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Charcot-Marie-Tooth type 1A disease (CMT1A) is most frequently caused by a tandem DNA duplication of a 1.4-Mb genomic fragment in the 17p11.2-12 chromosomal region. The disease is probably the product of a dosage effect of the peripheral myelin protein 22 gene located within the duplicated segment. We sought to study the largest reported Brazilian family with suspected diagnosis of CMT1A using eight short tandem repeat microsatellite markers. In addition, we analyzed the informativeness of these markers in the normal Brazilian population. The duplication was found in 12 members of the family. In two patients with CMT1A symptoms, the duplication was not detected, and one asymptomatic subject showed the duplication. D17S2230, D17S9B, D17S2220, D17S2227, D17S9A, and D17S4A markers showed the highest heterozygosity rates, and D17S2228 and D17S2224 markers were the least informative in our analysis.

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Ketamine is an N-methyl-D-aspartate antagonist that induces cognitive dysfunctions. The purpose of the present study was to investigate the effects of a subanesthetic dose of ketamine on human information processing, using the additive factor method. During perfusion of a subanesthetic dose of ketamine (0.5 mg/kg over 60 min) or a placebo (randomized double-blind, cross-over design), eight adults (aged 22-33, mean=27) performed a two-choice visual reaction time (RT) task. Signal intensity, stimulus-response mapping, and foreperiod duration were manipulated. The effects of these three variables were found to be additive on RT, indicating that three independent stages - namely, stimulus preprocessing, response selection and motor selection- were manipulated. Ketamine altered RT performance in a specific way: it interacted with foreperiod duration but its effect was additive with those of signal intensity and stimulus-response mapping. These results show that ketamine specifically affects the stage of motor adjustment, which suggests that the glutamatergic system plays an important role in motor processes.

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The activity of the agonist muscles was recorded during the performance of a two-choice visual reaction time (RT) task in which the compatibility of the stimulus-response mapping was manipulated. Correct trials were distinguished according to whether or not the activation of the agonist of the required response was preceded by an activation of the agonist of the nonrequired response. Double activation trials were more numerous for the incompatible than for the compatible mapping. Furthermore, these trials yielded longer RTs than the single muscular activation trials. These results suggest that initial activations of nonrequired responses are more frequently aborted and corrected when the mapping is incompatible than when it is compatible. This finding supports the dimensional overlap model of stimulus-response compatibility (S. Kornblum, T. Hasbroucq, & A. Osman, 1990).

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The aim of the present study was to assess levodopa (L-Dopa)-induced drowsiness in healthy volunteers using two parameters: choice reaction time and a subjective rating of sedation. Sixteen subjects participated in a randomized, double-blinded, crossover study. A single dose of 200 mg L-Dopa or placebo was administered at 9:00 AM. To limit peripheral side effects connected with L-Dopa, subjects were treated with 20 mg domperidone three times daily. Subjective rating of sedation consisted of visual analogue scale. Reaction time was measured by means of responses to two light-emitting diodes. The illumination of one of these diodes constituted the imperative signal. Manual responses were performed on two buttons located under the right and left index fingers. Results demonstrated a positive correlation between sedation level and reaction time (r = 0.70, p = 0.0026). Adverse events of L-Dopa were nausea (four cases) and excitation (one case). Subjects who did not develop adverse events were faster under L-Dopa than under placebo (p = 0.02), whereas subjects who had nausea or excitation were slower. A single dose of L-Dopa either deteriorated or improved choice reaction time in healthy volunteers according to whether it was sedative and whether it generated disruptive adverse events.

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Sternberg introduced the additive factor method as a tool for discovering and studying in choice reaction time situations in human subjects. Underlying the method is the notion that if information processing consists of successive stages, then different factors affecting different stages must have additive effects on reaction-time measurements. The additive factor method has been extensively used in humans but few attempts have been made to examine whether or not additive reaction time patterns were obtainable in rats. In the present work, the subjects (13 Long-Evans rats) had to press down a lever and to respond to a visual (right or left) stimulus by releasing the lever and introducing the head into a lateral (right or left) operandum. The present findings show an additive pattern of effects of signal luminance and foreperiod duration on the mean reaction time which suggests that we have successfully manipulated two stages of rat information processing - the preprocessing stage and the motor adjustment stage, respectively. Accordingly, the present study sets the basis for the basis for investigating the effects of invasive manipulations (pharmacological and/or lesional) on information processing stages.

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The aim of the present study was to investigate the modulations in amplitude of H reflexes elicited in a hand muscle, the flexor pollicis brevis, during the performance of a choice reaction time (RT) task in which this muscle was directly involved. Ten subjects were to choose between a left- or a right-thumb key-press according to the lateral location of a flash of light. The stimulus-response mapping was either compatible or incompatible. Hoffman reflexes were elicited at different times during the RT by stimulation of the median nerve. Twenty-five milliseconds before the voluntary response, the amplitude of the H reflex suddenly increased when the muscle was involved in the response and decreased symmetrically when the muscle was not involved in the response. Mapping compatibility exerted no detectable influence on the changes in spinal excitability. The latter result supports the assumptions that are at the core of Sternberg's additive factor method.

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Choice reaction time (RT) is shorter when the stimulus corresponds spatially to the response than when the stimulus does not, even when the stimulus location is irrelevant to the task. We used electromyographic measures to document that this effect is the result of a response conflict. The activity of the prime movers of two alternative responses was recorded during the performance of a visual RT task in which the irrelevant spatial correspondence between the stimuli and the responses was varied. Only the premotor component of RT was affected by the stimulus-response correspondence. Correct trials were distinguished according to whether or not the activation of the prime mover involved in the required response was preceded by an activation of the prime mover involved in the alternative response. Double muscular activation trials were more numerous for noncorresponding than for corresponding stimulus-response associations. Furthermore, these trials yielded longer RTs than the single muscular activation trials.

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We report a case of slow-resolving pneumonia secondary to bronchiolitis obliterans organizing pneumonia (BOOP) in a 73-year-old woman. Owing to a delayed diagnosis of BOOP, the clinical course was quite long. This syndrome is caused by a nonspecific inflammatory pneumonitis, either idiopathic or associated with infectious or irritant agents (or drugs). It generally presents as a flu-like illness, followed by progressive dyspnea, cough, fever, and bilateral patchy alveolar infiltrates, and lasts several weeks. The diagnostic work-up of slow-resolving pneumonia is discussed.

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Changes in cortico-spinal excitability related to time and event preparation were investigated by transcranial magnetic stimulation (TMS) of the motor cortex during the foreperiod of a movement-precuing task. Subjects performed a four alternative choice reaction time (RT) task involving a button-press with the index or middle finger (FI) of the left or right hand. Advance information about the to-be-signaled response was provided by a precue, which preceded the response signal by a 1 s foreperiod. The precue either indicated the hand (right or left) or FI (index or middle) with which the response would be executed or was uninformative. TMS was delivered to the left or right cortical hand area at one of five possible times during the foreperiod: -1000, -500, -333, -166 or 0 ms prior to the response signal. Surface EMG activity from a prime mover involved in flexion of the response FIs (Flexor digitorum superficialis) was used to measure the magnitude of the motor evoked potential (MEP) elicited by TMS. Cortico-spinal excitability--as assessed by the magnitude of the MEP evoked in the target muscle contralateral to the stimulated hemisphere--progressively decreased during the foreperiod. The identity of the precued responses, however, had no effect on MEP magnitude. These results suggest that preparation to respond at a particular time inhibited excitability of the cortico-spinal tract, while advance preparation to perform specific responses affected more central structures only.

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Previous studies have shown that fluvoxamine, an inhibitor of serotonin reuptake, shortens choice reaction time. The present study, was intended to explore this effect by using two complementary approaches: (i) Sternberg's additive factor method, and (ii) the analysis of the electromyographic activity of a prime mover. Eight healthy subjects who received either a single oral dose of fluvoxamine (100 mg) or a placebo participated in a choice reaction time experiment in which imperative signal intensity, stimulus-response mapping, and response repertoire were manipulated. Previous results were replicated. Moreover, it was shown that fluvoxamine shortens the interval between prime mover activation and overt response. This supports the hypothesis proposed in a previous study that fluvoxamine affects motor processes. A possible mechanism of this effect is discussed.

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In a previous study where reaction-time methods were combined with transcranial magnetic stimulation (TMS) of the motor cortex, cortico-spinal excitability was shown to reflect time preparation. Provided that subjects can accurately estimate time, the amplitude of motor-evoked potentials (MEPs) diminish progressively during the interval separating the warning signal from the response signal (i.e., the foreperiod). On the other hand, several experiments have demonstrated that the amplitude of the Hoffman (H) reflex elicited in prime movers diminishes during the foreperiod of reaction-time tasks. The aim of the present study was to compare the time course of the respective decrements of H-reflex and MEP amplitude during a constant 500-ms foreperiod. The subjects (n=8) participated in two experimental sessions. In one session, H-reflexes were induced in a tonically activated, responding hand muscle, the flexor pollicis brevis, at different times during the foreperiod of a visual-choice reaction-time task. In the other session, motor potentials were evoked in the same muscle by TMS of the motor cortex delivered in the same behavioral conditions and at the same times as in the first session. The results show that both H-reflexes and MEPs diminish in amplitude during the foreperiod, which replicates and extends previous findings. Interestingly, the time constants of the two decrements differed. There was a facilitatory effect of both electrical and magnetic stimulations on the subject's performance: reaction time was shorter for the trials during which a stimulation was delivered than for the no-stimulation trials. This facilitation was maximal when the stimulations were delivered simultaneously with the warning signal and vanished progressively with stimulation time.

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We report a case of Guillain-Barré syndrome (GBS), requiring prolonged mechanical ventilation, associated at its presentation with thrombocytopenia, in a 50-year-old woman. She was treated with immunoglobulin, and short-term corticosteroids for thrombocytopenia. In spite of the severe presentation we observed a very good and rapid recovery, which could have been determined by the therapeutic association. The incidence of thrombocytopenia in GBS patients could be underestimated, and should be kept in mind in order to avoid hemorrhagic complications.

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Fluvoxamine is a specific serotonin reuptake inhibitor. Recent evidence suggests that this antidepressive drug shortens the reaction time (RT) of healthy volunteers. The first objective of the present study was to decipher whether this effect is due to an improvement in information processing per se or to the adoption of an error-prone strategy. The second objective was to locate the effect of fluvoxamine within the series of information processing stages by means of Sternberg's additive factor method. After administration of a single oral dose of fluvoxamine (100 mg) or a placebo (randomized double-blind, cross-over design), eight healthy volunteers performed a choice RT task in which stimulus intensity, stimulus-response compatibility and response repertoire were manipulated. Fluvoxamine shortened RT without decreasing the accuracy of the responses. This demonstrates that fluvoxamine improves information processing per se. The effect of fluvoxamine was additive on RT with the respective effects of stimulus intensity and stimulus-response compatibility. This result suggests that fluvoxamine spares the processing stages of stimulus preprocessing and response selection.

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A case of severe sepsis caused by Clostridium difficile infection in a 66-year-old cirrhotic female is described. Severe systemic symptoms evolved rapidly to septic shock and ARDS, with signs and symptoms suggesting an acute abdomen requiring exploration for exclusion of surgical treatable diseases. The delayed diagnosis of Clostridium difficile infection probably contributed to the severity of the clinical course.

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It has been shown that transcranial magnetic stimulation can delay simple reaction time; this happens when the stimulation is delivered during the reaction time and over the cortical area which commands the prime mover of the required response. Although it is agreed that magnetic stimulation could be a useful tool for studying information processing in man, we argue that, because of the use of simple reaction time, the results reported so far are difficult to interpret within this theoretical framework. In the present paper, three experiments are reported. Six subjects participated in experiment 1 in which magnetic stimulation was delivered, at different times, during choice reaction time. The effects of the magnetic stimulation of the cortical area involved in the response (induced current passing forward over the motor representation of the responding hand), were compared to the effects of an electrical stimulation of the median nerve (H-reflex). In a first control experiment (experiment 2a; 5 subjects), the coil was placed over the ipsilateral motor cortex (induced current passing backward over the motor representation of the non-responding hand) thus minimizing the probability to excite the same neural nets as in the first experiment. In a second control experiment (experiment 2b; 4 subjects), the coil was placed a few centimeters away from the subject's scalp thus ensuring no stimulation of any neural nets. The results show that: (1) the noise and the smarting of the skin associated with the coil discharge produce an intersensory facilitation thereby shortening reaction time (experiment 2a), (2) actually, the noise produced by the stimulation is sufficient to produce such a facilitatory effect (experiment 2b), (3) a stimulation over the area at the origin of the motor command causes a reaction time delay which counteracts this intersensory facilitation effect (experiment 1), (4) in this latter case, the closer the stimulation to the actual overt response, the longer the delay and (5) there is no trace of correlation between the amplitude of the motor evoked potential and the reaction time change.

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In order to investigate the preparatory modulations of cortico-spinal excitability, reaction time (RT) methods were combined with transcranial magnetic stimulation (TMS) of the motor cortex. We analyzed the variations in the amplitude of motor potentials evoked in a prime mover (flexor digitorum sublimis) by TMS delivered during the foreperiod of a visual choice RT task. In experiment 1 (n = 10), the TMS was delivered either simultaneously with the warning signal or simultaneously with the response signal in two conditions of foreperiod duration: short (500 ms) and long (2500 ms). The peak amplitude of the motor evoked potentials diminished during the short foreperiod but not during the long foreperiod. Since RT was shorter when the foreperiod lasted 500 ms than when it lasted 2500 ms, this result suggests that the excitability of the cortico-spinal structures is minimal when the subject is optimally ready to react. In experiment 2 (n = 10), the time-course of this decrement was further explored. With this aim, only the short foreperiod was used and the TMS was delivered either 500 ms, 333 ms, 167 ms or 0 ms before the response signal. Cortico-spinal excitability decreased during the first 333 ms and then remained stable until the occurrence of the response signal. In light of previous studies, the present results suggest that the decrement of cortico-spinal excitability during the short foreperiod reflects an adaptative mechanism which increases the sensitivity of the motor structures to the forthcoming voluntary command.

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OBJECTIVE: To validate the TRISS method as an audit system on a group of patients with severe trauma admitted to an Italian general intensive care unit (ICU). DESIGN: Prospective, cohort study of consecutive admissions to the ICU. SETTING: A 6-bed general ICU in a 500-bed general hospital. PATIENTS: 190 patients with severe trauma admitted from January 1992 to December 1993 were considered eligible. Patients lacking the data necessary to calculate the TRISS probability of survival, or for whom the ultimate outcome was unknown, were excluded. 162 patients were included in the study. INTERVENTIONS: None. OUTCOME MEASURE: Vital status at discharge from the last hospital that admitted the patient for the trauma being considered. RESULTS: The Hosmer-Lemeshow goodness-of-fit tests were: H = 16.9, df = 10, p = 0.076; C = 5.8, df = 10, p = 0.831; H 3.5, df = 3, p = 0.31. The area under the receiver operating characteristic curve was 0.963 (SE +/- 0.019). Classification measures at a decision criterion of 0.5 were: sensitivity 0.857, specificity 0.964, positive predictive value 0.782, negative predictive value 0.978, total correct classification 0.950, and the Youden index 0.821. The positive likelihood ratio (LHR) was 24.17, whereas the negative LHR was 0.14. CONCLUSIONS: The results of the validation of the TRISS method showed adequate calibration and high discriminatory power in Italian ICU trauma patients also, allowing confidence in the use of this method as an audit tool in our ICU. Some caution is advisable in extending these results to patients with operable intracranial injuries, due to the relatively low number of such cases included in the study.

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