Pseudohypoaldosteronism: successful treatment with home electrolyte monitoring.
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Electrolytes↗
Biomedical subjects
J K Smith
Publications and source records attributed to J K Smith.
Obstructive sleep apnea syndrome.
Over the past 2 decades, we have gained great insight into the sleep apnea syndromes. Though progress in this field continues, many problems, including an incomplete understanding of the disease and its natural history, remain. Future work should clarify these areas as well as provide a better understanding of our available therapeutic options.
Humans↗
The rostral and caudal ventrolateral medulla in young spontaneously hypertensive rats.
This study was designed to compare the cardiovascular influences of the rostral ventrolateral medulla (RVLM) and the caudal ventrolateral medulla (CVLM) in young (5-6 weeks) spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. SH and WKY groups had similar pressor and depressor responses to microinjection of L-glutamate into the RVLM and the CVLM, respectively. In addition the results of this study indicate a reduced tonic sympathoinhibitory function of the CVLM in young SH rats, which may contribute to the development of hypertension in the spontaneously hypertensive rat.
Animals↗
Cardiovascular effects of L-glutamate and tetrodotoxin microinjected into the rostral and caudal ventrolateral medulla in normotensive and spontaneously hypertensive rats.
The purpose of this study was to compare the responsiveness of the rostral and caudal ventrolateral medulla in spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats to microinjection of L-glutamate, and to estimate tonic output of these areas by microinjecting the neurotoxin tetrodotoxin. Rats were anesthetized with 1.25 g/kg urethane s.c., implanted with arterial (femoral) and venous (femoral) catheters, artificially ventilated and paralyzed with gallamine triethiodide (10 mg/kg). Using a ventral approach to the brainstem, the mean arterial pressure and heart rate responses to microinjection (30 nl) of L-glutamate (1, 10 and 100 mM) and tetrodotoxin (10 microM) into the rostral and caudal ventrolateral medulla were compared in SH (n = 7) and WKY (n = 7) groups. Microinjection of L-glutamate into the rostral ventrolateral medulla produced equivalent increases in mean arterial pressure (maximum +33 +/- 3 and +36 +/- 6 mm Hg, SH and WKY groups respectively) and minimal changes in heart rate. Similar administration of L-glutamate into the caudal ventrolateral medulla caused decreases in mean arterial pressure and heart rate; changes in mean arterial pressure were significantly greater in the SH group than in the WKY group (-52.3 +/- 2.9 mm Hg for SH, -22.6 +/- 2.6 mm Hg for WKY). Bilateral microinjection of tetrodotoxin into the caudal ventrolateral medulla produced significantly larger increases of mean arterial pressure in WKY rats (+8 +/- 4 vs +46 +/- 8 mm Hg for SH vs WKY). These data indicate that SH rats may have a lower tonic activity of neurons in the caudal ventrolateral medulla, resulting in a lower restraining influence on sympathetic outflow in the SH rat.
Action Potentials↗
GABAergic responses in ventrolateral medulla in spontaneously hypertensive rats.
Gamma-Aminobutyric acid (GABA) and the GABA antagonist bicuculline methiodide were used to investigate the role of GABAergic transmission in the rostral and caudal ventrolateral medulla in 12- to 13-wk-old spontaneously hypertensive (SH) (n = 7) and normotensive, control Wistar-Kyoto (WKY) (n = 7) rats. Animals were anesthetized with urethan (1.25 g/kg sc), paralyzed with gallamine triethiodide (10 mg/kg iv), and artificially ventilated. Femoral arterial and venous catheters were inserted for the measurement of mean arterial pressure (MAP) and heart rate responses and for intravenous infusions. The ventral surface of the brain stem then was exposed. The responsiveness of the rostral ventrolateral medulla to GABA was compared in SH and WKY rats using unilateral microinjections (30 nl) of GABA at 1, 10, and 100 mM concentrations, which produced significantly (P less than 0.05) larger decreases of MAP in SH rats compared with WKY at the 10 and 100 mM concentrations (-37.3 +/- 2.8 mmHg for SH vs. -27.3 +/- 2.7 mmHg for WKY at 100 mM). Tonic GABAergic inhibition was gauged using bilateral microinjections (30 nl) of bicuculline (2 and 4 mM) into the rostral ventrolateral medulla, which caused significantly larger increases in MAP in the WKY group (+84.8 +/- 8.5 mmHg at 4 mM) compared with the SH group (+14.9 +/- 5.8 mmHg at 4 mM). In contrast, the ability to drive sympathetic outflow by microinjection of L-glutamate in the rostral ventrolateral medulla was not significantly different between WKY and SH rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training.
The purposes of this study were to determine whether exercise training induces increases in skeletal muscle antioxidant enzymes and to further characterize the relationship between oxidative capacity and antioxidant enzyme levels in skeletal muscle. Male Sprague-Dawley rats were exercise trained (ET) on a treadmill 2 h/day at 32 m/min (8% incline) 5 days/wk or were cage confined (sedentary control, S) for 12 wk. In both S and ET rats, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities were directly correlated with the percentages of oxidative fibers in the six skeletal muscle samples studied. Muscles of ET rats had increased oxidative capacity and increased GPX activity compared with the same muscles of S rats. However, SOD activities were not different between ET and S rats, but CAT activities were lower in skeletal muscles of ET rats than in S rats. Exposure to 60 min of ischemia and 60 min of reperfusion (I/R) resulted in decreased GPX and increased CAT activities but had little or no effect on SOD activities in muscles from both S and ET rats. The I/R-induced increase in CAT activity was greater in muscles of ET than in muscles of S rats. Xanthine oxidase (XO), xanthine dehydrogenase (XD), and XO + XD activities after I/R were not related to muscle oxidative capacity and were similar in muscles of ET and S rats. It is concluded that although antioxidant enzyme activities are related to skeletal muscle oxidative capacity, the effects of exercise training on antioxidant enzymes in skeletal muscle cannot be predicted by measured changes in oxidative capacity.
Animals↗
Neutrophil-mediated microvascular dysfunction in postischemic canine skeletal muscle. Role of granulocyte adherence.
Recent studies implicate a role for granulocytes in the genesis of the microvascular and parenchymal cell dysfunction, which occurs upon reperfusion of ischemic tissues. Although the molecular mechanisms underlying this neutrophil-mediated injury are not completely understood, it is clear that an essential first step in granulocyte migration from the vascular lumen to the interstitial space is adherence to vascular endothelium. The purpose of this study was to determine whether prevention of neutrophil adherence with monoclonal antibody IB4 directed against the neutrophil CD11/CD18 glycoprotein adherence complex or neutrophil depletion with a specific polyclonal antineutrophil serum would attenuate the microvascular dysfunction seen in postischemic skeletal muscle. Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in isolated canine gracilis muscle subjected to ischemia/reperfusion, ischemia/reperfusion plus antineutrophil serum, or ischemia/reperfusion plus IB4. Estimates of sigma averaged 0.83 +/- 0.04 in nonischemic, control gracilis muscles, while ischemia/reperfusion was associated with a marked increase in vascular permeability (decrease in sigma to 0.54 +/- 0.04) and vascular resistance (increased by 135 +/- 41% over the control value). Prevention of neutrophil adherence or neutrophil depletion prevented this increase in vascular permeability (sigma = 0.80 +/- 0.03 and 1.01 +/- 0.06, respectively) and resistance (decrease of 16.51 +/- 8.0% and increase of 2.4 +/- 4.6% over control values, respectively). The results of this study suggest that neutrophils play a critical role in the genesis of microvascular dysfunction in postischemic skeletal muscle. Furthermore, neutrophil adherence to vascular endothelium appears to be a prerequisite for the production of this injury.
Animals↗
Classroom behavior of children and adolescents with learning disabilities: a meta-analysis.
Meta-analysis was used to review the results of 25 studies that compared the classroom behavior of children and adolescents with learning disabilities (LD) to children without learning disabilities. The data were analyzed from several different methodological perspectives. Results showed that both methodologically strong and weak studies demonstrated significant behavioral deficits of children with learning disabilities compared to their nondisabled peers in each of five overall areas: on-task behavior, off-task behavior, conduct disorders, distractibility, and shy/withdrawn behavior. Both observational and teacher rating data demonstrated these differences. Effect sizes for both groups of studies seemed to cluster around 1 standard deviation, suggesting noticeable and educationally significant impairment in the behavior of children with disabilities. Analysis of grade-level effect sizes suggests some explanation for the large number of referrals often witnessed during the elementary school years. Educational implications of these behavioral differences in terms of implications for mainstreaming are discussed.
Child↗
Effect of exercise on complement activity.
Complement measurements of C1, C1q, C2, C3, C4, C5; the anaphylatoxins, C3a, C4a, and C5a; and total hemolytic activity of the classical and alternative pathways were made in 26 experienced adult runners before and after shortterm aerobic exercise. The baseline results were compared with those of nonexercising age-matched controls. In most subjects tested, running resulted in nanogram increases in C3a and C4a with corresponding decreases in the hemolytic activity of C4 (C4H). Baseline values of C3 and C4H were decreased significantly in runners when compared with nonexercising controls. Preliminary studies measuring the effect of exercise on C3a levels were also done in three asthmatic runners. Mean resting and postexercise levels, and exercise-induced increases in C3a anaphylatoxin in the asthmatic subjects were significantly higher than in the nonasthmatic subjects. The findings indicate that short-term exercise results in the activation of C3 and C4 and subsequent generation of C3a and C4a anaphylatoxins, and suggest that both activation of the classical pathway of complement and a selective downregulation of C3 production may occur in persons regularly engaged in aerobic exercise. The exaggerated generation of C3a by asthmatic subjects during exercise raises the possibility that anaphylatoxins play an etiologic role in exercise-induced asthma.
Adult↗
Training and education of persons with disabilities in the Soviet Union: report by a Very Special Arts delegation.
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Adolescent↗
Functional expression of plant acetolactate synthase genes in Escherichia coli.
Acetolactate synthase (ALS; EC 4.1.3.18) is the first common enzyme in the biosynthetic pathways leading to leucine, isoleucine, and valine. It is the target enzyme for three classes of structurally unrelated herbicides, the sulfonylureas, the imidazolinones, and the triazolopyrimidines. A cloned ALS gene from the small cruciferous plant Arabidopsis thaliana has been fused to bacterial transcription/translation signals and the resulting plasmid has been used to transform Escherichia coli. The cloned plant gene, which includes sequences encoding the chloroplast transit peptide, is functionally expressed in the bacteria. It is able to complement genetically a strain of E. coli that lacks endogenous ALS activity. An ALS gene cloned from a line of Arabidopsis previously shown to be resistant to sulfonylurea herbicides has been similarly expressed in E. coli. The herbicide-resistance phenotype is expressed in the bacteria, as assayed by both enzyme activity and the ability to grow in the presence of herbicides. This system has been useful for purifying substantial amounts of the plant enzyme, for studying the sequence parameters involved in subcellular protein localization, and for characterizing the interactions that occur between ALS and its various inhibitors.
Journal Article↗
Severely heated therapeutic factor VIII concentrate of high specific activity.
A new method for the manufacture of a heated factor VIII concentrate of high specific activity (2-6 IU factor VIII:C/mg protein) has been developed. Addition of heparin to cryoprecipitate extract at acid pH precipitated fibrinogen and fibronectin. Factor VIII was then recovered from the supernatant by precipitation with glycine and sodium chloride. After re-solution and desalting on Sephadex G-25, the concentrate was sterile-filtered and lyophilised. The dried product was stable to heating in the final container at 80 degrees C for 72 h. Data from 25 consecutive batches of concentrate prepared from 1,200-1,500 kg plasma pools are presented. The mean final yield of heated product was 190 IU factor VIII:C/kg plasma. The concentrate has been found to be safe and effective in clinical use.
Chemical Precipitation↗
Hypoxic reperfusion attenuates postischemic microvascular injury.
The results of several recent studies have demonstrated that reactive oxygen metabolites are responsible for a major portion of ischemia/reperfusion (I/R) injury in skeletal muscle. Presumably, the cytotoxic oxidants are produced during reperfusion when molecular oxygen (the source of the reactive oxygen metabolites) is reintroduced to the tissues. The purpose of this study was to test the hypothesis that molecular oxygen must be provided at reperfusion to produce I/R injury in skeletal muscle. Isolated, maximally vasodilated (papaverine) canine gracilis muscles were reperfused, after 4 h of inflow occlusion, from reservoirs containing autologous blood equilibrated with either 95% O2-5% CO2 or 95% N2-5% CO2 gas mixtures. Arterial PO2 fell from approximately 120 mmHg to less than 3-5 mmHg, during the use of nitrogen. The solvent drag reflection coefficient for total plasma proteins (sigma f) and total vascular resistance was determined for the following conditions: control (no ischemia), reperfusion with oxygenated blood after 4 h ischemia; and reperfusion (after 4 h ischemia), first with anoxic blood and then oxygenated blood. Reperfusion with oxygenated blood, after 4 h of ischemia, significantly reduced solvent drag reflexion coefficient (sigma f) from 0.93 +/- 0.02 to 0.63 +/- 0.02, indicating a dramatic increase in vascular permeability. Total vascular resistance increased from 6.1 +/- 1.1 mmHg.ml-1.min.100 g during the preischemic period to 12.9 +/- 3.0 mmHg.ml-1.min.100 g during normoxic reperfusion. In muscles reperfused with anoxic blood, sigma f averaged 0.82 +/- 0.06, whereas vascular resistance increased by 56 +/- 13%.(ABSTRACT TRUNCATED AT 250 WORDS)
Algorithms↗
Free radical defense mechanisms and neutrophil infiltration in postischemic skeletal muscle.
A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radicals may mediate the microvascular and parenchymal injury produced by reperfusion of ischemic skeletal muscle. One potential source of these reactive oxygen metabolites is the inflammatory neutrophil. To assess neutrophil accumulation in postischemic skeletal muscle, we measured tissue myeloperoxidase (MPO) activity in skeletal muscle biopsies taken during control, after 4 h of ischemia, and after 1 h of reperfusion. Tissue levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were measured in the same samples to identify alterations in tissue free radical defense mechanisms due to ischemia-reperfusion. Reperfusion of ischemic skeletal muscle was associated with a dramatic increase in tissue neutrophil content (as reflected by a 26-fold increase over control in tissue MPO activity after 1 h of reperfusion) and a concurrent 50% decrease in GSH content. Tissue CAT and SOD activities were unaffected by ischemia-reperfusion. These results suggest a possible relationship between ischemia-reperfusion-induced injury, neutrophil infiltration, and the reduction in tissue GSH.
Animals↗
Role of iron in postischemic microvascular injury.
Iron-catalyzed formation of hydroxyl radicals has been postulated to occur during reperfusion of ischemic tissues. To assess the role of iron-catalyzed oxidant production in ischemia/reperfusion (I/R) injury to skeletal muscle, we examined the effects of deferoxamine (an iron chelator) and apotransferrin (an iron-binding protein) on the increased vascular permeability produced by I/R in isolated, pump-perfused rat hindquarters. Solvent drag reflection coefficients (sigma) were measured in hindquarters subjected to 2 h of ischemia and 30 min of reperfusion with either no pretreatment, pretreatment with 50 mg/kg deferoxamine, 200 mg/kg apotransferrin, or iron-loaded deferoxamine (50 mg/kg). I/R alone was associated with an increase in vascular permeability as indicated by the significantly lower estimates of sigma obtained after I/R (0.68 +/- 0.03) compared with those obtained in nonischemic preparations (0.82 +/- 0.02). Pretreatment with deferoxamine or apotransferrin attenuated this permeability increase (sigma = 0.83 +/- 0.03 and 0.86 +/- 0.02, respectively), whereas pretreatment with iron-loaded deferoxamine afforded no protection (sigma = 0.71 +/- 0.02). These findings are consistent with the hypothesis that iron-catalyzed oxidant production is important in the genesis of microvascular injury following I/R. Since the enzyme xanthine oxidase has been implicated as a major source of oxidants generated during reperfusion, we also measured tissue levels of xanthine oxidase and xanthine dehydrogenase in muscle samples obtained from the same hindquarters in which we measured permeability changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Role of xanthine oxidase in postischemic microvascular injury in skeletal muscle.
Previous reports indicate that allopurinol, a xanthine oxidase inhibitor, attenuates the microvascular injury produced by reperfusion of ischemic skeletal muscle. To further assess the role of xanthine oxidase in ischemia/reperfusion (I/R) injury, we examined the effect of xanthine oxidase depletion or inhibition on the increase in microvascular permeability produced by I/R. Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in rat hindquarters subjected to 2 h of ischemia and 30 min of reperfusion in xanthine oxidase-replete and -depleted animals and in animals pretreated with the xanthine oxidase inhibitor oxypurinol. Xanthine oxidase depletion was accomplished by administration of a tungsten-supplemented (0.7 g/kg diet), molybdenum-deficient diet. In animals fed the tungsten diet, muscle total xanthine dehydrogenase plus xanthine oxidase activity was decreased to less than 10% of control values. Estimates of sigma averaged 0.85 +/- 0.04 in nonischemic (continuous perfusion for 2.5 h) hindquarters, whereas muscle xanthine oxidase activity averaged 3.3 +/- 0.4 mU/g wet wt. I/R was associated with a marked decrease in sigma (0.54 +/- 0.02), whereas xanthine oxidase activity was increased to 5.8 +/- 0.5 mU/g wet wt. These results indicate that I/R produced a dramatic increase in vascular permeability coincident with an increase in muscle xanthine oxidase activity. Xanthine oxidase depletion with the tungsten diet or pretreatment with oxypurinol attenuated this permeability increase (sigma = 0.72 +/- 0.03 and 0.77 +/- 0.7, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Posterior hypothalamic influences on cardiovascular effects of aortic nerve stimulation.
The purpose of this study was to examine the influence of stimulation of the posterior hypothalamus on the baroreflex responses produced by stimulation of the aortic depressor nerve. Animals were initially anesthetized and implanted with a bipolar electrode in the posterior hypothalamus. Three to 5 days later, animals were anesthetized with urethan, and the left aortic depressor nerve was dissected and placed on a bipolar platinum-iridium electrode. The effects of electrical stimulation of the posterior hypothalamus (0, 160, and 280 microA) were examined in baroreflex-intact and acutely sinoaortic baroreceptor-denervated animals, and the responses to aortic nerve stimulation (2, 8, 16, and 32 Hz) were examined during each level of hypothalamic stimulation. The first set of experiments was performed in baroreceptor-intact animals; e.g., in animals with arterial baroreceptor inputs intact from both carotid sinus regions in addition to intact right aortic baroreceptor afferent pathways. In that group, stimulation of the posterior hypothalamus attenuated the bradycardia and depressor effects of aortic nerve stimulation. When influences from other baroreceptor inputs were removed with acute sinoaortic baroreceptor denervation, posterior hypothalamic stimulation interrupted the reflex bradycardia due to aortic nerve stimulation; however, the depressor response to aortic nerve stimulation was not attenuated. Similar to the arterial pressure response, hypothalamic stimulation did not attenuate the decreases in mesenteric and iliac vascular resistance produced by aortic nerve stimulation in the baroreflex-denervated group. We conclude that posterior hypothalamic stimulation attenuates baroreflex-mediated bradycardia but does not alter baroreflex control of arterial pressure and peripheral vascular resistance.
Animals↗
Disseminated echovirus infection in a patient with multiple myeloma and a functional defect in complement. Treatment with intravenous immunoglobulin.
A man with IgG1 multiple myeloma developed fever, confusion, and progressive muscle weakness resulting in paralysis. Echovirus type 11 was isolated from cerebrospinal fluid, pleura, pleural fluid, and muscle, and muscle biopsy disclosed changes consistent with viral myositis. Immunologic evaluation revealed low serum levels of polyclonal IgG subtypes 1 and 3, reduced blood levels of T-helper/inducer and T-suppressor/cytotoxic cells, and a complement abnormality involving the function of the classical pathway C3 convertase, C4b2a. Therapy with intravenous immunoglobulin was associated with clinical recovery. This is the first reported case of disseminated central nervous system enteroviral infection in an adult with a B-cell malignancy, and in association with a documented complement abnormality. The findings suggest the efficacy of immunotherapy in this disease.
Complement Activation↗