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Biomedical subjects

Elizabeth A Davis

Publications and source records attributed to Elizabeth A Davis.

29 records · Page 2Linked to original sources

Effects of exercise training on vascular function in obese children.

OBJECTIVES: Atherosclerosis is a disease that begins in childhood; endothelial dysfunction is its earliest detectable manifestation, and primary prevention strategies are likely to be most effective if instituted early. The aim of this study was to characterize the impact of obesity on vascular function in young children and to determine whether an exercise program improves abnormalities in vascular function. STUDY DESIGN: The influence of 8 weeks of exercise training was examined in 14 obese subjects, 8.9 +/- 0.4 years of age, with the use of a randomized crossover protocol. Conduit vessel endothelial function was assessed by means of high-resolution ultrasound and flow-mediated dilation of the brachial artery (FMD). RESULTS: Exercise training did not change subcutaneous fat mass, body weight, or body mass index. FMD in the obese group was significantly impaired relative to matched control subjects at entry (6.00% +/- 0.69% to 12.32% +/- 3.14%, P <.0001). FMD significantly improved with exercise training (7.35% +/- 0.99%, P <.05) in the obese group. CONCLUSIONS: Conduit vessel FMD, a validated surrogate measure of early atherosclerosis, was impaired in obese children but improved as a result of exercise training. This study supports the value of an exercise program in the treatment of obese children in a primary prevention setting.

Analysis of Variance↗

Lack of effect of oral glucose loading on conduit vessel endothelial function in healthy subjects.

The aim of the present study was to investigate the impact of an oral glucose load on circulating insulin and glucose levels and arterial function in healthy non-diabetic subjects. Thirty-nine non-obese, healthy subjects (24 female, 15 male), aged 21.0+/-1.8 years of age, were randomly assigned to undergo either an OGTT (oral glucose tolerance test; 75 g of glucose) or administration of a placebo. Analyses of lipids, liver function and HbA(1c) (glycated haemoglobin) at baseline revealed results which were within the standard reference range. Insulin and glucose levels as well as vascular function [FMD (flow-mediated dilation)] were measured at 0, 60 and 120 min. Compared with baseline, the control subjects did not exhibit any significant changes in glucose or insulin levels, whereas, in the OGTT group, blood glucose levels at both 60 (5.4+/-1.7 mmol/l) and 120 (5.0+/-1.1 mmol/l) min increased significantly relative to baseline (4.1+/-0.4 mmol/l; both P<0.001) and, similarly, insulin levels were higher at both 60 (30.1+/-21.3 m-units/l) and 120 (34.9+/-23.6 m-units/l) min compared with baseline (4.7+/-4.3 m-units/l; both P<0.001). Although blood glucose and insulin levels changed, FMD did not significantly differ between time-points or between groups. In summary, despite significantly elevated glucose and insulin concentrations in these subjects, we observed no change in vascular function, suggesting that acute elevations of glucose and insulin within the clinically normal range are not associated with impaired vascular function in vivo.

Administration, Oral↗

Functional deletion of the calcium-sensing receptor in a case of neonatal severe hyperparathyroidism.

Heterozygous inactivating mutations of the calcium-sensing receptor (CaR) cause familial hypocalciuric hypercalcemia, whereas homozygous or compound heterozygous inactivating mutations normally cause neonatal severe hyperparathyroidism. In a case of neonatal severe hyperparathyroidism characterized by moderately severe hypercalcemia and very high PTH levels, coupled with evidence of hyperparathyroidism and effects on brain development not previously demonstrated, we detected point mutations on separate alleles of the CaR, resulting in premature stop codon substitutions at G94 and R648. This led to severely truncated receptors and an effective so-called knockout of functional CaR. FLAG-tagged, truncated receptors were expressed in HEK293 cells for functional analysis. Confocal microscopy demonstrated cytoplasmic localization of the G94stop receptor, whereas the R648stop receptor was present both in the cytoplasm and associated with the cell membrane. Only the R648stop receptor could be detected by Western analysis. Functional assays in which R648stop and wild-type receptor were cotransfected into HEK293 cells demonstrated a reduction in wild-type Ca(2+)-responsiveness by the R648stop receptor, even at physiological Ca(2+) levels, thus simulating familial hypocalciuric hypercalcemia in relatives of the infant who were heterozygous for the R648stop mutation. The R648stop receptor alone was nonresponsive to Ca(2+). This case contributes to our understanding of the clinical manifestation of a CaR knockout.

Alleles↗

The impact of a decade of changing treatment on rates of severe hypoglycemia in a population-based cohort of children with type 1 diabetes.

OBJECTIVE: To determine the impact of changes to treatment on the incidence of severe hypoglycemia and its risk factors in a large population-based cohort of children with type 1 diabetes. RESEARCH DESIGN AND METHODS: The cohort consisted of 1,335 children (age at entry 9.5 +/- 4.3 years [mean +/- SD], range 0-18), yielding 6,928 patient-years of data. The mean follow-up period was 4.7 +/- 3.1 years (range 0-10.7). Prospective assessment of severe hypoglycemia (an event leading to loss of consciousness or seizure) and associated clinical factors and outcomes was made between 1992 and 2002. Patients were reviewed every 3 months. Data were analyzed using the negative binomial regression model. RESULTS: A total of 944 severe events were recorded. The incidence of severe hypoglycemia increased significantly by 29% per year for the first 5 years but appeared to plateau over the last 5 years. The overall average HbA1c significantly decreased (by 0.2% per year) over the whole follow-up period. An increased risk of severe hypoglycemia was associated with lower HbA1c, younger age, higher insulin dose, male sex, and lower parental socioeconomic status. Of insulin therapies, only pump treatment was associated with reduced rates of severe hypoglycemia. CONCLUSIONS: Severe hypoglycemia remains a major problem for children and adolescents with type 1 diabetes. Recent approaches to therapy may be allowing a degree of improved control without the expected increased risk of severe hypoglycemia but further monitoring will be important.

Adolescent↗

Functional role of angiotensin II AT2 receptor in modulation of AT1 receptor-mediated contraction in rat uterine artery: involvement of bradykinin and nitric oxide.

The aim of the present study was to explore the mechanisms underlying angiotensin II AT2 receptor modulation of AT1 receptor-mediated vasoconstriction in the rat isolated uterine artery, since previous studies have suggested that AT2 receptors may oppose AT1 receptor-mediated effects. Segments of uterine artery were obtained from Sprague-Dawley rats and mounted in small vessel myographs. Concentration-response (CR) curves to angiotensin II (0.1 nm-0.1 microM) were constructed in the absence and presence of PD 123319 (AT2 antagonist; 1 microM), HOE 140 (bradykinin B2 antagonist; 0.1 microM), Nomega-nitro-l-arginine (NOLA) (NOS inhibitor; 30 microM), as well as combinations of these inhibitors. Contractile responses to angiotensin II were expressed as a percent of the response to a K+ depolarizing solution. PD 123319 (1 microM) potentiated angiotensin II-induced contractions; reflected by a significant four-fold leftward shift of the angiotensin II CR curve. HOE 140 (0.1 microM) significantly increased the pEC50 of the angiotensin II CR curve. The combination of HOE 140 plus PD 123319 did not produce additive potentiation. NOLA (30 microM) significantly enhanced sensitivity to angiotensin II, seen as a five-fold leftward shift of the curve, and an augmented maximum contractile response. Combinations of PD 123319 (1 microM) plus NOLA, and of HOE 140 (0.1 microM) plus NOLA, both induced a similar magnitude of potentiation. Cyclic GMP measurements confirmed angiotensin II-induced activation of the nitric oxide (NO) pathway. In conclusion, AT2 receptor-mediated inhibition of angiotensin II-induced contraction of the rat uterine artery involves NO production; a component of which occurs through a bradykinin B2 receptor pathway.

Angiotensin II↗

Hypoglycemia in children with type 1 diabetes: current issues and controversies.

Hypoglycemia is a common complication of insulin therapy, particularly in the young. For children and adolescents with diabetes, the risk of hypoglycemia may not only prevent optimal glycemic control but can also add significantly to the psychosocial burden of the disease. Recently, surveys employing prospective monitoring techniques have allowed more precise information to be gained about rates of hypoglycemia, its clinical associations, and the impact of new therapies and technologies. A number of reports have estimated rates of hypoglycemic comas and convulsions to be approximately 20 events per 100 patient years in children on current conventional therapy. There is evidence that the introduction of new analog short- and longer-acting insulins and the more widespread use of continuous subcutaneous infusion therapies may allow improvements in glycemic control to occur without the usual increased rate of severe hypoglycemic episodes. The use of glucose sensor technology has brought into focus the widespread occurrence of asymptomatic hypoglycemia. Asymptomatic hypoglycemia has long been recognized, particularly at night, when the combination of excessive insulin action and suppressed counter-regulatory hormone responses put children at special risk of hypoglycemia. Hypoglycemia unawareness is common in the young and is associated with an increased risk of severe hypoglycemia. Whether episodes of severe hypoglycemia have long-term consequences is controversial. Early studies suggesting that the developing brain is sensitive to permanent neurological damage as a result of hypoglycemia have not been confirmed in more recent reports. Many studies have not found convincing evidence of neurological sequelae of the hypoglycemic events that are an inevitable complication of insulin therapy. The question, however, remains under active investigation. Continued prospective monitoring of hypoglycemia rates and consequences has become an essential component of diabetes management.

Adolescent↗

A case series of low-dose fenoldopam in seventy cardiac surgical patients at increased risk of renal dysfunction.

OBJECTIVE: To evaluate the usefulness of low-dose fenoldopam mesylate in patients at risk of developing renal dysfunction after cardiac surgery requiring cardiopulmonary bypass. DESIGN: A prospective, single-center, observational study. SETTING: University teaching hospital. PARTICIPANTS: Seventy patients scheduled for elective cardiac surgery with one or more predefined risk factors for renal dysfunction. INTERVENTIONS: After induction of anesthesia, fenoldopam (0.03 microg/kg/min) was administered throughout surgery and into the postoperative period, until the patient was stable and weaned from all other vasoactive agents. Perioperatively, fenoldopam was also used as a second-line antihypertensive agent as required. MEASUREMENTS AND MAIN RESULTS: No patient developed renal failure that required dialysis, whereas 7.1% (5/70) developed non-dialysis-dependent renal dysfunction. Four out of these 5 patients had 2 or more risk factors (9.5%). Higher preoperative creatinine levels, a history of hypertension, myocardial infarction within 5 days of surgery, and a preoperative diagnosis of chronic renal insufficiency were all good predictors of postoperative non-dialysis-dependent renal dysfunction. Discharge serum creatinine levels were lower than preoperative levels (1.16 +/- 0.36 mg/dL v 1.26 +/- 0.34 mg/dL, p < 0.05). CONCLUSION: These findings suggest that renal function was preserved in patients at increased risk for renal dysfunction after cardiac surgery when low-dose fenoldopam was used in the perioperative period. However, a randomized, controlled trial is required to establish efficacy.

Aged↗

Lasik enhancements: a comparison of lifting to recutting the flap.

PURPOSE: To compare the visual outcomes and incidence of complications of lifting with recutting the lamellar flap in laser in situ keratomileusis (LASIK) enhancement surgery. DESIGN: Retrospective case-control study. PARTICIPANTS: Two hundred twelve consecutive eyes undergoing a LASIK enhancement procedure at a single surgery location during a 5-year period. METHODS: Charts of participants were obtained and outcome measures obtained. MAIN OUTCOME MEASURES: Uncorrected visual acuity, best-corrected visual acuity, refractive error, complications. RESULTS: Relifting of flaps was performed in 164 of 212 eyes (77.4%), and recutting of flaps was performed in 48 of 212 eyes (22.6%). There were no significant differences in early visual outcomes between the two groups. At 1 year patients had significantly better uncorrected vision if the flap was lifted rather than recut (20/24.7 vs. 20/31.3, P < 0.008). In addition, the flap lift group had a significantly more stable refraction at 1 year than did the recut group (change in spherical equivalent: +0.05 diopters (D) vs. -0.57 D). The incidence of complications did not significantly differ between the two groups. CONCLUSIONS: LASIK enhancement surgery can be performed safely and effectively by either lifting or recutting a flap. Lifting the flap may show better long-term stability of refractive error and uncorrected acuity.

Adult↗

Immunohistochemical detection of polychlorinated biphenyls in field collected damselfish (Abudefduf sordidus; Pomacentridae) embryos and larvae.

Antibodies against polychlorinated biphenyls (PCBs) were used to determine if immunohistochemical methods could detect PCBs in embryos and larvae of a territorial coral reef fish (Abudefduf sordidus; Pomacentridae) collected from Johnston Atoll, Central Pacific Ocean. Sites with differing levels of contamination were sampled, one with relatively high sediment PCB concentrations of up to 389.0 ng/g and another with low PCB concentrations of only 0.5 ng/g. Immunostaining suggested that PCB concentrations were higher in fish larvae from the PCB contaminated site and that PCB concentrations within abnormal embryos were higher than normal embryos from the same nest. This technique will be useful for detecting exposed populations in the field and assessing correlations with adverse effects, particularly in potential indicator organisms such as Abudefduf sordidus.

Animals↗

Nomogram considerations with the Technolas 217A for treatment of myopia.

PURPOSE: To determine whether surgeon-specific nomogram adjustments are useful when using the Technolas 217A excimer laser for treating myopia and myopic astigmatism. METHODS: We conducted a prospective evaluation of 216 consecutive eyes with 6 months follow-up after treatment of myopia or myopic astigmatism with the Technolas 217A laser. Attempted vs. achieved change in refraction was analyzed with a statistical analysis software program. Factors such as age, corneal thickness (pachymetry), preoperative spherical equivalent refraction, preoperative cylinder, and optical zone were studied to evaluate their role in predicting refractive outcome at 6 months after LASIK. RESULTS: The mean value of attempted spherical equivalent refraction was -5.32 +/- 2.72 D. The mean achieved refractive correction at 6 months was -5.55 +/- 2.78 D, with a mean spherical equivalent of 0.13 +/- 0.54 D. The percent achieved effect at 1 month was 105%, and at 6 months, 103%. Preoperative spherical equivalent refraction and optical zone size were strong predictors of 6-month LASIK outcome. There was a 9% difference in the percent achieved effect between a 4 and 7-mm optical zone. There was no correlation between age, preoperative cylinder, or surgeon and 6-month outcome. CONCLUSIONS: Surgeons using the planoscan software on the Technolas 217A may experience a small initial overcorrection. There may be a benefit to reducing the treatment given with larger optical zones and smaller corrections.

Adult↗