The production of monodisperse explosive particles with piezo-electric inkjet printing technology.

We have developed a method to produce discrete microparticles from compounds dissolved in nonpolar or polar solvents using drop-on-demand inkjet printer technology. A piezoelectric inkjet printhead located atop a drying tube produces precise droplets containing defined quantities of analyte. Droplets solidify into microparticles with known composition and size as they traverse down the drying tube. Because this is a drop-on-demand printing process, a known number of droplets are produced providing quantitative particle delivery to a variety of substrates. Particular emphasis is placed on the development and characterization of the drying tube in this work. The drying tube was modeled using computational fluid dynamics and experimentally evaluated using laser-based flow visualization techniques. A notable design feature of the drying tube is the ability to push heated air through the tube rather than the need to pull air from the exit. This provides the ability to place a known number of well-defined particles onto almost any substrate of interest, rather than having to collect particles onto a filter first and then transfer them to another surface. Several types of particles have been produced by this system, examples of which are pure particles of cyclotrimethylenetrinitramine ranging from 10 µm to 30 µm in diameter, and ammonium nitrate particles of 40 µm diameter. The final particle size is directly related to the solute concentration of the printing solution and the size of the initial jetted droplet.

Synergistic anorectic effect of dehydroepiandrosterone and d-Fenfluramine on the obese Zucker rat.

Fasted obese, female Zucker rats accustomed to eating a single high fat meal within 1 h a day were treated with intraperitoneal injections of dehydroepiandrosterone (DHEA) and dextrofenfluramine (d-fen), either individually or in combination. Caloric intake was measured over a 1-h period 2 h after drug administration, and results compared to that of vehicle-treated controls. At 50 mg/kg body weight, DHEA did not affect food intake. At doses of < or = 2 mg/kg d-fen did not affect food intake. Together, however, DHEA 50 mg/kg and d-fen < or = 2 mg/kg significantly decreased food intake. At doses of > or = 3 mg/kg d-fen diminished caloric intake by itself, and the addition of DHEA significantly augmented this effect. Neurotransmitter levels in select regions of the hypothalamus of animals treated using a similar drug protocol showed several changes in the levels of serotonin and its metabolite 5 hydroxyindole acetic acid (5-HIAA). It is hypothesized that DHEA augments the production of serotonin while d-fenfluramine enhances its release, and together these two actions may account for the synergistic action of DHEA and d-fenfluramine.

Elemental and molecular imaging of human hair using secondary ion mass spectrometry.

Secondary ion mass spectrometry (SIMS) is used to image the spatial distribution of elemental and molecular species on the surface and in cross sections of doped human hair using a magnetic sector SIMS instrument operated as an ion microprobe. Analysis of electrically insulating, non-planar hair samples requires one of two different methods of charge compensation to be used depending on the polarity of the sputtered secondary ions. For detection of positive secondary ions, the hair is imaged using a approximately 0.5 micron diameter, 19.5 keV impact energy, O- microbeam with no auxiliary electron bombardment. For detection of negative secondary ions, a approximately 0.2 micron diameter, 14.5 keV impact energy Cs+ microbeam is used in conjunction with normal incidence, low-energy electron bombardment. Both of these methods allow submicrometer spatial resolution elemental and molecular secondary ion images to be obtained from hair samples without metallic coating of the sample surface prior to analysis. Several examples are presented that reflect potential application areas for these analytical methods.

Preliminary evaluation of an SF5+ polyatomic primary ion beam for analysis of organic thin films by secondary ion mass spectrometry.

Organic vapor deposited thin films of pure biomolecules, polymer films and biomolecules dispersed in gelatin and biological tissue have been analyzed in a magnetic sector secondary ion mass spectrometer using an SF5+ primary ion beam at keV impact energies. In comparison to Ar+ bombardment under identical conditions, bombardment with SF5+ gives a 10 to 50 fold enhancement in the secondary ion yields for characteristic molecular ions. The SF5+ primary ion beam can be focussed to a small spot allowing molecular ion images to be obtained at micrometer spatial resolution with enhanced sensitivity. More importantly, the decay in molecular ion signal as a function of primary ion dose commonly observed in SIMS using monoatomic primary ions is either eliminated or greatly reduced, allowing molecular depth profiles to be obtained of organic thin films. By continuing to sample intact molecules as sputtering proceeds into the sample, the total number of detected characteristic secondary ions is increased by as much as a factor of approximately 700 for SF5+ bombardment as compared to Ar+ bombardment under identical analytical conditions. This effect is thought to be a result of the high erosion rate and the low penetration depth inherent in the use of a polyatomic primary projectile.

A structured approach to the interpretation and reporting of ventilation/perfusion scans.

The aim of this study was to develop a structured approach to the reporting and in particular the clinical interpretation of ventilation/perfusion (V/Q) scan results. An initial audit indicated that there were significant variations in the clinical management of patients particularly after a non-diagnostic V/Q scan report. There were also differences in the approaches used to interpret the scan itself. In an attempt to improve this, a set of interpretation guidelines was produced based on the revised PIOPED data. To combat the problems with clinical interpretation, a standard method for assessing the pre-test clinical probability of pulmonary embolism was established. This clinical risk was then combined with the V/Q scan result to give an overall probability for the presence of pulmonary embolism. The more precise risk stratification which resulted allowed explicit clinical advice on patient management to be incorporated into the final report. A second audit was performed with the revised methodology in place. The level of inter-observer variability for scan reporting decreased from 30% to 12%. The prior assessment of clinical risk and the standardized method of combining this with the scan result led to an improvement in patient management. This was particularly true for the non-diagnostic group, in whom additional investigations were more appropriately used. A structured approach which allows the pre-test probability of pulmonary embolism to be combined in an explicit fashion with the V/Q scan result can provide a more precise risk stratification allowing appropriate recommendations to be made. Such an approach can result in improved patient management.

Comparison of mean cerebral transit time and single-photon emission tomography for estimation of stroke outcome.

Mean cerebral transit time (MCTT) scanning is a possible alternative to cerebral single-photon emission tomography (SPET) for early assessment of cerebral perfusion after acute ischaemic stroke. Although MCTT is rapid, inexpensive and does not require sophisticated equipment, the relationship between MCTT and functional outcome is unknown. This study aimed to compare the effectiveness of SPET and MCTT in the prediction of functional outcome. Sixty-three patients undergoing cerebral computed tomography (CT), technetium-99m MCTT, and technetium-99m-labelled hexamethylpropylene amine oxime SPET soon after acute ischaemic stroke had outcome assessed after 3 months. Cerebral CT, SPET and MCTT scans were interpreted without reference to the clinical data; a single independent observer assessed outcome using the Barthel Index. The 3-month Barthel score in survivors was significantly correlated with volume of lesion on SPET (Spearman's r=-0.425, P<0.005) and with the ratio of mean affected hemisphere transit times to mean unaffected hemisphere transit times (Spearmen's r=-0.356, P <0.01), but not with CT lesion volume (Spearman's r = -0.175, P >0.1). Stepwise logistic regression identified volume of lesion on SPET as the only significant predictor of good functional outcome (Barthel score>70). The overall predictive accuracy was 73%. It is concluded that MCTT, although significantly correlated with functional outcome, failed to predict good functional recovery in individual stroke survivors. Since SPET provides more detailed localisation of perfusion deficits, and since SPET lesion volume can be used to predict functional outcome, SPET remains preferable to MCTT when perfusion imaging is required.

A reappraisal of current methods for the assessment of planar gamma camera performance.

This study reappraises the acquisition parameters defined by three current protocols for the specification of planar gamma camera performance. These are the manufacturer Standards of the National Electrical Manufacturers' Association [1] and the International Electrotechnical Commission [2], and the user-orientated protocol of the UK Department of Health (DoH, formerly DHSS) Gamma Camera Performance Assessment Group [3]. The study looks specifically at three major planar performance characteristics: intrinsic non-uniformity, intrinsic spatial resolution and intrinsic non-linearity (spatial distortion). Acquisition parameters specified for these characteristics are investigated by testing a range of values for each parameter around those figures currently advocated by the three protocols. Those acquisition parameters which may be relaxed without loss of data integrity are identified and the adoption of revised parameters for some measurements within the DoH assessment protocol is suggested. Reviewing the data obtained, observations are made regarding the accuracy of some tests performed regularly for quality control purposes. The feasibility and advantages of incorporating some suitably modified DoH performance assessment tests within a routine quality assurance protocol for the gamma camera are also discussed.

Lack of effect of concomitant clobazam on interictal 123I-iomazenil SPECT.

Single photon emission computed tomography (SPECT) is being increasingly used as an adjunctive technique in the localisation of epileptogenic foci prior to surgery. Fourteen patients (five male, nine female; mean age 31 years) with refractory complex partial seizures, all of whom had abnormal 99Tc HM-PAO SPECT scans, were imaged again using the benzodiazepine receptor ligand 123I-iomazenil. Eleven of these patients displayed the same abnormality on both scans. The magnitude of the deficit, however, was slightly greater (P < 0.05) on the iomazenil scan compared with the HM-PAO study. These 11 patients were then randomised into two groups. Group 1 (n = 7) received clobazam 20 mg/day for a minimum of 7 days before a second iomazenil study was performed. Patients in group 2 (n = 4) underwent a second iomazenil scan at the same time interval as those in group 1, but without the additional clobazam. The resultant scans were reported blind to treatment. There were no qualitative or quantitative differences between the first and second iomazenil studies in either group. Patients can be imaged using 123I-iomazenil without withdrawing clobazam therapy. From this preliminary study, there seems little advantage in using iomazenil in place of HM-PAO to delineate the extent of the zone of epileptogenesis. Whether iomazenil SPECT will prove to be more sensitive in identifying the site of the epileptic focus remains to be determined.

Formation and emission of tetraalkylammonium salt molecular ions sputtered from a gelatin matrix.

A gelatin matrix was simultaneously doped with nine equimolar, homologous, tetraalkylammonium salts ranging in mass from 210 to 770 Da. Bombardment of the sample with kiloelectronvolt ions resulted in a nonidentical distribution of relative cation intensities with a maximum at m/z 242 for samples with a total salt concentration of 0.004 g of salt/g of gelatin. A rapid increase in relative intensities with increasing mass is observed for the low mass salts and is believed to be linked to changes in the ionization efficiencies. The changes in ionization efficiencies are likely related to decreasing coulombic attractive forces between the organic cation and the counterion. Disappearance cross sections, determined from decay curves, indicate that sputter-induced damage increases with increasing mass of the cation. Fragment-to-intact cation ratios also suggest that damage accumulates fastest in the heaviest salts. These observations indicate that desorption yields of the organic salts in a gelatin matrix decrease with increasing mass. In addition, suppression of lower mass tetraalkylammonium salt intact cation intensities was observed for salt-in-gelatin concentrations greater than 10(-3) g/g.

Doped gelatin films as a model matrix for molecular secondary ion mass spectrometry studies of biological soft tissue.

Porcine gelatin films doped with a number of biological compounds at various concentrations and prepared by spin-casting have been used as model biological tissue matrices for studying organic ion emission in molecular secondary ion mass spectrometry. For many compounds, portions of the working curves were found to be linear over several orders of magnitude in concentration. Detection limits for the, analyzed compounds were in the parts per million range for several organic salt compounds but high (0.1 wt%) for others. Owing to the presence of a significant chemical background, the poorest detection limits were generally obtained from compounds with low molecular weights. Secondary ion yield matrix effects, indicated by a reduction in ionization efficiency at higher concentrations, were observed for several organic salt compounds.

Interictal HM-PAO SPECT: a routine investigation in patients with medically intractable complex partial seizures?

Single photon emission computed tomography (SPECT) is increasingly being used as an adjunctive technique in the localisation of epileptogenic foci prior to surgery. As yet, few studies have been undertaken to establish the clinical associations of areas of reduced cerebral perfusion. Sixty-three consecutive patients (15 male, 48 female; median age 30 years, range 14-57 years) with medically intractable complex partial seizures (median/month 8, range 1-36) were investigated as outpatients. All had normal high resolution computerised X-ray tomography (CT) of brain. Twenty-seven (47%) exhibited significant perfusion defects on SPECT scanning with a rotating gamma camera system using Tc-99 HM-PAO. There were no significant differences between patients with normal and abnormal scans in terms of age at scanning or at onset of epilepsy or number of seizures. Patients with perfusion defects did, however, have longer median histories of epilepsy than those with normal scans (normal: 10 years, abnormal: 22 years; P = 0.01). Patients with abnormal scans were no more likely to have suffered febrile convulsions in early childhood. The correlation of abnormal SPECT scans with routine surface EEG recordings was poor with only 41% of cases showing clear agreement between the site of hypoperfusion and focal epileptic activity. It is not yet possible to predict clinically those patients who will exhibit perfusion defects on interictal TC-99 HM-PAO SPECT scanning.

An investigation of the magnitude and causes of count loss artifacts in SPECT imaging.

A quantitative evaluation and an investigation of the mechanism of the count losses that can occur in SPECT imaging is described. The most common clinical example of the artifacts which result from this is encountered when sections are taken through the femoral heads in skeletal studies of the pelvis. From some simple phantom studies, it was identified that the count losses were associated with the presence of a high dynamic range in the projection data. Further information was obtained from simulation studies. It was found that the count loss phenomenon is caused by the combined effects of the presence of a high count density area and a structure with a relatively high attenuation level. An appreciation of the presence, magnitude, and mechanism of this effect is important if erroneous clinical findings are to be avoided. This is particularly relevant because of the existence of a variety of techniques that can be used to remove the resulting artifacts.

Molecular ion imaging and dynamic secondary ion mass spectrometry of organic compounds.

An ion microscope equipped with a resistive anode encoder imaging system has been used to acquire molecular secondary ion images, with lateral resolution on the order of 1 microns, from several quaternary ammonium salts, an amino acid, and a polynuclear aromatic hydrocarbon which were deposited onto copper transmission electron microscope grids. All images were generated by using the secondary ion signal of the parent molecular species. The variation of parent and fragment molecular ion signals with primary ion dose indicates that, for many bulk organic compounds, bombardment-induced fragmentation of parent molecules saturates at primary ion doses of (1-8) X 10(14) ions/cm2. Subsequent ion impacts cause little further accumulation of damage in the sample, and intact parent molecular ions are sputtered even after prolonged ion bombardment (i.e. primary ion doses greater than 1 X 10(16) ions/cm2). This saturation process allows molecular images to be obtained at high primary ion doses and allows depth profiles to be obtained from simple molecular solid/metal test structures.

Cardiac responses to acute insulin-induced hypoglycemia in humans.

The effects of acute hypoglycemia on the heart and cardiovascular system were examined in humans using radioisotopic techniques, complemented by measurement of heart rate and blood pressure. The heart rate increased from 62 +/- 3 to 87 +/- 3 beats/min in response to hypoglycemia; this increase was accompanied by a significant increase in systolic blood pressure, a fall in diastolic blood pressure, with no change in the mean arterial blood pressure. The left ventricular ejection fraction increased from 47 +/- 3 (SE) to 72 +/- 5% in response to hypoglycemia. The increases in heart rate and ejection fraction were abolished during parenteral nonselective beta-adrenergic blockade with propranolol but were unaffected by either alpha-adrenergic blockade with phentolamine or cholinergic blockade with atropine. During beta-adrenergic blockade, there were significant increases in diastolic and mean arterial blood pressure in response to hypoglycemia. During alpha-adrenergic blockade the systolic, diastolic, and mean arterial pressures fell significantly after hypoglycemia. The blood pressure responses to hypoglycemia were unaffected by cholinergic blockade. Thus the increases in ejection fraction and in heart rate in response to hypoglycemia are mediated by beta-adrenoreceptors, whereas the blood pressure responses to hypoglycemia are mediated by alpha- and by beta-adrenoreceptors.

Splenic responses to acute insulin-induced hypoglycaemia in humans.

1. The effects of acute hypoglycaemia on the spleen were examined in normal humans using radioisotopic techniques, complemented by ultrasonic examination of the spleen. Hypoglycaemia had a modest effect on splenic area, measured by ultrasonography, which declined to 62 +/- 6% (mean +/- SEM) of the basal value after the onset of the acute hypoglycaemic reaction. 2. Hypoglycaemia had a pronounced effect on the splenic radioactivity, which decreased significantly to a mean of 10 +/- 7% of basal radioactivity at 15 min after the onset of hypoglycaemia. The splenic image completely disappeared at some time after hypoglycaemia in all subjects. 3. The reduction of splenic radioactivity was abolished during non-selective alpha-adrenergic blockade with phentolamine, but was unaffected by beta-adrenergic blockade with propranolol, or cholinergic blockade with atropine, which suggests that the response of vessels perfusing the spleen is mediated by alpha-adrenoceptors.

Simultaneous measurement of left ventricular function and perfusion.

A new radiopharmaceutical, methylisobutyl isonitrile (MIBI), has been developed as a technetium-99m-labelled alternative to thallium 201 for myocardial imaging. By virtue of the high specific activity of 99mTc, some 600 MBq may be administered as a 0.3 ml bolus, permitting the acquisition of a first-pass nuclear angiogram at rest and at peak exercise. The agent was assessed in ten sequential patients referred for routine cardiac catheterisation, who also underwent an exercise electrocardiographic (ECG) test. Good quality nuclear angiograms, planar perfusion and tomographic perfusion images were obtained; the results correlated well with the catheterisation data. Of 30 myocardial segments for which wall motion was judged normal/abnormal from the nuclear angiogram, results concordant with contrast studies were obtained in 27 (90%). In the case of the 50 segments analysed from the perfusion images, concordant results were obtained in 43 (86%) from the planar studies and in 42 (84%) from the tomographic studies. All normal segments were classified correctly.

Twice-daily low-dose captopril in diuretic-treated hypertensives.

Twice-daily captopril (25 mg) and placebo were compared in ten hypertensive patients who were already receiving bendrofluazide. After six weeks therapy, captopril produced significant antihypertensive effects one to six hours after dosing but these did not persist at eleven to twelve hours. Plasma renin concentration was increased for twelve hours after captopril but inhibition of angiotensin II activity was lost by twelve hours. During the period when captopril reduced blood pressure significantly, effective renal plasma flow and hepatic blood flow were unchanged although renal vascular resistance was reduced. There was no evidence that captopril altered plasma sodium, potassium or magnesium concentrations following bendrofluazide. Thus, in thiazide-treated patients, captopril 25 mg produces significant blood pressure reduction for at least six hours after dosing, without impairing renal or hepatic blood flow. However, twice-daily low-dose captopril does not adequately control blood pressure throughout the dosage interval.

Digital filtering of the bladder in SPECT bone studies of the pelvis.

A data processing technique for the removal of bladder activity from single photon emission computed tomographic bone studies of the pelvis has been developed. The method involves the replacement of count values in the bladder on all projection views by data which are representative of the activity in surrounding structures. Reconstruction is then performed using the amended set of projection views. The method was tested by examining a group of 13 patients referred for investigation of avascular necrosis of the femoral head. Significant improvements in image quality were observed, particularly with respect to the level of artifact production, which increased the number of cases in which a confident and correct diagnosis was made.

Neuroendocrine activation after acute myocardial infarction.

The extent of neuroendocrine activation, its time course, and relation to left ventricular dysfunction and arrhythmias were investigated in 78 consecutive patients with suspected acute myocardial infarction. High concentrations of arginine vasopressin were found within six hours of symptoms, even in the absence of myocardial infarction (n = 18). Plasma catecholamine concentrations also were highest on admission, whereas renin and angiotensin II concentrations rose progressively over the first three days, not only in those with heart failure but also in patients with no clinical complications. Heart failure, ventricular tachycardia, and deaths were associated with extensive myocardial infarction, low left ventricular ejection fraction, and persistently high concentrations of catecholamines, renin, and angiotensin II up to 10 days after admission, whereas in uncomplicated cases concentrations had already returned to normal.