Clonidine treatment of Alzheimer's disease.

A loss of cortical noradrenergic innervation may contribute to the intellectual deterioration in Alzheimer's disease. To test the hypothesis that noradrenergic replacement may confer symptomatic benefit, a double-blind, placebo-controlled therapeutic trial with clonidine hydrochloride (Catapres), a centrally active noradrenergic receptor agonist, was undertaken in eight patients with the clinical diagnosis of Alzheimer's disease. No statistically significant changes in cognitive function were found over a range of doses, including those that produced clinically observable side effects.

Morning increase in onset of ischemic stroke.

The time of onset of ischemic stroke was determined for 1,167 of 1,273 patients during the collection of data by four academic hospital centers between June 30, 1983, and June 30, 1986. More strokes occurred in awake patients from 10:00 AM to noon than during any other 2-hour interval. The incidence of stroke onset declined steadily during the remainder of the day and early evening.

Carbamazepine in Fabry's disease: effective analgesia with dose-dependent exacerbation of autonomic dysfunction.

Seven patients with Fabry's disease and severe pain received carbamazepine (CMZ). Five of 7 patients had moderate to complete relief based upon self-assessment of pain levels. Preexisting autonomic dysfunction was exacerbated by CMZ in 2.

A method for determining optimal interelectrode spacing for cerebral topographic mapping.

Inappropriately large interelectrode spacing may result in significant errors of localization and erroneous measurements of amplitudes, due to aliasing. Oversampling with very large numbers of scalp electrodes is impractical. We present a generally applicable method for determination of optimal interelectrode spacing.

A new surface electrode for recording from the posterior cricoarytenoid muscle.

A new pharyngeal surface electrode for recording posterior cricoarytenoid muscle activity through the hypopharyngeal mucosa has been evaluated. The electrode was passed through one nasal passage into the hypopharynx. Correct electrode location was verified by increased activity during inhalation, with decreased activity during phonation.

Whole-cell patch-clamp analysis of voltage-dependent calcium conductances in cultured embryonic rat hippocampal neurons.

1. Voltage-dependent calcium currents in embryonic (E18) hippocampal neurons cultured for 1-14 days were investigated using the whole-cell patch-clamp technique. 2.

The role of a placebo-treated control group in combination drug trials.

In order to satisfy regulatory requirements for fixed-dose combination drug products, clinical trials must demonstrate that each component contributes to the claimed effect of the combination. Thus, the comparisons of primary interest are usually of the combination versus combination minus one component, and do not involve placebo. However, a placebo-treated group can be useful for interpreting the primary comparisons and for clarifying the nature of effects in the presence of interactions.

Implantation of dispersed cells into primate brain.

Although several experimental therapies such as dopaminergic cell implantation in parkinsonian models and intratumoral placement of lymphokine-activated killer cells require intracerebral deposition of dispersed cell suspensions, a successful technique of needle implantation of cells into primate brain has not been demonstrated. The authors have sought to establish a stereotaxic technique to predictably deposit dispersed cells in primate brain. Human lymphocytes were cultured in recombinant interleukin-2, labeled with sodium 51 chromate (51Cr), and stereotaxically injected into the frontal white matter of six anesthetized rhesus monkeys.

Vascular endothelium in immunology and infectious disease.

During infection the vascular endothelial cell (EC) undergoes important immunologic alterations leading to increased leukocyte-EC adherence and initiation of a host inflammatory response. ECs express class 2 immune response genes and the interleukin 1 gene to a greater degree during infection and thus may be capable of amplifying the lymphocytic proliferative process. Lymphokines generated from stimulated lymphocytes, notably interferon-gamma, may in turn further enhance EC-leukocyte adherence and class 2 antigenic presentation by ECs.

Dynein is the motor for retrograde axonal transport of organelles.

Vesicular organelles in axons of nerve cells are transported along microtubules either toward their plus ends (fast anterograde transport) or toward their minus ends (retrograde transport). Two microtubule-based motors were previously identified by examining plastic beads induced to move along microtubules by cytosol fractions from the squid giant axon: (i) an anterograde motor, kinesin, and (ii) a retrograde motor, which is characterized here. The retrograde motor, a cytosolic protein previously termed HMW1, was purified from optic lobes and extruded axoplasm by nucleotide-dependent microtubule affinity and release; microtubule gliding was used as the assay of motor activity.

Characteristics of B cell proliferation and activation in murine AIDS.

A syndrome characterized by lymphadenopathy, hypergammaglobulinemia, and immunodeficiency develops in C57BL/6 mice inoculated with LP-BM5 murine leukemia viruses. By studying the number and antigenic specificity of B cells activated in the course of this disease, we found that a series of reproducible changes in the humoral immune system were induced by retroviral infection. The rate of B cell proliferation and the proportion of B cells activated to secrete Ig increased by nearly 10-fold at 4 wk post inoculation.

Plasma dihydroxyphenylglycol for estimation of noradrenaline neuronal re-uptake in the sympathetic nervous system in vivo.

1. Neuronal re-uptake is the primary means for terminating the actions of endogenously released noradrenaline. A portion of the recaptured noradrenaline is deaminated to form dihydroxyphenylglycol.

Niemann-Pick disease types C and D.

Patients grouped into categories termed type C Niemann-Pick disease and the Nova Scotia isolate called type D Niemann-Pick disease are characterized by mild to moderate hepatosplenomegaly, sea-blue histiocytes in the bone marrow, supranuclear gaze paresis in the vertical plane, slowly progressing ataxia, and mental deterioration. These signs are caused by abnormal intracellular cholesterol homeostasis. Cholesterol that enters cells from the circulation through the LDL receptor is not processed in a timely, normal manner by cells in parenchymal organs and the CNS.

Intratumoral LAK cell and interleukin-2 therapy of human gliomas.

Adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) offers the possibility of a new treatment for patients with malignant glial tumors. In a clinical trial, the effectiveness of a 5-day treatment cycle of direct intratumoral administration of both LAK cells and IL-2 via a reservoir/catheter system in patients with recurrent malignant gliomas was studied. Ten patients were entered into the study, nine of whom were treated with 15 cycles of LAK cells (0.

Opposite effects of chronic cortisol treatment on pre- and postsynaptic actions of clonidine in pithed rats.

1. Both clinical and experimental studies have shown that chronic elevation of plasma cortisol levels are attended by altered adrenergic receptor function. In the present study we examined the effects of chronic cortisol treatment (25 mg kg-1 day-1 for 7 days by minipumps) on the peripheral cardiovascular responses of pithed, adrenal demedullated vagotomized rats.

Plasma dihydroxyphenylalanine and total body and regional noradrenergic activity in humans.

Dihydroxyphenylalanine (DOPA) is the immediate product of the rate-limiting step in catecholamine biosynthesis, hydroxylation of tyrosine. This study examined whether plasma concentrations of DOPA are related to tyrosine hydroxylase activity. Plasma concentrations of DOPA, norepinephrine, and the norepinephrine metabolites 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in arterial blood and blood draining the heart, brain, and forearm of 21 patients undergoing cardiac catheterization.

Immunocytochemical characterization of neurofibrillary tangles in amyotrophic lateral sclerosis and parkinsonism-dementia of Guam.

Cryostat-cut sections of formalin-fixed and unfixed hippocampus from 23 Guamanian Chamorros with clinically and neuropathologically verified amyotrophic lateral sclerosis (ALS) (8 cases) and parkinsonism-dementia (PD) (15 cases) and from 12 neurologically normal Guamanians (5 with and 7 without neurofibrillary degeneration) were evaluated by the immunoperoxidase technique, using monoclonal antibodies against phosphorylated neurofilament, human fetal microtubule-associated protein tau, and paired helical filaments. On immunostaining, all three antibodies showed intracellular tangles in the hippocampal neurons of patients with ALS, patients with PD, and in neurologically normal Guamanians with neurofibrillary pathology, but the correlation of immunostaining between these antibodies was not absolute. Extracellular or ghost tangles were immunostained only with the antibody against paired helical filaments.

Fear episodes due to limbic seizures with normal ictal scalp EEG: a subdural electrographic study.

The authors present the case of a 13-year-old girl with episodes characterized by either staring with preserved consciousness or fear in whom functional illness was suspected. Video-EEG telemetry revealed no changes during 30 of 32 attacks. Subdural electrode recordings revealed epileptiform discharges in 30 of 37 episodes.

Reciprocal inhibition in patients with hand cramps.

We studied inhibition of median nerve H-reflex produced by radial nerve stimulation in both arms of 14 patients with hand cramps and 15 normal volunteers. Median nerve stimulation was delivered 1 and 0.5 msec before and 0, 0.

CSF acetylcholinesterase levels are reduced in multiple system atrophy with autonomic failure.

Diminished CSF levels of acetylcholinesterase in patients with multiple system atrophy attended by autonomic failure suggest that CNS cholinergic involvement may occur in this disorder. The lack of correlation between the low enzyme levels and low CSF levels of monoamine metabolites in these patients indicates that the acetylcholinesterase reduction is not directly related to disruption in these neurotransmitter systems. Normal CSF acetylcholinesterase levels in those patients with pure autonomic failure are consistent with functional integrity of central cholinergic pathways and support a pathophysiologic involvement limited to the peripheral nervous system.

Modulation of short latency cutaneous excitation in flexor and extensor motoneurons during fictive locomotion in the cat.

We examined modulation of transmission in short-latency, distal hindlimb cutaneous reflex pathways during fictive locomotion in 19 decerebrate cats. Fictive stepping was produced either by electrical stimulation of the mesencephalic locomotor region (MLR) or by administration of Nialamide and 1-DOPA to acutely spinalized animals. Postsynaptic potentials (PSPs) produced by electrical stimulation of low threshold afferents (less than 2.

The effect of interleukin-2 on the blood-brain barrier in the 9L gliosarcoma rat model.

Carbon-14-labeled aminoisobutyric acid was used to determine local blood-to-tissue transfer constants in 22 Fischer rats with intracerebral 9L gliosarcomas that received either high-dose parenteral interleukin-2 (IL-2) or a control injection. In tumor and peritumoral tissue, the transfer constants in the IL-2-treated animals (89.6 +/- 14.