PubMed Health⌕ Search

Biomedical subjects

E A Ryan

Publications and source records attributed to E A Ryan.

At least 19 recordsLinked to original sources
PubMed2007

Changes in renal function after clinical islet transplantation: four-year observational study.

Tight glycemic control can reduce progression of diabetic nephropathy (DN) while the histological changes may regress after pancreas transplantation. Clinical islet transplantation (CIT) can restore euglycemia but the effects of CIT and concomitant immunosuppression on renal function are not known. Renal function (modification of diet in renal disease estimated glomerular filtration rate [GFR]) is reported in 41 type 1 diabetes subjects followed for 29.8 (6-57) months after CIT who received sirolimus and tacrolimus. HbA(1c) improved by 3 months (6.1 +/- 0.5 vs. 8.1 +/- 1.3%, p < 0.001) and was sustained. Over 4 years estimated GFR (eGFR) declined (repeated measures ANOVA: p = 0.0011). The median rate of change in eGFR was -0.39 mL/min/1.73 m(2)/month but was highly variable (range: +1.62 to -2.79 mL/min/1.73 m(2)/month). Progression of albuminuria was observed in ten individuals while regression of microalbuminuria was observed in only one (chi square = 22.51, df = 4, p = 0.0002). Despite improved glycemia, CIT and concomitant immunosuppression, was associated with a fall in eGFR and progression of albuminuria over 4 years of observation. The rate of decline in eGFR was extremely variable and difficult to predict. The risk of progressive nephrotoxicity with decline in eGFR should be discussed with prospective CIT candidates and the risk: benefit ratio carefully considered in individuals with pre-existing renal impairment.

Adult↗
PubMed2005

HIV prevention heuristics and condom use among African-Americans at risk for HIV.

The goal of this study was to improve understanding of whether incorrect HIV/AIDS heuristics and characteristics-based risk theories are barriers to HIV prevention among young African-Americans at increased risk for HIV. We explored: (1) the beliefs of men and women regarding disease prevention strategies, and (2) the relationship of such beliefs to safer sexual behaviours. In Phase I, semistructured individual interviews were conducted with both members of 22 heterosexual couples at increased risk for HIV/STIs. Subsequently, in Phase II, structured individual interviews were conducted with another 40 women and 40 men (not couples). Participants in Phase I reported use of condoms and monogamy as major strategies for disease prevention. The beliefs that were endorsed by the largest percentage of Phase II participants were related to the 'known partners are safe partners' and 'trusted partners are safe partners' heuristics. Moreover, stronger endorsement of the 'known partners' heuristic was negatively associated with measures of condom use and pregnancy prevention behaviour. Our findings highlight the need for interventions and programmes to encourage intimate partners to consistently use condoms until both members of the dyad are tested and agree to mutual monogamy.

Adolescent↗
PubMed2005

Prevention of bleeding after islet transplantation: lessons learned from a multivariate analysis of 132 cases at a single institution.

Islet transplantation is being offered increasingly for selected patients with unstable type 1 diabetes. Percutaneous transhepatic portal access avoids a need for surgery, but is associated with potential risk of bleeding. Between 1999 and 2005, we performed 132 percutaneous transhepatic islet transplants in 67 patients. We encountered bleeding in 18/132 cases (13.6%). In univariate analysis, the risk of bleeding in the absence of effective track ablation was associated with an increasing number of procedures (2nd and 3rd procedures with an odds ratio (OR) of 9.5 and 20.9, respectively), platelets count <150,000 (OR 4.4), elevated portal pressure (OR 1.1 per mm Hg rise), heparin dose > or =45 U/kg (OR 9.8) and pre-transplant aspirin (81 mg per day) (OR 2.6, p = 0.05). A multivariate analysis further confirmed the cumulative transplant procedure number (p < 0.001) and heparin dose > or =45 U/kg (p = 0.02) as independent risk factors for bleeding. Effective mechanical sealing of the intrahepatic portal catheter tract with thrombostatic coils and tissue fibrin glue completely prevented bleeding in all subsequent procedures (n = 26, p = 0.02). We conclude that bleeding after percutaneous islet implantation is an avoidable complication provided the intraparenchymal liver tract is sealed effectively.

Acute Disease↗
PubMed2003

Acarbose in the treatment of elderly patients with type 2 diabetes.

AIMS: To study the effect of acarbose, an alpha-glucosidase inhibitor, on glycemic control in elderly patients with type 2 diabetes. METHODS: Elderly patients with type 2 diabetes treated with diet alone were randomly treated in a double-blind fashion with placebo (n=99) or acarbose (n=93) for 12 months. RESULTS: After 12 months of therapy, there was a statistically significant difference in the change in glycated haemoglobin (HbA(1c)) (-0.6%) in the acarbose group versus placebo, as well as in the incremental post-prandial glucose values (-2.1 mmol h/l) and mean fasting plasma glucose (-0.7 mmol/l). Although there was no effect of acarbose on insulin release, there was a clear effect of acarbose to decrease relative insulin resistance (-0.8) (HOMA method). In addition, acarbose was generally well tolerated and safe in the elderly; most discontinuations were due to gastrointestinal side effects such as flatulence and diarrhea. There were no cases of hypoglycemia reported, and no clinically relevant changes in laboratory abnormalities or vital signs during the study. CONCLUSIONS: Acarbose improves the glycemic profile and insulin sensitivity in elderly patients with type 2 diabetes who are inadequately controlled on diet alone.

Acarbose↗
PubMed2001

A single Glu(62)-to-Lys(62) mutation in the Mos residues of the R7Delta447Gag-tMos protein causes the mutant virus to induce brain lesions.

We previously reported that R7Delta447, a 2954-base-pair (bp) laboratory-generated Moloney murine sarcoma virus, induced subcutaneous tumors in about 14% of infected mice but did not induce brain lesions. We now report that R7Delta447K, a spontaneous mutant of R7Delta447, induced brain lesions as well as subcutaneous tumors in all injected mice. The genomes of the two viruses differ in a single base pair: the deduced Glu(62) of the Mos residue of the R7Delta447 Gag-tMos protein is changed to Lys(62). More R7Delta447 than R7Delta447K focus-forming units were detected in both NIH3T3 and mouse cerebral vascular endothelial (MCVE) cells. However, R7Delta447K transformed NIH3T3 and MCVE cells more acutely than did R7Delta447. A distinctive feature that distinguished the morphologic transformation of R7Delta447- and R7Delta447K-infected MCVE cells is the markedly prolonged spindle-shaped phase exhibited by R7Delta447-infected MCVE cells. In addition, R7Delta447K was more efficient in inducing the phosphorylation of ERK1/2 than R7Delta447 in both MCVE and NIH3T3 cells. Moreover morphologic transformation was inhibited, and levels of phosphorylated ERK1/2 were reduced when R7Delta447- or R7Delta447K-infected NIH3T3 or MCVE cells were grown in the presence of the MEK1/2-specific inhibitor PD98095. Thus, we have identified a key residue in the Gag-tMos protein that profoundly affects activation of the Mos/MEK/ERK pathway, virus and cell replication, morphologic transformation in vitro and pathogenicity in vivo.

3T3 Cells↗
PubMed2001

Use of alternative medicines in diabetes mellitus.

AIMS: Enormous advances have been made in medical care but more people are still using herbal or alternative remedies. In chronic conditions such as diabetes patients may turn to alternative remedies that have been purported to improve glycaemic control. This study surveyed diabetic and control subjects about their use of all prescribed medication, over-the-counter supplements, and alternative medications. METHODS: Subjects were prospectively contacted in person or by telephone. Five hundred and two diabetic subjects and 201 control subjects were asked to provide details about themselves, their diabetes (for the diabetic subjects) and their use of prescribed medication, over-the-counter supplements and alternative medications. Subjects were asked to rank their assessment of the effectiveness of each medication. Costs were calculated on a per month basis from average prices obtained from five alternative health stores and five chemist shops. RESULTS: Of the diabetic subjects, 78% were taking prescribed medication for their diabetes, 44% were taking over-the-counter supplements and 31% were taking alternative medications. Of the control subjects, 63% were taking prescribed medication, 51% were taking over-the-counter supplements, and 37% were taking alternative medications. Multivitamins, vitamin E, vitamin C, calcium and aspirin were the most commonly used over the counter supplements. Garlic, echinacea, herbal mixtures, glucosamine were the most commonly used alternative medications. Chromium was used only by diabetic subjects and then only rarely. Subjects rated the effectiveness of the alternative medications significantly lower than for prescribed medications but still thought them efficacious. Alternative medications purported to have some hypoglycaemic effect were little used by diabetic subjects. Diabetic subjects spent almost as much money on over-the-counter supplements and alternative medications together as they did on their diabetic medications. CONCLUSIONS: One-third of diabetic patients are taking alternative medications that they consider efficacious but this is no more than in the control group. The money spent on alternative and non-prescription supplements nearly equals that spent on prescription medications. In view of the money spent in this area the time is past due to evaluate these remedies and to establish what merit they have.

Alberta↗
PubMed2001

Pancreatic islet transplantation in the treatment of diabetes mellitus.

This chapter reviews current developments and future directions in clinical islet transplantation. With the recent introduction of glucocorticoid-free immunosuppressive therapies and improved methods for islet isolation, the success of the procedure has increased substantially. Challenges ahead include progress with international multicentre trials, development of single donor protocols, progress in clinical tolerance based therapies to lower overall risk of immunosuppression, and ultimately finding an alternative source to provide effective therapy for more patients with diabetes. Recent advances in stem cell biology and xenotransplantation may soon provide this opportunity.

Diabetes Mellitus, Type 1↗
PubMed2001

Accuracy of glucose meter use in gestational diabetes.

Glucose monitoring is essential for the successful management of gestational diabetes. The accuracy of glucose meters is typically determined over a much wider range of glucose values than that commonly encountered in gestational diabetes. The objective of our study was to look at the accuracy of self-monitoring glucose meters in a clinic setting over a range of glucose values seen in gestational diabetes. We retrospectively analyzed 107 case records of subjects with gestational diabetes, each of whom had three simultaneous laboratory and glucose meter glucose tests. The results were compared using the performance goals that (1) all of glucose meters should have readings within 10% of the reference value and (2) the error grid analysis in the standard format and a modified version suitable for gestational diabetes. We also examined the range of the differences from the reference value. Nearly half of the values (47%) were in excess of 10% of the reference range (either above or below). Close to 15% were in excess of 20% difference from the reference range. Standard error grid analysis showed that 96% of the values fell within sections A of the error grid which are considered acceptable, and 100% fell within sections A and B, differences which are generally considered to have no major impact on care. The modified version of the error grid analysis demonstrated that 39% of the values were outside the acceptable range. Within subjects, a substantial number (26%) had a range of differences that exceeded 20% difference between each other. Although the meters give reasonable results that might be acceptable for general diabetes care, the results provide some cause for concern in the management of gestational diabetes. Given the need for precision in the setting of pregnancy particularly in making the decision of whether to start or withhold insulin therapy, caregivers need to be cognizant of these inaccuracies.

Blood Chemical Analysis↗
PubMed2001

Coats' disease.

Explore the source record for details and available documents.

Adult↗
PubMed2001

Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol.

Islet transplantation offers the prospect of good glycemic control without major surgical risks. After our initial report of successful islet transplantation, we now provide further data on 12 type 1 diabetic patients with brittle diabetes or problems with hypoglycemia previous to 1 November 2000. Details of metabolic control, acute complications associated with islet transplantation, and long-term complications related to immunosuppression therapy and diabetes were noted. Insulin secretion, both acute and over 30 min, was determined after intravenous glucose tolerance tests (IVGTTs). The median follow-up was 10.2 months (CI 6.5-17.4), and the longest was 20 months. Glucose control was stable, with pretransplant fasting and meal tolerance-stimulated glucose levels of 12.5+/-1.9 and 20.0+/-2.7 mmol/l, respectively, but decreased significantly, with posttransplant levels of 6.3+/-0.3 and 7.5+/-0.6 mmol/l, respectively (P < 0.006). All patients have sustained insulin production, as evidenced by the most current baseline C-peptide levels 0.66+/-0.06 nmol/l, increasing to 1.29+/-0.25 nmol/l 90 min after the meal-tolerance test. The mean HbA1c level decreased from 8.3+/-0.5% to the current level of 5.8+/-0.1% (P < 0.001). Presently, four patients have normal glucose tolerance, five have impaired glucose tolerance, and three have post-islet transplant diabetes (two of whom need oral hypoglycemic agents and low-dose insulin (<10 U/day). Three patients had a temporary increase in their liver-function tests. One patient had a thrombosis of a peripheral branch of the right portal vein, and two of the early patients had bleeding from the hepatic needle puncture site; but these technical problems were resolved. Two patients had transient vitreous hemorrhages. The two patients with elevated creatinine levels pretransplant had a significant increase in serum creatinine in the long term, although the mean serum creatinine of the group was unchanged. The cholesterol increased in five patients, and lipid-lowering therapy was required for three patients. No patient has developed cytomegalovirus infection or disease, posttransplant lymphoproliferative disorder, malignancies, or serious infection to date. None of the patients have been sensitized to donor antigen. In 11 of the 12 patients, insulin independence was achieved after 9,000 islet equivalents (IEs) per kilogram were transplanted. The acute insulin response and the insulin area under the curve (AUC) after IVGTT were consistently maintained over time. The insulin AUC from the IVGTT correlated to the number of islets transplanted, but more closely correlated when the cold ischemia time was taken into consideration (r = 0.83, P < 0.001). Islet transplantation has successfully corrected labile type 1 diabetes and problems with hypoglycemia, and our results show persistent insulin secretion. After a minimum of 9,000 IEs per kilogram are provided, insulin independence is usually attained. An elevation of creatinine appears to be a contraindication to this immunosuppressive regimen. For the subjects who had labile type 1 diabetes that was difficult to control, the risk-to-benefit ratio is in favor of islet transplantation.

Adult↗
PubMed2000

Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen.

BACKGROUND: Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8 percent are free of the need for insulin therapy at one year. METHODS: Seven consecutive patients with type 1 diabetes and a history of severe hypoglycemia and metabolic instability underwent islet transplantation in conjunction with a glucocorticoid-free immunosuppressive regimen consisting of sirolimus, tacrolimus, and daclizumab. Islets were isolated by ductal perfusion with cold, purified collagenase, digested and purified in xenoprotein-free medium, and transplanted immediately by means of a percutaneous transhepatic portal embolization. RESULTS: All seven patients quickly attained sustained insulin independence after transplantation of a mean (+/-SD) islet mass of 11,547+/-1604 islet equivalents per kilogram of body weight (median follow-up, 11.9 months; range, 4.4 to 14.9). All recipients required islets from two donor pancreases, and one required a third transplant from two donors to achieve sustained insulin independence. The mean glycosylated hemoglobin values were normal after transplantation in all recipients. The mean amplitude of glycemic excursions (a measure of fluctuations in blood glucose concentrations) was significantly decreased after the attainment of insulin independence (from 198+/-32 mg per deciliter [11.1+/-1.8 mmol per liter] before transplantation to 119+/-37 mg per deciliter [6.7+/-2.1 mmol per liter] after the first transplantation and 51+/-30 mg per deciliter [2.8+/-1.7 mmol per liter] after the attainment of insulin independence; P<0.001). There were no further episodes of hypoglycemic coma. Complications were minor, and there were no significant increases in lipid concentrations during follow-up. CONCLUSIONS: Our observations in patients with type 1 diabetes indicate that islet transplantation can result in insulin independence with excellent metabolic control when glucocorticoid-free immunosuppression is combined with the infusion of an adequate islet mass.

Adult↗
PubMed2000

Effect of acarbose on insulin sensitivity in elderly patients with diabetes.

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on insulin release and insulin sensitivity in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Elderly patients with type 2 diabetes were randomly treated in a double-blind fashion with placebo (n = 23) or acarbose (n = 22) for 12 months. Before and after randomization, subjects underwent a meal tolerance test and a hyperglycemic glucose clamp study designed to measure insulin release and sensitivity. RESULTS: After 12 months of therapy there was a significant difference in the change in fasting plasma glucose levels (0.2 +/- 0.3 vs. -0.5 +/- 0.2 mmol/l, placebo vs. acarbose group, respectively; P < 0.05) and in incremental postprandial glucose values (-0.4 +/- 0.6 vs. -3.5 +/- 0.6 mmol/l, placebo vs. acarbose group, P < 0.001) between groups. There was a significant difference in the change in HbA(1c) values in response to treatment (0.4 +/- 0.2 vs. -0.4 +/- 0.1%, placebo vs. acarbose group, P < 0.01). The change in fasting insulin in response to treatment (-2 +/- 2 vs. -13 +/- 4 pmol/l, placebo vs. acarbose group, P < 0.05) and incremental postprandial insulin responses (-89 +/- 26 vs. -271 +/- 59 pmol/l, placebo vs. acarbose group, P < 0.01) was also significantly different between groups. During the hyperglycemic clamps, glucose and insulin values were similar in both groups before and after therapy However, there was a significant difference in the change in insulin sensitivity in response to treatment between the placebo and the acarbose groups (0.001 +/- 0.001 vs. 0.004 +/- 0.001 mg/kg x min(-1) [pmol/l](-1), respectively, P < 0.05) CONCLUSIONS: Acarbose increases insulin sensitivity but not insulin release in elderly patients with diabetes.

Acarbose↗
PubMed2000

Studies on the pathology, especially brain hemorrhage and angioendotheliomas, induced by two new mos-containing viruses.

Recombinant virus 7 (R7), a spontaneous deletion mutant of SV7, which is itself a molecular clone of Moloney murine sarcoma virus 124 (MoMuSV 124), induces brain lesions and tumors of the subcutaneous tissue and spleen in all infected mice. In contrast, SV7 only induces tumors of the spleen and subcutaneous tissues. One of the genetic differences between R7 and SV7 is that R7 encodes a Gag-Mos protein whereas SV7 encodes an Env-Mos protein. To investigate whether the novel R7 gag-mos oncogene is required for brain lesion induction, two viruses (SV7d1 and SVM1) were constructed in which the R7 gag-mos sequences and the adjacent 53 bp of the 5' noncoding sequence were replaced by either the SV7 or myeloproliferative sarcoma virus (MPSV) env-mos oncogenes, respectively. Like R7, SV7d1 and SVM1 induced brain lesions and tumors in the spleen and subcutaneous tissues. A prominent component of R7-, SV7d1-, and SVM1-induced tumors of the brain, subcutaneous tissues, and spleen was the presence of abnormally enlarged cells with eccentric nuclei lining vessels, scattered singly or in small clusters. Their size, localization to the luminal surface of distended vessels, and binding to Bandeiraea simplicifolia (BS-1) lectin, an endothelial cell (EC) marker, suggest that they are most likely transformed ECs. Our findings therefore indicate that the induction of brain lesions is not limited to the expression of the R7 Gag-Mos protein. However, our findings also indicate that expression of the different forms of the Mos protein results in differences in the relative abundance of ECs in brain angioendotheliomas and subcutaneous and spleen tumors induced by these viruses.

3T3 Cells↗
PubMed2000

Herbal tea in the treatment of diabetes mellitus.

OBJECTIVE: To evaluate the effects of a native herbal tea in patients with type 2 diabetes. DESIGN: Randomized, placebo-controlled, single-blind study. SETTING: The Metabolic Centre at the University of Alberta Hospitals. SUBJECTS: Forty volunteers with type 2 diabetes. INTERVENTIONS: After a 1 month "run-in" period, subjects drank 250 mL/d of either the herbal tea or a placebo tea for 10 days, and were followed up for a further 4 weeks. OUTCOME MEASURES: A responder analysis defined as a 10% change in mean blood glucose levels based on 4 capillary glucose readings daily. Secondary end points included changes in HbA1c, fructosamine and response to a meal challenge using Ensure. RESULTS: The responder analysis showed no benefit from the herbal tea. Fructosamine levels before and after tea therapy decreased significantly in both study groups. Mean HbA1c levels and incremental areas under the glucose curve (AUC) in the meal challenge did not change in either study group. These data were reanalysed in hyperglycemic subjects with HbA1c levels greater than 120% of normal. The responder analysis and HbA1c levels did not change in either group. Mean (and standard deviation) fructosamine levels, before and after tea therapy, were significantly lower in the herbal tea group than in the placebo tea group (361 [98] versus 338 [100] micromol/L, p < 0.01 compared with 338 [60] versus 323 [49] micromol/L, p = 0.08). In the hyperglycemic subgroup the mean AUC during the meal challenge, before versus after tea therapy, was 776 (369) versus 639 (331) mmol/L (p = 0.22) in the herbal tea group and 433 (125) versus 420 (173) mmol/L (p = 0.90) in the placebo group. CONCLUSIONS: Although the responder analysis failed to show an effect of the herbal tea, the data suggest there may be a short-term benefit from the tea in subjects with poor glycemic control.

Aged↗
PubMed1999

Structural origins of fibrin clot rheology.

The origins of clot rheological behavior associated with network morphology and factor XIIIa-induced cross-linking were studied in fibrin clots. Network morphology was manipulated by varying the concentrations of fibrinogen, thrombin, and calcium ion, and cross-linking was controlled by a synthetic, active-center inhibitor of FXIIIa. Quantitative measurements of network features (fiber lengths, fiber diameters, and fiber and branching densities) were made by analyzing computerized three-dimensional models constructed from stereo pairs of scanning electron micrographs. Large fiber diameters and lengths were established only when branching was minimal, and increases in fiber length were generally associated with increases in fiber diameter. Junctions at which three fibers joined were the dominant branchpoint type. Viscoelastic properties of the clots were measured with a rheometer and were correlated with structural features of the networks. At constant fibrinogen but varying thrombin and calcium concentrations, maximal rigidities were established in samples (both cross-linked and noncross-linked) which displayed a balance between large fiber sizes and great branching. Clot rigidity was also enhanced by increasing fiber and branchpoint densities at greater fibrinogen concentrations. Network morphology is only minimally altered by the FXIIIa-catalyzed cross-linking reaction, which seems to augment clot rigidity most likely by the stiffening of existing fibers.

Blood Coagulation↗