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Objective: The aim of this study was to investigate the accuracy of locating parathyroid adenomas using dual-Isotope subtraction single-photon emission computed tomography-computed tomography (SPECT-CT) in comparison with clinical follow-up and pathology findings from surgery., Patients and Methods: A retrospective cohort study of dual-isotope subtraction SPECT-CT was carried out on 224 consecutive patients who were diagnosed with primary hyperparathyroidism. All the patients were injected with 20 MBq of iodine-123-iodide, followed 20 min later by 900 MBq of technetium-99m-sestamibi. Planar neck and chest views and SPECT-CT images were acquired 15 min after administration, followed by an additional planar image set at 2 h to view washout; all images were dual energy. In all, 115 out of 224 of the patients imaged underwent parathyroid surgery. The imaging results were compared with pathology findings when available and, in those who did not undergo surgery, and in some complex cases, with clinical measures after a 2-year clinical follow-up period., Findings: Out of the 224 patients, 135 patients had complete pathology and/or clinical follow-up data and were included in the analysis. The sensitivity of the subtraction SPECT-CT findings was measured to be 95%, with a specificity of 89% for the detection and localization of parathyroid adenomas. The positive predictive value was found to be 97% and the negative predictive value was found to be 83%. The accuracy of the technique was 94% in detecting parathyroid adenoma and 92% in accurate localization., Conclusion: Dual-isotope subtraction SPECT-CT imaging has a very high sensitivity and specificity in detecting and locating a parathyroid adenoma, showing that it is a very reliable preoperative imaging technique in primary hyperparathyroidism.

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12-15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Human studies showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF.

As emphasized in Part 1 of these guidelines, the diagnosis of pulmonary embolism (PE) is confirmed or refuted using ventilation/perfusion scintigraphy (V/P(SCAN)) or multidetector computed tomography of the pulmonary arteries (MDCT). To reduce the costs, the risks associated with false-negative and false-positive diagnoses, and unnecessary radiation exposure, preimaging assessment of clinical probability is recommended. Diagnostic accuracy is approximately equal for MDCT and planar V/P(SCAN) and better for tomography (V/P(SPECT)). V/P(SPECT) is feasible in about 99% of patients, while MDCT is often contraindicated. As MDCT is more readily available, access to both techniques is vital for the diagnosis of PE. V/P(SPECT) gives an effective radiation dose of 1.2-2 mSv. For V/P(SPECT), the effective dose is about 35-40% and the absorbed dose to the female breast 4% of the dose from MDCT performed with a dose-saving protocol. V/P(SPECT) is recommended as a first-line procedure in patients with suspected PE. It is particularly favoured in young patients, especially females, during pregnancy, and for follow-up and research.

Pulmonary embolism (PE) can only be diagnosed with imaging techniques, which in practice is performed using ventilation/perfusion scintigraphy (V/P(SCAN)) or multidetector computed tomography of the pulmonary arteries (MDCT). The epidemiology, natural history, pathophysiology and clinical presentation of PE are briefly reviewed. The primary objective of Part 1 of the Task Group's report was to develop a methodological approach to and interpretation criteria for PE. The basic principle for the diagnosis of PE based upon V/P(SCAN) is to recognize lung segments or subsegments without perfusion but preserved ventilation, i.e. mismatch. Ventilation studies are in general performed after inhalation of Krypton or technetium-labelled aerosol of diethylene triamine pentaacetic acid (DTPA) or Technegas. Perfusion studies are performed after intravenous injection of macroaggregated human albumin. Radiation exposure using documented isotope doses is 1.2-2 mSv. Planar and tomographic techniques (V/P(PLANAR) and V/P(SPECT)) are analysed. V/P(SPECT) has higher sensitivity and specificity than V/P(PLANAR). The interpretation of either V/P(PLANAR) or V/P(SPECT) should follow holistic principles rather than obsolete probabilistic rules. PE should be reported when mismatch of more than one subsegment is found. For the diagnosis of chronic PE, V/P(SCAN) is of value. The additional diagnostic yield from V/P(SCAN) includes chronic obstructive lung disease (COPD), heart failure and pneumonia. Pitfalls in V/P(SCAN) interpretation are considered. V/P(SPECT) is strongly preferred to V/P(PLANAR) as the former permits the accurate diagnosis of PE even in the presence of comorbid diseases such as COPD and pneumonia. Technegas is preferred to DTPA in patients with COPD.

Background and Aim: Radio-labelled Aprotinin has been shown to bind with amyloid fibrils in vitro as well as in vivo. The aim was to test the usefulness of 99mTc-Aprotinin imaging in systemic amyloidosis., Methods: Thirty-five cases who had 99mTc-Aprotinin scans for the assessment of systemic amyloidosis were reviewed retrospectively. Eighteen had biopsy-proven amyloidosis and 17 were controls (amyloidosis was excluded by negative biopsies and non-invasive tests). Five of 18 patients with amyloidosis had final diagnosis of cardiac amyloid., Results: Physiological uptake of 99mTc-Aprotinin was noted in the urinary tract (kidneys and bladder) and in the liver of all patients and controls; and non-specific uptake of 99mTc-Aprotinin was visualised in the spleen and oro-facial structures in the majority of both groups. Myocardial 99mTc-Aprotinin uptake was noted in all five patients with final diagnosis of cardiac amyloidosis and in none of the 30 subjects who did not have cardiac amyloid. The median heart to background uptake ratio was 2.0 in cardiac amyloid patients and 1.1 in subjects without cardiac amyloid (P = 0.0004). Single Photon Emission Tomography (SPECT) studies of the thorax confirmed that the site of uptake lay within the myocardium. In the amyloidosis group, site-specific 99mTc-Aprotinin uptake was also identified in the subcutaneous tissue of the legs and in a breast nodule shown to be positive for amyloidosis on biopsy., Conclusions: 99mTc-Aprotinin imaging may be a useful non-invasive method for the assessment of the presence and extent of extra-abdominal amyloid, particularly cardiac amyloidosis. It has little role in diagnosis of amyloidosis involving the oro-facial and abdominal structures.

Background: Glomerular filtration rate (GFR) has major prognostic implications in heart failure. Our objective was to validate the MDRD prediction equations for GFR in patients with advanced heart failure, and to compare their predictive performance to that of the Cockcroft-Gault (CG) equation., Methods: We analysed GFR in 45 patients referred for heart transplantation evaluation. 51Cr-EDTA-measured GFR was compared to GFR estimates obtained by MDRD1 and MDRD2 equations, CG equation using actual body weight, and ideal body weight. Regression analyses and Pearson correlations were performed, and Bland and Altman plots were drawn. ROC curves were obtained to illustrate each equation's ability to predict a GFR less than 60 ml/min/1.73 m2 (moderate renal impairment)., Results: Patients had a mean age of 52 years, and 69% were in NYHA class III. The mean EDTA-measured GFR was 46.9+/-17.2 ml/min/1.73 m2. The MDRD1 equation provided the best predictive model (narrowest limits of agreement; r = 0.766, p < 0.001), and the highest performance in predicting a GFR less than 60 ml/min/1.73 m2 (area under curve: 0.901)., Conclusions: MDRD equations, especially MDRD1, adequately predict GFR in advanced heart failure, with higher accuracy than the CG equation. MDRD1 also has higher performance in predicting a GFR less than 60 ml/min/1.73 m2.

Background: Clinical and laboratory assessment of activity in Crohn's disease (CD) correlate poorly with endoscopic findings. Calprotectin is a calcium-binding protein abundant in neutrophil cytosol, and extremely stable in faeces. Faecal calprotectin (FC) is an excellent surrogate marker of neutrophil influx into the bowel lumen., Aim: To assess whether FC concentration from a spot stool sample reliably detects active inflammation in patients with CD., Design: Cross-sectional comparative study., Methods: Subjects had a previously confirmed diagnosis of CD and were suspected on clinical grounds to be in the midst of a relapse. Thirty-five entered the study; they underwent radiolabelled white cell scanning (WCS) and had a stool sample collected for calprotectin measurement on the same day. A Crohn's disease activity index (CDAI) was also calculated for each. The WCS scans were scored at six standard sites to give a mean total, 'extent', 'severity' and 'combined extent and severity' scores., Results: FC was significantly and positively correlated with mean total (r = 0.73, p < 0.001), 'extent' (r = 0.71, p < 0.001), 'severity' (r = 0.64, p < 0.001) and combined 'extent and severity' WCS scores (r = 0.71, p < 0.001). A cut-off of faecal calprotectin > 100 microg/g gave a sensitivity of 80%, specificity of 67%, positive predictive value of 87% and a negative predictive value of 64% in identifying those with and without any inflammation on WCS. There was, however, no significant correlation between CDAI and mean total WCS score (r = 0.21, p = 0.24), nor between CDAI and FC (r = 0.33, p = 0.06)., Discussion: While the CDAI does not accurately reflect inflammatory activity in CD, a one-off FC reliably detects the presence or absence of intestinal inflammation in adult patients with CD, compared to WCS.

Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) white cell scintigraphy is invaluable for assessing the presence and extent of disease activity in patients with inflammatory bowel disease. Interpretation of images can be compromised by physiological excretion of tracer into the bowel via the biliary tree. This study assesses the effect of intravenous pethidine administered with the labelled white cells in an attempt to reduce the enterohepatic circulation of the tracer. Ninety-one subjects with proven or suspected inflammatory bowel disease were included in this study, all of whom underwent 99mTc-HMPAO white cell scintigraphy. The control group of 50 subjects underwent the standard protocol for this study performed in our department. The other 41 subjects received an intravenous injection of 0.3 mg/kg of pethidine at the same time as re-injection of the labelled white cells. Images were graded using a five-point scale at both 1 and 2.5 h and categorised as positive, negative or non-diagnostic. Each scan was also assessed for the presence of a visible gall-bladder. The pethidine group had significantly fewer non-diagnostic scans than the control group (P=0.003), and significantly (P=0.001) more studies in which the gall-bladder was visualised. It is concluded that the use of pethidine appears to reduce biliary excretion of tracer during 99mTc-HMPAO white cell scintigraphy. This may allow the delayed images, and early images with low-grade tracer uptake in the bowel, to be interpreted with greater confidence and thereby reduce the number of scans classified as non-diagnostic.

Radioiodinated meta-iodobenzylguanidine (MIBG) is used routinely for imaging and targeted radiotherapy of tumours derived from the neural crest. Since active uptake of MIBG by the noradrenaline transporter (NAT) makes a greater contribution to total drug accumulation than passive uptake when MIBG is present at low concentrations, tumour-specific uptake should be enhanced by the administration of lower molar amounts of MIBG. This could be achieved through the use of MIBG with a high specific activity. Commercially available preparations of 123I-MIBG have specific activities of approximately 200 MBq.mg-1. We have synthesized and used no-carrier-added (n.c.a.) 123I-MIBG produced by an iododesilylation reaction (specific activity 0.7 TBq.mg-1). We report here the first clinical studies comparing the commercially available and n.c.a. MIBG diagnostic preparations. Five patients with known phaeochromocytoma were studied. Unlike studies in animal models, no consistent improvement in tumour uptake was observed with the n.c.a. material. A larger patient group is required to determine whether there are significant differences between the two preparations, before proceeding to studies at therapeutic activity levels of n.c.a. 131I-MIBG. Even with no improvement in tumour uptake, n.c.a. MIBG may be the favoured formulation for therapeutic applications to reduce the molar amount of drug injected.

Orofacial granulomatosis is a granulomatous inflammatory disorder, affecting the soft tissues of the face and mouth. The predominant feature is disfiguring lip swelling. Patients with this condition may be exhibiting a Type IV hypersensitivity reaction to dietary or environmental allergens, or these may be the orofacial manifestations of underlying gastrointestinal Crohn's disease. The results of 99Tcm-HMPAO leucocyte labelling of the gastrointestinal tract in 14 patients with orofacial granulomatosis and 15 patients with known gastrointestinal Crohn's disease are presented, indicating that this is a useful and non-invasive screening test for the identification of gastrointestinal Crohn's disease in paediatric and young adult patients presenting with orofacial granulomatosis.

Background: Idiopathic slow-transit constipation may be a pangastrointestinal motility disorder. We have screened patients referred to surgery for constipation for the presence of biliary dyskinesia., Method: Patients had cholecystokinin-augmented trimethyl-3-bromo iminodiacetic acid scans to measure gallbladder ejection fraction., Results: There is a significant difference in gallbladder ejection fraction between patients with idiopathic slow-transit constipation (median value, 28.5) compared with patients with other causes of constipation (median value, 71; Mann-Whitney, P = 0.0025)., Conclusion: Idiopathic slow-transit constipation may be a pangastrointestinal motility disorder.

A retrospective study of the management of patients with suspected acute deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) in a general and maternity hospital was conducted over a two month period in 1992. Ninety six patients with suspected DVT/PTE were identified, of whom only two were pregnant. Forty four patients had suspected DVT and confirmatory investigations were performed in 84%. The most common risk factor for DVT was intra-venous drug (IVD) use. Unfractionated heparin was prescribed to all patients except one with acute DVT at an average daily dose of 25,000 iu. In patients receiving heparin, 68% had measurements of the activated partial thromboplastin time (APTT) ratio and on 38% of occasions the result was subtherapeutic. Complications of heparin therapy were infrequent. Fifty two patients had suspected PTE and 50 underwent ventilation/perfusion (V/Q) scanning. No patient underwent pulmonary angiography. The management of patients with normal, low and high probability V/Q scans was in keeping with the guidelines, but only 8% [corrected] of patients with an intermediate V/Q scan result had further investigations and 33% received heparin. This study revealed suboptimal anticoagulation of patients with acute DVT and scope for improvement in the management of patients with an intermediate V/Q scan result.

To assess the effects of selective sleep loss on ventilation during recovery sleep, we deprived 10 healthy young adult humans of rapid-eye-movement (REM) sleep for 48 h and compared ventilation measured during the recovery night with that measured during the baseline night. At a later date we repeated the study using awakenings during non-rapid-eye-movement (NREM) sleep at the same frequency as in REM sleep deprivation. Neither intervention produced significant changes in average minute ventilation during presleep wakefulness, NREM sleep, or the first REM sleep period. By contrast, both interventions resulted in an increased frequency of breaths, in which ventilation was reduced below the range for tonic REM sleep, and in an increased number of longer episodes, in which ventilation was reduced during the first REM sleep period on the recovery night. The changes after REM sleep deprivation were largely due to an increase in the duration of the REM sleep period with an increase in the total phasic activity and, to a lesser extent, to changes in the relationship between ventilatory components and phasic eye movements. The changes in ventilation after partial NREM sleep deprivation were associated with more pronounced changes in the relationship between specific ventilatory components and eye movement density, whereas no change was observed in the composition of the first REM sleep period. These findings demonstrate that sleep deprivation leads to changes in ventilation during subsequent REM sleep.

Because successive rapid-eye-movement (REM) sleep periods in the night are longer in duration and have more phasic events, ventilation during late REM sleep might be more affected than in earlier episodes. Despite the increase in eye movement density (EMD) in late REM sleep, average minute ventilation was, however, not reduced compared with that in early REM sleep. Decreases in rib cage motion (mean inspiratory flow of the rib cage) in association with increasing EMD were offset by increments in respiratory frequency. Apart from expiratory time, there were no significant changes in the slopes of the relationships between EMD and specific ventilatory components, from early to late REM sleep periods. However, there was an increase in the number of episodes when ventilation was reduced during late REM sleep. Changes in ventilatory pattern during late REM sleep are due to changes in the underlying nature of REM sleep. The ventilatory response during eye movements is, however, subject specific. Some subjects exhibit large decrements in mean inspiratory flow of the rib cage and increments in respiratory frequency during bursts of eye movement, whereas other individuals demonstrate only small changes in these ventilatory parameters.

A case of pleural mesothelioma with diffuse spinal meningeal thickening as shown by magnetic resonance imaging is reported.

Three hundred diabetic and 100 nondiabetic hospital outpatients (both groups of comparable age and sex distribution) were assessed for the presence of generalized and localized pruritus. Pruritus vulvae was significantly more common in diabetic women (18.4%) than in controls (5.6%) and was significantly associated with poor diabetes control (mean glycosylated hemoglobin level less than 12%). Other forms of localized pruritus were equally common in diabetic and nondiabetic patients, regardless of glycosylated hemoglobin levels. Generalized pruritus was present in 14 diabetic patients, but in 5 cases the symptom was ascribed to intercurrent illness or drug administration. Thus, generalized pruritus without apparent cause was present in only 8 diabetic patients (2.7%) and was not significantly more common than in nondiabetic patients. It is doubtful if diabetes mellitus per se should be regarded as a cause of generalized or localized pruritus, other than pruritus vulvae.

The case of a young man with a previously undescribed myopathy associated with polydactyly is reported. Although both limb girdles were affected, the major effect of the disease was upon the respiratory muscles leading to his presentation with life-threatening respiratory failure. A further feature was pronounced stiffness of the vertebral column and limb girdles, similar in some respects to the 'rigid spine syndrome'. Muscle biopsy appearances were unique but showed some similarities to both nemaline myopathy and myotonic dystrophy. Ventilatory assistance at night using a rocking bed led to a marked improvement and has enabled the patient to return to full-time employment.

Haemodynamic studies at rest and during exercise together with radionuclide ventriculography, pulmonary function and clinical well-being assessment were evaluated in ten patients with COPD and secondary pulmonary hypertension (mean PAP 25 mm Hg), before and after 6 months therapy with pirbuterol 20 mg thrice daily. Despite the continued pharmacological action of pirbuterol on the heart and systemic circulation during peak pirbuterol levels at 6 months, no significant effect on the pulmonary circulation was observed. Seven patients reported an improvement in the level of fatigue, the partial pressure of carbon dioxide fell significantly (6.5 +/- 0.9 to 6.1 +/- 0.9 kPa: P less than 0.01) and there was a slight bronchodilator effect [forced expiratory volume in 1s (FEV1) 0.60 +/- 0.18 to 0.71 +/- 0.2 1s-1: P less than 0.02] after 6 months. The drug was generally well tolerated but three patients with pre-existing biliary tract disease developed obstructive jaundice.

Abnormalities of pulmonary function in Crohn's disease have been described, although the results are conflicting and anecdotal accounts of lung involvement are few. In this study we assessed the prevalence of lung function abnormalities in Crohn's disease, and the relative contributions of age, sex, smoking and past medical history, and Crohn's disease activity to the pulmonary abnormalities found. Twenty-nine patients with Crohn's disease and 29 age-, sex- and smoking-matched volunteer controls underwent detailed respiratory assessment. Airways obstruction due to chronic bronchitis and asthma was present in 13 patients with Crohn's disease, but was not more prevalent than in the control group. FEV1 was similar in both Crohn's disease and control subjects (84.2 +/- 21.2% predicted, mean +/- SD; 93.7 +/- 16.3%, respectively: n.s.). The vital capacity was significantly lower in the Crohn's disease patients than in controls (86.7 +/- 16.6%; 95.9 +/- 12.7%; P less than 0.01), but this may have been influenced by the higher prevalence of past or intercurrent medical illnesses affecting the chest in Crohn's disease patients. No patient had evidence of fibrosing alveolitis or bronchiectasis. The haemoglobin corrected transfer factor was significantly lower in the Crohn's disease patients than in controls (100.4 +/- 17.4%; 113.2 +/- 25.1: P less than 0.05) but the diffusing coefficient was not significantly different. There was a significant correlation (r = 0.44, P less than 0.05) between the residual volume and the Crohn's disease activity index but otherwise no close relationship was observed between Crohn's disease activity, extent or duration and the indices of lung function. These findings suggest that the lungs are relatively unaffected by Crohn's disease.

Angiotensin converting enzyme inhibitors cause cough in some patients, but the mechanism of this effect is not known. Six patients in whom these inhibitors had caused cough and a further two patients in whom they were suspected to have caused worsening of bronchial asthma were studied. Nine patients in whom angiotensin converting enzyme inhibitors had not been associated with cough served as controls. In the controls lung function and bronchial reactivity were measured once; for the study patients these and the cough index were measured twice before rechallenge for two weeks with an angiotensin enzyme inhibitor and once afterwards. Rechallenge with drug for two weeks caused a significant decrease in the mean concentration of histamine causing a 35% fall in airways conductance and a significant increase in the cough index. Patients with cough showed bronchial hyperactivity compared with the controls, which increased after rechallenge with the inhibitors. Cough associated with converting enzyme inhibitors may be a variant of the cough in asthma.

The activity of the renin-angiotensin (RA) system and the ability of the lungs to generate angiotensin II (AII) were studied in 11 patients with stable cor pulmonale and respiratory failure caused by chronic obstructive bronchitis and emphysema. Angiotensin I concentrations (18.7 +/- 8.3 pmol/L) were normal, and transpulmonary AII formation rates (TRAIIFR) (14.2 +/- 18.1 pmol/min) were not significantly different from those recorded in nonedematous cardiac subjects (19.9 +/- 20.1 pmol/min), matched for sex, age, and diuretic therapy. The main determinant of TPAIIFR was the mixed venous AI concentration. Administration of oxygen for 30 min led to a small increase in TPAIIFR in the majority of patients. This increase could not be accounted for by changes in mixed venous AI. There was no correlation between serum angiotensin-converting enzyme levels and either the TPAIIFR or the systemic arterial AII concentrations.