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Biomedical subjects

J Cameron

Publications and source records attributed to J Cameron.

At least 19 recordsLinked to original sources

Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid.

Retinoid response pathways are mediated by two classes of receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). A central question is whether distinct response pathways are regulated by these two classes of receptors. The observation that the stereoisomer 9-cis-retinoic acid binds with high affinity to RXRs suggested that this retinoid has a distinct role in controlling RXR activity, but it was almost simultaneously discovered that RXRs function as auxiliary receptors for RARs and related receptors, and are essential for DNA binding and function of those receptors. Hence, although RARs seem to operate effectively only as heterodimeric RAR/RXR complexes, RXRs themselves apparently function predominantly, if not exclusively, as auxiliary receptors. Here we report that 9-cis-retinoic acid induces RXR homodimer formation. Our results demonstrate a new mechanism for retinoid action by which a ligand-induced homodimer mediates a distinct retinoid response pathway.

Animals

Clinical results and quality of life after percutaneous transluminal coronary angioplasty: a preliminary report.

To evaluate the effect of percutaneous transluminal coronary angioplasty (PTCA) on quality of life, data on symptomatic status, functional capacity, life satisfaction, and psychological wellness were collected on 102 patients at 1 day pre-PTCA and 2 months post-PTCA, and on the first 50 of these patients at 10 months post-PTCA. There were highly significant changes (p < 0.001) in all quality of life measures between pre-PTCA and the 1st follow-up measurements. No further significant changes occurred in these measures between the 1st and 2nd follow-up measurements, indicating that the initial improvement in quality of life was sustained over this period. Data on primary success rate, complications, and pre- and post-PTCA risk factor scores are also reported.

Adult

The effects of ciguatoxin on the nerves of the teleost fish, Sillago ciliata.

The absolute refractory period, relative refractory period, and the duration and magnitude of the supernormal period were measured after incubation of fish nerves with ciguatoxin and other channel modifying compounds, tetrodotoxin, veratridine, verapamil, and lignocaine. In vitro electrophysiological studies were carried out on the lateral line nerve of the whiting, Sillago ciliata Cuvier. Electrophysiological changes in fish nerves after exposure to ciguatoxin (0.3 MU.ml-1) and veratridine (1 x 10(-5) M) are similar to changes that occur in mammalian nerves and include an increase in the absolute refractory period, the relative refractory period, and the magnitude and duration of supernormality. The effects of ciguatoxin (0.3 MU.ml-1) in fish nerves were antagonised by tetrodotoxin (5 x 10(-10) M), verapamil (5 x 10(-7) M), and lignocaine (1 x 10(-5) g/ml-1). The nerves of Sillago ciliata used in this study responded to ciguatoxin and its antagonists in a similar manner to mammalian nerves, suggesting that these teleost nerves have no specific electrophysiological mechanism to cope with this toxin.

Animals

Arterial elastic properties in man: a comparison of echo-Doppler indices of aortic stiffness.

Non-invasive assessment of mechanical properties of the aorta may prove useful in the early detection of atheroma. We have evaluated several of the available echocardiographic indices using ability to detect age-related changes in putatively disease-free vessels as a measure of sensitivity to changes in aortic mechanical properties. Suprasternal imaging was used in 49 healthy non-smoking volunteers to measure minimum and maximum aortic arch diameters. Maximal flow velocities, with corresponding acceleration times and heart periods, were determined in the descending aorta in 24 of these subjects. Blood pressure was recorded non-invasively immediately after the echocardiographic study. Doppler derived measurements of aortic flow acceleration did not relate to age (P greater than 0.05). Three different 2D echo assessments of aortic distensibility, however, all showed a close relationship to age. Ep elastic modulus and Beta index (derived from different stress-strain mechanical relationships) were significantly related to age with r = 0.69 and 0.65 respectively. There were no significant effects of gender or left ventricular systolic function on these relationships. There was a tendency for the relationship between these distensibility indices and age more closely to fit an exponential than a linear relationship. We conclude that 2D echocardiographic assessment of aortic distensibility is able to detect sensitively changes in aortic mechanical properties. Even in the absence of risk factors for cardiovascular disease there is a marked reduction in aortic distensibility with increasing age.

Adult

Effects of ciguatoxin on nerve excitability in rats (Part I).

Ciguatera poisoning is the most common fish food poisoning encountered in man. Electrophysiological studies were performed on the ventral nerve of the tail on adult rats following intraperitoneal injection of toxic fish extract. Significant slowing of both mixed and motor nerve conduction velocities and F wave responses were recorded. Motor and mixed nerve amplitudes were significantly reduced. Both absolute and supernormal periods were significantly prolonged together with an exaggeration of the supernormal response. These findings indirectly suggest that ciguatoxin acts on mammalian nerve by prolonging sodium channel activation.

Action Potentials

Electrophysiological studies on ciguatera poisoning in man (Part II).

Fifteen cases of acute ciguatera poisoning were subjected to electrical studies on the sural and common peroneal nerves. Significant slowing of sensory conduction velocity and prolongation of the absolute refractory, relative refractory and supernormal periods were recorded. These findings indirectly suggest that ciguatoxin causes an abnormally prolonged sodium channel opening in nerve membranes.

Australia

High incidence of contact dermatitis in leg-ulcer patients--implications for management.

A retrospective review of patch test results from all new patients with venous leg ulcers was performed for the preceding 11 months. Eighty one patients referred from general practitioners and district nurses with venous stasis ulcers were included. Positive patch tests were found in 54 patients (67%), including a continued high incidence of allergy to lanolin and topical antibiotics. Multiple allergies were found in 48 patients (58%). In addition, a new problem of allergy to cetearyl alcohol, a constituent of commonly used creams and paste bandages, was identified in 13 patients. There is a continuing high incidence of contact sensitivity in patients with venous stasis ulcers which has important implications for the management of these patients.

Anti-Bacterial Agents

Radiation dosimetry.

This article summarizes the basic facts about the measurement of ionizing radiation, usually referred to as radiation dosimetry. The article defines the common radiation quantities and units; gives typical levels of natural radiation and medical exposures; and describes the most important biological effects of radiation and the methods used to measure radiation. Finally, a proposal is made for a new radiation risk unit to make radiation risks more understandable to nonspecialists.

Abnormalities, Radiation-Induced

Diaphragmatic paralysis following cervical herpes zoster.

A 74-year-old man was found to have a paralysed left hemidiaphragm within four months of the appearance of a typical herpes zoster rash involving his left shoulder and neck. Investigations, including bronchoscopy and computed tomography of the chest, failed to detect a cause for the diaphragmatic paralysis. We believe that the cervical zoster and diaphragmatic paralysis were causally related, a rare but recognised association.

Aged

Mexiletine: pharmacology and therapeutic use.

Mexiletine is a Class IB antiarrhythmic which has basic and clinical electrophysiologic properties similar to lidocaine. Like other Class I antiarrhythmic agents, mexiletine blocks the rapid inward sodium current responsible for phase 0 of the action potential. It has been noted in the clinical electrophysiology laboratory to have minimal effect on sinus node function and AV nodal and His-Purkinje system conduction. Pharmacokinetic studies have shown that oral absorption is rapid with bioavailability of 80-90%. Mexiletine is predominantly metabolized by the liver with elimination half-life of 9 to 12 hours. The antiarrhythmic effects of the primary drug's metabolites remain to be defined. Hemodynamic studies have shown mexiletine to have a lesser negative inotropic effect than procainamide or disopyramide. Although mexiletine as a single agent successfully suppresses 60 to 80% of spontaneous ventricular arrhythmias, it has lower efficacy in suppression of induced ventricular arrhythmias. Multiple studies have shown that as monotherapy mexiletine is effective in preventing the induction of ventricular tachycardia in approximately 20% of patients. When used in combination with a Class IA antiarrhythmic drug for suppression of induced ventricular arrhythmias, multiple investigators have reported greater efficacy. Neurological side effects (tremor, dizziness, memory loss) occur in approximately 10% of patients while gastrointestinal side effects (nausea, anorexia, gastric irritation) occur in up to 40% of patients. Proarrhythmia or other serious toxicity from the drug is uncommon.

Anti-Arrhythmia Agents

Stiffness of the distal tip of bipolar pacing leads.

The stiffness of a bipolar pacing lead, particularly between anode and cathode, may be responsible for myocardial penetration and perforation. Following an unprecedented 7% incidence of high threshold exit block with a single model bipolar ventricular endocardial lead, a study was undertaken to compare pacing lead stiffness between anode and cathode of six models of bipolar leads from two manufacturers; Telectronics (T) and Medtronics (M). Four leads had polyurethane insulation; T 030-284 (Laser Dish), T 329-259 (Cordis, Encor), M 4012 (Target Tip), and M 4004 (Capsure). Two leads had silicone rubber insulation; M 5026 (Capsure) and M 5024 (Capsure SP). All leads were subjected to two stiffness tests. The Tip Deflection Test involved securing the lead at 45 degrees at the indifferent electrode and applying a force to deflect the tip 5 mm. The three point bending test involved placing the lead over two fixed bars in contact with the anode and cathode. Midway a third bar was pushed onto the lead and the force to deflect the lead 2 mm was recorded. The results showed that pacing leads with polyurethane insulation were much stiffer than those with silicone rubber insulation. The T 030-284 because of its construction was found to be the stiffnest. The next stiffnest was the M 4012. Both these leads had an unacceptable incidence of high threshold exit block; 7% with the T 030-284 (89 implants) and 3% with the M 4012 (102 implants). No cases of high threshold exit block were documented with the other four pacing leads and in particular the silicone rubber M 5026 (344 implants).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial

Periampullary neoplasms in von Recklinghausen's disease.

A case of neurofibromatosis is reported in a patient who was initially seen with obstructive jaundice caused by a carcinoid tumor originating from the ampulla of Vater. An extensive review of the literature suggests that patients with von Recklinghausen's disease are at significant risk for periampullary neoplasms of neural-crest and non-neural-crest origin. The tendency of those tumors to arise from the ampulla of Vater has diagnostic and therapeutic implications.

Adult

Pre-pubertal gynaecomastia as the presenting feature of late-onset 21-hydroxylase deficiency.

We describe an 8-year-old boy with pre-pubertal gynaecomastia as the presenting feature of late-onset 21-hydroxylase deficiency, an association not previously reported. Although absolute oestrogen levels were not higher than previously described in 21-hydroxylase deficiency, the gynaecomastia may have arisen through a relative disproportion of the C18 to C19 steroids.

Adrenocorticotropic Hormone

Differences in norepinephrine activation and diltiazem inhibition of calcium channels in isolated rabbit aorta and mesenteric resistance vessels.

The mechanisms of norepinephrine stimulation of calcium ion entry in isolated rabbit aorta and mesenteric resistance vessels were studied through measurements of effects on calcium-45 influx, tension, and membrane potential. The resistance vessels were considerably less sensitive to norepinephrine than the aorta. The aorta exhibited complex dose-response curves for norepinephrine-stimulated calcium influx and contraction, whereas these were simple in the arterioles. Both vessels were depolarized with increasing concentrations of potassium. Norepinephrine did not depolarize the aorta, whereas it did depolarize the mesenteric resistance vessels. This result supports the contention that norepinephrine opens receptor-operated channels to induce calcium entry in the aorta, while it may activate potential sensitive calcium channels in the mesenteric resistance vessels. However, the maximum depolarization with norepinephrine (10(-4) M) in the arterioles was completely blocked by 10(-5) M diltiazem, whereas that induced by 80 mM potassium was unaltered by the diltiazem. Furthermore, 10(-4) M norepinephrine was able to stimulate virtually the same contraction and calcium influx in 80 mM potassium-depolarized arterioles as in normal polarized tissues. These results are consistent with norepinephrine opening of receptor-operated channels to allow calcium entry in the rabbit mesenteric resistance vessels. That the behavior of norepinephrine-activated channels in the aorta is more complex than in the arterioles is further illustrated by a dramatically decreasing sensitivity of norepinephrine-stimulated calcium influx to diltiazem with increasing norepinephrine in the aorta but not in the arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals