We collected data on growth, psychomotor development, speech and language development, and intellectual function on a cohort of 100 males with the fragile X chromosome and 95 carrier females. The data include information on prenatal growth (33 males), growth during the preadult years (32 males), psychomotor development during the first 2 years (25 males), speech and language development (15 males and 5 females), and intellectual function (93 males, 33 females, and 10 obligate carriers who were cytogenetically normal). Birth measurements appeared normal when plotted on the Usher/McLean curves of newborn infants (mean head circumference - OFC - at 40th centile, length at 60th centile and weight at 55th centile). Following birth, OFC rose above the 50th percentile and continued above average throughout the preadult years, whereas average length was above average for the first 5 years only and weight did not deviate from the normal mean. Psychomotor development lagged behind the norm from birth with affected males requiring nearly twice as long as expected to sit alone, walk unassisted, and say first words clearly. All males and females studied had significant language delay; all except one male had abnormalities of articulation. All on whom a clear voice sample was obtained had low voice pitch, and 80% had a hoarse or harsh quality of voice. Five males had word repetitions or perseverative speech during the preadult years. The mean IQ of the 93 males studied was 33 and regression analysis demonstrated a decrease in intellectual performance with age. Four fifths of the female carriers who expressed the fra(X) had intellectual performance in the mentally retarded range and showed similar decrease in performance with age. Obligate female carriers who did not express the fra(X) site had normal IQs (IQ 102 +/- 13.3).

Adolescent↗

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Fragile X syndrome: incidence, clinical and cytogenetic findings in the black and white populations of South Carolina.

Individuals in South Carolina with the Fragile X [fra(X)] or Martin-Bell syndrome have been ascertained by referral for evaluation of facial abnormalities, macroorchidism or mental deficit; by screening patients in residential and day programs for the mentally retarded; and by family follow up after an index case has been identified. Between 1982 and 1987, 100 positive fra(X) males were diagnosed. Of these, 35 were residents of residential facilities for the mentally retarded representing 2.5% of the population of institutionalized males. Another 23 were found in community day programs for the mentally retarded. Of these 58 cases, 28 (48%) were ascertained by screening for the craniofacial characteristics of the Martin-Bell syndrome, namely long face, midface hypoplasia, prominent forehead, large mandible and large simple pinnae. Although this screening procedure proved to be productive, it was found that the craniofacial traits of long face, midface hypoplasia, large jaw and simple pinnae were found less frequently in black fra(X) positive males and in prepubertal boys of both races.

Black People↗

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Dorsal medullary oxytocin, vasopressin, oxytocin antagonist, and TRH effects on gastric acid secretion and heart rate.

Injections of oxytocin and TRH (11 picomoles), centered on the dorsal motor nucleus of the vagus, substantially increased gastric acid secretion. Additionally, oxytocin, but not TRH, simultaneously produced a consistent reduction in heart rate. Vasopressin injected into the same locus, at doses of 11 and 110 picomoles, had no effect on either function. Both the gastric and cardiac effects of oxytocin were eliminated by the central injections of oxytocin antagonist dEt2Tyr(Et)Orn8Vasotocin (ETOV; 6 picomoles) or peripheral administration of atropine (300 micrograms/kg, IP). Application of oxytocin or TRH to the area postrema, at double the dosage (22 picomoles) yielded no consistent effects on either gastric secretion or heart rate. These findings indicate that oxytocin in the dorsal motor nucleus of the vagus may act as a regulator of vagally-mediated gastric and cardiovascular functions while TRH effects, in this medullary area, seem limited to the regulation of gastric function.

Animals↗

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Hypothalamic paraventricular nucleus stimulation-induced gastric acid secretion and bradycardia suppressed by oxytocin antagonist.

Unilateral microstimulation of the medial parvocellular division of the hypothalamic paraventricular nucleus (PVNmp) elicits significant increases in gastric acid secretion and bradycardia. An injection of 25 picomoles of the oxytocin antagonist dET2Tyr(Et)Orn8 Vasotocin (ETOV), suspended in 5 nanoliters of artificial of cerebrospinal fluid (CSF), into the dorsal motor nucleus of the vagus (DMN) immediately preceding microstimulation of the PVNmp suppresses this change in gastric acid secretion and heart rate. The injection of an equal volume (5 nanoliters) of artificial CSF vehicle solution into this region of the DMN, prior to PVNmp microstimulation, has no effect on either the subsequent stimulation-evoked changes in acid secretion or cardiac activity. This suppression of PVNmp stimulation-evoked changes in gastric acid levels and heart rate by the presence of the oxytocin antagonist, ETOV, within the DMN supports the hypothesis that oxytocin may be a neurotransmitter used for descending communication from the PVNmp to neurons within the DMN that regulates these two functions.

Animals↗

PubMedDate not supplied

Oxytocin, oxytocin antagonist, TRH, and hypothalamic paraventricular nucleus stimulation effects on gastric motility.

The roles of thyrotropin releasing hormone (TRH) and oxytocin as central regulators of gastric motility were investigated. Picomolar (4 picomoles) quantities of TRH injected into the dorsal motor nucleus of the vagus (DMN) elicited a significant increase in gastric motility while the same quantity of oxytocin elicited a reduction in phasic contractile activity and tone. The action of these peptides mimics the excitatory and inhibitory effects of stimulating the paraventricular nucleus of the hypothalamus (PVN); it is likely that this hypothalamic structure regulates gastric function through its peptidergic connections with medullary vagal structures. This hypothesis is supported by our observations that injections of an oxytocin antagonist into the DMN produced a disinhibition of gastric motility and an increase in the motility evoked by subsequent PVN stimulation. Vagotomy eliminated all subsequent central effects on motility of these peptides.

Animals↗

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Dissociation of the effects of nucleus raphe obscurus or rostral ventrolateral medulla lesions on eliminatory and sexual reflexes.

Rat preparations were used to investigate long-term changes in external anal sphincter (EAS) contractions and reflexive penile erection following electrolytic lesions of the nucleus raphe obscurus (nRO) or the rostral ventrolateral medulla. EAS contractions were measured electromyographically (EAS EMG) following distention of the EAS with a 5-mm probe. Penile erections were measured using a standard ex copula reflex testing paradigm. At 48 h postlesion, 100% of nRO-lesioned animals displayed reflexive erections and the magnitude of EAS EMG was significantly greater in lesioned animals than in sham controls. These results suggested EAS hyperreflexia following destruction of the nRO. By 14 days postlesion, EAS responsiveness in nRO-lesioned animals had returned to levels comparable to nonlesioned animals. No measures of penile erection were affected by nRO lesions. In animals with nucleus gigantocellularis (Gi) and lateral nucleus paragigantocellularis (Gi-lPGi) lesions, no significant changes to EAS reflexes were observed at any time point. At 48 h postoperative, Gi-lPGi lesions significantly reduced the latency to first erection and increased the number of erections elicited relative to controls. Similar facilitation of erection latency was observed at 14 days postlesion, while erection number and flip total were no longer significantly different from controls. These and previous studies suggest that the nRO regulates defecatory reflexes in the rat. These data further suggest that the comingled EAS and bulbospongiosus (BS) motoneurons are controlled by discrete and separate brainstem circuits and that increases in EAS and penile reflexes after spinal cord lesions are mediated by loss of different descending inputs.

Anal Canal↗

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Afferent projections to the dorsal motor nucleus of the vagus.

The afferent projections to the dorsal motor nucleus of the vagus (DMN) were investigated by iontophoretically infusing horseradish peroxidase (HRP) into that neural region of the rat. After the tetramethylbenzidine histochemical procedure was performed on the HRP-injected brains, projections to the DMN from several areas were observed including the nucleus reticularis parvocellularis and gigantocellularis, the nucleus of the solitary tract, the nucleus raphe obscuris, the principal sensory trigeminal nucleus, and the paraventricular nucleus of the hypothalamus. The pathway originating in the paraventricular nucleus was the only forebrain projection to the DMN, a finding compatible with observation of other investigators.

Afferent Pathways↗

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Tumor necrosis factor-alpha in the dorsal vagal complex suppresses gastric motility.

Gastric hypomotility, loss of appetite, nausea, and vomiting frequently accompany critical infectious illness, radiation sickness, and carcinogenesis. The present studies examined the possibility that the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), may be responsible for provoking some of these autonomic signs associated with illness. Gastric motility of urethane-anesthetized rats was prestimulated with intracisternal applications of thyrotropin-releasing hormone (TRH), a peptide known to activate parasympathetic vagal excitatory pathways to the stomach. Microinjection of TNF-alpha (as low as 0.02 fmol) directly into the dorsal vagal comples (DVC) suppressed TRH-stimulated gastric motility for prolonged periods of time. Duration of suppression ranged from 5 min to more than an hour, dependent on both the dose of TNF-alpha and accuracy of placement of the microinjection within the DVC. This suppression demonstrated a dose-dependent effect of TNF-alpha that required an intact vagal pathway. These studies indicate that TNF-alpha may represent a unique cytokine 'afferent' signal which directly regulates the excitability of vago-vagal reflex circuits resulting in altered gastric motility during disease states.

Afferent Pathways↗

PubMedDate not supplied

Heterotopic calcification in severe head injury: a preventive programme.

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Adult↗