Preclinical assessment of a new magnetic resonance-based technique for determining bone quality by characterization of trabecular microarchitecture.

The utility of HR-CT to study longitudinal changes in bone microarchitecture is limited by subject radiation exposure. Although MR is not subject to this limitation, it is limited both by patient movement that occurs during prolonged scanning at distal sites, and by the signal-to-noise ratio that is achievable for high-resolution images in a reasonable scan time at proximal sites. Recently, a novel MR-based technique, fine structure analysis (FSA) (Chase et al. Localised one-dimensional magnetic resonance spatial frequency spectroscopy. PCT/US2012/068284 2012, James and Chase Magnetic field gradient structure characteristic assessment using one-dimensional (1D) spatial frequency distribution analysis. 7932720 B2, 2011) has been developed which provides both high-resolution and fast scan times, but which generates at a designated set of spatial positions (voxels) a one-dimensional signal of spatial frequencies. Appendix 1 provides a brief introduction to FSA. This article describes an initial exploration of FSA for the rapid, non-invasive characterization of trabecular microarchitecture in a preclinical setting. For L4 vertebrae of sham and ovariectomized (OVX) rats, we compared FSA-generated metrics with those from CT datasets and from CT-derived histomorphometry parameters, trabecular number (Tb.N), bone volume density (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). OVX caused a reduction of the higher frequency structures that correspond to a denser trabecular lattice, while increasing the preponderance of lower frequency structures, which correspond to a more open lattice. As one example measure, the centroid of the FSA spectrum (which we refer to as fSAcB) showed strong correlation in the same region with CT-derived histomorphometry values: Tb.Sp: r -0.63, p < 0.001; Tb.N: r 0.71, p < 0.001; BV/TV: r 0.64, p < 0.001, Tb.Th: r 0.44, p < 0.05. Furthermore, we found a 17.5% reduction in fSAcB in OVX rats (p < 0.0001). In a longitudinal study, FSA showed that the age-related increase in higher frequency structures was abolished in OVX rats, being replaced with a 78-194% increase in lower frequency structures (2.4-2.8 objects/mm range), indicating a more sparse trabecular lattice (p < 0.05). The MR-based fine structure analysis enables high-resolution, radiation-free, rapid quantification of bone structures in one dimension (the specific point and direction being chosen by the clinician) of the spine.

Mycobacterium terrae: a potential surrogate for Mycobacterium tuberculosis in a standard disinfectant test.

The susceptibility of Mycobacterium tuberculosis and Mycobacterium avium-intracellulare to the disinfections used for spillage and heat sensitive instruments has received much attention in recent years. The use of clinical isolates of M. tuberculosis and M. avium-intracellulare as test organisms is considered unsuitable for standard tests due to their hazardous nature (category 3 pathogens and slow growth rates). This has led to much debate in standards committees on the selection and use of a possible surrogate which would be safer and more practical to use and yet mimic the susceptibility of clinical isolates. This study compared the susceptibility of one possible surrogate Mycobacterium terrae NCTC 10856, with that of clinical isolates of M. tuberculosis H37 Rv and M. avium-intracellulare using a quantitative suspension test. The instrument and environmental disinfectants tested were a chlorine-releasing agent, sodium dichloroisocyanyurate (NaDCC) at 1000 ppm and 10,000 ppm av. Cl, chlorine dioxide at 1100 ppm av. ClO2 (Tristel, HayMan MediChem), 0.35% peracetic acid (NuCidex, Johnson & Johnson), 70% industrial methylated spirit (IMS), 2% alkaline glutaraldehyde (Asep, Galen), 10% succine dialdehyde and formaldehyde mixture (Gigasept, Schulke and Mayr). Results showed that the clinical isolate of M. avium-intracellulare was the most resistant of the three test organisms. M. terrae, which is not a category 3 pathogen, was slightly more resistant than M. tuberculosis and this would appear to be a suitable surrogate for establishing tuberculocidal activity. However, with an increase in the clinical significance of M. avium-intracellulare, particularly in human immunodeficiency virus (HIV) and immunocompromised patients, a more resistant surrogate is required. In the absence of such a surrogate, testing with M. avium-intracellulare in a clinical laboratory equipped for handling category 3 pathogens is still advised to establish mycobactericidal activity.

Mycobactericidal activity of selected disinfectants using a quantitative suspension test.

In this study, a quantitative suspension test carried out under both clean and dirty conditions was used to assess the activity of various instrument and environmental disinfectants against the type strain NCTC 946 and an endoscope washer disinfector isolate of Mycobacterium chelonae, Mycobacterium fortuitum NCTC 10,394, Mycobacterium tuberculosis H37 Rv NCTC 7416 and a clinical isolate of Mycobacterium avium-intracellulare (MAI). The disinfectants tested were; a chlorine releasing agent, sodium dichloroisocyanurate (NaDCC) at 1000 ppm and 10,000 ppm av Cl; chlorine dioxide at 1100 ppm av ClO2 (Tristel, MediChem International Limited); 70% industrial methylated spirits (IMS); 2% alkaline glutaraldehyde (Asep, Galan); 10% succinedialdehyde and formaldehyde mixture (Gigasept, Schulke & Mayr); 0.35% peracetic acid (NuCidex, Johnson & Johnson); and a peroxygen compound at 1% and 3% (Virkon, Antec International). Results showed that the clinical isolate of MAI was much more resistant than M. tuberculosis to all the disinfectants, while the type strains of M. chelonae and M. fortuitum were far more sensitive. The washer disinfector isolate of M. chelonae was extremely resistant to 2% alkaline activated glutaraldehyde and appeared to be slightly more resistant than the type strain to Nu-Cidex, Gigasept, Virkon and the lower concentration of NaDCC. This study has shown peracetic acid (Nu-Cidex), chlorine dioxide (Tristel), alcohol (IMS) and high concentrations of a chlorine releasing agent (NaDCC) are rapidly mycobactericidal. Glutaraldehyde, although effective, is a slow mycobactericide. Gigasept and Virkon are poor mycobactericidal agents and are not therefore recommended for instruments or spillage if mycobacteria are likely to be present.

Plasma acid hydrolases in normal adults and children, and in patients with some lysosomal storage diseases.

Optimal assay conditions are described for plasma alpha-galactosidase, beta-glactosidase, beta-glucuronidase, alpha-mannosidase, alpha-glucosidase, N-acetyl-beta-glucosaminidase, alpha-fucosidase, N-acetyl-alpha-glucosaminidase, acid phosphatase and arylsulphatase A. The levels of these activities in normal adults and children, and the stabilities of the activities on storage at -20 degrees C or 4 degrees C, are reported. The levels of these enzymic activities in plasma from patients with Fabry, Pompe, Sanfilippo A, Sanfilippo B, Tay Sachs and Hunter diseases, GM1-gangliosidosis and metachromatic leucodystrophy are described, and the possibility of using plasma hydrolase activities in the diagnosis of these conditions is discussed.

Radiation protection consequences of the care of a terminally ill patient having received a thyroid ablation dose of 131I-sodium iodide.

The death of a patient soon after an ablation dose of 131I-sodium iodide is a rare occurrence. We report a case of a patient who died, following emergency surgery to treat gastric bleeding, whilst still radioactive. The doses received by clinical staff involved in management of the patient were measured and were found to be within acceptable limits. However, there was an appreciable level of unsealed radioactivity in the Intensive Care Unit. The issues raised by this case are discussed in the context of legislative requirements and the worst case scenario. The event highlights the need for close liaison between the different specialities to ensure that clinical staff are properly advised and that necessary safety precautions are taken to avoid compromising the safety of staff or the care of the patient.

The role of 99Tcm-HMPAO white cell imaging in suspected orthopaedic infection.

Accurate diagnosis is essential for the effective management of suspected bone infection. Current imaging techniques have had limited success and further work is required. Although white cell labelling techniques have been available for many years the radiopharmaceuticals employed have disadvantages, particularly in their availability and suitability for imaging. These problems have been overcome by the use of 99Tcm-HMPAO as an in vitro leukocyte labelling agent. The aims of this study were to assess retrospectively its role and accuracy in imaging orthopaedic infection and to compare the results with three-phase bone imaging. 30 patients with suspected bone infection underwent three-phase methylene diphosphonate (MDP) bone imaging and labelled leukocyte imaging on separate occasions. 16 bone scans were positive for infection, of which 14 were subsequently confirmed, and there were no false negatives. There were no false positive white cell studies and only one infection was not identified. 99Tcm-HMPAO white cell imaging has been shown to be an accurate technique for the diagnosis of bone infection but should be performed only following a positive finding on three-phase bone scanning, since the latter is highly sensitive but significantly less expensive, making it a more appropriate screening procedure.

White cell scanning for inflammatory bowel disease: are biochemical markers useful referral criteria?

The aim of this study was to determine whether biochemical markers for inflammation could prove effective in identifying the most appropriate patients with suspected inflammatory bowel disease (IBD) for labelled white cell scanning. One hundred and twenty-five patients referred for 99mTc-HMPAO labelled white cell scans were investigated. The values of C-reactive protein (CRP), antichymotrypsin (ACT) and acid glycoprotein (AGP) were measured in 73 patients, AGP and CRP in 10 and CRP only in a further 42. Sensitivity and specificity of each test were calculated using the white cell scan result as the 'gold standard'. ACT had the highest specificity (1.0), but the lowest sensitivity (0.27) of the three markers. CRP (using specified limits) had the lowest specificity (0.67) and the highest sensitivity (0.79). The corresponding values for AGP are 0.87 and 0.48. The low sensitivity of ACT and AGP preclude them from being useful referral criteria. CRP (using specified limits) is the most sensitive marker, but not sensitive enough to be useful as a referral indicator. However, by lowering the upper limit of normal to 5 mg.l-1, the sensitivity of the test increases to 0.96. Using this threshold to select the patients, 30% would not have been scanned and only one patient out of the 22 with IBD would have been missed. Where there is high demand for white cell scans this may provide a useful strategy for rationalizing the requests with minimal consequence on clinical management.

Is there an effect of acupuncture on the resting EEG?

OBJECTIVE: To investigate if acupuncture has a measurable effect on the resting electron EEG. SUBJECTS: 14 healthy volunteers with no neurological condition took part in the study. METHODS: Using a digital storage EEG recorder and quantitative frequency analysis techniques data were obtained before, during and after acupuncture stimulation. To minimize the effect of artefacts all data were collected with the subject alert, but with eyes closed. Manual stimulation of the LI 4 acupuncture site was undertaken for periods of 0.5, 1.0 and 2.0 min. Frequency analysis of the EEG data from each acupuncture event was compared to the baseline data to show any significant changes over the bandwidth 0.3 to 30 Hz. Only changes greater than 2 standard deviations were considered significant. RESULTS: In 10 subjects the frequency spectra remained unchanged during acupuncture, but in three significant increases were recorded in the amplitude of very low frequencies between 0.5 and 2 Hz and in one subject there was an increase in the amplitude of the alpha band during acupuncture. All spectra returned to their baseline values immediately after acupuncture. OUTCOME: The changes recorded in the delta band of individuals during acupuncture were large but highly variable. They arose at a frequency that is on the limit of the recording equipment and where recording and physiological artefacts are known to occur, although there was no evidence of artefactual contamination of the data. The one case in which there was an increase in the alpha band is attributed to suppression of the dominant rhythm initially brought about by anxiety concerning the procedure which subsequently disappeared during acupuncture as the subject relaxed. CONCLUSION: It is clear that there are no changes brought about by acupuncture in the resting EEG in the frequency range 2-30 Hz and no evidence to attribute changes below 2Hz to a direct affect of acupuncture.

Monitoring of recovery following exercise in the Doppler ultrasound evaluation of lower limb arterial disease.

Measurement of the ratio of ankle to brachial systolic blood pressure (pressure index) is an integral part of the Doppler ultrasound investigation of lower limb arterial disease. The recovery of this index following exercise gives further information regarding the clinical significance of the disease. However, serial sphygmomanometry may prolong recovery time by intermittent reduction of blood flow and for certain categories of patients the technique may prove impossible or will lead to unreliable results. The aim of this study was to investigate the use of Pourcelot's Resistance Index, measured from the Doppler blood velocity spectrum, as an alternative means of monitoring recovery. The results show that peripheral resistance is likely to fall following pressure measurement, indicating a potential effect on recovery time. There is reasonable correlation between post-exercise pressure and resistance indices (r = 0.69, P less than 0.001), and good correlation between their recovery times (r = 0.84, P less than 0.001) with no systematic deviation. Resistance index is therefore a viable alternative to pressure index for the monitoring of post-exercise recovery, and overcomes the problems associated with sphygmomanometry.

A week in the life of Mary: the impact of microtechnology on a severely handicapped person.

Microtechnology has an important role to play in maximizing the independence of severely handicapped people, especially those with few reliable voluntary movements. Such movements must be harnessed efficiently to provide control over all aspects of life including communication, mobility and the immediate environment. To highlight the role of microtechnology in the day to day life of a severely handicapped person living at home, a case study is presented. The systems Mary uses for communication and environmental control are described and their limitations discussed. Adaptive man-machine interfaces are proposed and foreseeable developments in the fields of speech technology and robotics are considered. Successful introduction of high technology devices requires a full appreciation of medical and social factors as well as those relating to the technology. This is achieved through close partnership between the clinical engineer and the rehabilitation consultant to the benefit of the severely handicapped person.

Glutaraldehyde-resistant Mycobacterium chelonae from endoscope washer disinfectors.

Glutaraldehyde is used to disinfect flexible and other heat-sensitive endoscopes often with the aid of automated systems. Mycobacterium chelonae is being isolated with increasing frequency from these washer disinfectors and processed endoscopes. This has, on occasions, led to misdiagnosis and iatrogenic infections. Recent reports suggest that disinfecting machines, on a sessional or regular basis, with 2% glutaraldehyde may have selected and therefore encouraged the growth of strains of Myco. chelonae, possibly in biofilm, with decreasing susceptibility to glutaraldehyde. In view of this, the resistance of three strains of Myco. chelonae var. chelonae (the type strain NCTC 946 and two machine isolates) was tested against 2% glutaraldehyde and a wide range of alternative disinfectants. Disinfectants tested were a chlorine releasing agent, sodium dichloroisocyanurate at 1000 ppm and 10,000 ppm av Cl, 0.35% peracetic acid (NuCidex, Johnson & Johnson), 70% industrial methylated spirit (IMS), 1% peroxygen compound ('Virkon', Antec International) and 10% succine dialdehyde ('Gigasept', Sanofi Winthrop). Suspension and carrier tests were carried out in the presence and absence of an organic load. Results showed the type strain, which had not been exposed to the selective pressure of disinfectant usage, to be very sensitive to most disinfectants with the exception of 1% Virkon. The washer disinfector isolates, on the other hand, were extremely resistant to 2% glutaraldehyde and showed greater resistance to 1% Virkon and 1000 ppm NaDCC. Purchasing machines in which the entire fluid pathways, including those for delivering rinse water, are disinfected with an appropriate agent during each cycle are preferred. If this is not possible then sessional cleaning and disinfection at the start of each day and regular maintenance should prevent biofilm formation and contamination with disinfectant-resistant strains of mycobacteria. In addition to machine disinfection, the use of sterile or bacteria-free (filtered < 0.45 microm) water is essential for bronchoscopes and all invasive endoscopes. If there is doubt that the effectiveness of the machine disinfection procedure or water quality, the channels and surfaces of endoscopes may be rinsed with 70% IMS after automated processing.

Sensitometry of films for nuclear medicine.

A method is described for the determination of characteristic curves for films used in nuclear medicine imaging. Such characteristic curves are presented for a number of commercially available film types and their significance is discussed.

The influence of acute hypoxia and sleep states on the electrical activity of the cerebellum in the sheep fetus.

The experiments were designed to examine (1) the effects of acute hypoxia and (2) the influence of sleep states on the electrical activity of the cerebellum in the fetus. Five fetal sheep were instrumented between 106 and 133 days of gestation and survived in utero until term (140-146 days). Insulated stainless steel electrodes (75 microns diam.) were introduced into the cerebellar cortex and cemented in place. Electrodes were also implanted into 4 fetuses to monitor the electrocorticogram, rapid eye movements and the EMG of the dorsal neck (nuchal) muscles. Recordings of cerebellar activity were made for 252 h in 4 fetuses. The recordings were derived from many units (probably Purkinje cells) with a high level of basal discharge. The mean firing frequency was related to fetal sleep state. The highest frequencies coincided with episodes of rapid eye movements with low-voltage electrocortical activity and the lowest occurred during high-voltage electrocortical activity when rapid eye movements are absent. Acute hypoxaemia (fetal pa O2 6-10 mm Hg for up to 30 min) abolished rapid eye movements and caused a marked reduction in cerebellar activity. High-voltage electrocortical activity and nuchal EMG activity were maintained indicating that the effects of hypoxia on the cerebellum were not due simply to a general CNS depression. Cerebellar neural activity returned to normal at the termination of the hypoxic stimuli demonstrating that fetal Purkinje cells can withstand short episodes of severe hypoxia.

Persistent 24-h variations of urinary 6-hydroxy melatonin sulphate and cortisol in Antarctica.

Bright light (2000-3000 lux) of sufficient intensity to suppress human melatonin secretion, acts as a strong zeitgeber in the entrainment of circadian rhythms in man. In polar conditions, light of this intensity is not experienced for several weeks during the winter. The entrainment of human circadian rhythms, in particular that of melatonin, is clearly of interest in these circumstances. Urinary 6-hydroxy melatonin sulphate (aMT6s) is a good index of melatonin secretion in man. In a limited study of seven male volunteers living on an Antarctic base the overall 24-h rhythm of aMT6s excretion was maintained at four different times of year (spring, summer, autumn and winter) and no significant seasonal effects were noted. Cortisol excretion, appeared to be markedly affected by the season although other factors such as social and environmental stress cannot be discounted. These observations suggest that in the absence of a strong light-dark cycle melatonin production may be entrained by other factors.

Staging breast cancer: role of bone scanning.

Bone scans using technetium-99m phosphate complexes and a rectilinear scanner were carried out on 192 women with primary operable breast cancer four to six weeks after operation. The lymph node status of all these patients was assessed histologically from triple node biopsy specimens. Only nine patients had positive scans, although 94 patients had histological evidence that the tumour had already spread beyond the confines of the breast. Bone scanning, although accurate as a prognostic guide, is helpful only in a very few cases, and serves mainly to confirm prognostic information obtained more simply and less extensively by histological examination of lymph node biopsy specimens.