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Biomedical subjects

E A Davis

Publications and source records attributed to E A Davis.

At least 19 recordsLinked to original sources
PubMed2003

Subcutaneous glucose sensor values closely parallel blood glucose during insulin-induced hypoglycaemia.

AIMS: To assess the accuracy of the Minimed continuous glucose monitoring system (CGMS) in estimating blood glucose concentration during a controlled reduction in blood glucose. RESEARCH DESIGN AND METHODS: We studied nine adolescent diabetics (age 14 +/- 1.5 years) wearing the CGMS during hyperinsulinaemic hypoglycaemic clamp studies. The glucose values obtained by the CGMS were compared with the venous blood samples taken during the studies and measured at the bedside using a glucose oxidase technique. RESULTS: Blood glucose was lowered from euglycaemia to a mean of 2.8 mmol/l over 120 min and maintained at that level for a further 40 min. A total of 429 paired glucose measurements were available for analysis. Analysis using weighted Deming regression and t-tests revealed small differences between the methods, with blood glucose levels slightly higher than interstitial fluid levels. The mean difference across all values was 0.13 mmol/l. The observed difference was greatest at blood glucose values < 3.3 mmol/l. CONCLUSIONS: This study suggests that during a fall in systemic glucose the subcutaneous glucose sensor provides an accurate reflection of blood glucose. However, a small difference is apparent at blood glucose values < 3.3 mmol/l.

Adolescent↗
PubMed2001

Experimental confirmation of the predicted shallow donor hydrogen state in zinc oxide.

We confirm the recent prediction that interstitial protium may act as a shallow donor in zinc oxide, by direct spectroscopic observation of its muonium counterpart. On implantation into ZnO, positive muons--chemically analogous to protons in this context--form paramagnetic centers below about 40 K. The muon-electron contact hyperfine interaction, as well as the temperature and activation energy for ionization, imply a shallow level. Similar results for the cadmium chalcogenides suggest that such shallow donor states are generic to the II-VI compounds. The donor level depths should serve as a guide for the electrical activity of interstitial hydrogen.

Journal Article↗
PubMed2001

Astigmatism management: ablation patterns.

Treatment of astigmatism is possible with the excimer laser. Results with this technology are more predictable and accurate than with incisional techniques. Ablation profiles differ for the various types of astigmatism, and the best approach is the one in which the least amount of tissue is removed from the cornea. Surgical success requires appropriate preoperative counseling, careful preoperative measurements, and meticulous intraoperative technique. Reported outcomes are excellent and future developments will lead to even better results.

Astigmatism↗
PubMed2001

Psychometric evaluation of four HIV disease-specific quality-of-life instruments.

OBJECTIVE: To provide a comparative evaluation of psychometric properties for three or more HIV disease-specific quality-of-life (QoL) instruments. METHODS: Four instruments were selected using the following criteria: multiple publiations of instrument, focus of instrument on QoL, psychometric validation publication or comparison with prevoiusly validated questionnaire, stages of HIV/AIDS used or evaluated in the study, and inclusion of sample items or the instrument in at least one publication. The four HIV-specific QoL instruments were: HIV/AIDS-Targeted Quality of Life Instrument, Medical Outcomes Study HIV questionnaire (MOS-HIV), Functional Assessment of Human Immunodeficiency Virus Infection, and HIV Overview of Problems -- Evaluation System. These instruments were evaluated using combined criteria derived from McHorney and Tarlov and Shumaker et al. The criteria include: administration, content, depth, reliability, validity, and responsiveness. A letter grade scale (A,B,C,D) was used in rating the criteria. RESULTS: No instrument demonstrated ideal psychometric properties. The MOS-HIV questionnaire was the only instrument that published results for seven of the eight categories. Therefore, a decision cannot be made about the best instrument to use for measuring QoL in an HIV-positive patient. CONCLUSIONS: Published data for these questionnaires had common limitations of sample size, study design, and population demograhpics, Hence, further testing of these questionnaires is recommended before use in any study to determine suitability, reliability and validity.

HIV Infections↗
PubMed2000

Corneal thickness and visual acuity after phacoemulsification with 3 viscoelastic materials.

PURPOSE: To determine whether differences exist in visual acuity and corneal thickness after phacoemulsification using various viscoelastic substances. SETTING: Phillips Eye Institute, Minneapolis, Minnesota, USA. METHODS: Fifty patients having routine phacoemulsification cataract extraction and intraocular lens implantation by a single surgeon using the same technique were randomly assigned to receive intraoperative administration of 1 of 3 viscoelastic substances: Amvisc Plus(R) (sodium hyaluronate 1.6%), OcuCoat(R) (hydroxypropyl methylcellulose 2%), or Viscoat(R) (chondroitin sulfate 4%-sodium hyaluronate 3%). Visual acuity and corneal thickness on the first postoperative day were compared between groups. RESULTS: Patients with a best corrected visual acuity (BCVA) of 20/40 or better 1 day postoperatively had significantly thinner corneas (596 microm) than those with a BCVA worse than 20/40 (639 microm). There were no differences in postoperative BCVA or percentage increase in central corneal pachymetry among the 3 viscoelastic groups. CONCLUSION: Viscoat, Amvisc Plus, and OcuCoat were comparable in their ability to produce clear corneas and good vision after routine phacoemulsification.

Chondroitin↗
PubMed2000

Laser in situ keratomileusis after intracorneal rings. Report of 5 cases.

PURPOSE: To examine the results of laser in situ keratomileusis (LASIK) after removal of intracorneal ring (ICR) segments. SETTING: Active refractive surgery practice. METHODS: The effect of ICR (0.45 mm) placement, the rapidity of refractive recovery after explantation, and the results of subsequent LASIK were examined in 5 eyes. RESULTS: Four eyes developed induced astigmatism after ICR implantation. In 2 of these eyes, retained astigmatism was evident by manifest refraction or corneal topography even after ICR explantation. In 1 eye, the ICR procedure was aborted because of an intraoperative complication. All 5 eyes had subsequent uneventful LASIK. CONCLUSIONS: Intracorneal rings can induce astigmatism that may be retained even after explantation. Careful wound manipulation may reduce the incidence of this complication. Laser in situ keratomileusis after ICR removal appears to be safe and effective.

Adult↗
PubMed1999

Cell-biological assessment of human glucokinase mutants causing maturity-onset diabetes of the young type 2 (MODY-2) or glucokinase-linked hyperinsulinaemia (GK-HI).

Mutations in the glucokinase (GK) gene cause type-2 maturity-onset diabetes of the young type 2 (MODY-2) and GK-linked hyperinsulinaemia (GK-HI). Recombinant adenoviruses expressing the human wild-type islet GK or one of four mutant forms of GK, (the MODY-2 mutants E70K, E300K and V203A and the GK-HI mutant V455M) were transduced into glucose-responsive insulin-secreting beta-HC9 cells and tested functionally in order to initiate the first analysis in vivo of recombinant wild-type and mutant human islet GK. Kinetic analysis of wild-type human GK showed that the glucose S(0. 5) and Hill coefficient were similar to previously published data in vitro (S(0.5) is the glucose level at the half-maximal rate). E70K had half the glucose affinity of wild-type, but similar enzyme activity. V203A demonstrated decreased catalytic activity and an 8-fold increase in glucose S(0.5) when compared with wild-type human islet GK. E300K had a glucose S(0.5) similar to wild-type but a 10-fold reduction in enzyme activity. E300K mRNA levels were comparable with wild-type GK mRNA levels, but Western-blot analyses demonstrated markedly reduced levels of immunologically detectable protein, consistent with an instability mutation. V455M was just as active as wild-type GK, but with a markedly reduced S(0.5). The effects of the different GK mutants on glucose-stimulated insulin release support the kinetic and expression data. These experiments show the utility of a combined genetic, biochemical and cell-biological approach to the quantification of functional and structural changes of human GK that result from MODY-2 and GK-HI mutations.

Adenoviridae↗
PubMed1999

Mutants of glucokinase cause hypoglycaemia- and hyperglycaemia syndromes and their analysis illuminates fundamental quantitative concepts of glucose homeostasis.

AIMS/HYPOTHESIS: Mutations of the glucokinase gene cause hyperglycaemia or hypoglycaemia. A quantitative understanding of these defects of glucose homeostasis linked to the glucokinase gene was lacking. Therefore a database of kinetic variables of wild-type and 20 missense mutants of glucokinase was developed and used in mathematical modelling to predict the thresholds for glucose-stimulated insulin release. METHODS: Recombinant human glucokinase was generated in E. coli. The k(cat), glucose S(0.5), ATP K(m), and Hill number of glucokinase were determined. Inhibition by Stearoyl CoA and glucokinase regulatory protein and thermal stability were assayed for all mutants kinetically similar to wild-type glucokinase. A mathematical model predicting the threshold for glucose-stimulated insulin release was constructed. This model is based on the two substrate kinetics of glucokinase and the kinetic variables of the database. It is assumed that both glucokinase gene alleles are equally expressed in beta-cells and that induction of glucokinase occurs as a function of basal blood glucose. RESULTS: Large changes, varying greatly between mutants were found in nearly all variables. Glucokinase flux at threshold for glucose-stimulated insulin release was about 25 % of total phosphorylating potential in the normal beta-cell and this was used to predict thresholds for the mutant heterozygotes. Clinical data for maturity onset diabetes of the young type linked to the glucokinase gene and familial hyperinsulinaemic hypoglycaemia linked to the glucokinase gene and the glucokinase kinetic data of this study were used to test the model. The model predicts fasting blood glucose between 3 and 7 mmol/l in these cases. CONCLUSION/INTERPRETATION: A kinetics database of wild-type and 20 mutants of glucokinase was developed. Many kinetic differences were found for the mutants. The mathematical model to calculate the threshold for glucose-stimulated insulin release predicts fasting blood glucose between 3 and 7 mmol/l in subjects with glucokinase gene mutations. [Diabetologia 42: 1175-1186]

Adaptor Proteins, Signal Transducing↗
PubMed1999

Structural model of human glucokinase in complex with glucose and ATP: implications for the mutants that cause hypo- and hyperglycemia.

Mutations in human glucokinase are implicated in the development of diabetes and hypoglycemia. Human glucokinase shares 54% identical amino acid residues with human brain hexokinase I. This similarity was used to model the structure of glucokinase by analogy to the crystal structure of brain hexokinase. Glucokinase was modeled with both its substrates, glucose and MgATP, to understand the effect of mutations. The glucose is predicted to form hydrogen bond interactions with the side chains of glucokinase residues Thr 168, Lys 169, Asn 204, Asp 205, Asn 231, and Glu 290, similar to those observed for brain hexokinase I. The magnesium ion is coordinated by the carboxylates of Asp 78 and Asp 205 and the gamma-phosphate of ATP. ATP is predicted to form hydrogen bond interactions with residues Gly 81, Thr 82, Asn 83, Arg 85, Lys 169, Thr 228, Lys 296, Thr 332, and Ser 336. Mutations of residues close to the predicted ATP binding site produced dramatic changes in the Km for ATP, the catalytic rate, and a loss of cooperativity, which confirmed our model. Mutations of residues in the glucose binding site dramatically reduced the catalytic activity, as did a mutation that was predicted to disrupt an alpha-helix. Other mutations located far from the active site gave smaller changes in kinetic parameters. In the absence of a crystal structure for glucokinase, our models help rationalize the potential effects of mutations in diabetes and hypoglycemia, and the models may also facilitate the discovery of pharmacological glucokinase activators and inhibitors.

Adenosine Triphosphate↗
PubMed1998

Decreased epinephrine responses to hypoglycemia during sleep.

BACKGROUND: In patients with type I diabetes mellitus, hypoglycemia occurs commonly during sleep and is frequently asymptomatic. This raises the question of whether sleep is associated with reduced counterregulatory-hormone responses to hypoglycemia. METHODS: We studied the counterregulatory-hormone responses to insulin-induced hypoglycemia in eight adolescent patients with type I diabetes and six age-matched normal subjects when they were awake during the day, asleep at night, and awake at night. In each study, the plasma glucose concentration was stabilized for 60 minutes at approximately 100 mg per deciliter (5.6 mmol per liter) and then reduced to 50 mg per deciliter (2.8 mmol per liter) and maintained at that concentration for 40 minutes. Plasma free insulin, epinephrine, norepinephrine, cortisol, and growth hormone were measured frequently during each study. Sleep was monitored by polysomnography. RESULTS: The plasma glucose and free insulin concentrations were similar in both groups during all studies. During the studies when the subjects were asleep, no one was awakened during the hypoglycemic phase, but during the final 30 minutes of the studies when the subjects were awake both the patients with diabetes and the normal subjects had symptoms of hypoglycemia. In the patients with diabetes, plasma epinephrine responses to hypoglycemia were blunted when they were asleep (mean [+/-SE] peak plasma epinephrine concentration, 70+/-14 pg per milliliter [382+/-76 pmol per liter]; P=0.3 for the comparison with base line), as compared with when they were awake during the day or night (238+/-39 pg per milliliter [1299+/-213 pmol per liter] P=0.004 for the comparison with base line, and 296+/-60 pg per milliliter [1616+/-327 pmol per liter], P=0.004, respectively). The patients' plasma norepinephrine responses were also reduced during sleep, whereas their plasma cortisol concentrations did not increase and their plasma growth hormone concentrations increased slightly. The patterns of counterregulatory-hormone responses in the normal subjects were similar. CONCLUSIONS: Sleep impairs counterregulatory-hormone responses to hypoglycemia in patients with diabetes and normal subjects.

Adolescent↗
PubMed1998

Refractive and keratometric results after the triple procedure: experience with early and late suture removal.

OBJECTIVE: The objective of this study was to determine the outcome of early and late suture removal after the triple procedure (i.e., penetrating keratoplasty, cataract extraction, lens implant). DESIGN AND PARTICIPANTS: The refractive and keratometric results of 106 eyes undergoing the triple procedure were reviewed. The target postoperative refractive error was -1 diopter (D). RESULTS: Average length of follow-up was 40.3 months. Twenty eyes had sutures removed early (<18 months after surgery), 39 had sutures removed late (> or = 18 months after surgery), and 47 had sutures still intact at last follow-up. A best spectacle-corrected visual acuity of 20/40 or better was achieved in 90% of eyes with sutures removed early, 82.1% with sutures removed late, and 70.2% with sutures in place. For all eyes, the mean spherical equivalent at last follow-up was -2.50 D, with 75% of eyes falling between -4 and +2 D. The mean final refractive error was -3.40 +/- 3.53 D for eyes with sutures removed early and -1.79 +/- 3.99 D for eyes with sutures removed late. Eyes with sutures remaining had a mean final refractive error of -0.33 +/- 2.25 D. There was an overall decrease in refractive and keratometric astigmatism after both early and late suture removal with no significant difference between groups. However, there was a wide range of change with some eyes experiencing a decrease and others an increase in astigmatism. Mean postoperative K readings increased significantly for both groups after suture removal (final mean K, 47.00 D) but remained stable for eyes with sutures in. CONCLUSION: The authors data suggest that the final refractive error and net change in refractive and keratometric astigmatism after the triple procedure are not dependent on the timing of suture removal.

Aged↗
PubMed1998

Use of automated external defibrillators by police officers for treatment of out-of-hospital cardiac arrest.

OBJECTIVE: To determine the feasibility of police officers providing defibrillation with automated external defibrillators (AEDs) and to assess the effectiveness of this strategy in reducing time to defibrillation of victims of out-of-hospital sudden cardiac arrest. METHODS: This was a prospective, interventional cohort study with historical controls conducted in 7 suburban communities in which police usually arrived at the scene of medical emergencies before EMS personnel. All adult patients who suffered cardiac arrest before EMS arrival and on whom EMS personnel attempted resuscitation were enrolled. Police officers who were trained to use and equipped with AEDs during the intervention phase were dispatched simultaneously with EMS to medical emergencies. Police were instructed to use the AED immediately on determination of pulselessness. Outcome measures were the difference between control and intervention phases in interval from the time the call was received at dispatch to the time of first defibrillation and in rate of survival to hospital discharge for patients initially in ventricular fibrillation. RESULTS: EMS personnel attempted 183 resuscitations in the control phase and 283 during the intervention; of these, 80 (44%) and 127 (45%), respectively, involved patients with initial ventricular fibrillation rhythms. Mean time to defibrillation decreased from 11.8+/-4.7 minutes in the control phase to 8.7+/-3.7 minutes in the intervention phase (P<.0001). Survival to hospital discharge of patients in ventricular fibrillation did not differ between phases (6% control versus 14% intervention, P=.1). When police arrived before EMS personnel, shock administered by police compared with shock administered by EMS was associated with improved survival (26% [12/46] versus 3% [1/29], P=.01). Logistic regression analysis revealed AED use was an independent predictor of survival to hospital discharge. CONCLUSION: In 7 suburban communities, police use of AEDs decreased time to defibrillation and was an independent predictor of survival to hospital discharge.

Adult↗
PubMed1998

Modulation of AT1 receptor-mediated contraction of rat uterine artery by AT2 receptors.

The aim of this study was to characterize the angiotensin II receptors in isolated uterine arteries from non pregnant and pregnant rats, since it has been reported from binding studies that ovine uterine arteries contain AT2 receptors. Uterine arterial segments were obtained from virgin, non-pregnant and late pregnant (18-21 days) Sprague-Dawley rats and mounted in small vessel myographs. Concentration-response curves were constructed to angiotensin II (1 nM-10 microM) in the absence and presence of various angiotensin II receptor subtype selective compounds. These included losartan (AT1 antagonist; 1, 10 and 100 nM), PD 123319 (AT2 antagonist; 1 microM) and CGP 42112 (AT2 agonist; 1 microM). Responses to angiotensin II were measured as increases in force (mN) and expressed as a per cent of the response to a K+ depolarizing solution. Losartan (1, 10 and 100 nM) caused significant concentration-dependent rightward shifts of the angiotensin II concentration-response curve in uterine arteries from non-pregnant and pregnant rats. The pA2 values calculated from these data were 9.8 and 9.2, respectively, although the slope of the Schild plot in the non-pregnant group was less than unity. PD 123319 (1 microM) caused significant 6- and 3 fold leftward shifts of the angiotensin II concentration-response curve in uterine arteries from non-pregnant and pregnant rats, respectively. In vessels from pregnant rats, PD 123319 also significantly increased the maximum response to angiotensin II. CGP 42112 (1 microM) attenuated the response to angiotensin II of uterine arteries from non-pregnant rats. This was reflected by a 14 fold rightward shift of the angiotensin II concentration-response curve and a decrease in the maximum response. In uterine arteries from pregnant rats, CGP 42112 (1 microM) caused a 3 fold rightward shift of the angiotensin II concentration-response curve, but had no effect on the maximum response. PD 123319 (1 microM) and CGP 42112 (1 microM) had no effect on the concentration-response curves to phenylephrine (PE) of uterine arteries from non-pregnant or pregnant rats. In addition, CGP 42112 (1 nM-1 mM) had no vasodilator effect on tissues precontracted with phenylephrine. These results suggest that the contractile responses of the rat uterine artery are mediated by the AT1 receptor. Furthermore, in this vascular preparation, the AT2 receptor appears to inhibit the response mediated by the AT1 receptor, although, this is not uniform between the non-pregnant and pregnant states.

Angiotensin II↗
PubMed1998

Impact of improved glycaemic control on rates of hypoglycaemia in insulin dependent diabetes mellitus.

Increased emphasis on strict glycaemic control of insulin dependent diabetes mellitus (IDDM) in young patients may be expected to cause increases in rates of significant hypoglycaemia. To evaluate whether this is the case for a large population based sample of IDDM children and adolescents rates of severe (coma, convulsion) and moderate (requiring assistance for treatment) hypoglycaemia were studied prospectively over a four year period. A total of 709 patients were studied yielding 2027 patient years of data (mean (SD) age: 12.3 (4.4); range 0-18 years, duration IDDM: 4.9 (3.8) years). Details of hypoglycaemia were recorded at clinic visits every three months when glycated haemoglobin (HbA1c) was also measured. Overall the incidence of severe hypoglycaemia was 7.8 and moderate was 15.4 episodes/100 patient years. Over the four years mean (SD) clinic HbA1c steadily fell from 10.2 (1.6)% in 1992 to 8.8 (1.5)% in 1995. In parallel with this there was a dramatic increase in the rate of hypoglycaemia, especially in the fourth year of the study, when severe hypoglycaemia increased from 4.8 to 15.6 episodes/100 patient years. This increase was particularly marked in younger children (< 6 years) in whom severe hypoglycaemia increased from 14.9 to 42.1 episodes/100 patient years in 1995. It is concluded that attempts to achieve improved metabolic control must be accompanied by efforts to minimise the effects of significant hypoglycaemia, particularly in the younger age group.

Adolescent↗