Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth.

Contact-dependent axon growth inhibitory activity is present in CNS myelin, but the inhibitory proteins have not been fully characterized. We report here that at least two peaks of inhibitory activity can be separated by fractionating solubilized CNS myelin proteins by DEAE chromatography. A major peak of inhibitory activity corresponded to the elution profile of myelin-associated glycoprotein (MAG). Immunodepletion of MAG from these inhibitory fractions removed neurite growth inhibition, whereas recombinant MAG (ectodomain) was a potent inhibitor of neurite outgrowth. Immunodepletion of MAG from total extracts of CNS myelin restored neurite growth up to 63% of control levels. These results establish that MAG is a significant, and possibly the major, inhibitor in CNS myelin; this has broad implications for axonal regeneration in the injured mammalian CNS.

Total cerebral ischemia: effect of alterations in arterial PCO2 on cerebral microcirculation.

Radiolabeled 15-microns microspheres were used to examine alterations in regional CBF and cerebrovascular resistance in response to changes in arterial PCO2. Flow measurements were obtained before and 1-3 and 24 h after 12 min of total cerebral ischemia. Striking sensitivity of blood flow in all areas of the central nervous system was shown to changes in arterial PCO2 between 24 and 50 mm Hg during the control nonischemic period. Following 12 min of total cerebral ischemia, cerebrovascular resistance increased, producing a decrease in regional blood flow when the important controlling variables for CBF were held constant. One to 3 h after total cerebral ischemia, the effect of variations in arterial PCO2 on cerebral blood flow was almost completely abolished. Within 24 h after total cerebral ischemia, the sensitivity of CBF to changes in PCO2 was almost completely restored, whereas the secondary severe neurologic deficit remained. Therapeutic interventions following global cerebral ischemia, designed to ameliorate the "no-reflow" phenomenon and minimize residual ischemic neurologic damage, must take into account this marked early post-ischemic reduction in sensitivity to normally potent cerebrovasodilatory influences.

Subnormal concentrations of serum selenium and plasma carnitine in chronically tube-fed patients.

Forty-seven tube-fed nursing home patients were investigated with regard to serum or plasma selenium (Se), carnitine, and red blood cell (RBC) glutathione peroxidase (GSH-Px). Thirty-six patients were tube fed with Isocal, and 11 were tube fed with Compleat B, an L-carnitine-containing formula. Eighteen elderly nursing home patients and 10 young adults served as controls. Serum Se and plasma carnitine were lowest (p less than 0.05) in the Isocal patients. In all 36 Isocal subjects, Se was below normal, and in 26% of Isocal patients RBC GSH-Px was also below normal. Free and total carnitine were below normal in most Isocal subjects. All 11 Compleat B patients had subnormal serum Se, but most had normal carnitine concentrations. These data suggest that enteral formulae in nursing homes should contain greater than 100 micrograms Se and on the order of a mmol carnitine/1600 kcal.

Isaacs syndrome with laryngeal involvement: an unusual presentation of myokymia.

A woman with widespread myokymia presented initially at age 19 with hoarseness and mild dyspnea on exertion. The diagnosis of Isaacs syndrome was suggested by the clinical findings of widespread continuous muscle activity and depressed tendon reflexes, although she lacked the usually prominent increased muscle tone. The diagnosis was confirmed by the electromyographic demonstration of continuous spontaneous muscle action potentials that were abolished by neuromuscular blockade but not by local nerve blockade. Pulmonary function tests were consistent with fixed extrathoracic obstruction. The vocal cords were closely approximated. Electromyographic studies of the laryngeal muscles under general anesthesia revealed continuous muscle activity, which accounted for the hoarseness and much of the exertional dyspnea. The patient responded well to treatment with phenytoin and carbamazepine. This unusual syndrome should be considered in the differential diagnosis of patients with respiratory complaints and muscle fasciculations, even though they have normal muscle tone.

Plasma testosterone in nursing home men.

Plasma testosterone (T) was measured at 8-9 a.m. in 44 men chronically institutionalized in a Veterans Administration Nursing Home, and correlated with an extensive clinical data base (including age, diagnoses, drugs, laboratory tests, anthropometric measurements, and mortality during the year after the T analysis). Age averaged 76.4 years (range 60-95). Plasma T was below the lower limit of the normal range for healthy young men (i.e. less than 300 ng/dl) in 46% of the men studied. Samples containing low T (less than 300 ng/dl) also contained subnormal unbound T, but normal concentrations of thyroxine and cortisol. Of the low T samples, 45% contained elevated LH, FSH or both (over 20 mU/ml), and the remaining 55% contained LH and FSH levels below this threshold, these two subgroups representing peripheral and central hypogonadism respectively. Plasma T was significantly (p less than 0.02) correlated in a direct relationship with hemoglobin, serum cholesterol, and the occurrence of seizures.

Simultaneous measurements of cerebral blood flow by the xenon/CT method and the microsphere method. A comparison.

Simultaneous measurements of cerebral blood flow have been performed in baboons to assess the correlation between the acute and invasive nondiffusible microsphere technique and the noninvasive xenon-enhanced CT method. Blood flows in small tissue volumes (approximately 1 cm3) were directly compared. The results of these studies demonstrate a statistically significant association between the two methods (P less than .001). Similar correlations were obtained by both the Kendall tau (tau) and the Spearman (r) methods. The problems and limitations of such correlations are discussed.

Antecedents of death in the men of a Veterans Administration nursing home.

This study aims to learn whether the annual clinical and laboratory screening of nursing home residents provides significant information about their chance of dying during the following year. In August 1984, a comprehensive clinical data base was compiled for 176 male residents of this VA nursing home. During the next 14 months, 12 men were discharged to other locations and were dropped from the study; among the remaining 166, who comprised the study group of this report, 24 died. The most common immediate causes of death were infections (67%) and cardiac disorders (25%). Twenty of the deaths occurred after transfer to the acute hospital services. Among the 67 items in the clinical data base (including absence or presence of 17 diagnoses and 16 drugs), eight were significantly correlated with death rate. Age and functional impairment were directly related, and inversely related were the following: body weight as percent of ideal, triceps skin fold, hematocrit, hemoglobin, serum albumin, and serum cholesterol. Multivariate analysis showed cholesterol and hematocrit to be the most informative of the eight mortality predictors and to correlate with death independently of age and functional level. Subgroups defined on the basis of combinations of mortality-related attributes differed many fold in their death rates. For example, men with cholesterol less than or equal to 156 mg/dl and hematocrit less than or equal to 41% died at a rate 42 times the rate of men with values above both thresholds. For each mortality-related attribute, death rate varied with the level of the attribute. This relationship extended into the generally accepted "normal ranges" for cholesterol, hematocrit, hemoglobin, and albumin.

Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with codeine, and placebo after dental extraction.

Tramadol hydrochloride is a novel, centrally acting analgesic with two complementary mechanisms of action: opioid and aminergic. Relative to codeine, tramadol has similar analgesic properties but may have fewer constipating, euphoric, and respiratory depressant effects. A two-center randomized double-blind controlled clinical trial was performed to assess the analgesic efficacy and reported side effects of tramadol 100 mg, tramadol 50 mg, codeine 60 mg, aspirin (ASA) 650 mg with codeine 60 mg, and placebo. Using a third molar extraction pain model, 200 healthy subjects were enrolled in a 6-hour evaluation after a single dose of drug. Of the 200 patients enrolled, seven provided incomplete efficacy data or discontinued prematurely and one was lost to follow-up. Using standard measures of analgesia, including total pain relief score (TOTPAR), maximum pain relief score (MaxPAR), sum of pain intensity difference scores (SPID), peak pain intensity difference (Peak PID), remedication, and global evaluations, all active treatments were found to be numerically superior to placebo. ASA/codeine was found to be statistically superior to placebo for all measures of efficacy. Tramadol 100 mg was statistically superior to placebo for TOTPAR, SPID, and time of remedication, whereas tramadol 50 mg was statistically superior to placebo onlyfor remedication time. Codeine was not found to be statistically superior to placebo for any efficacy measure. A greater TOTPAR response compared with all other active measures was seen for ASA/codeine during the first 3 hours of study. The 6-hour TOTPAR scores for the tramadol groups and ASA/ codeine group were not significantly different. Gastrointestinal side effects (nausea, dysphagia, vomiting) were reported more frequently with tramadol 100 mg, ASA/ codeine, and codeine 60 mg than with placebo.

Glutamate participates in the peripheral modulation of thermal hyperalgesia in rats.

While the effects of excitatory amino acids have been well characterized in the central nervous system, relatively little is known about their possible modulation of elements responsible for hyperalgesia within peripheral tissue. The presented experiments demonstrate that the intraplantar (i.pl.) injection of L-glutamate (30 nmol) evokes a thermal hyperalgesic response in the paw withdrawal latencies of normal rats which is stereospecific. In addition, the i.pl. injection of either the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (10 nmol) or the competitive alpha-amino-3-hydroxy-4-methyl-5-isoxazolepropionic acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)(100 nmol) into hindpaws inflamed with carrageenan significantly reduced the thermal hyperalgesic response in rats. Collectively, these results suggest that excitatory amino acids activate a peripheral target which facilitates a hyperalgesic behavioural response to thermal stimulation via a receptor mediated process.

Activation of excitatory amino acid receptors in bovine dental pulp evokes the release of iCGRP.

The activation of excitatory amino acid (EAA) receptors within the central nervous system is associated with numerous centrally mediated phenomena, including hyperalgesia. However, relatively little is known about the peripheral mechanisms which these receptors may regulate when activated. This research evaluated the hypothesis that EAA receptors in bovine dental pulp activate a population of peptidergic sensory neurons as measured by the release of immunoreactive calcitonin gene-related peptide (iCGRP), a neuropeptide associated with neurogenic inflammation. In vitro superfusion of bovine dental pulp was used to evaluate the regulation of iCGRP secretion by the EAA receptor agonists AMPA, kainate, NMDA, and L-glutamate. Both AMPA and kainate stimulated the release of iCGRP in a concentration-dependent manner (AMPA EC50 = 0.27 +/- 3.3 nM; kainate EC50 = 3.2 +/- 1.1 microM). Pre-treatment and co-administration of the AMPA/kainate receptor antagonist CNQX significantly reduced the iCGRP release evoked by either of these agonists. In contrast, neither NMDA nor L-glutamate induced any consistent changes in iCGRP release. These results suggest that the activation of AMPA and kainate receptors in dental pulp may contribute to peripheral release of vasoactive neuropeptides which mediate a neurogenic component of inflammation.

Intrinsic regulation of CGRP release by dental pulp sympathetic fibers.

Neurotransmission from sympathetic and peptidergic afferent fibers participates in the regulation of pulpal blood flow (PBF) via opposing effects. In this study, we directly tested the hypothesis that activation of pulpal sympathetic terminals inhibits exocytosis of immunoreactive calcitonin gene-related peptide (iCGRP) from peptidergic afferents innervating bovine dental pulp. The results demonstrate that norepinephrine inhibits capsaicin-evoked iCGRP release. The application of alpha-adrenergic antagonists (phentolamine or phenoxybenzamine) increased spontaneous release of iCGRP. Moreover, administration of agents that evoke the release of sympathetic neurotransmitters (guanethidine or reserpine) inhibited capsaicin-evoked iCGRP release. Collectively, these results indicate that sympathetic neurotransmission inhibits exocytosis from pulpal peptidergic afferent fibers. Analysis of these data supports the hypothesis that peripheral sympathetic vasomotor control may operate by a direct mechanism (vasoconstriction) as well as by an indirect mechanism (e.g., inhibition of exocytosis from afferent fibers). Since capsaicin-sensitive neurons are nociceptors, it is possible that certain sympathetic neurotransmission may modulate pain.

beta 2-Adrenoceptor regulation of CGRP release from capsaicin-sensitive neurons.

Previous studies have suggested that neurotransmitter substances from the sympatho-adrenomedullary system regulate pulpal blood flow (PBF), in part, by the inhibition of vasoactive neuropeptide release from pulpal sensory neurons. However, no study has evaluated the role of beta-adrenoceptors. We evaluated the hypothesis that activation of beta-adrenoceptors inhibits immunoreactive calcitonin gene-related peptide (iCGRP) release from capsaicin-sensitive nociceptive neurons via in vitro superfusion of bovine dental pulp. Either norepinephrine or epinephrine inhibited capsaicin-evoked iCGRP. The norepinephrine effect was blocked by the selective beta(2)-adrenoceptor antagonist, ICI 118,551, but not by pre-treatment with the selective beta(1)-adrenoceptor antagonist, atenolol. In addition, application of albuterol, a selective beta(2)-adrenoceptor agonist, significantly blocked capsaicin-evoked release of iCGRP. Collectively, these studies demonstrate that activation of beta(2)-adrenoceptors in dental pulp significantly reduces exocytosis of neuropeptides from capsaicin-sensitive nociceptors. This effect may have physiologic significance in regulating PBF. Moreover, since capsaicin selectively activates nociceptors, beta(2)-adrenoceptor agonists may have clinical utility as peripherally acting therapeutics for dental pain and inflammation.

Pressure-pain thresholds and MRI effusions in TMJ arthralgia.

It has been suggested that MRI-depicted effusions identify patients with TMJ arthralgia. The Research Diagnostic Criteria (RDC) propose a pressure-pain threshold (PPT) of 1 pound for the identification of TMJ arthralgia. The hypotheses in this study were that: (1) there is no association between MRI-depicted effusions and TMJ arthralgia, and (2) a PPT of 1 pound does not discriminate between subjects with and those without arthralgia. Thirty females with TMJ disc displacement with reduction were divided into two groups based on the presence or absence of the self-report of TMJ pain. Bilateral TMJ PPTs and MRIs were obtained. Increasing palpation pressure from 1 to 3 pounds increased the sensitivity for identifying arthralgia from 22% to 100%, with a corresponding decrease in the specificity from 100% to 81%. The sensitivity and specificity of effusions for identifying arthralgia were 85% and 28%, respectively. These results suggest that the use of palpation pressures greater than 1 pound is a valid test for TMJ arthralgia. However, TMJ effusions lack adequate specificity for identifying TMJ arthralgia and were not associated with pain.

Tarsal tunnel syndrome in runners.

Tarsal tunnel syndrome has only recently been noted to be a cause of foot and ankle pain in runners. The tarsal tunnel is located just posterior to the medial malleolus and may compress the posterior tibial nerve as it passes through it, producing numbness and paraesthesia in the foot. While the aetiology of this condition is frequently multifactorial, abnormal foot and ankle mechanics and excessive training tend to be the most commonly cited aetiological factors. Successful treatment of tarsal tunnel syndrome requires an accurate diagnosis by differentiating it from plantar fasciitis and Achilles tendinitis and then making proper biomechanical and training changes in the runner. Conservative treatment is generally successful, but occasionally surgical treatment is required to decompress the nerve.

Relation of serum albumin concentration to death rate in nursing home men.

Serum albumin was measured in 126 men (average age 70.6; range 40 to 96) of a Veterans Administration Nursing Home, and was correlated with other items in an extensive clinical data base, including death or survival during the year after the analysis. The reason for institutionalization was chronic neurologic disease or other disabling physical condition in 63 men (group A), and psychiatric disorder in 63 men (group B). In group A, the proportions of men with albumin less than 3.5, 3.5-4.0, and greater than 4.0 g/dl were 6%, 37%, and 57%, respectively. In this group, the serum albumin level was significantly (p less than 0.05) correlated with death rate, hemoglobin, hematocrit, serum cholesterol, and serum lactic dehydrogenase. The death rate in group A during the year after the albumin analysis was 25%. For the patients with albumin level less than 3.5, 3.5-4.0, and greater than 4.0 g/dl, the death rates were 50%, 43%, and 11% respectively (p less than 0.01 for comparison of the former two groups with the latter). The subgroup with albumin 3.5-4.0 g/dl represented only 37% of the men in group A, but accounted for 63% of the group's deaths. In group B, serum albumin level was not significantly correlated with any other clinical variable. Death rate during the year after the albumin analysis was only 2% in group B, and did not correlate with the albumin level. These data indicate that, in nonpsychiatric Nursing Home men, the desirable level for the serum albumin concentration is higher than 3.5 g/dl.

Prognostic significance of serum cholesterol in nursing home men.

Serum cholesterol was measured in 129 men (average age 70.6; range 41-96) of a Veterans Administration Nursing Home, and was correlated with other items in an extensive clinical data base. Serum cholesterol was less than 150 mg/dl in 13% of the subjects, and was less than 160 mg/dl in 18%. Cholesterol greater than 280 mg/dl occurred in 8%. Serum cholesterol varied directly (p less than 0.02) with: body weight, serum albumin, serum total protein, serum sodium, ability to walk, and ability to feed oneself; and indirectly (p less than 0.02) with death rate, degree of functional dependence, and serum SGOT and LDH. Nursing home men with cholesterol less than 150 mg/dl had a death rate of 63% during the 14 months after the cholesterol analysis, compared to a death rate of 9% in men with cholesterol greater than 150 mg/dl (p less than 0.05). Death rate during the year after the analysis was 52% if cholesterol was below 160 mg/dl, compared to 7% if it was above this threshold (p less than 0.05).

Tarsal tunnel syndrome in athletes. Case reports and literature review.

Tarsal tunnel syndrome is being seen in increasing frequency in the athletic population, especially in the running athlete. The sports medicine physician must be cognizant of this entity, including proper diagnostic testing and management.

Racial differences on the Conners Teacher Rating Scale.

Factor congruence and mean differences on the Conners Teacher Rating Scale were assessed across African-American and Caucasian school children. Factor analyses conducted separately by gender revealed similar factors across races for males and females. The main differences in factor structure within gender were the presence of an Antisocial factor in black males and an Inattention factor in white females. Across both males and females, teachers tended to rate black children higher than white children on factors relating to externalizing behaviors. Whether mean differences are a result of teacher bias or actual behavioral differences in the classroom needs further research.

Multidrug intravenous sedation: determinants of the sedative dose of midazolam.

OBJECTIVES: The efficacy of multidrug intravenous sedation regimens in oral surgery is based on the ability to titrate opioids, benzodiazepines, and barbiturates to a desired level of relaxation. Dosage requirements to reach the initial sedation end points of slurred speech and ptosis of eyelids vary widely from one patient to another. STUDY DESIGN: An assessment of physical, cardiovascular, behavioral, and pharmacologic factors that might predict midazolam dosage requirements for the initial sedation titration was carried out with data collected from a large controlled clinical trial of fentanyl, midazolam, and methohexital sedation for third molar surgery. RESULTS: Dosage requirements for the initial titration of midazolam were found to be significantly higher when fentanyl was not included in the sedation regimen and when presedation heart rate and presedation systolic blood pressure were elevated.

Preoperative nonsteroidal anti-inflammatory medication for the prevention of postoperative dental pain.

It is predictable for patients to experience postoperative pain and inflammation. Until recently, therapeutic strategies for the management of these sequelae have been symptomatic rather than preventive. This article reviews prophylactic use of nonsteroidal anti-inflammatory medication for preventing postoperative discomfort, and includes recommendations on patient selection and medication regiment.