False ascending aortic aneurysm.
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Aortic Aneurysm↗
Biomedical subjects
J Wright
Publications and source records attributed to J Wright.
Orbicularis muscle pathology after botulinum toxin injection.
A 49-year-old woman underwent 1 year (six injections) of botulinum toxin treatments for essential blepharospasm. When she became dissatisfied with the need for repeat injections, she elected to undergo an orbicularis muscle stripping procedure for control of spasms. Pathologic examination of the orbicularis muscles showed only minimal degenerative changes. Botulinum toxin injection into the orbicularis is known to provide only temporary relief of essential blepharospasm. This may be because the resulting orbicularis atrophy is insufficient to maintain permanent control of these spasms.
Atrophy↗
Emergency surgery in patients with post-traumatic myocardial contusion.
Little information concerning the prognostic and functional significance of post-traumatic myocardial contusion appears to exist. During a 10-month period, 19 patients with major blunt thoracic trauma were diagnosed as having myocardial contusion using clinical findings, serial ECG and CPK-MB isoenzyme determinations, and biventricular radionuclide angiocardiography (RA). All patients had associated thoracic and extrathoracic injuries. ECG and RA were useful and complementary tests, detecting abnormalities in 90% and 47% of patients, respectively. Only one patient had an abnormally elevated CPK-MB. All patients required operative treatment for associated injuries, 15 (79%) on the day of admission. Eleven patients required perioperative cardiac inotropic support and one needed IABP. No late complications were attributable to the cardiac contusions per se; no patients died. Emergency surgery for associated injuries in patients with myocardial contusion can be safely performed using hemodynamic monitoring to guide cardiac inotropic support measures. Myocardial contusion does not constitute an absolute contraindication to necessary operations in polytraumatized patients.
Adolescent↗
The effects of exogenous melatonin on endocrine function in man.
At two different times of year (spring and autumn) an oral preparation of the pineal neurohormone melatonin, or placebo, was administered to 12 healthy volunteers (10 men and two women in spring: the same group minus one man in autumn) daily at 1700 h for 1 month (spring), or 3 weeks (autumn) using a double-blind cross-over protocol. The daily dose was 2 mg melatonin in 5 ml corn-oil, and placebo consisted of the vehicle only. In spring the anterior pituitary hormones LH, PRL, GH together with T4, cortisol, testosterone and melatonin were measured at 1- to 6-h intervals for 24 h in plasma on the day following the last dose. In autumn PRL, cortisol and melatonin levels were measured on the last day of treatment. Subjective fatigue, mood and sleep records were kept throughout the studies. Melatonin increased early evening fatigue and actual sleep, but had no effect on mood: these results are reported in full elsewhere. Melatonin administration had no effect on the levels or 24-h rhythm of LH, GH, T4, testosterone or cortisol. An earlier fall in the nocturnal PRL was observed on both occasions. Overall PRL levels were higher in spring than in autumn. In five of the subjects, the secretion of endogenous melatonin was advanced by 1-3 h in the presence of exogenous melatonin. These observations suggest that the potential therapeutic use of melatonin as a hypnotic or in the treatment of jet lag is unlikely to be complicated by undesirable endocrine effects.
Adult↗
Proton secretion by the sodium/hydrogen ion antiporter in the human neutrophil.
The reducing equivalents used by the human neutrophil respiratory burst oxidase are derived from NADPH generated by the hexose monophosphate shunt. The CO2 generated by the HMP shunt is spontaneously hydrated and the protons (H+) are secreted upon the dissociation of carbonic acid. The mechanism and significance of H+ secretion by the resting and stimulated neutrophil was investigated. A basal rate of H+ secretion by resting neutrophils observed in a choline buffer was augmented with the addition of sodium (Na+) (Km for Na+ was 3.22 +/- 0.32 mM). Amiloride, a Na+/H+ antiporter inhibitor, reduced H+ secretion in Na+-containing buffers with a Ki = 1.02 microM. This Na+/H+ exchange mechanism was also operative in cells stimulated with a variety of agonists, and an increased H+ flux, relative to resting cells, was observed at higher Na+ concentrations. Cytoplasts incorporating acridine orange were also used to assess Na+-H+ flux. Cytoplasts were used to avoid alteration of the fluorescent pH probe by HOCl formed in intact neutrophils. Alkalinization of the cytoplasm was dependent on extracellular Na+ in concentrations similar to that found to augment H+ secretion in intact cells. Also, amiloride competitively inhibited H+ secretion by the cytoplasts. Both superoxide (O2-) production and lysozyme release in cells stimulated with opsonized zymosan or concanavalin A was significantly inhibited in the absence of Na+, restored to normal with the addition of Na+ in low concentrations, and inhibited again in the presence of amiloride. A Na+/H+ antiporter similar to that found in other cell types is present in the human neutrophil and appears linked to activation of the respiratory burst and degranulation.
Amiloride↗
Kasokero virus: a new human pathogen from bats (Rousettus aegyptiacus) in Uganda.
Two virus strains were isolated by mouse inoculation from blood of Rousettus aegyptiacus fruit-eating bats collected from Kasokero Cave in Uganda. Shortly after these strains were introduced in the laboratory, four additional strains were recovered from laboratory workers who had developed mild to severe illnesses presumably as a result of laboratory infection. Serological studies established that these six isolates are strains of the same virus. Serological tests showed also that this virus is related to Yogue, an unclassified virus.
Animals↗
Arthritis, vasculitis, and cryoglobulinemia associated with relapsing hepatitis A virus infection.
Hepatitis A virus, unlike hepatitis B virus, has rarely been associated with extrahepatic features. Two patients developed relapsing hepatitis A complicated by arthritis in both cases and cutaneous vasculitis in one. Both patients had cryoglobulinemia, with cryocrit values of 4.3% and 8.6%. Serologic studies showed that the cryoglobulin consisted of polyclonal IgM and IgG. The washed cryoglobulin was analyzed by sucrose density gradient ultracentrifugation under neutral (pH 7.4) and acidic (pH 2.8) conditions. Enzyme-linked immunosorbent assay techniques were used to characterize the native and dissociated cryoglobulin. The cryoglobulin contained acid-dissociable IgG complexes greater than 19S, and high molecular weight rheumatoid factors of both IgG and IgM isotypes that could be dissociated to 7S and 19S forms, respectively. Dissociation of the cryoglobulin augmented 7S anti-hepatitis A virus IgG 2.27-fold, but augmented total 7S IgG only 1.12-fold, suggesting enrichment of antiviral antibody in the cryoglobulin.
Adult↗
Variant chronic granulomatous disease: modulation of the neutrophil defect by severe infection.
The present studies document the cellular and biochemical processes involved in granulocyte O2- production in three patients from two kindreds with variant chronic granulomatous disease (CGD). Rates of O2- production were 9% to 30% of normal, depending on the individual tested and the stimulus; the two brothers from one family responded to each stimulus with rates very similar to each other. Kinetic analysis of NADPH-dependent O2- production in subcellular fractions revealed all three to have NADPH oxidases with both diminished substrate affinity for NADPH (high Kmapp) and decreased maximal velocities of O2- production. Their granulocytes had normal lag times for activation of the respiratory burst but abnormal rates of stimulus-induced membrane depolarization. Cytochrome b was not found in granulocytes or subcellular fractions despite the use of a spectrophotometric assay sensitive enough to detect the cytochrome if its content were proportional to the residual rate of O2- generation. A striking finding in one patient from each kindred was a threefold to tenfold decrease in the rate of O2- production accompanying serious infection. The residual O2(-)-generating activity of CGD variants helps to explain their relative freedom from the recurrent infections of the classic disease. However, the marked decrease described in the present study indicates the potential for a vicious cycle in which an infection, once established, leads to increasing impairment of host defense.
Abscess↗
Effects of thioglucoses on sensitivity to insulin hypoglycemic convulsions.
Based on the effects of gold thioglucose (GTG), we have previously proposed a regulatory center in brain which adjusts the convulsive response to insulin hypoglycemia. The sensitivity to insulin hypoglycemic convulsions is decreased 24 hr and increased 1 week after a single i.p. injection of GTG. The differences are in the brain's convulsive response to equal hypoglycemia, as the blood glucose response to insulin is unchanged. The generalized convulsive threshold, reflected in the sensitivity to nonmetabolic pentylenetetrazol (Metrazol) convulsions, is not altered. Despite its systemic administration, GTG causes lesions focused in the ventromedial hypothalamus. In the present study, this regulatory center was explored further by the ability of two thioglucoses to substitute for GTG. beta-D-Thioglucose had no effect. 5-Thioglucose simulated the early (24 hr) action of GTG but had no effect at 1 week. However, unlike GTG, 5-thioglucose did not cause the ventromedial hypothalamus lesion. The early (24 hr) and late (1 week) components are thus dissociated. The early effect on insulin hypoglycemic convulsions does not require a ventromedial hypothalamus lesion. Structure-activity relationships and relationships to glucoregulatory systems are discussed.
Animals↗
Cigarette smoke increases the penetration of asbestos fibers into airway walls.
For study of the penetration of asbestos fibers into airway walls, guinea pigs were given amosite asbestos by intratracheal instillation. Half of the animals were also exposed to cigarette smoke. Animals were sacrificed at 1 week and 1 month, and numbers of fibers in airway walls were counted in histologic sections. In both smoke-exposed and nonexposed groups, numbers of fibers per square millimeter of airway wall increased from 1 week to 1 month in the respiratory bronchioles. At each time period, smoke-exposed animals had significantly higher numbers of fibers in the airway walls, compared with nonexposed animals. It is concluded that 1) continued transport of fibers into interstitial tissues may be the reason that asbestosis can progress after cessation of exposure; 2) cigarette smoke increases the penetration of fibers into airway walls. This effect may play a role in the increased incidence of disease seen in smoking, compared with nonsmoking, asbestos workers.
Animals↗
Effect of ascorbic acid on the production of singlet oxygen by purified human myeloperoxidase.
We have previously studied purified human myeloperoxidase-hydrogen peroxide-halide ion systems as models of possible singlet oxygen production by granulocytes. While myeloperoxidase could efficiently produce singlet oxygen, the yield of singlet oxygen at a physiological pH with Cl- was very small due to enzyme inactivation. In that Bolscher et al. [(1984) Biochim. Biophys. Acta 784, 189-191] observed that micromolar concentrations of ascorbic acid prevented inactivation of myeloperoxidase and increased the production of hypochlorous acid, we examined whether ascorbic acid would augment singlet oxygen production by the myeloperoxidase-hydrogen peroxide-halide ion systems. Ascorbic acid, however, fails to increase the singlet oxygen yield, suggesting that it does not augment singlet oxygen production in the intact granulocyte by a myeloperoxidase-dependent mechanism.
Ascorbic Acid↗
Some effects of melatonin and the control of its secretion in humans.
Whether or not the pineal gland has a significant physiological role in humans is not known. There has nevertheless been speculation about the potential therapeutic use of melatonin (in view of its hypnotic and possible zeitgeber properties) in conditions such as insomnia and jet lag, and in shift-workers. Our work concerns the effects of melatonin administration in humans and the interactions between melatonin and other circadian variables. Chronic (one month), timed (1700 h), low-dose (2 mg daily) melatonin administration to normal subjects without environmental control consistently increased evening fatigue and slightly modified the 24 h prolactin rhythm without effect on cortisol, growth hormone, luteinizing hormone, thyroxine, testosterone or self-rated mood. In five out of 11 subjects the endogenous melatonin rhythm was advanced by one to three hours. During fractional desynchronization of circadian rhythms by increasing imposed 'day' length (26-29 h, 24 days, 500 lux), 5 mg melatonin per os at lights-out in two subjects resulted in better entrainment of the fatigue rhythm to the zeitgeber than in five out of six control subjects, without major consistent effects on other measured circadian variables. Using a new radioimmunoassay for 6-hydroxymelatonin sulphate (aMT6s), the major melatonin metabolite, we have shown that the urinary aMT6s rhythm is closely correlated to that of melatonin in plasma and is completely suppressed by an acute dose of atenolol (100 mg per os), a peripheral beta-adrenergic antagonist. During fractional desynchronization by increasing imposed 'day' length in one subject and decreasing imposed 'day' length in two subjects, the urinary aMT6s rhythm behaved similarly to that of core temperature. The results suggest that fatigue (or alertness) may be entrained by melatonin, but whether critical performance rhythms can be suitably manipulated remains to be clarified. It is likely that melatonin production is linked to the so-called 'strong' circadian oscillator.
Circadian Rhythm↗
Histopathological lesions in the pancreas of the BB Wistar rat as a function of age and duration of diabetes.
Pancreatic histopathology was studied in 121 BBWd, 43 BBWnd, and 33 Wistar rats. Insulitis was the most common inflammatory lesion in both BBW and BBWnd rats. The incidence was inversely associated with age and with duration of diabetes in BBWd rats, but there was no age-related pattern in BBWnd rats. Small end-stage islets were typical of BBWd rats but were not seen in BBWnd rats. Several BBWd rats showed hyperplastic islets months after the onset of diabetes, a pattern that is also seen in a small percentage of human JOD patients. Several non-specific exocrine inflammatory lesions occurred in both BBWd and BBWnd rats: acute and/or chronic pancreatitis, eosinophilic infiltrates, granulomatous lesions and acute and/or chronic interstitial inflammation. Only chronic interstitial inflammation was seen in outbred Wistar rats.
Age Factors↗
Management of patients with acute temporomandibular joint disorders.
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Acute Disease↗
Plasma concentrations of melatonin in man following oral absorption of different preparations.
The plasma concentrations of melatonin in man, fasting and fed, were determined after ingestion of three different oral preparations. A dose of 2 mg was given as either a gelatine capsule, a solution in corn oil or as a slow-release pill. Gelatine capsules and the corn oil preparation gave reproducibly timed peak plasma concentrations, 30 to 60 min after ingestion regardless of nutritional status, and plasma melatonin remained at or above endogenous night-time levels for 3-4 h with mean elimination half-lives of 0.54 to 0.67 h. The slow-release preparation usefully extended high plasma melatonin concentrations for 5-7 h after ingestion but the timing of peak concentrations was very dependent on nutritional status. These preparations should be of use in the study of timed melatonin administration in man.
Adult↗
Randomised placebo controlled trial of aspirin and dipyridamole in the prevention of coronary vein graft occlusion.
Treatment with the combination of aspirin and dipyridamole is believed to reduce the incidence of coronary vein graft occlusion. A double blind randomised controlled trial was carried out in which aspirin 990 mg and dipyridamole 225 mg daily or placebo were added to the routine postoperative management (warfarin for three months) of 320 patients undergoing coronary bypass grafting. The trial treatment was given for 12 months, after which the results were assessed by coronary and graft angiography. The two randomised groups, each of 160 patients, were comparable in age, sex, symptomatic state, angiographic findings, and operative procedure. Repeat coronary arteriography was carried out on 266 patients, 133 in each group. All grafts and distal anastomoses were patent in 68% (91/133) of the placebo patients and in 75% (100/133) of those receiving active treatment. Overall graft patency was 87% (306/352) and 89% (342/385) respectively. Retrospective subgroup analysis showed patency rates of 72% (26/36) and 78% (39/50) of grafts to vessels requiring preliminary endarterectomy, and 80% (36/45) and 91% (40/44) of distal anastomoses to vessels measured at operation to have a diameter of less than or equal to 1 mm. None of these differences was significant at the 5% level. Thus in this group of patients with high graft patency rates, treatment with aspirin and dipyridamole conferred no appreciable advantage.
Adult↗
Systolic blood pressure and heart rate in the growing beagle puppy.
Systolic blood pressure and heart rate were measured in beagle puppies from 1 week to 6 months of age. A significant increase in blood pressure and decrease in heart rate occurred with growth. These changes are qualitatively similar to those observed in young infants and children. The beagle puppy may be a useful animal model for the study of normal and abnormal maturational changes in blood pressure and heart rate and for the evaluation of pharmacologic agents currently used in the treatment of cardiovascular disease in the growing and developing infant.
Animals↗
Immunoassay of 6-hydroxymelatonin sulfate in human plasma and urine: abolition of the urinary 24-hour rhythm with atenolol.
An assessment of the rhythmic characteristics of melatonin secretion in man and other species requires the determination of 24-h secretion profiles. Measurement of a major excreted metabolite would allow noninvasive study of pineal function, applicable in particular to pediatric and long term circadian rhythm studies. This report describes a simple and rapid RIA for 6-hydroxymelatonin sulfate in human plasma and urine. Physiological studies revealed that both plasma and urinary levels of 6-hydroxymelatonin sulfate were closely related to plasma melatonin, and that the urinary 24-h rhythm was abolished by the beta 1-adrenergic anagonist atenolol.
Animals↗