Involvement of Cerulospinal Glutamatergic Neurotransmission in Fentanyl-induced Muscular Rigidity in the Rat

Background: Investigators in the authors' laboratory previously established the critical participation of the cerulospinal noradrenergic pathway in muscular rigidity elicited by fentanyl. The identification of colocalization of glutamate with tyrosine hydroxylase in most locus ceruleus neurons suggests a role for cerulospinal glutamatergic neurotransmission in fentanyl-induced muscular rigidity. This suggestion and the subtype(s) of glutamate receptors involved were investigated here.

Methods: Electromyographic signals activated by bilateral microinjection of 2.5 micro gram fentanyl into the locus ceruleus were recorded differentially from the left sacrococcygeus dorsi lateralis muscle of adult male Sprague-Dawley rats. The effect of intrathecal administration at the lower lumbar spinal cord of various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists or agonists on this index of muscular rigidity was studied. Rats were under mechanical ventilation, and intravenous infusion of ketamine (30 mg [center dot] kg sup -1 [center dot] h sup -1) was maintained until 10 min before fentanyl was administered.

Results: Microinjection of fentanyl bilaterally into the locus ceruleus increased the root mean square and decreased the mean power frequency values of electromyographic signals. The efficacy of fentanyl to elicit muscular rigidity in this manner was significantly reduced by previous intrathecal administration of either 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), D-(-)-2-amino-5-phosphonovaleric acid (AP5), or (+/- (CPP). Intrathecal administration of kainic acid or NMDA also resulted in significant electromyographic activation.     

Daughters caregiving for hispanic and non-hispanic alzheimer patients: Does ethnicity make a difference?

This study assessed Cuban-American Hispanic and White non-Hispanic daughters who were major caregivers for their mothers suffering from Alzheimer's Disease. Although patients in both ethnic groups did not differ in their level of cognitive and functional impairment, Cuban-American Hispanic patients were significantly more likely to be living in their daughters' homes while the White non-Hispanic patients resided in institutional settings. Caregivers were equivalent in their knowledge and utilization of community services, but Cuban-American daughters were significantly more aware of financial aid resources. Cuban-American patients were significantly more depressed than their White non-Hispanic counterparts with daughters showing similar but nonsignificant trends. The impact of cultural factors on caregiving is discussed.     

Effects of a brisk walk on lipoprotein lipase activity and plasma triglyceride concentrations in the fasted and postprandial states

This study aimed to determine whether changes in plasma heparin-releasable lipoprotein lipase (LPL) activity following a brisk walk were associated with decreases in fasting and/or postprandial triglyceride (TG) concentrations. Two groups of pre-menopausal women participated. In one group (fasting study group, n=10), TG concentrations and post-heparin plasma LPL activity were measured in the fasted state on two occasions: ~18 h after a 2-h treadmill walk at 50% maximal oxygen uptake (exercise trial); and after a day of no exercise (control trial). The other group (postprandial study group, n=9) undertook two oral fat tolerance tests (blood samples taken fasting and for 6 h after a high-fat meal), with plasma LPL activity measured 6 h after meal ingestion. Pre-conditions were the same as for the fasting study group (i.e. control and prior exercise). Prior exercise reduced fasting TG concentrations by 23 (7)% (fasting study group) [mean (SEM)] and by 18 (9)% (postprandial study group) (both P<0.05), and the postprandial TG response by 23 (6)% (postprandial study group) (P<0.01). Plasma LPL activity was not significantly increased by exercise in either the fasting or postprandial study groups. However, exercise-induced changes in both fasting and postprandial LPL activity were significantly correlated with the respective exercise-induced changes in fasting TG concentration and the postprandial TG response (r=−0.70 and −0.77 respectively, P<0.05 for both). These data suggest that increased LPL activity may contribute to the hypotriglyceridaemic effect of moderate exercise, although other mechanisms are also likely to be involved. Electronic Publication     

Identifying amino acid residues that influence plasma clearance of murine IgG1 fragments by site-directed mutagenesis

Site-directed mutagenesis has been used to change amino acid residues of a recombinant Fc-hinge fragment derived from the murine immunoglobulin (Ig)G1 molecule, and the effects of these mutations on the pharmacokinetics of the Fc-hinge fragment have been determined. Specifically, Ile-253, His-310 and Gln-311 of the CH2 domain and His-433 and Asn-434 of the CH3 domain have been changed. In the three dimensional structure of an antibody, these amino acids are in close proximity to each other at the CH2-CH3 domain interface. The mutated Fc-hinge fragments have been purified from recombinant Escherichia coli cells and their pharmacokinetic parameters determined in mice and compared with those of the wild-type Fc-hinge fragment. The results show that the site of the IgG1 molecule that controls the catabolic rate (the ‘catabolic site’) is located at the CH2-CH3 domain interface and overlaps with the Staphylococcal protein A binding site.     

Advance Quantity Meal Preparation Pilot Program Improves Home-Cooked Meal Consumption,Cooking Attitudes,and Self-Efficacy

ObjectiveTo evaluate the effects of a group-based Advance Quantity Meal Preparation (AQMP) program on the consumption of home-cooked meals, cooking attitudes, and self-efficacy in healthy adults.MethodsParticipants (n = 10) in a group setting prepared healthy meals weekly consisting of 10 entrees and 5 snacks for 6 weeks. A survey assessing cooking attitudes, cooking self-efficacy, and cooking behavior and consumption at 3 time points: preprogram, postprogram (T2), and 3 months postprogram (T3).ResultsThe AQMP program increased the proportion of overall home-cooked meal consumption (T2, P = 0.03), home-cooked dinner consumption (T2, P = 0.04), cooking attitudes (T3, P = 0.01), and cooking self-efficacy (T2, P = 0.002).Conclusions and ImplicationsThis pilot study indicates that AQMP may increase home-cooked meal consumption, cooking attitudes, and cooking self-efficacy.     

Weight Change and Glycemic Control After Diagnosis of Type 2 Diabetes

BACKGROUND  Limited community-based data describe weight change after diabetes diagnosis. OBJECTIVE  To evaluate weight change patterns and associations in the 1st year after diabetes mellitus type 2 diagnosis. DESIGN  Retrospective cohort study. PARTICIPANTS  Patients aged 21–75 with diabetes mellitus type 2 diagnosed between 1 January 1997 and 31 December 2004, identified from electronic medical records in Kaiser Permanente Northwest, a health maintenance organization. Eligible patients met weight measurement criteria (a baseline and three additional weight measurements) and did not have a condition associated with unintentional weight change (n = 4,135). MEASUREMENTS  We estimated 12-month patient weight trajectories using growth curve analyses, grouped similar trajectories using cluster analysis, and compared characteristics among groups. RESULTS  The four weight trajectory groups were “higher stable weight” (n = 757; 18.3%), “lower stable weight” (n = 2,236; 54.1%), “weight gain” (n = 664; 16.0%), and “weight loss” (n = 478; 11.6%). After adjustments, members of the weight-loss group were more likely than those in the weight-gain group to be older, female, take fewer medications, have had nutritionist visits, and have a lower mean HbA_1c. Those in the weight-loss group were less likely to be in a race group at higher risk for obesity, have depression or dyslipidemia, or have taken >30 days of a sulfonylurea alone or with metformin. CONCLUSIONS  A small-but-substantial group of patients had a mean weight trajectory that included a clinically significant weight loss. Weight-loss trajectories were strongly associated with better glycemic control when compared to weight gain. Patients with certain characteristics may need more support for weight loss. This study was supported by grant no. R21 DK073546–02 (Weight in Secondary Prevention) from the National Institute of Diabetes and Digestive and Kidney Diseases     

Sensitivity and Specificity of MMPI-2 Validity Scales and Indicators to Malingered Neurocognitive Dysfunction in Traumatic Brain Injury

The present study used a known-groups design to determine the classification accuracy of 10 MMPI-2 validity scales and indicators in the detection of cognitive malingering in traumatic brain injury. Participants were 259 traumatic brain injury and 133 general clinical patients seen for neuropsychological evaluation. The TBI patients were subdivided into groups based on a comprehensive examination of effort following Slick, Sherman, and Iverson's (1999 Slick , D. J. , Sherman , E. M. S. , & Iverson , G. L. ( 1999 ). Diagnostic criteria for malingering neurocognitive dysfunction: Proposed standards for clinical practice and research . The Clinical Neuropsychologist , 13 , 545 – 561 . [INFOTRIEVE] [CSA] [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) criteria. More extreme scores demonstrated excellent specificity; often impressive sensitivity was seen even while maintaining a low false positive error rate. Specificity was good even in stroke, memory disorder, and psychiatric patients without incentive. The results of this study are presented in frequency tables that can be easily referenced in clinical practice.     

Detecting Malingering in Traumatic Brain Injury and Chronic Pain: A Comparison of Three Forced-Choice Symptom Validity Tests

Individual and joint malingering detection accuracy of the Portland Digit Recognition Test (PDRT), Test of Memory Malingering (TOMM), and Word Memory Test (WMT) was examined in traumatic brain injury (TBI; 43 non-malingering, 27 malingering) and chronic pain (CP; 42 non-malingering, 58 malingering) using a known-groups design. At published cutoffs, the PDRT and TOMM were very specific but failed to detect about 50% of malingerers; the WMT was sensitive but prone to false positive errors. ROC analyses demonstrated comparable accuracy across all three tests. Joint classification accuracy was superior to that of the individual tests. Clinical and research implications are discussed.