Pediatric headaches: what do the children want?

One hundred consecutive children (aged 3 to 17 years), drawn from primary care pediatric clinics, with a greater than 3-month history of headaches completed surveys to determine the type and associated features of their headache and to query their reasons for wanting to see a physician. Additionally, the children were asked to draw pictures of how they felt when they had a headache to assess their nonverbal perceptions. Over 90% of the headaches were migrainous (65% common, 23% classic, 5% basilar). The children wanted three answers from the physician: what was the cause of their headache, what would make it better, and reassurance that they had no life-threatening illness. Furthermore, 33% of the children's illustrations disclosed depressive features of helplessness, frustration, and anger. Over 20% of the adolescents depicted themselves as dead, dying, or about to be killed by their headache.

Antihistamine effects on the central nervous system, cognitive performance and subjective states.

Diphenhydramine causes drowsiness and performance decrements in some tasks whereas terfenadine generally does not. This study examined central nervous system (CNS) differences in response to the administration of diphenhydramine (50 mg) and terfenadine (60 mg) up to 3 h after drug administration. Two evoked potential measures, the Brainstem Auditory Evoked Potential and the Pattern Reversal Evoked Potential (PREP), assessed CNS function. Other measures of CNS function, cognitive performance and subjective states administered included Critical Flicker Fusion, the Baddeley Grammatical Reasoning Test, Digit Symbol Substitution, the Profile of Mood States, and the Environmental Symptoms Questionnaire. Significant increases in PREP latencies (N75, P100 and N145) occurred after orally ingesting diphenhydramine. No other significant drug effects were observed. The significant increase in the PREP latencies indicate diphenhydramine's presence in the cerebral cortex results in a slowing of visual information processing. The lack of significant findings for terfenadine is probably a result of its difficulty in penetrating the blood-brain barrier.

Nimodipine improves spatial working memory and elevates hippocampal acetylcholine in young rats.

The calcium channel blocker nimodipine has been reported to improve cognitive performance in aged and brain-damaged animals. In the present study, the effects of nimodipine and placebo on spatial working memory and hippocampal acetylcholine were studied in young Fischer-344 rats. Nimodipine or placebo was administered via subcutaneously implanted, sustained-release pellets. Each active pellet contained 20 mg of nimodipine and released the drug over approximately 21 days. Two days after the drug or placebo pellets were implanted, training in the 8-arm radial maze started and continued for 12 days. Rats were required to learn a win-shift surgery. Nimodipine-treated animals learned the maze more rapidly than a placebo-treated group as indicated by the number of correct choices out of the first eight arms visited (p less than 0.001). Treated rats also made twice as many choices per unit time during the first week of training (p = 0.005). To assess hippocampal acetylcholine release, in vivo microdialysis was performed while animals were awake and unrestrained, 19-21 days after pellet implantation. A probe with a 3 mm semipermeable tip was placed in the hippocampus (CA1 and dentate gyrus), and individual microliters dialysate samples were collected at 2 microliters/min and immediately analyzed by high performance liquid chromatography with electrochemical detection. Significantly higher extracellular ACh levels were found in nimodipine-treated rats (71.4 +/- 3.6 nM; n = 4) compared to controls (52.5 +/- 2.5 nM; n = 5) (p = 0.003) and in another group of rats of the same age that received identical drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclo (His-Pro), d-amphetamine and striatal dopamine: a microdialysis study.

Extracellular levels of dopamine (DA) and its metabolites (DOPAC and HVA) were monitored in the striatum of rats using in vivo microdialysis, in an attempt to elucidate the mechanism of cyclo (His-Pro) (histidyl-proline-diketopiperazine, CHP) on dopaminergic activity. Pretreatment with CHP (0.5 mg/kg SC) (n = 5) or the equivalent volume of saline (n = 5) was followed 30 min later by 5 mg/kg IP of d-amphetamine. Dialysate samples were collected and analyzed by high performance liquid chromatography with electrochemical detection (HPLC-EC). Following the initial increase in DA caused by d-amphetamine, DA levels of CHP-treated rats were significantly lower than saline-treated rats across time (p less than 0.05). No difference was observed for DOPAC or HVA. It is therefore unlikely that CHP interferes with the d-amphetamine-induced inhibition of DA reuptake. Other neurotransmitter systems may be involved in the CHP-induced augmentation of amphetamine's behavioral effects. Our data, as well as previous findings, suggest that attenuation of the dopaminergic response to d-amphetamine might be best explained on the basis of striatal DA depletion, possibly via tyrosine hydroxylase (TH) inhibition. This study also indicates that a dissociation may exist between the behavioral and the striatal DA response to acute amphetamine. The data support the hypothesis that amphetamine releases DA from a newly synthesized, extravesicular cytoplasmic pool, and that intracellular striatal DA is present in considerable excess relative to the extracellular DA.

Altitude symptomatology and mood states during a climb to 3,630 meters.

Ascents to altitudes above 3,050 m have been shown to cause adverse changes in symptoms and moods. The severity of these changes may depend not only on the altitude and rate of climb, but also on the length of stay and the effort expended to reach the desired altitude. In order to better understand how these factors influence symptom and mood changes during a climb, this study systematically assessed symptoms and moods during an ascent to 3,630 m. Self-rated symptoms and moods were determined in seven male volunteers over a period of 7 days (d) during a climb to 3,630 m of Mount Sanford, AK. The subjects were tested five times--twice at 2,225 m, then at 2,530, 3,080, and 3,630 m. Symptoms and moods were assessed with the Environmental Symptoms Questionnaire (ESQ) and the Profile of Mood States (POMS), respectively. Seven symptom factors and two mood factors were found to be adversely affected over time by the changes in altitude. More specifically, the subjects experienced more respiratory acute mountain sickness (AMS), exertion stress, and muscular discomfort and they were also colder, less alert, less vigorous, and more fatigued at higher elevations. These changes occurred primarily at 3,630 m and most also occurred at 3,080 m.(ABSTRACT TRUNCATED AT 250 WORDS)

Tyrosine pretreatment reverses hypothermia-induced behavioral depression.

Cold exposure accelerates the firing frequency of norepinephrine (NE) neurons, enhancing NE release and leading to NE depletion in specific regions of the brain. The accelerated firing activates the enzyme tyrosine-hydroxylase, making it more tyrosine sensitive. The reduction of brain NE is accompanied by a behavioral depression on the open field test. Two experiments were performed on adult male rats. First, it was determined whether systematic lowering of core body temperature produced behavioral depression in the swim test. Second, treatment with the NE precursor tyrosine was employed in an attempt to prevent hypothermia-induced behavioral depression. In Experiment 1, two levels of hypothermia were highly effective in producing behavioral depression in rats forced to swim in a narrow cylinder. In Experiment 2, treatment with tyrosine (400 mg/kg, IP) thirty minutes prior to the hypothermia procedure completely reversed the behavioral depression found in Experiment 1. Tyrosine administration did not significantly influence the rate of deep body cooling during the hypothermia treatment.

Atropine sulfate impairs selective parameters of performance in the Morris water maze.

Twelve rats were trained to learn the location of a spatially fixed platform hidden in a Morris water maze. Asymptotic performance was achieved over six training days (10 trials/day). Then retention of the spatial task was assessed 30 min after treatment with 5, 25, 50, 75, or 100 mg/kg, ip, atropine sulfate or the equivalent volume of saline. There was a significant drug effect on escape latency, swim distance, swim speed and swim path measures of spatial performance. There was no significant drug effect on heading error; atropinized animals initially headed toward the escape platform over the first 12 cm of their swim path. However, treatment with atropine sulfate significantly disrupted the usual, direct swim path used to reach the hidden escape platform. Atropinized animals frequently swam a spiraled or looping pattern to locate the platform. We suggest that cholinergic blockade may significantly disrupt the processing of visual cues which rats use in place navigation tasks.

Hyperthermia impairs retrieval of an overtrained spatial task in the Morris water maze.

Fifteen rats were trained to learn the location of a spatially fixed platform hidden in a Morris water maze (40 +/- 2 degrees C). Then retention of the spatial task was assessed immediately after raising core body temperature (Tc) to 42 or 40 degrees C or stabilizing at 37 degrees C (the normothermic control). The hyperthermic treatment order was counterbalanced according to a Latin-square design. Hyperthermia at 42 degrees C Tc significantly impaired spatial performance. Hyperthermic animals were cooled to normothermia (Tc = 37 degrees C) and spatial performance was tested again approximately 30 min later. Cooling resulted in a complete recovery of spatial performance. These results demonstrate that hyperthermia-induced amnesia can be obtained on an overtrained spatial-mapping strategy and cooling to normothermia initiates recovery of spatial performance.

Hypothermia impairs performance in the Morris water maze.

Fifteen rats were trained to learn the location of a spatially fixed platform hidden in a Morris water maze (14-16 degrees C). Asymptotic performance was achieved over six training days (10 trials/day). Then retention of the task was assessed immediately after lowering core body temperature (Tc) to 28 degrees or 30 degrees C or stabilizing at 37 degrees C (the normothermic control). The hypothermia treatment order was counterbalanced according to a Latin-square design. Hypothermia significantly impaired all measures of spatial performance. Hypothermic animals were then rewarmed in a 40 degrees C water bath to 37 degrees C Tc and spatial performance tested again. Artificial rewarming resulted in complete recovery of all measures of spatial performance. These results demonstrate that hypothermia impairs performance in the Morris water maze, possibly by an amnesic mechanism, and that returning Tc to normothermic levels initiates recovery of performance.

Low doses of atropine sulfate impair retention of a well-learned spatial task.

Retention of a well-learned spatial task was assessed in rats 10 minutes prior to, and 10, 20, 30, 40, and 50 minutes after treatment with 3, 10 or 30 mg/kg, iv, atropine sulfate or the equivalent volume of saline, iv. There was a variable dose effect for escape latency and choice accuracy measures of spatial retention. A relatively large dose of atropine sulfate (30 mg/kg, iv) significantly impaired choice accuracy and escape latency compared with the control group. Moreover, impairment in choice accuracy was observed with smaller doses of atropine sulfate (3, 10 mg/kg, iv) than have previously been shown to disrupt spatial retention.

Retention of a spatial task after intraperitoneal, subcutaneous or intravenous injections of equal doses of atropine.

The retention of a well-learned spatial task was assessed in rats after equal doses of atropine sulfate (30 mg/kg) were administered by intraperitoneal, subcutaneous or intravenous injection. Atropine sulfate disrupted first choice accuracy and escape latency measures of spatial retention. Intravenous and intraperitoneal atropine sulfate produced significant impairments in choice accuracy. However, only intravenous atropine sulfate produced a significant impairment in escape latency. Atropine sulfate administered subcutaneously never produced a significant impairment in spatial retention compared to the intravenous saline control. One would predict from the present findings that a centrally active drug might produce a highly variable effect on a specific behavior as a function of the parenteral route of administration.

Job satisfaction in the practice of clinical pharmacy.

Two groups of pharmacists (n = 69) assigned to 35 US Army Medical Treatment Facilities were surveyed to assess job satisfaction. Pharmacists providing patient care were significantly more satisfied on intrinsic job satisfaction measures than pharmacists not providing patient care. On the other hand, no significant difference in satisfaction was found between pharmacy groups on extrinsic job satisfaction measures. The results are discussed relative to intrinsic and extrinsic sources of job satisfaction and patient care.

The additive effects of two mutant genes on otolith formation in mice: an animal model to assess otolith function.

This study examined the additive effects of two mutant genes, pallid (pa) and tilted head (th), on otolith formation in mice. Four strains of mice were bred: (1) a control strain, heterozygous for both pa and th. (2) a pallid strain, homozygous for pa, (3) a tilted head strain, homozygous for th, and (4) a double mutant strain, homozygous for both pa and th. The results were confirmed (1) behaviorally, by the animals' ability to swim, and (2) by histological examination of the inner ear. The findings suggest significant differences in mean otolith scores between all possible pairs of strains. As expected, the controls had normal otoliths and the pa/th strain the most severe otolith defects. Furthermore, there was a significant directional asymmetry in mean otolith scores between the utricle and saccule of the R and L ears for both pa and th strains. The results also showed a highly significant linear relationship between poor swimming ability and reduction of otoconia (r = 0.94, F = 92.14, p less than .001).