculatus (cv. Grasslands Goldie), L. pedunculatus (cv. Grassland Maku), Dorycnium pentophyllum, and Dorycnium rectum. Trials were carried out in summer (warm) and in autumn (cool and moist). In summer, egg viability was evaluated in vitro with egg hatch and larval development assays. In both seasons faeces were placed on pasture to compare recovery of eggs and larvae from faeces and larvae from herbage on the high and low fertility farmlets on the AgResearch Ballantrae Hill Country Research Station. D. rectum and D. pentophyllum diets decreased (P<0.01) egg hatching and larval development in laboratory assays relative to other diets. In summer, the number of larvae recovered from faeces placed on pasture was far greater (P<0.001) if the lambs had been fed lucerne than any other diet, whereas recovery was always lowest from faeces of sheep fed D. rectum and D. pentophyllum. Although dietary differences were lower in autumn than in summer, larval recoveries were lower (P<0.05) from faeces of lambs fed D. rectum and L. corniculatus than from white clover, lucerne and sulla diets. This study indicates that the diet of the host can have a significant impact on egg hatching and the subsequent development of T. colubriformis larvae in the laboratory and in the field. In particular, D. rectum consistently reduced T. colubriformis development. Effects measured in vitro generally under-estimated effects measured under field conditions.

Animal Feed↗

Initial ethanol exposure results in decreased heart rate variability in ethanol-naive rhesus monkeys.

Ethanol's effects on heart rate variability may contribute to the increased cardiac disease and mortality observed in alcoholics. We assessed cardiac response to ethanol in seven previously ethanol-naive monkeys given a standard dose of ethanol, or saline. Ethanol exposure reduced cardiac signal complexity [mean+/-S.D. (ethanol: Hurst parameter=0.39+/-0.02; saline: Hurst parameter=0.32+/-0.06)] and increased the spectral exponent (ethanol: beta=1.36+/-0.35; saline: beta=1.12+/-0.35) when compared to saline, while heart rate itself was unaffected (saline: interbeat interval=303.57+/-24.57; ethanol: interbeat interval=308.14+/-20.45). Taken together with data that show autonomic disregulation in alcoholics, these findings provide further evidence of deleterious ethanol effects on cardiac signal dynamics.

Animals↗

Gender differences in carbohydrate loading are related to energy intake.

We demonstrated that female endurance athletes did not increase their muscle glycogen concentration after an increase in the dietary carbohydrate intake (58 --> 74%), whereas men did (Tarnopolsky MA, SA Atkinson, SM Phillips, and JD McDougall, J Appl Physiol 78: 1360-1368, 1995). This may have been related to a lower energy or carbohydrate intake by the women or due to an inherent gender difference in glycogen storage capacity. We examined whether well-trained men (n = 6) and women (n = 6) increased muscle glycogen concentration after an increase in both the relative (58 --> 75%) and absolute energy and carbohydrate intake and whether potential gender differences were related to muscle hexokinase enzyme activity. Subjects were randomly allocated to three diets [Hab, habitual; CHO, high carbohydrate (75%); and CHO + E, extra energy + CHO ( upward arrow~34%)] for a 4-day period before a muscle biopsy for analysis of total and pro- and macroglycogen and hexokinase activity. Total glycogen concentration was higher for the men on the CHO and CHO + E trials compared with Hab (P < 0.05), whereas women increased only on the CHO + E trial compared with Hab (P < 0.05). There were no gender differences in the proportion of pro- and macroglycogen or hexokinase activity. A low energy intake may explain the previously reported lower capacity for women to glycogen load compared with men.

Adult↗

Caffeine ingestion decreases glucose disposal during a hyperinsulinemic-euglycemic clamp in sedentary humans.

The purpose of this investigation was to examine the effect of caffeine (an adenosine receptor antagonist) on whole-body insulin-mediated glucose disposal in resting humans. We hypothesized that glucose disposal would be lower after the administration of caffeine compared with placebo. Healthy, lean, sedentary (n = 9) men underwent two trial sessions, one after caffeine administration (5 mg/kg body wt) and one after placebo administration (dextrose) in a double-blind randomized design. Glucose disposal was assessed using a hyperinsulinemic-euglycemic clamp. Before the clamp, there were no differences in circulating levels of methylxanthines, catecholamines, or glucose. Euglycemia was maintained throughout the clamp with no difference in plasma glucose concentrations between trials. The insulin concentrations were also similar in the caffeine and placebo trials. After caffeine administration, glucose disposal was 6.38 +/- 0.76 mg/kg body wt compared with 8.42 +/- 0.63 mg/kg body wt after the placebo trial. This represents a significant (P < 0.05) decrease (24%) in glucose disposal after caffeine ingestion. In addition, carbohydrate storage was 35% lower (P < 0.05) in the caffeine trial than in the placebo trial. Furthermore, even when the difference in glucose disposal was normalized between the trials, there was a 23% difference in the amount of carbohydrate stored after caffeine administration compared with placebo administration. Caffeine ingestion also resulted in higher plasma epinephrine levels than placebo ingestion (P < 0.05). These data support our hypothesis that caffeine ingestion decreases glucose disposal and suggests that adenosine plays a role in regulating glucose disposal in resting humans.

Administration, Oral↗

Influence of close-up dry period protein supplementation on productive and reproductive performance of Holstein cows in their subsequent lactation.

Holstein cows on a commercial dairy were assigned to close-up dry groups and offered an 11.7% crude protein (CP) ration based on corn silage, alfalfa cubes, oat hay, corn, and barley grain without (Control; C) or with (Supplemented; S) 0.8 kg/d per cow of a high CP supplement of SoyPass, distillers dried grains, ring dried blood meal, feather meal, and corn gluten meal. Heifers (C: 37, S: 44) and mature cows (C: 96, S: 81) were allocated to one of four groups based upon their time in the close-up groups (i.e., 1 to 4, 5 to 8, 9 to 12, and 13 to 19 d) within parity (i.e., heifers or mature) for statistical analysis. Full lactation means of all response parameters for cows confirmed to be pregnant that completed a lactation (i.e., lactating at 305 d in milk or dried off before 305 d in milk but not culled; C: 28, S: 23 for heifers and C: 48, S: 43 for mature cows) were analyzed by ANOVA. Lactation curves were evaluated by parallel curve analysis to assess differences in lactation curve shape, and curve separation, due to treatments. Protein supplementation had no impact on full-lactation milk or milk component yields of heifers, determined by ANOVA, although parallel curve analysis showed higher milk and milk protein yield with protein supplementation. As the number of days cows spent consuming their assigned close-up dry rations increased, heifers produced more milk, milk fat and milk protein, although the maximum yield for milk and milk protein occurred for those fed close-up rations for 9 to 12 d. For mature cows, neither time close up or close-up period protein supplementation influenced any mean response parameter, by ANOVA, although parallel curve analysis showed higher milk and protein yield for supplemented cows as time close up increased. Overall, results suggest the optimum close-up period length was 9 to 12 d, with a protein content intermediate between 11.7 and 14.4% of DM, for heifers. In contrast, results do not support any substantive benefit of a close up period, or protein contents above 11.7%, for mature cows.

Analysis of Variance↗

Increasing revenue through A/R recovery, revenue-cycle redesign.

After experiencing operating losses of more than $15 million and a growing number of days in accounts receivable and payment denials, Capital Health System implemented a multidisciplinary recovery program to redesign its revenue cycle. The system reorganized its business office staff, outsourced some collection activities, and stepped up its efforts to review coding, analyze billing errors and edits, update its charge description master, and track payment denials. Although this work is ongoing, during the initial revenue-cycle redesign, the system increased its cash flow by more than $30 million and increased patient-service revenue by 7 percent annually between January 1999 and July 2001. Capital has received more than $10 in new collected revenue for every dollar spent on accounts-receivable recovery and revenue enhancement.

Accounts Payable and Receivable↗

omega-3 fatty acids decrease endothelial adhesion of human colorectal carcinoma cells.

BACKGROUND: Diets rich in omega-3 fatty acids have been shown to decrease both the initiation and promotion of colon carcinogenesis although their effect on hepatic metastasis formation is less well understood. Since adhesion of human colorectal carcinoma (HCRC) cells to hepatic endothelial cells is an important step in the metastatic cascade, the effect of membrane omega-3 fatty acid alterations on endothelial cell adhesion was studied. MATERIALS AND METHODS: CX-1 cells, a moderately differentiated HCRC cell line known to produce hepatic metastases in an athymic mouse intrasplenic injection model, were used. Cells were grown in omega-3 fatty acid-enriched medium and membrane-free fatty acid modifications confirmed with gas chromatography. Both human umbilical vein and hepatic sinusoidal endothelial cells were used in the binding assays. Adhesion assays were performed in a standard fashion using (51)Cr-labeled cells to tumor necrosis factor (TNF)-stimulated endothelial cell monolayers. Immunohistochemical analysis was performed for sialyl-Lewis(x), the receptor involved in endothelial adhesion on the surface of control and fatty acid-modified cells. RESULTS: Gas chromatographic analysis confirmed membrane fatty acid modification of CX-1 cells by growth in docosahexanoic acid (omega-3) (4.761 nmol/10(6) cells vs 0.057 nmol/10(6) cells for controls). Binding of CX-1 to both human umbilical vein and hepatic sinusoidal endothelial cells decreased from 38.4 +/- 0.44 to 11.58 +/- 0.87% (P < 0.01). Immunocytochemical analysis showed a decrease in sialyl-Lewis(x) expression with omega-3 treatment. CONCLUSIONS: These data indicate that omega-3 fatty acids may also be protective against the formation of hepatic metastases. The mechanism for this may be decreased endothelial cell adhesion which in turn may be due to decreased expression of the endothelial receptor sialyl-Lewis(x).

Animals↗

Dose rate-dependent marrow toxicity of TBI in dogs and marrow sparing effect at high dose rate by dose fractionation.

We evaluated the marrow toxicity of 200 and 300 cGy total-body irradiation (TBI) delivered at 10 and 60 cGy/min, respectively, in dogs not rescued by marrow transplant. Additionally, we compared toxicities after 300 cGy fractionated TBI (100 cGy fractions) to that after single-dose TBI at 10 and 60 cGy/min. Marrow toxicities were assessed on the basis of peripheral blood cell count changes and mortality from radiation-induced pancytopenia. TBI doses studied were just below the dose at which all dogs die despite optimal support. Specifically, 18 dogs were given single doses of 200 cGy TBI, delivered at either 10 (n=13) or 60 (n=5) cGy/min. Thirty-one dogs received 300 cGy TBI at 10 cGy/min, delivered as either single doses (n=21) or three fractions of 100 cGy each (n=10). Seventeen dogs were given 300 cGy TBI at 60 cGy/min, administered either as single doses (n=5) or three fractions of 100 cGy each (n=10). Within the limitations of the experimental design, three conclusions were drawn: 1) with 200 and 300 cGy single-dose TBI, an increase of dose rate from 10 to 60 cGy/min, respectively, caused significant increases in marrow toxicity; 2) at 60 cGy/min, dose fractionation resulted in a significant decrease in marrow toxicities, whereas such a protective effect was not seen at 10 cGy/min; and 3) with fractionated TBI, no significant differences in marrow toxicity were seen between dogs irradiated at 60 and 10 cGy/min. The reduced effectiveness of TBI when a dose of 300 cGy was divided into three fractions of 100 cGy or when dose rate was reduced from 60 cGy/min to 10 cGy/min was consistent with models of radiation toxicity that allow for repair of sublethal injury in DNA.

Animals↗

Gender differences in cardiovascular and catecholamine responses to cold-air exposure at rest.

Metabolic and cardiovascular responses were examined in 8 men and 9 women during 2 hrs of sitting at rest in 5 degrees C. The men and women had similar body fatness and both groups responded with similar changes relative to control in cardiac output, blood pressure, total peripheral resistance, VO2, respiratory exchange ratio, and rectal temperature. However, greater increases in stroke volume and decreases in heart rate and skin temperature were observed in men compared to women (p < 0.05). The contribution of CHO and fat to the total energy expended differed (p < 0.05) between genders; the CHO:fat ratio was 47:53 in men and 36:64 in women. No gender differences could be observed in plasma catecholamines. It is concluded that there are striking cardiovascular and metabolic gender differences in response to cold stress which cannot be accounted for by body fatness or catecholamine responses.

Adrenergic alpha-Agonists↗

Muscle glycogen accumulation after a marathon: roles of fiber type and pro- and macroglycogen.

Muscle glycogen remains subnormal several days after muscle damaging exercise. The aims of this study were to investigate how muscle acid-soluble macroglycogen (MG) and acid-insoluble proglycogen (PG) pools are restored after a competitive marathon and also to determine whether glycogen accumulates differently in the various muscle fiber types. Six well-trained marathon runners participated in the study, and muscle biopsies were obtained from the vastus lateralis of the quadriceps muscle before, immediately after, and 1, 2, and 7 days (days 1, 2, and 7, respectively) after the marathon. During the race, 56 +/- 3.8% of muscle glycogen was utilized, and a greater fraction of MG (72 +/- 3.7%) was utilized compared with PG (34 +/- 6.5%). On day 2, muscle glycogen and MG values remained lower than prerace values, despite a carbohydrate-rich diet, but they had both returned to prerace levels on day 7. The PG concentration was lower on day 1 compared with before the race, whereas there were no significant differences between the prerace PG concentration and the concentrations on days 2 and 7. On day 2 the glycogen concentration was particularly low in the type I fibers, indicating that local processes are important for the accumulation pattern. We conclude that a greater fraction of human muscle MG than of PG is utilized during a marathon and that accumulation of MG is particularly delayed after the prolonged exercise bout. Furthermore, factors produced locally appear important for the glycogen accumulation pattern.

Adult↗