Uric acid and renal function in multiple sclerosis.

OBJECTIVE: The purpose of this study was to examine the circadian distribution of creatinine and uric acid clearances in subjects with Multiple Sclerosis. MATERIALS AND METHODS: Eleven subjects with MS, 6 women (48+/-7y) and 5 men (58+/-5y) volunteered for this circadian study. Thirteen healthy females (39+/-11y) served as controls. Data of seven healthy male controls (64+/-8 y) were extracted from a similar circadian study conducted previously. Each MS patient, and each male control had blood samples drawn around the clock, at 3h intervals (8/24h), and each collected urines over 3h periods (8/24h). Each female control contributed only one blood sample and one complete 24h urine collection. Blood and urine samples were analyzed for a number of relevant analytes: ELAM, IL-6, NO, insulin, ACTH, aldosterone, cortisol, electrolytes, lymphocytes, monocytes including creatinine and uric acid clearances. Those were standardized to an average body surface area of 1.73 m2. RESULTS: The relevant analytes demonstrated increased synthesis of insulin, IL-6, ELAM, monocytes, and reduced concentrations of serum NO. The creatinine clearances were significantly lower in MS females than in female controls, 63+/-22 vs.108+/-18 ml/min. They were also lower than those of MS males and male controls, 107.8+/-17, 97.5+/-8.2 ml/min. Uric acid clearances in MS females were also lower 6.9+/-2.4 vs. 10.5+/-4.4 ml/min. The uric acid clearance in MS males was higher than in male controls, 7.0+/-4.5 vs. 4.0+/-1.0 ml/min. CONCLUSIONS: The alterations in selected relevant analytes and the reduced creatinine and uric acid clearances in females but not in males, suggest a renal dysfunction in MS females. These observations may contribute to understanding better the mechanism of renal dysfunction in female patients and perhaps this may be an additional factor contributing to greater frequency of MS in females than in male subjects.

Circadian distribution of iron and ferritin in serum of healthy and type 2 diabetic males.

AIM: We examined the circulating levels of iron and ferritin in serum of seven healthy and three insulin non-dependent diabetic (Type 2) males in order to compare their circadian characteristics. METHODS: Blood samples were collected every 3h over a 24h period and were analyzed for serum iron and ferritin. RESULTS: The mean Fe level was significantly higher in healthy than in diabetic subjects: 80.0 +/- 3.3 vs. 63.0 +/- 3.7 microg/dL. The ferritin level was significantly lower in healthy than in diabetic men: 79.8 +/- 4.7 vs. 186.3 +/- 110.5 microg/L. A significant (p < 0.001) time-effect was found by ANOVA and circadian rhythm was detected at p < 0.001 in all data sets when a 24h cosine was fitted to the normalized data. Acrophases were located in mid to late morning for Fe (11:30, vs. 09:22h) and for ferritin (11:10 vs. 11:46h). DISCUSSION: We concluded that there is significant circadian variation in both serum Fe and ferritin, with predictable peaks in the mid to late morning.

Cardiac reactions to two psychological stressors, acting in combination.

56 student volunteers (mean age 21 yr.) participated in a study designed to assess how the Stroop procedure and delayed auditory feedback affect cardiac activity when they are used individually as well as when they are combined in the same task. In a preliminary study, listening to tape-recorded instructions on how to relax produced a significant decrease in cardiac activity. In the major study, when used individually, both the Stroop procedure and delayed auditory feedback produced significant increases in cardiac activity. The largest increase, however, occurred with systolic blood pressure and was induced by delayed auditory feedback. When the Stroop procedure was used in combination with delayed auditory feedback, systolic blood pressure again increased, but this effect was no greater than when delayed auditory feedback was used alone. This pattern of results implies that, when combined, the Stroop procedure and delayed auditory feedback have largely independent effects on cardiac activity and that, when tested under similar conditions, delayed auditory feedback has the larger effect.

Comparison of reflex modification procedures and auditory brainstem response in high-risk neonates.

This study compared the results of reflex modification (RM)--an objective technique for assessing brainstem sensorineural processing--with those of auditory brainstem response (ABR) for a group of high-risk infants at comparable postconceptional ages. For the RM procedure, an eyeblink-eliciting tap to the glabella was presented either alone or accompanied by a brief 90dB SPL tone. 37 high-risk infants were tested with both RM and ABR at a mean postconceptional age of 37.3 weeks. Seven had an increased brainstem conduction time ('failed ABR') and eight did not exhibit significant reflex augmentation ('failed RM'), seven of whom also failed the ABR. These data provide evidence that sensory stimuli which affect the neural mechanisms responsible for the organization of the startle response and auditory processing share essential neural components.

The blink reflex: maturation and modification in the neonate.

The onset and development of the delayed blink response, elicited by a tap to the glabella, and its modification by an acoustic stimulus (tone), were studied longitudinally in 36 healthy preterm and 43 term infants. Blink amplitude increased with gestational age. By term postconceptional age, the responses of the preterm infants to tap alone, and to both tap and tone, were not significantly different from those of the term infants. These results suggest that neurological development, as reflected by the blink reflex and its modification, proceeds in an orderly, sequential fashion and that the mechanisms affecting these brainstem processes are not altered by environmental influences.

Altered brainstem sensory processing as assessed by reflex modification procedures in infants at risk for apnea.

Reflex modification procedures were used to test sensory processing in premature infants to examine the relationship between respiratory abnormalities and brainstem neuronal function. A total of 73 premature infants at risk for apnea and/or infants receiving methylxanthine therapy was given a 12-h pneumocardiogram and reflex modification test at a comparable postconceptional age, before discharge. Reflex modification was tested using a controlled eyeblink-eliciting tap to the glabella presented either alone or with a 1 kHz 90-dB SPL tone. The amplitude of the glabellar tap eyeblink and acoustically modified blink were lower in infants discharged on cardiac/apnea monitors (n = 36) than in the unmonitored group (1.44 and 1.59 volts versus 2.15 and 2.39 V, p less than 0.005, respectively). At follow-up, 12 monitored infants had clinically significant apnea after discharge. The records of this subgroup of infants revealed a significantly lower augmentation of the glabellar eyeblink response when compared to all infants screened for respiratory abnormalities and to the other monitored babies (p less than 0.01). The data suggest that abnormalities of the ventilatory pattern and occurrence of clinical apnea in preterm infants may in some measure be related to acoustic sensory processing, implying an alteration of brainstem neuronal function and organization.

Sensory processing in the term and preterm infant: use of reflex modification procedures.

The present study uses the glabellar reflex and reflex modification procedures to assess acoustic and tactile sensory processing capabilities in the human neonate. Fourteen term infants and 28 clinically stable preterm infants were given identical test paradigms. Augmentation testing consisted of a 16 V dc tap presented simultaneously with a 90 dB SPL tone; inhibition testing consisted of a 16 V tap preceded 900 msec. by an identical tap. All 14 term infants showed augmentation with 8 of 14 at p less than 0.05 level and eleven of 14 showed significant inhibition at the 900 msec intertap interval. However, only 12 of 28 preterm infants demonstrated significant augmentation and none showed reliable inhibition. These data indicate that areas of the central nervous system that process sensory stimuli are not fully developed at the time of birth even in the term infant. Further, the neural system for augmentation and inhibition may be independent of each other.

Reflex modification audiometry: assessment of acoustic sensory processing in the term neonate.

Behavioral and physiological work in animals and adult humans have established the sensitivity of various procedures and allowed delineation of the neuroanatomical pathways involved in sensory processing. Herein we used the glabellar reflex and reflex modification procedures to assess acoustic sensory processing capabilities in the term newborn infant. The eyeblink-eliciting device consisted of a miniature solenoid which could deliver a controlled tap. A photoreflective densitometer attached to a TDH-39 earphone assessed the eyeblinks. A total of 98 term infants was studied to determine how a response to a reflex-eliciting event (tap) was modified (either augmented or inhibited) by a mild exteroceptive stimulus (tone) which was presented at an appropriate lead interval. Ninety adult subjects were given identical testing procedures and their data were compared to that of the infants. The results of this study showed that newborn infants reliably exhibited an eyeblink response after a tap to the glabella. With fixed intensity tones, frequencies from 1 to 4 kHz produced equivalent amounts of reflex augmentation in infants and adult subjects. Blink amplitude increased as a function of increased tap and tone intensity in both infants and adults. State change was shown to affect the amplitude of the reflexive eyeblink, but not the augmentation effect. However, neonates failed to show inhibition to either acoustic lactile stimuli at an interstimulus interval that produced significant inhibition in the adult. These data indicate that reflex modification procedures provide an objective assessment of acoustic sensory processing in the term neonate.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of the eyeblink reflex in the human infant.

In human adults the eyeblink elicited by a given stimulus can be inhibited if that stimulus is preceded by another stimulus at an appropriate lead interval. In the present work, pairs of eyeblink-eliciting stimuli separated by 300-1200 msec were presented to sleeping preterm and full-term infants as well as to adults. Preterm infants did not exhibit reliable inhibition at any interval. Full-term infants did so, but they required longer interstimulus intervals than were needed for inhibition in the adult subjects. Results imply that the neural systems that mediate reflex inhibition are functional at birth, but that they are relatively slow to act.

Reflex augmentation of a tap-elicited eyeblink: the effects of tone frequency and tap intensity.

The amplitude of the human eyeblink elicited by a mild tap between the eyebrows can be increased if a brief tone is presented simultaneously with the tap. In two experiments we examined how this reflex augmentation effect varies with changes in the frequency characteristics of the tone and with changes in the intensity of the tap. We also examined how these effects change in the course of development. For newborn infants and for adults, fixed intensity tones with frequencies of either 1, 2, or 4 kHz produced equivalent amounts of reflex augmentation. Furthermore, while blink amplitude was an increasing function of tap intensity in both populations, the amount of reflex augmentation engendered by a simultaneously presented tone was independent of the intensity of the tap.

Reflex modification by acoustic signals in newborn infants and in adults.

This research asked whether the reflexive eyeblink elicited by a tap to the glabella (the flat region of skin between the eyebrows) is modified by acoustic signals which either precede or accompany the tap. Five experiments employing identical reflex modification procedures on neonates and adults suggest developmental differences in processing auditory stimuli. Neonates failed to exhibit reflex inhibition by either prior acoustic or tactile stimuli. Adults exhibited robust reflex inhibition to these same stimuli. Neonates, however, exhibited reliable reflex augmentation when mild (70 dB re: 0.0002 dyne/cm2) tones were presented simultaneously with the tap. For adults, tone intensities of at least 90 dB were necessary to obtain reliable reflex augmentation. The developmental processes implied by these findings are discussed.

Reflex modification in the rat: the inhibitory effects of intensity and frequency changes in steady tones.

In laboratory rats (as in humans) a low-intensity tone that precedes a high-intensity burst of noise by approximately 100 ms can reduce the amplitude of the startle reaction elicited by the burst of noise. A series of four experiments with rats investigated the relation between the inhibitory effects of tonal frequency change and the length of the silent period (gap) preceding it. The major findings were the following: (a) A gap in an otherwise continuous pure tone inhibited startle when the gap occurred approximately 100 ms prior to the noise burst. (b) Although an increase in gap duration increased the inhibition afforded by the gap, the maximum inhibition was yielded by gaps of 100 ms and greater; this maximum was equivalent to the inhibition yielded by the presentation of a postgap tone alone. (c) A shift in tonal frequency across a 10-ms gap yielded more inhibition than did the same gap with no frequency shift; again the shift yielded equivalent inhibition to the presentation of the postgap tone alone. (d) An increase in the frequency shift increased inhibition when the shift occurred across a 10-ms gap, but not when the shift occurred across a 100-ms gap.