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Biomedical subjects

E J Barrett

Publications and source records attributed to E J Barrett.

At least 37 records · Page 2Linked to original sources
PubMed1999

Hyponatremia: evaluating the correction factor for hyperglycemia.

PURPOSE: There are no controlled experimental data that assess the accuracy of the commonly used correction factor of a 1.6 meq/L decrease in serum sodium concentration for every 100 mg/dL increase in plasma glucose concentration. The purpose of this study was to evaluate experimentally the hyponatremic response to acute hyperglycemia. SUBJECTS AND METHODS: Somatostatin was infused to block endogenous insulin secretion in 6 healthy subjects. Plasma glucose concentrations were increased to >600 mg/dL within 1 hour by infusing 20% dextrose. The glucose infusion was then stopped and insulin given until the plasma glucose concentration decreased to 140 mg/dL. Plasma glucose and serum sodium concentrations were measured every 10 minutes. RESULTS: Overall, the mean decrease in serum sodium concentration averaged 2.4 meq/L for every 100 mg/dL increase in glucose concentration. This value is significantly greater than the commonly used correction factor of 1.6 (P = 0.02). Moreover, the association between sodium and glucose concentrations was nonlinear. This was most apparent for glucose concentrations >400 mg/dL. Up to 400 mg/dL, the standard correction of 1.6 worked well, but if the glucose concentration was >400 mg/dL, a correction factor of 4.0 was better. CONCLUSION: These data indicate that the physiologic decrease in sodium concentration is considerably greater than the standard correction factor of 1.6 (meq/L Na per 100 mg/dL glucose), especially when the glucose concentration is >400 mg/dL. Additionally, a correction factor of a 2.4 meq/L decrease in sodium concentration per 100 mg/dL increase in glucose concentration is a better overall estimate of this association than the usual correction factor of 1.6.

Adult↗
PubMed1999

Tissue composition affects measures of postabsorptive human skeletal muscle metabolism: comparison across genders.

Despite clear anthropomorphic differences, gender differences in human skeletal muscle protein and carbohydrate metabolism have not been carefully examined. We compared postabsorptive forearm glucose, oxygen, and lactate balances and forearm protein kinetics between 40 male and 36 female subjects. Forearm composition was measured in a subset of 17 subjects (8 males and 9 females) using multislice magnetic resonance imaging. Oxygen uptake, net phenylalanine release, and estimated rates of forearm protein synthesis and degradation were greater in male than in female subjects when expressed as the rate per 100 mL forearm volume (P < 0.05). In males, however, muscle accounted for 58% of forearm volume, compared with 46% in females (P < 0.001). When phenylalanine balance, protein degradation and synthesis, and glucose and oxygen uptake were expressed per 100 mL forearm muscle, there were no significant differences across gender. Likewise, the extraction fractions for oxygen, glucose, phenylalanine, and labeled phenylalanine were comparable in males and females. We conclude that cross-gender comparisons of metabolic variables must accommodate differences in tissue composition. These data indicate that in the postabsorptive state, skeletal muscle metabolism of glucose, protein, and oxygen do not differ by gender in healthy young humans.

Adult↗
PubMed1999

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

Insulin-mediated changes in blood flow are associated with altered blood flow distribution and increased capillary recruitment in skeletal muscle. Studies in perfused rat hindlimb have shown that muscle metabolism can be regulated by vasoactive agents that control blood flow distribution within the hindlimb. In the present study, the effects of a vasoconstrictive agent that has no direct effect on skeletal muscle metabolism but that alters perfusion distribution in rat hindlimb was investigated in vivo to determine its effects on insulin-mediated vascular action and glucose uptake. We measured the effects of alpha-methylserotonin (alpha-met5HT) on mean arterial blood pressure, heart rate, femoral blood flow, hindlimb vascular resistance, and glucose uptake in control and euglycemic insulin-clamped (10 mU x min(-1) x kg(-1)) anesthetized rats. Blood flow distribution within the hindlimb muscles was assessed by measuring the metabolism of 1-methylxanthine (1-MX), an exogenously added substrate for capillary xanthine oxidase. Alpha-met5HT (20 microg x min(-1) x kg(-1)) infusion alone increased mean arterial blood pressure by 25% and increased hindlimb vascular resistance but caused no change in femoral blood flow. These changes were associated with decreased hindlimb 1-MX metabolism indicating less capillary flow. Insulin infusion caused decreased hindlimb vascular resistance that was associated with increased femoral blood flow and 1-MX metabolism. Treatment with alpha-met5HT infusion commenced before insulin infusion prevented the increase in femoral blood flow and inhibited the stimulation of 1-MX metabolism. Alpha-met5HT infusion had no effect on hindlimb glucose uptake but markedly inhibited the insulin stimulation of glucose uptake (P < 0.05) and was associated with decreased glucose infusion rates to maintain euglycemia (P < 0.05). A significant correlation (P < 0.05) was observed between 1-MX metabolism and hindlimb glucose uptake but not between femoral blood flow and glucose uptake. The results indicate that in vivo, certain types of vasoconstriction in muscle such as elicited by 5HT2 agonists, which prevent normal insulin recruitment of capillary flow, cause impaired muscle glucose uptake. Moreover, if vasoconstriction of this kind results from stress-induced increase in sympathetic outflow, then this may provide a clue as to the link between hypertension and insulin resistance that is often observed in humans.

Allopurinol↗
PubMed1998

Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo.

An inhibitor of human liver glycogen phosphorylase a (HLGPa) has been identified and characterized in vitro and in vivo. This substance, [R-(R*, S*)]-5-chloro-N-[3-(dimethylamino)-2-hydroxy-3-oxo-1-(phenylmethyl)pr opyl]-1H-indole-2-carboxamide (CP-91149), inhibited HLGPa with an IC50 of 0.13 microM in the presence of 7.5 mM glucose. CP-91149 resembles caffeine, a known allosteric phosphorylase inhibitor, in that it is 5- to 10-fold less potent in the absence of glucose. Further analysis, however, suggests that CP-91149 and caffeine are kinetically distinct. Functionally, CP-91149 inhibited glucagon-stimulated glycogenolysis in isolated rat hepatocytes (P < 0.05 at 10-100 microM) and in primary human hepatocytes (2.1 microM IC50). In vivo, oral administration of CP-91149 to diabetic ob/ob mice at 25-50 mg/kg resulted in rapid (3 h) glucose lowering by 100-120 mg/dl (P < 0.001) without producing hypoglycemia. Further, CP-91149 treatment did not lower glucose levels in normoglycemic, nondiabetic mice. In ob/ob mice pretreated with 14C-glucose to label liver glycogen, CP-91149 administration reduced 14C-glycogen breakdown, confirming that glucose lowering resulted from inhibition of glycogenolysis in vivo. These findings support the use of CP-91149 in investigating glycogenolytic versus gluconeogenic flux in hepatic glucose production, and they demonstrate that glycogenolysis inhibitors may be useful in the treatment of type 2 diabetes.

Amides↗
PubMed1998

Facilities and resources for diabetes care at regional health facilities in southern Ghana.

In the fall of 1995, each of the five provincial hospitals in southern Ghana was visited and facilities and resources for diabetes care assessed. In addition, health facilities and standards of care questionnaires were completed. Only Korle Bu Teaching Hospital run a diabetes clinic and had diabetologists. Only two facilities had an eye specialist or trained dietician. None of the five facilities had a trained diabetes educator or chiropodist. Except for sphygmomanometers, basic equipment for clinical care were lacking. Basic biochemistry tests were available at all facilities. Creatinine clearance and 24-h urine protein, glycated haemoglobin, fasting triglyceride, total cholesterol and HDL cholesterol were available at only one centre. None of the facilities measured C-peptide, islet cell antibody and urine microalbumin. None of the facilities had chronic haemodialysis service. Insulin supply was erratic at two institutions. Three regions had active diabetes associations. The facilities and system of diabetes care in southern Ghana revealed in this study are far from satisfactory. Training of health care personnel in diabetes management and education may enhance diabetes care despite the existing constraints. Furthermore, the development of international and regional guidelines for facilities and resources may facilitate implementation of international resolutions and clinical practice guidelines.

Diabetes Mellitus↗
PubMed1998

The influence of storage conditions on the clonogenic capacity of periodontal ligament cells: implications for tooth replantation.

Viable periodontal ligament (PL) cells are required for PL healing of avulsed teeth following replantation. If immediate replantation cannot be accomplished, the ability of PL progenitor cells to reproduce (clonogenic capacity) and recolonize the wound may be extended by prevention of desiccation and storage in physiological media. This investigation examined the effects of storage in saliva, milk, Hank's balanced salt solution (HBSS) and Eagle's medium (alpha MEM) on the clonogenic capacity of human PL progenitor cells at 30 and 60 min extra-alveolar time. Twenty erupted human premolar teeth extracted as atraumatically as possible for orthodontic purposes were used in the present study. Fifteen premolars were placed immediately in freshly collected autologous saliva at room temperature, (+ 23 degrees C) for 15 min. These 15 premolars were next divided into three groups of five and stored in either saliva, milk or HBSS at + 4 degrees C in plastic cups surrounded by ice. The remaining five teeth served as positive controls and were immediately placed in alpha MEM at + 4 degrees C. PL tissue was scraped from one-half of the root surface with a scalpel at 30 and 60 min total extra-alveolar duration. Cells were released from the tissue sample with a 30 min enzymatic digestion procedure and the cells from the tissue samples analyzed for clonogenic capacity. There was a reduction in clonogenic capacity with time for all protocols. Periodontal ligament cells stored in alpha MEM showed the least reduction between 30 and 60 min and the greatest reduction was observed for PL cells stored in saliva. The difference in clonogenic capacity following transfer from saliva to milk or HBSS was not significant at 30 min. At 60 min, cells transferred from saliva to HBSS had a statistically higher percentage of clonogenic cells than those transferred to milk (5.9% vs. 3.5%; P < 0.05). We conclude that immediate storage of avulsed teeth in autologous saliva, followed by transfer to chilled milk, preserves the presence of sufficient progenitor cells in the PL to warrant replantation and the possibility of PL healing at 60 min extra-alveolar duration.

Animals↗
PubMed1998

The effect of training and epinephrine infusion on ratings of perceived exertion (RPE).

Seven untrained males (mean age [+/-SD] = 25.6+/-3.9 yr, mean ht = 177.0+/-5.9 cm, mean wt = 65.8+/-7.4 kg) completed a 6-week exercise program (cycle ergometer). Prior to training, and at the end of each week of training, each subject performed a 20 min constant-power exercise test (absolute power was the same each week). At the end of the six week training program (within a few days), an additional 20 min constant-power test was performed, during which epinephrine was infused at a rate of 100 ng x kg(-1) x min(-1) over the final 10 min of exercise. Training significantly (P<0.05) reduced end-exercise ratings of perceived exertion (RPE), plasma epinephrine concentration [Epi], plasma norepinephrine concentration [NE], blood lactate concentration [La-], minute ventilation (V(E)), heart rate (HR), and blood glucose concentration [Glc]. Epinephrine infusion failed to increase RPE despite significant (p < 0.05) increases in [Epi], [La-], V(E) and [Glc]. Therefore, the present data indicate that RPE during exercise is not causally related to changes in plasma [Epi]. It also appears that modest changes in plasma [NE], blood [La-], V(E) and blood [Glc] during constant-power cycle ergometry (as observed during Epi infusion) do not impact RPE.

Adrenergic Agonists↗
PubMed1998

Extreme hyperinsulinemia unmasks insulin's effect to stimulate protein synthesis in the human forearm.

Insulin clearly stimulates skeletal muscle protein synthesis in vitro. Surprisingly, this effect has been difficult to reproduce in vivo. As in vitro studies have typically used much higher insulin concentrations than in vivo studies, we examined whether these concentration differences could explain the discrepancy between in vitro and in vivo observations. In 14 healthy volunteers, we raised forearm insulin concentrations 1,000-fold above basal levels while maintaining euglycemia for 4 h. Amino acids (AA) were given to either maintain basal arterial (n = 4) or venous plasma (n = 6) AA or increment arterial plasma AA by 100% (n = 4) in the forearm. We measured forearm muscle glucose, lactate, oxygen, phenylalanine balance, and [3H]phenylalanine kinetics at baseline and at 4 h of insulin infusion. Extreme hyperinsulinemia strongly reversed postabsorptive muscle's phenylalanine balance from a net release to an uptake (P < 0.001). This marked anabolic effect resulted from a dramatic stimulation of protein synthesis (P < 0.01) and a modest decline in protein degradation. Furthermore, this effect was seen even when basal arterial or venous aminoacidemia was maintained. With marked hyperinsulinemia, protein synthesis increased further when plasma AA concentrations were also increased (P < 0.05). Forearm blood flow rose at least twofold with the combined insulin and AA infusion (P < 0.01), and this was consistent in all groups. These results demonstrate an effect of high concentrations of insulin to markedly stimulate muscle protein synthesis in vivo in adults, even when AA concentrations are not increased. This is similar to prior in vitro reports but distinct from physiological hyperinsulinemia in vivo where stimulation of protein synthesis does not occur. Therefore, the current findings suggest that the differences in insulin concentrations used in prior studies may largely explain the previously reported discrepancy between insulin action on protein synthesis in adult muscle in vivo vs. in vitro.

Adult↗
PubMed1998

The role of insulin and other hormones in the regulation of amino acid and protein metabolism in humans.

While realizing the difficulties with the various methods used to study hormonal control of protein metabolism, there appear to be clear effects of both rapid-acting and slower-acting hormones. Moreover, some of these hormones affect protein metabolism in a dose dependent manner. Insulin and IGF-I appear to have differing effects at lower doses, with insulin primarily inhibiting protein degradation and IGF-I stimulating protein synthesis. At higher doses, infusions of insulin and IGF-I both seem to inhibit protein degradation and stimulate protein synthesis. Epinephrine primarily inhibits protein degradation whereas growth hormone primarily increases protein synthesis. Infusion of amino acids themselves can also increase protein synthesis. Thyroid hormone excess increases protein synthesis and protein degradation, with the latter effect predominating. Sex steroids appear to increase protein synthesis. To date, most interventions studying the metabolic effects of these hormones on protein metabolism have involved varying the concentration of one hormone at a time. In the complex milieu of many pathologic states (e.g. sepsis, renal failure or even the transition from fasting to feeding) multiple hormones change simultaneously. How interactions among these factors determine the overall response of body and muscle protein remains to be defined.

Amino Acids↗
PubMed1998

Interim storage of avulsed permanent teeth.

This literature review examines the effects of extra-alveolar duration and storage conditions on the healing of the periodontal ligament (PL) of avulsed teeth following replantation. A critical assessment of the so-called "reconstitution theory" for PL cells is also presented. The ideal treatment for an avulsed tooth is immediate replantation (i.e. less than five minutes). Unfortunately, immediate replantation is not the norm, and most avulsed teeth experience delayed replantation. The greatest risk to the vitality of the PL cells attached to the root of an avulsed tooth is desiccation. Not surprisingly, storage media affect PL healing. Storing avulsed teeth in an isotonic liquid is superior to dry storage. Numerous studies support the use of Modified Eagle's Medium, Hank's Balanced Salt Solution (HBSS), ViaSpan, saline, milk, and saliva as storage media. A recent study has suggested that chicken egg white may also prove to be a suitable storage medium for avulsed teeth. Of these media, only saliva is always present at the scene of an accident, however. Milk can usually be obtained on short notice, but even 10 minutes of desiccation can affect the outcome of replantation. From a practical standpoint, milk packed in ice seems to be the best alternative for the temporary storage of avulsed teeth, due to its wide availability and the minimal detrimental effects it has on PL cells. There is no evidence to support the suggestion that HBSS or any other media will "reconstitute" the PL cells when the extra-alveolar duration of avulsed teeth is greater than 30 minutes.

Adenosine↗
PubMed1997

Avulsed permanent teeth: a review of the literature and treatment guidelines.

Dental trauma represents one of the few situations where dentists are called upon to make unscheduled diagnostic and treatment decisions in an area that is outside their routine experience. Since patients who sustain an avulsion present infrequently, except in child-oriented or emergency-based practices, clinicians often make diagnostic and management decisions based upon their previous rare treatment experiences. Clinicians also rely on published guidelines for this aspect of their practice and expect these standards to be up-to-date and based on current research information. None of the current protocols has been tested by a prospective longitudinal outcome study in humans. Nevertheless, current guidelines have become the standard for clinical practice around the world. An effort must be made to develop treatment protocols that are based upon the biological mechanisms that underlie periodontal wound healing.

Animals↗
PubMed1997

Survival of avulsed permanent maxillary incisors in children following delayed replantation.

The purpose of this study was to identify the variables that significantly influenced the survival of incisors replanted after extended extra-alveolar duration at The Hospital for Sick Children, Toronto, Canada, between June 1988 and December 1993. Survival analysis was used to identify variables that significantly influence the retention of replanted incisor teeth. Survival was defined as the time that elapsed between the replantation of an avulsed incisor and the time it was finally lost. Information on 9 variables was collected for 38 patients (25 males; 13 females) and 52 replanted permanent maxillary incisors. The mean extra-alveolar duration for the sample was 123 min. The mean follow-up interval was 942 days (range: 364-2126 days). Incisors replanted with open apices had a significantly decreased survival compared with teeth with mature apices (P = 0.04; relative risk 4.2). There was also a significant association between increased survival and obturation of the root canal with gutta-percha and sealer (P = 0.006; relative risk 10.0). A trend towards improved survival of replanted incisors was found for children older than 11 years old at the time of replantation (P = 0.09; relative risk 2.8). These results are consistent with previous studies and may assist clinicians and parents in the decision-making process associated with the management of avulsed teeth in children.

Child↗
PubMed1997

Hemodynamic actions of insulin in rat skeletal muscle: evidence for capillary recruitment.

Insulin-induced increases in blood flow are hypothesized to enhance overall glucose uptake by skeletal muscle. Whether the insulin-mediated changes in blood flow are associated with altered blood flow distribution and increased capillary recruitment in skeletal muscle is not known. In the present study, the effects of insulin on hemodynamic parameters in rat skeletal muscle in vivo were investigated. Mean arterial blood pressure, heart rate, femoral blood flow, hind leg vascular resistance, and glucose uptake were measured in control and euglycemic insulin-clamped (10 mU x min(-1) x kg[-1]) anesthetized rats. Blood flow distribution within the hind leg muscles was assessed by measuring the metabolism of 1-methylxanthine (1-MX), an exogenously added substrate for capillary xanthine oxidase. Insulin treatment had no effect on heart rate but significantly increased arterial blood pressure (12 mmHg) and femoral blood flow (80%) and decreased hind leg vascular resistance (31%). Changes were similar in magnitude and in time of onset to those reported in humans. Insulin treatment increased hind leg glucose uptake approximately fourfold and also increased hind leg 1-MX metabolism by 50%, suggesting increased exposure to endothelial xanthine oxidase. To ascertain whether the increased 1-MX metabolism was simply due to increased bulk femoral blood flow, epinephrine was infused at a dose (0.125 microg x min(-) x kg[-1]) chosen to match the insulin-induced increase in femoral blood flow. This dose of epinephrine had no significant effects on arterial blood pressure or heart rate but increased femoral blood flow and lowered hind leg vascular resistance to a similar extent as insulin. Epinephrine did not significantly alter 1-MX metabolism as compared with control animals. These results demonstrate that insulin increases total hind leg blood flow and metabolism of 1-MX, suggesting a recruitment of capillary blood flow in rat hind leg not mimicked by epinephrine.

Animals↗
PubMed1997

Pain management for children.

Dentists are often called upon to perform painful procedures on children. This may present a management problem for the practitioner who is unfamiliar with accepted behavioural management techniques or prescribing analgesics for paediatric patients. This article will review techniques that may be used to guide a child patient's behaviour through painful procedures as well as addressing the need for post-operative analgesics in the paediatric population.

Analgesics↗