Differential effects of nicotine on P50 amplitude, its gating, and their neural sources in low and high suppressors.

Sensory gating impairment in schizophrenia has been documented in the form of aberrant middle latency P50 event-related brain potential responses to S(1) and/or S(2) stimuli in a paired (S(1)-S(2)) auditory stimulus paradigm. Evidenced by a failure to suppress S(2) P50 or by attenuated S(1) P50s, these sensory deficits have been associated with increased smoking behaviour in this disorder, and may be related to the putative ameliorating effects of smoke-inhaled nicotine on neural mechanisms regulating gating. Comparison of healthy controls with low versus high gating efficiency has been forwarded as a model for investigating the actions of antipsychotic agents on aberrant gating functions. In the current study, the effect of a single dose (6 mg) of nicotine gum on P50, gating indices, and their cortical sources indexed with sLORETA (standardized low resolution electromagnetic tomography), was examined in healthy non-smokers (n=24) stratified for low and high gating levels. Scalp surface recordings revealed nicotine modulation of P50 and its gating to be differentially exhibited in high (decreasing gating) and low (increasing gating) suppressors while the underlying cortical sources influenced by nicotine (middle frontal gyrus, inferior/superior parietal lobules, pre- and post-central gyri) were seen only in low suppressors. These findings suggest that nicotine impacts sensory gating in healthy volunteers and as the gating enhancing effects were dependent on low baseline gating efficiency, nicotinic receptor agonists may be associated with unique P50 modulating actions in schizophrenia.

Effectiveness of immediate preoperative injection of radiopharmaceutical and blue dye for sentinel node biopsy in patients with breast cancer.

BACKGROUND: Sentinel node biopsy (SNB) in breast cancer conventionally utilises a preoperative radioisotope injection and lymphoscintigraphy, which is time consuming and painful. The aim of this study was to evaluate a potentially more efficient and practical technique of immediate preoperative injection of blue dye and radiopharmaceutical by the surgeon (without involvement of a nuclear medicine department). METHOD: One hundred and sixty three clinically node negative patients with invasive breast cancer undergoing breast-conserving surgery were included. The radiopharmaceutical was delivered to the operating suite and injected by the surgeon in the subareolar region immediately after induction of anaesthesia. Sentinel node biopsy was performed in conjunction with removal of any palpable axillary lymph nodes (axillary node sampling). RESULTS: Sentinel nodes (SNs) were detected in 161 of 163 women. On average, 3.0 sentinel nodes were identified. Twenty nine patients had involved nodes of whom 28 had a positive sentinel node. Of the two patients with failed identification, one had involved axillary lymph nodes on sampling and the other had an involved intramammary lymph node. CONCLUSION: This method produces results identical to those obtained with other techniques. This study shows that sentinel node biopsy can be performed safely without involvement of a nuclear medicine department with the added benefits of no preoperative injection and improved efficiency in the operating suite.

Evaluation of an experimental system for the in vitro assessment of ultrasonic contrast agents.

The ultrasonic properties of microbubble contrast agents need to be fully understood if reproducible images and quantitative results are to be produced. Additional aspects of the physical and chemical environment into which the contrast agents are introduced also need to be taken into account, and their effect on contrast agent performance evaluated. A setup that provides an accurate and reproducible data-acquisition system is presented and evaluated in this paper. The linear range of this system is assessed, as well as its accuracy and precision. A new approach to the investigation of contrast agents, based on normalised backscatter, is discussed. Also, a common technique of degassing, widely used in other areas, is described and evaluated to determine its appropriateness to contrast agent studies.

A randomized controlled trial of fall prevention strategies in old peoples' homes.

BACKGROUND: Falls are a major cause of morbidity in old age. A small number of fall prevention trials in cognitively intact community-dwelling older people have been effective. This study set out to examine the preventability of falls in older people living in institutional care. OBJECTIVE: To evaluate the effectiveness of falls risk factor assessment/modification and seated balance exercise training in reducing falls among elderly people living in residential care. METHODS: 133 residents with a mean age of 84+/- (SD) 6.8 years were allocated at random by home to receive either a 6-month falls risk factor assessment/modification and seated balance exercise training programme (n = 77) or 6 months of reminiscence therapy (n = 56). The risk factors targeted were postural hypotension, polypharmacy, visual acuity, and ambient lighting levels. Falls risk factor assessments and recommendation for modifications were performed at baseline in the intervention group and assessments repeated at 6 months. Functional reach, reaction time, timed up-and- go, grip strength, spinal flexibility, and Philadelphia Geriatric Centre Morale Scale and Mini-Mental State Examination scores were determined at baseline and at 6 months by a 'blind' observer. Falls and fractures were then monitored in both groups during a 7- to 12-month falls-monitoring follow-up period. RESULTS: Only 90 of 133 (67.7%) residents completed the 6-month intervention period, and 84 (63.2%) completed the 7- to 12-month falls-monitoring follow-up period. Both prevalence of postural hypotension (p = 0.0005) and poor visual acuity (p = 0.04) were reduced in the intervention group. There was no difference between the groups in the number of falls sustained, the risk of falling [odds ratio 0.45 (95% CI 0.19-1.14)], or in the risk of recurrent falling [odds ratio 1.07 (95% CI 0.40-2.97)]. No significant differences were found between the groups with regard to change in other outcome measures. CONCLUSIONS: The high drop-out rate reduced the power of this study to detect any effect of the interventions used. It is possible that either the exercises were not sufficiently vigorous or that to improve balance exercises must be performed standing. Further research is required to identify effective fall prevention strategies for elderly people in residential settings.

Artefacts in the thin-layer chromatographic analysis of 99Tcm-tetrofosmin injections.

In an evaluation of techniques for dispensing 99Tcm-tetrofosmin injections, variability in radiochemical purity measured by the recommended 'cut-and-count' thin-layer chromatographic (TLC) analytical technique was observed. This was due to inconsistency in the position of the 99Tcm-tetrofosmin on the chromatography plate. An investigation was therefore undertaken to identify the factors which influence the Rf value of 99Tcm-tetrofosmin and the subsequent effect on the values obtained in the measurement of radiochemical purity. TLC was performed on an ITLC/SG stationary phase with a mobile phase of dichloromethane:acetone (65:35). On a satisfactory chromatogram, the main peak had an Rf of approximately 0.5 and the radiochemical purity was measured at > 90%. The Rf of the main peak and the measured radiochemical purity were found to increase as the size of the sample applied to the plate was increased. Force-drying the sample spot after application to the TLC plate gave a single peak with an Rf of 0. The dimensions of the tank and the time allowed for mobile phase saturation did not affect the outcome of the analysis. Small variations in the composition of the mobile phase affected the Rf of the main peak but not the measured radiochemical purity. TLC plates that were dried at 11 degrees C before use were found to give distorted chromatograms and unreliable measurements of radiochemical purity. In conclusion, when using TLC to measure the radiochemical purity of 99Tcm-tetrofosmin, the following precautions should be observed: (1) the sample spot applied to the TLC plate should be in the range 10-20 microliters; (2) the spot should not be force-dried with air; and (3) ITLC/SG plates should not be dried before use.

Preparation of 99Tcm-MAG3: no confirmation that sodium chloride injections from plastic containers affect radiochemical purity.

Reports have suggested that when sodium chloride injections from a plastic ampoule are used during the preparation of 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3), the radiochemical purity of the final product might be reduced. A study was therefore undertaken to examine the effect of sodium chloride injections from five manufacturers on the radiochemical purity and stability of 99Tcm-MAG3. One sodium chloride injection was supplied in a glass vial, three in plastic ampoules and one in a plastic infusion bag. Three batches of sodium chloride injections from each manufacturer were tested. The radiopharmaceutical was prepared at a radioactive concentration of 1.1 GBq in 10 ml according to the instructions of the manufacturer of TechneScan MAG3. Analysis of radiochemical purity was performed by high-performance liquid chromatography immediately after preparation and 6 h later. Using 95% as the minimum acceptable radiochemical purity, all the products were satisfactory over the 6 h test period. No manufacturer's sodium chloride injection was found to have a statistically significant effect on the radiochemical purity. Based on the 15 batches of sodium chloride injection tested, this study cannot confirm that sodium chloride injections from a plastic container affect the radiochemical purity of 99Tcm-MAG3. However, in view of the known sensitivity of some 99Tcm radiopharmaceuticals to external influences, it is probably good practice to test radiochemical purity when new batches of ancillary materials, such as sodium chloride injections, are introduced.

A comparison of three methods of measuring 99mTc-DTPA lung clearance and their repeatability.

The lung clearance of technetium-99m diethylenetriamine penta-acetic acid (99mTc-DTPA) is a measure of respiratory epithelial permeability. Many factors may contribute to the wide range of normal values, including the method of correction for background activity. The aim of this study was to compare three methods of analysis, including their repeatability. 99mTc-DTPA lung clearance imaging was performed on eight nonsmokers (age 32+/-2 yrs, forced expiratory volume in one second (FEV1) 102.8+/-3.3% predicted yrs, mean+/-SEM and seven smokers (age 46+/-4 yrs, p<0.01, versus nonsmokers; FEV1 88.9+/-8.9%, p<0.05 versus nonsmokers) on two occasions each. The smokers were asked to refrain from smoking for 12 h. An uncorrected analysis was compared with two methods corrected for recirculating background activity using an intravenous correction and inter-renal and shoulder background regions of interest. The uncorrected method gave higher mean values for 50% lung clearance of 99mTc-DTPA (t50) values than the inter-renal (p<0.001) and shoulder (p<0.001) methods of correction in nonsmokers and the inter-renal method gave lower values than the shoulder-corrected method (p<0.05). In smokers there was no difference. There were no differences in mean t50 values obtained on two separate visits. There was no difference in the repeatability of the three methods of analysis. The three methods of analysis produced comparable results with no differences in repeatability.

A computer database for the preparation of transport documents for radiopharmaceuticals.

The preparation of radiopharmaceuticals in central radiopharmacies for distribution to several hospitals is practised widely. Transport of the radiopharmaceuticals is usually by road and this activity is regulated by legislation. Two requirements of the legislation are that the consignor issues a transport document for each consignment and maintains a record of all transport of radioactive material. This paper describes a computer database that has been developed for use in a central radiopharmacy to achieve these requirements.

Validation of a technique for the preparation of individual patient doses of 14C-urea.

A breath test employing 14C-urea is commonly used to detect the presence of Helicobacter pylori in the stomach of patients with peptic ulcer. 14C-urea is not available commercially as a radiopharmaceutical. It is available only as non-pharmaceutical grade material. A technique for preparing individual patient doses was therefore validated and methods for demonstrating the quality of the 14C-urea raw material and final product were developed. Individual patient doses, each containing 100 kBq 14C and 350 mg urea in 1 ml, were prepared and stored at -20 degrees C. Each batch consisted of approximately 400 doses. The activities of samples from each batch were measured by liquid scintillation counting immediately after preparation (99.6 +/- 4.9 kBq) and 6 months later (98.2 +/- 4.7 kBq). The chemical identity of the 14C-urea was demonstrated by a thin-layer chromatographic technique in which the 14C was shown to have the same Rf value as stable urea. The high radiochemical purity of the final product was demonstrated by the presence of only one peak on the thin-layer chromatogram. The radionuclide identity of the 14C-urea was demonstrated by beta-ray spectroscopy. This technique of preparing individual patient doses of 14C-urea results in a product that is stable for at least 6 months.

Effect of source and age of sodium pertechnetate Tc 99m on radiochemical purity of technetium Tc 99m exametazime.

The radiochemical purities of technetium Tc 99m exametazime prepared with one-hour-old or six-hour-old sodium pertechnetate Tc 99m from two manufacturers' generators were compared. Eluates from each manufacturer's generators were diluted immediately to provide two solutions of sodium pertechnetate Tc 99m. For the one-hour-old solution, eluate was diluted with 0.9% sodium chloride injection to a concentration of radioactivity of 38 mCi in 5.5 mL and used one hour later. For the six-hour-old solution, eluate was diluted to 65 mCi in 5.5 mL and used six hours later. Technetium Tc 99m exametazime was prepared by injecting 5.0 mL of one of the solutions into an exametazime kit to provide 30 mCi of technetium Tc 99m in 5.0 mL. At 2, 30, and 60 minutes after reconstitution of each kit, the radiochemical purity was measured by high-performance liquid chromatography with radiation detection. At two minutes, all the preparations retained high radiochemical purities. However, at 30 and 60 minutes, the radiochemical purities of technetium Tc 99m exametazime prepared with six-hour-old sodium pertechnetate Tc 99m were significantly lower than those of technetium Tc 99m exametazime prepared with one-hour-old sodium pertechnetate Tc 99m. Similar results were found for each manufacturer's generators. The radiochemical purity of technetium Tc 99m exametazime was affected by the age of the sodium pertechnetate Tc 99m from which it was prepared but not by the generator from which the sodium pertechnetate Tc 99m was obtained.

A routine method for using sodium iodide to stabilize sodium pertechnetate [99Tcm] dispensed for the preparation of 99Tcm-exametazime.

When preparing 99Tcm-exametazime, it is important to use sodium 99Tcm-pertechnetate that is less than 2 h old. The addition of sodium iodide (NaI) to 99Tcm-pertechnetate is known to extend this time to 6 h. This paper describes a technique for implementing this in routine practice. Sterile kits consisting of 440 micrograms NaI and 1.0 ml sodium chloride injection in a vial with a nitrogen atmosphere were prepared and stored at room temperature, 4 degrees C and -22 degrees C. Titrimetric analysis of iodide showed that under each storage condition, kits were stable for 8 weeks. To determine the effectiveness of the kits, the radiochemical purity (RCP) of 99Tcm-exametazime was measured by high-performance liquid chromatography (HPLC). The validity of this technique was determined by simultaneous analysis with the conventional thin-layer/paper chromatography (TLC/PC) technique on 24 occasions, over a range of RCP (94.5-54.6%). Radiochemical purities measured by HPLC and TLC/PC were 81.2 +/- 10.2 and 81.5 +/- 10.5%, respectively, and did not differ significantly (P greater than 0.30). The correlation between the techniques was high (r = 0.98). 99Tcm-exametazime was prepared using 1 h-old 99Tcm-pertechnetate, 6 h-old 99Tcm-pertechnetate and 6 h-old 99Tcm-pertechnetate dispensed in a NaI kit. At the recommended expiry time for this radiopharmaceutical, i.e. 30 min after preparation, RCPs were found to be 88.4 +/- 2.4, 80.9 +/- 2.0 and 89.3 +/- 3.0%, respectively (n = 5 for each technique).(ABSTRACT TRUNCATED AT 250 WORDS)

99Tcm-MAG3: in vitro stability and in vivo behaviour at different times after preparation.

A kit for preparing technetium-99m mercaptoacetyltriglycine (99Tcm-MAG3), a new radiopharmaceutical for gamma camera renography, is available commercially. A drawback to the use of this kit is the recommended 1h expiry for 99Tcm-MAG3. This short expiry is a consequence of the possible growth of an impurity which undergoes hepatobiliary excretion and might interfere with renal imaging. Radiochemical purity of 99Tcm-MAG3 was measured by high performance liquid chromatography at 0, 1 and 6 h after preparation and was found to be consistently greater than 95. 99Tcm-MAG3 was shown to contain five impurities, one of which increased from 0.5% to 1% over 6 h. Dilution of 99Tcm-MAG3 eliminated this effect. A two-part clinical study was undertaken. For Part I, 99Tcm-MAG3 was prepared at 400 MBq/4 ml. For Part II, 99Tcm-MAG3 was prepared at 1 GBq/4 ml then subdivided and diluted to give single doses of 175 MBq/2.5 ml. In both parts, 10 patients were injected within 1 h after preparation and 10 were injected 5-6 h after preparation. From gamma camera images of the abdomen acquired 30 min after injection, the % injected 99Tcm in gall bladder and liver were calculated. In both parts, the % injected 99Tcm in gall-bladders and livers of the 1 h group were compared with those in the 5-6 h group and not found significantly different (p greater than 0.05). In conclusion, 99Tcm-MAG3 prepared according to the methods described, can be used up to 6 h after preparation.

A comparison of cobalt (57Co) bleomycin scanning and contrast-enhanced CT scanning for assessment of the mediastinum in lung cancer.

Sixty patients with histologically proven lung cancer who had been accepted for mediastinoscopy or thoracotomy were prospectively entered into a study to evaluate computed tomographic (CT) scanning, 57Co-bleomycin scanning, and barium swallow in preoperative assessment of mediastinal lymph node metastasis. Fifty-six patients had thoracotomy at which all accessible lymph nodes were sampled. Twenty-four patients were found to have mediastinal tumor on histologic analysis of the resected mediastinal lymph nodes. Neither 57Co-bleomycin scanning nor barium swallow were clinically useful, with sensitivities of 21 percent and 11 percent respectively, whereas CT scanning was helpful. However, there was no clear cutoff point of node size to optimize sensitivity and specificity for CT scanning. When nodes greater than or equal to 15 mm were taken to indicate likely malignancy, the sensitivity was 58 percent and the specificity was 87 percent and when greater than or equal to 10 mm was used the sensitivity was 80 percent but the specificity was only 55 percent. There was no clear relationship between the size of the largest resected lymph node in each patient and the presence of malignant lymph nodes. Only 42 percent of patients with resected nodes greater than or equal to 2 cm had histologic evidence of metastases. We conclude that CT scanning should be used to indicate the presence and site of mediastinal lymph nodes, which, when visualized, should always be sampled and histologically examined prior to resection of primary tumor.

An investigation of factors that might influence the radiochemical purity and stability of 99mTc-MAG3.

Technetium 99m mercaptoacetyltriglycine (99mTc-MAG3) was prepared from a commercial kit by various techniques to assess the effect of a number of variables on radiochemical purity and stability. Its radiochemical purity was determined by high performance liquid chromatography at 0 and 6 h after preparation and was found to be consistently greater than 95%. It has been demonstrated that the radiochemical purity of 99mTc-MAG3 prepared according to the manufacturer's instructions is not influenced by the volume of 99mTc generator eluate used, agitation, the presence of air in the reaction vial or the use of a 99mTc generator eluate with a 99Tc:99mTc ratio of 16:1. A modified method of preparation in which the MAG3 kit is reconstituted with saline before addition of 99mTc-pertechnetate has been shown to yield a satisfactory product and should help to minimise the radiation dose to the fingers of radiopharmacy staff.

Neutrophil activation during cell separation procedures.

Leucocytes labelled with 111In or 99Tcm are used as diagnostic agents for detecting sites of infection by scintigraphy. Before radiolabelling is performed, leucocytes are isolated from whole blood. The effect of isolation procedures on neutrophil activation has been studied by measuring the neutrophil elastase produced during incubation of whole blood with three erythrocyte sedimentation agents (dextran 70, hydroxyethyl starch and methylcellulose) and two density gradient media (Percoll and Mono-Poly Resolving Medium). Neutrophil elastase was measured using a standard radioimmunoassay. At 21 degrees C, dextran caused no elastase release while hydroxyethyl starch and methylcellulose induced significant release (p = 0.01 and p less than 0.01 resp.). All three agents caused significant elastase release at 37 degrees C. When whole blood was incubated with Percoll and Mono-Poly Resolving Medium, no release of neutrophil elastase was observed. These results show that neither density gradient medium induces neutrophil activation but that certain erythrocyte sedimentation agents do. Of the three sedimentation agents investigated, dextran is the agent of choice if neutrophil activation is to be minimized.