A STUDY OF THE SPINAL CORD BY NISSL'S METHOD IN TYPHOID FEVER AND IN EXPERIMENTAL INFECTION WITH THE TYPHOID BACILLUS

(1) The application of the Nissl method to the study of the motor cells of the spinal cord, and the nerve cells of the dorsal root ganglia in typhoid fever, shows that these cells regularly suffer pathological changes in the course of the infection. (2) The alterations in the motor cells are more constant and of a severer grade than are those in the cells of the sensory ganglia. The more characteristic changes consist of disintegration, solution and destruction of the chromatic substance of the cell starting from the axone hillock and proceeding toward the nucleus. Coincidently the nuclei of the affected cells seek the periphery. Alterations are also suffered by the nucleus and nucleolus. (3) While this central form of ehromatolysis is the prevailing type of pathological change, disintegration, etc., of the Nissl bodies situated in the periphery of the cell and in the dendrites is also observed (peripheral chromatolysis). (4) In experimental infection with typhoid bacilli in rabbits a similar series of lesions in the corresponding nerve cells in the spinal cord and ganglia is encountered. (5) The main or central type of lesions discovered is identical with that found in man and animals after section, destruction, or even slight injury of the peripheral nerves. (6) The examination of the peripheral nerves arising from the lumbar segment of the cord (the site in man and rabbit of the most profound changes) in rabbits inoculated with typhoid bacilli showed well-marked evidences of parenchymatous degeneration. (7> It is probable that lesions of the peripheral nerves in typhoid fever in human beings are common and that the post-typhoid hyper sthesias and paralyses are due to this cause. (8) Restitution of the chromatic granules may take place in the affected nerve cells, the new formation beginning about the nucleus and extending through the protoplasm.     

Two automated locomotor activity tests for dopamine autoreceptor agonists

In the first test (exploratory activity), pretreated rats explored a novel environment in the dark. The potential autoreceptor agonists apomorphine HCl, N-n-propylnorapomorphine (NPA), and N-n-propyl-3-(3-hydroxyphenyl)-piperidine (3-PPP) and its enantiomers decreased the total distance travelled while at the same time paradoxically increasing the number of discrete movements. This is a very different pattern from that of the typical antipsychotic drugs haloperidol HCl and chlorpromazine HCl, and the atypical antipsychotic drug clozapine, which also decreased the total distance travelled but decreased the number of movements. Both groups decreased the distance/movement. In the second test, rats were habituated to the monitors in the light and then treated with test drug and stimulant (d-amphetamine sulfate or apomorphine HCl). Apomorphine HCl, NPA, and (+)3-PPP antagonized amphetamine-stimulated locomotor behavior (total distance) without antagonizing apomorphine-stimulated behavior, suggesting a presynaptic dopamine autoreceptor agonism. EMD 23448 gave equivocal activity. On the other hand, haloperidol HCl, chlorpromazine HCl, and clozapine decreased both amphetamine- and apomorphine-stimulated behavior, suggesting a postsynaptic dopamine antagonism. 3-PPP and (-)3-PPP showed neither pattern in this test.     

Studies of the relationship between molecular structure and hallucinogenic activity

The nature of the stereochemistry and aromatic ring substituents and their importance to biological activity for phenethylamine-type hallucinogens is presented. The possibility of a hydrophobic site to bind to the 4-substituent and its likely geometry is described. A brief discussion of the structure-activity relationships for tryptamines such as psilocin and DMT is also given, with comments about the stereochemistry of alpha-methyltryptamines. Evaluation of a series of N(6)-alkyl-nor-LSD derivatives indicated that selected members such as N(6)-ethyl, allyl and propyl were as potent as, if not more potent than LSD, both in a two-lever drug discrimination assay in rats, and in man. N(6)-alkyl groups longer than n-propyl, such as n-butyl or 2-phenethyl, gave compounds that were greatly reduced in activity.     

Posterior longitudinal ligament ossification myelopathy and hypothyroidism

Two elderly white women with a long history of hypothyroidism and myelopathy showed ossification in posterior longitudinal ligament at their cervical spine. Case histories are presented and the reported association of PLLO with other conditions discussed.     

Assessment of left ventricular mechanical dyssynchrony by phase analysis of ECG-gated SPECT myocardial perfusion imaging

Cardiac resynchronization therapy (CRT) has shown benefits in patients with severe heart failure. However, at least 30% of patients selected for CRT by use of traditional criteria (New York Heart Association class III or IV, depressed left ventricular [LV] ejection fraction, and prolonged QRS duration) do not respond to CRT. Recent studies with tissue Doppler imaging have shown that the presence of LV dyssynchrony is an important predictor of response to CRT. Phase analysis has been developed to allow assessment of LV dyssynchrony by gated single photon emission computed tomography myocardial perfusion imaging. This technique uses Fourier harmonic functions to approximate regional wall thickness changes over the cardiac cycle and to calculate the regional onset-of-mechanical contraction phase. Once the onset-of-mechanical contraction phases are obtained 3-dimensionally over the left ventricle, a phase distribution map is formed that represents the degree of LV dyssynchrony. This technique has been compared with other methods of measuring LV dyssynchrony and shown promising results in clinical evaluations. In this review the phase analysis methodology is described, and its up-to-date validations are summarized.