Recurrent tonsillitis. The role of Chlamydia and Mycoplasma.

The core tissue microflora of 40 patients who underwent tonsillectomies were examined with cultures, DNA probe tests, enzyme immunoassays, and direct immunofluorescence antibody tests for Chlamydia and Mycoplasma. We believe this is the largest and most accurate prospective study that has examined the role of Chlamydia and Mycoplasma in the core tonsil tissue of patients with recurrent or chronic tonsillitis. The data strongly indicate that, unlike acute tonsillopharyngitis, Chlamydia and Mycoplasma are not involved in recurrent or chronic tonsillitis.     

Ethical dilemmas in child and adolescent consultation psychiatry.

Ethical issues in child and adolescent psychiatry consultation arise frequently but seldom are discussed in a public setting. This case of an adolescent victim of a surgical accident illustrates many aspects of consultation psychiatry. The consult question itself, of behavior management, is not unusual, although in this case the question is complicated by the sequelae of trauma, psychosocial chaos, and the staff's angry feelings toward the patient. In addition, potential surgical wrongdoing at the referring hospital brings up the more difficult ethical questions of the consultant's responsibilities, which must be to the patient and his family, as well as to the attending and referring physicians.     

Neutrophil cytochemistry in bacterial infection.

A new cytochemical technique, sensitive to altered lysosomal membrane permeability of blood neutrophils, has been evaluated as a screening test for bacterial infection. This technique, for the lysosomal enzymes acid phosphatase and chloroacetate esterase, was compared with the neutrophil alkaline phosphatase and nitroblue tetrazolium tests. The mean score for each method was significantly higher in infected patients than in normal controls. There was, however, considerable overlap of individual scores between infected patients and ill, but uninfected, patients. This overlap limits the diagnostic value of existing cytochemical screening methods.     

Interactions of a non-selective monoamine oxidase inhibitor, phenelzine, with inhibitors of 5-hydroxytryptamine, dopamine or noradrenaline re-uptake

Interactions of combined antidepressants which occur in man were reproduced in rats pretreated with phenelzine, features elicited including myoclonic phenomena, an augmented lower limb flexor reflex, muscle fasiculation and fatalities, particularly with combinations incorporating 5-hydroxytryptamine (5-HT) re-uptake inhibitors. Combinations of antidepressants included phenelzine with 5-HT re-uptake inhibitors (paroxetine, fluoxetine, clomipramine); with "mixed" re-uptake inhibitors affecting 5-HT and noradrenaline (imipramine, amitriptyline); with noradrenaline re-uptake inhibitors (desipramine, maprotiline, nisoxetine) and with dopamine re-uptake inhibitors (benztropine, nomifensine). Myoclonic phenomena such as forelimb flexor-extensor movements, head and body twitches, occurred in phenelzine pretreated rats after paroxetine, fluoxetine, clomipramine, imipramine, amitriptyline and desipramine. Wet dog shakes, the most intense phenomenon, were obtained only after paroxetine, fluoxetine, clomipramine and imipramine. Myoclonic features were prevented when pretreatment included p-chlorophenylalanine but were unaffected when this incorporated alpha-methyl-p-tyyrosine; there were attenuated by methysergide, cyproheptadine, clozapine or pimozide. The myoclonic phenomena were reproduced by combination of 5-hydroxytryptophan but not L-3,4-dihydroxyphenylalanine with clomipramine. Electrocortical changes observed included 2-4 Hz, 5-8 Hz, large amplitude potentials unrelated to the myoclonic incidents and unaffected by sensory stimulation. Following phenelzine, brain monoamine oxidase (MAO) A inhibition was 99% and that of MAO B, 88%; 5-HT concentration was significantly elevated in the cortex and hypothalamus, as was hypothalamic noradrenaline. Peak and basal tensions of a lower-limb flexor reflex were elevated in phenelzine pretreated spinal rats by fluoxetine, paroxetine, clomipramine and imipramine, effects attenuated by cyproheptadine. Forelimb flexor-extensor movements and body twitches were elicited by fluoxetine and paroxetine in phenelzine pretreated spinal rats in the presence of electrical stimulation of the central stump of a divided posterior tibial nerve. Pressor responses were observed in phenelzine pretreated spinal rats given 5-HT re-uptake inhibitors, "mixed" re-uptake inhibitors and those affecting noradrenaline re-uptake; ECG anomalies occurred in such rats given clomipramine.     

Behavioral effects of MK-801 in the rat

Several experiments were conducted to study the effects of the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, on learning and memory in the rat. Rats displayed impaired performance on several sensorimotor tests and appeared grossly intoxicated when treated IP with 0.2 mg/kg MK-801, but not when treated with lower doses (0.05 or 0.1 mg/kg). Postacquisition performance on two spatial learning tasks involving working memory protocols (reinforced alternation and radial arm maze) was impaired by MK-801 at intoxicating doses (0.2 mg/kg) but not at lower doses (0.05 or 0.1 mg/kg). Using a position habit reversal task, we found that rats could learn to reverse a position habit while under the influence of a nonintoxicating dose of MK-801 (0.1 mg/kg), but when tested on the following day performed as if they did not recall what they had learned. Thus, acute administration of a nonintoxicating dose of MK-801 disrupts the retention of new information learned under the influence of the drug but does not interfere with the performance of tasks that are well learned before the drug is administered. Whether the performance deficits on the spatial learning tasks observed only following intoxicating doses of MK-801 reflect an effect on memory is not clear.     

Differential regulation of platelet aggregation by matrix metalloproteinases-9 and -2

We have recently found matrix metalloproteinase-2 (MMP-2) in human platelets and reported that the release of this enzyme during platelet activation stimulates aggregation. We have now identified matrix metalloproteinase-9 (MMP-9) in human platelets and resistance-sized (approximately 200 microm) arteries. Resting platelets released small quantities of pro-MMP-9. Maximal release of MMP-9 was detected during partial (appr. 30% maximum) aggregation with thrombin. However, maximal release of MMP-2 was associated with maximal aggregation. MMP-9 antibodies induced aggregation of resting platelets and potentiated aggregation of platelets induced by thrombin and collagen. Moreover, MMP-9 microisolated from arteries as well as recombinant human MMP-9 (0.1-30 ng/ml) inhibited thrombin and collagen-induced aggregation. We conclude that MMP-9 is an inhibitor of aggregation and in this action opposes the effects of MMP-2. The MMP-2/MMP-9 system may play an important role in the regulation of platelet-platelet and platelet-vessel wall interactions.     

MK-801 neurotoxicity in male mice: histologic effects and chronic impairment in spatial learning

Several histological and behavioral experiments were conducted to investigate the neurotoxic effects of MK-801 in male mice. Moderate subcutaneous (s.c.) doses of MK-801 (0.5 and 1.0 mg/kg) induced the formation of intracytoplasmic vacuoles in pyramidal neurons in layers III and IV of the posterior cingulate/retrosplenial (PC/RS) cortex in 50% and 100% of the mice from the two respective treatment groups. Electron microscopic analysis of the vacuoles indicated that mitochondria and endoplasmic reticulum are the cellular organelles most prominently involved in this pathomorphological change. Treating mice with a high systemic dose of MK-801 (10 mg/kg s.c. or intraperitoneal (i.p.)) caused selective, irreversible degeneration of a small number of PC/RS cortical neurons. Compared to saline controls, the acquisition performance of mice treated i.p. with 10 mg/kg MK-801 was chronically impaired on a spatial learning task (modified hole board food search task) when tested at several posttreatment intervals (up to at least 5 months), although the groups did not differ on activity or sensorimotor tests conducted 2 weeks posttreatment. In summary, MK-801 caused histopathological changes in the mouse brain similar to those observed in the rat. Furthermore, high dose MK-801 treatment that killed a small number of mouse PC/RS cortical neurons resulted in a chronic acquisition impairment in spatial learning, an effect not previously demonstrated in any species.