The relationship of pineal calcification and melatonin secretion to the pathophysiology of tardive dyskinesia and Tourette's syndrome.

Despite current intensive research, the pathophysiology of tardive dyskinesia (TD), a serious neurological side effect of neuroleptic treatment, is poorly understood. Prompted by the observation of an increased incidence and severity of abnormal perioral movements in neuroleptic-treated pinealectomized, as compared to intact rats, we suggested that the pineal gland exerts a protective effect which mitigates against the development of TD and, by inference, that reduced melatonin secretion may be related to the pathophysiology of TD. To investigate this proposition further, we studied the association of TD with pineal calcification (PC) on CT scan in chronic schizophrenic patients. Our findings revealed a significant association between TD and PC and suggest, furthermore, that PC may be a neuroradiological marker of TD. Since PC may reflect diminished secretory activity of the gland, these findings support the hypothesis that the pathophysiology of TD is linked to disturbances of melatonin secretion. The clinical and therapeutic implications of these novel findings are discussed. In the following communication, in which we introduce the hypothesis that disturbances of 5-HT and melatonin secretion are related to the pathophysiology of TD. Subsequently, we present a series of studies which relate to the association of TD with PC. We conclude by presenting the hypothesis that disturbances in melatonin secretion may also be relevant to the pathophysiology of Tourette's syndrome.     

The abdomen, thigh, and arm as sites for subcutaneous sodium heparin injections.

The purpose of this study was to evaluate three subcutaneous injection sites for low-dose heparin therapy (5,000 units). One hundred and one subjects were randomly placed in one of three groups. Group A received injections in the abdomen, Group B, in the thigh, and Group C in the arm. Each subject received three injections at the one site. Activated partial thromboplastin time (APTT) was measured prior to initiation of heparin and again four hours after the first injection. Bruising was measured at 48, 60, and 72 hours postinjection. There were no statistically significant differences among groups for either changes in APTT or bruising at 60 and 72 hours postinjection. Thus the clinical practice of utilizing the abdomen as the only or preferred site for subcutaneous heparin injections was not supported.     

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.     

<Emphasis Type="Italic">Bcl11b</Emphasis>mutations identified in murine lymphomas increase the proliferation rate of hematopoietic progenitor cells

Background  

The telomeric region of mouse chromosome 12 has previously shown frequent allelic loss in murine lymphoma. The Bcl11b gene has been identified and suggested as a candidate tumor suppressor gene within this region. In this study, we aimed to elucidate whether Bcl11b is mutated in lymphomas with allelic loss, and whether the mutations we detected conferred any effect on cell proliferation and apoptosis.     

Chronic exposure of rats to cognition enhancing drugs produces a neuroplastic response identical to that obtained by complex environment rearing.

Recent data suggest that Alzheimer's patients who discontinue treatment with cholinesterase inhibitors have a significantly delayed cognitive decline as compared to patients receiving placebo. Such observations suggest cholinesterase inhibitors to provide a disease-modifying effect as well as symptomatic relief and, moreover, that this benefit remains after drug withdrawal. Consistent with this suggestion, we now demonstrate that chronic administration of tacrine, nefiracetam, and deprenyl, drugs that augment cholinergic function, increases the basal frequency of dentate polysialylated neurons in a manner similar to the enhanced neuroplasticity achieved through complex environment rearing. While both drug-treated and complex environment reared animals continue to exhibit memory-associated activation of hippocampal polysialylated neurons, the magnitude is significantly reduced suggesting that such interventions induce a more robust memory pathway that can acquire and consolidate new information more efficiently. This hypothesis is supported by our findings of improved learning behavior and enhanced resistance to cholinergic deficits seen following either intervention. Furthermore, the level of enhancement of basal neuroplastic status achieved by either drug or environmental intervention correlates directly with improved spatial learning ability. As a combination of both interventions failed to further increase basal polysialylated cell frequency, complex environment rearing and chronic drug regimens most likely enhanced cognitive performance by the same mechanism(s). These findings suggest that improved memory-associated synaptic plasticity may be the fundamental mechanism underlying the disease modifying action of drugs such as cholinesterase inhibitors. Moreover, the molecular and cellular events underpinning neuroplastic responses are identified as novel targets in the search for interventive drug strategies for the treatment of neurodegenerative and neuropsychiatric disorders.