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Biomedical subjects

E J Rayfield

Publications and source records attributed to E J Rayfield.

At least 19 recordsLinked to original sources
PubMed2001

Cranial design and function in a large theropod dinosaur.

Finite element analysis (FEA) is used by industrial designers and biomechanicists to estimate the performance of engineered structures or human skeletal and soft tissues subjected to varying regimes of stress and strain. FEA is rarely applied to problems of biomechanical design in animals, despite its potential to inform structure-function analysis. Non-invasive techniques such as computed tomography scans can be used to generate accurate three-dimensional images of structures, such as skulls, which can form the basis of an accurate finite element model. Here we have applied this technique to the long skull of the large carnivorous theropod dinosaur Allosaurus fragilis. We have generated the most geometrically complete and complex FEA model of the skull of any extinct or extant organism and used this to test its mechanical properties and examine, in a quantitative way, long-held hypotheses concerning overall shape and function. The combination of a weak muscle-driven bite force, a very 'light' and 'open' skull architecture and unusually high cranial strength, suggests a very specific feeding behaviour for this animal. These results demonstrate simply the inherent potential of FEA for testing mechanical behaviour in fossils in ways that, until now, have been impossible.

Animals↗
PubMed1997

Mechanisms determining course and outcome of diabetic patients who have had acute myocardial infarction.

PURPOSE: To review the pathogenic mechanism that lead to the poor prognosis of diabetic patients after myocardial infarction and to determine the efficacy of current interventions for myocardial infarction in these patients. DATA SOURCES: Search of the MEDLINE database from 1985 to 1995, using the keywords diabetes, myocardial infarction, and cardiomyopathy, and a search of the reference citations of relevant articles. STUDY SELECTION: Experimental and clinical studies on myocardial infarction in diabetic patients and basic research studies relevant to this topic. DATA SYNTHESIS: The excess in-hospital mortality of diabetic patients results primarily from an increased incidence of congestive heart failure. Several combined mechanisms reduce the compensatory ability of the noninfarcted myocardium; such mechanisms include preexisting congestive heart failure caused by diabetic cardiomyopathy, severe coronary artery disease, decreased vasodilatory reserve of epicardial and resistance arteries, and possibly abnormal metabolism of myocardial substrate. Late mortality results from increased reinfarction rates caused by the diffuse nature of the atherosclerotic disease and hypercoagulable state. Platelet hyperactivity, reduced fibrinolytic capacity, increased concentrations of hemostatic proteins, and endothelial dysfunction promote thrombosis at the site of plaque rupture. Autonomic neuropathy predisposes patients to ventricular arrhythmias. Thrombolytic agents, aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors are effective in patients with diabetes. CONCLUSIONS: In the thrombolytic era, mortality rates of diabetic patients who have had acute myocardial infarction remain 1.5 to 2 times higher than those in nondiabetic patients. This increased mortality rate is caused by diverse mechanisms that affect myocardial function and blood supply and by the tendency toward thrombosis in diabetic patients. Current therapies for myocardial infarction are effective in these patients. Improved metabolic control may also decrease mortality rates.

Cardiomyopathies↗
PubMed1996

Potential mechanisms promoting restenosis in diabetic patients.

Diabetes is associated with greater restenosis rates after successful balloon angioplasty. The metabolic alterations that occur as a result of hyperglycemia or hyperinsulinemia can accelerate many of the pathophysiologic processes that lead to restenosis. Diabetes results in endothelial dysfunction and accelerated platelet deposition, which increase the propensity to thrombosis. Several growth factors known to promote the restenosis process are overexpressed in the presence of hyperglycemia. Advanced glycosylation promotes inflammatory cell recruitment and smooth muscle cell proliferation. Many of the potential mechanisms promoting restenosis in diabetic patients can be ameliorated by improved metabolic control.

Angioplasty, Balloon, Coronary↗
PubMed1994

Reactive glycosylation endproducts in diabetic uraemia and treatment of renal failure.

In diabetes and ageing, glucose-derived advanced glycosylation endproducts (AGEs) cross-link proteins and cause vascular tissue damage. Elimination of circulating low-molecular weight AGE-modified molecules (LMW-AGEs) by the kidney is impaired in diabetic patients with end-stage renal disease, a group subject to accelerated atherosclerosis. We determined the effectiveness of current renal replacement treatments on elimination of serum LMW-AGEs in diabetic and non-diabetic patients with end-stage renal disease. Although diabetic patients receiving high-flux haemodialysis achieved 33% lower steady-state serum LMW-AGE than did those in conventional haemodialysis (p < 0.005), LMW-AGE concentrations remained 3.5-6 fold above normal, whether high-flux dialysis, conventional haemodialysis, or chronic ambulatory peritoneal dialysis were used. High-flux haemodialysis markedly reduced AGE during each treatment session (47.9% in the diabetic, p < 0.001 and 60.6% in the non-diabetic group, p < 0.001) but concentrations returned to pre-treatment range within 3 hours. In contrast, normal LMW-AGE concentrations were maintained in patients with functioning renal transplants. We found that LMW-AGEs with an apparent molecular weight of 2000-6000 circulate and retain strong inherent chemical reactivity--when exposed to collagen in vitro, up to 77% attached covalently to form AGE-collagen, and the AGE-crosslink inhibitor aminoguanidine completely inhibited this reaction. The results suggest that LMW-AGEs comprise a set of chemically-reactive molecules that are refractory to removal by current dialysis treatments. Through covalent reattachment onto vascular matrix or serum components, LMW-AGEs may exacerbate vascular pathology associated with end-stage renal disease.

Adult↗
PubMed1994

Erectile function and penile blood pressure in diabetes mellitus.

Thirty-seven diabetic men selected to exclude the confounding effects of other medical illnesses and nondiabetic medications and 53 healthy controls underwent extensive psychosexual and medical evaluations and penile blood pressure assessments by ultrasonic Doppler measurement and mercury strain-gauge plethysmography. There was a significant negative correlation between age and the penile-brachial index (PBI) in the diabetic but not in the control group. The impotent diabetic group had significantly lower PBI than nondysfunctional diabetic and healthy control subjects. Diabetic type, complications, and adequacy of metabolic control were not statistically related to PBI. Although the PBI may not have diagnostic utility for individual patients, it may provide a valuable noninvasive physiologic measure of penile vascular changes in studies on the aged and the medically ill. The processes that mediate the interaction of diabetes and aging on penile blood pressure and erectile capacity deserve further investigation.

Blood Pressure↗
PubMed1993

Diabetes, sleep disorders, and male sexual function.

The prevalence and role of sleep disorders in the sexual problems of diabetic patients remain unexplored. This study was conducted on 40 diabetic men carefully screened to exclude the confounding effects of other medical illnesses or drugs likely to impair sexual function and 40 age-matched healthy volunteers. They underwent an extensive psychosexual interview, medical and psychiatric evaluations, and three recorded nights in a sleep laboratory. Electroencephalogram, eye movements, muscle tone, and nocturnal penile tumescence were monitored continuously. Respiratory airflow and bilateral anterior tibialis recordings were obtained during the first sleep session. Diabetic men had significantly higher prevalences of respiratory and periodic leg movement disturbances during sleep. There was clinical, although not nocturnal penile tumescence, evidence suggesting that respiratory abnormalities during sleep are associated with erectile difficulties in diabetic men. Future studies should include blood oxygenation and respiratory effort measures to clarify the significance of sleep-related airflow disturbances in diabetic patients.

Comorbidity↗
PubMed1993

Diabetes mellitus and male sexual function: a controlled study.

There is an extensive clinical literature on the erectile disorders of diabetic men but a paucity of controlled studies that have taken into account the effects of age, concurrent illnesses and medication on sexual function. This investigation was carried out on 40 diabetic men free from other illness or drugs that could affect sexual capacity and 40 age-matched healthy control subjects. Each subject and his female partner underwent semistructured interviews and the men had comprehensive medical evaluations and polygraphic assessment of sleep and nocturnal penile tumescence in the sleep laboratory during three nights. In comparison to control subjects, diabetic patients reported significant decreases in sexual desire, subjective arousal, erectile capacity, coital frequency and sexual satisfaction. The diabetic group also had significant decrements in duration of rapid eye movement sleep and in frequency, duration and degree of nocturnal penile tumescent episodes. There were no differences between Type 1 (insulin-dependent) and Type 2 (non-insulin dependent) diabetic patients in prevalence of sexual problems or in nocturnal tumescent measures. Significant relations were observed between lack of metabolic control, diabetic complications and impaired nocturnal tumescence. Sexually non-dysfunctional diabetic men had significant nocturnal penile tumescence abnormalities. Diabetic men without coital failures may have a subclinical impairment in erectile function which, although of not significant magnitude to interfere with penetration, is reflected in nocturnal penile tumescent measures. This result raises a note of caution in the interpretation of the nocturnal penile tumescence test for the differential diagnosis of diabetic erectile impotence.

Case-Control Studies↗
PubMed1991

Advanced glycosylation end products in patients with diabetic nephropathy.

BACKGROUND: Glucose reacts nonenzymatically with proteins in vivo, chemically forming covalently attached glucose-addition products and cross-links between proteins. The excessive accumulation of rearranged late-glucose-addition products, or advanced glycosylation end products (AGEs), is believed to contribute to the chronic complications of diabetes mellitus. METHODS: To elucidate the relation of AGEs to diabetic complications, we used a radioreceptor assay to measure serum and tissue AGEs in diabetic (Types I and Type II) and nondiabetic patients with different levels of renal function. Serum AGEs were measured as a low-molecular-weight (less than or equal to 10 kd) peptide fraction and a high-molecular-weight (greater than 10 kd) protein fraction. RESULTS: The mean (+/- SD) AGE content of samples of arterial-wall collagen from 9 diabetic patients was significantly higher than that of samples from 18 nondiabetic patients (14.5 +/- 5.2 vs. 3.6 +/- 1.5 AGE units per milligram, P less than 0.001). Moreover, diabetic patients with end-stage renal disease had almost twice as much AGE in tissue as diabetic patients without renal disease (21.3 +/- 2.8 vs. 11.5 +/- 1.9 AGE units per milligram, P less than 0.001). The AGE levels in both serum fractions were elevated in the patients with diabetes, and the levels of AGE peptides correlated directly with serum creatinine (P less than 0.001) and inversely with creatinine clearance (P less than 0.005), suggesting that levels of AGE peptides increased with the severity of diabetic nephropathy. In six patients with diabetes who required hemodialysis, the levels of AGE peptides were five times higher than in eight normal subjects (82.8 +/- 9.4 vs. 15.6 +/- 3.4 AGE units per milliliter, P less than 0.001). In another group of diabetic patients the mean serum creatinine level, which decreased by 75 percent during a session of hemodialysis, whereas the level of AGE peptides decreased by only 24 percent. Serum levels of AGE peptides were normal in two patients with normal serum creatinine levels after renal transplantation. CONCLUSIONS: AGEs accumulate at a faster-than-normal rate in arteries and the circulation of patients with diabetes; the increase in circulating AGE peptides parallels the severity of renal functional impairment in diabetic nephropathy.

Adult↗
PubMed1986

Virus-induced alterations in cyclic adenosine monophosphate generation in hamster islets of Langerhans.

Inoculation of golden Syrian hamsters with Venezuelan encephalitis (VE) virus results in a sustained diminution in glucose-stimulated insulin release that is correctable by cyclic (c) AMP analogs and phosphodiesterase inhibitors. This suggested the importance of directly measuring cAMP content in VE-infected and control islets in response to insulin secretagogues. The basal cAMP content of VE-infected islets (0.14 +/- 0.02 pmol/micrograms islet DNA) was approximately half that of control islets (0.27 +/- 0.02 pmol/micrograms islet DNA) (P less than 0.05). In the presence of 10 microM glucagon (and 3 mM glucose), the rate of cAMP generation in VE-infected islets was only half that of control islets. With 10 mM alpha-ketoisocaproic acid, the rates of cAMP generation were indistinguishable between control and experimental groups. In response to 20 mM glucose and 3-isobutyl-1-methylxanthine (IBMX) (a phosphodiesterase inhibitor), cAMP generation in VE-infected islets was 81% (NS) of the control rate. When a more specific phosphodiesterase inhibitor, RO 20-1724, was used with 20 mM glucose, cAMP generation in the infected islets was only 44% (P less than 0.001) of the control value. Insulin secretion over the perifusion period paralleled the cAMP levels. In the presence of 10 mM alpha-ketoisocaproic acid, there was no difference in insulin secretion between VE-infected and control islets, while there was a statistically significant (P less than 0.05) difference with 10 microM glucagon or 20 mM glucose (in 1 mM RO 20-1724). These data point to a defect in the cAMP generation system of VE-infected islets, although additional factors involved in insulin secretion may also be impaired by the virus.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Rubella virus-induced diabetes in the hamster.

The congenital rubella syndrome provides the best documentation in humans that a viral infection is associated with the subsequent development of insulin-dependent diabetes mellitus. We have developed an animal model in neonatal golden Syrian hamsters infected with rubella virus passaged in beta-cells that closely parallels the diabetes observed with congenital rubella. The hamsters develop hyperglycemia and hypoinsulinemia, which are sustained throughout the 15-wk study period. A mononuclear infiltration of the islets, isolation of rubella virus from whole pancreas, the presence of viral antigen in beta-cells by immunofluorescent localization, and cytoplasmic islet cell antibodies (40%) are demonstrated. These data suggest that an autoimmune process and diabetes develop after rubella virus infection in neonatal hamsters. This model may uncover the precise mechanism by which rubella virus induces similar disease in humans.

Animals↗
PubMed1985

Patterns of foot examination in a diabetes clinic.

Peripheral vascular disease is a well-known source of morbidity and potential mortality in diabetic patients. Sixty-five subjects with diabetes were studied in order to describe the contributions of the patient, the physician, and the health care system to the performance of a preventive foot examination. The incidences of foot examination on the day of study (12.3 percent) and during the previous year (49.2 percent) were similar to those found by other investigators. The feet of patients at higher risk for limb amputation were not examined with greater frequency at the clinic, although such patients were more often referred to a podiatrist. The most significant determinants of physician foot examination were patient recall of foot-related education received at the clinic and inter-physician variability. These data suggest that the patient, physician, and clinic routine all play an important role in the success of a foot screening program for patients with diabetes.

Amputation, Surgical↗
PubMed1984

Elevated hemoglobin A1c and low-density lipoprotein cholesterol levels in thiazide-treated diabetic patients.

Despite the well-known hyperglycemic effect of thiazide diuretics, these agents are often administered to diabetic patients. This study compared 89 insulin-treated diabetic patients receiving hydrochlorothiazide, 57 receiving furosemide, and 255 receiving no diuretic. Hemoglobin A1c level was 7.2 +/- 1.8 percent (mean +/- SD) with hydrochlorothiazide, significantly higher than the levels of 5.9 +/- 2.3 percent with furosemide and 6.4 +/- 2.0 percent with no diuretic. Low-density lipoprotein cholesterol level was 154 +/- 43 mg/dl with hydrochlorothiazide, but 134 +/- 42 mg/dl with furosemide and 130 +/- 42 mg/dl with no diuretic. Multivariate analysis showed that the associations remained significant after adjustment for age, sex, race, type and duration of diabetes, body mass index, blood pressure, serum potassium level, insulin dose, and treatment with other medications. These findings suggest that treatment with thiazide diuretics in the diabetic population may increase low-density lipoprotein cholesterol and hemoglobin A1c levels.

Cholesterol↗
PubMed1982

Infection and diabetes: the case for glucose control.

This review summarizes data concerning the host resistance to infection in diabetes and the influence of an acute infection upon the endocrinologic-metabolite status of the diabetic patient. While it is well known that acute infections lead to difficulty in controlling blood sugar levels and the infection is the most frequently documented cause of ketoacidosis, controversy persists as to whether or not patients with diabetes mellitus are more susceptible to infection than age- and sex-matched nondiabetic control subjects. Our data obtained from the charts of 241 diabetic patients who were being followed as outpatients show a striking direct correlation between the overall prevalence of infection (p less than 0.001) and the mean plasma glucose levels (representing three or more fasting glucose determinations taken at times when no evidence of infection existed). There is a significant diminution in intracellular bactericidal activity of leukocytes with Staphylococcus aureus and Escherichia coli in subjects with poorly controlled diabetes in comparison with the control group. Serum opsonic activity for both Staph. Aureus and E. coli were significantly lower than in the control subjects. Taken together, the results from published reports as well as our data suggest to us that good control of blood sugar in diabetic patients is a desirable goal in the prevention of certain infections (Candida vaginitis, for example) and to ensure maintenance of normal host defense mechanisms that determine resistance and response to infection.

Antibody Formation↗
PubMed1982

HLA antigens, cytoplasmic islet cell antibodies, and carbohydrate tolerance in families of children with insulin-dependent diabetes mellitus.

Cytoplasmic pancreatic islet cell antibodies were found in 21% of 244 unaffected first degree relatives of type I diabetic patients. Twenty-five percent of HLA-identical, 35% of HLA-haploidentical, 16% of HLA-nonidentical siblings, and 14% of parents were ICA-positive. In the HLA-identical sibs, irrespective of ICA, and in the 18 ICA-positive parents but not the other groups, increased plasma glucose levels were observed after the administration of glucose. In most children, these were associated with reduced insulin levels, while in the adults elevated insulin responses were noted. In 48% of the ICA-positive children and 84% of the ICA-positive parents, other evidence of "autoimmunity" was obtained either by history or by testing for specific autoantibodies. Two of the originally unaffected HLA-identical and ICA-positive siblings developed diabetes during the course of the study. These findings, plus previously reported data in families with two diabetic sibs demonstrating that the empiric risk for developing IDDM is of the order of 30% for HLA-identical sibs but less than 5% for those that are HLA-haploidentical, suggest that HLA-identity may be a useful predictor of potential type I diabetes. The presence of ICA may, at times, portend the need for future antidiabetic therapy but prospective studies must be continued to fully elucidate this relationship.

Adolescent↗
PubMed1982

Neurophysiology.

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Autonomic Nervous System Diseases↗