Selective serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) have been reported to induce extrapyramidal signs and symptoms (EPS). The authors examined the change from ...baseline EPS, measured by an objective rating scale, in a group of elderly depressed patients participating in an ongoing randomized, double-blind comparison of nortriptyline and paroxetine. Mild baseline EPS were present in both groups. After 6 weeks of antidepressant treatment, patients in the nortriptyline group showed a significant decrease in total EPS scores. Patients in the paroxetine group showed a similar decrease in EPS from baseline, which did not reach statistical significance. There was no significant difference between nortriptyline and paroxetine in the change in EPS.
We isolated a large panel of human Abs directed against the respiratory syncytial virus (RSV) Ag from combinatorial phage display libraries. Following initial differentiation of the Fabs by BstNI ...restriction patterns, DNA sequence analysis revealed 10 different classes of VH paired with more than 35 different VL genes. All the Fabs bound with high affinity to the F Ag. However, most Fabs competed with the binding of a representative member of this group, suggesting that the Fabs recognized a common epitope on the F Ag, and none of them neutralized virus in vitro. To suppress repetitive isolation of these non-neutralizing Abs, a representative Fab was included during panning to block this common epitope on the F Ag. By this "epitope-blocked panning" approach, two novel Fabs, encoded by unique VH and VL genes, were isolated from a previously screened library. Competition binding analysis confirmed that the Fabs recognized epitopes distinct from that of the previously isolated Fabs. One of these Fabs, 516, neutralized RSV in cell culture. These activities of Fab-516 were retained upon its genetic conversion to a mAb (IgG1) and expression in mammalian cells. Our results suggest that the RSV F glycoprotein presents a dominant, non-neutralizing epitope to the human immune system, which may serve in evasion of host defenses. However, less prevalent, fusion-inhibiting Abs were revealed by blockade of this epitope during the panning process.
Although a considerable body of biological and clinical data has been accumulated on the mood disorders and organic disorders of late life, only a handful of studies have focused on aging ...schizophrenia patients. Using the results of a comprehensive evaluation of all elderly patients admitted over a 30-month period to a 26-bed acute care geriatric unit, we compared the demographic, social, and clinical characteristics of schizophrenia patients, patients with recurrent major depression with and without psychotic features, and patients with primary degenerative dementia of the Alzheimer's type with and without delusions. The main findings of this study are that elderly schizophrenia patients were younger, more often African-American, more often single, and poorer than the other groups. A concomitant history of substance abuse and institutionalization as an outcome were more frequent among schizophrenia patients. Like the older depressed and demented patients, schizophrenia patients were predominantly female and commonly presented with several medical disorders. The potential significance of these findings is discussed in the context of the literature on the long-term outcome of schizophrenia.
Glucokinase is a key regulator of glucose homeostasis and small molecule activators of this enzyme represent a promising opportunity for the treatment of Type 2 diabetes. Several glucokinase ...activators have advanced to clinical studies and demonstrated promising efficacy; however, many of these early candidates also revealed hypoglycemia as a key risk. In an effort to mitigate this hypoglycemia risk while maintaining the promising efficacy of this mechanism, we have investigated a series of substituted 2-methylbenzofurans as "partial activators" of the glucokinase enzyme leading to the identification of N,N-dimethyl-5-(2-methyl-6-((5-methylpyrazin-2-yl)-carbamoyl)benzo f uran-4-yloxy)pyrimidine-2-carboxamide as an early development candidate.
Risperidone is extensively metabolized to an active metabolite, 9-hydroxyrisperidone (9-OH), which is dependent on renal clearance. Risperidone and 9-OH clearances are reduced in the elderly when ...compared to young subjects. The objective of this study was to determine whether among elderly subjects, risperidone and 9-OH clearance would further decline with increasing age and decreasing creatinine clearance (CrCl). Twenty geriatric inpatients were evaluated in a naturalistic setting with regard to total daily risperidone dose and dosing interval. Creatinine clear ance was determined using an 8-hour urine collection. Risperidone and 9-OH concentrations were determined by radioimmunoassay. Spearman's correlation coefficients were used to examine the impact of age and CrCl on con centrations of risperidone, 9-OH, their sum, and the quotient of 9-OH/risperidone. Mean age was 76.4 ± 9 years (range 56-91). Mean CrCl was 55.4 ± 32.8 mL/min/1.73 m2 (range 17-142 mL/min/1.73 m2). Mean risperidone daily dose was 1.3 ± 0.7 mg. Steady-state risperidone and 9-OH concentrations were 4.1 ± 5.3 ng/mL and 9.1 ± 6.2 ng/mL, respectively. Mean 9-OH/risperidone was 6.2 ± 6.1. Concentrations of risperidone, 9-OH, their sum, and 9-OH/risperi done were not significantly correlated with age or CrCl. These results were unchanged when concentrations were corrected for total daily risperidone dose. Among elderly subjects, risperidone and 9-OH clearance do not decline with increasing age or declining CrCl. (J Geriatr Psychiatry Neurol 2002; 15:77-81).
Recently, large samples of visually classified early-type galaxies (ETGs) containing dust have been identified using space-based infrared observations with the Herschel Space Telescope. The presence ...of large quantities of dust in massive ETGs is peculiar as X-ray halos of these galaxies are expected to destroy dust in 10 Myr (or less). This has sparked a debate regarding the origin of the dust: is it internally produced by asymptotic giant branch (AGB) stars, or is it accreted externally through mergers? We examine the 2D stellar and ionised gas kinematics of dusty ETGs using IFS observations from the SAMI galaxy survey, and integrated star-formation rates, stellar masses, and dust masses from the GAMA survey. Only 8% (4/49) of visually-classified ETGs are kinematically consistent with being dispersion-supported systems. These "dispersion-dominated galaxies" exhibit discrepancies between stellar and ionised gas kinematics, either offsets in the kinematic position angle or large differences in the rotational velocity, and are outliers in star-formation rate at a fixed dust mass compared to normal star-forming galaxies. These properties are suggestive of recent merger activity. The remaining 90% of dusty ETGs have low velocity dispersions and/or large circular velocities, typical of "rotation-dominated galaxies". These results, along with the general evidence of published works on X-ray emission in ETGs, suggest that they are unlikely to host hot, X-ray gas consistent with their low stellar mass when compared to dispersion-dominated galaxies. This means dust will be long lived and thus these galaxies do not require external scenarios for the origin of their dust content.
Vitamin B12 deficiency is common in elderly persons, yet its role in dementia and psychiatric illness is unclear. The authors examined the relationship between vitamin B12 serum levels and cognitive ...and neuropsychiatric symptoms in dementia. Community-dwelling elderly subjects (N=643) meeting NINCDS-ADRDA criteria for probable or possible Alzheimer disease (AD) underwent comprehensive neuropsychiatric evaluation and measurement of vitamin B12 serum levels. Thirty-seven subjects (5.7%) had low B12 serum levels (200 pcg/ml or less). Subjects with low B12 levels were significantly older and had significantly lower scores on the Mini-Mental State Exam and higher scores on the Blessed Dementia Scale, but not a different pattern of cognitive or behavior disturbances compared with the normal-B12 subjects. In AD, the prevalence of low vitamin B12 serum levels is consistent with that found in community-dwelling elderly persons in general but is associated with greater overall cognitive impairment.
The diagnosis of Ewing's sarcoma has been based classically in large part on the exclusion of other similar small round-cell tumors by light microscopic and histochemical criteria. This study was ...undertaken to explore the use of a recently developed immunohistochemical stain directed against the glycoprotein p30/32MIC2 antigen (the gene product of MIC2), as a diagnostic tool and as a probe for the examination of potential interrelationships among the putative members of the family of peripheral primitive neuroectodermal tumors. Fifty-six small round-cell tumors of bone were selected for study from the files of the Armed Forces Institute of Pathology and Rhode Island Hospital; all tissues had been formalin fixed and paraffin embedded. Nine of 10 Ewing's sarcomas were MIC2 positive, as were 2 of 3 atypical Ewing's sarcomas (small round-cell tumors that diverged from the classic pattern of Ewing's sarcoma by exhibiting a greater degree of cytologic atypia and pleomorphism), and 7 of 8 Askin tumors of the thoracopulmonary region. Ten of 11 mesenchymal chondrosarcomas, 1 primitive neuroectodermal tumor of bone, 10 small cell osteosarcomas, 10 malignant lymphomas, and 3 sarcomas of bone (not additionally subclassified) were negative. The finding of MIC2 positivity in the majority of Ewing's sarcomas and Askin tumors provides additional support for earlier proposals (based on a shared cytogenetic abnormality, among other criteria) that these lesions be considered members of the same family, the peripheral primitive neuroectodermal tumors. The present study, drawing on archival and current case material (including decalcified and undecalcified specimens), indicates that neither the specimen age nor the application of any of a variety of decalcification solutions appears to adversely influence MIC2 staining of paraffin-embedded tissues. This suggests that this antibody has use in retrospective and prospective studies. The rare occurrence of false negative (in the case of Ewing's sarcoma) and positive results in tumors other than peripheral primitive neuroectodermal tumors (as in 1 of the mesenchymal chondrosarcomas) suggests that MIC2 staining should not be relied on as the sole criterion for identification or exclusion of Ewing's sarcomas and related tumors.
Extrapyramidal symptoms (EPS) occur more frequently in dementia of the Alzheimer's type (DAT) than in normal aging. Other late-life mental disorders, however, have also been associated with EPS. To ...examine whether EPS are increased in DAT patients relative to neuropsychiatric control subjects, the authors compared EPS in 127 neuroleptic-free elderly patients diagnosed with either DAT, major depressive disorder (MDD), or a psychotic disorder (SCHIZ/DELUS). They also examined whether depressive or psychotic symptoms were associated with EPS independently of diagnosis. Severity of parkinsonian rigidity was found to be independently associated with DAT. Rank order of rigidity was DAT > MDD > SCHIZ/DELUS. Bradykinesia, although not associated with diagnostic group, was positively correlated with withdrawn depression. These findings suggest that rigidity is associated with DAT independently of any concurrent psychotic or depressive process, whereas bradykinesia does not appear to be specific to DAT among late-life neuropsychiatric illnesses.
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