Biomedical subjects
Publications and source records attributed to W R Reed.
A combination of computed tomography (CT) scan and retrograde urethrogram is routinely employed to simulate treatment portals prior to radiation therapy for prostate cancer. These procedures can be performed more efficiently with the use of a standard magnitude grid and a prepared urethrogram kit.
The authors assess prevalence of anemia in a population of patients anticipating radiation therapy. They also characterize the anemia and determine its relationship to stage, inflammation, and mortality. Blood counts were recorded for 81 of 103 patients surveyed during August 1988. When available, iron studies were used to characterize anemia. Stage, treatment, and 3-year mortality were obtained from tumor registry data. Many patients had anemia of chronic disorders. Therefore, 16 adults with solid tumors anticipating radiation therapy were evaluated with complete blood counts, iron studies, chemistries, erythropoietin, and measures of inflammation. Of 81 patients, more than half were anemic. Thirteen of 17 patients with anemia and with iron studies had anemia of chronic disorders. Two-thirds of patients with anemia had advanced cancer, versus one third of patients without anemia. Twice as many patients with anemia compared with those without anemia died within 3 years. Of 16 patients studied intensively, 4 had anemia, advanced cancer, and died within 6 months, whereas all 12 patients without anemia lived longer. The 4 patients with anemia had an elevated iron index (7.95), erythrocyte sedimentation rate (86 mm per hour), and C-reactive protein (4.48 mg/dL) versus those of 12 patients without anemia and 10 volunteers. Erythropoietin levels were not different significantly among groups. Anemia indicated a poor prognosis during and before radiotherapy, and anemia of chronic disorders was associated with advanced cancer and a short survival rate.
The methylxanthine derivative pentoxifylline, widely used as a hemorrheologic agent in the treatment of peripheral vascular disease, is now being evaluated for potential applications in patients with cancer. Recent studies have shown that pentoxifylline can modulate a number of neutrophil functions at in vitro concentrations of at least 50 micrograms/ml. Using a standard51chromium-release assay, we studied the suppressive effects of pentoxifylline on natural killer (NK) cell activity and found that pentoxifylline, at concentrations of 50 and 100 micrograms/ml, suppressed the in vitro NK cell activity of healthy volunteers by 25% and 75%, respectively. Postreaction supernatants from chromium-release studies were then assayed for prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) by using enzyme-linked immunosorbent assay. Concentrations of both PGE2 and TNF-alpha were increased by more than five times in those assay wells containing pentoxifylline. Moreover, the addition of 1 microgram/ml indomethacin to the NK assay system containing pentoxifylline, completely inhibited PGE2 production and abrogated the pentoxifylline-induced NK suppression. The addition of PGE2 (1 x 10(-6) mol/L) to the assay system suppressed NK activity, whereas addition of 1 or 10 ng/ml TNF-alpha did not. Theophylline, another methylxanthine, failed to suppress NK activity like pentoxifylline at equimolar concentrations. Our studies provide the first evidence that concentrations of pentoxifylline of at least 50 micrograms/ml suppressed NK cell function by inducing PGE2 synthesis from effector peripheral-blood mononuclear cells.
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The genioglossus (GG) muscle activity of four infants with micrognathia and obstructive sleep apnea was recorded to assess the role of this tongue muscle in upper airway maintenance. Respiratory air flow, esophageal pressure, and intramuscular GG electromyograms (EMG) were recorded during wakefulness and sleep. Both tonic and phasic inspiratory GG-EMG activity was recorded in each of the infants. On occasion, no phasic GG activity could be recorded; these silent periods were unassociated with respiratory embarrassment. GG activity increased during sigh breaths. GG activity also increased when the infants spontaneously changed from oral to nasal breathing and, in two infants, with neck flexion associated with complete upper airway obstruction, suggesting that GG-EMG activity is influenced by sudden changes in upper airway resistance. During sleep, the GG-EMG activity significantly increased with 5% CO2 breathing (P less than or equal to 0.001). With nasal airway occlusion during sleep, the GG-EMG activity increased with the first occluded breath and progressively increased during the subsequent occluded breaths, indicating mechanoreceptor and suggesting chemoreceptor modulation. During nasal occlusion trials, there was a progressive increase in phasic inspiratory activity of the GG-EMG that was greater than that of the diaphragm activity (as reflected by esophageal pressure excursions). When pharyngeal airway closure occurred during a nasal occlusion trial, the negative pressure at which the pharyngeal airway closed (upper airway closing pressure) correlated with the GG-EMG activity at the time of closure, suggesting that the GG muscle contributes to maintaining pharyngeal airway patency in the micrognathic infant.
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.
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.
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.
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OBJECTIVE: To evaluate chiropractic management of primary nocturnal enuresis in children. DESIGN: A controlled clinical trial for 10 wk preceded by and followed by a 2-wk nontreatment period. SETTING: Chiropractic clinic of the Palmer Institute of Graduate Studies and Research. PARTICIPANTS: Forty-six nocturnal enuretic children (31 treatment and 15 control group), from a group of 57 children initially included in the study, participated in the trial. INTERVENTION: High velocity, short lever adjustments of the spine consistent with the Palmer Package Techniques; or a sham adjustment using an Activator at a nontension setting administered to the examiner's underlying contact point. Two 5th-year chiropractic students under the supervision of two clinic faculty performed the adjustments. MAIN OUTCOME MEASURES: Frequency of wet nights. RESULTS: The post-treatment mean wet night frequency of 7.6 nights/2 wk for the treatment group was significantly less than its baseline mean wet night frequency of 9.1 nights/2 wk (p = 0.05). For the control group, there was practically no change (12.1 to 12.2 nights/2 wk) in the mean wet night frequency from the baseline to the post-treatment. The mean pre- to post-treatment change in the wet night frequency for the treatment group compared with the control group did not reach statistical significance (p = 0.067). Twenty-five percent of the treatment-group children had 50% or more reduction in the wet night frequency from baseline to post-treatment while none among the control group had such reduction. CONCLUSIONS: Results of the present study strongly suggest the effectiveness of chiropractic treatment for primary nocturnal enuresis. A larger study of longer duration with a 6-month follow-up is therefore warranted.