Cardiac 123I-MIBG normal uptake values are population-specific: Results from a cohort of controls over 60 years of age.

PURPOSE: Cardiac 123I-MIBG image interpretation is affected by population differences and technical factors. We recruited older adults without cognitive decline and compared their cardiac MIBG uptake with results from the literature. METHODS: Phantom calibration confirmed that cardiac uptake results from Japan could be applied to our center. We recruited 31 controls, 17 individuals with dementia with Lewy bodies (DLB) and 15 with Alzheimer's disease (AD). Images were acquired 20 minutes and four hours after injection using Siemens cameras with medium-energy low-penetration (MELP) collimators. Local normal heart-to-mediastinum (HMR) ratios were compared to Japanese results. RESULTS: Siemens gamma cameras with MELP collimators should give HMRs very close to the calibrated values used in Japan. However, our cut-offs with controls were lower at 2.07 for early and 1.86 for delayed images. Applying our lower cut-off to the dementia patients may increase the specificity of cardiac MIBG imaging for DLB diagnosis in a UK population without reducing sensitivity. CONCLUSIONS: Our local HMR cut-off values are lower than in Japan, higher than in a large US study but similar to those found in another UK center. UK centers using other cameras and collimators may need to use different cut-offs to apply our results.

123I-MIBG scintigraphy utility and cut-off value in a clinically representative dementia cohort.

OBJECTIVE: To determine the utility of 123I-metaiodobenzylguanidine cardiac scintigraphy (MIBG), and optimum heart: mediastinum ratio (HMR) for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) in a clinically representative population, comparing findings with those of 123I-2ß -carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) SPECT. METHODS: We recruited subjects with probable DLB (n = 17) and probable AD (n = 16) from clinical services. Each participant underwent clinical examination, cardiac MIBG scintigraphy and FP-CIT SPECT. Diagnosis was made on the basis of clinical symptoms using validated criteria. Cardiac MIBG uptake was measured by the planar HMR, blind to clinical diagnosis, with values below a cut-off taken from a previous study (<2.2 at four hours) defining scans as abnormal. FP-CIT scans were blindly rated according to a visual rating scale. RESULTS: MIBG had a sensitivity, specificity and overall accuracy of 71%, 81% and 76% for distinguishing DLB from AD. FP-CIT demonstrated a sensitivity, specificity and accuracy of 82%, 88% and 85%. Using a lower HMR cut-off to distinguish between abnormal and normal MIBG scans improved the accuracy of MIBG, raising specificity (100%) and overall accuracy (85%) without compromising sensitivity (71%). Neither prescription of potentially interfering medications, nor a history of myocardial infarction (MI), had a significant effect on HMR. CONCLUSION: We found that MIBG did not demonstrate superior sensitivity and overall accuracy to FP-CIT. HMR cut-off influences biomarker utility, and clinical and Caucasian populations may require a lower cut-off than those reported elsewhere. Future MIBG studies should include clinically representative cohorts as neither medications nor previous MI appear to influence HMR.

Willingness to pay for drug rehabilitation: implications for cost recovery.

OBJECTIVES: This study estimates the value that clients place on methadone maintenance and how this value varies with the effectiveness of treatment and availability of case management. We provide the first estimate of the price elasticity of the demand for drug treatment. METHODS: We interviewed 241 heroin users who had been referred to, but had not yet entered, methadone maintenance treatment in Baltimore, Maryland. We asked each subject to state a preference among three hypothetical treatment programs that varied across three domains: weekly fee paid by the client out-of-pocket ($5-$100), presence/absence of case management, and time spent heroin-free (3-24 months). Each subject was asked to complete 18 orthogonal comparisons. Subsequently each subject was asked if they likely would enroll in their preferred choice among the set of three. We computed the expected willingness to pay (WTP) as the probability of enrollment times the fee considered in each choice considered from a multivariate logistic model that controlled for product attributes. We also estimated the price elasticity of demand. RESULTS: The median expected fee subjects were willing to pay for a program that offered 3 months of heroin-free time was $7.30 per week, rising to $17.11 per week for programs that offered 24 months of heroin-free time. The availability of case management increased median WTP by $5.64 per week. The price elasticity was -0.39 (S.E. 0.042). CONCLUSIONS: Clients will pay more for higher rates of treatment success and for the presence of case management. Clients are willing to pay for drug treatment but the median willingness to pay falls short of the estimated program costs of $82 per week. Thus a combined approach of user fees and subsidization may be the optimal financing strategy for the drug treatment system.

Similar dose-response and persistence of erythema with broad-band and narrow-band ultraviolet B lamps.

Psoriasis may be treated with ultraviolet B from lamps that have a broad emission spectrum or, more effectively, with lamps that have a narrow emission spectrum at 311 +/- 2 nm. There are conflicting reports of either greater or lesser burning episodes with narrow-band compared to broad-band ultraviolet B, even when treatments are based on predetermined minimal erythema dose measurements. This suggests that either the characteristics of the dose-response curve for erythema or the time course for erythema may be different for the two lamps. We examined the erythemal response to narrow-band and broad-band ultraviolet B in 12 patients with psoriasis. A geometric series of 10 doses from each lamp type were used on nonlesional skin on the back. Dose-response curves were constructed from reflectance measurements of erythema at 24 h and 72 h after irradiation. No significant difference was found in steepness of the erythema dose-response curve for the two lamps at 24 or 72 h. Persistence of erythema was assessed as the percentage of erythema remaining at 72 h. The mean persistence was 63% for narrow-band and 64% for broad-band lamps (p = 0.94). Therefore, in terms of erythemal response, no evidence has been found for a difference in burning potential for the two lamps.

The contribution of single photon emission tomography to the clinical differentiation of degenerative cortical brain disorders.

The accurate clinical diagnosis of degenerative cortical brain disorders is a necessary prerequisite for patient management and the critical evaluation of new treatments. This study has evaluated the ability of single photon emission tomography (SPET) to differentiate between Alzheimer's disease (AD) and different forms of non-Alzheimer lobar atrophy (LA), using a multi-purpose system in widespread routine clinical use. 99mTc-HMPAO SPET was carried out in patients with AD and three clinical syndromes associated with LA: frontotemporal dementia (FTD), progressive non-fluent aphasia (PA) and semantic dementia (SD). Principal component (PC) analysis was performed on regional cerebral blood flow (rCBF) data and inter-group comparisons were performed for PC scores using multiple t-tests. Three PCs explained 86.5% of the variation in rCBF values between individual patients and normal controls. The first PC reflected the average rCBF value and separated patient groups from normal controls but failed to distinguish between patient groups. The second PC reflected anterior-posterior asymmetry and separated AD from all three forms of LA. This PC also separated FTD and SD from controls but failed to distinguish between FTD, PA and SD. The third PC reflected left-right asymmetry and separated PA from all other groups. 99mTc-HMPAO SPET is able to differentiate between degenerative cortical brain disorders in a simple and physiological meaningful way, thereby showing considerable potential as a routine tool in the clinical evaluation and differentiation of AD and LA.

A 99mTc-HMPAO single-photon emission computed tomography study of Lewy body disease.

The purpose of this study was to investigate patterns of 99mTc-HMPAO single-photon emission computed tomography (SPECT) abnormality in Lewy body disease (LBD) and to compare findings with those encountered in Alzheimer's disease (AD). The study group comprised 20 consecutive patient referrals fulfilling clinical criteria for LBD. All patients had fluctuating cognitive impairment and 'subcortical' dysfunction with or without perceptuospatial and/or linguistic impairment. Six patients had asymmetrical signs of parkinsonism (three left-sided and three right-sided), and 14 patients had symmetrical features of extrapyramidal involvement. 99mTc-HMPAO SPECT imaging was performed on LBD patients and findings compared with those of 57 patients with 'probable' AD and 11 normal age-matched controls. Within the LBD and AD groups, patterns of cortical and subcortical blood-flow abnormality were compared with patterns of cognitive and neurological breakdown. LBD was associated with bilateral posterior cortical blood flow abnormality, a pattern strikingly similar to that found in AD. Within the LBD group, cortical blood-flow abnormality was found to reflect patterns of neurological dysfunction (parkinsonism) indicative of subcortical involvement. In contrast, cortical blood-flow changes did not reflect patterns of neuropsychological impairment suggestive of cortical dysfunction. Within the AD group, cortical blood-flow changes were mirrored by the pattern of neuropsychological impairment. Findings support the notion that cortical blood-flow abnormality in LBD might reflect a combination of direct cortical pathology and cortical deafferentation secondary to subcortical Lewy body pathology. It would appear that 99mTc-HMPAO SPECT imaging is of limited value in the clinical differentiation of LBD and AD.

Evaluation of 99Tcm Technegas ventilation scintigraphy in the diagnosis of pulmonary embolism.

In the diagnosis of pulmonary embolism, perfusion lung scintigraphy offers high sensitivity but low specificity. The specificity can be significantly increased by the use of combined ventilation and perfusion studies. Most aspects of perfusion lung scintigraphy are uniformly accepted but the technique of ventilation imaging varies from centre to centre. This study describes a new technique for the performance of ventilation scintigraphy using a suspension of ultrafine carbon particles labelled with 99Tcm ("Technegas"). The technique combines the ready availability of 99Tcm and its optimal imaging properties with an easily administered radiopharmaceutical of particle size sufficiently small to deposit in the alveoli. Of 63 patients studied by conventional perfusion scintigraphy plus Technegas ventilation scintigraphy, images of diagnostic quality were obtained in all. 31 of these patients also had a ventilation study using 81Krm gas and in only one instance did the two methods of ventilation imaging lead to differing interpretations. We conclude that high quality diagnostic images may be obtained using this new technique, which can be made available on both a routine and an emergency basis, thus improving the service provided for patients suspected of having pulmonary embolism.

The incidence and severity of hypoxia associated with 99Tcm Technegas ventilation scintigraphy and 99Tcm MAA perfusion scintigraphy.

Inhalation of the ventilatory radiopharmaceutical 99Tcm Technegas leads, in some patients, to symptoms that may be attributed to temporary lowering of oxygen saturation. In order to evaluate this, oxygen saturation was measured by pulse oximetry in a series of patients undergoing Technegas ventilation scintigraphy. A decrease in oxygen saturation was recorded in 87% of the patient group. The mean change, as a percentage of the initial value, was 8.3% (range 1-24%). Hypoxia arising in association with Technegas administration may be reduced by pre-oxygenation. In patients who were pre-oxygenated, oxygen saturation did not fall below 85% (PaO2: 50 mmHg) but in 39% of those not pre-oxygenated the value fell below this level. Oxygen saturation was also monitored in a series of patients undergoing perfusion scintigraphy. In 17% of patients a decrease was recorded (range 2-11%). In view of the large number of perfusion scans performed annually in this department and elsewhere without untoward effect, such temporary decreases in oxygen saturation presumably present no hazard to the patient.

99Tcm-Technegas and krypton-81m ventilation scintigraphy: a comparison in known respiratory disease.

Krypton-81m gas, by virtue of its imaging characteristics, is often considered the "gold standard" for ventilation scintigraphy but its use is restricted by its high cost and limited availability. The new radiopharmaceutical 99Tcm-Technegas, a suspension of ultrafine technetium-99m labelled carbon particles, produces high-quality images of ventilation and has the advantage of continuous availability. As part of our evaluation of Technegas the two were compared in 40 patients with a variety of established respiratory diseases. Disparities were seen in five patients in five diagnostic groups and may be a consequence of the differing physical properties of the two agents and the different inhalation techniques used. In addition two interesting features were noted on the Technegas images. (1) Hot spots were seen in 50% of patients, particularly in those with a degree of airways obstruction; (2) preferential basal deposition of activity was seen in 30%, particularly in patients with idiopathic pulmonary fibrosis. Both features were significantly associated with parameters of pulmonary function indicating obstructive lung disease in the former case and restrictive lung disease in the latter.

Quantifying the value of diagnostic tests.

This paper considers the different statistics that can be derived from studies on the value of diagnostic tests. Well-accepted quantities, such as sensitivity and specificity, are reviewed and the value of the likelihood ratio in communicating particular test results is highlighted. A new quantity, the 'diagnostic value index', is proposed and various examples of its application in nuclear medicine studies are presented. This new index is based on a weighted average of the likelihood ratios for all possible outcomes of the test, the average being weighted according to how frequently a particular outcome occurs. This index provides an objective and quantitative means of comparing the diagnostic value of different tests, or of comparing the value of a given test in different patient groups. It is hoped that this will be a useful aid to clinical decision-making concerning referrals for diagnostic tests.

Contamination levels and doses to staff arising from the use of Technegas.

The aim of this work was to assess the levels of airborne activity and contamination arising from Technegas ventilation scintigraphy and to estimate doses to staff. The maximum air concentration was below the 99Tcm-derived air concentration limit and considerably lower than reported levels for conventional radioaerosols. The level of contamination on staff gloves and aprons exceeded the body surface contamination limit in 63 and 9% of cases, respectively. Levels of contamination and air concentration were generally higher if the patient had difficulty with the administration procedure. Room surface contamination was very low. In 24% of cases activity was detectable on staff (either in the hair or nose) using gamma camera imaging. Annual skin doses from these sources are calculated to be below the limit for deterministic effects. Whole body effective doses are calculated to be similar to those received by staff performing other nuclear medicine studies. However, care should be exercised to keep exposure from both airborne and fixed sources to a minimum and a regular review of contamination levels is recommended. We recommend the wearing of gloves for all Technegas administrations and disposable hats and masks may be considered in certain cases.

Texture analysis of technegas lung ventilation images.

Technegas lung ventilation images sometimes have 'hot spots', particularly in patients with respiratory disease. A novel technique is presented for quantifying this 'spottiness' using morphological texture analysis. A set of 32 images from patients with various respiratory diseases is studied. Images are filtered at a range of scales using morphological opening, and the slopes of image metrics versus structuring element size are used as texture parameters. The results are compared with the opinions of three experienced nuclear medicine physicians who have classified the images into two groups, 'spotty' and 'non-spotty', and have ranked the former. For the spotty images, the computer and observer ranks are compared; the highest correlation is rs = 0.66 (p = 0.01) for a single parameter, and rs = 0.71 (p < 0.01) for a combination of two parameters. Using a pair of parameters, 83% and 90% correct classification rates are obtained for the spotty and non-spotty classes, respectively. It is concluded that these texture parameters provide a useful measure of image spottiness, and it is demonstrated that this technique is superior to previously published methods. The practical value of the technique is illustrated using two applications.

The use of a spectrophotometric intracutaneous analysis device in the real-time diagnosis of melanoma in the setting of a melanoma screening clinic.

BACKGROUND: Skin imaging devices to aid melanoma diagnosis have been developed in recent years but few have been assessed clinically. OBJECTIVES: To investigate if a spectrophotometric skin imaging device, the SIAscope, could increase a dermatologist's ability to distinguish melanoma from nonmelanoma in a melanoma screening clinic. METHODS: Eight hundred and eighty-one pigmented lesions from 860 patients were prospectively assessed clinically and with the aid of the spectrophotometric device by a dermatologist. Assessment before and after spectrophotometric imaging was made and compared with histology, where available, or with the clinical diagnosis of a dermatologist with 20 years of experience. RESULTS: One hundred and seventy-nine biopsies were performed, with 31 melanomas diagnosed. Sensitivity and specificity for melanoma diagnosis before and after spectrophotometry were 94% and 91% vs. 87% and 91%, respectively, with no significant difference in the area under the receiver operating characteristic curves (0.932 and 0.929). CONCLUSIONS: Our study provides no evidence for the use of SIAscope by dermatologists to help distinguish melanoma from benign lesions.

Sunscreen ingredients and labelling: a survey of products available in the UK.

BACKGROUND: In Europe, where sunscreens are classified as cosmetics, products may contain one or several of 27 permitted 'ultraviolet filters'. We were unable to find published data on the frequency of usage of individual ultraviolet (UV)-absorbing chemicals in currently available sunscreens. AIM: To record the active ingredients and labelling characteristics of sunscreens available in the UK. METHODS: In 2005, two dermatologists visited seven retail outlets, which stocked a large range of sunscreens. Manufacturers were also contacted. For each product, the names of UV-protective ingredients and the labelling information, including sun protection factor (SPF), UVA protection and age group for which the product was marketed were recorded. RESULTS: Data on 308 skin sunscreen products and 21 lip sunscreens were recorded. For skin products, the SPF ranged from 2 to 60. In total, 23 different UV-absorbing ingredients were found, 4 of which were found in > 25% of products. The child and baby skin sunscreens (n = 52) had a significantly higher median SPF of 40, compared with 15 for the remaining 256 adult products (P < 0.001). The number of UV-absorbing chemicals and the frequency of those commonly used did not differ substantially between child and adult products. Of skin sunscreens marketed for babies, 60% contained 2-6 UV-absorbing chemicals. Nearly half of the skin sunscreens contained at least one of nine UV-absorbing chemicals not available in patch testing formulations from commercial suppliers. CONCLUSIONS: The results of this survey indicate current sunscreen content and labelling, and are a benchmark from which new developments can be tracked. More standard sunscreen labelling, particularly separate listing of active ingredients, would be helpful. It was surprising to find UV-absorbing chemicals in products sold for use on babies.

Variation in calibration of hand-held ultraviolet (UV) meters for psoralen plus UVA and narrow-band UVB phototherapy.

BACKGROUND: Phototherapy units should regularly use hand-held ultraviolet (UV) meters to assess the output of treatment lamps, and these meters should be accurately calibrated. Several medical physics departments in the U.K. can calibrate UV meters traceable to national standards, but there is concern that there may be disagreement among departments. In particular, there may be difficulty in calibration for narrow-band UVB phototherapy lamps (TL-01). OBJECTIVES: To ascertain the level of agreement in UV meter calibration at expert centres in the U.K., and to survey methodology at these centres, consider sources of errors and to make recommendations on calibration methods. METHODS: The same UV meter with two detectors (for UVA and UVB) was calibrated by seven medical physics departments. A questionnaire on methods was also distributed and measured spectral outputs from each centre were examined. RESULTS: The calibration factors for the meter varied by +/- 18% for the UVA detector and by +/- 60% for the UVB detector (2 standard deviations). Six centres performed calibration using a spectroradiometer and one centre used a reference meter method. The spectra of lamps used for calibration were similar. For the spectroradiometric methods there were some differences in methodology and instrumentation that may account for the differences in calibration factors. CONCLUSIONS: UV meter calibration in the U.K. shows unacceptable variability, particularly for TL-01 lamps. An accuracy of around of +/- 10% would be clinically acceptable and should be technically achievable.

Recent weapon carrying and substance use among United States Virgin Islands youth.

The objective of the present study was to estimate the strength of the associations between recent weapon carrying and alcohol, cigarette, and illicit drug use among US Virgin Islands (USVI) youth. Data from 1,124 students in Grades 7-12 were analyzed using the conditional form of multiple logistic regression. Compared with youth who did not carry a weapon. youth who carried a weapon were more likely to be male and recent cigarette, alcohol, and illicit drug users. After matching on school and controlling for age, sex, race, neigborhood characteristics, and affiliation with friends who use alcohol and illegal drugs, the associations with cigarette smoking and illicit drug use remained both moderate and statistically significant (odds ratio [OR] = 4.31, p < .001; OR = 2.99, p < .001, respectively). These findings identify a potentially high-risk population that could be targeted for interventions to reduce weapon carrying among youth.

Response of psoriasis to sunbed treatment: comparison of conventional ultraviolet A lamps with new higher ultraviolet B-emitting lamps.

BACKGROUND: Sunbeds fitted with conventional ultraviolet (UV) A lamps that have about 0.7% UVB emission are widely used by patients with psoriasis even though they are minimally effective. A new fluorescent sunbed lamp has been developed that emits a higher proportion of UVB (4.6%) than conventional lamps and also requires shorter exposure times to achieve equivalent erythema. OBJECTIVES: To perform a randomized, within-patient comparison of conventional sunbed lamps (Cleo Performance) with the new lamps (Cleo Natural) in the treatment of psoriasis. METHODS: A sunbed and canopy unit were modified to allow exposure to Cleo Performance lamps on one side of the body (front and back) and Cleo Natural lamps to the other side of the body. Two studies were done. In study 1, equal erythemal doses were given from the two lamp types. In study 2, equal exposure times were given. We treated 34 patients with psoriasis, giving 12 exposures over a period of 4 weeks. Assessment was made using a modified Psoriasis Area and Severity Index (PASI) score, individual plaque assessment and patient questionnaire. RESULTS: Fourteen patients completed each study. In study 1, there was no significant difference in median improvement in half-body PASI score for the two lamp types. In study 2, there was a significant difference in PASI score improvement between the two lamps (median Cleo Performance change minus median Cleo Natural change was - 2.20; 95% confidence interval - 3.75 to - 0.65; P = 0.006). CONCLUSIONS: That no difference in response was found when equal erythemal doses were given suggests that the spectral emission of the Cleo Natural lamp is of no greater advantage for clearance of psoriasis than conventional lamps. However, the Cleo Natural lamps are more erythemally powerful, and exposure times similar to those used in conventional sunbeds result in a significant improvement of psoriasis. The risk of non-melanoma skin cancer from different patterns of exposure to Cleo Natural lamps can be estimated using established numerical models.

A clinical role for 99mTc-HMPAO SPECT in the investigation of dementia?

OBJECTIVES: To provide the clinician with a guide to the clinical utility of 99mTc-HMPAO single photon emission computed tomography (SPECT) and to the interpretation of specific test results in the differential diagnosis of dementia. METHODS: Three hundred and sixty three patients with dementia were studied prospectively for a median three (range 1-6) years and classified into disease groups on the basis of established clinical criteria. The degree to which different patterns of cerebral blood flow (CBF) abnormality found on 99mTc-HMPAO SPECT imaging at the time of initial patient presentation modified clinical diagnoses was determined by calculating the likelihood ratios for pairwise disease group comparisons. The optimal clinical usage of 99mTc-HMPAO SPECT was determined by calculating the percentage of significant test results for each pairwise disease group comparison. RESULTS: Bilateral posterior CBF abnormality was found to significantly increase the odds of a patient having Alzheimer's disease as opposed to vascular dementia or frontotemporal dementia. Bilateral anterior CBF abnormality significantly increased the odds of a patient having frontotemporal dementia as opposed to Alzheimer's disease, vascular dementia, or Lewy body disease. "Patchy" CBF changes significantly increased the odds of a patient having vascular dementia as opposed to Alzheimer's disease. Unilateral anterior, unilateral anterior plus unilateral posterior, and generalised CBF abnormality failed to contribute to the differentiation of any of these forms of dementia. CONCLUSIONS: 99mTc-HMPAO SPECT was found to be most useful in distinguishing Alzheimer's disease from vascular dementia and fronto temporal dementia, and least useful in differentiating between Alzheimer's disease and Lewy body disease, and between vascular dementia, frontotemporal dementia, and progressive aphasia. It is suggested that CBF SPECT should be used selectively and as an adjunct to clinical evaluation and CT.