Duodenal expression of iron transport molecules in untreated haemochromatosis subjects

Background and aims: In HFE associated hereditary haemochromatosis, the duodenal enterocyte behaves as if iron deficient and previous reports have shown increased duodenal expression of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (Ireg1) in affected subjects. In those studies, many patients had undergone venesection, which is a potent stimulus of iron absorption. Our study investigated duodenal expression of DMT1 ( IRE and non-IRE), Ireg1, hephaestin, and duodenal cytochrome-b (Dyctb) in untreated C282Y homozygous haemochromatosis patients, iron deficient patients, and iron replete subjects. Methods: Total RNA was extracted from duodenal biopsies and expression of the iron transport genes was assessed by ribonuclease protection assay. Results: Expression of DMT1 ( IRE) and Ireg1 was increased 3 - 5-fold in iron deficient subjects compared with iron replete subjects. Duodenal expression of DMT1 ( IRE) and Ireg1 was similar in haemochromatosis patients and iron replete subjects but in haemochromatosis patients with elevated serum ferritin concentrations, both DMT1 ( IRE) and Ireg1 expression were inappropriately increased relative to serum ferritin concentration. Hephaestin and Dcytb levels were not upregulated in haemochromatosis. DMT1 ( IRE) and Ireg1 levels showed significant inverse correlations with serum ferritin concentration in each group of patients. Conclusions: These findings are consistent with DMT1 ( IRE) and Ireg1 playing primary roles in the adaptive response to iron deficiency. Untreated haemochromatosis patients showed inappropriate increases in DMT1 ( IRE) and Ireg1 expression for a given level of serum ferritin concentration, although the actual level of expression of these iron transport genes was not significantly different from that of normal subjects.

Blunted prolactin response to D-fenfluramine in post-stroke major depression

Background: This study investigated whether patients suffering from post-stroke depressive disorder had a similar disturbance in central serotonergic function to that described in non-brain injured depressed patients. Methods: Twenty-three depressed patients (nine major, 14 minor) and 38 non-depressed patients were examined 4-8 weeks post-stroke with a structured interview, rating scales and MRI brain scans. Patients were administered 30 mg D-fenfluramine orally and plasma prolactin and D-fenfluramine concentrations were measured for 6 h post-dose. Results: The prolactin response was significantly blunted in major depression compared to minor depression and non-depressed patients as measured by both delta prolactin and area under the prolactin versus time curve. There was no significant relationship between prolactin response and lesion lateralization or any of the measured clinical characteristics. Limitations: The major limitation of the study is the relatively small number in each depressive group. Conclusions: Patients suffering from major depression in the post-stroke period have a blunted prolactin response to D-fenfluramine. This indicates a serotonergic abnormality consistent with that found in major depression where neurological disease is not present. (C) 2003 Elsevier B.V. All rights reserved.

Noninvasive tests for arterial structure, function, and compliance: Do they identify risk or diagnose disease?

Background: Brachial artery reactivity (BAR), carotid intima-media thickness (IMT), and applanation tonometry for evaluation of total arterial compliance may provide information about preclinical vascular disease. We sought to determine whether these tests could be used to identify patients with coronary artery disease (CAD) without being influenced by their ability to identify those at risk ford CAD developing. Methods: We studied 100 patients and compared 3 groups: 35 patients with known CAD; 34 patients with symptoms and risk factors but no CAD identified by stress echocardiography (risk group); and 31 control subjects. BAR and IMT were measured using standard methods, and total arterial compliance was calculated by the pulse-pressure method from simultaneous radial applanation tonometry and pulsed wave Doppler of the left ventricular outflow. Ischemia was identified as a new or worsening wall-motion abnormality induced by stress. Results: In a comparison between the control subjects and patients either at risk for developing CAD or with CAD, the predictors of risk for CAD were: age (P = .01); smoking history (P = .002); hypercholesterolemia (P = .002); and hypertension (P = .004) (model R = 0.82; P = .0001). The independent predictors of CAD were: IMT (P = .001); BAR (P = .04); sex (P = .005); and hypertension (P = .005) (model R = 0.80; P = .0001). Conclusion: IMT, BAR, and traditional cardiovascular risk factors appear to identify patients at risk for CAD developing. However, only IMT was significantly different between patients at risk for developing CAD and those with overt CAD.

Use of tissue Doppler imaging to facilitate the prediction of events in patients with abnormal left ventricular function dobutamine echocardiography

The extent of abnormality in patients with positive do-butamine echocardiography (DE) is predictive of risk, but the wall motion score (WMS) has low concordance among observers. We sought whether quantifying the extent of abnormal wall motion using tissue Doppler (TD) could guide risk assessment in patients with abnormal DE in 576 patients with known or suspected coronary artery disease; standard DE was combined with color TD imaging at peak dose. WMS was assessed by an expert observer and studies were identified as abnormal in the presence of 2:1 segments with resting or stress-induced wall motion abnormalities. Patients with abnormal DE had peak systolic velocity measured in each segment. Tissue tracking was used to measure myocardial displacement. Follow-up for death or infarction was per-formed after. 16 +/- 12 months. Of 251 patients with abnormal DE, 22 patients died (20 from cardiac causes) and 7 had nonfatal myocardial infarctionis. The average WMS in patients with events was 1.8 +/- 0.5, compared with 1.7 +/- 0.5 in patients without events (p = NS). The average systolic velocity in patients with events was 4.9 +/- 1.7 cm/s and 6.4 +/- 6.5 cm/s in the patients without events (p <0.001). The average tissue tracking in patients with events was 4.5 +/- 1.5 mm and was significant. (5.7 +/- 3.1 mm),in those,without events (p <0.001). Thus, TD is an alternative to WMS for quantifying the total extent of abnormal left ventricular function-at DE, and appears to be superior for predicting adverse outcomes. (C) 2004 by Excerpta Medica, Inc.

The effects of ambient music on simulated anaesthesia monitoring

We examined the effect of no music, classical music or rock music on simulated patient monitoring. Twenty-four non-anaesthetist participants with high or low levels of musical training were trained to monitor visual and auditory displays of patients' vital signs. In nine anaesthesia test scenarios, participants were asked every 50-70 s whether one of five vital signs was abnormal and the trend of its direction. Abnormality judgements were unaffected by music or musical training. Trend judgements were more accurate when music was playing (p = 0.0004). Musical participants reported trends more accurately (p = 0.004), and non-musical participants tended to benefit more from music than did the musical participants (p = 0.063). Music may provide a pitch and rhythm standard from which participants can judge changes in vital signs from auditory displays. Nonetheless, both groups reported that it was easier to monitor the patient with no music (p = 0.0001), and easier to rely upon the auditory displays with no music (p = 0.014).

Burning mouth syndrome: an update on recent findings

Burning mouth syndrome (BMS) is characterized by a burning sensation of the oral mucosa in the absence of mucosal abnormality Various local, systemic and psychological factors are associated with BMS, but its aetiology is not fully understood. Recently, significant inroads have been made, producing a better understanding of this complex condition. The aim of the current paper is to explore the condition of BMS in an educational context with the specific outcome of increasing awareness of the condition.

The relationship of cervical joint position error to balance and eye movement disturbances in persistent whiplash

Cervical joint position error (JPE) has been used as a measure of cervical afferent input to detect disturbances in sensori-motor control as a possible contributor to a neck pain syndrome. This study aimed to investigate the relationship between cervical JPE, balance and eye movement control. It was of particular interest whether assessment of cervical ME alone was sufficient to signal the presence of disturbances in the two other tests. One hundred subjects with persistent whiplash-associated disorders (WADs) and 40 healthy controls subjects were assessed on measures of cervical JPE, standing balance and the smooth pursuit neck torsion test (SPNT). The results indicated that over all subjects, significant but weak-to-moderate correlations existed between all comfortable stance balance tests and both the SPNT and rotation cervical ME tests. A weak correlation was found between the SPNT and right rotation cervical JPE. An abnormal rotation cervical JPE score had a high positive prediction value (88%) but low sensitivity (60%) and specificity (54%) to determine abnormality in balance and or SPNT test. The results suggest that in patients with persistent WAD, it is not sufficient to measure ME alone. All three measures are required to identify disturbances in the postural control system. (C) 2005 Elsevier Ltd. All rights reserved.

Inheritance of proportionate dwarfism in Angus cattle

Objective To determine the mode of inheritance of congenital proportionate dwarfism in Angus and Angus crossbred cattle, initially detected in two commercial beef herds in northern New South Wales. Design Matings of normal carrier sires to unrelated cows of diverse breeds, and of one carrier sire to his unaffected daughters. An unrelated Piedmontese bull was also mated to unaffected daughters of the carrier sires. Procedure Two carrier Angus bulls and nine unaffected daughters, all of whom were completely indistinguishable from normal animals, were purchased for controlled breeding studies under known nutritional and disease conditions. Affected and carrier individuals were examined for the presence of obvious chromosomal abnormalities. Results Angus dwarfism has been successfully reproduced under controlled experimental conditions over successive years using unrelated dams and is undoubtedly heritable. The high frequency of occurrence of affected individuals (23/61 = 0.38 +/- .06) among the progeny of matings of the Angus sires to unrelated females of diverse breeding is not compatible with recessive inheritance, because of the negligible frequency of proportionate dwarfism in the breeds of the dams. Both paternal and maternal transmission of the defect was demonstrated, so that imprinting in the strict sense of a gene that is only expressed when received from the male parent appears not to be involved. Tested individuals showed no evidence of gross chromosomal abnormality. Dominant autosomal inheritance with incomplete penetrance was indicated by the lack of expression of the defective gene in the two Angus sires and in three unaffected daughters who produced dwarf calves from matings to the Piedmontese bull. Conclusions The mode of inheritance is that of a single autosomal dominant gene with a penetrance coefficient of 0.75 +/- 0.12, estimated from the observed incidence of 23/61 affected offspring of the two carrier Angus bulls mated to unrelated dams. Simple genetic models involving either (i) an unstable mutant which changes at high frequency to the expressed dominant dwarfing allele during gametogenesis, or (ii) a dominant allele with penetrance determined by an unlinked modifying locus, are shown to be compatible with the experimental data. Both models indicate that penetrance of the dwarfing gene may possibly be higher in matings involving carrier daughters of the two Angus bulls.

Influence of arterial compliance on presence and extent of ischaemia during stress echocardiography

Objective: To seek an association between total arterial compliance (TAC) and the extent of ischaemia at stress echocardiography. Design: Cohort study. Setting: Regional cardiac centre. Methods: 255 consecutive patients (147 men; mean (SD) age 58 (8)) presenting for stress echocardiography for clinical indications were studied. Wall motion score index (WMSI) was calculated and ischaemia was defined by an inducible or worsening wall motion abnormality. Peak WMSI was used to reflect the extent of dysfunction (ischaemia or scar), and Delta WMSI was indicative of extent of ischaemia. TAC was assessed at rest by simultaneous radial applanation tonometry and pulsed wave Doppler in all patients. Results: Ischaemia was identified by stress echocardiography in 65 patients (25%). TAC was similar in the groups with negative and positive echocardiograms (1.08 (0.41) v 1.17 (0.51) ml/ mm Hg, not significant). However, the extent of dysfunction was associated with TAC independently of age, blood pressure, risk factors, and use of a beta blocker. Moreover, the extent of ischaemia was determined by TAC, risk factors, and use of a b blocker. Conclusion: While traditional cardiovascular risk factors are strong predictors of ischaemia on stress echocardiography, TAC is an independent predictor of the extent of ischaemia.

Injuries associated with continuous miners, shuttle cars, load-haul-dump and personnel transport in New South Wales underground coal mines

In the three years to June 2005, 959 injuries associated with continuous miners (CMs), shuttle cars (SCs), load–haul–dump and personnel transport (PT) were reported by NSW underground coal mines, comprising 23% of all injuries reported. The present paper reports an analysis of the narrative field accompanying these reports to determine opportunities for controlling injury risks. The most common combinations of activity and mechanism were: strain while handling CM cable (96 injuries); caught between or struck by moving parts while bolting on a CM (86 injuries); strains while bolting on CM (54 injuries); and slipping off a CM during access, egress or other activity (60 injuries). For the other equipment considered, the common injury mechanism was the vehicle running over a pothole or other roadway abnormality causing the driver or passengers to be injured (169 injuries). Potential control measures include: monorails for CM services; hydraulic cable reelers; handrails on CM platforms; redesign of CM platforms and bolting rigs to reduce reach distances during drilling and bolting; improvements to guarding of bolting controls; standardisation and shape coding of bolting controls; two handed fast feed; improvements in underground roadway maintenance, vehicle suspension, visibility and seating; and pedestrian proximity warning devices.

Can myocardial contrast echo provide incremental benefit to exercise echo? Implications of the intensity and duration of hyperaemia

Background. Stress myocardial contrast echo (MCE) is technically challenging with exercise (Ex) because of cardiacmovementandshort duration ofhyperemia.Vasodilators solve these limitations, but are less potent for inducing abnormal wall motion (WM). We sought whether a combined dipyridamole (DI; 0.56 mg/kg i.v. 4 min) and Ex stress protocol would enable MCE to provide incremental benefit toWManalysis for detection of CAD. Methods. Standard echo images were followed by real time MCE at rest and following stress in 85 pts, 70 undergoing quantitative coronary angiography and 15 low risk pts.WMAfrom standard and LVopacification images, and then myocardial perfusion were assessed sequentially in a blinded fashion. A subgroup of 13 pts also underwent Ex alone, to assess the contribution of DI to quantitative myocardial flow reserve (MFR). Results. Significant (>50%) stenoses were present in 43 pts, involving 69 territories. Addition of MCE improved SE sensitivity for detection of CAD (91% versus 74%, P = 0.02) and better appreciation of disease extent (87% versus 65%territories, P=0.003), with a non-significant reduction in specificity. In 55 territories subtended by a significant stenosis, but with no resting WM abnormality, ability to identify ischemia was also significantly increased by MCE (82% versus 60%, P = 0.002). MFR was less with Ex alone than with DIEx stress (2.4 ± 1.6 versus 4.0 ± 1.9, P = 0.05), suggesting prolongation of hyperaemia with DI may be essential to the results. Conclusions. Dipyridamole-exercise MCE adds significant incremental benefit to standard SE, with improved diagnostic sensitivity and more accurate estimation of extent of CAD.