Reproducibility of a semi-quantitative lobar pulmonary ventilation and perfusion technique using SPET and CT.

OBJECTIVE: Evaluation of regional lung function is valuable prior to lung surgery in patients with chronic lung disease. Our aim was to evaluate the reproducibility of a locally developed single photon emission tomography/computed tomography (SPET/CT) programme between and within three observers in assessing lobar pulmonary volumes, perfusion and ventilation. SUBJECTS AND METHODS: Twelve lung transplantation candidates had VQ SPET and diagnostic CT to determine lobar pulmonary function and plan surgery. Their data were used retrospectively in an in-house developed programme which delineates the lung fissures on the diagnostic CT as an anatomical template used to estimate the volume of each of 5 lung lobes. These anatomical volumes were then applied to the corresponding ventilation (99m Tc technegas) and perfusion (99m Tc MAA) SPET studies. The data were anonymised, duplicated and then processed in random order blindly by 3 readers several weeks apart. Nine studies could be adequately processed. The programme failed in delineating lung volumes in 2 subjects and there was data corruption in the third. The results were evaluated for inter- and intra- observer variability using an intra-class Correlation Coefficient (ICC). An ICC score was calculated for each lobe for volume, ventilation and perfusion. RESULTS: Inter- and intra- observer ICC scores for ventilation, and perfusion scans were all very high. Similar very strong ICC concordance scores were noted for volume except intra-observer ICC scores for left upper lobe (0.76) and right mid lobe (0.66) where scores showed strong concordance by standard statistical descriptors. The method was sensitive enough to demonstrate the expected gradient of ventilation/perfusion even in these patients with substantial pathology. CONCLUSION: Our method of lobar VQ SPET with CT quantitation has high inter- and intra- observer concordance and in this preliminary data set seems to be a reliable and reproducible test for semi-quantitation of differential volume, ventilation and perfusion of the lobes of the lungs.

Is there an added clinical value of "true"whole body(18)F-FDG PET/CT imaging in patients with malignant melanoma?

Accurate and reliable staging of disease extent in patients with malignant MM is essential to ensure appropriate treatment planning. The detection of recurrent or residual malignancy after primary treatment is important to allow for early intervention and to optimise patient survival. 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) PET or PET computed tomography (PET/CT) is indicated for surveillance of malignant MM due to its high sensitivity and specificity for soft-tissue or nodal recurrences and metastases. It has been claimed that including lower extremities and skull in addition to 'eyes to thigh' images in PET/CT evaluation of metastatic MM routinely is warranted. We have studied retrospectively the reports of whole-body PET/CT scans in all patients with MM scanned in our Department from April 2005 to December 2010. All PET abnormalities in the brain/scalp and lower extremities were tabulated by location and whether they were 'expected' or 'unexpected'. Findings were correlated with pathology, other imaging studies, and clinical follow-up. In this study, 398 PET/CT examinations in 361 patients with MM were included. Results showed that twelve of the 398 (3%) scans had brain/scalp abnormalities, with only 4 (1.0%) showing unexpected abnormalities. Twenty nine of the 398 (7.2%) scans showed lower extremity abnormalities, with only 5 (1.2%) showing unexpected abnormalities. In no case was an isolated unexpected malignant lesion identified in the brain/scalp or lower extremities. In conclusion, whole body PET/CT scan showed about 1% unexpected primary or metastatic MM lesions involving the head or lower extremities, which seldom offered significant additional clinical benefit and were unlikely to change clinical management. No clinically significant change in staging would have occurred. Routine 'eyes to thighs' images were adequate for this subset of patients.

Glucose absorption and gastric emptying in critical illness.

INTRODUCTION: Delayed gastric emptying occurs frequently in critically ill patients and has the potential to adversely affect both the rate, and extent, of nutrient absorption. However, there is limited information about nutrient absorption in the critically ill, and the relationship between gastric emptying (GE) and absorption has hitherto not been evaluated. The aim of this study was to quantify glucose absorption and the relationships between GE, glucose absorption and glycaemia in critically ill patients. METHODS: Studies were performed in nineteen mechanically-ventilated critically ill patients and compared to nineteen healthy subjects. Following 4 hours fasting, 100 ml of Ensure, 2 g 3-O-methyl glucose (3-OMG) and 99mTc sulphur colloid were infused into the stomach over 5 minutes. Glucose absorption (plasma 3-OMG), blood glucose levels and GE (scintigraphy) were measured over four hours. Data are mean +/- SEM. A P-value < 0.05 was considered significant. RESULTS: Absorption of 3-OMG was markedly reduced in patients (AUC240: 26.2 +/- 18.4 vs. 66.6 +/- 16.8; P < 0.001; peak: 0.17 +/- 0.12 vs. 0.37 +/- 0.098 mMol/l; P < 0.001; time to peak; 151 +/- 84 vs. 89 +/- 33 minutes; P = 0.007); and both the baseline (8.0 +/- 2.1 vs. 5.6 +/- 0.23 mMol/l; P < 0.001) and peak (10.0 +/- 2.2 vs. 7.7 +/- 0.2 mMol/l; P < 0.001) blood glucose levels were higher in patients; compared to healthy subjects. In patients; 3-OMG absorption was directly related to GE (AUC240; r = -0.77 to -0.87; P < 0.001; peak concentrations; r = -0.75 to -0.81; P = 0.001; time to peak; r = 0.89-0.94; P < 0.001); but when GE was normal (percent retention240 < 10%; n = 9) absorption was still impaired. GE was inversely related to baseline blood glucose, such that elevated levels were associated with slower GE (ret 60, 180 and 240 minutes: r > 0.51; P < 0.05). CONCLUSIONS: In critically ill patients; (i) the rate and extent of glucose absorption are markedly reduced; (ii) GE is a major determinant of the rate of absorption, but does not fully account for the extent of impaired absorption; (iii) blood glucose concentration could be one of a number of factors affecting GE.

Lymphatic mapping with 99mTc-Evans Blue dye in sheep.

OBJECTIVE: 99mTc-Evans Blue (EB) is an agent that contains both radioactive and color signals in a single dose. Earlier studies in animal models have suggested that this agent when compared with the dual-injection technique of radiocolloid/blue dye can successfully discriminate the sentinel lymph node. The aim of this study was to investigate the potential of 99mTc-EB as an agent to map the lymphatic system in an ovine model. METHODS: Doses of 99mTc-EB (23 MBq) containing EB dye (4 mg) were administered intradermally to the limbs of four anesthetized sheep, and they were then imaged over 20-30 min using a gamma camera. The study protocol was repeated using 99mTc-antimony trisulfide colloid (ATC) and Patent Blue V dye. The lymph nodes (popliteal, inguinal, and iliac for hind limbs or prescapular for fore limbs) were identified with a gamma probe during the operative exposure, then dissected and counted in a large volume counter. RESULTS: Simple and complex (dual) drainage patterns were visible on the scans, and the sentinel node was more radioactive than higher tier nodes in a chain, for both radiotracers. For 99mTc-EB, maximum radioactive uptake was achieved at 3-6 min for popliteal lymph nodes, 12-14 min for iliac nodes, and 13-14 min for prescapular nodes. 99mTc-ATC resulted in maximum radioactive uptake at 4-6 min for popliteal lymph nodes, 13 min for an inguinal node, 13-20 min for iliac nodes, and 18 min for a prescapular node. Following 99mTc-EB injection, 15/15 lymph nodes harvested were all radioactive and blue. For 99mTc-radiocolloid/Patent Blue V injection, 8/14 nodes were radioactive and blue, and 6/14 nodes were radioactive only. CONCLUSIONS: The soluble radiotracer 99mTc-EB appeared to be a useful lymphoscintigraphic agent in sheep, in which radioactive counts from superficial lymphatic channels and lymph nodes were sufficient for planar imaging. In comparison with 99mTc-antimony trisulfide colloid, both tracers discriminated the sentinel lymph node up to 50 min after administration; however, 99mTc-EB had the advantage of providing radioactive (gamma probe) and color signals simultaneously during the operative exposure.

18-Fluoride labeled sodium fluoride positron emission tomography with computer tomography: the impact of pretreatment staging in intermediate- and high-risk prostate cancer.

BACKGROUND: 18-Fluoride labeled sodium fluoride (Na-18-F) positron emission tomography with computer tomography (PET/CT) has a better sensitivity and specificity than whole body bone scan (WBBS) in detecting osseous metastatic prostate cancer. We performed a pilot study of 20 men to examine what level of impact Na-18-F PET/CT has on management plans when used for staging newly diagnosed prostate cancer. MATERIALS AND METHODS: Twenty men were prospectively enrolled into the study in South Australia. Men were eligible if they had newly diagnosed, untreated, and biopsy-confirmed intermediate- or high-risk prostate cancer (D'Amico classification). WBBS and Na-18-F PET/CT scans were performed within 1 week of each other. Following review of the WBBS, treatment type and intent was documented by the treating urologist. The Na-18-F PET/CT scan was then reviewed. The impact of the Na-18-F PET/CT was measured on whether treatment modality or intent was subsequently altered: high impact = treatment intent or modality was changed; medium impact = treatment modality was modified; low impact = no change in treatment. RESULTS: In 18 men (90%), the WBBS and Na-18-F PET/CT were negative for osseous metastases. In one man (5%), the WBBS demonstrated widespread osseous metastases which were similarly demonstrated on the Na-18-F PET/CT. One man (5%) had a normal WBBS; however, the Na-18-F PET/CT demonstrated widespread osseous metastases. Subsequently, in 19 men (95%), the results of the two scans were congruent and the addition of the Na-18-F PET/CT scan demonstrated a low impact on management. In one man (5%), the addition of the Na-18-F PET/CT had a high impact as treatment type and intent was altered. CONCLUSIONS: Our pilot study is the first of its kind in Australia, and our findings suggest that Na-18-F PET/CT is a safe and feasible modality for staging prostate cancer. However, its true impact on prostate cancer management warrants further investigation.

The tissue distribution of Evans blue dye in a sheep model of sentinel node biopsy.

BACKGROUND: Tc-Evans blue is a 'single dose' agent for lymphatic mapping combining radioactivity and blue dye for sentinel node identification. The mechanism and distribution of blue dye retention in the lymph node is not clearly understood. OBJECTIVE: To demonstrate the cellular distribution of Tc-Evans blue in sheep sentinel lymph nodes by measuring the radioactivity of different tissue components and correlating this with pathological examination. METHODS: Tc-Evans blue was used to identify sheep lymph nodes. Part of each node was sent for pathological examination including imprint cytology, and frozen and permanent section examination. Sections were examined without stains, with only red stains and conventional haematoxylin & eosin staining. The remaining nodal tissue was homogenized and components separated by enzymatic digestion and density gradient centrifugation. Fractions representing each tissue component were counted in a gamma counter and the distribution of Tc-Evans blue calculated. RESULTS: A dispersed population of blue staining cells was found. Their distribution, number and size indicated that they were histiocytes such as macrophages or antigen presenting cells. Radioactivity was distributed throughout the lymph node. Over 70% remained in the plasma, 19% in the leukocyte layer, and 10% was associated with erythrocytes and undigested tissue. CONCLUSION: The accumulation of radioactivity and blue colour in the lymph nodes indicates the mechanism of retention is a result of the binding interaction between Tc-Evans blue-protein and lymph node histiocytes including macrophages and antigen presenting cells.

Regenerating lizard tails: a new model for investigating lymphangiogenesis.

Impaired lymphatic drainage in human limbs causes the debilitating swelling termed lymphoedema. In mammals, known growth factors involved in the control of lymphangiogenesis (growth of new lymph vessels) are vascular endothelial growth factors-C and -D (VEGF-C/D). Here we characterize a model of lymphangiogenesis in which the tail of lizards is regenerated without becoming oedematous. Three weeks after the tail is shed (autotomy), there are a small number of large diameter lymphatic vessels in the regenerated tail. Thereafter, the number increases and the diameter decreases. A functional lymphatic network, as determined by lymphoscintigraphy, is established 6 wk after autotomy. The new network differs morphologically and functionally from that in original tails. This lymphatic regeneration is associated with an up-regulation of a reptilian homologue of the VEGF-C/D protein family (rVEGF-C/D), as determined by Western blot analysis using a human reactive VEGF-C polyclonal antibody. Regenerating lizard tails are potentially useful models for studying the molecular basis of lymphangiogenesis with a view to developing possible treatments for human lymphoedema.

Pharmacokinetics and normal scintigraphic appearance of 99mTc aprotinin.

OBJECTIVE: To confirm the pharmacokinetics and biodistribution of 99mTc aprotinin in normal volunteers and to determine the optimum time for scanning post-injection, prior to further investigations of 99mTc aprotinin as an imaging agent for amyloidosis. METHODS: Five patients (three men and two women, average age 49 years, age range 38-66 years) without a history of amyloidosis or any of the associated diseases, were included in this prospective study. Blood and urine were collected and images were performed of the whole body and wrists. CONCLUSIONS: Normal biodistribution of 99mTc aprotinin includes early cardiac and lung activity in the blood pool phase with subsequent hepatic activity and renal excretion with variable splenic activity. There is variable bowel uptake on later images. The best quality images were obtained 90 min post-intravenous administration, and this is likely to be the optimum time for clinical imaging.

Liquid gastric emptying in the pig: effect of concentration of inhaled isoflurane.

UNLABELLED: An animal model of gastric emptying may have use in the study of gastric physiology and pharmacoscintigraphy. The pig has anatomy and physiology similar to that of humans. Our aim was to develop a model of gastric emptying in the pig. It was not possible to perform this study in conscious pigs; therefore, an anesthetic model was developed. METHODS: Fifteen studies were performed on 4 pigs (age, 2-6 mo; weight, 20-100 kg). After acclimatization and training, pigs were fasted overnight before the study. Pigs were anesthetized using inhaled isoflurane without the use of injected premedication agents. An orogastric tube was inserted for the administration of a liquid meal, which consisted of (99m)Tc-diethylenetriaminepentaacetic acid either in water (nonnutrient) or with dextrose (nutrient meal). The pig was laterally positioned to enable right lateral dynamic acquisition to be performed. Anesthesia was maintained at 2% +/- 0.5% isoflurane in 4 studies and 0.8% +/- 0.5% in 11 studies (4 nutrient, 7 nonnutrient). RESULTS: With 2% +/- 0.5% isoflurane, there was delayed gastric emptying with a mean 50% emptying time (+/-SEM) of 141 +/- 14 min. With 0.8% +/- 0.5% isoflurane, the liquid meal emptied in an exponential manner similar to that of humans, with mean 50% emptying times (+/-SEM) of 30 +/- 7 min (nutrient) and 31 +/- 4 min (nonnutrient). CONCLUSION: The results indicate that high-dose anesthesia inhibits gastric emptying, but with low-dose anesthesia a useful pig model of liquid gastric emptying can be developed.

Outcomes of patients referred for confirmation of brain death by 99mTc-exametazime scintigraphy.

OBJECTIVE: To review clinical outcomes in patients referred for confirmation of brain death by (99m)Tc-labelled exametazime scintigraphy and to assess any tangible benefit. DESIGN AND SETTING: A retrospective casenote review in the intensive care unit and nuclear medicine department of a tertiary-level acute care hospital. PATIENTS AND PARTICIPANTS: 66 consecutive patients, in whom a clinical diagnosis of brain death was not possible, undergoing (99m)Tc-labelled exametazime scintigraphy from February 1993 to March 2002, and for 56 of whom casenotes were available for review. MEASUREMENTS AND RESULTS: Brain death was confirmed in 77% on the basis of absent supratentorial and infratentorial uptake. Where brain death was not confirmed, a normal scan was seen in 30%, the remainder showing patchy reduced infratentorial and/or supratentorial uptake. All patients with the scintigraphic appearance of brain death subsequently died. Even when brain death could not be confirmed, 11 of 13 patients died soon afterwards. Two patients with normal brain scintigraphy regained consciousness and survived for an extended period. When brain death was not confirmed by scintigraphy, elapsed time to certification of death was longer (44.7 vs. 7 h) and organ donation was less common even when a subsequent clinical diagnosis was made. CONCLUSIONS: The results indicate that patient prognosis remains poor regardless of the findings on (99m)Tc-labelled exametazime scintigraphy, but that the scan result influences the elapsed time to withdrawal of therapy or organ donation, providing a significant cost benefit, and occasionally a long-term survivor is seen.

Sentinel node biopsy and lymphoscintigraphy with a technetium 99m labeled blue dye in a rabbit model.

BACKGROUND: Lymphatic mapping for sentinel node biopsy in breast cancer and melanoma usually involves initial peritumoral injection of a radioisotope, gamma camera detection of the sentinel lymph node several hours prior to the operation, and separate perioperative injection of a blue dye. We have developed a combined approach using technetium 99m labeled blue dye (Evans Blue) for use in lymphoscintigraphy that may be injected as a single dose just prior to the operation. METHODS: In an anesthetized rabbit model we dissected a hind limb to display the popliteal node and afferent lymphatic. Technetium 99m Evans Blue ((99m)Tc-EB) (22 MBq; 0.5 mL) was injected subdermally in the dorsum of the paw. Simultaneous digital and gamma camera images were obtained at 14 time intervals to 30 minutes post injection. For each of these time intervals the percentage of radioactivity and percentage blueness of the popliteal node were determined. Urine and afferent lymphatic fluid were analyzed by chromatography. The popliteal node was excised post mortem, placed into solvent solutions and analyzed for blueness and radioactivity. RESULTS: Time-activity curves for radioactivity and time-blueness curves for Evans Blue uptake showed strong correlation (r = 0.958). Lymph analysis suggested (99m)Tc-EB is mainly bound to endogenous proteins. Urine was radioactive but not colored, (99m)Tc-EB being metabolized and excreted in the urine as 1,7-diamino-8-naphthol-2,4-disulfonic acid. Prolonged exposure of node to solvents did not dissociate any blue coloration or radioactivity. CONCLUSIONS: (99m)Tc-EB and Evans Blue are simultaneously retained and concentrated in the sentinel lymph node. This process is rapid and reproducible. (99m)Tc-EB migrates at the same rate as Evans Blue in lymph, where it is transported as bound to endogenous proteins. These dye molecules are metabolized by reductive cleavage in the liver and then excreted renally as colorless, radioactive metabolites. This novel agent has the potential to facilitate lymphatic mapping and subsequent sentinel node biopsy for a range of solid malignancies including breast cancer and melanoma.

Gastric emptying is slow in chronic fatigue syndrome.

BACKGROUND: Gastrointestinal symptoms are common in patients with Chronic Fatigue Syndrome (CFS). The objective of this study was to determine the frequency of these symptoms and explore their relationship with objective (radionuclide) studies of upper GI function. METHODS: Thirty-two (32) patients with CFS and 45 control subjects completed a questionnaire on upper GI symptoms, and the 32 patients underwent oesophageal clearance, and simultaneous liquid and solid gastric emptying studies using radionuclide techniques compared with historical controls. RESULTS: The questionnaires showed a significant difference in gastric (p > 0.01) symptoms and swallowing difficulty. Nocturnal diarrhoea was a significant symptom not previously reported.5/32 CFS subjects showed slightly delayed oesophageal clearance, but overall there was no significant difference from the control subjects, nor correlation of oesophageal clearance with symptoms. 23/32 patients showed a delay in liquid gastric emptying, and 12/32 a delay in solid gastric emptying with the delay significantly correlated with the mean symptom score (for each p < 0.001). CONCLUSIONS: GI symptoms in patients with chronic fatigue syndrome are associated with objective changes of upper GI motility.

Liver density measured by DEXA correlates with serum ferritin in patients with beta-Thalassemia Major.

Patients with beta-Thalassemia Major have a requirement for repeated blood transfusion, which ultimately results in liver iron- and whole body iron-overload. These patients are also at risk of reduced bone mineral density (BMD). Seventeen patients (9 female, age 19-32 yr) were referred for bone density estimations of the hip, spine, and whole body. As well as calculating the usual indices of body composition, we superimposed regions of interest over the liver, and expressed the result as "BMD" (g/cm2). This was compared with the serum ferritin as a noninvasive indication of total body iron status. Twelve patients were studied at least twice, more than 18 mo apart. This group showed a significantly below average BMD (T-spine -2.1, T-femoral neck -1.2, T-whole body -1.7, p < 0.001). The group's hepatic density correlated significantly with initial serum ferritin (r = 0.90, p < 0.001). Changes in individual liver density did not correlate significantly with changes in ferritin levels (p = 0.15), possibly due to wide variability in individual results. DEXA may be a useful noninvasive technique for estimating liver-iron concentration.

Retention and distribution of two 99mTc-DTPA labelled vaginal dosage forms.

UNLABELLED: To objectively evaluate the performance of new vaginal dosage forms, it is important to determine their time of residence and their distribution. This paper describes the in vivo characteristics of a reference and test product in this situation. METHOD: A randomised cross-over study was performed in the same phase of the menstrual cycle in eight pre-menopausal women. The retention and distribution of a commercially available vaginal clotrimazole cream and a test gel product, each "labelled" with 99mTc-DTPA was assessed by gamma scintigraphy for 24 h after administration of the products. Mass balance analysis was attempted by collecting and counting sanitary napkins worn for the study time. RESULTS: Within individuals there was little variation in the clearance of the formulations, but wide variation between individuals with a range between 81 and 1% of the administered doses retained by 24 h. The losses appeared to occur mainly at times of urination with 12 +/- 8% (cream) and 20 +/- 23% (gel) collected on the sanitary napkins, but 46 +/- 34% (cream) and 38 +/- 22% gel activity not accounted for by 24 h. The intravaginal distribution of activity was similar for each product. CONCLUSIONS: Radioactive tracer methods are useful in assessing and comparing vaginal dosage forms.

Same-day lymphoscintigraphy and sentinel node biopsy for early breast cancer.

BACKGROUND: Lymphoscintigraphy and sentinel node biopsy are currently being assessed as an alternative to axillary dissection for staging in early breast cancer. However, little is known about the optimum timing of surgery following injection of the radio-isotope into the breast. The aim of the present study was to establish whether lymphoscintigraphy on the morning of surgery allowed efficacious and accurate sentinel node identification and biopsy. METHODS: We reviewed our experience of 216 consecutive cases of lymphoscintigraphy in early breast cancer using peritumoural injections of technetium99m antimony sulphide colloid and subsequent sentinel node biopsy using a hand-held gamma probe and blue dye. The time interval between radioisotope injection and successful intraoperative identification of the sentinel node was assessed and whether this was associated with certain clinical and histological variables. RESULTS: The sentinel node was identified by lymphoscintigraphy in 160 cases (74%) at a median time duration of 40 min post injection. The median time duration between isotope injection and surgery was 5 h. Of the 160 cases where the sentinel node was visualized at lymphoscintigraphy, sentinel node biopsy was successfully performed in 155 cases (97%). This compares with 25/56 (45%) cases where lymphoscintigraphy failed to localize the sentinel node (P < 0.0001). There was no association found between the injection of the radioisotope greater or less than 5 h before surgery and the successful intraoperative identification of the sentinel node. Failure to identify the sentinel node at lymphoscintigraphy beyond 3 h was associated with a low intraoperative identification rate. There was no correlation found between intraoperative identification of the sentinel node according to the duration of isotope injection in relation to surgery and the various clinical and histological factors assessed. CONCLUSIONS: In our experience, the chance of identifying the sentinel node at the time of surgery does not increase with longer isotope injection duration using technetium99m antimony sulphide colloid. As soon as a sentinel node is identified at lymphoscintigraphy, one can proceed to surgery. Scanning beyond 3 h does not appear to be effective in sentinel node localization. Given that the median time for successful lymphoscintigraphic mapping was only 40 min, lymphoscintigraphy can easily be completed during the morning to allow surgery to take place the same day.

Simultaneous 13C/14C dual isotope breath test measurement of gastric emptying of solid and liquid in normal subjects and patients: comparison with scintigraphy.

BACKGROUND: To develop a simple method for simultaneous solid and liquid gastric emptying assessment using a dual isotope labelled breath test. MATERIAL AND METHODS: 13 patients were given 100 g ground beef labelled with 25 MBq (99m)Tc sulphur colloid and 74 KBq (14)C octanoic acid, and 150 ml 10% glucose drink labelled with 8 MBq (67)Ga citrate and 150 mg (13)C acetate. 10 normal volunteers were given the same test meals but labelled with (14)C and (13)C only. Breath was collected at baseline and regularly for 4 hours. The (14)CO(2) and (13)CO(2) activity was measured with liquid scintillation counting and mass spectroscopy. The times to maximum (14)CO(2) and (13)CO(2), were determined. Comparison was made between times to maximum (14)CO(2) with scintigraphic retention of (99m)Tc at 100 minutes and times to maximum (13)CO(2) with the scintigraphic half-clearance time of (67)Ga. RESULTS: For the solid meal, the times to maximum (14)CO(2) were: 60-120 minutes in the 8 patients with normal gastric emptying of (99m)Tc; 75-145 minutes for the 10 healthy volunteers; 75-180 minutes for the remaining 5 patients with abnormal gastric emptying of (99m)Tc. There was a weak but significant correlation (r = 0.56, p < 0.025) between the time to maximum (14)CO(2) and gastric retention of (99m)Tc at 100 minutes. For the liquid meal, times to maximum (13)CO(2) were: 20-35 minutes for the 4 with normal gastric emptying of (67)Ga; 15-40 minutes for the 10 healthy volunteers; 20-75 minutes for the remaining 9 patients with abnormal gastric emptying of (67)Ga. There was a strong and significant correlation (r = 0.88, p < 0.005) between times to maximum (13)CO(2) and gastric half-clearance time of (67)Ga. CONCLUSIONS: Breath tests utilising test meals labelled with *C isotopes are valid alternatives to scintigraphic studies using (99m)Tc and (67)Ga for the simultaneous assessment of gastric emptying of solids and liquids.

Illicit stimulant use is associated with abnormal substantia nigra morphology in humans.

Use of illicit stimulants such as methamphetamine, cocaine, and ecstasy is an increasing health problem. Chronic use can cause neurotoxicity in animals and humans but the long-term consequences are not well understood. The aim of the current study was to investigate the long-term effect of stimulant use on the morphology of the human substantia nigra. We hypothesised that history of illicit stimulant use is associated with an abnormally bright and enlarged substantia nigra (termed 'hyperechogenicity') when viewed with transcranial sonography. Substantia nigra morphology was assessed in abstinent stimulant users (n = 36; 31±9 yrs) and in two groups of control subjects: non-drug users (n = 29; 24±5 yrs) and cannabis users (n = 12; 25±7 yrs). Substantia nigra morphology was viewed with transcranial sonography and the area of echogenicity at the anatomical site of the substantia nigra was measured at its greatest extent. The area of substantia nigra echogenicity was significantly larger in the stimulant group (0.273±0.078 cm(2)) than in the control (0.201±0.054 cm(2); P<0.001) and cannabis (0.202±0.045 cm(2); P<0.007) groups. 53% of stimulant users exhibited echogenicity that exceeded the 90(th) percentile for the control group. The results of the current study suggest that individuals with a history of illicit stimulant use exhibit abnormal substantia nigra morphology. Substantia nigra hyperechogenicity is a strong risk factor for developing Parkinson's disease later in life and further research is required to determine if the observed abnormality in stimulant users is associated with a functional deficit of the nigro-striatal system.