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Biomedical subjects

B Crabtree

Publications and source records attributed to B Crabtree.

At least 19 recordsLinked to original sources

Case managers and physicians: communication and perceived problems.

OBJECTIVE: To describe case managers' perceptions of the physician-case manager relationship. DESIGN: A qualitative field study using in-depth open-ended interviews was used to elicit case managers' experiences and practices. A multidisciplinary team analyzed transcripts using an adaptation of the "grounded theory" approach of Glaser and Strauss. PARTICIPANTS/SETTING: Case managers were selected for interview using a maximum variation sampling strategy within an established state-wide case management agency. MAIN OUTCOME MEASURES: Transcript analysis allowed for the organization of observations into themes, which were merged across interviews to generate theses. RESULTS: Case managers report that: (1) The case manager role is poorly understood by physicians. (2) Physicians lack insight into the social and environmental aspects of home-bound elderly people. (3) Access to physician services is often difficult to obtain. (4) Power struggles occasionally surface in care planning. (5) Decisions by physicians and case managers regarding the care of frail elderly are often made from different agenda. CONCLUSIONS: From the perspective of case managers, gaps in interprofessional communication may hinder the optimal care of frail elderly individuals.

Aged

Serum albumin and prealbumin as predictors of clinical outcomes of hospitalized elderly nursing home residents.

OBJECTIVE: To investigate the prevalence of hypoalbuminemia and hypoprealbuminemia in hospitalized, elderly, skilled nursing facility residents and to correlate these findings with clinical outcomes. DESIGN: Prospective cohort study. SETTING: A 300-bed community hospital. PARTICIPANTS: Eighty-one hospitalized, skilled nursing facility patients, average age 83.1 years. INTERVENTIONS: None. OUTCOME MEASURES: Serum albumin and prealbumin (transthyretin) were measured at admission, mid-week, 1 week, and 1 month. Patients were followed for 90 days for the outcomes of length of hospitalization and mortality. RESULTS: The prevalence of hypoalbuminemia was 99% and of hypoprealbuminemia, 79%. Both means dropped significantly from admission to midweek nadirs of 25 g/L for albumin and 14 mg/L for prealbumin. Severe hypoalbuminemia at mid-week predicted mortality (RR = 4.1 95%, CI 2.0-8.5) and extended length of hospitalization (RR = 5.2 95%, CI 2.8-9.8). Severe hypoprealbuminemia predicted extended hospitalization (RR = 3.2, CI 1.5-6.7) but not mortality. CONCLUSIONS: Hypoalbuminemia and hypoprealbuminemia are very common in this clinical setting and vary in parallel fashion over time. Severe hypoalbuminemia was a stronger predictor than hypoprealbuminemia of 90-day mortality and extended length of stay. Serum albumin on admission was not as strong a predictor of outcomes as serum albumin at mid-week.

Aged

The effects of propionate and butyrate on acetate metabolism in rat hepatocytes.

1. Two mM propionate or butyrate inhibited the mitochondrial uptake of acetate by rat hepatocytes. 2. With propionate the inhibition was so strong that the net formation of acetate in the cytoplasm, usually masked by the mitochondrial uptake, appeared directly as a net output of acetate into the medium; showing that this net formation of acetate, reported by [Crabtree B., Gordon M.-J. and Christie S. L. (1990) Biochem. J. 270, 219-225] is not an artefact arising from a misinterpretation of isotopic data. 3. The results also suggest that propionate and butyrate inhibit peroxisomal metabolism.

Acetates

A method for identifying external control sites in metabolic systems.

A graphic method is presented for the identification of control sites in a metabolic system. This method is based on the matrix method for calculating net sensitivities developed by Crabtree and Newsholme (Biochem. J. 247: 113-120, 1987) and avoids the misidentification of control sites that can result from a simple inspection of a system. The method is easily adapted for analysis by computer and may be used for preliminary investigations of metabolic systems to identify potential control sites for further more quantitative investigations.

Animals

A method for testing the stability of a steady-state system during the calculation of a response to large changes in regulator concentrations.

A modification of the 'finite decomposition' method (Crabtree and Newsholme (1985) Curr. Top. Cell. Regul. 25, 21-76) for calculating physiological responses from sensitivities is described, to enable the system to be tested for stability at each step of the procedure. Instability is indicated by a change of sign of the determinant of the square matrix (N) in the governing equation for the system. The method cannot be used to predict a change of sign of the determinant of the square matrix (N) in the governing equation for the system. The method cannot be used to predict responses beyond any step at which instability occurs.

Allosteric Regulation

Measurement of the rates of acetyl-CoA hydrolysis and synthesis from acetate in rat hepatocytes and the role of these fluxes in substrate cycling.

1. Acetyl-CoA hydrolysis, acetyl-CoA synthesis from acetate and several related fluxes were measured in rat hepatocytes. 2. In contrast with acetyl-CoA hydrolysis, most of the acetyl-CoA synthesis from acetate occurred in the mitochondria. 3. Acetyl-CoA hydrolysis was not significantly affected by 24 h starvation or (-)-hydroxycitrate. 4. In the cytoplasm there was a net flux of acetyl-CoA to acetate, and substrate cycling between acetate and acetyl-CoA in this compartment was very low, accounting for less than 0.1% of the total heat production by the animal. 5. A larger cycle, involving mitochondrial and cytoplasmic acetate and acetyl-CoA, may operate in fed animals, but would account for only approx 1% of total heat production. 6. It is proposed that the opposing fluxes of mitochondrial acetate utilization and cytoplasmic net acetate production may provide sensitivity, feedback and buffering, even when these fluxes are not linked to form a conventional substrate cycle.

Acetates

Seat belt use and stress in adolescents.

This study explored the association of adolescent seat belt use with psychosocial risk factors in an urban minority population after the enactment of a mandatory seat belt law. Data on seat belt use, family support, feelings of being down, suicidal ideation, substance abuse, sexual activity, school troubles, and problems with the law were obtained from 541 self-report intake forms administered to an adolescent medicine clinic population from 1986 to 1987. Respondents were almost exclusively black and Hispanic; 315 (59%) were females and 222 (41%) males, with a mean age of 15.4. Seat belt use was reported by 249 (46%) and no or intermittent use by 292 (54%). Chi-square and Wilcoxon rank sums tests were used to examine associations between seat belt use and risk factors. Results showed that the group comprised of those reporting no and intermittent seat belt use was significantly more likely to feel down, have decreased home support, have problems with school and the law, have been on probation, and feel that life in general was not going very well. No association was found between seat belt use and cigarette, drug, or alcohol use or sexual activity without contraceptives. Taking into account the lack of observed behavioral information to validate such self-report questionnaires, these data nevertheless point to the nonuse or intermittent use of seat belts as a possible manifestation of a lack of self-care due to feeling down and/or preoccupation with family, school, or societal problems.

Adolescent

A simplified method for calculating complex metabolic sensitivities by using matrix partitioning.

The matrix method for calculating the overall sensitivities (including control coefficients) of a metabolic system, described by Crabtree & Newsholme [Biochem. J. 247, 113-129 (1987)], is simplified by a preliminary partitioning of the initial matrix equation. This reduces the size of the matrix to be inverted and thereby removes a major drawback with the original method. The resulting procedure is simpler and more systematic than the alternative methods currently available, especially when the system is extensively branched.

Mathematics

Evidence that the production of acetate in rat hepatocytes is a predominantly cytoplasmic process.

By using [1-14C]butyrate, the fluxes of butyrate to acetate and fatty acids were measured in rat hepatocytes. Both fluxes were inhibited to a similar extent by (-)-hydroxycitrate, with no significant effect on butyrate uptake. These results indicate that acetate formation takes place in the cytoplasm, presumably via ATP-stimulated acetyl-CoA hydrolase. Since acetate formation occurred despite a net uptake of acetate, the results are also consistent with the operation of a substrate cycle between acetate and acetyl-CoA, recently proposed by other workers, and suggest that this cycle is cytoplasmic.

Acetates

The derivation and interpretation of control coefficients.

1. Equations for control coefficients are derived by using a method that generates all the control coefficients for a system in a single procedure. This requires solving fewer simultaneous equations than an equivalent method based on 'control theorems'. 2. The interpretation of control coefficients is discussed: in particular, it is shown that these functions are unsatisfactory as measures of 'control' and are perhaps best used as a means of testing control theories (models).

Mathematics

Measurement of the rate of substrate cycling between acetate and acetyl-CoA in sheep muscle in vivo. Effects of infusion of acetate.

1. The rate of substrate cycling between acetate and acetyl-CoA in sheep hindlimb muscle was measured from the decrease of [14C]acetate specific radioactivity across the tissue in vivo. 2. The rate of cycling was 0.005-0.015 mumol/min per g and, in two of the three sheep investigated, was approximately doubled as a result of infusing 2 mol acetate/day intravenously. 3. The results indicate that this cycle contributes only approx. 0.5% of the total heat produced by the animal and would probably make only a relatively small contribution to any heat increment of feeding associated with diets producing large amounts of acetate.

Acetates

Hormonal regulation of the rate of the glycogen/glucose-1-phosphate cycle in skeletal muscle.

A method is presented which allows simultaneous estimation of rates of glycogen synthesis and glycogenolysis in an isolated incubated skeletal muscle, thus allowing measurement of the glycogen/glucose-1-phosphate substrate cycling rate. In the absence of hormonal additions, the measured rates of glycogen synthesis and breakdown were similar [respectively, 0.54 +/- 0.12 (8) and 0.74 +/- 0.10 (8) mumol glucosyl equiv. h-1 (g tissue)-1]. Incremental addition of insulin stimulated glycogen synthesis up to threefold and reduced glycogenolysis by about sevenfold; the half-maximally effective concentration of insulin on both processes was about 100 microU/ml (0.7 nM). Incremental addition of adrenaline (in the presence of 1 mU insulin/ml) caused a dramatic increase in the glycogenolytic rate (about 15-fold), but a much less marked inhibition of glycogen synthetic rate. In addition to hormonal manipulation of the muscle preparation in vitro, the effects of cold exposure, the hyperthyroid state, a single exercise bout and exercise-training of animals in vivo on the rates of glycogen synthesis and breakdown in the isolated incubated muscle preparation have been investigated. Significant changes in measured glycogen synthesis, breakdown and glycogen/glucose-1-phosphate cycling have been observed, both under basal conditions and in response to hormonal additions in vitro. The results are discussed with respect to the possible physiological importance of this substrate cycle.

Adaptation, Physiological

A metabolic switch produced by enzymically interconvertible forms of an enzyme.

A system of enzymically interconvertible enzyme forms (interconversion cycle) is known to increase the sensitivity to regulators. Here it is shown that this system may also provide a discrete switching mechanism in which the response is maintained when the stimulus is removed. These switches may be important in producing discontinuous metabolic changes such as those associated with cell differentiation.

Cell Differentiation

The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells.

The rates of utilization of both glucose and glutamine are high in rapidly dividing cells such as enterocytes, lymphocytes, thymocytes, tumour cells; the oxidation of both glucose and glutamine is only partial, glucose to lactate and glutamine to glutamate, alanine or aspartate; and these partial processes are termed glycolysis and glutaminolysis respectively. Both processes generate energy and also provide precursors for important biosynthetic processes in such cells. However, the rates of utilization of precursors for macromolecular biosynthesis are very low in comparison to the rates of partial oxidation, and energy generation per se may not be the correct explanation for high rates of glycolysis and glutaminolysis in these cells since oxidation is only partial and other fuels can be used to generate energy. Both the high fluxes and the metabolic characteristics of these two processes can be explained by application of quantitative principles of control as applied to branched metabolic pathways (Crabtree & Newsholme, 1985). If the flux through one branch is greatly in excess of the other, then the sensitivity of the flux of the low-flux pathway to regulators is very high. Hence, it is suggested that, in rapidly dividing cells, high rates of glycolysis and glutaminolysis are required not for energy or precursor provision per se but for high sensitivity of the pathways involved in the use of precursors for macromolecular synthesis to specific regulators to permit high rates of proliferation when required - for example, in lymphocytes in response to a massive infection.

Animals