Modifications in aerodynamic variables by persons who stutter under fluency-evoking conditions.

The purposes of this study were to (a) compare the effects of fluency-evoking conditions on aerodynamic variables in 10 persons who stutter with those previously reported for 12 individuals who do not stutter; (b) determine if any changes demonstrated in the amplitude and/or timing of aerodynamic variables were accounted for by changes in speech intensity; and (c) determine if any amplitude or timing changes in flow and intraoral pressure were related to improved fluency. The fluency-evoking conditions were choral reading (CR), metronome-pacing (MET), delayed auditory feedback (DAF), and noise (NOISE). From 8 words beginning with plosive consonants in CVC contexts read aloud in sentences, measures were made of 8 variables, including closure duration, amplitude and time to maximum airflow and intraoral pressure for initial plosives, and the duration and intensity of the following vowel. Speech rate was also computed. Only fluently produced target words from persons who stutter were analyzed. All persons who stutter showed improved fluency under all conditions. Both groups demonstrated significant (p < or = 0.006) condition effects for peak flow, vowel intensity, and pressure rise time. Thus, fluency-evoking conditions affected these variables regardless of speaker type. Both groups changed peak pressure in similar directions from baseline depending on condition, but not significantly for each group in the same conditions. Persons who stutter significantly increased speech rate for CR, DAF, and NOISE; and persons who do not stutter significantly decreased rate under DAF. The reported changes in peak pressure and peak flow could not be accounted for by changes in vowel intensity. Larger improvements in fluency occurred under conditions when peak flow and peak pressure values were decreased from baseline. Thus, variables that were modified by both groups when speaking under conditions were also the variables related to changes in fluency for the persons who stutter.

Duration of human singleton pregnancy. A population-based study.

We have analysed the duration of pregnancy for singleton births in Sweden during 1976-80 by means of data from the Swedish Birth Registry. Information, which was obtained from special forms with standard questions, include date of first day of last menstrual period (LMP) and whether that date was considered reliable or not. Recording was done prospectively, starting at the first antenatal visit. In 10% of cases the dates were labelled uncertain. Information on LMP and birth dates, parity, age of mother, sex of child, and/or mode of delivery was missing in 5.5% of the singleton cases, leaving 427,581 singleton births for analysis. In cases of reliable menstrual dates, the average duration from LMP to vaginal birth was 282 days (median), 281 days (mean) and 283 days (mode), remaining constant over the years of study. One standard deviation of the mean was approximately 13 days, varying slightly with age and parity. Ten per cent of these women gave birth post term (past 294 days). The duration of cesarean section births became shorter over the years, in spite of little change in cesarean section frequency (9.5% in 1976-7 and 10.9% in 1979-80). Mothers aged 35 and over tended to give birth 2 days earlier than those below 35. Second and subsequent children of mothers below 35 had slightly shorter gestations than first-borns. Boys were born earlier than girls, on average. When LMP was unreliable, the distribution of gestational lengths was wide. We also noted a seasonal rhythmicity in average duration of pregnancy, with consistent shortening in the month of December.

Cysteamine therapy for children with nephropathic cystinosis.

We treated 93 children with nephropathic cystinosis with oral cysteamine (mean dose, 51.3 mg per kilogram of body weight per day) for up to 73 months. This agent is known to be effective in depleting cells of cystine. In our study, the mean cystine depletion from leukocytes was 82 percent. A historical control group of 55 children received either ascorbic acid (27 children) or placebo (28). At age six, 2 of 17 controls had a serum creatinine level less than 1.0 mg per deciliter, as compared with 17 of 27 patients treated with cysteamine for at least one year (odds ratio, 12.8; 95 percent confidence interval, 2.1 to 33.9). At the end of the study, creatinine clearance was higher in the cysteamine group than in the control group (38.5 vs. 29.7 ml per minute per 1.73 m2; 95 percent confidence limits on the difference, 1.8 and 15.8), even though the cysteamine group was on average 1.4 years older than the control group. Cysteamine also improved growth; those in the cysteamine group between two and three years of age grew at 93 percent of the normal velocity, as compared with 54 percent in the control group. Fourteen percent of the patients could not tolerate the taste and smell of cysteamine. Concurrent controls treated in a blinded fashion with a placebo were not included in this study. With this limitation in mind, we conclude that oral cysteamine, by depleting cells of cystine, helps maintain renal glomerular function, improves growth, and constitutes the current treatment of choice for nephropathic cystinosis.

Prophylaxis of migraine attacks with a calcium-channel blocker: flunarizine versus methysergide.

In this study, flunarizine, a selective calcium-channel blocker, was employed in the prophylactic treatment of headache and was compared with methysergide in terms of efficacy. The trial was conducted with 104 patients (53 treated with flunarizine and 51 treated with methysergide) and lasted six months--one month of pretreatment and five months of therapy. Patients in both groups experienced a highly significant reduction in the number and duration of migraine attacks. Unlike those in the methysergide group, patients treated with flunarizine achieved a significant reduction in the intensity of attacks with very negligible side effects.

Ultradian rhythms in human fetal heart rate: a computerised time series analysis.

Even though fetal heart rate recordings are widely used to monitor fetal health, both antenatally and in labour, the underlying physiology is not well understood. For example, it is not known with any certainty whether the oscillations seen in fetal heart rate are highly organised, in reflection of underlying ultradian rhythms, or whether they are entirely random and haphazard. In order to answer this question, therefore, we have used mathematical techniques of time series analysis to look for clear evidence of ultradian rhythms in fetal heart rate recordings. We have found that specific short-term ultradian rhythms are indeed present, and that they can be measured objectively in terms of their frequency, amplitude and phase. Such rhythms have cycle lengths of 10 to 90 s and they can persist for long periods of time. They may also disappear and later reappear, locking back into synchrony again with previous oscillations. Individual rhythms may undergo amplitude change, phase shift, and perhaps even frequency shift.

Male sexual development in the monkey. II. Cross-sectional analysis of pulsatile hypothalamic-pituitary secretion in castrated males.

Pulsatile secretion of serum gonadotropins was studied in 16 castrated monkeys from 4 weeks of age through adult life. Animals were castrated at various ages from birth through adult life. Although some studies of the gonadotropin-secretory patterns were longitudinal in nature, most comparisons were cross-sectional. On the basis of our observations, we have arbitrarily grouped the animals into 4 developmental ages: postnatal (less than 7 months), prepubertal or juvenile (7-27 months), pubertal (28-59 months), and adult (greater than or equal to 60 months). In carrying out these studies, blood was withdrawn at 15-min intervals over 24 h without anesthesia using a mobile vest and tether assembly to support an indwelling catheter. GnRH challenge tests were done on 1 or more occasions on all animals. Plasma samples were analyzed for concentrations of FSH and LH by established RIAs and an in vitro bioassay for LH. During the frequent sampling period (24 h for all except postnatal animals), the amplitude of gonadotropin pulses was greatest in adult animals followed by postnatal and pubertal monkeys. During pubertal development, there was a marked increase in the magnitude of gonadotropin pulses, and remarkedly, there was a substantial increase in the LH bioassay: RIA (greater than 5:1) by adult life. GnRH challenge tests of gonadotropins correlated with these observations. Time series analysis was applied to the data for objective statistical characterization of cyclic patterns. Our findings can be summarized: 1) during pubertal maturation there is a change in amplitude but not frequency of gonadotropin pulses, 2) pubertal development of the hypothalamic-pituitary axis advances in the absence of gonadal feedback, and 3) there is a significant increase in the LH bioassay: RIA during pubertal development. We conclude that the castrate monkey is a valuable adjunct to direct clinical investigations of the mechanisms controlling human sexual development.

Male sexual development in the monkey. I. Cross-sectional analysis of pulsatile hypothalamic-pituitary-testicular function.

Pulsatile secretion of serum gonadotropins and testosterone was studied in 46 monkeys of varying ages from 9 days of age through adult life. Although some of the hormonal analysis was longitudinal in nature, most comparisons were cross-sectional. On the basis of pulsatile secretory patterns, hCG and GnRH stimulation, skeletal age, testicular volume, and histology, we have arbitrarily defined four developmental age groups: postnatal (less than 7 months), prepubertal or juvenile (7-27 months), pubertal (28-59 months), and adult (greater than or equal to 60 months). In accomplishing the pulsatile studies, blood was withdrawn at 15-min intervals over 24 h without anesthesia using a mobile vest and tether assembly to support an indwelling cannula. GnRH and hCG challenge tests were done on one or more occasions on all animals. Plasma samples were analyzed for concentrations of FSH, LH, testosterone, dihydrotestosterone and delta 4-androstenedione by established RIAs and an in vitro bioassay for LH. During the frequent sampling period of 24-h duration for all except postnatal animals, testosterone pulses of large amplitude (up to 8-fold) occurred in postnatal, pubertal, and adult animals. Pulsatile gonadotropin secretion was seen at all ages; however, the highest pulses (up to 15-fold) occurred in prepubertal animals even though this was an infrequent occurrence. Time series analysis techniques were applied for objective statistical characterization of cyclic patterns. Basic rhythms corresponding to 50- to 90-min frequency cycles in gonadotropin secretion were identified. Substantive differences between LH concentrations by bioassay and RIA were seen infrequently. Our findings illustrate that: 1) circulating gonadotropin and testosterone pulses change in amplitude but not necessarily frequency during pubertal development, and 2) primate models are a useful paradym for the longitudinal study of human male sexual development. We conclude that where direct human investigation may be limited, much can be learned by study of these primate surrogates.

Interval estimation of the attributable risk for multiple exposure levels in case-control studies.

In case-control studies, exposure to a risk factor often occurs at several levels, so the attributable risk at each level is of interest. In this paper, estimation for the 2 X 2 table (case-control status versus dichotomous exposure) and the 2 X k table (case-control status versus exposure at several levels) are reviewed along with an example. A method for finding confidence intervals for attributable risk in the 2 X k table is proposed, and its application to estimates adjusted across strata (the 2 X k X s case) is indicated. The results of a Monte Carlo study of the procedure demonstrate that the nominal and actual coverage probabilities agree satisfactorily for practical applications.