Guidance for doctors on the assessment of mental health for the purpose of recommending on appropriate adult under PACE.

This is a new feature for the Journal. A case report is described and those with a particular interest in the field are asked to comment. Further submissions are invited and welcomed.

Crisis, grief and loss.

At one time or another, many of us experience a life-threatening crisis that proves to be a turning point in our lives. I had such a crisis while working as a medic on the oil-rig Vinland, offshore of Nova Scotia, in 1984.

Zirconium molybdate gel as a generator for technetium-99m--I. The concept and its evaluation.

A new 99mTc generator for the preparation of radiopharmaceuticals has been developed. Its elution characteristics and chemical stability merit its consideration as a replacement for present generators. The 99Mo is present as a zirconium molybdate gel, the high molybdate content of which allows the use of (n, gamma) 99Mo. The resulting generator is as effective and as convenient to use as chromatographic generators that are based on fission product 99Mo. Laboratory evaluations of the concept at low levels of radioactivity described in this paper show that the gel can be prepared in a form which is stable when used in a generator and from which TcO4- can be eluted in yields of 80-85%. The influence of formulation variables on gel properties was established. The performance of this generator using 99Mo with specific activities between 4 and 13 GBq g-1 is described in a further paper.

Zirconium molybdate gel as a generator for technetium-99m--II. High activity generators.

The characteristics of zirconium molybdate gels were described in Part I of this paper. Here it is shown that zirconium molybdate gel, prepared from neutron irradiated molybdenum oxide with 99Mo specific activities between 4.3 and 13.5 GBq g-1 is sufficiently stable for use as a matrix in preparation of high activity 99mTc generators. Elution efficiencies of generators containing from 2 to 6 g of gel ranged from 83 to 50% for 10 mL elutions. Generators containing 150 g of gel were eluted with efficiencies of 80-98%, with the activity peak in the first 50 mL. Radionuclidic impurities were considerably below the limits set by the British Pharmacopoeia. Although the pH of eluates was less than 4, subsequent treatment with a small zirconium oxide bed provided adjustment to within BP limits, and reduced 99Mo impurity levels tenfold to values near 10(-4)%. No significant differences were found between the biodistributions in rats of radiopharmaceuticals prepared with pertechnetate from gel generators and those from other generators.

Capillary gas chromatographic analysis of volatile and non-volatile organic acids from biological samples as the t-butyldimethylsilyl derivatives.

A quantitative procedure for the analysis of volatile organic acids and lactic acid in silage is described. The samples were extracted with diethyl ether, derivatized by t-butyldimethylsilylation, and then separated by capillary gas chromatography. The same procedure was useful for the identification by gas chromatography/mass spectrometry of organic acids in samples such as the metabolic fermentation products of anaerobic bacteria.

Effect of anaemia on red cell metabolism in cattle.

Six enzymes: glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glutathione reductase (GR), glutathione peroxidase (GSHPx), catalase and superoxide dismutase (SOD), and three metabolites: 2,3-diphosphoglycerate (DPG), adenosine triphosphate (ATP) and reduced glutathione (GSH), were measured in the red blood cells of cattle during experimental anaemia. There was a significant rise in the mean levels of DPG (from 0.85 to 1.69 mumol/gHb) and ATP (from 2.16 to 3.25 mumol/gHb) in the early phase of recovery. Enzyme activities also increased during the early recovery period.

Disposition and metabolism of codorphone in the rat, dog, and man.

The disposition and metabolism of codorphone, 17-cyclopropyl-methyl-4,5 alpha-8 beta-ethyl-3-methoxymorphinan-6-one (I), a new narcotic antagonist, analgesic agent, have been studied in the rat, dog, and man. Rats and dogs were given single 100- and 50-mg/kg po doses, respectively, of I-3H; human volunteers received single 10- to 30-mg doses of unlabeled I po. The compound appeared to be well absorbed in the three species. In rats the highest levels of radioactivity were in liver, adrenals, kidneys, spleen, and lungs. Excretion was primarily fecal in rats and dogs. In man about 50% of the dose appeared in the 24-hr urine. I was about 95% metabolized by each species. The major metabolites in rats resulted from 3- and/or 17-dealkylation. Metabolism in dogs was characterized primarily by 17-dealkylation. The major pathways of I metabolism in man were 17-dealkylation and 6-reduction. In the three species significant glucuronic acid conjugation of metabolites occurred.

Methodology for the identification of the urinary metabolites of the analgesic-narcotic antagonist, codorphone, by gas chromatography mass spectrometry.

Methodology is presented for the identification of codorphone and its metabolites in urine samples using gas chromatography mass spectrometry. The procedure focuses on the clean-up of biological samples and a derivatization technique suitable for these samples. Sep-Pak C-18 cartridges were employed in the clean-up procedure permitting the biological sample to be derivatized in a relatively small volume of reagents. The derivatization procedure incorporated a one-step trimethylsilyloxime reaction to prevent enol formation while simultaneously derivatizing free hydroxyl groups with the excess trimethylsilylimidazole present in the reaction mixture. This was followed by the addition of BSTFA directly to this reaction mixture to complete derivatization of any metabolites possessing dealkylation of the nitrogen. Using this derivatization scheme, synthetic metabolites were analyzed by gas chromatography mass spectrometry, and their mass spectra were characterized emphasizing the diagnostic fragment ions observed in the spectra. To illustrate the usefulness of this methodology, a urine sample obtained from a dog that had been dosed with codorphone was analyzed by gas chromatography mass spectrometry, and the metabolites were identified by comparison to the mass spectra of the synthetic derivatives.

The Sun's Influence on the Earh's Atmosphere and Interplanetary Space.

The bulk of the sun's radiation is in the visible and infrared. Solar radiation at these wavelengths controls the weather in the lowest levels of the earth's atmosphere. The rate at which this energy is emitted (the so-called solar constant) varies by a few tenths of 1 percent over a time scale of days. Longer period variations may exist, but have yet to be detected. Far more variable are the amounts of energy emitted as ultraviolet, extreme ultraviolet, and x-rays, and in the continuous outflow of ionized solar particles. The latter controls the properties of the space between the earth and the sun as well as those of the earth's magnetosphere. The ultraviolet and particle emissions control the properties of the earth's upper atmosphere, including the global wind circulation and changes therein associated with intense auroral storms. While considerable progress has been made in exploring the solar-terrestrial system since the advent of space research, many problems remain. These include the question of how magnetic energy is converted into ionized particle energy in the sun and in the earth's magnetosphere, the way in which solar and terrestrial magnetic fields join or merge, and how large electric fields are generated and sustained a few thousand kilometers above the earth's poles. Perhaps the most intriguing question concerns the possible relation between solar variability and the earth's weather and climate.

Direct quantitative analysis of indicine-N-oxide in cancer patient samples by gas chromatography using the internal standard heliotrine-N-oxide including a mass spectral comparison of their trimethylsilyl derivatives.

Indicine-N-oxide was analyzed quantitatively in biological samples using a direct partial purification method involving acetonitrite precipitation or methanol precipitation followed by ion exchange chromatography. Trimethylsilyl derivatization of the resultant provided either of two derivatives, depending on the reaction conditions used, both of which had good gas chromatographic qualities. Heliotrine-N-oxide was used as the internal standard for this work. Data are presented to show that this is a reliable and useful internal standard based on its behavior in the partial purification method and on the gas chromatographic characteristics of its two derivatives. In addition, both low and high resolution mass spectral data indicate that heliotrine-N-oxide produces two trimethylsilyl derivatives analogous to those produced by indicine-N-oxide under the same conditions. Application of this procedure to urine and blood samples from cancer patients in clinical trials indicates that over 95% of the drug is removed from the circulation and excreted in the urine over the course of 48 h.

Aporphines. 25-trimethylislyl derivatives of N-methyl and N-propyl aporphines: gas chromatographic and mass spectrometric properties.

A series of synthetic, semisynthetic and naturally occurring aporphine alkaloids were converted to the O-trimethylsilyl derivatives, and analyzed by gas chromatography mass spectrometry. A discussion of structurally informative fragment ions along with gas chromatographic data is presented. Their applicability to the analysis of biological metabolites of apomorphine, a CNS active structural analog of dopamine, is discussed.

The gas chromatographic mass spectrometric analysis of the new antitumor drug indicine-N-oxide utilizing a novel reaction accompanying trimethylsilylation.

Indicine-N-oxide was analyzed by gas chromatography mass spectrometry with nanogram sensitivity after trimethylsilylation. Two different products were produced by altering the conditions of this reaction. Mass spectral evidence is presented to show that one of these was the expected trisubstituted pyrrolizidine product while the other was a trisubstituted pyrrole. The latter derivative is useful for distinguishing between indicine-N-oxide and indicine which dies not form this novel product under the same conditions. Analogous pyrrole and pyrrolizidine products were formed from heliotrine-N-oxide, a compound that can serve as an internal standard from measuring indicine-N-oxide and its metabolites in biological samples. A method for purifying such samples by strong cation exchange chromatography prior to derivatization is also discussed.