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Biomedical subjects

D W Warren

Publications and source records attributed to D W Warren.

At least 91 records · Page 5Linked to original sources

Increased nasal resistance induced by the pressure-flow technique and its effect on pressure and airflow during speech.

Although the validity of the pressure-flow technique has been verified in a number of laboratories, some questions still remain. The purpose of this study was to determine whether the procedures involved in estimating orifice size affect the pressure and airflow variables being measured. Twenty subjects with demonstrated velopharyngeal inadequacy on pressure-flow testing (VPO greater than or equal to 0.10 cm2) were assessed under two contrasting conditions. Subjects were asked to produce (p) in the word "hamper" with a) one nostril occluded by a cork as in pressure-flow testing and b) both nostrils patent. The results indicate that the increased nasal resistance resulting from occlusion of one nostril does not appreciably affect pressure and airflow associated with plosive consonant production in patients with velopharyngeal inadequacy.

Adolescent↗

Alterations in velopharyngeal function after maxillary advancement in cleft palate patients.

Velopharyngeal function was assessed aerodynamically prior to surgery and at least 1 year following surgery in 24 cleft palate patients who underwent maxillary advancement. In 5 patients (23%) deterioration and in 5 patients (23%) improvement of velopharyngeal function was observed. In those patients whose velopharyngeal function improved, a pharyngeal flap was in place at surgery. Of the 5 patients whose velopharyngeal function deteriorated, 4 had adequate and 1 borderline adequate velopharyngeal function prior to surgery. In the remaining 14 patients, velopharyngeal function was unchanged. No relationship between the amount of maxillary advancement or the "need ratio" and velopharyngeal function was observed.

Adolescent↗

The effect of in utero ethinyl oestradiol exposure on the risk of cryptorchid testis and testicular teratoma in mice.

Epidemiological findings indicate that both cryptorchid testis and testicular germ cell cancer may be a result of high maternal oestrogen levels early in pregnancy. An experiment was conducted with a mouse strain (129 Sv-S1 C P) in which the males are susceptible to testicular teratomas to determine if the frequency of undescended testis and testicular teratoma in male offspring could be increased by administration of ethinyl oestradiol (EE) to pregnant mice before day 13 of gestation. This point in gestation marks the completion of the migration of germ cells to the gonadal ridge in mice and other studies with these mice have shown that the tumours are initiated in this critical time period. EE mixed with corn oil was administered by subcutaneous injection in doses of 0.02 (n = 76) and 0.2 (n = 102) mg kg-1 of body weight on gestational days 11 and 12. These mice were allowed to deliver their offspring and the males were killed at 15 days of age. Since the tumours are present from birth, this amount of time was allowed to permit the tumours to reach sufficient size for easy visual identification. Compared to controls (n = 63), who received corn oil alone, the treated mothers produced offspring who were significantly more likely to have a cryptorchid testis (P = 0.0001) and who had an increased risk, although not significant, of a testicular teratoma.

Animals↗

The modified tongue-anchor technique as a screening test for velopharyngeal inadequacy: a reassessment.

Pressure-flow assessment of velopharyngeal (v-p) orifice size was used to test the accuracy with which tongue-anchor task results categorize patients differing in v-p adequacy status. The results indicate that this screening task was fairly accurate in identifying patients with v-p adequacy as defined by aerodynamic assessment (specificity = 0.85). It was not quite as accurate in correctly categorizing patients with inadequacy (sensitivity = 0.78). The predictive power of this screening test and its utility in a school setting are discussed.

Adolescent↗

Steroidogenic enzyme activities, morphology, and receptor studies of a testicular adrenal rest in a patient with congenital adrenal hyperplasia.

Steroid-secreting tumors of the testis have generally been considered to be of Leydig cell origin. Testicular tumors in patients with congenital adrenal hyperplasia have been thought to be adrenal rests, but no conclusive evidence supporting the hypothesis has been presented. We report a morphological and biochemical analysis of a patient with 21-hydroxylase deficiency who developed bilateral nodular hyperplasia of steroid-secreting tissue within the testis, despite suppression therapy with both exogenous glucocorticoids and testosterone. The tissue was formed of confluent nodules of homogenous cells. Electron microscopy showed the cells to have abundant smooth endoplasmic reticulum, well developed Golgi apparatus, and mitochondria with predominantly tubular cristae, features characteristic of steroid-secreting cells of adrenocortical origin. Crystals of Reinke were not observed. Functional studies in vivo showed a marked response to ACTH infusion, with 17-hydroxyprogesterone rising from 56 to 13,500 ng/mL, cortisol from less than 2 to 19 micrograms/dL, and testosterone from 369 to 629 ng/dL, with an attendant increase in testicular size and pain over 48 h. Receptor studies in vitro revealed no gonadotropin receptors, but abundant angiotensin-II receptors. Enzyme activity analysis in vitro showed undetectable 21-hydroxylase activity and an enzyme profile consistent with adrenocortical cells rather than Leydig cells. Based on these morphological and biochemical findings, we conclude that the nodular steroidogenic tissue that replaced this patient's testes was of adrenal origin. The study documents for the first time the development of adrenocortical tumors from adrenal rest tissue within the testis.

Adrenal Glands↗

Effect of age on nasal cross-sectional area and respiratory mode in children.

Although nasal cross-sectional size has been reported for adults, no information is available concerning the effects of age on nasal area and breathing mode in children. Determination of the effect of age on nasal size is necessary in order to define nasal airway impairment in children. The purpose of this study was to determine mean nasal cross-sectional size in children between the ages of 6 and 15 years. One hundred two children were assessed during resting breathing. The pressure-flow technique was used to estimate nasal cross-sectional size, and inductive plethysmography was used to assess nasal-oral breathing. The results indicate that nasal airway size increased approximately 0.032 cm2 each year. Mean nasal cross-sectional area increased from 0.21 +/- 0.05 cm2 at age 6 to 0.46 +/- 0.15 cm2 at age 14. The percentage of nasal breathing also increased with age.

Adolescent↗

The relationship between nasal airway size and nasal-oral breathing in cleft lip and palate.

Clefts of the lip and palate generally result in reduced size of the nasal airway. Procedures such as the placement of a pharyngeal flap tend to further compromise nasal breathing. The purpose of this study was to determine how size of the nasal airway affects the mode of breathing in adults with cleft lip and/or palate. A heterogeneous population of 50 adult subjects with cleft lip and/or palate was studied. Nineteen of the subjects had pharyngeal flaps. Respiratory inductive plethysmography was used in combination with an integrating pneumotachograph to measure percent nasal breathing. Pressure-flow studies were used to estimate nasal airway size. The data revealed that a majority of subjects had an airway size of less than 0.4 cm2, which constitutes impairment. Mean cross-sectional area for all subjects was 0.38 cm2 +/- 0.20 SD. Seventy percent of the subjects studied were oral breathers to some extent. A Spearman rank correlation coefficient of 0.725 (p less than 0.0001) indicated that oral-nasal breathing mode was related to airway size. Airway size in the subgroup with pharyngeal flaps was even smaller (0.31 cm2), while percent nasal breathing was lower. Mouthbreathing was observed in all subjects whose airway size was less than 0.38 cm2.

Adolescent↗

Maintaining speech pressures in the presence of velopharyngeal impairment.

Most, but not all, individuals with velopharyngeal inadequacy maintain consonant pressures greater than 3 cm H2O even with decreased velar resistance. The purpose of this study was to identify variables that might differentiate those who achieve adequate pressures from those who do not. Forty-four cleft lip and/or palate subjects were assessed during production of /p/ in the word "hamper." Twenty-three subjects achieved pressures greater than 3 cm H2O and 21 did not. The pressure-flow technique was used to assess velopharyngeal orifice size, nasal resistance, velar resistance, and nasal airflow during speech. Nasal cross-sectional area was measured during breathing. The data were analyzed by age and gender. Results indicate that the inability to achieve adequate consonant pressures in the presence of velopharyngeal inadequacy is more likely to occur in adults than in children. Although children are known to produce consonants at higher pressures than adults, the age disparity between groups did not account for the pressure differences. The most significant factor differentiating adequate and low pressure speakers was the magnitude of nasal plus velar resistance. This difference was consistent across age and gender.

Adolescent↗

The aerodynamic characteristics of speech produced by normal speakers and cleft palate speakers with adequate velopharyngeal function.

Pressure-flow data were obtained on 20 noncleft adults with normal speech and 26 adults with repaired cleft palate. All subjects had adequate velopharyngeal function as determined by preliminary aerodynamic assessment. Subjects were considered to have adequate closure if they had velopharyngeal areas no greater than 0.049 cm2 during production of /p/ in the word "hamper." Although the subjects in both groups demonstrated velopharyngeal adequacy, the subjects with cleft palate produced speech with significantly less nasal airflow. In addition, their intra-oral pressure curve was shifted forward in time. These differences suggest that speakers with cleft palate and adequate velopharyngeal function make certain compensatory adjustments that may be necessary because of differences in velopharyngeal movement capabilities. The potential significance of this for treatment planning is discussed.

Adolescent↗

Effect of airway obstruction upon facial growth.

This article explores both sides of the controversy concerning respiratory behaviors and dentofacial development. The literature is replete with statements that airway impairment alters facial and dental growth, but there also is substantial evidence to the contrary. Much of the confusion stems from the subjective criteria frequently used in defining the terms impairment and mouth breathing. Additionally, respiratory mechanics have often been viewed simplistically rather than in the realistic sense of a complex regulation/control system. Unfortunately, lack of objectivity may lead to an incorrect diagnosis and even worse, inappropriate treatment. Newer respirometric techniques offering more quantitative assessment of respiratory behaviors are now providing more relevant information and more objective definitions of airway impairment and mouth breathing. More recent findings suggest that nasal-oral breathing per se is not necessarily harmful to growth. However, in instances when the nasopharyngeal or oropharyngeal airspace is small, exaggerated postural responses in obligatory nasal-oral breathers may be detrimental to growth.

Adolescent↗

Quantitative assessment of the biological effects of follicle regulatory protein on dihydrotestosterone-maintained spermatogenesis in hypophysectomized rat.

Follicle regulatory protein (FRP) isolated from porcine ovarian follicles influences folliculogenesis through a paracrine mechanism. A similar protein has been found in the testes and seems to have some inhibitory effects on spermatogenesis when administered to intact male experimental animals. On the basis of female and male studies, it has been ascertained that the effects of FRP are at the level of gonads and not the pituitary or the hypothalamus. In the studies with intact males it was not possible to determine the exact site of FRP action on the testes. Dihydrotestosterone (DHT) has been shown to maintain spermatogenesis in hypophysectomized rats. In order to determine if the inhibitory effects of FRP are at steps prior to the formation of DHT, FRP was administered to hypophysectomized rats that were injected with DHT. Groups of adult rats were hypophysectomized and treated daily with FRP, DHT, FRP + DHT, or vehicle alone for 30 days. At necropsy, body, testes, prostate glands, and seminal vesicle weights were recorded. One testis and sexual accessory glands were fixed for histological evaluation. The contralateral testis was decapsulated, six 2 mm segments of seminiferous tubules, representing defined stages of spermatogenesis, were isolated by transillumination-assisted microdissection, and spermatogenic cells were quantified by DNA flow cytometry. Histologically, the seminiferous tubules of vehicle-treated hypophysectomized controls showed advanced regression. Rats treated with FRP alone showed similar degeneration. On the other hand, rats treated with DHT showed maintenance of spermatogenesis comparable to normal controls. The testes of rats treated with FRP + DHT were indistinguishable from those treated with DHT only. Flow cytometric quantification of germinal cells from all groups confirmed the histological findings. In this study FRP did not exert deleterious effects on DHT-maintained spermatogenesis. This finding suggests that the inhibitory effects of FRP on spermatogenesis in intact animals may not be a direct effect on spermatogenic cells but may impair androgen action or production or DHT formation.

3-Hydroxysteroid Dehydrogenases↗

Effects of velar resistance on speech aerodynamics.

The level of intelligibility attained by speakers with cleft palate reflects not only the ability to achieve adequate velopharyngeal closure but other complex variables as well. When closure is inadequate, performance is influenced by compensatory responses of the tongue, vocal folds, respiratory muscles and nasal valve. The purpose of the present study was to determine how a loss of velar resistance associated with velopharyngeal inadequacy affects speech pressures and airflow. The pressure-flow technique (Warren, 1979) was used to assess mean airflow rate, mean intraoral and nasal pressures and velopharyngeal orifice areas in 211 subjects diagnosed as having cleft palate or velopharyngeal inadequacy. The data revealed that resistance fell as velopharyngeal orifice area increased. Intraoral pressures also fell as resistance dropped while nasal pressures and airflow rate increased. These findings suggest that individuals with velar inadequacy and associated low velar resistance compensate by increasing airflow rate in an attempt to maintain adequate pressures for consonant sound production.

Adolescent↗

Development of the inhibitory guanine nucleotide-binding regulatory protein in the rat testis.

The functional development of the inhibitory guanine nucleotide-binding regulatory protein (Gi) and anti-diuretic hormone (ADH) activity was investigated in rat testes. Adult (90-day-old), adolescent (40-day-old), prepubertal (23-day-old), and fetal (20.5 days of gestation) testis cells were cultured with 100 ng/ml pertussis toxin for 24 h. The cells were then cultured with human chorionic gonadotropin (hCG), the ADH agonist arginine vasotocin (AVT), or a combination of the two. Testis cells from rats 23, 40, and 90 days of age that were incubated with hCG increased testosterone production when compared with controls. Preincubation of the cells from postnatal rats with pertussis toxin significantly increased hCG-stimulated testosterone secretion when compared to cells preincubated in medium only at all three ages. AVT suppressed hCG-stimulated testosterone secretion, but this suppression was partially reversed in cells from all postnatal ages preincubated with pertussis toxin. Fetal testis cells showed no response to preincubation with pertussis toxin, even when levels were increased to 400 ng/ml or when pertussis toxin treatment was continued throughout the culture period. AVT also had no effect on fetal testis cells. These results indicate that the Gi protein and AVT are not functional in fetal testes but are active from prepubertal stages of development through maturity.

Animals↗

Respiratory response to a decrease in velopharyngeal resistance.

Individuals with congenital velopharyngeal impairment generally maintain adequate levels of intraoral pressures during consonant production by increasing respiratory effort. The purpose of the present study was to determine if normal individuals respond to a decrease in velopharyngeal resistance in a similar way. The velar mechanism was perturbed by having subjects voluntarily lower the soft palate during a series of words involving plosive consonants. The pressure-flow technique was used to measure oral pressures, calculate velopharyngeal orifice resistance, and estimate velopharyngeal orifice area. Inductive plethysmography was used to measure breathing volumes associated with the words. The data indicate that, in most instances, intraoral pressure remained at appropriate levels (greater than 3.0 cm H2O) after velar lowering. Speech breathing volume did not change during inspiration, but increased during speech expiration when the velopharyngeal port was open. The difference was statistically significant (p less than 0.01). Duration of the utterance did not change across conditions. A mechanical model was then used to determine how intraoral pressure would be affected by simulating the same conditions in a passive system. The modeling data revealed that pressure would drop threefold. It was concluded that increased respiratory volumes tend to stabilize intraoral pressure when vocal tract resistance is experimentally reduced.

Humans↗

The rat 78,000 dalton glucose-regulated protein (GRP78) as a precursor for the rat steroidogenesis-activator polypeptide (SAP): the SAP coding sequence is homologous with the terminal end of GRP78.

Based on the striking sequence identity between the amino acid sequence of rat steroidogenesis-activator polypeptide (SAP) and the carboxyl terminus of the 78,000 dalton glucose-regulated protein (GRP78), the precursor-product relationship between GRP78 and SAP was investigated in Leydig cells. Immunoblot analysis with peptide antibodies specific for GRP78 and SAP showed that the putative SAP precursor is also immunoreactive with the anti-GRP78 antibody. Genomic blot hybridizations further revealed that GRP78 is neither rearranged nor amplified in the H-540 Leydig cell tumor, the original source for SAP. Further, there appears to be a single copy of the SAP coding sequence within the rat genome. This sequence resides within the last exon of GRP78. Our observations support the hypothesis that, in steroidogenic cells, SAP is likely to be derived from posttranslational processing of a very minor fraction of GRP78.

Amino Acid Sequence↗

The speech regulating system: temporal and aerodynamic responses to velopharyngeal inadequacy.

Temporal and respiratory responses to a loss of velar resistance were measured in 107 subjects demonstrating varying degrees of velopharyngeal inadequacy. The subject data were compared to data generated by a mechanical model representing a passive system. The pressure-flow technique was used to estimate velopharyngeal orifice size and measure respiratory and temporal characteristics of aerodynamic events associated with the production of the nasal-plosive blend /mp/ in the word "hamper". Subjects were categorized as having adequate closure (less than 0.05 cm2), adequate/borderline closure (0.05-0.09 cm2), borderline/inadequate closure (0.10-0.19 cm2) and inadequate closure (greater than or equal to 0.20 cm2). The data revealed that intraoral pressure fell 10-fold in the model as velopharyngeal orifice area changed from adequate closure to inadequate. The subject data demonstrated only a 1.4-fold drop in pressure. Airflow data indicated that there was a 10-fold increase in respiratory volume in the subject data corresponding to the change from adequacy to inadequacy. When respiratory and temporal responses were assessed together, the findings revealed that airflow and temporal changes minimized the fall of pressure as velar resistance declined across groups.

Adolescent↗