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Biomedical subjects

J L Roberts

Publications and source records attributed to J L Roberts.

At least 199 records · Page 11Linked to original sources

Observations made on severe apneic spells in two infants at risk for sudden death.

We have studied the sequence of events during prolonged apneic spells in two infants who, by virtue of multiple risk factors or ultimate death, were at risk for sudden death. Using techniques to quantitate airflow and pharyngeal airway pressures, we have reported many descriptive aspects of the apnea in these infants. Specifically, we have noted that severe apneic spells in these infants were accompanied by a wide spectrum of lengths and types of shorter apneas. In the case of infant A, the most severe spells occurred in clusters. Physiologic phenomena usually considered normal (sighs, swallows, etc.) often occurred in association with the apneic spells. In addition, we found that: 1) mixed apnea was the clinically significant form of apnea; 2) in mixed apnea, the site of obstruction was in the pharynx; 3) obstruction often occurred at the beginning of the spells; and 4) this obstruction occurred progressively over a series of breaths prior to the spell and resolved in a similar fashion. Theophylline, in one infant, decreased the incidence of apnea.

Airway Resistance↗

Necrotizing tracheobronchitis: a new indication for emergency bronchoscopy in the neonate.

Necrotizing tracheobronchitis (NTB) is a recently recognized cause of tracheal obstruction in the mechanically ventilated neonate. This process involves inflammation and necrosis of the mucosa of the distal trachea and mainstem bronchi. The sloughing of this material into the tracheal lumen results in plugging and acute respiratory distress. We documented this diagnosis in 19 infants. Four were diagnosed at autopsy. Fifteen had emergency bronchoscopy performed in the neonatal intensive care unit with removal of the obstructing debris. Ten of these 15 neonates survived (66.7%). The diagnosis of necrotizing tracheobronchitis should be suspected in those neonates requiring positive pressure ventilation in whom a sudden unexplained increase in ventilatory requirements develops. This is often associated with hypercarbia and a history of high-peak inspiratory pressures with or without hypoxia. Emergency bronchoscopy in these neonates is necessary both for diagnosis and treatment of the necrotizing tracheobronchitis.

Bronchitis↗

Assessment of pharyngeal airway stability in normal and micrognathic infants.

A current hypothesis for obstructive sleep apnea states that 1) negative airway pressure during inspiration can collapse the pharyngeal airway, and 2) neural control of pharyngeal airway-dilating muscles is important in preventing this collapse. To test this hypothesis we performed nasal mask occlusions to increase negative pharyngeal airway pressures during inspiration in eight normal and five micrognathic infants. Both groups developed midinspiratory pharyngeal obstruction, but obstruction was more frequent in micrognathic infants and varied in some infants with sleep state. The airway usually reopened with the subsequent expiration. The occasional failure to reopen was presumably due to pharyngeal wall adhesion. If airway obstruction occurred in sequential breaths during multiple-breath nasal mask occlusions in normal infants, there was a breath-by-breath change in the airway pressure associated with airway closure (airway closing pressure); the airway closing pressure became progressively more negative. Micrognathic infants showed less ability to improve the airway closing pressure, but this ability increased with age. These findings suggest that nasal mask occlusion can test the competence of the neuromuscular mechanisms that maintain pharyngeal airway patency in infants. Micrognathic infants had spontaneous midinspiratory pharyngeal airway obstructions during snoring. Their episodes of obstructive apnea began with midinspiratory pharyngeal obstruction similar to that seen during snoring and nasal mask occlusions. These findings imply a similar pathophysiology for snoring, spontaneous airway obstruction, and obstruction during snoring.

Airway Obstruction↗

Factors influencing regional patency and configuration of the human infant upper airway.

To study factors influencing patency and configuration of the upper airway, we studied 11 infant cadavers using endoscopy and photography. In most cases, studies were performed shortly after death. The naso-, oro-, and hypopharynx and the larynx were studied. The upper airway was sealed at the nose and mouth so that transmural airway pressure could be raised or lowered. As pressure was lowered airway closure was seen in each of the four regions studied. With respect to closing pressure, the oropharynx was the most compliant region and the larynx the least compliant. In the naso-, oro-, and hypopharynx, lowering the transmural pressure was associated with inward movement of the anterior, posterior, and lateral airway walls. In the larynx, closure occurred by vocal cord opposition in the midline. Tension applied to the genioglossus and geniohyoid tongue muscles had an effect opposite to that of airway suction, causing a more or less symmetrical dilation of the naso- and oropharynx. When the airway was closed, additional tension was needed to produce airway reopening, suggesting that adhesion forces act to maintain airway closure. Neck flexion caused pharyngeal closure, and neck extension caused pharyngeal dilation. Secretions adherent to the walls of the airway visibly narrowed its lumen. The relevance of these findings for the obstructive sleep apnea and laryngomalacia syndromes is discussed.

Airway Resistance↗

Corticotrope response to removal of releasing factors and corticosteroids in vivo.

In the intact rat, adrenalectomy (ADX) is known to result in increased ACTH synthesis, content, and secretion from the anterior pituitary compared with those in the sham-adrenalectomized control. Treatment of adrenalectomized, rats with corticosterone prevents or reverses these changes in ACTH. Because corticosterone is known to act both at the corticotrope and at the level of CRF secretion, it is not clear to what extent the ACTH response to ADX is a result of removal of glucocorticoids from the pituitary per se. To test the role of brain input as well as the role of glucocorticoids on the corticotrope response to ADX, we performed the following experiment. Rats were prepared with anterolateral hypothalamic deafferentations (lesion) which severed CRF and arginine vasopressin cell bodies in the hypothalamus from their axonal endings in the median eminence and posterior pituitary. Control rats were subjected to sham lesions. Two days later, half of the rats in each group were subjected to either ADX or sham ADX; a subgroup of the lesioned rats was provided at the time of adrenal surgery with a constant infusion of rat CRF. Five days later, all rats were killed, and anterior pituitary levels of proopiomelanocortin (POMC) mRNA, ACTH, and protein; plasma ACTH and corticosterone, and adrenal and thymus weights were measured. In sham-lesioned rats, ADX resulted in increases in POMC mRNA, and plasma ACTH of 2.5- and 12-fold, respectively, compared to sham-adrenalectomized controls. In the absence of hypothalamic drive (lesion only), there were no responses of any of these variables to ADX. In lesioned rats driven with CRF, ADX resulted in increases in POMC mRNA and plasma ACTH of 2.2- and 2.6-fold, respectively, compared to sham ADX. After consideration of the three variables indicating ACTH synthesis, storage, and secretion and comparison of the results of ADX vs. sham ADX within and across the sets of animals, we conclude that 1) there is no autonomous response of the corticotrope to ADX; 2) the removal of corticosterone from the anterior pituitary may account for the majority of the effects of ADX on ACTH synthesis; and 3) the normal response to ADX requires secretion of CRF and increased secretion of another ACTH-releasing factor (possibly arginine vasopressin) that causes increased secretion but little synthesis of ACTH.

Adrenal Glands↗

Estrogen decreases rat hypothalamic proopiomelanocortin messenger ribonucleic acid levels.

Ovariectomy and estrogen (E) or E plus progesterone treatment has previously been shown to alter both hypothalamic content and portal plasma levels of beta-endorphin. To determine if these changes were accompanied by changes in beta-endorphin synthesis, we used a RNA dot blot method to quantify proopiomelanocortin (POMC) mRNA levels in the arcuate nucleus-median eminence region of rats. Animals were bilaterally ovariectomized, implanted with Silastic capsules containing E or oil, and killed 1 or 3 days after implantation. Total nucleic acid was isolated from dissections of the arcuate-median eminence by proteinase-K/sodium dodecyl sulfate/phenol extraction, and POMC mRNA was quantified by dot blot analysis. Although 1 day of E treatment had no effect on hypothalamic POMC mRNA levels, 3 days of E treatment caused a significant reduction of approximately 40% of POMC mRNA levels relative to oil controls in two replicate experiments. These results suggest that the decreases in hypothalamic POMC peptide levels after E administration reported previously may be due to a decrease in POMC peptide biosynthesis resulting from a decrease in hypothalamic POMC mRNA.

Animals↗

Castration increases luteinizing hormone subunit messenger RNA levels in male rat pituitaries.

The effect of castration on pituitary common alpha and LH-beta subunit mRNA levels was examined in adult male rats in a dot-blot hybridization assay using cytosolic mRNA and 32P labelled plasmids containing cDNA encoding sequences of the subunits. Orchidectomy increased alpha subunit mRNA levels threefold by day 4 with no further rise at 2 months. The LH-beta subunit mRNA levels increased by threefold at 2 months. Serum LH levels increased by up to fortyfold (2 months). Pituitary LH content increased by fourfold at 2 months, though was reduced at 4 days after castration. These results suggest that transcription of the alpha and LH-beta genes are similarly regulated after castration. However the greater magnitude of serum LH increase after castration than that of both LH subunit mRNA levels and the bidirectional changes in pituitary LH content implies additional translational/post-translational control of gonadotrophin biosynthesis by gonadal hormones.

Animals↗

Glucocorticoid regulation of pro-opiomelanocortin gene transcription in the rat pituitary.

The effect of glucocorticoids on pro-opiomelanocortin (POMC) gene transcription in the rat pituitary has been investigated by an in vitro nuclear runoff transcription assay. Both dexamethasone and corticosterone had rapid inhibitory effects on POMC transcription in the anterior lobe but not in the intermediate lobe of the pituitary. These effects were maximal during the first hour after injection of the steroid. Bilateral adrenalectomy had a time-dependent stimulatory effect on anterior lobe POMC transcription, presumably because of the removal of endogenous glucocorticoids. This study shows that the well documented inhibitory effects of glucocorticoids on POMC mRNA in the pituitary anterior lobe are due at least in part to an inhibition in POMC mRNA synthesis.

Animals↗

Benzyl alcohol toxicity in a neonatal intensive care unit. Incidence, symptomatology, and mortality.

We unknowingly "screened" all NICU infants for elevated levels of serum benzyl alcohol (Bz-OH) over a three-month period. The fortuitous "screening" procedure resulted from the interference by Bz-OH with a routine blood CO2 assay used for all infants; validity was proved by (1) replication of the interference pattern with Bz-OH or benzoic acid; (2) confirmation of elevated benzoic acid levels in serum in two of the four screening positive infants tested but not in control infants, and (3) disappearance of the interference patterns when Bz-OH solutions were discontinued in affected infants. Screened Bz-OH-positive infants were compared to screened negative control infants, matched for weight (less than 1000 g), severity of RDS (on respirators), exposure to Bz-OH, and survival for longer than 48 hours. Intraventricular hemorrhage (IVH), metabolic acidosis appearing prior to IVH, and mortality were increased in Bz-OH-positive infants (P less than .05 in each case); hyperbilirubinemia and thrombocytopenia were not. Gasping respirations were not a major symptom. It is concluded that Bz-OH poisoning was a major cause of morbidity and mortality in NICU infants weighing less than 1000 g at birth during the three-month screening period. A retrospective review of patient records covering a 16-month period showed significant improvement in the survival rate of infants weighing less than 1000 g following the discontinuation of Bz-OH solutions.

Acidosis, Respiratory↗

Food borne infection by a Norwalk like virus (small round structured virus).

Two outbreaks of gastrointestinal illness with identical symptoms occurred in parties attending banquets on consecutive evenings at a large hotel. The illness was typical of epidemic winter vomiting disease. Small round structured viruses resembling those seen in the Norwalk Ohio outbreak were identified by electron microscopy in stools of victims from one episode. One food handler was found to be excreting the virus, and there was evidence of a poor standard of hygiene in the kitchen. A food history analysis showed the illness to be significantly associated with eating cold cooked ham.

Disease Outbreaks↗

Pharyngeal airway-stabilizing function of sternohyoid and sternothyroid muscles in the rabbit.

The upper airway is vulnerable to collapse from negative intraluminal pressures during inspiration. The tongue muscles, the genioglossi and geniohyoids, by contracting during inspiration, appear to function to resist this collapse. This study supports the hypothesis that two cervical strap muscles, the sternohyoid and sternothyroid, have a similar function. First, phasic inspiratory electromyographic activity was recorded from the sternohyoid and sternothyroid muscles of nine anesthetized rabbits during tidal breathing. Furthermore, each muscle showed a progressive increase in electromyographic activity with airway occlusion. Second, in eight rabbits, by determining the amount of negative pressure required to collapse the upper airway (airway closing pressure determination), it was shown that upper airway stability improved with electrical stimulation of either the paired sternohyoid or sternothyroid muscles. In addition, in 12 freshly killed rabbits, mechanical tension, mimicking the contraction of either the sternohyoid or sternothyroid, improved airway stability. Finally, observations of the pharyngeal lumen utilizing a fiber-optic endoscope, revealed concentric narrowing of the oro- and nasopharynx when airway pressure was lowered and concentric widening when tension was increased in the sternohyoid or sternothyroid muscles. These findings support the hypothesis that phasic inspiratory contraction of the sternohyoid and sternothyroid muscles functions to resist pharyngeal airway collapse due to negative intraluminal pressures.

Animals↗

Clinical and pathological features of membranous glomerulonephritis of systemic lupus erythematosus.

The prognostic significance of glomerular inflammation in patients with lupus membranous glomerulonephritis (MGN) was evaluated by classifying 100 renal biopsies from lupus patients according to World Health Organization (WHO) criteria and correlating the histology with clinical data. There were 22 cases of MGN: in 3 the lesion was pure MGN (Va); in the remainder, diffuse MGN was modified by superimposed mesangial proliferation in 6 (Vb), segmental glomerulonephritis (GN) or sclerosis in 10 (Vc), and diffuse GN in 3 (Vd). Patients in the four categories had similar clinical presentations. When the 4 patients with active proliferative glomerulonephritis (PGN) were grouped and compared to those without PGN, they had more active serologies. Quantitation of glomerular electrondense deposits in MGN showed variation in the percentage of basal lamina covered by subepithelial deposits, segmental subepithelial deposits in 4 cases, focal segmental subendothelial deposits in most cases and massive subendothelial deposits in 5 biopsies. 4 of the latter patients had active PGN, suggesting that only extensive subendothelial deposits are pathogenetically significant. The predicted 5-year survival for all MGN patients was 90%, and the only 2 deaths were not related to renal failure. Thus, it appears valid to include mixed lesions in the membranous category, but it is our impression that the immediate course and prognosis of SLE and associated PGN depends upon the extent and reversibility of the inflammatory lesions.

Glomerulonephritis↗

Regulation of upper airway maintaining muscles during progressive asphyxia.

The electromyographic activity of an upper airway muscle (genioglossus, GG) and the diaphragm were studied in 10 adult and three young anesthetized rabbits during progressive asphyxia induced by airway occlusion. Results were similar for both age groups. Peak inspiratory activity of GG muscle increased more than that of the diaphragm during both the hyperpnea and gasping (P less than 0.05). The increase in GG activity during gasping was not significantly different from that during hyperpnea even though an important stimulus, arousal, was absent during gasping. During end stage asphyxia, as the strength of gasps grew weaker, the rate of loss of GG muscle activity was greater than that of the diaphragm. However, GG activity remained greater than that of the diaphragm at the time of the last spontaneous gasp. As asphyxia progressed, inspiratory duration and the inspiratory contour of integrated electromyogram activity of both muscles changed. These data indicate differences in the control mechanism of the genioglossus and diaphragm during acute severe asphyxia. Increased upper airway muscle activity seen during gasping should help preserve upper airway patency and facilitate autoresuscitation by gasping. These observations of coordinated changes in timing and activity of two functionally different respiratory muscles support the concept that gasping is a highly organized function of the respiratory centers.

Airway Resistance↗

Evidence for only one beta-luteinizing hormone and no beta-chorionic gonadotropin gene in the rat.

We have examined the rat genome and placenta for the presence of a mRNA or gene which codes for a protein identical or similar to the beta-subunit of LH. A cDNA clone was isolated that encodes for amino acids 44 through 121 of the mature beta-subunit of rat LH (rLH). This r beta LH cDNA was used as a hybridization probe to study the structure of the gene(s) which encode for the beta-subunit of either LH or a LH-like protein in the rat genome. Restriction enzyme digestion analysis of rat genomic DNA using Southern blots revealed only one fragment that hybridized to 32P-labeled r beta LH cDNA. In contrast, restriction enzyme analysis of human and rhesus monkey genomic DNA (known to have both LH and CG) gave multiple fragments which hybridized to a 32P-labeled human beta LH DNA. We have also examined the possibility of a mRNA which can encode the beta-subunit of either LH or CG in the rat placenta. Northern blot analysis of total RNA isolated from rat placenta and rat anterior pituitary revealed that only the anterior pituitary contains a mRNA which is complementary to rLH cDNA. These results suggest that: there is only one gene which encodes the beta-subunit of LH in the rat haploid genome; there is no gene which encodes for a beta-subunit of a CG molecule in the rat; there is no mRNA in the rat placenta which encodes for the beta-subunit of LH or an LH-like molecule.

Amino Acid Sequence↗