Around the clock surveillance: simple graphic disturbance in patients with hemispatial neglect carries implications for the clock drawing task.

BACKGROUND: Drawing, and the clock drawing task in particular, is widely used as a diagnostic tool in the study of hemispatial neglect. It is generally assumed that the errors in graphic production, such as the misplacement of numbers, reflect a visuospatial deficit, and that drawing production itself (for example, producing the circle) is unimpaired. OBJECTIVES: To test this assumption by examining whether the production of simple circles is affected by neglect. METHODS: 16 right hemisphere stroke patients copied circles of various sizes and their drawings were measured for size accuracy. RESULTS: Patients with more severe neglect produced greater scaling errors, consistently drawing the circle smaller than the original. Errors were not in the horizontal axis alone--shrinkage occurred equally in both height and width axes. CONCLUSIONS: Neglect can co-occur with constructional difficulties that serve to exacerbate the symptoms presented. This should be taken into account in the assessment of even apparently simple drawing tasks.

Monoarthritis induces complex changes in mu-, delta- and kappa-opioid binding sites in the superficial dorsal horn of the rat spinal cord.

Recently, an experimental model of monoarthritis was described in the rat induced by injection with Freund's adjuvant of the tibio-tarsal joint of one hindlimb. After injection, the clinical and behavioural signs of arthritis are stable from weeks 2 to 6 post-injection. Our purpose was to study the regulation of mu-, delta- and kappa-opioid binding sites in the superficial layers (laminae I-II) of the lumbar and cervical enlargements of the spinal cord 2, 4 and 6 weeks post-injection. Using quantitative receptor autoradiography and highly selective opioid ligands, we found complex changes consisting of a bilateral increase in specific [3H]DAMGO (Tyr*-D-Ala-Gly-NMe-Phe-Gly-ol) and [3H]pCl-DPDPE (Tyr*-D-Pen-Gly-Cl-Phe-D-Pen) binding at 2 weeks post-injection and a bilateral decrease in [3H]U-69593 ((5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-[7-(1-pyrrolidinyl)-1- oxaspiro(4,5)dec-8-yl]) specific binding at 4 weeks post-injection. These changes were restricted to the lumbar level. At 6 weeks post-injection, there was a bilateral increase in [3H]pCl-DPDPE specific binding at both lumbar and cervical levels. Altogether, these results suggest that, after probable local changes in endogenous opioid peptides, the three types of opioid binding sites are differentially involved in the development of the pathological process. These results contrast with the lack of significant modification in mu-, delta- and kappa-opioid binding classically reported at various levels of the spinal cord in polyarthritic rats at 3 weeks post-injection and verified for 2, 4 and 6 weeks post-injection in the present study.

Decreased cerebrospinal fluid neuropeptide-converting enzyme activity in monoarthritic rats.

The activity in rat cerebrospinal fluid (CSF) of dynorphin-converting enzyme (DCE) and substance P endopeptidase (SPE) was determined in control animals and in rats with monoarthritis. Enzymatic activities were measured with specific radioimmunoassays toward the N-terminal products Leu-enkephalin-Arg6 and substance P1-7, respectively. A monoarthritis stable during weeks 2-6 post-injection was induced by injection (0.05 ml) into one joint with Freund's adjuvant. Both SPE and DCE were significantly decreased 15 days after the intraarticular injection. Despite the degree of arthritis that was sustained equally at four weeks after inoculation, both DCE and SPE were back to control levels at that time. It can therefore be concluded that arthritis from a single joint is sufficient to elicit changes in CSF convertase activities, and that these effects disappear between 2 and 4 weeks after injection, although the arthritis persists.

Pharmacologic treatment of low back pain.

This article provides basic pharmacologic and behavioral principles and facts to simplify drug therapy for low back pain. It outlines basic protocols for symptom control while definitive treatments are beginning or healing occurs.

Increase in "pain sensitivity" induced by exercise applied during the onset of arthritis in a model of monoarthritis in the rat.

We have recently developed, in the rat, a model with a limited arthritic process for chronic pain studies. Intra-articular injection (0.05 ml) of complete adjuvant containing 300 micrograms Mycobacterium butyricum in the tibio-tarsal joint produces a predictable monoarthritis stable clinically and behaviourly from weeks 2 through 6 post-injection. This model appears to be a suitable alternative for the polyarthritic rat for chronic studies based on both its ethical and scientific advantages. In the present work we report results of experiments on the effects of exercise on the pain behaviour and development of arthritis in this model. A group of rats prepared with the above protocol was submitted at 2 weeks post-inoculation to mild exercise (swimming [water 37 degrees C] three times per week) increasing from 5 to 15 min during 4 weeks. As revealed by analyses of the arthritis score, the stiffness score and the mobility score, no aggravation of arthritis occurred in these rats. However the threshold for struggle in response to paw pressure was further decreased (as compared to control arthritic rats) in these animals. These results are discussed in view of observations made in human studies.

Resistance to atracurium in thermally injured rats. The roles of time, activity, and pharmacodynamics.

Thermal injury induces resistance to nondepolarizing muscle relaxants in patients. Because the mechanism of the resistance is unknown, the authors have sought to establish thermally injured rats as a suitable model for subsequent detailed studies of mechanisms. Two hundred twenty-five- to 250-g rats sustained a 30% total body surface area thermal injury while anesthetized with pentobarbital. Another group had sham injury. Animal activity was monitored both by periods of direct observation and by use of activity cages. At 10, 20, 30, 40, 60, and 90 days after injury, rats were anesthetized and ventilated and the strength of contraction of their gastrocnemius produced by supramaximal stimulation of the sciatic nerve was measured before and after a bolus of atracurium (2.0 mg/kg) was administered. The plasma concentration required to diminish contraction to 50% of the preceding value (Cp50) was determined by atracurium infusion. Animals displayed the greatest resistance to atracurium at 40 days. The Cp50 value was also greatest at this time. The protein binding of atracurium was identical for both sham and injured groups. Activity for thermally injured resistant rats and for sham animals was not different. It appears that pharmacodynamic mechanisms are involved, and inactivity and disuse atrophy are not necessary in rats for development of resistance to nondepolarizing muscle relaxants after thermal injury.

Opiate analgesia and its antagonism in dental event-related potentials: evidence for placebo antagonism.

The analgesic effects of the synthetic opiate fentanyl citrate (0.1 mg) on subjective pain reports (SPR) and late-wave event-related potentials (ERP) recorded during painful dental stimulation were examined in human subjects. Such waves have been shown to reflect the contribution of cognitive variables, such as expectancy and belief, to perception. In addition, the study was intended to demonstrate a dose-related narcotic antagonism with injection of naloxone (1.2 or 0.4 mg) or normal saline (double-blind) following IV fentanyl administration. Fentanyl reduced both ERP waveform amplitudes and SPR as have previously studied analgesic agents, such as nitrous oxide, acupuncture, and aspirin. Naloxone injection reversed both ERP and SPR changes, but surprisingly, a reversal of narcotic analgesia equal to that of 0.4 mg naloxone was seen with saline injection. By chance, all subjects were health-science students or professionals who were knowledgeable in opiate pharmacology, and so placebo reversal was hypothesized. Alternatively, it was hypothesized that fentanyl cleared more rapidly than predicted, thus, producing apparent reveal. In a second experiment involving similarly knowledgeable subjects with identical procedures and testing intervals, subjects received 0.1 mg fentanyl, but no reversal injection. The fentanyl effect was constant across this time period. The data, thus, support the hypothesis where the subjects were knowledgeable in opiate pharmacology, was placebo opiate antagonism.

Blockade of the pressor response to muscle ischemia by sensory nerve block in man.

Differential nerve block from peridural anesthesia was used to determine a) if the pressor response to muscle ischemia in man is caused by stimulation of small sensory nerve fibers and b) if these fibers contribute to cardiovascular-respiratory responses during dynamic exercise. Four men exercised at 50-100 W for 5 min. Muscle ischemia and a sustained pressor response were produced by total circulatory occlusion of both legs beginning 30 s before the end of exercise and continuing for 3 min postexercise. During regression of full motor and sensory block, motor strength recovered while sensory block continued; the pressor response was blocked as long as sensory anesthesia persisted (two subjects). During blockade of the pressor response, cardiovascular-respiratory responses to exercise gradually returned from augmented to normal (preblock) levels. Sensory blockade was incomplete in two subjects and the pressor response was not fully blocked. We conclude that stimulation of small sensory fibers during ischemia elicits the pressor response, but that these fibers appear not to contribute to cardiovascular-respiratory responses during mild dynamic exercise with adequate blood flow.

Analgesic strength of 33 percent nitrous oxide: a signal detection theory evaluation.

Radiant heat stimulation was applied to volunteers and rating scale responses were obtained to assess the analgesic properties of 33 percent nitrous oxide. The methodology of signal detection theory was applied to the data to demonstrate that nitrous oxide reduces both sensitivity to pain and willingness to report pain. This method is superior to threshold estimation for the evaluation of analgesics.