The sleep of reason produces monsters -- human costs of economic sanctions.
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Commerce↗
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Results for “MALINGERING”
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Pain and public policy.
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Disability Evaluation↗
Divided loyalties in a brain injury case.
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Brain Injuries↗
Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54.
We have recently described a molecular gatekeeper of the hypothalamic-pituitary-gonadal axis with the observation that G protein-coupled receptor 54 (GPR54) is required in mice and men for the pubertal onset of pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion to occur. In the present study, we investigate the possible central mode of action of GPR54 and kisspeptin ligand. First, we show that GPR54 transcripts are colocalized with gonadotropin-releasing hormone (GnRH) neurons in the mouse hypothalamus, suggesting that kisspeptin, the GPR54 ligand, may act directly on these neurons. Next, we show that GnRH neurons seem anatomically normal in gpr54-/- mice, and that they show projections to the median eminence, which demonstrates that the hypogonadism in gpr54-/- mice is not due to an abnormal migration of GnRH neurons (as occurs with KAL1 mutations), but that it is more likely due to a lack of GnRH release or absence of GnRH neuron stimulation. We also show that levels of kisspeptin injected i.p., which stimulate robust LH and FSH release in wild-type mice, have no effect in gpr54-/- mice, and therefore that kisspeptin acts directly and uniquely by means of GPR54 signaling for this function. Finally, we demonstrate by direct measurement, that the central administration of kisspeptin intracerebroventricularly in sheep produces a dramatic release of GnRH into the cerebrospinal fluid, with a parallel rise in serum LH, demonstrating that a key action of kisspeptin on the hypothalamo-pituitary-gonadal axis occurs directly at the level of GnRH release. The localization and GnRH release effects of kisspeptin thus define GPR54 as a major control point in the reproductive axis and suggest kisspeptin to be a neurohormonal effector.
Animals↗
Reaction of nucleic acids and cis-diamminedichloroplatinum(II) in the presence of intercalating agents.
The reaction of cis-diamminedichloroplatinum(II) and several synthetic or natural double-stranded polydeoxyribonucleotides has been carried out in the presence of such intercalating agents as ethidium bromide, proflavine, and acridine. After incubation of the reaction mixtures at 37 degrees C for 24 hr, some ethidium or proflavine, but no acridine, molecules are tightly bound to nucleic acids. Tight binding is defined by resistance to extraction with butanol, assayed by filtration at acid pH or by thin-layer chromatography at basic pH. In the ternary complexes, there is about one tightly bound ethidium (or proflavine) per platinum residue. At 37 degrees C, but not at 4 degrees C, tightly bound ethidium exchanges with free ethidium, whereas platinum residues do not exchange. The binding and the release of tightly bound ethidium are very slow (several hours). It is suggested that in the ternary complexes, nucleic acid-cis-Pt(NH3)2-intercalating agent, a bidentate adduct (guanine-ethidium or -proflavine)-cis-Pt(NH3)2, is formed. No tightly bound ethidium or proflavine is found when cis-diamminedichloroplatinum(II) is replaced by trans-diamminedichloroplatinum(II). Competition experiments between cis-diamminedichloroplatinum(II), poly(dG-dC), and poly(dG)-poly(dC) or poly(dA-dT) show that the presence of ethidium bromide, proflavine, or acridine interferes with the distribution of platinum between the polynucleotides. These results might help to explain the synergism for drugs used in combination with cis-diamminedichloroplatinum(II) and in the design of new chemotherapeutic agents.
Acridines↗
Possible catalytic activity of DNA in the reaction between the antitumor drug cis-diamminedichloroplatinum(II) and the intercalator N-methyl-2,7-diazapyrenium.
The platinum(II) complex cis-[Pt(NH3)2(N7-N-methyl-2-diazapyrenium)Cl]2+ formed in the reaction between cis-diamminedichloroplatinum(II) and N-methyl-2,7-diazapyrenium reacts with N7 of guanine residues in DNA. The resulting adduct is kinetically inert within single-stranded DNA. Within double-stranded DNA, it is kinetically inert in 1 M NaClO4 and becomes labile as the salt concentration is decreased. Two products, cis-[Pt(NH3)2(N7-N-methyl-2-diazapyrenium)H2O]3+ and N-methyl-2,7-diazapyrenium, are released. The conformation of the platinated DNA is different in low- and high-salt conditions as shown by the chemical probe diethyl pyrocarbonate. These results are discussed in relation with a possible catalytic role played by the double-stranded DNA.
Base Sequence↗
Binding discrimination of MutS to a set of lesions and compound lesions (base damage and mismatch) reveals its potential role as a cisplatin-damaged DNA sensing protein.
The DNA mismatch repair (MMR) system plays a critical role in sensitizing both prokaryotic and eukaryotic cells to the clinically potent anticancer drug cisplatin. It is thought to mediate cytotoxicity through recognition of cisplatin DNA lesions. This drug generates a range of lesions that may also give rise to compound lesions resulting from the misincorporation of a base during translesion synthesis. Using gel mobility shift competition assays and surface plasmon resonance, we have analyzed the interaction of Escherichia coli MutS protein with site-specifically modified DNA oligonucleotides containing each of the four cisplatin cross-links or a set of compound lesions. The major 1,2-d(GpG) cisplatin intrastrand cross-link was recognized with only a 1.5-fold specificity, whereas a 47-fold specificity was found with a natural G/T containing DNA substrate. The rate of association, kon, for binding to the 1,2-d(GpG) adduct was 3.1 x 104 m-1 s-1 and the specificity of binding was essentially dependent on koff. DNA duplexes containing a single 1,2-d(ApG), 1,3-d(GpCpG) adduct, and an interstrand cross-link of cisplatin were not preferentially recognized. Among 12 DNA substrates, each containing a different cisplatin compound lesion derived from replicative misincorporation of one base opposite either of the 1,2-intrastrand adducts, 10 were specifically recognized including those that are more likely formed in vivo based on cisplatin mutation spectra. Moreover, among these lesions, two compound lesions formed when an adenine was misincorporated opposite a 1,2-d(GpG) adduct were not substrates for the MutY-dependent mismatch repair pathway. The ability of MutS to sense differentially various platinated DNA substrates suggests that cisplatin compound lesions formed during misincorporation of a base opposite either adducted base of both 1,2-intrastrand cross-links are more plausible critical lesions for MMR-mediated cisplatin cytotoxicity.
Adenosine Triphosphatases↗
California Verbal Learning Test indicators of suboptimal performance in a sample of head-injury litigants.
Cutoff scores suggested by Millis, Putnam, Adams, and Ricker (1995) for detecting suboptimal performance on indices from the California Verbal Learning Test (CVLT) were evaluated using data from 193 compensation-seeking participants. All participants claimed to have suffered a blow to the head in an accident causing subsequent deterioration in cognitive function. The participants were divided into those with negligible or possible mild brain injuries and those with clear evidence of moderate to severe brain injuries. In addition to the CVLT, all participants were administered the Computerized Assessment of Response Bias (CARB), a two-alternative forced choice test of recognition memory that is used to detect feigned cognitive impairment. For all CVLT indices, the distributions of outcome (valid vs. suboptimal performance) was unrelated to age and brain injury severity, and only weakly associated with education. However, a significantly higher proportion of males than females obtained scores in the suboptimal performance range. The CVLT indices were not fully redundant with each other with respect to binary participant classifications; substantial disagreement between pairwise classifications was found among those participants who obtained at least one score in the suboptimal performance range. CVLT index classifications were also found to be non-redundant with classifications based on CARB scores. The CVLT may thus add useful data over and above that obtained from symptom validity testing. However, the data suggest that the use of the strategy where any one or more below-cutoff CVLT scores are considered a positive indicator of suboptimal performance may be associated with a higher than acceptable false-positive error rate.
Adolescent↗
Information/Orientation subtest of the Wechsler Memory Scale-Revised as an indicator of suspicion of insufficient effort.
The utility of the Information/Orientation (IO) subtest of the Wechsler Memory Scale-Revised in identifying insufficient effort was examined. Performances of 50 benefit-seeking patients were compared to previously generated norms based on a clinical sample. Of the 50 benefit-seeking patients, 6 (12%) had IO scores that were outside the performance ranges of the entire clinical sample. An additional 6 of 50 (24%) had performances that were comparable to less than 2% of the normative sample. These results are consistent with previously published estimates of insufficient effort base rates in benefit-seeking populations and demonstrate the utility of IO as an indicator of suspicion of insufficient effort.
Adolescent↗
Comparison of premorbid and postinjury mmpi-2 profiles in late postconcussion claimants.
A comparison of premorbid and postinjury MMPI-2 profiles was performed in 23 patients with mild cranial/cervical injuries. All claimants attributed major personality change to their injuries during the course of compensation-related neuropsychological examinations. Their premorbid MMPI-2 profiles were all abnormal and the modal code-type indicated somatoform psychopathology. The post-accident MMPI profiles showed continuous somatization trends, but they unexpectedly showed (a) increased defensiveness and (b) a general decrease in global psychopathology. The findings did not support an 'eggshell plaintiff' theory of chronic postconcussive complaints. The view that chronic postconcussive complaints require a wider focus on non-neuropsychological factors is enhanced.
Accidents, Traffic↗
Noncredible cognitive performance in the context of severe brain injury.
In two litigating patients with histories of severe brain injury (i.e., coma > or =2 days and residual brain imaging abnormalities), noncredible cognitive symptomatology was demonstrated by: (1) "failed" performance on multiple cognitive "effort" tests, (2) noncredible performance on standard neuropsychological instruments, (3) questionable validity of personality inventory profiles, and (4) marked inconsistency in test performance across testing evaluations or marked inconsistency between test scores and activities of daily living documented through surveillance videotapes. Some patients with severe traumatic brain injury show substantial, if not full recovery, and in a litigating context, may feign cognitive symptoms. These cases indicate that tests to verify cognitive effort should be routinely administered to all patients in litigation or who have other motive to feign symptoms, not just patients with mild or questionable brain injury.
Adult↗
Relationships between eight measures of suspect effort.
Previous studies have recommended that multiple measures be employed concurrently to provide converging evidence regarding the presence of suspect effort during neuropsychological assessment. However, if the tests are highly correlated they do not represent independent sources of information. To date, no study has examined correspondence between effort tests. The present study assessed the relationships between eight measures which can be used to assess effort (Rey 15-item, Rey Dot Counting Test, Rey Word Recognition Test, RAVLT recognition trial, Rey-Osterrieth Complex Figure Test effort equation, Digit Span, Warrington Recognition Memory Test-Words, and "b" Test) in a sample of 105 patients in litigation or attempting to obtain/maintain disability compensation and who displayed noncredible symptoms based on psychometric performance and behavioral criteria. Modest to moderate correlations were observed between test summary scores with only two measures sharing more than 50% score variance (Digit Span and Dot Counting). Moderate correlations were also observed between individual test scores reflecting indices of response time, free recall, recognition, and false positive errors, providing possible evidence that patients may use specific strategies when producing noncredible performances. Overall the results suggest that the use of these various tests generally provides nonredundant data regarding patient credibility in neuropsychological evaluations.
Adolescent↗
Personality characteristics of patients showing suboptimal cognitive effort.
This study examined the relationship between performance on the Portland Digit Recognition Test (PDRT) and the MMPI-2 in a group of veterans who were suspected of having motivation to exaggerate cognitive and/or psychiatric symptoms. Number correct on "easy" trials on the PDRT correlated inversely with MMPI-2 measures of psychopathology, whereas number correct on "hard" trials positively correlated with the same scales. Some individuals performed poorly across both types of PDRT trials and had significant MMPI-2 elevations, whereas others performed poorly only on "hard" PDRT trials and had less extreme MMPI-2 elevations. This study reinforces the need to assess the validity of both cognitive and psychiatric symptom complaints.
Adult↗
Effectiveness of the Rey-Osterrieth Complex Figure Test and the Meyers and Meyers recognition trial in the detection of suspect effort.
The Rey-Osterrieth Complex Figure Test (ROCFT) is a popular measure of visuoconstructive skills and visual memory. A recognition memory trial was recently developed by Meyers and Meyers (1995) and attached to the standard administration of the ROCFT. The addition of this recognition paradigm (comprised of 12 small designs from the original ROCFT stimulus interspersed among 12 foils) makes ROCFT a potentially useful instrument in capturing suspect effort because patients attempting to feign memory difficulties typically operate from the misconception that recognition memory is as impaired as free recall in brain injury and, as a result, suppress recognition performance. The ROCFT (copy, immediate recall [i.e., 3-min recall], and the recognition trial) was administered to four sets of participants: 58 patients with suspect effort; 23 neuropsychology clinic patients with verbal memory impairment, 17 clinic patients with visual memory impairment, and 30 clinic patients without memory impairment. Group comparisons revealed significant group differences in direct copy, immediate recall, and recognition scores of the ROCFT (p<.0001), with the suspect effort group displaying significantly lower performance on the copy and immediate recall scores than the verbal memory impaired and nonmemory impaired clinic patient groups, and significantly lower recognition scores than all three clinical groups. Furthermore, qualitative examination of the recognition trial revealed the presence of "atypical recognition errors" that were endorsed with significantly higher frequency by the suspect effort patients. A combination score incorporating the copy, true positive recognition, and atypical recognition error scores yielded a sensitivity of 74% while misclassifying only approximately 4% of verbal memory impaired clinic patients, 12% of visual memory impaired clinic patients, and 3% of nonmemory impaired clinic patients. Thus, the ROCFT+recognition trial show considerable potential for detecting noncredible effort.
Adolescent↗
Detection of incomplete effort on the Wechsler Adult Intelligence Scale-Revised: a cross-validation.
This study determined whether the Vocabulary-Digit Span difference score and discriminant function based on subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) developed by Mittenberg et al. (1995) could differentiate patients with moderate and severe traumatic brain injuries (n = 50) from persons with financially compensable mild head injuries who were giving incomplete effort (n = 50). Employing modified cutoff scores, the discriminant function and Vocabulary-Digit Span difference score accurately classified 90% and 79% of the cases, respectively. Persons with traumatic brain injuries may produce WAIS-R subtest patterns that can be differentiated from individuals showing incomplete effort. These WAIS-R algorithms appear useful in making that distinction.
Adult↗
A longitudinal study of the relationship between financial compensation and symptoms after treated mild traumatic brain injury.
Demographic, injury-related, and symptom variables at intake, 3 months, and 12 months postinjury were compared between 50 treated adults with mild traumatic brain injury (MTBI) who were not seeking or receiving financial compensation at any time and 18 who were at each time. Compensation seekers/receivers reported symptom incidence and severity as approximately 1 SD higher at each time. The level of difference between the groups did not significantly differ across time. No demographic variables distinguished the groups. No injury-related variable other than more immediate postinjury prescription medication use was predictive of the greater symptom complaints for the patients seeking or receiving compensation. However, this medication effect did not explain away the compensation effect when medication use was co-varied in an analysis. Our study appears to be the first to examine the relationship between financial compensation and symptom report in an MTBI sample specifically treated for their condition. Our results indicate that even highly patient-rated treatment is not adequate to wash out the strong relationship between financial compensation status and symptom report after MTBI.
Adult↗
Detecting incomplete effort on the MMPI-2: an examination of the Fake-Bad Scale in mild head injury.
The current study is an investigation of the MMPI-2 Fake Bad Scale ( FBS ) in the detection of incomplete effort in mild head injury (MHI). Using ROC curve analysis, we found that a cutoff score of 21 had a sensitivity of 90% and specificity of 90%, providing an overall correct classificatory rate of 90%. In addition, traditional indices of faking bad on the MMPI-2, the F and F-K indices, fared relatively poorly by comparison and added no predictive power over the FBS. Finally, multivariate analyses revealed that although the FBS shares a number of items with Hs and Hy scales, the FBS carried the majority of variance in predicting incomplete effort in our MHI sample. Overall, these findings indicate that the FBS has high sensitivity and specificity in identifying incomplete effort in mild head injury.
Adult↗
The simulation and dissimulation of multiple personality disorder.
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Diagnosis, Differential↗