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Biomedical subjects

D W Warren

Publications and source records attributed to D W Warren.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effects of odorants and irritants on respiratory behavior.

A technique that combines psychophysical measurements with continuous recording of nasal patency and respiratory behavior was used to study the psychophysical and respiratory responses of 10 subjects to well-controlled stimulation with three compounds differing in relative stimulatory effectiveness for nasal olfactory and trigeminal chemoreceptors. All four concentrations of acetic acid, amyl acetate, and phenethyl alcohol were well above the odor detection threshold. The magnitudes of both the increase in odor strength and nasal irritation and the decreases in tidal volume were greatest for acetic acid and least for phenethyl alcohol. Among the odorants, differences in nasal irritation were greater than those in odor strength, and tidal volume appeared to have a reasonably close and inverse relationship to nasal irritation.

Acetates↗
PubMed1994

Ontogeny of the inhibitory guanine nucleotide-binding regulatory protein in the rat testis: mRNA expression and modulation of LH and FSH action.

The ontogeny of function and mRNA expression of the inhibitory guanine nucleotide-binding regulatory protein (Gi) was studied in the rat testis. Dispersed testis cells of animals aged 8, 15, 20 and 30 days were cultured with or without 100 micrograms/l pertussis toxin (PT) for 24 h. The cells were then cultured for another 24 h with medium only, cholera toxin (CT), PT, or their combination, and the amount of testosterone and cAMP production was measured. PT preincubation increased CT-stimulated cAMP production at all ages, thus indicating the presence of a functional Gi-protein in the postnatal testis. However, when testosterone production was measured, the enhancing effect of PT was absent at the age of 8 days only, indicating that Leydig cells at this age did not have functional Gi-protein. We then cultured 2-day-old and 8-11-day-old testis cells, after 24 h pretreatment with PT, in the presence of ovine follicle-stimulating hormone (FSH) (1 mg/l). The FSH-stimulated cAMP production was enhanced at both ages, thus indicating the presence of a functional Gi-protein in neonatal Sertoli cells. In Northern blot analyses, fetal and postnatal testis tissue had very similar levels of G alpha i2 and G alpha i3 mRNAs; the mRNA level of Gi1 in Northern blots remained low compared to those of Gi alpha 2 and Gi alpha 3. In conclusion, the Gi protein appears in the developing rat testis in utero but the activity first seems to be confined to non-Leydig cells including the Sertoli cell. In Leydig cells, the functional Gi-protein appears between days 8-15 post partum. This finding may be related to the fact that the fetal-neonatal population of Leydig cells possesses a high steroidogenic capacity and an apparent lack of the ability to respond to high gonadotropic stimulation with LH receptor down-regulation and steroidogenic enzyme desensitization.

Aging↗
PubMed1994

Transcriptional and translational regulation of LH, prolactin and their testicular receptors by hCG and bromocriptine treatments in adult and neonatal rats.

Effects of altered gonadotropin and prolactin (PRL) secretion on luteinizing hormone (LH), PRL and their testicular receptors (R) were studied in neonatal and adult rats. Changes in gene expression were monitored by measurements of steady-state mRNA levels. Five-day and 90-day-old male rats received a single s.c. injection of hCG (600 IU/kg), 1 mg/kg bromocriptine (BR) twice daily, or their combination. After 2 or 8 days, the responses of LH, PRL, their testicular R, and testosterone (T) were assessed, including measurements of the appropriate mRNA levels. Vehicle-treated age-matched animals served as controls. hCG suppressed serum LH in 2 days in adult rats from 0.85 +/- 0.16 to 0.04 +/- 0.01 microg/l, and in neonates from 0.59 +/- 0.29 to levels below 0.01 microg/l (p < 0.01 for both). This was accompanied at both ages by a 60% decrease in pituitary content of the LH beta-subunit mRNA (p < 0.01), but a decrease in the alpha-chain (40%, p < 0.05) occurred only in neonates. hCG increased serum PRL in adult rats in 8 days over 2-fold (p < 0.01); this did not occur in neonates. In neonates, BR increased the LH subunit mRNAs 2-fold in 8 days (p < 0.01) without a concomitant effect on serum LH; no BR effects on the LH parameters were seen in adult animals. BR decreased pituitary PRL protein and mRNA levels at both ages (p < 0.01-0.05), but serum PRL decreased only in the adults. The homologous down-regulation of testicular LHR (near 100%) was accompanied in adults by a 30% decrease in LHR mRNA (p < 0.05). Also BR at this age decreased LHR binding (75% in 8 days, p < 0.01), but in this case no change occurred in the cognate mRNA. hCG and BR slightly up-regulated in adults PRLR binding, but only the 2-day effect of BR was accompanied by a 60% increase in PRLR mRNA (p < 0.05). In neonates, both hCG and BR increased testicular LHR and PRLR mRNA levels (p < 0.01-0.05). In adult animals, both hCG and BR suppressed testicular and serum T levels after 8 days (40-70%, p < 0.01-0.05); only BR was inhibitory to T by 8 days in the neonates (p < 0.05). In conclusion, the homologous and heterologous regulatory effects of hCG and BR on LH, PRL and their testicular R levels were only partly explained by changes in steady-state levels of the respective mRNAs. In general, the autoregulatory effects on LHR and PRLR appeared to affect steady-state levels of cognate mRNAs, whereas heteroregulation predominately involved changes at the protein level. The responses of the neonatal pituitary-gonadal axis to hCG and/or BR differed greatly from those observed in the adult, indicating that the mechanisms involved in these regulatory events in adult animals are a result of gradual postnatal development.

Animals↗
PubMed1994

Pharmacokinetics from multiple intraosseous and peripheral intravenous site injections in normovolemic and hypovolemic pigs.

OBJECTIVES: To examine: a) the rate and extent of delivery of radioactive tracers to the central circulation from the tibial, medial malleolar, distal femoral, and humeral intraosseous sites, as well as from a peripheral intravenous site; and b) the end-tidal CO2 response to injected sodium bicarbonate at these sites. DESIGN: Prospective, descriptive study. SETTING: Animal laboratory at a university medical center. SUBJECTS: Twenty anesthetized and mechanically ventilated piglets were cannulated with 18-gauge bone marrow needles at intraosseous sites and 22-gauge Teflon catheters in peripheral veins. A 22-gauge angiocath was placed in the right carotid artery of each subject. Drug kinetics were studied in the normovolemic and hypovolemic (acute bleeding of 25 mL/kg) states. INTERVENTIONS: Sodium bicarbonate (1 mEq/kg) was injected into each of the three intraosseous and one intravenous sites with simultaneous monitoring of end-tidal CO2. A 10-min period for stabilization was allowed between injections. Aliquots of 99mtechnetium were injected at randomly selected sites and blood samples were obtained at 1.5-sec intervals via carotid artery for radioactive counts. Experiments were repeated after withdrawal of 25 mL/kg of blood. MEASUREMENTS AND MAIN RESULTS: Assessment by end-tidal CO2 monitoring after 1-mEq/kg injections of bicarbonate demonstrated a mean initial end-tidal CO2 increase at 12.8 secs and a mean maximal end-tidal CO2 increase of 8 torr (1.06 kPa), with no significant site differences noted. Radioactive tracer injections were detected in the carotid artery after 15.4 secs in normovolemic animals and after 21.4 secs in hypovolemic animals, with no significant site differences detected. The proportion of injected tracer at 2, 5, 10, 20, 30, and 40 mins identified no significant differences between various intraosseous and intravenous sites. CONCLUSIONS: Our study demonstrated similar rapid transit and proportion of bicarbonate and radioactive tracers, reaching the central circulation from multiple intraosseous sites and a peripheral intravenous site. This finding suggests that adjustments in drug dosage may not be required, using various intraosseous locations as an alternative to peripheral intravenous drug therapy.

Animals↗
PubMed1994

Preliminary data on the effect of pharyngeal flaps on the upper airway in children with velopharyngeal inadequacy.

Seven patients who received pharyngeal flaps for velopharyngeal incompetence (VPI) were studied to assess the effect of the procedure on nasal airway size. The findings suggest that the pharyngeal flap does not significantly decrease the upper airway in all patients. The effect of the flap did not correlate with the type of cleft, and was most pronounced in the inspiratory phase of the breathing cycle. Reasons for this variable effect, assumed to be related to an already impaired nasal airway in most cleft patients, are discussed.

Airway Resistance↗
PubMed1994

Hypernasality and velopharyngeal impairment.

Although the primary cause of hypernasality is impaired velopharyngeal (VP) function, a variety of other factors influence the outcome perceived by the listener. The purpose of the current study was to assess the relationship between oral-nasal resonance balance and (1) velopharyngeal orifice area; (2) nasal airflow rate; and (3) duration of nasal airflow. The pressure-flow technique was used to estimate VP area and measure nasal airflow rate and duration. Ratings of oral-nasal balance were made on a 6-point equal-appearing interval scale. Results indicated a moderate correlation between hypernasality rating and VP area (0.66), nasal airflow (0.61), and nasal airflow duration (0.53). Adults tended to be perceived as more hypernasal than children for a given degree of VP impairment. Finally, when the degree of VP opening was small, perceived oral-nasal resonance balance appeared to be related to duration of the opening-closing movements.

Adolescent↗
PubMed1993

Comparison of fluid infusion rates among peripheral intravenous and humerus, femur, malleolus, and tibial intraosseous sites in normovolemic and hypovolemic piglets.

STUDY OBJECTIVES: To compare infusion rates from various intraosseous sites (tibial, medial malleolar, distal femoral, and humeral) and at a peripheral IV site under gravity and pressure flow in normovolemic and hypovolemic states. DESIGN AND SETTING: A piglet model was used to assess rates of infusion under varying conditions in a university hospital animal laboratory. Analysis of variance was used to evaluate site differences. PARTICIPANTS: Twenty-three Yorkshire-Landrace mix pigs (weight, 12 to 23 kg) were studied. INTERVENTIONS: Animals were anesthetized and intubated before cannulation with 18-gauge bone marrow needles at intraosseous sites and 22-gauge Teflon catheters in peripheral vessels. Infusion rates under gravity and 300 mm Hg pressure were determined. Infusion rates under similar conditions were repeated in hypovolemic animals with acute bleeding of 25 mL/kg. MEASUREMENTS AND MAIN RESULTS: Mean infusion rates (mL/min) for gravity versus 300 mm Hg pressure in normovolemic pigs were 13.1 versus 40.9 for peripheral IV, 11.1 versus 41.3 for humerus, 9.3 versus 29.5 for femur, 8.2 versus 24.1 for malleolus, and 4.3 versus 17.0 for tibia. Hypovolemia resulted in average decreased rates of 32%. Infusion rates were significantly different between sites and between normovolemia and hypovolemia (P = .0001). CONCLUSION: Intravenous access is the most efficacious method of acute volume replacement. Intraosseous sites differ in the infusion rates obtained--descending order is humerus, femur, malleolus, and tibia, but each is a reasonable alternative for short-term vascular access.

Animals↗
PubMed1993

Nasal airway size in cleft and noncleft children.

Although the effects of cleft lip and palate on nasal airway size and breathing have been reported for adults, little information is available on children. The present study assessed the effect of age on nasal cross-sectional size and, in particular, whether type of cleft influenced the outcome. The results indicate that, while the cleft nose continues to grow with age, it remains about 30% smaller than the noncleft nose. The airway is smallest in patients with unilateral cleft lip and palate and is largest in those with bilateral clefts. The prevalence of oral breathing is considerably higher in the cleft population in comparison to noncleft.

Adolescent↗
PubMed1993

Hypernasality in the presence of "adequate" velopharyngeal closure.

In some instances, hypernasality occurs despite an instrumental assessment of "adequate" velopharyngeal closure. The pressure-flow technique was used to assess the timing characteristics associated with velopharyngeal closure in 11 such subjects. The group's performance was compared to the aerodynamic characteristics of two other subject groups. One was comprised of 13 cleft palate subjects with adequate closure and normal nasal resonance, while the second group consisted of 16 noncleft subjects who also manifested normal speech. The data indicate that there are several unique timing features that differentiate the hypernasal but "adequate" group from the two control groups. These include a delay of about 50 ms in achieving closure, a longer interval of nasal emission, and a shorter duration of actual closure. Hypernasality seems to be associated with the actual time the velopharyngeal mechanism is open, rather than the volume of air escaping from the nasal chamber.

Airway Resistance↗
PubMed1993

Perceptual assessment of resonance distortion in unoperated clefts of the secondary palate.

The purpose of this study was to examine the frequency with which five speech-language pathologists made judgments of hypernasality during the clinical assessment of young children with unoperated and repaired clefts of the secondary palate. Among the 293 nonsyndromic patients with secondary palate clefts included in this study, 219 were between 1 and 2 years of age. Of those, 83 had undergone primary palatoplasty whereas 136 had not. The remaining 74 children were between the ages of 4 and 5 years and presented with repaired secondary palatal clefts. The results showed that the clinicians were unable or unwilling to assess hypernasality in 31% of the 1 to 2 year old children with unoperated clefts. The same clinicians failed to evaluate oral-nasal resonance balance in only 12% of the children in the 1- to 2-year age group who had undergone palate repair. Only 1 of the 74 older children (1.4%) was not evaluated for hypernasality. Possible explanations for these findings are presented and discussed.

Child Language↗
PubMed1993

Sex-dependent parameters related to electrolyte, water and glycoprotein secretion in rabbit lacrimal glands.

The lacrimal glands of males and females of various species differ with respect to several morphological, biochemical and functional characteristics. The purpose of this study was to determine the effect of sexual maturation on Na+,K(+)-ATPase, muscarinic cholinergic receptors and beta-adrenergic receptors, which are closely related to the secretion of electrolytes and fluid by the gland, and on other membrane-associated enzymes, specifically galactosyltransferase and alkaline and acid phosphatase. Soluble and total membrane fractions were obtained from lacrimal glands of prepubertal (1.0 kg), pubertal (2 kg), and mature (4 kg) of New Zealand white rabbits of both sexes. Prepubertal and pubertal rabbits exhibited no sex differences in the total amount of lacrimal gland protein or in any of the enzymes or receptors, with the exception of galactosyltransferase and alkaline phosphatase. Galactosyltransferase had higher total and specific activities in prepubertal and pubertal males, and alkaline phosphatase had higher specific activity in prepubertal males. As animals matured, total protein and activities of the enzymes increased, and several quantitative differences between males and females became apparent. Samples from mature females contained significantly less DNA and membrane and total protein. Specific activities of Na+,K(+)-ATPase, cholinergic receptors, galactosyltransferase, and acid and alkaline phosphatase were 40% to 80% greater (p < 0.05) in mature females. Total and specific activity for beta-adrenergic receptors, on the other hand, were higher in the male rabbits. These findings suggest that sex hormones play a role in regulating the levels of expression of a number of enzymes and receptors, including several which are clearly involved in lacrimal secretory functions.

Aging↗
PubMed1993

Cleft nose. Form and function.

Clefts of the lip and palate frequently produce nasal deformities that tend to reduce the size of the nasal airway. Surgical correction of nasal, palatal, and pharyngeal structures may compromise breathing further. A significant number of individuals with cleft noses mouthbreathe to some extent because of the high prevalence of airway compromise.

Abnormalities, Multiple↗
PubMed1992

Assessing the effects of odorants on nasal airway size and breathing.

A technique was developed to obtain continuous measurements of both respiratory behavior and nasal patency in response to well-controlled odorant stimulation. An automated apparatus similar to that described by Walker et al. (27) was used to present precise concentrations of an odorant. The pressure-flow technique (28) was used to continuously measure nasal airway cross-sectional area, nasal airflow rate, air volume and time characteristics associated with breathing before and during odorant stimulation. Immediately following each odorant presentation, subjects entered their psychophysical responses into a microcomputer via an electronic mouse. Respiratory and psychophysical responses of ten normal subjects to four concentrations of acetic acid during eight odorant trials were recorded; eight clean-air trials were also conducted. At the highest concentration, changes in respiratory behavior were observed as early as 200 ms after stimulus onset in some subjects. Inspiratory volumes during odorant presentation were lower than those seen just before stimulation. The magnitude of this decrease was directly related to the concentration of acetic acid and to the perceived intensity of the odor and degree of nasal irritation.

Airway Resistance↗
PubMed1992

Clinical application of the ACCO appliance. Part 1.

Difficult Class II, Division 1 malocclusions can be successfully treated with a combination of fixed and removable appliances. The clinical application of the Margolis ACCO appliance is demonstrated in a variety of malocclusions through the use of before-treatment progress, and posttreatment records.

Adolescent↗