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Biomedical subjects

J Scherer

Publications and source records attributed to J Scherer.

11 recordsLinked to original sources

Decrease of D2 receptors indicated by 123I-iodobenzamide single-photon emission computed tomography relates to neurological deficit in treated Wilson's disease.

Single-photon emission computed tomography with 123I-iodobenzamide, a dopamine D2 receptor antagonist, was employed to study dopamine D2 receptor densities in 17 patients with biochemically proved Wilson's disease and stable neurological status with therapy and in 5 age-matched control subjects. Of the 17 patients with Wilson's disease, 5 were neurologically asymptomatic, 3 had cerebellar signs, 1 exhibited a mild parkinsonian syndrome, 7 showed a parkinsonian syndrome and cerebellar signs, and 1 had generalized dystonia and a parkinsonian syndrome. In 5 age-matched control subjects specific isotope binding as calculated by the basal ganglia to frontal cortex ratio was 1.57 +/- 0.04 (mean +/- standard deviation). The ratio in patients with Wilson's disease ranged from 1.56 +/- 0.05 (n = 5, asymptomatic patients) to 1.17 +/- 0.02 (n = 4, marked neurological impairment). We observed an almost linear correlation between the reduction of 123I-iodobenzamide (IBZM) binding and the severity of neurological signs at the time of IBZM-SPECT (correlation coefficient, -0.84; p < 0.01). We suggest that the reduction of postsynaptic striatal dopamine D2 receptors as detected by IBZM-SPECT reflects striatal neuronal damage in Wilson's disease.

Adolescent

Intraorbital transection of the rabbit optic nerve: consequences for ganglion cells and neuroglia in the retina.

Rabbit retinae were stained with antibodies to glial fibrillary acidic protein (GFAP) at various times up to 5 months after complete unilateral intraorbital optic nerve transection, which is known to induce degeneration of ganglion cell axons and perikarya in the retina. A transient immunoreactivity for GFAP was observed in Müller glial cells that normally lack this marker. Müller-cell GFAP immunoreactivity became detectable 4 days after the lesion, but Müller cells were no longer labeled 3 months later. GFAP-labeled astrocytes located in the nerve fiber layer showed no change in immunoreactivity at any stage after transection. Application of horseradish peroxidase to the left and right superior colliculus of a rabbit whose optic nerve had been transected unilaterally 2 years before confirmed the completeness of the transection. Yet electron microscopy showed the presence of some healthy-looking ganglion cell axons in the lesioned retina, although these cells were deprived of their target. Labeling retinal wholemounts with neurofilament antibodies confirmed the presence of some ganglion cell axons and perikarya in the retina more than 2 years after transection. The course of these axons suggested that they were remnants of axons. Using antibodies to galactocerebroside (GC) we found that, as in the normal rabbit, these persisting ganglion cell axons were myelinated in the medullary rays. Although many ganglion cell axons had disappeared after 2 years, the number of neuroglial cells (including astrocytes and oligodendrocytes) present in the medullary ray region was not altered. The cell bodies of some oligodendrocytes were covered with a myelin sheath, an aberrant feature not seen normally.

Animals

Confidence intervals for weighted sums of Poisson parameters.

Directly standardized mortality rates are examples of weighted sums of Poisson rate parameters. If the numbers of events are large then normal approximations can be used to calculate confidence intervals, but these are inadequate if the numbers are small. We present a method for obtaining approximate confidence limits for the weighted sum of Poisson parameters as linear functions of the confidence limits for a single Poisson parameter, the unweighted sum. The location and length of the proposed interval depend on the method used to obtain confidence limits for the single parameter. Therefore several methods for obtaining confidence intervals for a single Poisson parameter are compared. For single parameters and for weighted sums of parameters, simulation suggests that the coverage of the proposed intervals is close to the nominal confidence levels. The method is illustrated using data on rates of myocardial infarction obtained as part of the WHO MONICA Project in Augsburg, Federal Republic of Germany.

Adult

Microglial cell responses in the rabbit retina following transection of the optic nerve.

The response of retinal microglial cells, which accompanies retrograde degeneration of ganglion cell axons and perikarya (induced by transection of the optic nerve), was studied in whole-mounted rabbit retinae labeled enzyme-histochemically for nucleoside diphosphatase (NDPase), which is a microglial cell marker. A few days after transection, the number of microglial cells/mm2, as well as their staining intensity, began to increase in the inner plexiform layer. The mosaic-like distribution of the star-shaped microglial cells present in the inner plexiform layer of a normal rabbit retina was preserved during ganglion cell degeneration. As in the normal retina, processes of individual cells never overlapped with those of neighboring cells in the inner plexiform layer because individual cells in the "degenerating" retina acquired shorter processes, i.e., the cells occupied a smaller territory compared to the normal retina. In the nerve fiber layer the number and staining intensity of NDPase-labeled microglial cell processes (most of which are aligned in parallel with degenerating ganglion cell axons) transiently increased and returned to normal values by 5 months post-transection. Microglial cells that are not detectably NDPase labeled in the outer plexiform layer of a normal rabbit retina acquire intense staining a few days after the nerve is cut. The functional significance of the increased NDPase activity in the plasma membrane of microglial cells during degeneration remains to be determined.

Acid Anhydride Hydrolases

The rabbit retina: a suitable mammalian tissue for obtaining astroglia-free Müller cell cultures.

Monolayer cultures were prepared from two distinct parts of early postnatal rabbit retinae. Cell suspensions obtained from the developing medullary ray (MR) region contained neurons, Müller (glial) cells, and astrocytes, cells obtained from the remainder (peripheral) part of the retina contained neurons and Müller cells, but no astrocytes. Müller cells lack glial fibrillary acidic protein (GFAP) immunolabeling in situ but some of them acquire faint GFAP labeling in both types of cultures. Strongly GFAP-labeled cells, most likely astrocytes, were seen in MR cultures only. We propose that the periphery of the rabbit retina is ideal for obtaining astroglia-free Müller cell cultures to study their functional properties in vitro.

Animals

[Predictive and rehabilitative perspectives in heart transplantation].

27 patients who underwent heart transplantation one to five years ago, were evaluated concerning psychological and social adjustment after heart transplantation. Prior to cardiac transplantation, predictors for good rehabilitation status were absence of psychopathology, clear motivation, good social background, advanced physical debility (being bedridden as opposed to ambulatory), absence of a history of excessive alcohol consumption. Age was not found to be a predictor of outcome. Criteria for good rehabilitation status after cardiac transplantation were absence of psychopathology, good compliance, social reintegration, return to work, psychological well-being, satisfaction with the quality of life and good exercise capacity. The criteria for good rehabilitation correlate positively with the predictors specified and with each other. Psychopathology after cardiac transplantation was related to psychopathology prior to the intervention, motivation, social background, postoperative compliance, social reintegration, return to work, psychological well-being and satisfaction with the quality of life. Compliance was related with the predictors motivation, social background, history of excessive alcohol consumption, psychopathology after transplantation and return to work. Social reintegration was correlated with social background and post-transplantation psychopathology. Return to work was related to motivation, post-transplantation psychopathology and compliance. While physical well-being was not associated with the predictors except motivation, it was related to the rehabilitation factors of post-transplantation psychopathology, social reintegration, and return to work. Satisfaction with the quality of life correlated with only the rehabilitation factors of post-transplantation psychopathology and psychological well-being. Physical exercise capacity was related to psychological well-being after transplantation.

Adaptation, Psychological

Haloperidol plasma level after a test dose as predictor for the clinical response to treatment in acute schizophrenic patients.

In a fixed-dose, double-blind study, the clinical response of schizophrenic patients to a high (0.40 mg/kg) or a low (0.15 mg/kg) dose of haloperidol (HL) was compared. The relationship between HL steady-state plasma levels and clinical improvement was examined. The utility of HL plasma level after a single test dose (0.05 mg/kg) in predicting the clinical response to treatment was evaluated. No difference in clinical improvement was observed between the two groups as a whole, although the high-dose group had a faster initial improvement. The high-dose group showed more extrapyramidal effects during treatment. No relationship was found between HL steady-state levels and clinical improvement. For the low-dose group, HL plasma level after the test dose was significantly positively correlated with the improvement after eight days of treatment. The test dose HL plasma level was no predictor of the clinical response to treatment in the high-dose group. The possibility of predicting the clinical response of schizophrenic patients to treatment from the plasma level after a test dose is still an open question that requires further studies.

Acute Disease

Reliability of adverse drug reaction assessment in psychiatric inpatients.

Within an ongoing drug surveillance program in psychiatric hospitals the applicability of an algorithm for judgment on probability of causal relationship of adverse events and drug therapy was tested. Algorithmic interrater agreement was compared to agreement obtained with the conventional criteria used so far within the program in 80 cases by two raters, who had participated in the drug surveillance program since its beginning in 1979. With the use of the algorithm raters agreed on imputed drugs in 86% of all cases; total agreement on drugs and degree of probability was obtained in 69% (weighted kappa 0.618). Raters agreed on total score for the imputed medication in 49% and also on all subscores for the different axes of the algorithm in 43% of all cases. Differentiation of drug-related from illness-related changes, the use of judgmental terms within the algorithm and specific problems created by the frequent use of combinations of drugs with similar profiles of adverse drug reactions (ADR) in psychiatric patients were identified as the main sources of disagreement. Agreement on total judgment was comparable to results from similar studies in the literature using various algorithms, but in contrast to all these studies a higher percent of agreement (80%) was obtained with the use of the conventional criteria in this study.

Antidepressive Agents

Differential shunting in the diagnosis of patent ductus arteriosus with Eisenmenger physiology by radionuclide angiography.

Radionuclide angiography and static whole body imaging performed with technetium-99m-labeled particulates can clearly demonstrate differential shunting in patients with patent ductus arteriosus (PDA) with Eisenmenger physiology. The anatomic arterial relationships in this condition which direct deoxygenated blood into the lower body (differential cyanosis) produce specific radionuclide images characterized by differential shunting of the technetium-99m-labeled particulates into the abdomen and lower extremity.

Adult