Decrease of mucosal glutamine concentration in the nutritionally depleted patient

A diminished glutamine delivery by peripheral tissues is suggested to play an important role in the etiology of postoperative complications of nutritionally depleted patients. Decreased glutamine supply to the gut mucosa in these nutritionally depleted patients may have important consequences for the integrity of the gut mucosa barrier. To evaluate whether glutamine concentration in the gut mucosa of depleted patients is altered, patients with either a fat-free mass index below 90% or percentage ideal body weight below 90% as a result of weight loss were studied. 22 patients admitted to the University Hospital Maastricht and 14 controls were studied. After an overnight fast, venous blood was sampled and duodenal biopsies were obtained by endoscopy. Plasma and tissue amino acids were measured. Fat-free mass was determined by bioelectrical impedance measurement. In 10 depleted patients glutamine concentration in the duodenal mucosa was 2883 +/- 250 mumol/kg dry weight. Concentration of alanine was 2570 +/- 263 mumol/kg dry weight. In the non-depleted patients glutamine and alanine concentrations were respectively 3463 +/- 171 mumol/kg dry weight and 3540 +/- 315 mumol/kg dry weight. Concentrations in controls were 3296 +/- 176 mumol/kg dry weight for glutamine and 3682 +/- 372 mumol/kg dry weight for alanine. Concentrations for alanine and glutamine were significantly lower in depleted patients compared to non-depleted patients (p < 0.05). Also, alanine and glutamine concentrations were significantly correlated with percentage ideal body weight (r=0.43, p < 0.005 for glutamine and r=0.62, p < 0.001 for alanine) and fat-free mass index (r=0.42, p < 0.05 for glutamine and r=0.48, p < 0.01 for alanine) This study suggests that in patients depletion appears to be related to decreased plasma and mucosa glutamine and alanine concentrations.     

Dietary and physical activity correlates of long-term weight loss

Covariations in body mass index (BMI), physical activity, macronutrient intake, and the frequency of consumption of specific foods were examined among 82 men and 75 women participating in a behavioral weight loss program over a period of 18 months. Results of repeated measures analyses of covariance showed that BMI change was inversely related to change in physical activity and change in frequency of vegetable consumption. BMI change was positively related to change in calorie intake from fat and change in frequency of consumption of beef, hot dogs, and sweets. Change in fat calories predicted BMI change better than change in total calories. In addition, change in the frequency of consumption of specific foods accounted for a larger percentage of the variance in BMI change than did change in macronutrients (10.4% vs. 5.2%). No differences were found between predictors of weight loss vs. weight maintenance.     

Determinants of free-living energy expenditure in normal weight and obese women measured by doubly labeled water

Total free-living energy expenditure (TEE) was measured in 9 normal weight controls and 5 obese women using the doubly labeled water (DLW) method. Resting energy expenditure (REE) and the thermic effect of food (TEF) were measured by indirect calorimetry and the energy cost of physical activity (PA) calculated by deduction, in order to quantify the components and identify determinants of free-living TEE. Although REE was quantitatively the major component of TEE in both groups, PA best explained the variability, contributing 76% to the variance in free-living TEE. The obese women had elevated values for TEE (12397 +/- 2565 vs. 8339 +/- 1787 kJ/d, mean +/- SD; p < 0.005), compared with the control women. PA (5071 +/- 2385 vs. 2552 +/- 1452; p < 0.05) and REE (6393 +/- 678 vs. 5084 +/- 259; p < 0.0005) were also raised in the obese, whereas TEF was not significantly different between the groups, accounting for 7.6% of energy expenditure for the obese and 8% for the control subjects. Body weight was the single best determinant of mean daily free-living TEE across both groups. We conclude that PA and body weight are the main determinants of free-living TEE.     

Discriminative-stimulus effects of azaspirodecanedione anxiolytics in baboons trained to discriminate beta-carboline-3-carboxylic acid ethyl ester or pentylenetetrazole

Baboons were trained to discriminate either pentylenetetrazole (PTZ) or beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) from the no-drug condition. Both drugs specifically bind sites in the gamma-aminobutyric acid A (GABA(A)) receptor complex and decrease GABAergic transmission. beta-CCE occasioned drug-lever responding in baboons trained to discriminate PTZ and vice versa. Flumazenil, the benzodiazephine receptor antagonist, blocked beta-CCE, consistent with beta-CCE's receptor binding activity. The azaspirodecanedione anxiolytics buspirone and ipsapirone produced full generalization in all baboons; gepirone and tandospirone yielded full generalization in some baboons and partial in others. These anxiolytics are inactive in the GABA(A) complex and potently bind 5-HT(1A) sites. A specific 5-HT(1A) ligand, 8-hydroxy-2-(di-n-propylamino)tetralin, produced generalization similar to gepirone and tandospirone, which show the most specific 5-HT(1A) binding. The major azaspirodecanedione metabolite, 1-(2-pyrimidinyl)piperazine (an alpha(2)-adrenergic antagonist), occasioned the least drug-appropriate responding. Full generalization to buspirone and ipsapirone may have resulted from dopaminergic or alpha(1)-adrenergic activity combined with 5-HT(1A) activity. The molecular mechanism of the generalization profile for PTZ and beta-CCE shown by the present results is unclear. The data may reflect altered relationships between GABAergic and serotonergic transmission, and altered stimulus effects of the training drugs, in the context of chronically decreased GABAergic transmission.     

In vitro bacterial contamination of amniotic fluid: effects on fluorescence polarization lung maturity testing

Objective: We sought to determine the effect of bacteria on fluorescence polarization (FPOL) testing of amniotic fluid.Methods: Fusobacterium necrophorum and Escherichia coli were inoculated at concentrations of 10(3) and 10(6)/ml in amniotic-fluid specimens from 4 patients with no clinical or laboratory evidence of infection. The FPOL results were obtained at inoculation and again at 24 h of incubation. The results were compared using analysis of variance (ANOVA).Results: The FPOL results from inoculated specimens were all within 2% of the uninoculated controls. The specimens incubated with bacteria showed a < 1-19% variation when compared with the time-zero uninoculated controls. However, uninoculated controls incubated for 24 h exhibited a 2-12% variation when compared with the time-zero controls, suggesting that the variation present was not secondary to the bacterial co-incubation.Conclusions: In vitro, neither bacterial inoculation nor prolonged co-incubation influences FPOL results beyond the effect of incubation alone. FPOL appears to be an appropriate test to assess fetal lung maturity in patients in whom intraamniotic infection is a concern.     

Provider-assisted suicide: a survey of PA attitudes. Results of the 1994 Michigan survey conducted by the Michigan Academy of Physician Assistants Public Policy Committee

Assisted suicide continues to be a topic of debate among health care providers, including PAs. The Public Policy Committee of the Michigan Academy of Physician Assistants surveyed all licensed PAs in Michigan regarding assisted suicide in an effort to determine whether a public policy statement should be developed, and whether that could be extrapolated into a resolution to be taken to the House of Delegates (HOD) of the American Academy of Physician Assistants in 1994. Based on the divergent results of the survey, the Michigan delegation did not submit a resolution to the HOD.     

Alternative routes of immunization for the induction of experimental autoimmune uveoretinitis (EAU) in rodents: a comparison

Experimental autoimmune uveoretinitis (EAU) in rodents is a widely used model of ocular autoimmunity. EAU has traditionally been elicited by injecting the uveitogenic protein in complete Freund's adjuvant (CFA) into the footpad(s) (FP). Because this route of immunization causes severe arthritis and inflammation, it is being banned by many institutions and investigators are switching to the subcutaneous (SC) route. However, there are no studies that systematically compare the outcome of these two immunization routes using defined clinical, histopathological and immunological criteria. We therefore undertook to compare the FP and SC routes of immunization in the Lewis rat and in the B 10. A mouse models of EAU. Animals were immunized with interphotoreceptor retinoid-binding protein (IRBP) or the retinal soluble antigen (S-Ag) in CFA, either by the traditional FP route or by the SC route. The parameters studied were kinetics and severity of EAU by clinical observation and by histopathology, respectively, as well as immunological responses by delayed-type hypersensitivity (DTH), serum antibody titers and lymphocyte proliferation to the uveitogen. In mice immunized with graded doses of IRBP, development of disease induced by the FP and SC methods had essentially identical kinetics. However, the SC method resulted in a somewhat higher incidence and severity of disease as well as higher DTH at the lower antigen doses. Antibody titers tended to be higher with FP immunization. In rats immunized with S-Ag, kinetics and severity of disease, DTH, proliferative responses of draining lymph node cells to the immunizing antigen, and serum antibody titers induced by FP and SC methods were similar. In rats immunized with IRBP, SC immunization resulted in somewhat higher responses across the board than FP. We conclude that at higher doses of antigen disease scores and immunological responses in animals immunized SC are comparable to those of FP-immunized animals. At limiting doses of antigen, however, the SC route appears to result in more severe disease than the traditional FP method.     

Variations in the behavioral responses to apomorphine in different strains of rats

The present experiments compared patterns of locomotor activity during repeated acclimation sessions and determinations of locomotion and stereotypy elicited by administration of the direct dopamine receptor agonist apomorphine in five inbred strains of rats: the results suggest that each strain can be differentiated phenotypically according to these behavioral responses. Brown Norway rats demonstrated the greatest locomotion during acclimation sessions. Low doses of apomorphine (0.1 and 0.32mg/kg) produced a flat body posture in Lewis animals. A higher dose of apomorphine (1.0mg/kg) markedly increased locomotion in Fisher rats. Buffalo animals showed licking during control sessions and the greatest increase in gnawing at higher doses of apomorphine. DA rats were less responsive than the other strains of apomorphine. Between-strains autoradiographic determination of dopamine receptor densities revealed several differences in D1 receptors labeled by (3)H-SCH 23390 and D2/D3 receptors labeled by (125)I-NCQ 298 in the caudate-putamen and nucleus accumbens. However, the heterogeneity of dopamine receptor densities was not sufficient to explain the strain-specific behavioral responses. These experiments demonstrate variations in behavioral and neurochemical characteristics of inbred strains of rats which could be used to model genetically determined differences in dopamine-mediated behavioral responses.