Hallucinations and associated factors in Alzheimer's disease.

In a consecutive sample of 230 community-dwelling patients with probable Alzheimer's disease, a structured interview yielded evidence of current hallucinations in 29.1% and misperceptions in another 11.3%. Visual and auditory modalities were similarly represented in apparent hallucinations. Hallucinations prior to the current monitoring period were rare among patients with misperceptions or with no perceptual abnormality. The probability of hallucinations was associated with the severity of cognitive dysfunction, the degree of other behavioral disturbances, and the presence of extrapyramidal signs. A logistic regression model predicting hallucinations based on these diverse clinical features accurately classified 87.0% of the sample.     

Cerebral type 2 astroglia are heterogeneous with respect to their ability to respond to neuroligands linked to calcium mobilization.

Very little information is available concerning the pharmacology of type 2 astroglia. During the past decade it has become apparent that two distinct lineages of astroglial cells can be defined in vitro. These two lineages are commonly referred to as type 1 and type 2 and are distinguished from each other on the basis of their morphological features and antigenic phenotypes. In contrast to type 1 astroglia, very little is known about the pharmacology of type 2 astroglia. The lack of information concerning the responsiveness of these cells stems primarily from difficulties encountered in isolating large numbers of type 2 astroglia free of other cell types. In the present study video- and photometer-based imaging systems were used to monitor the influence of a series of neuroligands on the intracellular calcium levels of individual cerebral type 2 astroglia in order to assess their expression of calcium-mobilizing receptors. The responses of 85 immunocytochemically identified cerebral type 2 astroglia to bradykinin (BK), norepinephrine (NE), histamine (HIST), carbachol (CARB), 2-methyl-thio ATP (2MT-ATP), glutamate (GLUT), and serotonin (5-HT) were analyzed. Approximately 50% of cerebral type 2 astroglia responded to BK, NE, HIST, CARB, and 2MT-ATP whereas only 16% and 9% of the cells responded to GLUT and 5-HT, respectively. The number of neuroligands that increased calcium in individual cells ranged from 0 to 6. These responses are quite similar to those previously demonstrated in cultured cerebral type 1 astroglia. No pattern of receptor co-expression was observed for the different neuroligands tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for motility and pinocytosis in ramified microglia in tissue culture

Ramified microglial cells were investigated in primary cultures of dissociated cerebral cortical tissue from rats. The identification of these cells was confirmed through immunohistochemical staining with 7 monoclonal antibodies selective for microglia. While there was significant variation in staining intensity with different antibodies, all stained the identified ramified cells; the antibodies OX-42 and ED1 yielded the most intense immunoreactivity. Based on distinctive morphological features, the microglia could be identified in living cultures where they were monitored using time-lapse video recording. This technique revealed extremely dynamic features of cellular plasticity and motility. Ramified microglia exhibited constant and rapid alterations in the size and shape of their cell body with an associated extension and retraction of processes; concomitantly, the cells moved about in a circumscribed area. These features of plasticity and motility were unique to this cell type, and correlated with OX-42 immunostaining. The microglia also possessed a differentially high level of pinocytotic activity; this too was correlated with OX-42 staining. From the nature of their morphological plasticity and motility, high pinocytosis, and cellular distribution, it is hypothesized that the ramified microglia specifically function as a system of fluid cleansing in normal brain tissue.     

Dissociable roles of the ventral, medial and lateral striatum on the acquisition and performance of a complex visual stimulus-response habit.

The effects of discrete bilateral ibotenic acid lesions to 3 areas of striatum were examined on a conditional visual discrimination task involving temporal frequency (SLOW vs FAST flashes) that had previously been shown to be sensitive to the effects of dorsal striatal dopamine depletion. Two of the groups, namely, those with nucleus accumbens (ACC) and lateral caudate-putamen (LCP) lesions, were very disrupted in the acquisition of the task. The nature of the respective impairments of the 2 groups was dissociable, however. The performance of the ACC group could be improved either by manipulations of stimulus duration or inter-stimulus interval, implying an attentional deficit. In contrast, the rats with lesions of the LCP were not significantly improved by any of the behavioural challenges. Their performance was characterised by a bias to respond to the SLOW discriminandum. Under conditions of non-reward, the LCP group extinguished their responding at a similar rate to control rats whereas the ACC group were very much more persistent. Lesions of the medial caudate-putamen failed to affect any index of performance significantly. These data suggest that the LCP is necessary for the acquisition of arbitrary stimulus-response rules and that damage to an equivalent area in humans, such as in Huntington's disease, may explain deficits of procedural memory. The second part of the experiment investigated the effects of ACC lesions on established performance of the schedule. The lesioned group behaved identically to the ACC group that had been lesioned prior to acquisition, both in terms of accuracy and degree of persistence in extinction, further implying the role of attentional factors and inflexibility in the lesion-induced deficit.     

Interethnic variation of drug metabolism

There are many examples of differences between ethnically defined populations with regard to drug-metabolizing enzymes i.e. enzymes that serve as defences against exogenous chemicals. The prevalence of variants of enzymes such as monooxygenases, dehydrogenases, esterases and some transferases is not uniform, and this leads to differences in metabolism of drugs such as aspirin and diazepam, among others. Werner Kalow explains why the mere counting of a genetic variant may not be sufficient to uncover more major problems such as may be posed by multiple allelism or heterozygosity, and why it may be predicted that a large number of drugs will display interethnic differences in function.     

Homogeneous, micelle quenching fluoroimmunoassay for detecting amphetamines in urine

We developed a homogeneous fluoroimmunoassay for detecting amphetamines in urine. Only fluorescence intensity need be measured because the emission of non-protein-bound fluorescein-labeled amphetamine is preferentially quenched by detergent micelles. In a previous reported prototype assay system for measuring gentamicin in serum we used fluorescein and dodecyl sulfate (Anal Chem 1985; 57:1928-30). We have found that favorable hydrophobic and (or) ionic character of the analyte and unfavorable polar and (or) ionic character of the fluor are important determinants of the desired interactions. An anionic detergent and fluorescein, therefore, should be appropriate for apolar of cationic analytes, such as gentamicin and amphetamines. A greater [H+] at the anionic micelle surface is important for quenching emission from the fluor moiety. Millimolar concentrations of dodecyl sulfate rapidly denature immunoglobulin unless hapten is bound with sufficiently high affinity. Affinity was sufficiently high for the antibody used in the prototype gentamicin assay but not for the amphetamine antibody. Thus for the amphetamine assay, we used a non-denaturing detergent, dodecyl(oxyethylene)12 sulfate. The assay requires 30 microL of specimen in 2 mL of total assay volume. Amphetamine(d-,dl-, and meth-), at a concentration of 1 mg per liter of urine, is readily detected.     

Screening for psychosis in the general population with a self-report interview

This analysis applies methods of screening to the problem of psychosis. A probability sample of 810 individuals from the Eastern Baltimore Mental Health Survey was interviewed in the self-report modality with the Diagnostic Interview Schedule and shortly thereafter by a psychiatrist. It is shown that a configuration of responses in the self-report modality can screen moderately well for psychosis, as measured by psychiatrists in the clinical modality.     

Cardiovascular intervention for high-risk families: the Heart Smart Program

The Heart Smart Family Health Promotion Program is a multidisciplinary, school-based program for cardiovascular risk reduction among high-risk children and their families. As a program that includes young adults at high risk, it is adaptable to a clinical practice. Nineteen fourth and fifth graders were selected as probands for elevated risk factors after a general screening to identify families for an intervention program. Twenty-three parents participated in a 12-week program focused on eating, exercise, and smoking behavior changes enhanced by behavicral support strategies. Weekly sessions were held in the auditorium/cafeteria of the elementary school and consisted of orientation and presentations, cardiovascular (CV) screening with medical feedback, activities, self-monitoring, counseling, and contingency contracting. Information gathered before and after the program included medical history, CV health knowledge and relevant behavior, blood pressure, serum lipid and lipoprotein values, anthropometric measurements, and urine electrolyte excretion. Both children and parents showed positive changes in eating habits and physical activity and significant changes in knowledge and blood pressure levels, while the children halted their weight gain. We believe this multidisciplinary, behavior-oriented, school-based program can be an effective cardiovascular risk intervention adaptable for a clinical office practice.     

Computed tomography in CNS tuberculosis

Computed tomography (CT) was performed in 14 cases of tuberculous meningitis (TBM), 12 of which were examined during the acute phase of the disease. CT findings in these cases included internal hydrocephalus (6/12), internal combined with external hydrocephalus (2/12), focal lesions consistent with localized encephalitis (3/12), diffuse brain edema (1/12), and middle cerebral artery infarction (1/12). In comparison to 32 cases of nonspecific bacterial meningitis, internal hydrocephalus was found significantly more often in TBM than in nonspecific meningitis (p less than 0.01) making CT an additional tool for the differentiation of these conditions in doubtful cases. In addition, CT features of 2 cases of cerebral tuberculoma are presented.