Showing papers by "University of Texas Medical Branch published in 1984"

Efficacy of Methylprednisolone in Acute Spinal Cord Injury

Abstract: A multicenter double-blind randomized trial was conducted to examine the efficacy of a high dose of methylprednisolone (1,000-mg bolus and daily thereafter for ten days) compared with a standard dose (100-mg bolus and daily thereafter for ten days) in 330 patients with acute spinal cord injury. No difference in neurological recovery of motor function or pinprick and light touch sensation was observed between the two treatment groups six weeks and six months after injury. The lack of a treatment effect was independent of the severity of the initial lesion or the time from injury to starting treatment. Although not statistically significant, early case fatality was greater in the high-dose protocol (relative risk of 3.1 and 1.9, ≤ 14 and 15 to 28 days after injury, respectively) but not from 29 to 210 days after injury. Wound infections of both trauma and operative sites were more prevalent in the high-dose regimen (relative risk of 3.6). (JAMA1984;251:45-52)

Electrogenic Na-Ca exchange in retinal rod outer segment.

Abstract: Previous work has suggested that a Na-Ca exchanger may have a key role in visual transduction in retinal rods. This exchanger is thought to maintain a low internal free Ca2+ concentration in darkness and to contribute to the rod's recovery after light by removing any internally released Ca2+. Little else is known about this transport mechanism in rods. We describe here an inward membrane current recorded from single isolated rods which appears to be associated with such external Na+-dependent Ca2+ efflux activity. External Na+, but not Li+, could generate this current; high external K+ inhibited it while small amounts of La3+ (10 microM) completely abolished it. The exchanger can also transport Sr2+, but not Ba2+ or other divalent cations. The exchange ratio was estimated to be 3Na+:1Ca2+. As well as demonstrating clearly the Na-Ca exchanger in the rod outer segment, our experiments also cast serious doubt on the commonly held view that light simply releases internal Ca2+ to bind to and block the light-sensitive conductance.

The agonist effect of dihydropyridines on Ca channels

Abstract: Dihydropyridines (DHP) have great potential for clinical use because of their inotropic and vasomotor effects. The mechanism of action is unknown although Ca currents have been implicated1,2. Here we report measurements of single channel and whole cell cardiac Ca currents after application of two DHP agonists BAY K 8644 and CGP 28 392. Whole cell Ca currents from individual myocytes were increased and the 50% effective doses (ED50) were similar to those reported for contractility in rabbit aorta and guinea pig heart1 and catecholamine release from cat adrenal glands3. The measured ED50 was also consistent with the apparent dissociation constant (Kd) of a high affinity binding site present in cardiac sarcolemmal vesicles4–7. We propose that the molecular basis for these results is an increase in the probability that a single Ca channel, having opened and closed, will subsequently re-open during membrane depolarization. At high concentrations of BAY K 8644 and in the presence of 96 mM Ba, different effects are observed, primarily a marked prolongation of open time8.

Effects of iontophoretically released amino acids and amines on primate spinothalamic tract cells.

Abstract: The effects of glutamate (Glu), gamma-aminobutyric acid (GABA), glycine (Gly), serotonin (5-HT), norepinephrine (NE), dopamine (DA), and acetylcholine (ACh) were examined in this study by iontophoretic application onto primate spinothalamic tract (STT) neurons identified antidromically by stimulation in the contralateral thalamus. Drugs were tested for effects on background activity, Glu-induced firing, and activity evoked by pinching of the skin. Whereas Glu excited STT cells and was thus used for tests of the other compounds, the amino acids GABA and Gly inhibited Glu- and pinch-induced activity in all STT cells examined. STT cells were also inhibited by 5-HT, NE, and DA. Only two cases of excitation by 5-HT were seen (of 58 cells tested). ACh also had inhibitory actions on STT cells, although 3 of 21 cells exhibited some enhancement of activity. The effects of these compounds on identified STT cells resemble previous demonstrations of the effects of these drugs on dorsal horn interneurons. The results suggest that GABA, Gly, 5-HT, NE, and DA may be inhibitory neurotransmitters on nociceptive STT cells.

Cation selectivity of light-sensitive conductance in retinal rods.

Abstract: Vertebrate photoreceptors respond to light by a membrane hyperpolarization which is thought to result from the decrease of a Na-selective conductance in the outer segment1–6. One hypothesis is that light increases intracellular free Ca which reversibly blocks the Na conductance7,8; at least part of this Ca is then extruded to the cell exterior by a Na–Ca exchanger at the plasma membrane9–14. We describe experiments here which show that the light-sensitive conductance in rods is also highly permeable to K. While external Na acts to keep the conductance open, external K tends to keep it closed, both actions probably involving the Na–Ca exchanger. The conductance is also permeable to the monovalent cations Li, Rb and Cs and the divalent cations Ca, Sr and Ba. The ability of both Na and K to go through the light-sensitive conductance explains the long-standing puzzle as to why the reversal potential for the light response is at 0 to +10 mV15–17.

Factors influencing peripheral nerve stimulation produced inhibition of primate spinothalamic tract cells.

Abstract: Several factors that influence the inhibition of primate spinothalamic tract (STT) cells produced by repetitive peripheral conditioning stimulation have been studied. Identified STT cells were recorded from the lumbosacral spinal cord in intact, anesthetized monkeys. In addition, presumed STT cells were recorded from unanesthetized, decerebrate or decerebrate, spinalized monkeys; these cells were identified by antidromic activation from the contralateral ventral lateral funiculus of the upper cervical spinal cord. Activity of the STT cells was evoked by electrically stimulating the sural nerve with pulses having an intensity strong enough to activate C fibers. The C fiber evoked STT cell activity was compared before, during and after repetitive conditioning stimuli applied to the tibial nerve for 5 min. By applying repetitive strengths of conditioning stimuli, it was found that the A delta fiber group is the most important for producing inhibition of STT cells, although significant additional effects were also produced by the A alpha beta and C fiber groups. Conditioning stimuli with fixed intensity at different frequencies showed that the higher the frequency the more powerful the inhibition within the range we tested (0.5-20 Hz). The inhibition produced by peripheral nerve stimulation was segmentally organized, so the most effective nerve in producing inhibition amongst those tested was the ipsilateral tibial nerve. The contralateral sciatic nerve, the ipsilateral median nerve and the contralateral median nerve were less effective in that order. The results of the present experiments suggest that the most effective way to produce analgesia by peripheral nerve stimulation would be by high frequency stimulation of a nerve innervating the area from which pain originates with an intensity at least strong enough to activate A delta fibers.

Reliability and Validity of Self Report of Aerobic Activity: Family Health Project

Abstract: Two studies are presented which deal with the reliability and validity of self-reports of aerobic activity. The first study compared two forms of self-report data obtained as part of a study of intervention strategy. The two forms were daily self-report and weekly retrospective report. Analyses covering the overlapping time period revealed differences in mean minutes engaged in activity, but modest and statistically significant correlations between the two forms among adults participating in the intervention group. No meaningful results were obtained among adults in the control group, nor among children in either group. The need for the development and testing of self-report forms among children was noted, and was the subject of the second study. In Study II, six different forms on which third to sixth grade children recorded their aerobic activity were compared against two days of continuous observations of their behavior. The six forms varied along two dimensions. The first dimension varied the...

Further evaluation of saline infusion for the diagnosis of primary aldosteronism.

Abstract: Normal subjects, normal-renin hypertensive patients, and low-renin hypertensive patients were evaluated by intravenous saline infusion and with a fludrocortisone acetate (Florinef) protocol to clarify diagnostic criteria for primary aldosteronism that are recommended for the saline infusion protocol. The patients consumed a 200 mEq sodium, 70 mEq potassium diet for 6 days, and on the last 3 days received Florinef 0.5 mg orally twice daily. On Days 3 and 6, urinary aldosterone and tetrahydroaldosterone excretions were determined, and on Days 4 and 7 plasma aldosterone (PA) was determined at 0600 after overnight recumbency and at 0800 after 2 hours of walking. Although the level of normal PA suppression by saline infusion has been commonly defined as 10 ng/dl, a value of 5 ng/dl was originally recommended. In 20 normal subjects and 45 normal-renin hypertensive patients, we found that the PA was almost always suppressed below 5 ng/dl. In 18 of 75 low-renin patients including five with aldosterone-producing adenoma (APA), the PA was never suppressed below 10 ng/dl; thus, these 18 patients had classical primary aldosteronism by generally accepted criteria. The Florinef protocol was performed in eight of these 18 patients and was abnormal in all. An abnormal Florinef protocol was also found in seven of 15 patients studied with PA suppression after saline infusion to between 5 and 10 ng/dl, but in only one of 24 patients studied with PA suppression below 5 ng/dl. Additional studies in the subgroup with abnormal results from the Florinef protocol indicated that none of these patients had evidence of APA, so they had nontumorous primary aldosteronism (NTPA).(ABSTRACT TRUNCATED AT 250 WORDS)

Prolonged inhibition of primate spinothalamic tract cells by peripheral nerve stimulation

Abstract: Inhibition of spinothalamic tract (STT) cells was produced by repetitive peripheral nerve conditioning stimulation with high intensity and low frequency pulses. Identified STT cells were recorded from the lumbosacral spinal cord of intact, anesthetized monkeys. In addition, presumed STT cells were recorded from both unanesthetized, decerebrated and decerebrated, spinalized monkeys. These cells were identified by antidromically activating them from the contralateral ventral lateral funiculus of the cervical spinal cord. Both C fiber activity evoked by electrical stimulation of the sural nerve and activity evoked by noxious heat were greatly inhibited by repetitive conditioning stimuli applied either to the common peroneal or tibial nerve with a strong enough intensity for activation of C fibers at 2 Hz for 15 min. The inhibition was maintained during the period of conditioning stimulation and often outlasted stimulation by 20–30 min. The inhibition of cells produced by peripheral nerve stimulation was observed in decerebrate and spinalized animals as well as in intact anesthetized monkeys, although the mean recovery time in the decerebrate group was faster. This indicates that anesthetics did not interfere with the inhibitory mechanism. Furthermore, the presence of inhibition in spinalized animals means the inhibition must depend in part on spinal cord neuronal circuitry. Intravenous injection of naloxone produced a significant but small reduction of the recovery phase of the inhibition. No pharmacological agent was found that substantially interfered with the powerful inhibition produced during peripheral conditioning stimuli. The experimental animal model used in these experiments seems appropriate for studying the mechanisms of analgesia produced by peripheral nerve stimulation.

Occupational repetition strain injuries. Guidelines for diagnosis and management.

Abstract: Occupational repetition strain injuries (RSI) are a major, unchecked source of disability in industry and commerce, and have considerable social and economic consequences. The long-term morbidity associated with these injuries is preventable, but a coordinated approach to awareness, diagnosis, management, and prevention has been lacking. Confusing diagnostic terminology on medical certificates makes it difficult to obtain accurate data on the incidence and prevalence of different types of repetition injury. The terminology in use at present includes RSI, "tenosynovitis" and "overuse injury". Uniformity of diagnosis on an anatomical basis in relation to repetition or static load would greatly assist in epidemiological study, and improve notification and the impact of prevention programmes. Therefore, the Occupational Repetition Strain Injuries Advisory Committee, which was convened by the Division of Occupational Health, New South Wales Government Department of Industrial Relations, has prepared a set of guidelines for the diagnosis and management of these injuries.

Measuring social support: A synthesis of current approaches

Abstract: Definitions and concepts of social support are reviewed in an attempt to develop a theoretical structure for future research. Fourteen techniques for measuring social support are assessed to ascertain the degree to which they reflect common theoretical elements. A paradigm that should help to focus research efforts on the construction of a systematic knowledge base about social support is proposed.

The pathophysiology of smoke inhalation injury in a sheep model

Abstract: This study describes an experimental model of smoke inhalation injury in sheep, in which the same pathophysiologic alterations occur as with clinical inhalation in man. Both the patients and the experimental sheep develop diffuse pulmonary mucosal sloughing, pulmonary edema, and a decrease in systemic oxygen tension. The results of this study indicate that the pulmonary edema is the result of an increase in microvascular permeability, characterized by increases in lung lymph flow (Qlym), lymph-to-plasma protein concentration ratio (L/P), and transvascular protein flux (Qlym X lung lymph protein concentration), while pulmonary vascular pressures remain constant. Neutrophil degranulation may contribute to the increased microvascular permeability.

The relation of megakaryocyte ploidy to platelet volume.

Abstract: To determine how alterations of megakaryocyte proliferation will affect platelet production, we measured mean platelet volume (MPV), platelet volume heterogeneity, platelet count, and mean megakaryocyte ploidy in 42 patients. In normal subjects, mean platelet volume and megakaryocyte ploidy were related inversely but nonlin-early to platelet count, whereas mean platelet volume and platelet volume heterogeneity were related directly. In patients with immune thrombocytopenic purpura (low platelet count, MPV above normal, and increased megakaryocyte ploidy), and in those with reactive thrombocytosis (high platelet count, low MPV and megakaryocyte ploidy), the relation of MPV to megakaryocyte ploidy, platelet volume heterogeneity, and platelet count resembled or extended the relations found in normal subjects. By contrast, in patients with aplastic anemia or megaloblastic anemia, or in patients who were undergoing chemotherapy for leukemia, heterogeneity was increased abnormally at any MPV, and both MPV and megakaryocyte ploidy were substantially lower, at any platelet volume, than in normals or the above other groups. The most common ploidy class was 8N in all patients, and the mean megakaryocyte ploidy correlated directly and linearly with mean platelet volume. The data show that bone marrow with megakaryocytes of higher ploidy produces platelets that are both larger and more heterogeneous.

Elevated urinary excretion of 18-oxocortisol in glucocorticoid-suppressible aldosteronism

Abstract: A radioimmunoassay procedure for the measurement of urinary 18-oxocortisol was developed. The antibody was raised against 18-oxocortisol 3-carboxymethyloxime-BSA and had relatively high specificity, except for aldosterone (26.3%). The RIA required a preliminary HPLC purification using a Lichrosorb diol column eluted with toluene:acetonitrile:isopropanol:acetic acid (83:11.9:5.1:0.01). The eluate portion corresponding to 18-oxocortisol was evaporated and subjected to RIA. The RIA procedure had an intraassay variability of 11% when using a pool containing 10.8 μg/24 hr (n=6) and 17% with a pool containing 3.28 μg/24 hr. The interassay variability was 11% (n=4). The recovery of added 18-oxocortisol was 90 ± 10%. The urinary excretion of 18-oxocortisol in 22 white normal subjects was 3.26 ± 1.98 (SD) μg/24 hr (range 0.8 to 7.1 μg/24 hr). The mean excretion of 18-oxocortisol in 4 patients with glucocorticoid-suppressible aldosteronism (GSA) was 38.6 μg/24 hr (range 25.5 to 54.6 μg/24 hr). The excretio...

Description of Sarcocystis falcatula stiles, 1893, a parasite of birds and opossums.

Abstract: Sarcocystis falcatula Stiles, 1893 is re-described. Intermediate hosts of the parasite which was earlier described as Sarcocystis debonei Vogelsang, 1929 are species of passeriform, psittaciform, and columbiform birds. In these birds, muscle zoites are 6.88 X 2.19 (4.8-8.4 X 1.2-3.6) micron and are enclosed in a cyst wall with regular protrusions, 1-5 micron long. The convoluted primary wall has multiple thin areas in the osmiophilic layer. Microtubules originate in the ground substance and extend to the tips of the protrusions. The only known definitive host is the opossum, Didelphis virginiana; rats, cats, a dog, and a ferret could not be infected from muscle cysts. Sporocysts from opossums infected from five different infected avian sources measure 11.2 X 7.4 (9.6-12.0 X 6.0-8.4) micron.

Incidence of breast-feeding in a low socioeconomic group of mothers in the United States: ethnic patterns.

Abstract: Breast-feeding has been shown to have increased in incidence during recent years in the United States However, this increase is not particularly evident in lower socioeconomic groups Factors associated with the decision to breast-feed or not were investigated in a population of 379 mothers Self-completed questionnaires were obtained from 945% of these mothers Data with respect to demographics, reproductive history, prenatal care, and education were collected Only 272% of the study population indicated that they intended to breastfeed Using the x2 test for equality of proportions, marital status, head of household, maternal and paternal ethnicity, maternal education, income, and number of pregnancy were found to be the most important variables associated with breast-feeding The effect of ethnicity predominated over that of the other demographic variables when they were examined jointly within ethnic groups The effect of ethnicity was apparent when the number of each ethnic group in the study population was compared with the percent of that group that intended to breast-feed: 145 Anglo-Americans, 435% breast-feeding; 131 black Americans, 92%; 62 Mexican Americans, 226%; 19 others, 421% The importance of ethnicity in the decision to breast-feed has probably been underestimated Efforts to increase breast-feeding in the United States ought to be designed with full consideration of this factor

Effects of iontophoretically released peptides on primate spinothalamic tract cells

Abstract: The peptides substance P (SP), methionine-enkephalin (M-ENK), leucine-enkephalin (L-ENK), and cholecystokinin (CCK) were released iontophoretically near spinothalamic tract (STT) cells in anesthetized monkeys and STT-like cells in decorticate, spinalized monkeys Peptide effects were observed on background discharges, firing induced by release of glutamate, and activity evoked by pinching the skin SP could have any of several actions on STT cells, including excitation, inhibition, or biphasic effects Multiple effects often resulted while recording from an individual cell when the dose or the electrode position was changed M-ENK and L-ENK generally inhibited STT cells, and in some cases it was possible to demonstrate a reversal of the inhibition by naloxone CCK also caused an inhibition that was additive with that produced by L-ENK The multiple actions of SP on STT cells suggests the possibility that there may be more than one type of SP receptor on STT cells, although alternative explanations should be considered Inhibition of STT cells by M- and L-ENK is consistent with the known analgesic action of opiates through spinal cord mechanisms CCK has an action on STT cells similar to that of the enkephalins

Initiation of proliferative events by human α‐thrombin requires both receptor binding and enzymic activity

Abstract: To determine the role of thrombin high-affinity receptor occupancy and enzymic activity in thrombin initiation of cell proliferation, we have utilized thrombin derivatives which separate these functions. We previously showed that enzymically active γ-thrombin stimulates ion fluxes without binding to high-affinity sites, whereas proteolytically inhibited DIP-α-thrombin which binds to high-affinity receptors does not. Since neither derivative initiates DNA synthesis by itself, this suggested that two separate sequences of events might be necessary for a complete initiation signal. We now report that the combination of DIP-α-thrombin and γ-thrombin initiate DNA synthesis and cell proliferation to levels approaching the maximal initiation by native α-thrombin. This combinatory effect is dose-dependent for both γ-thrombin and DIP-α-thrombin in the same concentration range as α-thrombin alone. Thus, these same concentrations of α-thrombin alone may be required to initiate each sequence of events. The combinatory stimulation could be achieved even if the derivatives were added individually up to 8 hr apart. Moreover, preincubation with either derivative shortened the lag period for initiation of DNA synthesis by native α-thrombin. These results indicate that both receptor occupancy and enzymic activity are necessary for thrombin initiation of cell proliferation and that each action initiates a sequence of early events which moves the cell forward toward entry into a proliferative cycle.

Probe evoked potentials: theory, method and applications.

Abstract: The probe evoked potentials method which involves recording brain responses to irrelevant stimuli during performance of a wide range of cognitive tasks, is used with increasing frequency to assess patterns of regional cerebral activation mediating distinct cognitive operations. This paper delineates the evolution of the method, describes its procedural and theoretical features, reviews its applications with normal adults, infants and children, and with neuropsychologically compromised individuals. The outcome of these studies points to the advantages of this method over traditional evoked potential procedures in the assessment of regional cerebral engagement in cognitive operations, free of confoundings due to stimulus and response-specific activity, in ecologically valid experimental situations.

Adenosine mediates a slow hyperpolarizing synaptic potential in autonomic neurones.

Abstract: Considerable evidence has accumulated suggesting that purines, adenosine and ATP function as neurotransmitters in the central and peripheral nervous systems1–4. Burnstock2 has proposed that purinergic receptors be classified into two types, P1 and P2, having adenosine and ATP, respectively, as agonist prototypes. Recent data suggest that ATP may mediate a synaptic potential in guinea pig vas deferons5,6, but no such evidence exists for adenosine. The presence of a non-cholinergic, non-adrenergic nerve supply to the urinary bladder has been postulated7,8 and termed purinergic1,2, as these nerves have been shown to release ATP7. Furthermore, atropine-resistant contractions of bladder smooth muscle are thought to be mediated by ATP, while in situ experiments9,10 in vesical parasympathetic ganglia have suggested that a purinergic modulatory mechanism may control urinary bladder function. We now report the presence of a slow hyperpolarizing synaptic potential (slow-h.s.p.) in neurones of cat vesical parasympathetic ganglia, produced by stimulating the preganglionic nerves, and provide evidence that the slow-h.s.p. is mediated by adenosine.

Food protein-induced enterocolitis: altered antibody response to ingested antigen.

Abstract: To evaluate the role of immunologic mechanisms in one specific syndrome of food intolerance in infants, food protein-induced enterocolitis, we measured class-specific serum antibodies to three food proteins, ovalbumin, soy, and cow milk, prior to diagnostic food challenges in 18 infants suspected to have this syndrome. Infants with positive challenge reactions to egg, soy, or cow milk had 5-10 times higher levels of IgA antibody directed against that food than did the infants with negative challenges. Levels of IgG antibody to soy and egg were also significantly higher (greater than 10-fold) in infants with positive challenge responses. There was no significant difference in levels of IgM food antibodies between the two groups. IgA anti-soy antibody levels rose in all 12 infants tested 2-10 weeks after a single soy feeding (challenge). However, IgM anti-soy antibody increased in the five infants who had a negative response to the challenge feeding and decreased in those seven with a positive response. The difference between the two groups was statistically significant (P less than 0.01). Some correlation existed (r = -0.68) between the increase in IgA anti-soy antibody and the decrease in IgM anti-soy antibody for infants with positive soy challenges. Although a pathogenic role for these antibodies is not proven, the findings suggest an altered immunologic response to ingestion of food antigens in infants with food protein-induced enterocolitis.