Motor neuron disease with neurofibrillary tangles in a non-Guamanian patient

Neurofibrillary tangles are described in Guamanian and post-encephalitic forms of motor neuron discase (MND) but not in sporadic MND. We report the neuropathological findings in a 79-year-old man who died after a 1-year history of MND without extrapyramidal features or dementia. There was no family history of neurological disease and he had not visited Guam. The spinal cord showed loss of anterior horn cells, and skeletal muscle typical changes of denervation. The brain appeared macroscopically normal but histology revealed many neurofibrillary tangles, particularly in medial temporal lobe structures, insula, nucleus basalis, hippocampus, oculomotor nucleus, raphe nuclei and locus ceruleus. Neurofibrillary tangles were not seen in the primary motor cortex, which appeared histologically unremarkable. Occasional tangles were present in the substantia nigra and pontine nuclei. None were seen in the cerebellum, medulla or spinal cord. The tangles were argyrophilic, and, in sections stained with thioflavin-S, both the intracellular and the extracellular tangles fluoresced strongly under ultraviolet light. The intracellular neurofibrillary tangles reacted strongly with an antibody to tau protein, and only occasional tangles showed weak ubiquitin immunoreactivity. Scattered neuropil threads were present in the cortex in the areas of neurofibrillary tangle formation. No plaques were present in any part of the brain and no A4/ protein immunoreactivity was detected. Ultrastructural examination revealed Alzheimer-type neurofibrillary tangles composed of paired helical filaments. The present findings further extend the spectrum of diverse neurological disorders associated with neurofibrillary tangles.     

Commitment to a regular physician: how long will patients wait to see their own physician for acute illness?

BACKGROUND: Continuity of care with a physician is associated with better health outcomes and greater patient satisfaction. Having a "regular doctor" could lead to greater continuity of care, but only if the patient consistently seeks care from this physician. How long will a patient wait for care if their usual physician is not available? Our study explored factors related to a patient's decision to seek care from another professional. METHODS: We analyzed the results of a statewide random digit dialing telephone survey of 658 Kentucky adults. Our study focused on the 466 adults who indicated they usually seek care from the same physician. Respondents were asked about seeing an alternate provider if they had an acute, non-life-threatening condition and their usual physician was not available. RESULTS: Of the respondents, 48.6% indicated they would seek care from another professional the same day, 41.6% would wait 1 day or more, and 9.8% would not see another professional. Patients with asthma were significantly more likely to wait for care from their regular physician (P <.05), as were patients who usually visited a physician's office instead of a clinic (P <.05). In a multivariate model, seeking alternate care the same day was significantly more likely among patients who were older, nonwhite, and who would seek alternate care at their usual site of care (P <.05). CONCLUSIONS: Maintaining continuity of care with their usual physician is important to patients. Patient and practice characteristics may influence the decision to wait for care in an effort to maintain continuity.     

Neuronal accumulation of poly(ADP-ribose) after brain ischaemia

Animal and in vitro studies suggest that overactivation of poly(ADP-ribose) polymerase (PARP) in response to oxidative DNA damage makes a substantial contribution to cell death after brain ischaemia. We have recently shown that global brain ischaemia due to cardiac arrest in man induces a rapid increase in the amount of neuronal and glial PARP that can be detected by immunohistochemistry. In the present study we sought evidence of a corresponding increase in the amount of poly(ADP-ribose) within the brain, as this would confirm PARP activation and imply resulting consumption of NAD⁺ . We also studied the distribution of poly(ADP-ribose) accumulation in relation to morphological evidence of ischaemic damage, and used double immunolabelling to investigate the types of cell that were affected. We found that global brain ischaemia did cause accumulation of poly(ADP-ribose), particularly during the first 2 days after cardiac arrest. The distribution of cells with accumulation of poly(ADP-ribose) corresponded in general to regions of ischaemic damage or immediately adjacent neocortex. Double immunolabelling for poly(ADP-ribose) and MAP2 showed many of the cells with poly(ADP-ribose) accumulation to be neurons. Our findings are in keeping with experimental evidence of a role for PARP in post-ischaemic necrosis and of the potential for reducing ischaemic brain damage by the use of PARP inhibitors.     

Effects of haloperidol or SCH-23390 on ethanol-induced conditioned taste aversion.

Dopaminergic systems are thought to play an important role in the motivational effects of ethanol. The present experiments examined the effects of haloperidol (a D2 antagonist) and SCH-23390 (a D1 antagonist) on the acquisition of ethanol-induced conditioned taste aversion. In four separate experiments, adult male Swiss-Webster mice were acclimated to a 2-h/day water restriction regimen. Subsequently they received four conditioning trials consisting of 1-h access to either 0.2 M NaCl (experiments 1-3) or 0.15 % w/v saccharin (experiment 4). After flavor access on trials 1-3, subjects received either haloperidol (0.1, 0.15, or 0.3 mg/kg), SCH-23390 (0.05 mg/kg), or saline followed 30 min later by 0, 2, or 4 g/kg ethanol. Ethanol-flavor pairings reduced subsequent flavor intakes, indicating the development of conditioned taste aversion. Neither haloperidol of SCH-23390 reduced flavor intakes in the absence of ethanol. However, both haloperidol and SCH-23390 reduced ethanol-conditioned aversion depending on ethanol dose and conditioned flavor. These results are consistent with the notion that dopaminergic processes are important for the development of ethanol-induced conditioned taste aversion, and the notion that dopaminergic receptor systems influence both positive and negative motivational effects of ethanol.     

Depletion of brain norepinephrine: differential influence on anxiolyic treatment effects

Rationale: Previous studies have demonstrated that anxiolytic-like anticonflict effects can be produced by either (1) acute administration of traditional anti-anxiety compounds (benzodiazepines or barbiturates) or (2) chronic administration of tricyclic (TCA) or monoamine oxidase inhibitor (MAOI) antidepressants. Objective: The present study determined the effects of noradrenergic neuronal depletion on these distinct anticonflict treatments. Methods: After 3 weeks of training in a repeated measures drink suppression conflict paradigm, water-restricted rats consumed 11–14 ml water/session (unpunished responding) and accepted 25–40 shocks/session (punished responding) during control (i.e., non-drug) 10-min test sessions. The noradrenergic neurotoxin DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride; 65 mg/kg, IP] or its vehicle (saline; 1 ml/kg) was administered after 3 weeks of conflict testing. Conflict behavior was then evaluated for 8 weeks post-treatment. In separate groups of DSP4- and vehicle-pretreated subjects, the effects of acute administration (10-min pretreatment) of phenobarbital (5–40 mg/kg) or alprazolam (0.3–2.5 mg/kg) were determined. In a third experiment, the effects of chronic treatment with the TCA desipramine (DMI; 5 mg/kg, twice daily for 8 weeks) or the non-selective MAOI phenelzine (4.0 mg/kg, twice daily for 8 weeks) on conflict behavior were determined in additional groups of DSP4- or vehicle-pretreated subjects. Results: DSP4 treatment produced a modest yet statistically significant decrease in punished responding (i.e., anxiogenic-like effect) relative to vehicle controls. DSP4 pretreatment did not alter the anticonflict effects of acute alprazolam or phenobarbital treatment. In contrast, DSP4 treatment completely abolished the anticonflict effects produced by chronic DMI or chronic phenelzine treatment. Conclusions: Thus, noradrenergic neuronal integrity appears to be required for the anxiolytic-like effects of chronic antidepressant treatment, but not for the anxiolytic-like effects of acute treatment with barbiturates and benzodiazepines. Received: 6 August 1998/Final version: 16 October 1998     

Identification of T cell stimulatory epitopes from the 18 kDa protein of Mycobacterium leprae

We have used different mouse strains to examine in vivo andin vitro responses to the 18 kDa protein of Mycobacterium leprae,which appears to be strongly immunogenic in both mice and humans.B and T cell stimulatory epitopes recognised by different strainsof mice have been mapped using overlapping peptides that spanthe entire 18 kDa protein. Previous work established that Immunizationof mice with the 18 kDa protein results in specific antibodyproduction to common B cell epitopes and immunization of micewith peptides containing these B cell epitopes resulted in theinduction of specific IgG to only a limited subset of epitopesin each strain. Now we report that T cells purified from miceimmunized with peptides that stimulate antibody production,proliferate in vitro when rechallenged. The proliferating Tcells produce levels of IL-2 and IFN-, that indicate antigen-specificT helper type 1 cells are present in significant numbers. Thus,a comparison of in vivo and in vitro data suggests that T cellsbearing the phenotype associated with potentially protectivecell-mediated responses can be primed in vivo by epitopes onsmall peptides. Since T cells from both strains of mice arecapable of responding to the immunogenic synthetic peptidesin vitro, but give different responses to the same peptidesin vivo, factors other than epltope structure appear to influenceT cell subset activation. This may have important implicationsfor diseases such as leprosy where a polarized T cell responseappears to develop and for the development of synthetic subunitvaccines.     

Eating disorders. Highlights of nursing assessment and therapeutics

Nurses providing care for individuals with eating disorders should identify and test the effectiveness of various milieu factors and nursing therapeutics employed in the treatment of these often-debilitating disorders. Nurses offer presence, role modeling, surveillance, and emotional and physiologic support while guiding reluctant patients to explore and experiment with new behaviors. Nurses provide flexibility, empathy, and rational limit setting in response to the unique and shifting needs of each patient. This interpersonal dynamic is often extremely different from that experienced in the patient's family of origin and, thus, contributes to the essential "interpersonal conditions" that are necessary for the patient to engage meaningfully in treatment. The prevalence of eating disorders suggests that nurses are likely to encounter people with eating disorders in many settings. Nurses should be skilled at spotting disordered eating among an array of clinical presentations (e.g., amenorrhea, disturbed family relationships, athletic injuries) because people engaged in disordered eating are hesitant to volunteer such information. In addition to the shame associated with disordered eating is the stigma associated with psychiatric treatment. Seeking help from a nurse may be perceived as less stigmatizing than seeking care from a psychiatrist. Thus, nurses may serve as important points of entry for the hesitant patient. The initial contact is so essential in setting the stage for the continuation and denouement of therapy. Finally, nurses and patients with disordered eating share at least one commonality. Both groups are predominantly women. The prevailing culture has been implicated repeatedly as a major factor in contributing to the prevalence of disordered eating. Nurses experience the influences of paternalism in their professional practice and confront daily the pressures of socially constructed feminine ideals. These gender-sensitive ways of knowing, which nurses bring to the treatment relationship, should be further analyzed as substantive dimensions with treatment and preventive potential.     

Bcl-2 immunoreactive cells with immature neuronal phenotype exist in the nonepileptic adult human brain

Bcl-2, a cell death suppressor protein, is expressed during brain development but is largely down-regulated in the adult central nervous system. We previously reported strong expression of bcl-2 in small, "oligodendrocyte-like" cells (OLC) found in glioneuronal hamartias. These hamartias are microscopic cell rests found in temporal lobe resections from patients with intractable epilepsy and are considered a form of cerebral microdysgenesis. However, a causative relationship between these rests and seizures is not clear. We now report the identification, lineage characterization, and postnatal ontogeny of hamartia-like cell rests in temporal lobes of nonepileptic humans. Postmortem temporal lobes from 28 patients without history of neurologic disease (mean age = 53 years; range = 20 to 83 years) were studied. Microscopic cellular aggregates containing immature-appearing, bcl-2-immunoreactive cells (BIC) (identical to OLC) were observed in 23 of 28 (82%) temporal lobes from nonepileptic individuals. BIC were strongly immunoreactive for neuronal-specific class III beta tubulin, neuronal nuclear antigen, and MAP-2, but were consistently negative for neurofilament proteins and Ki67. Such cells were localized to subventricular regions of the caudal amygdala and often extended into the adjacent subcortical white matter and periamygdaloid cortex. BIC became less abundant with advancing age. These findings suggest that hamartia-like rests containing immature postmitotic neurons are normally present in the human brain and that glioneuronal hamartias may not always represent a maldevelopmental lesion associated with epilepsy.