Indirect MR arthrography of the knee: effects of low-intensity ultrasound on the diffusion rate of intravenously administered Gd-DTPA in healthy volunteers

RATIONALE AND OBJECTIVES: To evaluate whether application of low-intensity ultrasound may increase the diffusion rate of intravenously administered gadopentetate dimeglumine (Gd-DTPA) and increase the amount of joint fluid on indirect magnetic resonance (MR) arthrography. METHODS: Conventional MR imaging, indirect MR arthrography, and power Doppler ultrasonography were performed before and after application of therapeutic, pulsed low-intensity ultrasound in 12 asymptomatic knees of 12 volunteers. Intra-articular diffusion of intravenously administered Gd-DTPA as measured by signal intensity differences of the intra-articular joint fluid before and after ultrasound treatment was assessed. In addition, the amount of joint fluid was rated, and differences in synovial blood flow as evidenced by power Doppler ultrasonography were noted. RESULTS: All volunteers tolerated well the application of therapeutic low-intensity ultrasound. A significant increase in intra-articular diffusion of intravenously administered Gd-DTPA was noted in all knees, and an increase in joint fluid was noted in 8 of 12 knees (66.6%). Detection of power Doppler flow signal in the synovium of the suprapatellar recess was possible in one instance at posttreatment exam. CONCLUSIONS: Use of pulsed, therapeutic low-intensity ultrasound may increase the diffusion rate of intravenously administered Gd-DTPA and may induce joint effusion.     

Mechanisms of multiple chemical sensitivity

Sensitivity to chemicals is a toxicological concept, contained in the dose-response relationship. Sensitivity also includes the concept of hypersensitivity, although controversy surrounds the nature of effects from very low exposures. The term multiple chemical sensitivity has been used to describe individuals with a debilitating, multi-organ sensitivity following chemical exposures. Many aspects of this condition extend the nature of sensitivity to low levels of exposure to chemicals, and is a designation with medical, immunological, neuropsychological and toxicological perspectives. The basis of MCS is still to be identified, although a large number of hypersensitivity, immunological, psychological, neurological and toxicological mechanisms have been suggested, including: allergy; autosuggestion; cacosomia; conditioned response; immunological; impairment of biochemical pathways involved in energy production; impairment of neurochemical pathways; illness belief system; limbic kindling; olfactory threshold sensitivity; panic disorder; psychosomatic condition; malingering; neurogenic inflammation; overload of biotransformation pathways (also linked with free radical production); psychological or psychiatric illness; airway reactivity; sensitisation of the neurological system; time dependent sensitisation, toxicant induced loss of tolerance. Most of these theories tend to break down into concepts involving: (1) disruption in immunological/allergy processes; (2) alteration in nervous system function; (3) changes in biochemical or biotransformation capacity; (4) changes in psychological/neurobehavioural function. Research into the possible mechanisms of MCS is far from complete. However, a number of promising avenues of investigation indicate that the possibility of alteration of the sensitivity of nervous system cells (neurogenic inflammation, limbic kindling, cacosomia, neurogenic switching) are a possible mechanism for MCS.     

How consultants, hospitals, trusts and deaneries affect pre-registration house officer posts: a multilevel model

OBJECTIVE: To examine variation in reported quality and working conditions of pre-registration house officer (PRHO) posts. To use multilevel modelling to determine how much of the variation was due to the effects of consultant firms, hospitals, trusts and deaneries, as well as variation at the level of the individual doctor. DESIGN: Questionnaire survey of national sample of PRHOs at the end of the pre-registration year. Multilevel modelling was carried out using MLwiN. SETTING: PRHOs working in UK approved medical and surgical posts in NHS hospitals from August 1996 to January 1999. PARTICIPANTS: One thousand, four-hundred and thirty-five PRHOs who had previously been part of an extended cohort study of medical student selection and training. They reported on a total of 4926 posts, on 2721 identifiable consultant firms, in 336 hospitals, in 264 trusts and in 17 deaneries. MAIN OUTCOME MEASURES: PRHOs' perceptions of the overall quality of all PRHO posts they had worked in, and working conditions in the current post. RESULTS: Twenty percent of PRHO posts were described as excellent and 34% as very good, through to 6% reported as not very good, poor or bad. The overall rating of the post showed highly significant variation at the level of hospital/trust, and consultant firm. Other aspects of posts, such as working conditions showed variation at the level of deanery, trust, hospital and firms, with different patterns for the different measures. Assessments of stress in PRHOs (GHQ, burnout, response to uncertainty), and a desire to leave medicine, showed no variation at the level of deanery, trust, hospital or firm. CONCLUSION: Some aspects of a PRHO post, in particular overall rated quality, but also many aspects of working conditions, show substantial variation at the level of hospital, trust and consultant firm, suggesting that differences reflect local variation in working practices and treatment of PRHOs, with the possibility of change and improvement. The lack of any variation at the level of deanery, trust, hospital or firm in stress of PRHOs suggests that these responses are idiosyncratic, individual responses by doctors themselves, rather than a general characteristic of posts, hospitals, trusts or deaneries.     

The dermal toxicity of cement

Cement and concrete are products used widely in the construction sector, with a traditional perception that any hazards that they have are limited to dermatitis in a small number of workers. In some cases, employers and builders do not think that concrete is a chemical. However, contact dermatitis is one of the most frequently reported health problems among construction workers. A review of the available literature suggests that cement has constituents that produce both irritant contact dermatitis and corrosive effects (from alkaline ingredients such as lime) and sensitization, leading to allergic contact dermatitis (from ingredients such as chromium). These findings indicate that cement and concrete should be treated as hazardous materials, and that workers handling such products should reduce exposure wherever possible. Initiatives to reduce the chromium content of cement have been shown to be successful in reducing the incidence of allergic dermatitis, although the irritant form remains.     

The toxicity of commercial jet oils

Jet oils are specialized synthetic oils used in high-performance jet engines. They have an appreciable hazard due to toxic ingredients, but are safe in use provided that maintenance personnel follow appropriate safety precautions and the oil stays in the engine. Aircraft engines that leak oil may expose others to the oils through uncontrolled exposure. Airplanes that use engines as a source of bleed air for cabin pressurization may have this source contaminated by the oil if an engine leaks. Examination of the ingredients of the oil indicates that at least two ingredients are hazardous: N-phenyl-1-naphthylamine (a skin sensitizer) and tricresyl phosphate (a neurotoxicant, if ortho-cresyl isomers are present). Publicly available information such as labels and MSDS understates the hazards of such ingredients and in the case of ortho-cresyl phosphates by several orders of magnitude.     

Metals in drinking water from new housing estates in the Sydney area

Metals in drinking water were measured in 95 new houses less than 18 months old in the Sydney metropolitan area. Three samples (first-flush, post-first-flush, and fully flushed water) were collected from each house, and "control" samples from the five Sydney Water points that supplied the houses, a total of 326 samples. They were analyzed for Pb, Cu, Mn, Zn, Cd, and Al. At the supply points, the levels of all metals were at or below Australian Drinking Water Guidelines (ADWG). In the houses, metal levels varied. Of the first-flush samples, Pb was above ADWG in 60% and above US EPA Guidelines in 81%, Cu was above ADWG in 12%, and Cd was above ADWG in 4%. Of the post-first-flush samples, Pb was above ADWG in 24%, Cu was above ADWG in 18%, Cd was above ADWG in 1%, and Zn was above ADWG in 1%. The other metal contaminants (Mn and Al) were within ADWG. In fully flushed water, the levels of all metals were well below ADWG.     

Progression of somatic CTG repeat length heterogeneity in the blood cells of myotonic dystrophy patients

The genetic basis of myotonic dystrophy (DM) is the expansion of an unstable CTG repeat in the 34 UTR of the DM protein kinase gene on chromosome 19. One of the principal features of the DM mutation is an extraordinarily high level of somatic mosaicism, due to an extremely high degree of somatic instability both within and between different tissues. This instability appears to be biased towards further expansion and continuous throughout the life of an individual, features that could be associated with the progressive nature of the disease. Although increasing measured allele size between patients clearly correlates with an increased severity of symptoms and an earlier age of onset, this correlation is not precise and measured allele length cannot be used as an accurate predictor of age of onset. In order to further characterize the dynamics of DM CTG repeat somatic instability, we have studied repeat length changes over time in 111 myotonic dystrophy patients with varying clinical severity and CTG repeat size over time intervals of 1-7 years. We have found a direct progression of the size heterogeneity over time related to initial CTG repeat size and the time interval and always biased towards further expansion. Attempts to mathematically model the dynamics have proved only partially successful suggesting that individual specific genetic and/or environmental factors also play a role in somatic mosaicism.      

Platelets and lipoprotein (a): a brief overview of their role in the pathogenesis of atherothrombosis

The relationship between lipids and the haemostatic mechanisms participating in the evolution of the atherosclerotic plaque have been undergoing extensive investigation for over a century. Circulating lipoproteins can enhance platelet activity. Among these lipid fractions, lipoprotein (a) (Lp(a)), a predictor of atherosclerotic disease, has been proposed as a link between lipids and haemostasis. In this review, we briefly consider lipid-platelet, and particularly Lp(a)-platelet, interactions which may be relevant to the pathogenesis of atherosclerotic disease and its complications.     

Reversal of phosphorylase activation in muscle despite continued contractile activity.

During studies of the regulation of phosphorylase activity and glycogenolysis in contracting muscle, it was found that conversion of phosphorlyase beta to alpha is transient. Reversal of phosphorylase activation during both continuous and intermittent stimulation in the plantaris might, in part, have been due to development of fatigue. However, a complete reversal of phosphorylase activation was also evident within 5 min in the absence of fatigue in soleus muscles stimulated tetanically with 100-ms-long trains at a rate of 60/min. These muscles showed no significant decline in contractile force. Glycogen breakdown stopped in the soleus when phosphorylase reverted to the beta form, providing evidence that phosphorylase beta was not active. This lack of activity is probably explained by the finding that ATP and AMP concentrations changed little, while glucose 6-phosphate increased. Reversal of phosphorlyase activation soon after the onset of steady-state work may be a mechanism for conserving glycogen when the supply of other substrates is adequate to meet the muscles' energy needs.