The changing maternal "self" hypothesis: a mechanism for maternal tolerance of the fetus.

Recent advances in placental biology and immunology lead us to propose a novel hypothesis for maternal tolerance of the semi-allogeneic fetus and amelioration of rheumatoid arthritis (RA) during pregnancy. The initial event in this hypothesis is extrusion of placental apoptotic syncytiotrophoblast debris recently identified to contain intracellular fetal HLA Class II molecules, into maternal blood. The second event is uptake of apoptotic syncytiotrophoblast by immature maternal dendritic cells and presentation of fetal HLA class II peptides. In addition to presenting foreign antigens, HLA molecules also present HLA self-peptides. In the setting of the non-inflammatory environment of pregnancy, this process is expected to induce peripheral tolerance of fetal antigens through T cell death, anergy or induction of regulatory T cells in the lymph nodes. This hypothesis suggests a mechanism by which the simultaneous presentation of fetal and self (RA-associated) HLA peptides by tolerogenic dendritic cells during pregnancy may explain the observed amelioration of RA as a secondary benefit of fetal tolerance. After delivery, apoptotic syncytiotrophoblast debris disappears from maternal blood, autoimmunity returns and RA recurs. Thus, during pregnancy maternal immunologic "self" includes fetal HLA Class II as a result of apoptotic syncytiotrophoblast uptake by maternal tolerogenic dendritic cells.

LPS induces translocation of TLR4 in amniotic epithelium.

Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) induced immune responses, which may contribute to preterm labor associated with intraamniotic gram-negative bacterial infections. The study objective was to investigate gestational age and LPS-induced changes in TLR4 subcellular localization within amniotic epithelium, the first line of host defense against intraamniotic bacteria. TLR4 localization in amniotic epithelium was assessed using immunohistochemistry on 24 placentas of different gestational ages: first trimester (n=6), second trimester (n=6), and third trimester (n=12). Immunofluorescence was used to determine TLR4 localization following ex vivo LPS stimulation of amnion from women undergoing cesarean section without labor at term. TLR4 was expressed in the cytoplasm of amniotic epithelium starting at 9weeks with apical polarization by 25weeks gestation. TLR4 localization to the basal membrane was significantly associated with chorioamnionitis (p=0.01). After LPS stimulation, TLR4 was expressed sequentially within the apical membrane, cytoplasm, and finally in the basal cellular compartment. This suggests that TLR4 expression in amniotic epithelium is poised to monitor amniotic fluid for pathogens. TLR4 translocation to the basal membrane may decrease LPS signaling early in an infection, but allow the amniotic epithelium to remain competent to invasive or intracellular bacteria.

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.

The Memory Assessment Scales in the detection of incomplete effort in mild head injury.

Despite differences in the constructs measured, the Memory Assessment Scales (MAS) remain an alternative to the Wechsler Memory Scales (WMS) as a broad-band instrument for assessing multiple aspects of attention and memory. Although a number of studies have examined indices of the WMS as indicators of malingering, few studies have similarly investigated the MAS. In this study, we examined the degree to which the MAS was effective in detecting incomplete effort in a clinical sample of patients referred for neuropsychological evaluation after mild head injury. Included in the sample were 21 financially compensable (FC) participants with alleged mild head injury and 21 participants who were not involved in litigation and suffered more serious head injuries. Examination of the four MAS domain indices indicated that Short-Term Memory was most useful at identifying incomplete effort. We also examined subscales of the MAS. Consistent with previous findings, brief tests such as Verbal and Visual Span had high rates of diagnostic sensitivity and specificity. Although tests based on a forced-choice recognition paradigm (e.g., Immediate and Delayed Visual Recognition) predicted group membership above chance levels, they failed to significantly add to prediction above Verbal and Visual Span subtests.

Spontaneous intracranial hypotension causing reversible frontotemporal dementia.

Spontaneous intracranial hypotension (SIH) causes postural headache and neurologic symptoms owing to traction and brain compression. A 66-year-old man with chronic headache and progressive personality and behavioral changes typical of frontotemporal dementia was examined. He had MRI findings of SIH with low CSF pressure. His headache, dementia, and imaging abnormalities abated after treatment with prednisone. SIH can cause reversible frontotemporal dementia, and should be considered when dementia and behavioral changes are accompanied by headache.

Practical and ethical issues pertaining to test revisions.

Revisions of clinical psychological tests are occurring at more frequent intervals than in the past. These revisions involve such practical issues as the goals of the revision, the economic considerations relating to the revision, the methodology of the revision, and the degree to which the revision meets the available scientific and ethical standards governing the use of these tests in individual assessment. A tension between practical and ethical issues in the test revision process is inevitable and demands the best of psychologists in their decision making. Test developers, psychologists, patients, and consumers of the test interpretations and recommendations have legitimate interests and a stake in seeing that test revisions are applied with maximal effectiveness and fairness in the broadest sense.

Decreased striatal monoaminergic terminals in severe chronic alcoholism demonstrated with (+)[11C]dihydrotetrabenazine and positron emission tomography.

We used (+)[11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter, with positron emission tomography to study striatal monoaminergic presynaptic terminals in 7 male severe chronic alcoholic subjects without Wernicke-Korsakoff disease compared with 7 male normal controls of similar ages. We found reduced specific binding in the caudate nucleus and putamen in the alcoholic group, and the difference reached significance in the putamen. Specific binding was not decreased in the thalamus, which was examined as a reference structure. We also detected deficits in blood-to-brain transfer rate, K1, in the same regions of the alcoholic group, with a significant difference in the putamen. K1 was unchanged in the thalamus. The finding of reduced striatal VMAT2 in severe chronic alcoholic patients suggests that nigrostriatal monoaminergic terminals are reduced, with or without loss of neurons from the substantia nigra. The findings suggest that the damaging effects of severe chronic alcoholism on the central nervous system are more extensive than previously considered.

Sequelae of unrecognized gestational diabetes.

OBJECTIVE: Prior studies have suggested that macrosomia is the only morbid condition associated with gestational diabetes and that this association is the result of confounding by maternal obesity rather than a result of gestational diabetes itself. We sought to determine whether unrecognized gestational diabetes is an independent predictor of macrosomia and other perinatal morbid conditions after controlling for confounding variables. STUDY DESIGN: A retrospective analysis of 472 consecutive cases of gestational diabetes diagnosed between 24 and 30 weeks' gestation was undertaken including 16 prospectively identified but clinically unrecognized cases, 297 cases treated with diet alone, and 76 treated with diet plus insulin. Unrecognized cases were matched to 64 nondiabetic controls for race, age, body mass index, parity, pregnancy weight gain, and gestational age at delivery. RESULTS: In the unrecognized gestational diabetes group versus the nondiabetic control versus gestational diabetes diet groups rates of large for gestational age infants (44% vs 5% vs 9%, p < 0.0005), macrosomia (44% vs 8% vs 15%, p < 0.01), shoulder dystocia (19% vs 3% vs 3%, p < 0.05), and birth trauma (25% vs 0% vs 0.3%, p < 0.001) were all significantly increased. These differences remained significant after controlling for maternal age, race, parity, body mass index, pregnancy weight gain, and gestational age at delivery. CONCLUSIONS: This study suggests that unrecognized gestational diabetes increases risks of large for gestational age infants, macrosomia, shoulder dystocia, and birth trauma independent of maternal obesity and other confounding variables. Clinical recognition and dietary control of gestational diabetes are associated with a reduction in these perinatal morbid conditions.

The significance of family history status in relation to neuropsychological test performance and cerebral glucose metabolism studied with positron emission tomography in older alcoholic patients.

Patients with severe chronic alcoholism have decreased rates of glucose metabolism in the medial frontal lobe and correlated abnormalities of neuropsychological functioning. The potential influence of family history of alcoholism has not been examined in these patients. In a retrospective study, we used neuropsychological tests and neuroimaging employing [18F]fluorodeoxyglucose with positron emission tomography to study 48 older subjects who had histories of severe, chronic alcohol dependence. These patients were divided into two groups: 27 with a first-degree relative with chronic alcoholism and 21 patients without first-degree relative with chronic alcoholism. No differences were found between groups on either neuropsychological or neuroimaging tests. These results suggest that a family history of alcoholism does not moderate the damaging effects of severe chronic alcoholism on the functioning of the medial frontal lobe.

Effects of abstinence and relapse upon neuropsychological function and cerebral glucose metabolism in severe chronic alcoholism.

Prolonged excessive consumption of alcohol has been associated with a variety of cognitive disorders accompanied by neuropathological and neurochemical abnormalities of the brain, particularly in the frontal lobes. Studies with positron emission tomography (PET) have shown decreased local cerebral metabolic rates for glucose (lCMRglc) in frontal regions, with correlated abnormalities on neuropsychological tests sensitive to executive functioning. This investigation was designed as a pilot study to examine the effects of abstinence and relapse in patients with severe chronic alcoholism studied longitudinally with PET and with neuropsychological evaluation to assess both general and executive functioning. Six patients, including 4 who remained relatively abstinent and 2 who relapsed following their initial evaluation, were studied twice, with inter-evaluation intervals ranging from 10 to 32 months. The patients who remained abstinent or who had minimal alcohol use showed partial recovery of lCMRglc in two of three divisions of the frontal lobes and improvement on neuropsychological tests of general cognitive and executive functioning, whereas the patients who relapsed had further declines in these areas. These results, although based upon a relatively small number of subjects, provide preliminary support for at least partial recovery of metabolic and cognitive functioning in individual patients who abstain from alcohol.

Impaired upper limb coordination in alcoholic cerebellar degeneration.

BACKGROUND: Alcoholic cerebellar degeneration (ACD) is a disorder resulting from severe chronic alcoholism and malnutrition and is characterized by cognitive disturbances, ataxia of gait, and truncal instability, with generally preserved coordination of the upper extremities. OBJECTIVES: To determine whether cognitive deficits in patients with ACD are the same as those seen in patients with severe chronic alcoholism without ACD and to determine whether upper limb motor coordination is different in the 2 groups. DESIGN: We examined cognitive function and upper limb coordination in 56 patients with severe chronic alcoholism, 13 with ACD and 43 without ACD, who had comparable levels of total alcohol intake. Neuropsychological and motor function was measured using an expanded Halstead-Reitan Neuropsychological Test Battery, including the Tactual Performance Test and Grooved Pegboard Test. RESULTS: Neither group had impaired coordination of upper limb function on clinical neurological examination. Both groups had impaired performance on neuropsychological tests involving executive function, but the patients with ACD had greater impairment of upper limb coordination than the patients without ACD as measured by the Tactual Performance Test and Grooved Pegboard Test. CONCLUSIONS: The findings suggest that these 2 groups have similar cognitive deficits but that upper extremity motor functions are more significantly impaired in the ACD group and that quantitative tasks of motor function reveal these impairments.

Accuracy of self-reported educational attainment among diverse patient populations: a preliminary investigation.

Despite speculation concerning the accuracy of self-reported information, particularly from certain patient populations, many neuropsychologists continue to estimate premorbid intellectual functioning on the basis of self-reported educational attainment. This study examined 116 individuals with diverse diagnoses [i.e., alcoholism, posttraumatic stress disorder (PTSD), schizophrenia or schizoaffective, and dementia] to determine the accuracy of their self-reported high school educational attainment. Results suggest that at least half of all participants were inaccurate as defined by discrepancies between actual and estimated GPA greater than.5 on a traditional 4-point grading scale. Most patients were inaccurate in the direction of overestimating their educational attainment. Patients diagnosed with alcoholism and PTSD were significantly less accurate in recalling their educational history when compared to a group of normal-control subjects. Several subjects, whose records could not be verified, were found to have not attended high school as they had claimed. These results underscore the potential inaccuracy that exists when estimating premorbid intelligence using self-reported information.

Effects of disulfiram on positron emission tomography and neuropsychological studies in severe chronic alcoholism.

Disulfiram is an aldehyde dehydrogenase inhibitor that is widely used as an adjunctive agent in the treatment of patients with severe chronic alcoholism. Recent positron emission tomography (PET) studies of local cerebral metabolic rates for glucose (ICMRglc) and benzodiazepine receptor binding in alcoholic patients have shown regional cerebral abnormalities; however, some of the patients were studied while receiving disulfiram, which could influence the biochemical processes under investigation. In a retrospective investigation, we examined the influence of disulfiram administration on the results of PET studies of ICMRglc and benzodiazepine receptor binding and neuropsychological tests of cognition and executive function in patients with severe chronic alcoholism. [18F]Fluorodeoxyglucose was used to measure ICMRglc in 48 male patients, including 11 receiving and 37 not receiving disulfiram in therapeutic doses. [11C]Flumazenil was used to measure benzodiazepine receptor binding in 17 male patients, including 3 receiving and 14 not receiving disulfiram. All patients studied with FMZ were also examined with fluorodeoxyglucose. PET studies of ICMRglc revealed significantly decreased global values in the patients receiving disulfiram compared with those not receiving disulfiram. PET studies of benzodiazepine receptor binding revealed decreased flumazenil influx and distribution volume in patients receiving disulfiram. The neuropsychological tests demonstrated no differences between the two groups of subjects. The findings suggest that disulfiram may influence the results of PET studies of glucose metabolism and benzodiazepine receptor binding.

Continuous passive motion use in hand therapy.

This paper discusses the indications and contraindications of continuous passive motion (CPM) in hand therapy. The pros and cons of portable and stationary CPMs available for the hand, wrist, forearm, elbow, and shoulders are reviewed.

The psychologist's role in assessing and facilitating patients' knowledge of advance directives in medical settings: A preliminary investigation.

In a time of budgetary shortfalls in the medical industry, an aging population, and an increased emphasis on health care choices, psychologists are being called upon to administer advance medical directive programs to patients. This study reports preliminary findings from a program to assess and facilitate patients' knowledge of advance directives (ADs) by the Psychology Service at the Ann Arbor VA Medical Center. The participant pool included 243 male veteran patients admitted to medical and surgical wards at the hospital. The intervention included the use of a computer-generated prompt for consultation, which was sent to the psychology staff in response to a patient inquiry regarding ADs. It also involved an increased emphasis on the delivery of written material on ADs by the admissions clerks. The intervention appeared to result in a modest increase in patients' knowledge of advance directives. Suggestions are offered for areas that should be emphasized in future attempts to increase patients' knowledge and utilization of advance directives.

Carpe societatem: a substantive debriefing for the INS member.

This paper reviews the development of the International Neuropsychological Society (INS) over the last 14 years in the term of the author as Executive Secretary. The problems and challenges that remain for the INS are presented in their historical context.

On perhaps becoming what you had previously despised: Psychologists as prescribers of medication.

The authors contend that organized psychology's efforts to gain limited prescriptive privileges may be misguided. The modification of psychology's traditional scope of practice may produce harm in the form of lessened patient regard, devaluation of nonpharmacologic elements of practice, and markedly increased exposure to claims of malpractice. The authors also decry the disingenuous use of psychopharmacologically "underserved" populations as rationales for the pursuit of prescriptive privileges. Psychology may mount a major effort to make this change without sufficient justification, in the view of the authors.