Corticofugal modulation of the information processing in the auditory thalamus of the cat

Summary Single unit activity of 355 cells was recorded in the auditory thalamus of anesthetized cats before, during, and after the inactivation by cooling of the ipsilateral primary auditory cortex (AI). Most of the units (n = 288) showed similar functional characteristics of firing before and after the cryogenic blockade of AI. The spontaneous firing rate remained unchanged by cooling in 20% of the units and decreased in the majority of them (60%). In some regions, i.e. dorsal division of the medial geniculate body (MGB), lateral part of the posterior group of the thalamus, and auditory sector of the reticular nucleus of the thalamus, the maximum firing rate evoked by white noise bursts was generally affected by cooling in the same direction and to the same extent as the spontaneous activity. Units in the ventral division of MGB showed a characteristic increase of signal-to-noise ratio during cortical cooling. The corticofugal modulation led to the appearance or disappearance of the best frequency of tuning in 51 units and changed it by more than 0.5 octave in 34 units. The bandwidths of different response patterns to pure tones stimulation were used to define a set of functional properties. During cryogenic blockade of AI, two cortically modulated sub-populations of units were usually distinguished that exhibited changes for a given functional property. The complexity and diversity of the effects of cortical inactivation suggest that the corticothalamic projection may be the support for selective operations such as an adaptive filtering of the incoming acoustic signal at the thalamic level adjusted as a function of cortical activity.     

Controversies in tuberculosis

Tuberculous infection among children continues to be a significant cause of morbidity. The symptom complex are so variable among children that the final diagnosis often rests on the laboratory tests. Proper interpretation of the tests, specially tuberculin test and radiographic studies, are necessary for establishing correct diagnosis. The usefulness of tuberculin test in both unimmunized and BCG vaccinated children is highlighted. BCG accelerated response as a test should be reserved for identifying serious form of pulmonary disease or CNS tuberculosis when the tuberculin test is negative. Radiographic assessment may be sensitive in some instances but not always specific and hence needs cautious interpretation. Tuberculosis among BCG vaccinated children though not uncommon, needs proper documentation. Current trends in the management of tuberculosis including CNS forms are briefly outlined.     

Embedding Medical Student Computer Tutorials into a Busy Emergency Department

Objectives
To explore medical students' use of computer tutorials embedded in a busy clinical setting; to demonstrate that such tutorials can increase knowledge gain over and above that attributable to the clinical rotation itself.
Methods
Six tutorials were installed on a computer placed in a central area in an emergency department. Each tutorial was made up of between 33 and 85 screens of information that include text, graphics, animations, and questions. They were designed to be brief (10 minutes), focused, interactive, and immediately relevant. The authors evaluated the intervention using quantitative research methods, including usage tracking, surveys of faculty and students, and a randomized pretest-posttest study.
Results
Over 46 weeks, 95 medical students used the tutorials 544 times, for an overall average of 1.7 times a day. The median time spent on completed tutorials was 11 minutes (average [SD], 14 [±12] minutes). Seventy-four students completed the randomized study. They completed 65% of the assigned tutorials, resulting in improved examination scores compared with the control (effect size, 0.39; 95% confidence interval = 0.15 to 0.62). Students were positively disposed to the tutorials, ranking them as "valuable." Fifty-four percent preferred the tutorials to small group teaching sessions with a preceptor. The faculty was also positive about the tutorials, although they did not appear to integrate the tutorials directly into their teaching.
Conclusions
Medical students on rotation in a busy clinical setting can and will use appropriately presented computer tutorials. The tutorials are effective in raising examination scores.     

Prolactin responses to haloperidol in drug-free and treated schizophrenic patients

Summary The prolactin response to 5 mg haloperidol i.m. was studied in 12 schizophrenic patients in a drug-free state and after a month treatment with haloperidol, as a possible index of dopamine receptor sensitivity and occupancy. Blood samples were taken at times 0, 60, 90 and 120 minutes. The increase in PRL observed in the drug-free state disappeared after drug treatment. The PRL plasma levels after treatment with 60 mg haloperidol per os were higher than the maximal PRL responses after 5 mg i.m. The increases in baseline PRL caused by the treatment correlated positively to the reduction in the BPRS score. The test was also performed in a group of 11 patients chronically treated with haloperidol during a daily dose of 60 mg, and 15 days after reduction of the dose to 30 mg. PRL increases after 5 mg haloperidol i.m. were observed only after reduction of the dose. It is suggested that the prolactin response to haloperidol is an index of the occupancy of receptors that are involved in the PRL releasing mechanisms, and could be used to verify their blockade by the neuroleptics, especially in patients that do not respond positively to drug treatment.     

Coronavirus induced primary demyelination: indications for the involvement of a humoral immune response

Coronavirus MHV-JHM infection of rodents can result in demyelinating encephalomyelitis. We analysed histological changes induced by coronavirus MHV-JHM infection in Lewis rats. Besides an acute disease (AE), chronic panencephalitis (CPE) and subacute demyelinating encephalomyelitis (SDE) were induced. These disease types were differentiated by the incubation period, the localization of lesions, the type of tissue damage and distribution of virus antigen. In AE and CPE, virus antigen was detected in neurons, astrocytes and oligodendrocytes, whereas in SDE neurons lacked virus antigen. Viral nucleocapsid protein (N) was present in the cytoplasm and the spike protein (S) was displayed on the surface of infected neural cells. However, expression of S protein relative to N protein was severely impaired in SDE lesions. Quantitative analysis of infiltrating inflammatory cells revealed that the number of macrophages and T cells were similar in lesions of AE, CPE and SDE. In contrast to that, SDE lesions contained a significantly higher number of IgG + B cells and plasma cells. In addition active demyelinating SDE lesions displayed an enhanced IgG content and deposits of complement C9. These results indicate that virus induced primary demyelination could be a consequence of antibody mediated cytotoxicity. Furthermore, a reduction in the number of cells producing spike protein in the chronic forms of the disease indicates down-regulation of this protein, possibly mediated by anti-S antibodies.     

Effects of the phosphodiesterase inhibitor rolipram on the acoustic startle response in rats

Systemic administration of the phosphodiesterase inhibitor rolipram (0.05–10.0 mg/kg, IP) produced a rapid and dose-related increase in the amplitude of the acoustic startle response in rats. The (−) isomer was more potent than the (+) isomer in enhancing startle amplitude. Rolipram increased startle responses that were elicited by brief electrical stimulation of the ventral cochlear nucleus or nucleus reticularis pontis caudalis, two brainstem relay nuclei of the startle neural circuit. A low (5 μg) dose of rolipram produced an excitatory effect on startle following spinal (lumbar intrathecal) infusion but not following supraspinal (lateral ventricle) infusion. Rolipram (0.5 mg/kg, IP) excitation of startle was not blocked by drugs which differentially disrupt the release of monoamines (DSP4, reserpine + alpha-methylpara-tyrosine, reserpine + para-chloro-phenylalanine) or by drugs which differentially block monoamine receptors (haloperidol, prazosin, idazoxan, cinanserin, or cyproheptadine). The marked increase in startle seen following systemic rolipram injection is attributable, at least in part, on an action in the lumbar spinal cord that directly or indirectly facilitates neural transmission along the reticulospinal component of the startle reflex neural pathway. The startle reflex should be a useful behavioral test system for studying the mechanism of action of rolipram and related compounds purported to selectively inhibit calmodulin-independent forms of phosphodiesterase.     

A Retrospective Review of the Use and Safety of Droperidol in a Large, High-risk, Inner-city Emergency Department Patient Population

Droperidol (DROP) is used in the emergency department (ED) for sedation, analgesia, and its antiemetic effect. Its ED safety profile has not yet been reported in patients (pts). OBJECTIVES: To document the use of DROP in high-risk pts (those with head injury, alcohol or cocaine intoxication, and/or remote or recent seizures), and to determine the number of serious and minor adverse events (AEs)-seizures, hypotension, extrapyramidal side effects (EPSEs)-after DROP. METHODS: The ED database (EmSTAT) was queried to determine who received intramuscular or intravenous DROP in the ED in 1998; further chart review was done if the patient was considered high risk for or had experienced an AE. Multiple regression analysis using a random-effects model determined the significance of each variable in the occurrence of AEs. RESULTS: 2,468 patients (aged 20 months to 98 years; 112 < or =17 years; 141 > or =66 years) received DROP for agitation (n = 1,357), pain (1,135), anxiety (99), vomiting (173), or other reasons (50). There were 945 pts considered high risk; 933 charts were reviewed (DROP mean dose 4.1 +/- 2.0 mg); of these, 50 patient visits did not meet the criteria for high risk. There were 622 pts with head trauma (401 with alcohol use), including 47 with computed tomography (CT) scans positive for brain injury, 64 with cocaine use, and 197 with recent or remote seizures (137 with alcohol use). Minor AEs such as transient hypotension occurred in 96 pts after DROP (73 with alcohol use); 20 received intravenous fluids, while an additional 28 pts (8 with alcohol use) received rescue medications for EPSEs. Six possible serious AEs occurred in pts with serious comorbidities; 2 cases of respiratory depression, 3 post-DROP seizures, and 1 cardiac arrest (resuscitated) 11 hours after DROP in a cocaine-intoxicated pt (normal QT interval). There was no significant difference among high-risk groups in the occurrence of AEs. CONCLUSIONS: The vast majority of pts who received DROP in the ED did not experience an AE. A few serious AEs were noted following DROP in patients with serious comorbidities; it is not clear that DROP was causative.     

Effects of propofol emulsion and thiopentone on T helper cell type-1/type-2 balance in vitro

We have earlier found increased percentages of T helper cells (CD4-positive lymphocytes) in the blood circulation after propofol infusion anaesthesia. Cytokines interferon-γ (IFNγ) and interleukin-4 (IL-4) are important in the differentiation of T helper cells into subtypes T helper type-1 (Th1) and type-2 (Th2). To study the effects of propofol emulsion, its solvent Intralipid^® and thiopentone on Th1/Th2 balance, measurements of IFNγ and IL-4 production by mononuclear leucocytes were carried out in vitro . As IL-2 has a central role in immune responses to surgery, its production was also measured. Concanavalin A-stimulated mononuclear cells were cultured in the presence of propofol emulsion at 3.5 or 10 μg.ml⁻¹, Intralipid^® 35 or 100 μg.ml⁻¹, or thiopentone 3 μg.ml⁻¹. Cytokine production was measured from the conditioned media of mononuclear cell cultures. Decreased IFNγ (p <0.001) and IL-4 concentrations (p < 0.01) were found in the presence of thiopentone, but IL-2 production was unaffected. By contrast, propofol emulsion or Intralipid^® had no effects on IFNγ, IL-2 or IL-4 concentrations. Propofol 10 μ.ml⁻¹ increased the IFNγ/IL-4 ratio from the control value median 243 (162–562) (25th–75th percentile) to 363 (195–1028) (p < 0.01), but thiopentone decreased it to 145 (60–214) (p < 0.01). These findings show that propofol and thiopentone have different effects in vitro on Th1/Th2 balance and suggest that they have different modulating effects on the immune response.     

临床肿瘤用药的统计分析

[目的]了解肿瘤用药的消费现状及发展趋势，为临床合理用药提供依据。[方法]对本院1996年-2002年抗肿瘤药、生物反应调节剂和升白细胞药的用药情况进行统计分析，以药品的年消耗金额作统计。[结果]抗肿瘤药、生物反应调节剂和升白细胞药分别占全部药品年消耗总金额的24．24％～33．73％、15．80％～23．33％和5．86％～9．11％。[结论]抗肿瘤药、生物反应调节剂和升白细胞药是用于肿瘤治疗的主要药品，尤其是抗肿瘤天然药物有着广阔的应用前景。