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Biomedical subjects

J S Williams

Publications and source records attributed to J S Williams.

At least 19 recordsLinked to original sources

Consequences of periodic augmented breaths on tongue muscle activities in hypoxic rats.

This study was designed to investigate the influence of hypoxia-evoked augmented breaths (ABs) on respiratory-related tongue protrudor and retractor muscle activities and inspiratory pump muscle output. Genioglossus (GG) and hyoglossus (HG) electromyogram (EMG) activities and respiratory-related tongue movements were compared with peak esophageal pressure (Pes; negative change in pressure during inspiration) and minute Pes (Pes x respiratory frequency = Pes/min) before and after ABs evoked by sustained poikilocapnic, isocapnic, and hypercapnic hypoxia in spontaneously breathing, anesthetized rats. ABs evoked by poikilocapnic and isocapnic hypoxia triggered long-lasting (duration at least 10 respiratory cycles) reductions in GG and HG EMG activities and tongue movements relative to pre-AB levels, but Pes was reduced transiently (duration of <10 respiratory cycles) after ABs. Adding 7% CO(2) to the hypoxic inspirate had no effect on the frequency of evoked ABs, but this prevented long-term declines in tongue muscle activities. Bilateral vagotomy abolished hypoxia-induced ABs and stabilized drive to the tongue muscles during each hypoxic condition. We conclude that, in the rat, hypoxia-evoked ABs 1) elicit long-lasting reductions in protrudor and retractor tongue muscle activities, 2) produce short-term declines in inspiratory pump muscle output, and 3) are mediated by vagal afferents. The more prolonged reductions in pharyngeal airway vs. pump muscle activities may lead to upper airway narrowing or collapse after spontaneous ABs.

Animals↗

Influence of posture and breathing route on neural drive to upper airway dilator muscles during exercise.

Our purpose was to determine the influence of posture and breathing route on electromyographic (EMG) activities of nasal dilator (NDM) and genioglossus (GG) muscles during exercise. Nasal and oral airflow rates and EMG activities of the NDM and GG were recorded in 10 subjects at rest and during upright and supine incremental cycling exercise to exhaustion. EMG activities immediately before and after the switch from nasal to oronasal breathing were also determined for those subjects who demonstrated a clear switch point (n = 7). NDM and GG EMG activities were significantly correlated with increases in nasal, oral, and total ventilatory rates during exercise, and these relationships were not altered by posture. In both upright and supine exercise, NDM activity rose more sharply as a function of nasal inspired ventilation compared with total or oral inspired ventilation (P < 0.01), but GG activity showed no significant breathing-route dependence. Peak NDM integrated EMG activity decreased (P = 0.008), and peak GG integrated EMG activity increased (P = 0.032) coincident with the switch from nasal to oronasal breathing. In conclusion, 1) neural drive to NDM and GG increases as a function of exercise intensity, but the increase is unaltered by posture; 2) NDM activity is breathing-route dependent in steady-state exercise, but GG activity is not; and 3) drive to both muscles changes significantly at the switch point, but the change in GG activity is more variable and is often transient. This suggests that factors other than the breathing route dominate drive to the GG soon after the initial changes in the configuration of the oronasal airway are made.

Adult↗

Stimulation of quiescent corneal endothelial cells by direct delivery of the SV40 large T-antigen protein.

PURPOSE: To determine whether the delivery of the SV40 large T-antigen is a feasible method for transiently inducing proliferation of corneal endothelial cells. METHODS: Liposome-mediated delivery of proteins into bovine corneal endothelial cells (BCEC) was utilized in this study. Initially, beta-galactosidase was used as a marker protein for cell delivery and cells were assayed colorimetrically for beta-galactosidase activity. Subsequently, SV40 large T-antigen protein was introduced into BCEC and positive cells were identified by immunohistochemistry 24 hours after liposome-protein treatment. Quiescent BCECs were double-labeled using BrdU as a measure of de novo DNA synthesis and the SV40 large T-antigen was detected by standard immunohistochemical methods. RESULTS: Beta-galactosidase or SV40 large T antigen were introduced into BCECs using liposome transfer methods. The transfer efficiency of beta-galactosidase was > 30% of the cells. SV40 large T antigen was successfully introduced and was localized to the nuclei of BCECs. The treatment of quiescent BCECs with large T antigen caused an increase in BrdU incorporation. Co-labeling confirmed that only cells containing SV40 large T antigen were positive for de novo DNA synthesis. CONCLUSIONS: This study demonstrates that proteins can be inserted directly into corneal endothelial cells. In the case of the SV40 large T-antigen, the protein localized to the nucleus and maintained its bioactivity by inducing DNA synthesis. This finding suggests that liposome-mediated delivery of transforming proteins could be a method to transiently induce corneal endothelial cell proliferation.

Animals↗

Effect of co-activation of tongue protrudor and retractor muscles on tongue movements and pharyngeal airflow mechanics in the rat.

1. The purpose of these experiments was to examine the mechanisms by which either co-activation or independent activation of tongue protrudor and retractor muscles influence upper airway flow mechanics. We studied the influence of selective hypoglossal (XIIth) nerve stimulation on tongue movements and flow mechanics in anaesthetized rats that were prepared with an isolated upper airway. In this preparation, both nasal and oral flow pathways are available. 2. Inspiratory flow limitation was achieved by rapidly lowering hypopharyngeal pressure (Php) with a vacuum pump, and the maximal rate of flow (VI,max) and the nasopharyngeal pressure associated with flow limitation (Pcrit) were measured. These experimental trials were repeated while nerve branches innervating tongue protrudor (genioglossus; medial XIIth nerve branch) and retractor (hyoglossus and styloglossus; lateral XIIth nerve branch) muscles were stimulated either simultaneously or independently at frequencies ranging from 20-100 Hz. Co-activating the protrudor and retractor muscles produced tongue retraction, whereas independently activating the genioglossus resulted in tongue protrusion. 3. Co-activation of tongue protrudor and retractor muscles increased VI, max (peak increase 44 %, P < 0.05), made Pcrit more negative (peak decrease of 44 %, P < 0.05), and did not change upstream nasopharyngeal resistance (Rn). Independent protrudor muscle stimulation increased VI,max (peak increase 61 %, P < 0.05), did not change Pcrit, and decreased Rn (peak decrease of 41 %, P < 0.05). Independent retractor muscle stimulation did not significantly alter flow mechanics. Changes in Pcrit and VI,max at all stimulation frequencies were significantly correlated during co-activation of protrudor and retractor muscles (r2 = 0.63, P < 0.05), but not during independent protrudor muscle stimulation (r2 = 0.09). 4. These findings indicate that either co-activation of protrudor and retractor muscles or independent activation of protrudor muscles can improve upper airway flow mechanics, although the underlying mechanisms are different. We suggest that co-activation decreases pharyngeal collapsibility but does not dilate the pharyngeal airway. In contrast, unopposed tongue protrusion dilates the oropharynx, but has a minimal effect on pharyngeal airway collapsibility.

Animals↗

Pulsatile tinnitus cured by angioplasty and stenting of petrous carotid artery stenosis.

Pulsatile tinnitus may result from turbulent flow within the ipsilateral internal carotid artery. Surgical endarterectomy and carotid artery ligation have been used to treat atherosclerotic stenosis with or without associated pulsatile tinnitus. To our knowledge, this is the first reported case of pulsatile tinnitus, attributable to internal carotid artery stenosis, successfully treated by angioplasty and stenting.

Angiography↗

Characterization of 2,3,7,8-tetrachlorodibenzofuran-dependent suppression and AH receptor pathway gene expression in the developing mouse mammary gland.

The AH receptor (AHR) is a ligand-activated transcription factor and member of a growing family of homologous proteins implicated in development. In this study we have characterized the actions of 2,3, 7,8-tetrachlorodibenzofuran (TCDF), a well-studied AHR ligand, and the expression of AHR and selected AHR signal transduction pathway genes in the developing mouse mammary gland. High levels of AHR protein were observed in the mammary glands of C57Bl/6J (AHR +/+) mice during estrous-stimulated growth and branching of terminal end buds (TEBs). Comparative analysis of mammary gland development in AHR -/- and +/+ littermates revealed a 50% reduction in TEBs and an increase in blunt-ended terminal ducts in the AHR null animals. Treatment of mammary glands, removed from estrogen/progesterone-primed C57Bl/6J mice and maintained in organ culture, with TCDF suppressed lobule development (greater than twofold decreases in lobule number and size), with a concomitant suppression of DNA synthesis, as judged by a 35 to 45% decrease in [3H]thymidine incorporation in the TEBs. Immunohistochemical staining patterns for AHR, aryl hydrocarbon nuclear translocator (ARNT; the heterodimerization partner of AHR), and two AHR-regulated genes, Cyp1A1 and Cyp1B1, were similar and not altered by treatment of mammary glands in organ culture with TCDF. The observed differences in the development of mammary glands from AHR +/+ and -/- mice, associated expression of the AHR protein with hormone-dependent lobule development, and suppressive actions of TCDF support the position that, in C57Bl/6J mice, development of the mammary gland is at least in part AHR dependent. Development occurs in the absence of exogenous AHR ligand, suggesting that the unoccupied receptor may function to support the proliferative stages required for full lobule development.

Animals↗

A prospective study of pain and analgesic use in outpatient endoscopic anterior cruciate ligament reconstruction.

A prospective study was undertaken to evaluate the postoperative pain and analgesic profiles of a group of 50 patients undergoing outpatient anterior cruciate ligament (ACL) reconstruction and to compare their profiles with those of a group of 50 patients undergoing outpatient non-ACL arthroscopic surgery. All patients received preoperative and postoperative ketorolac, intraincisional/intra-articular bupivacaine, intraoperative ketorolac, and propofol anesthetic. The percentage of patients receiving supplemental analgesia in the recovery room was 49% (average, 2.2 mg intravenous morphine sulfate) for the ACL group and 31% (average, 1.2 mg intravenous morphine sulfate) in the non-ACL group. Narcotic use and pain scores peaked in both groups on postoperative days 1 and 2. The ACL group used significantly more narcotic and had higher pain scores in the first week after surgery than did the non-ACL group. However, there were no subsequent admissions, readmissions, or emergency room visits for pain. All were satisfied with the outpatient nature of this surgery. Patients tolerate outpatient endoscopic ACL reconstruction with moderate pain and narcotic use. Outpatient endoscopic ACL reconstruction can be performed safely, effectively, and with considerable cost savings.

Adult↗

Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19).

Purified rabbit immunoglobulin raised against yeast-expressed recombinant FVO or 3D7 Plasmodium falciparum merozoite surface protein-1 (MSP-1) 19k-D C terminal fragment (MSP-1(19)) was transfused into malaria-naive Aotus nancymai monkeys that were immediately challenged with FVO asexual stage malaria parasites. Control monkeys received rabbit immunoglobulin raised against the sexual stage antigen Pfs25 or Aotus hyperimmune serum obtained from monkeys immunized by P. falciparum infection and drug cure. Passive transfer of rabbit anti-MSP-1(19) failed to protect against homologous or heterologous challenge and, when compared with negative controls, there were no differences in prepatent periods or time to treatment. Interestingly, rabbit anti-MSP-1(19), but not anti-Pfs25, immunoglobulin, and immune monkey serum prevented the development of antibodies directed against MSP-1(19) fragment by infected monkeys, indicating that the antibodies were reactive with native MSP-1(19) antigen in vivo. The prepatent period and time to treatment was greatly delayed in the two monkeys that received Aotus immune serum, both of which developed a chronic intermittent low level infection. In vitro parasite growth inhibition assays (GIAs) confirmed the presence of inhibitory activity (40% maximum inhibition) in concentrated anti-MSP-1(19) immunoglobulin (4.8 mg/ml), but the peak concentrations we achieved in vivo (1 mg/ml) were not inhibitory in vitro. Subinhibitory levels of anti-MSP-1(19) antibodies achieved by passive transfer were not protective against P. falciparum challenge.

Animals↗

Pediatric throwing injuries about the elbow.

Pediatric elbow injuries that result from repetitive throwing-type activities are common. These injuries differ from those seen in adults, because of anatomic differences. The purpose of this paper is twofold: first, to review the anatomy of the elbow and the mechanics of the throwing motion about the elbow, and second, to discuss the diagnosis, treatment, rehabilitation, and prevention of pediatric throwing injuries of the elbow.

Adolescent↗

Osteochondritis dissecans of the knee.

Osteochondritis dissecans is a separation of an articular cartilage subchondral bone segment from the remaining articular surface. This is a different entity from osteonecrosis, with which osteochondritis dissecans is commonly confused. In osteochondritis dissecans, the fragment separates from a vascular normal bony bed, while in osteonecrosis, the fragment typically is more peripheral and separates from an avascular bony bed. Osteochondritis dissecans is more common in adolescents and young adults, with the knee, elbow, and ankle being the most common sites. Injury to an area of fairly tenuous blood supply is the most likely cause. Treatment is typically nonoperative for stable lesions and operative for unstable lesions. Most patients do well with no long-term sequelae, but this depends on a variety of factors including the location and size of the lesion, patient age, and treatment.

Adolescent↗

Noncorrelation between thoracic skeletal injuries and acute traumatic aortic tear.

It is generally accepted that the presence of thoracic skeletal injuries has a predictive value for acute traumatic aortic tear (ATAT). The purpose of this study is to objectively assess the validity of that premise. The initial chest radiographs of 548 patients who underwent aortic angiography for suspected ATAT were reviewed for thoracic skeletal injuries. The incidence of thoracic skeletal injuries was compared between patients with and without angiographically confirmed ATAT. Rib fracture is the only thoracic skeletal injury whose incidence is statistically significantly higher in patients with ATAT (36 of 62, 58.1%) than in those without (207 of 486, 42.6%) (p = 0.0209). The positive predictive value of rib fractures in evaluating ATAT, however, is 14.8%, a rate similar to the incidence of ATAT at most trauma centers, and the specificity is 57.4%. The second most common finding in patients with ATAT, the absence of thoracic skeletal injury, is not statistically significantly different between patients with ATAT (24 of 62, 38.7%) and those without (220 of 486, 45.3%) (p = 0.3279). We conclude that (1) there is no clinically relevant correlation between thoracic skeletal injuries and ATAT, and (2) selection of patients requiring thoracic aortography must be based on appropriate mechanism of injury and radiographic evidence of mediastinal hematoma.

Aneurysm, False↗

Differences between estimates and measured PaCO2 during rest and exercise in older subjects.

Arterial PCO2 (PaCO2) has been estimated during exercise with good accuracy in younger individuals by using the Jones equation (PJCO2) (J. Appl. Physiol. 47: 954-960, 1979). The purpose of this project was to determine the utility of estimating PaCO2 from end-tidal PCO2 (PETCO2) or PJCO2 at rest, ventilatory threshold (VTh), and maximal exercise (Max) in older subjects. PETCO2 was determined from respired gases simultaneously (MGA 1100) with arterial blood gases (radial arterial catheter) in 12 older and 11 younger subjects at rest and during exercise. Mean differences were analyzed with paired t-tests, and relationships between the estimated PaCO2 values and the actual values of PaCO2 were determined with correlation coefficients. In the older subjects, PETCO2 was not significantly different from PaCO2 at rest (-1.2 +/- 4.3 Torr), VTh (0.4 +/- 2.5), or Max (-0.8 +/- 2.7), and the two were significantly (P < 0.05) correlated at Vth (r = 0.84) and Max (r = 0.87) but not at rest (r = 0.47). PJCO2 was similar to PaCO2 at rest (-1.0 +/- 3.9) and Vth (-1. 3 +/- 2.3) but significantly lower at Max (-3.0 +/- 2.6), and the two were significantly correlated at Vth (r = 0.86) and Max (r = 0. 80) but not at rest (r = 0.54). PETCO2 was significantly higher than PaCO2 during exercise in the younger subjects but similar to PaCO2 at rest. PJCO2 was similar to PaCO2 at rest and Vth but significantly lower at Max in younger subjects. In conclusion, our data demonstrate that PaCO2 during exercise is better estimated by PETCO2 than by PJCO2 in older subjects, contrary to what is observed in younger subjects. This appears to be related to the finding that PETCO2 does not exceed PaCO2 during exercise in older subjects, as occurs in the younger subjects. However, PaCO2 at rest is best estimated by PJCO2 in both younger and older subjects.

Adult↗

Comparison of screw post fixation and free bone block interference fixation for anterior cruciate ligament soft tissue grafts: biomechanical considerations.

Endoscopic (single-incision) anterior cruciate ligament (ACL) reconstruction with bone patellar tendon bone can usually be secured with interference screws on the femur and tibia. Infrequently, patella alta, which results in a longer tendinous component of the graft construct, can result in construct mismatch, resulting in a large portion of the tibial bone plug extruding from the tibial tunnel, requiring graft fixation with staples or a suture/screw and post technique. This study investigated the hypothesis that initial graft fixation could be enhanced if the bone plug was removed and press fit into the tibial tunnel and then secured with an interference screw in the scenario of graft construct mismatch. Initial biomechanical fixation strengths of bovine patellar tendon were compared using a screw and post suture fixation compared with a free bone plug, which was removed from the graft and sandwiched along with the soft tissue with an interference screw. Twenty-eight bovine knees were randomly divided into two groups. Graft fixation was performed with a free bone plug excised from the tibial tubercle portion of the bone tendon bone construct. Fixation was achieved with a cannulated 9-mm x 20-mm interference screw. Fixation was performed in group 2 patients with a Krackow suture of no. 5 Ticron secured over a screw and post. An Instron materials testing system was used and loading rates at 1 mm/sec until failure was performed. Statistically significant differences were noted for load to failure and stiffness (P < .001). Group 1 specimens' mean maximum load to failure was 669 N (range, 511 to 819 N), whereas the load to failure for group 2 patients was 374 N (range, 266 to 491 N). Group 1 stiffness was 90 N/mm (range, 50 to 122 N/m) compared with a mean stiffness of 24 N/m (range, 16 to 33 N/m) for group 2 knees. In our bovine model, free bone block interference fixation was stronger and stiffer than fixation using sutures tied over a post. This fixation method of securing a soft tissue graft with an interference screw warrants further clinical investigation and may offer an improvement to the alternative of suture/post fixation.

Animals↗

Prevention of pediatric mortality from trauma: are current measures adequate?

Trauma accounts for nearly half of pediatric deaths in the United States. We reviewed all pediatric trauma-related deaths that occurred over a 5-year period at two Georgia trauma centers to determine the number of trauma deaths in children, mechanism of injury, cause of death, and compliance with safety standards. Of the 69 fatalities, 31 were caused by motor vehicle accidents. Twenty-five of these victims (81%) were unrestrained; 17 were 4 years old or less, and only 1 of them was restrained in a car seat. Pedestrian versus vehicle accidents resulted in 19 deaths, 10 of the victims being 4 years old or less. Bicycle versus vehicle accidents resulted in 4 deaths, 2 of them due to closed head injury; none of the victims wore headgear. All-terrain vehicle accidents resulted in 2 deaths from massive head injury; neither victim wore a helmet. One death occurred from bicycle handlebar injury; 12 deaths resulted from causes other than vehicle accidents. Major causes of pediatric fatalities were motor vehicle accidents (45%), pedestrian-vehicle accidents (28%), and bicycle accidents (6%). This study indicates that when safety measures such as restraint systems, helmets, or proper supervision are ignored, children may die as a result of trauma.

Accidents↗