Moderate physical activity can increase dietary protein needs

Six healthy men completed three 1-hr bouts of treadmill walk-jogging at low (L; 42 +/- 3.9% VO2max), moderate (M; 55 +/- 5.6%), and high (H; 67 +/- 4.5%) exercise intensity in order to determine whether moderate physical activity affects dietary protein needs. Both sweat rate and sweat urea N loss were greater (p < .10) with increasing exercise intensity. Seventy-two hour postexercise urine urea N excretion was elevated (p < .05) over nonexercise control (26.6 +/- 2.96 g) with both M (31.0 +/- 3.65) and H (33.6 +/- 4.39), but not L (26.3 +/- 1.86), intensities. Total 72-hr postexercise urea N excretion (urine + sweat) for the M and H exercise was greater than control by 4.6 and 7.2 g, respectively. This suggests that 1 hr of moderate exercise increases protein oxidation by about 29-45 g, representing approximately 16-25% of the current North American recommendations for daily protein intake. These data indicate that the type of exercise typically recommended for health/wellness can increase daily protein needs relative either to sedentary individuals or to those who exercise at lower intensities.     

The effect of limb-length discrepancy on gait

We evaluated the gait of thirty-five neurologically normal children who had a limb-length discrepancy of the lower extremities that ranged from 0.8 to 15.8 per cent of the length of the long extremity (0.6 to 11.1 centimeters). The twenty-two boys and thirteen girls had an average age of thirteen years (range, eight to seventeen years). No patient had a substantial angular or rotational deformity of the lower extremities. We found no correlation between the actual discrepancy or the per cent discrepancy and any of the dependent kinematic or kinetic variables, including pelvic obliquity. Discrepancies of less than 3 per cent of the length of the long extremity were not associated with compensatory strategies. When a discrepancy was 5.5 per cent or more, more mechanical work was performed by the long extremity and there was a greater vertical displacement of the center of body mass. Clinically, this degree of discrepancy was manifested by the use of toe-walking as a compensatory strategy. Children who had less of a discrepancy were able to use a combination of compensatory strategies to normalize the mechanical work performed by the lower extremities.     

Comparative evolution of Alzheimer disease, vascular dementia, and mixed dementia

OBJECTIVE: To compare the evolution of Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia by cognitive domain. SETTING: The University of Western Ontario Dementia Study, which is a registry of cases of dementia seen for secondary and tertiary assessment in a university memory disorders clinica with extensive follow-up data and histopathological confirmation of clinical diagnoses. PATIENTS: One hundred twenty-nine patients with definite or probable AD, 12 patients with definite or probable VaD, and 36 patients with definite or probable mixed dementia. METHODS: Patients were grouped as having an early, moderate, or advanced stage of disease according to the extended scale for dementia (ESD). The ESD was subdivided into cognitive domains, and the domain scores were compared for each stage of disease by diagnostic category with the use of a 2-way analysis of variance with repeated measures. RESULTS: As expected, the scores in all domains decreased significantly with increasing severity. There was a significant difference in the decline in memory among the diagnostic groups (P = .02) that was mostly attributable to the difference between AD and mixed dementia (P = .03), with the difference between AD and VaD only approaching significance (P = .06). There was a similar finding for praxis. The interaction between diagnosis (AD and VaD) and severity was significant only for memory (P = .02), showing a less severe memory deficit at onset but a proportionately more rapid progression in VaD and arithmetic ability (AD and mixed dementia [P = .03]). CONCLUSIONS: Alzheimer disease, VaD, and mixed dementia evolve similarly as assessed using cognitive domains obtained by subdivision of the ESD in a patient population derived from a memory clinic and by analyzing VaD as a single entity. Only memory impairment evolves differently between AD and VaD, with this depending on the severity. Memory is more severely impaired in the early stage of AD; however, with increasing severity of dementia, memory impairment in VaD accelerates and catches up with AD at the level of moderate impairment. The differences between AD and mixed dementia are greater than those between mixed dementia and VaD, suggesting an important role for the ischemic component of mixed dementia. Simple neuropsychological tools (eg, the ESD) may be incapable of distinguishing between AD and VaD, and more focused instruments may be required. Inherent bias in case selection may prevent extrapolation of these results to VaD in general, but the neuropsychological criteria for VaD may need to vary, depending on the severity.     

3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase

BACKGROUND: The activation of protein kinase B (PKB, also known as c-Akt) is stimulated by insulin or growth factors and results from its phosphorylation at Thr308 and Ser473. We recently identified a protein kinase, termed PDK1, that phosphorylates PKB at Thr308 only in the presence of lipid vesicles containing phosphatidylinositol 3,4,5-trisphosphate (Ptdlns(3,4,5)P3) or phosphatidylinositol 3,4-bisphosphate (Ptdlns(3,4)P2). RESULTS: We have cloned and sequenced human PDK1. The 556-residue monomeric enzyme comprises a catalytic domain that is most similar to the PKA, PKB and PKC subfamily of protein kinases and a carboxy-terminal pleckstrin homology (PH) domain. The PDK1 gene is located on human chromosome 16p13.3 and is expressed ubiquitously in human tissues. Human PDK1 is homologous to the Drosophila protein kinase DSTPK61, which has been implicated in the regulation of sex differentiation, oogenesis and spermatogenesis. Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2. Overexpression of PDK1 in 293 cells activated PKB alpha and potentiated the IGF1-induced phosphorylation of PKB alpha at Thr308. Experiments in which the PH domains of either PDK1 or PKB alpha were deleted indicated that the binding of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2 to PKB alpha is required for phosphorylation and activation by PDK1. IGF1 stimulation of 293 cells did not affect the activity or phosphorylation of PDK1. CONCLUSIONS: PDK1 is likely to mediate the activation of PKB by insulin or growth factors. DSTPK61 is a Drosophila homologue of PDK1. The effect of Ptdlns(3,4,5)P3/Ptdlns(3,4)P2 in the activation of PKB alpha is at least partly substrate directed.     

Infrahepatic interruption of the inferior vena cava with azygos continuation: a potential mimicker of aortic pathology

Infrahepatic interruption of the inferior vena cava (IVC) with azygos or hemiazygos continuation is a rare finding. In this anatomic entity, the intrahepatic segment of the IVC is absent, and the hepatic veins empty directly into the right atrium. Venous blood flow from the lower body is directed from the IVC into the azygos system at the level of the renal veins, with resultant dilation of the azygos and/or hemiazygos veins. Because these enlarged vessels lie parallel to the descending thoracic aorta, they may be mistaken for aortic pathology (dissection, aneurysm, or rupture) during transesophageal echocardiography (TEE). We describe a case of azygos continuation of the IVC initially misdiagnosed by TEE as partial aortic rupture. Repeat TEE with intravenous agitated saline injection correctly identified the condition, and the echocardiographic features are described.     

Benchmarking the MCNP code for Monte Carlo modelling of an in vivo neutron activation analysis system

The Monte Carlo computer code MCNP (version 4A) has been used to develop a personal computer-based model of the Swansea in vivo neutron activation analysis (IVNAA) system. The model included specification of the neutron source (252Cf), collimators, reflectors and shielding. The MCNP model was 'benchmarked' against fast neutron and thermal neutron fluence data obtained experimentally from the IVNAA system. The Swansea system allows two irradiation geometries using 'short' and 'long' collimators, which provide alternative dose rates for IVNAA. The data presented here relate to the short collimator, although results of similar accuracy were obtained using the long collimator. The fast neutron fluence was measured in air at a series of depths inside the collimator. The measurements agreed with the MCNP simulation within the statistical uncertainty (5-10%) of the calculations. The thermal neutron fluence was measured and calculated inside the cuboidal water phantom. The depth of maximum thermal fluence was 3.2 cm (measured) and 3.0 cm (calculated). The width of the 50% thermal fluence level across the phantom at its mid-depth was found to be the same by both MCNP and experiment. This benchmarking exercise has given us a high degree of confidence in MCNP as a tool for the design of IVNAA systems.     

Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting

BACKGROUND: Graft coronary artery disease (CAD) is an increasingly important problem during long-term survival after heart transplantation, but the importance of cellular rejection, in particular late after transplantation, remains undetermined. METHODS and RESULTS: We analyzed 492 coronary angiographies (967+/-705 days after transplantation; range, 49 days to 9.4 years) and 5201 endomyocardial biopsies (518+/-648 days after transplantation) from 156 patients (age, 47+/-11 years). Patients with angiographically detectable graft CAD had significantly more episodes of rejection requiring augmentation of immunosuppressive therapy (i.e., International Society of Heart and Lung Transplantation score > or = 3A) than those without graft CAD during the first (3.7+/-2.6 vs. 2.2+/-2.0, P<0.001) as well as subsequent years after transplantation (1.2+/-1.9 vs. 0.4+/-0.9, P<0.01). Multivariate logistic regression analysis including established risk factors for CAD, ischemic time, gender and age of donors and recipients, number of mismatches, cytomegalovirus infection, and drug therapy showed that the number of rejections during the first [odds ratio (OR)=1.39, P<0.005] as well as subsequent years (OR=1.49, P<0.05), previous cytomegalovirus infection (OR=3.21, P<0.05), donor age >40 years (OR=2.97, P<0.05), and current or former smoker status (OR=2.76, P<0.05) were independent predictors of graft CAD. In patients without angiographically detectable graft CAD 1 year after transplantation, the number of rejections after the first year was even more strongly related to graft coronary artery disease than in the total patient population, underlining the importance of late cellular rejection (OR=1.74, P<0.005). CONCLUSION: Rejection requiring augmentation of immunosuppression early and late after transplantation is an independent risk factor for the development of angiographically detectable graft CAD. Hence, the search for and treatment of moderate or severe rejection seems to be prudent even late after transplantation.     

Kinetics of adhesion of IgE-sensitized rat basophilic leukemia cells to surface-immobilized antigen in Couette flow

Antigen-antibody systems provide the flexibility of varying the kinetics and affinity of molecular interaction and studying the resulting effect on adhesion. In a parallel-plate flow chamber, we measured the extent and rate of adhesion of rat basophilic leukemia cells preincubated with anti-dinitrophenyl IgE clones SPE-7 or H1 26. 82 to dinitrophenyl-coated polyacrylamide gel substrates in a linear shear field. Both of these IgEs bind dinitrophenyl, but H1 26.82 has a 10-fold greater on rate and a 30-fold greater affinity. Adhesion was found to be binary; cells either arrested irreversibly or continued at their unencumbered hydrodynamic velocity. Under identical conditions, more adhesion was seen with the higher affinity (higher on rate) IgE clone. At some shear rates, adhesion was robust with H1 26.82, but negligible with SPE-7. Reduction in receptor number or ligand density reduced the maximum level of adhesion seen at any shear rate, but did not decrease the shear rate at which adhesion was first observed. The spatial pattern of adhesion for both IgE clones is well represented by the first-order kinetic rate constant kad, and we have determined how kad depends on ligand and receptor densities and shear rate. The rate constant kad found with H1 26.82 was approximately fivefold greater than with SPE-7. The dependence of kad on site density and shear rate for SPE-7 is complex: kad increases linearly with antigen site density at low to moderate shear rates, but is insensitive to site density at high shear. kad increases with shear rate at low site density but decreases with shear at high site density. With H1 26.82, the functional dependence of kad with shear rate was similar. Although these data are consistent with the hypothesis that we have sampled both transport and reaction-limited adhesion regimes, they point out deficiencies in current theories describing cell attachment under flow.     

Fibromatosis colli of infancy: variability of sonographic appearance

PURPOSE: We describe the variable sonographic appearances of fibromatosis colli, a disease that presents as a mass-like enlargement of the sternocleidomastoid muscle during the first 8 weeks of life. METHODS: Sonograms and records of 12 infants who presented with a sternocleidomastoid mass or torticollis before they were 12 weeks old were retrospectively reviewed for sonographic features (presence of a mass, diffuse muscle enlargement, and echogenicity), medical history, and follow-up data. RESULTS: Sonographically, 6 infants had only a mass in the sternocleidomastoid muscle, 2 had a mass with fusiform muscle enlargement, and 4 had only muscle enlargement. Five masses were hyperechoic, and 1 mass was of mixed echogenicity. The 2 masses associated with muscle enlargement were hypoechoic. Three cases of diffuse muscle enlargement were of mixed echogenicity, and 1 was hypoechoic. Unusual variations included (1) a mass split longitudinally into 2 components and (2) a diffusely enlarged muscle with a striated pattern of mixed echogenicity. Follow-up in 10 patients at 4 months and in 7 patients at 6 months showed clinical improvement. CONCLUSION: Fibromatosis colli usually appears sonographically as a hyperechoic mass or diffuse sternocleidomastoid enlargement of mixed echogenicity. Variations in its appearance should not prevent the correct diagnosis as long as the abnormality is intramuscular and adjacent soft tissues are normal.