Intramuscular injection of botulinum toxin as an adjunct to arthrocentesis of the temporomandibular joint: preliminary observations.
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Biomedical subjects
Publications and source records attributed to B J Freund.
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OBJECTIVE: To see whether therapy with botulinum toxin A may prove to be an effective treatment for headache of musculoskeletal origin. BACKGROUND: Headache is a common finding associated with neck injury. Cervicogenic headache, which is believed to be attributable to injury of the ligaments, muscles, or joints of the cervical spine, is centered in the occipital region with pain referred to the frontotemporal region. Botulinum toxin A produces prolonged muscle relaxation, which is dose dependent and can be easily targeted to affected muscles. METHODS: This randomized, double-blind, placebo-controlled study compares outcome measures in 26 patients suffering from chronic headache subsequent to a cervical whiplash injury. One half of the patients received botulinum toxin A, 100 units, diluted in 1 mL of saline, while the other half received just saline (1 mL). Five cervical trigger points received 0.2 mL each of injectant via a 30-gauge needle. Outcome measures included subjective head pain based on visual analog scales, as well as range of neck motion. Follow-up assessments were carried out at 2 and 4 weeks after treatment. RESULTS: Fourteen subjects who received botulinum toxin A and 12 who received saline completed the study. At both 2 and 4 weeks post injection, the treatment group showed a significant improvement in pain and range of motion from preinjection levels (P<.01). The placebo group demonstrated no statistically significant changes at any posttreatment time.
OBJECTIVE: Up to 87% of patients with whiplash associated disorder (WAD) have some degree of muscle spasm that is contributory to both pain and dysfunction. Botulinum toxin A (BTX-A) produces prolonged muscle relaxation that is dose-dependent and can be easily targeted to affected muscles. BTX-A therapy may be an effective form of therapy offering an alternative or adjunct to conventional modalities. We investigated BTX-A as therapy in patients with WAD. METHODS: This randomized, double blind, placebo controlled study compares outcome measures in 26 patients with chronic neck pain (WAD-II chronic) subsequent to a motor vehicle accident. One-half of the patients received 100 units BTX-A, diluted in 1 ml saline, while the other half received just saline (1 ml). Five trigger points received 0.2 ml each of injectant via a 30 gauge needle. Outcome measures included total subjective neck, shoulder, and head pain based on visual analog scales; objective total range of neck motion (ROM), and the Vernon-Mior subjective function index. Followup assessments were carried out at 2 and 4 weeks post-treatment. RESULTS: Fourteen subjects receiving BTX-A and 12 receiving saline completed the study. The treatment group showed a trend toward improvement in ROM and reduction in pain at 2 weeks post-injection. At 4 weeks post-injection the treatment group was significantly improved from preinjection levels (p < 0.01). The placebo group showed no statistically significant changes at any post-treatment time. The Vernon-Mior scale revealed a trend to improvement for both groups. CONCLUSION: BTX-A treatment of subjects with chronic WAD II neck pain resulted in a significant (p < 0.01) improvement in ROM and subjective pain compared to a placebo group, but only a trend to improvement in subjective functioning.
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The effects of autologous erythrocyte infusion on improving exercise performance at high altitude have not previously been studied. The effects of erythrocyte infusion on 3.2-km (2-mile) run performance were evaluated during 3 days (HA3) and 14 days (HA14) exposure to high altitude (4300 m) in erythrocyte-infused (ER) and control (CON) subjects that were initially matched (P>0.05; n = 8 in each group) for age, body size and aerobic fitness. After sea-level runs (SL; 50 m), unacclimated-male subjects received either 700 ml of saline and autologous erythrocytes (42% hematocrit; ER) or saline alone (CON). The 3.2-km run times (min:s) did not differ (P>0.05) between groups at SL [mean (SEM) ER, 13:14 (00:19); CON, 13:39 (00:32)] or during HA3 [ER, 19:02 (00:18); CON, 19:44 (00:43)] and HA14 [ER, 17:44 (00:27); CON, 18:45 (00:55)] but times were slower (P<0.05) when comparing HA3 or HA14 to SL. Heart rates (HR) did not differ between groups at SL [ER, 188 (3) beats x min(-1); CON, 191 (3) beats x min(-1)], or during HA3 [ER, 170 (4) beats x min(-1); CON, 178 (4) beats x min(-1)] and HA14 [ER, 162 (6) beats x min(-1); CON, 169 (5) beats x min(-1)], but HR were lower (P<0.05) when comparing HA3 or HA14 to SL. Ratings of perceived exertion (local, central, and overall ratings) did not differ between groups at SL, HA3 or HA14, but local ratings were higher (P<0.05) at HA3 and HA14 compared to SL, and overall ratings were higher for HA3 than SL. Analysis of covariance (adjusted for SL group run times) revealed (min:s) 00:14 (HA3) and 00:28 (HA14) mean improvement tendencies (P>0.05) for ER compared to CON. Thus, no significant improvements in 3.2-km run performance were associated with erythrocyte infusion, although the ER group showed a tendency to run slightly faster at high altitude.
BACKGROUND: Exercise increases plasma arginine-vasopressin (PAVP), plasma atrial natriuretic peptide (PANP), plasma renin activity (PRA), and plasma aldosterone (PALDO) in an intensity-dependent manner. With acute exercise, urine osmolality (UOSM) is often decreased despite increased PAVP. The hyperbaric environment lowers PAVP and UOSM, and increases urine flow. HYPOTHESIS: If work produced similar renal effects at hyperbaria, greater than normal dehydration could result from larger free water losses. METHODS: To test this hypothesis, hormonal and renal responses were assessed during exercise at 80% of maximum heart rate at 46 atmospheres absolute (atm abs) in 3 males, and during maximum exercise at 37 atm abs in 4 males. RESULTS: This maximum exercise was performed at the highest pressure thus far reported and revealed no loss in peak power output. Maximum O2 consumption and heart rate were only slightly reduced, 9.5% and 7% respectively, despite a 41% reduction in maximum minute ventilation. Basal levels and the changes resulting from maximum exercise in PRA and PALDO were unaffected by pressure, but basal and exercise-stimulated levels of PANP and PAVP were reduced compared with 1.5 atm abs control values. UOSM was not significantly affected during maximal exercise at sea level, but during maximum exercise at 37 atm abs and submaximum exercise at 46 atm abs UOSM increased over 300 mosm.kg-1 and 180 mosm.kg-1, respectively. CONCLUSION: Contrary to the hypothesis, UOSM was increased by about 200 mosm.kg-1 by both exercise protocols during hyperbaric exposure and free water was conserved.
This study investigated whether autologous erythrocyte infusion would ameliorate the decrement in maximal O2 uptake (VO2max) experienced by lowlanders when they ascend to high altitude. VO2max was measured in 16 men (treadmill running) at sea level (SL) and on the 1st (HA1) and 9th (HA9) days of high-altitude (4,300 m) residence. After VO2max was measured at SL, subjects were divided into two matched groups (n = 8). Twenty-four hours before ascent to high altitude, the experimental group received a 700-ml infusion of autologous erythrocytes and saline (42% hematocrit), whereas the control group received only saline. The VO2max of erythrocyte-infused [54 +/- 1 (SE) ml.kg-1.min-1] and control subjects (52 +/- 2 ml.kg-1.min-1) did not differ at SL before infusion. The decrement in VO2max on HA1 did not differ between groups, averaging 26% overall, despite higher (P < 0.01) arterial hematocrit, hemoglobin concentration, and arterial O2 content in the erythrocyte-infused subjects. By HA9, there were no longer any differences in hematocrit, hemoglobin concentration, or arterial O2 content between groups. No change in VO2max occurred between HA1 and HA9 for either group. Thus, despite increasing arterial O2-carrying capacity, autologous erythrocyte infusion did not ameliorate the decrement in VO2max at 4,300-m altitude.
We studied sea-level residents during 13 days of altitude acclimatization to determine 1) altitude acclimatization effects on erythrocyte volume and plasma volume, 2) if exogenous erythrocyte volume expansion alters subsequent erythrocyte volume and plasma volume adaptations, 3) if an increased blood oxygen content alters erythropoietin responses during altitude acclimatization, and 4) mechanisms responsible for plasma loss at altitude. Sixteen healthy men had a series of hematologic measurements made at sea level, on the first and ninth days of altitude (4,300 m) residence, and after returning to sea level. Twenty-four hours before the ascent to altitude, one group received a 700-ml infusion of autologous erythrocytes (42% hematocrit), whereas the other group received only a saline infusion. Erythrocyte infusion increased erythrocyte volume by approximately 10%, whereas saline infusion had no effect; in addition, initially at altitude, blood oxygen content was 8% higher in erythrocyte-infused than in saline-infused subjects. The new findings regarding altitude acclimatization are summarized as follows: 1) erythrocyte volume does not change during the first 13 days and is not affected by prior exogenous expansion, 2) a modest increase in blood oxygen content does not modify erythropoietin responses, 3) plasma losses are related to vascular protein losses, and 4) exogenous erythrocyte volume expansion coincides with transient increases in plasma loss, vascular protein loss, and mean arterial pressure elevation. These findings better define human blood volume responses during altitude acclimatization.
To quantify the magnitude of dehydration and to identify predictors of dehydration by utilizing changes in total body water (TBW), 24 male Marines were studied during an 8d moderately cold-weather (1-3 degrees C) training exercise. Training consisted of approximately 12 h/d of moderately intense activity. Variables examined included body composition, TBW, and various blood and urinary parameters indicative of hydration. Dietary food and fluid records were also maintained. Body composition changes were consistently with the high energy expenditure and insufficient energy intake. Despite a decrease in TBW, significant dehydration as assessed by blood and urinary parameters did not occur over the 8d period, therefore no relationships were found between TBW and any of the clinical indicators of dehydration. The change in TBW was reflective of a decrease in lean body mass. These data suggest that during cold-weather military field exercise, despite high activity levels and a negative energy balance, body fluid balance can be maintained when particular attention is paid to fluid intake.
Glycerol ingestion has been shown to mediate hyperhydration; however, the mechanism(s) responsible for this improved fluid retention is not well understood. This study examined the hormonal, renal, and vascular fluid responses to glycerol hyperhydration in 11 resting male volunteers who ingested one of two experimental solutions and then a water bolus. The volume of fluid ingested was determined from the subjects' measured total body water (TBW; total volume = 37 ml/l TBW, 1,765 +/- 162 ml). Experimental solutions (5.0 ml/l TBW) were matched for color and taste and differed only in that one contained 1.5 g glycerol/l TBW (total osmolar load = 777 +/- 24 mosmol). Nine of the 11 subjects also completed a control trial during which no fluid was ingested. Glycerol ingestion (GI) resulted in greater fluid retention than the ingestion of water alone (WI; 60 vs. 32% 3-h posthyperhydration, P < 0.01). This improved fluid retention with GI resulted from lower urine flow rates (peak 6.2 vs. 10.5 ml/min, P < 0.01) associated with lower free water clearance rates (peak = 1.2 vs. 8.2 ml/min, P < 0.01). Hyperhydration had no effect on plasma atrial natriuretic peptide concentrations. Changes in plasma aldosterone were unrelated to differences in fluid retention. Antidiuretic hormone concentrations (ADH) were significantly reduced from prehyperhydration levels during both hyperhydration trials but tended (P = 0.07) to rise during GI compared with WI at the very time urine flow and free water clearance differences were also evident. This suggests that ADH may, in part, be responsible for glycerol's effectiveness, although differences in ADH concentrations were small and near the assay's sensitivity limits. Alternatively, glycerol's effectiveness may result from its directly increasing the kidneys' medullary concentration gradient and, hence, water reabsorption.
This study examined the effects of acute and chronic pyridostigmine bromide (PB) administration on thermoregulatory and metabolic responses to exercise in cold air (5 degrees C). Seven healthy men completed two 7-day trials in a double-blind, crossover experimental design: during one trial they received PB (30 mg three times daily) and during the other trial they received placebo. For each trial, subjects attempted four (3 h) exercise tests: low-intensity exercise (approximately 25% VO2max) and moderate-intensity exercise (approximately 50% VO2max), on days 2 and 3 and again on days 6 and 7. Metabolic rate, body temperatures, and venous blood samples were obtained before and during exercise. Red blood cell acetylcholinesterase inhibition induced by PB increased (p < 0.05) from 34% on day 1 to 43% on days 3-7. Metabolic rate, body temperatures, and regional heat conductance responses were not different between trials. Plasma glucose, glycerol, free fatty acid, lactate, sodium, and potassium concentrations were not different between trials. In addition, differences were not found between acute and chronic experiments for any thermoregulatory or metabolic responses. These findings demonstrate that the PB dosage used by military personnel, as a pharmacological defense against nerve-agent poisoning, should not cause any adverse thermoregulatory or metabolic effects during moderate activity in cold climates.
We investigated the effect of negative pressure breathing during the inspiratory phase only (intermittent NPB) in 9 healthy male subjects who were in a sitting position and had no food or fluid intake for 12 h before the study. Intermittent NPB was without effect on urine flow and urinary sodium excretion but caused a significant increase in creatinine clearance. Plasma renin activity was significantly reduced, whereas plasma antidiuretic hormone (ADH), atrial natriuretic factor (ANF), and aldosterone levels were unaffected. To determine whether the blunted urinary response to intermittent NPB was a postural phenomenon, the study was repeated in 6 of the subjects while supine. Under these conditions there was a significant increase in urine flow and plasma ANF levels, but no change in all other measured variables. These results are consistent with a role for ANF, but not ADH, in the diuresis seen in supine subjects during NPB.
A stretch stimulus of the cardiopulmonary receptors results in a diuresis and natriuresis in dogs due to a suppression of renal sympathetic nerve activity. In the present experiment, the stretch stimulus in humans was given by means of continuous negative-pressure breathing (CNPB), and muscle sympathetic nerve activity (MSNA), renal responses, and hormones were measured to examine whether MSNA response during CNPB correlated with the usual renal and hormonal responses for stretch stimulus of the cardiopulmonary receptors. Nine healthy males were subjected to CNPB at -11 mmHg for 60 min. MSNA in the peroneal muscle nerve fascicles was measured continuously before (pre-CNPB), during, and after CNPB (post-CNPB). A step and sustained decrease (P less than 0.05) in MSNA (30 +/- 6% for burst frequency and 37 +/- 4% for total activity from pre-CNPB level) was observed during CNPB and it returned to pre-CNPB level at post-CNPB. Urinary excretion increased by 58 +/- 18% (P less than 0.05) during CNPB, and the diuresis was entirely osmolal in nature because of a significant increase (P less than 0.05) in Na excretion and a constant free-water clearance. The plasma level of norepinephrine decreased significantly (P less than 0.05) during CNPB and remained decreased (P less than 0.05) at post-CNPB. A twofold increase (P less than 0.05) in plasma atrial natriuretic peptide and a 35 +/- 9% reduction (P less than 0.05) in plasma renin activity were observed during CNPB, whereas no change was observed in plasma aldosterone and arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)
Previous work indicates that the magnitude and direction of renal responses to exercise depend on the exercise intensity. To examine mechanisms responsible for these findings, renal and hormonal responses were studied in eight healthy male subjects (29.6 +/- 1.9 yr) before and immediately after four 20-min bouts of submaximal exercise (cycle ergometry) at work loads representing 25, 40, 60, and 80% of maximal oxygen consumption. Urine flow, osmotic clearance, glomerular filtration rate, and sodium excretion (UNa+V) all tended to rise at the 25% work load but were markedly reduced at the higher work intensities. Changes in urine flow paralleled changes in glomerular filtration rate (r = 0.91). Plasma vasopressin (ADH), aldosterone, and plasma renin activity tended to increase progressively with increases in work load, with the increases for all hormones reaching statistical significance when the level of exercise reached greater than or equal to 60% of maximal oxygen consumption. However, atrial natriuretic peptide was elevated (P less than 0.05) at all work loads from greater than 1.6-fold of control levels at the 25% work load to greater than 7-fold at the 80% work load. The increase in urine flow (6 of 8 subjects) and UNa+V (7 of 8 subjects) may be due to the increase in atrial natriuretic peptide and/or a 10% suppression (P less than 0.05) of ADH at the 25% work load.(ABSTRACT TRUNCATED AT 250 WORDS)
The present study was undertaken to determine the relative influence of the action of the central nervous system on the mechanism of water-immersion-induced diuresis by comparing physiological responses of quadriplegic (QP) and normal subjects. After overnight fasting seven male QP subjects with complete cervical cord transections (C5-C8) and six normal men were tested before, during, and after 3 h of head-out immersion (HOI) in thermoneutral water (34.5-35.0 degrees C). The reversible increase in urine flow and the total urine volume (309 +/- 53 ml in 3 h) in QP subjects were comparable with that of the normal subjects (318 +/- 96 ml in 3 h). While osmolal excretion was increased in QP subjects, its magnitude was less when compared with that of normal subjects. Instead, the increased urine flow in QP subjects was characterized by increased glomerular filtration rate (GFR) and free water clearance, in contrast to a predominantly osmotic diuresis with no changes in GFR in the normal subjects. The HOI elevated (P less than 0.05) systolic pressure only in QP subjects, whereas the increase in cardiac output was the same in both groups. While plasma renin activity and aldosterone responses to HOI in QP subjects were comparable with those of normal individuals, plasma atrial natriuretic factor (ANF) in QP subjects was twofold higher (P less than 0.05) during HOI, and the approximately threefold increase in ANF (P less than 0.05) in QP subjects due to HOI was the same as that of normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Hormonal, electrolyte, and renal responses were measured before, during, and after a marathon (42.2 km) in 14 runners: 8 young (Y) (mean age 27.8 yr) and 6 middle aged (MA) (mean aged 46.7 yr). No differences between groups in prerun values for heart rate (HR), plasma osmolality (OSM), antidiuretic hormone (ADH), aldosterone (ALDO), atrial natriuretic factor (ANF), or plasma renin activity (PRA) were found. Renal and urinary measurements were also similar between groups before the marathon. After 10 km of running, both groups had significant increases in HR, ALDO, ANF, and PRA, while OSM, Na+, and ADH remained unchanged from prerun values. The increase in plasma ANF concentrations at this point was significantly greater in the MA subjects compared with the Y (mean increase 104.1 vs. 42.8 pg/ml, respectively; P less than 0.01). Immediate postmarathon values for OSM, ADH, and Na+ were significantly higher than initial values in both groups, while HR, PRA, and ALDO continued to increase above the elevated levels found at 10 km. ANF values immediately postmarathon remained higher than prerun concentrations but were significantly reduced from those obtained at 10 km. In contrast, HR continued to rise until the completion of the run. These data are consistent with recent reports of an exaggerated ANF response in older subjects in response to central blood volume expansion.
Alterations in plasma lipids consequent to endurance training and beta-blockade. Med. Sci. Sports Exerc., Vol. 21, No. 3, pp. 288-292, 1989. The chronic use of beta adrenergic blockers (BAB) has been associated with reductions in HDL-cholesterol (HDL-C) and increases in triglycerides (TG). This study evaluated the impact of concurrent endurance exercise training and chronic medication with BAB on plasma lipid and lipoprotein profiles in healthy young adult males. Changes in plasma lipids and lipoproteins were investigated while exercise training under the influence of one of two nonselective BAB [sotalol (320 mg.d-1) and propranolol (160 mg.d-1)], one beta 1 selective BAB [atenolol (100 mg.d-1)], or a placebo control. Total cholesterol (TC), HDL-C, LDL-cholesterol (LDL-C), TG, and the ratios of TC/HDL and LDL/HDL were determined before and after endurance training programs of either 14 (N = 27, sotalol) or 15 (N = 47, propranolol/atenolol) wk duration. The subjects exhibited increases in maximal oxygen uptake of 12-20%. Despite increased endurance capacity, the subjects in both BAB and placebo control groups failed to demonstrate the expected increase in HDL-C and decrease in TG. In fact, HDL-C was significantly decreased post-training in the propranolol group. The placebo groups did decrease TC, LDL-C and the TC/HDL and LDL/HDL ratios, improving their CHD risk profile. Similar changes were not observed in the groups on BAB. Thus, with respect to the present population, BAB does appear to interfere with the usual training-induced improvements in the lipid profile. Endurance training may, however, reduce the deterioration in the lipid profile known to occur with BAB.
Endurance exercise training alters the regulation of body fluids. To investigate specifics of these alterations, hormonal, electrolyte, and renal responses to water ingestion (1% of lean body wt) were studied in six moderately trained (T) and 6 untrained (UT) male subjects. No differences between groups for base-line hormonal, electrolyte, or renal measurements were found. After water ingestion, atrial natriuretic factor remained unaltered in both groups. Predrink plasma antidiuretic hormone (ADH) levels of 0.51 +/- (SE) 0.19 (UT) and 0.47 +/- 0.07 microU/ml (T) remained unchanged in the T group but were reduced from min 9 through 90 in the UT group. At 30 min postdrink, UT subjects had lower ADH values than T subjects (0.18 +/- 0.02 vs. 0.33 +/- 0.05 microU/ml), while plasma osmolality was similarly reduced by approximately 3 mosmol/kg in both groups. Urine flow rates increased in both groups from similar values of 0.85 +/- 0.24 (UT) and 0.67 +/- 0.11 ml/min (T) to peak flows of 4.6 +/- 1.6 for UT and 2.7 +/- 1.1 ml/min (T) to peak T, P less than or equal to 0.05) at 60 min postdrink. Urine osmolality was reduced from similar values of 809.1 +/- 62.1 and 867.0 +/- 56.1 mosmol/kg to values of 248.8 +/- 87.6 and 469 +/- 146.1 mosmol/kg for UT and T, respectively (UT vs. T, P less than 0.05), at 60 min. Reduced ADH before reductions in plasma osmolality in the UT but not the T subjects suggests that T subjects have a reduced oropharyngeal inhibition of ADH.(ABSTRACT TRUNCATED AT 250 WORDS)