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Biomedical subjects

W J Doyle

Publications and source records attributed to W J Doyle.

At least 163 records · Page 9Linked to original sources

The effects of audiogenic stress on the growth of long bones in the laboratory rat (Rattus norvegicus).

It has been demonstrated that experimentally induced cold stress produces a stunting effect in the limbs of rodents. Such an effect has also been reported for the dentition and limbs in response to other stressors (heat, cold). Recent research into the effects of various stressors on the magnitude of fluctuating dental asymmetry demonstrated that general stress increases the magnitude of fluctuating dental asymmetry in experimental animals. However, no increase in the magnitude of fluctuating asymmetry of limb length was reported as a response of general stress. In the light of such studies the present research investigates the relationship between stress and the mass per unit length of limbs. The stressor chosen for the present study was audiogenic stress as it has been demonstrated to induce the general stress syndrome and also increase the magnitude of fluctuating dental asymmetry. Audiogenic stress is found to produce increases in the magnitude of fluctuating asymmetry of the mass per unit length of long bones in the laboratory rat. Also the absolute values of long bone length and mass per unit length are significantly smaller in stressed animals when compared with controls. The relationship between the stress induced stunting of linear dimensions and the increase in the magnitude of fluctuating asymmetry is discussed.

Animals↗

Antagonistic compensation as a function of reduced weight bearing.

The principle of antagonistic compensation was presented by RIESENFELD in 1966 to explain the relative shortening and broadening of hypofunctional bones. Few studies have concerned themselves with this phenomenon, even though the causative agent(s) have not been delineated. In this study, RIESENFELD induced the hypofunction by complete unilateral bilateral forelimb amputation. The resulting hypofunctional condition may be attributed to the lack of muscle function or to the lack of weight bearing or both in combination. In the present study weight bearing was eliminated in such a manner as to preserve muscle functioning. This was accomplished by two techniques: (1) unilateral forearm amputation and (2) unilateral humeral resection. Statistically significant differences in interindividual scapular length and breadth as well as humeral and ulnar lengths are reported. In all cases, the bones of the operated side were shorter than those of the unoperated side and the scapular breadth of the unoperated side was relatively greater. This confirms the hypothesis that weight bearing is, at least, partially responsible for the morphological changes induced by hypofunction and described by the principle of antagonistic compensation. However, as the reduction in length was of a lesser magnitude than that reported by RIESENFELD, the input of muscle function cannot be ignored. Rather, as both muscle functioning and weight bearing induce compressive force on long bones (including the scapula), both may serve to initiate the observed morphological changes through the vehicle of reduced compression.

Amputation, Surgical↗

The differential effects of prenatal and postnatal audiogenic stress on fluctuating dental asymmetry.

Audiogenic stress has been shown to have an effect on the development of molar teeth. The present study demonstrates the relative contribution of prenatal and postnatal stress components to increases in fluctuating dental asymmetry in the laboratory rat. It is shown that there is a limit to the amount of change which can be environmentally induced and that if this limit is reached with prenatal stress, postnatal stress will have no significant effect. Audiogenic stress is shown to effect differentially mandibular and maxillary first molars. Length is stable for the maxillary dentition and width is stable in the mandibular molars.

Animals↗

Stress and fluctuating limb asymmetry in various species of rodents.

Recent studies have shown that the dentition of rodents responds to stress, evidenced by an increase in fluctuating asymmetry. In the present study, three known stressors, noise, cold and behavioral modification, were employed in evaluating the effects of stress on limb asymmetry. None of the stressors employed produced significant increases in fluctuating limb asymmetry except in the humerus. As teeth are highly genetically determined and bone highly responsive to function, these results suggest a stress-related interference in the synchronization of genetically stable structures.

Animals↗

PCR-based detection of bacterial DNA after antimicrobial treatment is indicative of persistent, viable bacteria in the chinchilla model of otitis media.

PURPOSE: Bacterial deoxyribonucleic acid (DNA) has been previously detected by polymerase chain reactions (PCR) in a significant percentage of culturally-sterile pediatric middle-ear effusions. The current study was designed to determine whether this represents the existence of viable bacteria or the persistence of residual DNA in the middle-ear cleft. MATERIALS AND METHODS: The middle-ear cavities of two sets of chinchillas were inoculated with either: 1) 100 colony-forming units (CFU) of live Haemophilus influenzae, 2.2 x 10(6) CFU of pasteurized Moraxella catarrhalis, and 1000 ng of DNA (>10(8) genomic equivalents) from Streptococcus pneumoniae; or 2) 100 CFU of live S pneumoniae, 2.2 x 10(6) CFU of pasteurized M catarrhalis and 1000 ng of purified DNA from H influenzae. Animals were treated with ampicillin for 5 days beginning on day 3. A single-point longitudinal study design was used for sampling to eliminate the possibility of contamination. RESULTS: No DNA was detectable from the heat-killed bacteria or the purified DNA after day 3. However, DNA from the live bacteria persisted through day 21, even though all specimens were culture-negative following the initiation of antimicrobial therapy. CONCLUSION: These findings indicate that purified DNA and DNA from intact but nonviable bacteria do not persist in the middle-ear cleft in the presence of an effusion, even following high copy inoculation. In contrast, antibiotic-treated bacteria persist in some viable state for weeks as evidenced by the differential ability of the PCR-based assay systems to detect the live bacteria, but not detect the heat-killed organisms.

Ampicillin↗

Maturation of the auditory brain stem response (ABR): additional perspectives.

A retrospective, cross-sectional analysis of component latencies of the auditory brain stem response (ABR) was performed on 466 patients ranging in age from 30 weeks postconception to adulthood. The ontogeny of ABR component wave latencies was adequately described by two exponential curves having different slopes; the steeper curve represented an early, rapid maturation ending by 8 to 10 weeks post partum, and the ensuing, more gradual curve corresponded to developmental events which were completed by the beginning of the third year of extrauterine life. These observations conform to previous maturational concepts of peripheral versus central segments of the auditory pathway and to the gradual decrease in interwave latencies with increasing age. Unlike interwave latency, however, the ratio of the latencies of selected component waves was constant with increasing age. This was especially apparent in developing newborns less than 50 weeks postconception. The nonlinear bases of this phenomenon are outlined, and the insights which stem from this perspective are discussed.

Adolescent↗

Psychological stress, cytokine production, and severity of upper respiratory illness.

OBJECTIVE: The purpose of this study is to assess the role of psychological stress in the expression of illness among infected subjects and to test the plausibility of local proinflammatory cytokine production as a pathway linking stress to illness. METHODS: After completing a measure of psychological stress, 55 subjects were experimentally infected with an influenza A virus. Subjects were monitored in quarantine daily for upper respiratory symptoms, mucus production, and nasal lavage levels of interleukin (IL)-6. RESULTS: Higher psychological stress assessed before the viral challenge was associated with greater symptom scores, greater mucus weights, and higher IL-6 lavage concentrations in response to infection. The IL-6 response was temporally related to the two markers of illness severity, and mediation analyses indicated that these data were consistent with IL-6 acting as a major pathway through which stress was associated with increased symptoms of illness. However, this pattern of data is also consistent with increases in IL-6 occurring in response to tissue damage associated with illness symptoms. CONCLUSIONS: Psychological stress predicts a greater expression of illness and an increased production of IL-6 in response to an upper respiratory infection.

Cohort Studies↗

Normal and abnormal middle ear ventilation.

Studies in infants and children have suggested a functional rather than mechanical obstruction of the Eustachian tube as a predisposing factor in middle ear effusions (MEE). To simulate this condition in the laboratory, an animal model was prepared using juvenile Rhesus monkeys. The tensor veli palatini muscle was transected or expunged posterior to the hamulus of the medial pterygoid lamina. Transection of the muscle resulted in negative middle ear pressure without effusion, whereas when the muscle was expunged, the animals developed a brief episode of negative middle ear pressure followed by a persistent MEE that was sterile for bacteria. An acute bacterial MEE developed following instillation of Streptococcus pneumoniae into the nasopharynx of animals that had had a previous unilateral transection of the muscle. The condition of the middle ear was documented by impedance measurements and presence of the effusion was verified by myringotomy. Animals were periodically examined and tested for Eustachian tube ventilatory function over a period of one year. Before surgical alteration of the tensor muscle. Eustachian tube function tests demonstrated normal ventilatory function, whereas, functional Eustachian tube obstruction patterns similar to studies in children who had MEE were found during the postoperative period. Only after the development of a reliable animal model can current and future methods of management of MEE be tested under controlled laboratory conditions. These data suggest that the Rhesus monkey appears to be an excellent model for the study of normal as well as abnormal tubal function.

Animals↗

Morphology of tensor veli palatini, tensor tympani, and dilatator tubae muscles.

The relationships among the paratubal muscles were studied in human fetal and adult Eustachian tubes. That which has, in recent years, been labeled the tensor veli palatini muscle actually consists of two distinct groups of muscle fibers: a medial group, henceforth termed dilatator tubae, and a lateral group, called tensor veli palatini. The latter was found to have no Eustachian tube origin, but was continuous superiorly with the tensor tympani muscle. The dilatator tubae muscle was found to have a tubal attachment. The participation of this muscle system in the normal functioning of the Eustachian tube-middle ear system in man, and the problems inherent in the development of animal models simulating the physiology of the physiology of the human system, are discussed.

Adult↗

Dilation of the eustachian tube by electrical stimulation of the mandibular nerve.

The recent studies of the anatomy of the eustachian tube and related structures in the Rhesus monkey (Macaca mulatta) have shown that the monkey tubal system is similar to the human. This investigation in Rhesus monkeys was an attempt to verify previous studies in other animals that the tensor veli palatini muscle was the only dilator of the eustachian tube. Two unipolar stimulating electrodes were introduced into the foramen ovale, and the mandibular branch of the trigeminal nerve was electrically stimulated. Simultaneously, pressure-flow recordings through the eustachian tube were monitored. Stimulus-response relationships were obtained for five Rhesus monkeys. The degree of tubal dilation by the tensor veli palatini muscle contraction was shown to be a function of stimulating current levels. Artifically induced dilations were quite similar to the physiological dilations during swallowing when these animals were tested alert. Following complete transection of the tensor muscle, regardless of the stimulus level, no tubal dilations were observed. Stimulation of the nerve to the internal pterygoid and stimulation of the levator veli palatini muscle induced only constrictions of the tube. The tensor veli palatini muscle is the only paratubal muscle responsible for active dilation of the eustachian tube in the Rhesus monkey, and its motor innervation is the mandibular division of the trigeminal nerve.

Animals↗

Comparison of the anatomy of the eustachian tube in the rhesus monkey (Macaca mulatta) and man: implications for physiologic modeling.

The primate nasopharynx-eustachian tube-middle ear complex is being used to model both the normal and pathologic functions of the human eustachian tube by several researchers. An extensive search of the literature has indicated little detailed information on the primate eustachian tube/middle ear system. This study was undertaken to define the anatomical characteristic of the system in the Rhesus monkey (Macaca mulatta) and to determine the limits on the use of the monkey as a model of human eustachian tube function. Although the direct application of morphologic data to explain the function of a system is tenuous, the data on the Rhesus monkey eustachian tube appears to be consistent with that published for other mammals. The tensor veli palatni muscle appears to be the only muscle to act directly on the tube and effect tubal dilation. The muscle is attached to the lateral membranous tubal wall along its extrabullar extension. The muscle has an inferior attachment to the posterior hard palate and thus possesses a vector directed inferolaterally; contraction would appear to pull the membranous wall inferiorly and laterally, resulting in the tubal dilation. The eustachian tube relationships of the salpingopharyngeus, levator veli palatini, and internal pterygoid muscles are described. Their possible role in primate tubal function is minimal at best.

Animals↗

Eustachian tube function in an American Indian population.

A comparatively high prevalence of acute and chronic otitis media (OM) has been reported for the native American Indian population. The present study reports data on the function of the eustachian tube (ET) in 25 White Mountain Apache Indians ranging in age from 3 to 36 years. All study subjects had a history of OM and reported to the reservation clinic with tympanic membrane perforations and a dry middle ear (ME). The results of inflation-deflation tests on these subjects indicated that the Indians had lower forced opening pressures than had been measured in a group of Caucasians with perforations secondary to chronic OM. Of the 23 subjects studied, 67% equilibrated applied positive ME pressures and 38% equilibrate negative pressures by swallowing. During forced response testing, the passive resistance of the ET was found to be lower and the active resistance equivalent to that of a group of Caucasians with traumatic perforations and otherwise negative otologic histories. While the ET was predilated in these subjects by constant airflow, active swallowing further dilated the tube in 67% of the subjects, constricted the tube in 25%, and had no effect in 8%. This study indicated that the ET of the American Indian was functionally different from that of Caucasians previously studied and was characterized by comparatively abnormal, low passive tubal resistance which may be considered to facilitate ventilatory function and to impair protective function. The difference may account for the high prevalence of OM with perforation and the low incidence of cholesteatoma in this population.

Adolescent↗

Eustachian tube function in cleft palate children.

The cleft palate population has a high prevalence of chronic otitis media with effusion (OME). The present study attempts to relate this pathology to a functional obstruction of the eustachian tube (ET). Employing two methods, the forced-response test and the inflation-deflation test, various parameters of ET function were evaluated in 41 children and adolescents with cleft palates. The results indicated that cleft palate children have a limited ability to open the ET actively by swallowing, as evidenced by an inability to equilibrate applied positive or negative pressures. These children demonstrated little ability to alter pressure in the middle ear (ME) by either the Valsalva or Toynbee maneuver. Passive ET airflow resistance in these children is not different from that of a traumatic perforation group. However, in the majority of cases (73%), the resistance of the tube increased with swallowing, suggesting a constriction of the ET rather than a dilation. Further, for those individuals capable of tubal dilation, the efficiency of dilation as measured by the resistance ratio was significantly less than that reported for the traumatic perforation group. Eustachian tube function in this population was not demonstrably dependent on age, sex, or type of cleft. The cleft palate children of the present study had severe functional obstruction of the ET. This obstruction was primarily related to the inability of the tensor veli palatini (TVP) muscle to dilate the ET actively during swallowing and appears to be the major factor responsible for the pathogenesis of OME in this population.

Adolescent↗

Nonhuman primate model of cleft palate and its implications for middle ear pathology.

The present study is a preliminary report on the development of a nonhuman primate model of cleft palate and middle ear (ME) disease. The causal relationship between a surgical cleft of the soft palate only or a cleft of the hard and soft palate and otitis media with effusion (OME) was investigated in rhesus monkeys. Prior to clefting, ME status was documented by pneumatic otoscopy or otomicroscopic examination and tympanometry over a period of at least five months. A minimum of four preoperative eustachian tube (ET) function evaluations were performed employing the inflation-deflation and the forced-response tests. These procedures were repeated following surgery and during a long-term follow-up. Seventeen of the 18 ears developed a recurrent OME. Postoperative ME pressures were initially high negative values. After the first two postoperative months, high positive ME pressures were recorded. The forced-response test showed little to no long-term changes in passive and active tubal resistances or in the efficiency of tubal dilation as a result of surgery. The inflation-deflation test showed higher opening and closing pressures and a limited and more variable ability to equilibrate applied positive and negative ME pressures following surgery. Both ME status and ET function appeared to improve with time. These findings indicated that the pathogenesis of recurrent OME in this animal model may have been due to changes in ET function associated with an abnormal nasopharynx rather than aberrant tensor veli palatini (TVP) muscle function.

Animals↗

Effect of surgical alterations of the tensor veli palatini muscle on eustachian tube function.

Previous studies in humans have indicated that functional obstruction of the eustachian tube (ET) is an important factor in the pathogenesis of otitis media with effusion (OME). This type of obstruction appears to be related to the structural properties of the tube, or to an inefficient active tubal opening mechanism, or both. In this study, functional ET obstruction was created in 22 rhesus monkeys (Macaca mulatta) by surgically altering the tensor veli palatini (TVP) muscle using three different procedures: 1) complete excision of the muscle; 2) transection of the superficial muscle bundle; or 3) transposition of the muscle tendon medial to the hamular process. Prior to surgery, weekly tympanometry, pneumatic otoscopy, and otomicroscpic examinations were performed for a period of at least six months to document middle ear (ME) status. A minimum of four ET function tests were performed on each animal using the inflation-deflation and forced-response tests. Following surgery, these tests and examinations were continued for periods of up to one year. Postoperatively, the animals in which the TVP had been excised developed a sterile ME effusion which proved to be a chronic condition which persisted throughout the follow-up period. Eustachian tube function tests showed a complete absence of any active tubal dilation by swallowing. Animals that had the muscle transected developed abnormal ME pressures , or effusions, or both, which returned to normal in some ears, but which were recurrent or chronic in others. Eustachian tube function tests in these animals showed an initial loss of active tubal function which gradually improved, but not to normal levels, presumably as a result of healing of the muscle. In cases in which the muscle was transposed the ME pathology and ET dysfunction were similar after the surgery, but improved within a short period of time. These data suggest that alteration of the TVP muscle can create functional obstruction of the ET. The severity of ET obstruction depends upon the surgical procedure undertaken. The results of postoperative ET function tests were similar to those recorded from children with recurrent and chronic OME.

Animals↗

Gas absorption in the middle ear.

The middle ear (ME) pressure of alert and anesthetized rhesus monkeys was monitored by serial tympanograms in order to determine the gas absorption process in the ME cavity. During the four-hour observation period the ME pressure showed small, random fluctuations around zero pressure in the alert animals, whereas in the anesthetized animals, following an initial positive pressure phase, the ME pressure reached a plateau at an average pressure of -60 mm H2O. The ME gas composition was changed by air or oxygen gas politzerization in anesthetized animals to determine the effect of different initial gas compositions on the rate of absorption of the gas and on the magnitude of ME pressure. Politzerization with air and with oxygen gas resulted in average maximum ME pressures of -400 and -730 mm H2O, respectively. The experimental evidence suggested that the physiological composition of ME gases is nearly that of the surrounding environment and that the rate of gas absorption is low. When the gas composition of the ME is changed, the ME pressure decreases considerably. Based on these findings, a possible mechanism for the development of negative ME pressure is proposed.

Absorption↗

Comparison of normal eustachian tube function in the rhesus monkey and man.

Employing inflation-deflation and forced-response tests, the eustachian tube (ET) function was evaluated in six adult human subjects with traumatic perforation of the tympanic membrane and otherwise negative otologic histories; and 15 juvenile or adult rhesus monkeys with freshly created myringotomy perforations of the tympanic membrane and otherwise documented normal middle ears. The study findings demonstrated that the rhesus monkey ET functions as a scaled down model of the ET of man, exhibiting a shorter tubal dilation duration and a lesser capacity to pass air. When ET function in the two species was compared using a dimensionless measure expressing the tubal dilation efficiency, the operational biomechanics of both systems were found to be almost identical. These observed functional homologies between man and the rhesus monkey ET systems suggest that the rhesus monkey is a suitable animal model in which to study the pathogenesis of otitis media with effusion, stemming from ET dysfunction.

Adult↗