Professionals' beliefs about useful symptoms of hypoglycemia.
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Blood Glucose↗
Biomedical subjects
D J Cox
Publications and source records attributed to D J Cox.
The hemoglobins of the bullfrog, Rana catesbeiana. Deoxygenation-linked association of tetrameric components B and C to form the trimer BC2: sedimentation analysis and oxygen equilibria.
Hemolysates from the adult bullfrog, Rana catesbeiana, show an unusually high degree of cooperativity of oxygen binding with Hill coefficients greater than 4. The principal components of the tetrameric hemoglobin, B and C, do not show this high cooperativity when isolated, but it reappears when the components are mixed. Sedimentation velocity measurements show that the unusual behavior results from the mixed association of components B and C to form complexes larger than tetramers. Computer simulation of the sedimentation behavior of mixtures of deoxygenated B and C components shows that the gradient profiles can be satisfactorily described in terms of an equilibrium between the B and C tetramers and a BC2 trimer. The simplest model consistent with the results is the mixed association: B + C<-->BC and BC + C<-->BC2, with the second binding constant being higher than the first, indicating significant cooperativity. The extent of association is highest at low pH and low temperature. The dissociation of the B.C complex with low oxygen affinity to higher affinity B and C molecules during oxygenation results in greatly increased cooperativity of oxygen binding with higher Hill coefficients than possessed by either component alone in equilibria measured between 5 and 25 degrees C and between pH 6 and 8.
Animals↗
Sizing of bovine heart and kidney pyruvate dehydrogenase complex and dihydrolipoyl transacetylase core by quasielastic light scattering.
Quasielastic light scattering (QELS) measurements on several preparations of bovine heart and kidney pyruvate dehydrogenase complex yielded hydrodynamic radii (rH values) ranging from 25.7 to 30 nm. Gel filtration chromatography removed stable aggregates and generated preparations that gave essentially the same rH values of 24.3 +/- 0.6 nm for both complexes. The data were characteristic of a monodisperse system and agree with estimates using cryoelectron microscopy [Wagenknecht et al. (1991) J. Biol. Chem. 266, 24650-24656]. The equivalent hydrodynamic sizes for the heart and kidney complex indicate that the larger number of pyruvate dehydrogenase components in the heart complex (M(r) congruent to 9 x 10(6)) than the kidney complex (M(r) congruent to 7.5 x 10(6)) associate without radial expansion of the heart complex. That accommodation of additional mass is consistent with the space available since even in the more massive complex greater than 80% of the volume within the dimensions of the complex must be occupied by solvent. Preparations of the core of the complex are primarily composed of 60 dihydrolipoyl acetyltransferase (E2) subunits whose inner domains associate to form a pentagonal dodecahedron that is readily observed by electron microscopy (particle radius 10.7-11.3 nm). However, the bulk of E2's mass is present in an exterior multidomain structure. These mobile outer structures are very difficult to observe by standard electron microscopy techniques. Preparations of the core formed stable aggregates that were removed by gel filtration chromatography. QELS measurements gave an rH of 20.1 +/- 0.8 nm.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetyltransferases↗
Driving decrements in type I diabetes during moderate hypoglycemia.
Diabetic hypoglycemia produces cognitive-motor slowing, which is assumed to increase risk of automobile crashes. This study investigated driving decrements during and after hypoglycemia, and the patients' awareness of driving decrements. We used a randomized, single-blind, crossover design and conducted the study at the University of Virginia's General Clinical Research Center. We studied a volunteer sample of 27 consecutive adult type I diabetic patients who responded to newspaper ads. Two dropped out (final n = 25). Mean age (+/- SD) was 35.9 +/- 14 yr. Diabetes history was 14.6 +/- 10.5 yr, with HbA1 of 10.8 +/- 2.9%. Driving experience was 19 +/- 13.2 yr. Participants drove a state-of-the-art driving simulator on two consecutive days: Control day involved four euglycemia (mean blood glucose, 6.3 +/- 0.89 mM) driving tests; experimental day involved testing at euglycemia, mild hypoglycemia (mean blood glucose, 3.6 +/- 0.33 mM), moderate hypoglycemia (mean blood glucose, 2.6 +/- 0.28 mM), and again at euglycemia. Patients were blind to blood glucose manipulations and levels. Driving performance was not disrupted at mild hypoglycemia nor after recovery from moderate hypoglycemia. Moderate hypoglycemia disrupted steering, causing more swerving (P < 0.03), spinning (P < 0.03), time over midline (P < 0.05), and time off road (P < 0.01). It also resulted in an apparent compensatory slowing, with more very slow driving (P < 0.04). Global driving performance decrements were observed in 35% of the patients, only 50% of whom stated they would not drive under similar conditions. Driving decrements were unrelated to demographic, disease, or driving history variables.(ABSTRACT TRUNCATED AT 250 WORDS)
Accidents, Traffic↗
Disruptive effects of acute hypoglycemia on speed of cognitive and motor performance.
OBJECTIVE: To directly examine whether hypoglycemia differentially slows cognitive versus motor function, to evaluate the reliability of hypoglycemic-related slowing, and to examine factors contributing to individual differences. RESEARCH DESIGN AND METHODS: IDDM subjects (n = 10) were administered a pure cognitive and a pure motor neuropsychological test at euglycemia (5.4 mmol), blood glucose nadir (2.6 mmol), postnadir (3.6 mmol), and again at euglycemia (6.7 mmol). To assess the practice effect, matched control subjects were tested at similar time intervals. RESULTS: Concurrent and test-retest reliability for all tests was robust (r = 0.68-0.94). Only cognitive tasks demonstrated impairment at nadir (P < 0.04). Individual differences, in terms of cognitive impairment, were significantly correlated with levels of blood glucose at nadir and baseline performance. CONCLUSIONS: Cognitive tasks appear to be more sensitive to neuroglycopenia than motor tasks. Cognitive impairment caused by hypoglycemia is reliable and differs across subjects. Individuals who show reliable sensitivity to cognitive impairments of hypoglycemia should avoid moderately low blood glucose levels.
Adult↗
Hunger. A sensitive but nonspecific symptom of hypoglycemia.
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Awareness↗
Perceived symptoms in the recognition of hypoglycemia.
For people with diabetes, detection of hypoglycemic symptoms is a critical tool for the recognition and treatment of hypoglycemia. This is not a simple process involving only the occurrence of a hypoglycemic-relevant physiological event, such as sweating. We propose a four-step biological and psychological model that leads to the accurate recognition of hypoglycemia through symptoms. The model illustrates both the chronic and transient modifiers that can enhance and interfere with recognition of hypoglycemia. Three common methods are used to investigate the occurrence and utility of hypoglycemic symptoms that relate to this model. This article reviews the advantages and disadvantages of these methods, providing previously unpublished illustrative data. The field study hit/false alarm approach was shown to be the most useful method. The relevance of this model and data to the concept of hypoglycemic awareness/unawareness and blood glucose awareness training is discussed.
Adult↗
Deoxygenation-linked association of a tetrameric component of chicken hemoglobin.
Deoxygenation-dependent association of hemoglobin tetramers appears to be widespread among amphibians, reptiles, and possibly all or most birds. The evidence for this conclusion depends largely on oxygen equilibria of whole blood which have Hill coefficients that reach values as high as 5-7 at 80-90% oxygenation. Computer simulation of the sedimentation velocity behavior of the major components A and D of chicken hemoglobin shows that component D but not A self-associates to form dimers of tetramers. The gradient profiles at pH 7.5 were satisfactorily fitted with an association constant of 1.26 x 10(4) M-1 and sedimentation coefficients of 4.63 and 7.35 S for tetramer and (tetramer)2, respectively. Since components A and D share common beta chains we conclude that tetramer-tetramer contacts must depend on surface residues of the alpha chains. Comparison of the amino acid sequences of the alpha D and alpha A chains of the hemoglobins from 12 avian species ranging from sparrow to ostrich shows that 20 residues are conserved in the alpha D chains but not in the alpha A chains. Nine of these (45%) are clustered between positions E20 and FG2. Four of the latter, Lys71 (E20), Asn75 (EF4), Gln78 (EF7), and Glu82 (F3) are conserved in all alpha D chains even though they do not appear to participate in intratetramer contacts. Molecular modeling indicates that residues Lys71, Gln78, and Glu82 of the alpha chain are strong candidates for the primary tetramer-tetramer contacts.
Amino Acids↗
An alternative biofeedback-based behavior modification treatment for a case of chronic constipation.
A 31-year old female with chronic constipation was referred for treatment of a paradoxical contraction of the external anal sphincter (EAS) muscle during straining to defecate. The patient was dependent on laxative use and the digital removal of feces. The present program emphasized biofeedback training of the EAS utilizing the inexpensive, noninvasive procedure of disposable surface electrodes placed on the anal verge. Outcome of treatment resulted in an 89% decrease in laxatives used, complete termination of the digital removal of feces, and a notable decrease in EAS tension. The patient was able to maintain these gains at an 8 month follow-up.
Adult↗
Major developments in behavioral diabetes research.
Over the past decade, there has been a major increase in behavioral diabetes research. This review focuses on 6 areas: self-treatment, psychosocial impact, diabetes-specific assessment, psychological stress, weight loss intervention, and neuropsychological effects. There has been great progress in identifying factors that predict self-treatment behaviors and psychological adjustment. This research has produced a number of diabetes-specific assessment tools. Psychological stress appears to affect both the etiology and the control of diabetes, but underlying mechanisms remain unclear. Weight loss studies demonstrate the potential benefits of behavioral interventions for diabetes management. Both acute and chronic abnormalities in diabetic blood glucose cause neuropsychological impairments and may cause permanent deficits. The challenge for the next decade is to translate these findings into interventions that improve quality of life and physical well-being for individuals with diabetes.
Adaptation, Psychological↗
Introduction of intravenous lipid administration on the first day of life in the very low birth weight neonate.
OBJECTIVE: To investigate lipid tolerance in sick, ventilator-dependent, very low birth weight infants from the first day of life and the effects of early introduction of intravenously administered lipid (IVL) on glucose homeostasis. METHOD: Twenty-nine infants in the neonatal intensive care unit with birth weight less than 1500 gm received isocaloric, isonitrogenous parenteral feedings from day 1 with either IVL, 1 gm/kg from day 1 to 3 gm/kg from day 4 (group I; n = 16), or IVL added only from day 8 (group II; n = 13). Possible adverse clinical effects were monitored. Blood metabolites, nonesterified fatty acids, serum triglycerides, and insulin levels were determined daily. Arterial blood gases were measured and changes in partial pressures of oxygen and of carbon dioxide in arterial blood were compared between the two groups. RESULTS: Early lipid infusion did not appear to have deleterious effects on blood gas tensions or to increase respiratory morbidity. The incidence of other adverse clinical effects that may be associated with IVL was not increased by earlier introduction of lipid. Serum lipid values were comparable to those of preterm infants receiving IVL at a later postnatal age. Blood glucose concentrations were higher in group II (mean, 7.50 (SEM 0.43) mmol/L) than in group I (mean, 6.01 (SEM 0.28) mmol/L; p less than 0.05). There was no evidence of increased gluconeogenesis in infants in group I and no correlation between blood glucose concentrations and serum nonesterified fatty acid concentrations. CONCLUSION: When given infusion rates not exceeding 0.15 gm/kg/hr, sick, very low birth weight infants can tolerate IVL with stepwise dose increases from the first day of life without an increased incidence of possible adverse effects.
Birth Weight↗
Collaborations in art/science: Renaissance teams.
A Renaissance Team is a group of specialists who collaborate and provide synergism in the quest for knowledge and information. Artists can participate in Renaissance Teams with scientists and computer specialists for scientific visualization projects. Some projects are described in which the author functioned as programmer and color expert, as interface designer, as visual paradigm maker, as animator, and as producer. Examples are provided for each of these five projects.
Art↗
Environmental stress and blood glucose change in insulin-dependent diabetes mellitus.
Blood glucose (BG) response to psychological stress in insulin-dependent diabetes mellitus (IDDM) patients has not been firmly established. We report a study designed to address the gaps and methodological difficulties reviewed. Subjects with IDDM were exposed to two sessions (12 weeks apart) of two 20-min standardized stressors (active and passive) and a control condition administered in counterbalanced order. To measure BG response, subjects were connected to a glucose/insulin infusion system providing continuous BG measurement. Mood checklist measures were obtained at prestressor, poststressor, and recovery periods. During the first session of testing, the active stressor was associated with significantly more absolute change in BG response than the passive stressor. Results also indicate that IDDM subjects' BG response to this active stressor was idiosyncratic but significantly reliable over time.
Arousal↗
Survey of diabetes professionals regarding developmental changes in diabetes self-care.
There are no empirically obtained data defining appropriate developmental expectations for the acquisition of self-care independence by children with insulin-dependent diabetes mellitus. This study surveyed diabetes professionals about their estimates of ages at which children typically master 38 diabetes skills. The 229 survey respondents represented a broad range of professions and clinical settings and had extensive experience as diabetes professionals. Mean mastery age estimates were less than 14 yr for the 38 skills assessed. Responses to each item were variable among respondents, with a mean SD of 2.1 yr in estimated mastery ages for all items. Estimated mastery ages were below the age ranges recommended by the American Diabetes Association for 14 of 20 comparable skills. Physicians generally expected the diabetes skills to be mastered at later ages than did nurses or other health-care professionals. There were no other consistent response patterns related to respondent characteristics, i.e., years of clinical experience, employment setting, current patient load, or method of survey distribution.
Adolescent↗
Psychobehavioral metabolic parameters of severe hypoglycemic episodes.
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Adult↗
Isolation and characterization of folded fragments released by Staphylococcal aureus proteinase from the non-histone chromosomal protein HMG-1.
HMG-1 was isolated from newborn calf thymus without exposure to overt denaturing conditions. The purified protein was digested under several solvent conditions with the proteinase (endoproteinase GluC) from Staphylococcus aureus strain V8. We found that the preferred site of attack by the enzyme on HMG-1 was influenced markedly by ionic strength and temperature. In 0.35 M NaCl/50 mM Tris-phosphate (pH 7.8) at 37 degrees C, cleavage near the junction between the A and B domains is predominant, as previously reported by Carballo et al. (EMBO J. 2 (1983) 1759-1764). However, in 50 mM Tris-phosphate (pH 7.8) lacking NaCl and at 0 degrees C, cleavage between the B and C domains strongly predominates. Three major products of the digestions were purified and characterized. The fragment consisting of domains B and C was found by circular dichroism to contain a substantial amount of helix. This re-emphasizes the importance of avoiding overt denaturing conditions when working with members of the HMG-1 family.
Amino Acid Sequence↗
Mood changes associated with blood glucose fluctuations in insulin-dependent diabetes mellitus.
Individuals with insulin-dependent diabetes mellitus (IDDM) and their healthcare practitioners believe that extreme blood glucose (BG) fluctuations are characterized by changes in subjective mood states and emotional behavior, as well as physical symptoms. This study examined relationships between BG levels and self-reported mood in a group of 34 IDDM adults. The method followed a within-subject, repeated-measures design employed in previous studies of physical symptoms associated with diabetic glucose. Four times each day, participants completed a mood/symptom checklist just prior to a self-measurement of BG until 40 checklists had been completed. Half the items on the checklist described physical symptoms and half described mood states. In addition, half the mood items described negative states and half described positive states. Within-subject correlations and regressions showed that moods were related to BG for the majority of participants and that, like physical symptoms, mood-BG relationships were highly idiosyncratic. Low BG levels tended to be associated with negative mood states, primarily self-reported "nervousness." Positive mood items were almost always associated with high BG. High BG levels also frequently correlated with negative mood states, although the negative mood items that tended to relate to high glucose (anger, sadness) differed from those that tended to relate to low BG. The implications of these findings for self-treatment and glucose perception in the IDDM individual are discussed.
Adult↗