Biomedical subjects
R J Maxwell
Publications and source records attributed to R J Maxwell.
Effect of vasoactive drugs on tumour blood flow as determined by 2H nuclear magnetic resonance spectroscopy.
A selective reduction in tumour blood flow (TBF) could enhance the effects of hyperthermia treatment and of drugs toxic to hypoxic cells. Vasodilator-induced changes in TBF were monitored in transplanted rat fibrosarcomas by non-invasively measuring the uptake of D2O using 2H nuclear magnetic resonance spectroscopy. Hydralazine (1 or 5 mg kg-1) caused a large (45%) reduction in mean arterial blood pressure (MABP) and a 40-60% reduction in TBF. Low-dose hydralazine (0.1 mg kg-1) caused a 20% reduction in MABP but no significant change in TBF. The doses of prazosin (1 mg kg-1) and calcitonin-gene related peptide (CGRP, 1 nmol kg-1) which caused a 20% reduction in MABP led to a 50-60% reduction in TBF. These results demonstrate the advantage of prazosin and CGRP over hydralazine for the reduction of TBF despite a small hypotensive effect. CGRP may be the most suitable of these agents for clinical use because of its short physiological half-life.
Health care in cities.
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Isolation of sulfonamides from fortified chicken tissues with supercritical CO2 and in-line adsorption.
Improved recoveries and detectability of three sulfonamides from chicken tissues by supercritical fluid extraction (SFE), without modifiers, using an in-line adsorption trap, are reported. Following SFE, the analytes are recovered from neutral alumina with the HPLC mobile phase. Samples are injected directly onto high-performance liquid chromatographic columns without post-extraction cleanup. Mean recoveries of sulfamethazine, sulfadimethoxine, and sulfaquinoxaline from liver, breast tissue, and thigh muscle are 89, 95, and 77%, respectively. The analytes are detectable at less than 100 ppb with a minimum of background interference.
A puzzle for our times: using healthcare resources wisely and justly.
In the past fifty years health care has become one of the most challenging, expensive and dynamic of all sectors of human activity. The author's purpose in this short paper is to suggest that the key issues in the management of this sector are about individual and collective choices, that these choices are becoming harder and more constrained and that we have to become better at making them. With less certainty, he will suggest some of the ways in which we might tackle this dilemma, including some discussion of rationing.
Metachronous colonic lymphomas complicating chronic ulcerative colitis.
The gastrointestinal tract is the most common extranodal site of primary non-Hodgkin's lymphoma. Of these, 10-15% occur in the large bowel. Colonic lymphoma is a recognized complication of inflammatory bowel disease, particularly ulcerative colitis and, less commonly, Crohn's disease. We describe a unique case of two metachronous primary lymphomas of the large bowel in a patient with chronic ulcerative colitis.
Multiresidue recovery at PPB levels of 10 nitrosamines from frankfurters by supercritical fluid extraction.
The design of a laboratory-assembled supercritical fluid extractor is described for the efficient recovery of volatile nitrosamines from a common-cured meat product, frankfurters. The principal feature of the apparatus was a newly designed restrictor-collector interface where a commercial solid-phase extraction cartridge was directly attached to the micrometering valve. This reduced the path length between the discharge tube and the 1 g silica gel sorbent bed. The elapsed time for each 2.5 g sample extraction with supercritical CO2 was 17 min. The nitrosamines were separated and detected using a gas-chromatographic chemiluminescence (Thermal Energy Analyzer, Thermedics, Inc.; Woburn, MA) system. Recovery of 10 volatile aliphatic and alicyclic nitrosamines from frankfurters, fortified at the 20 ppb level, ranged from 84.3 to 104.8% with relative standard deviation of 2.34 to 6.13%.
New techniques in the pharmacokinetic analysis of cancer drugs. III. Nuclear magnetic resonance.
Nuclear magnetic resonance spectroscopy and imaging are non-invasive methods for monitoring the metabolism and distribution of anti-cancer drugs in tumours or other tissues. 19F NMR provides the easiest approach but requires a "built-in" fluorine atom in the drug of interest (eg 5-fluorouracil) or the incorporation of fluorine with minimal perturbance of a drug's properties. 2H NMR has also been used but has an effective sensitivity about 10- to 100-fold less than 19F. 1H and 13C are likely to be useful as non-perturbing NMR probes for future pharmacokinetic studies. The method is intrinsically insensitive, with a detection limit in the range of 0.01 to 0.1 mmol for fluorinated drugs. Techniques for absolute quantitation and for reliable localization to specific tissues and tumours are now available but have only rarely been applied in pharmacokinetic studies in the current literature. The incorporation of in vivo NMR measurements in a drug development programme should help to explain the differences found between drug activity in vitro, in solid animal tumour models and in cancer patients. It may also be possible to optimize drug selection or mode of administration for an individual patient.
Hyperparathyroid crisis and posterior mediastinal parathyroid adenoma: a case for preoperative localization.
Hyperparathyroid crisis is a rare, life-threatening condition that requires prompt removal of the involved parathyroid gland(s). This report describes a patient with hyperparathyroid crisis caused by a mediastinal parathyroid adenoma, which was localized before operation and removed at the initial operation, without neck exploration. Surgical approaches to hyperparathyroid crisis and the importance of preoperative localization studies are discussed.
Proton spectroscopy in vivo.
1H magnetic resonance spectroscopy (MRS) has attracted much attention in recent years. Since the proton is the most sensitive stable nucleus for MRS, and since almost all metabolites contain hydrogen atoms, it is possible to perform a noninvasive chemical analysis on tissues deep within the body of a subject. Technical solutions to the elimination of water and lipid signals as well as resolution of the large number of potential metabolite peaks have been found. Most current work is on the brain, much of it in humans. This review begins with a consideration of these technical problems and also localization, editing, quantitation, and interpretation of spectra. Two diseases are considered in detail: cerebral ischemia (including stroke and neonatal ischemic/hypoxic injury) and cancer; a further section briefly reviews studies on other diseases. In the immediate future, 1H MRS is likely to benefit from a number of technical advances: higher field magnets, better control of gradients and eddy currents, more sophisticated radiofrequency (RF) pulses, and 1H-observe/13C-edited spectroscopy all offer potential improvements. Another major improvement will come from increased user-friendliness of clinical spectrometers and use of automated objective methods for spectroscopic data analysis.
Mitochondrial DNA mutation associated with aging and degenerative disease.
Previous theories of aging based on somatic mutation neglected mtDNA, which has a high propensity for mutational error. Knowledge of yeast mtDNA mutations and their functional effects, and of human mtDNA mutations identified in the mitochondrial cytopathies, provides for a concept of aging based on the cumulative effect of mutations affecting human mtDNA. An essential feature of this concept is heteroplasmy, representing mixtures of normal and mutant mtDNA at the cellular and mitochondrial level, resulting in a "tissue mosaic" of focal bioenergetic deficits. Direct evidence for the concept is provided by (i) focal loss of staining for mitochondrially encoded enzymes, such as cytochrome c oxidase, in tissues of aged individuals (humans and rats) and (ii) an age-related increase in deletional mutations in mtDNA demonstrable by application of the polymerase chain reaction to DNA templates from individuals of different ages.
Western donors and the former Soviet Union.
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Multiple mitochondrial DNA deletions in an elderly human individual.
We have used the polymerase chain reaction (PCR) to study deletions in the mitochondrial DNA (mtDNA) of an elderly human individual. An extended set of PCR primers has been utilised to identify 10 mitochondrial DNA deletions in a 69-year-old female subject with no known mitochondrial disease. The particular deletions visualised as PCR products depended on the primer pairs used, such that the more distantly separated PCR primers enabled visualisation of larger deletions. Some deletions were common to the heart, brain and skeletal muscle, whereas others were apparently specific to individual tissues. DNA sequencing analysis of PCR products showed that short direct repeat sequences (5 to 13 bp) flanked all deletion breakpoints; in most cases one copy of the repeat was deleted. It is proposed that the accumulation of such multiple deletions is a general phenomenon during the ageing process.
An investigation of tumor 1H nuclear magnetic resonance spectra by the application of chemometric techniques.
1H nuclear magnetic resonance (NMR) spectra of tumors and normal tissue include signals from all hydrogen-containing metabolites and can therefore be considered multicomponent multivariate mixtures. We have obtained 1H spectra from perchloric acid extracts of three normal tissues (liver, kidney, and spleen) and five rat tumors (GH3 prolactinoma, Morris hepatomas 7777 and 9618a, LBDS1 fibrosarcoma, and Walker 256 carcinosarcoma). We have applied several different chemometric methods to analyze the data. First, we used principal component analysis, cluster analysis, and an optimized artificial neural network to develop a classification rule from a training set of samples of known origin or class. The classification rule was then assessed using a set of unknown samples. We were able to successfully determine the class of each unknown sample. Second, we used the chemometric techniques of factor analysis followed by target testing to investigate the underlying biochemical differences that are detected between the classes of samples.
Deuterium nuclear magnetic resonance imaging of the developmental pattern of tumour blood flow.
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Dimensions of quality revisited: from thought to action.
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19F nuclear magnetic resonance imaging of drug distribution in vivo: the disposition of an antifolate anticancer drug in mice.
The application of 19F nuclear magnetic resonance imaging to the study of drug distribution in vivo is discussed. CB3988 (C2-desamino-C2-methyl-N10-propargyl-2'-trifluoromethyl-5,8-dideazafolic acid) is a fluorinated representative of a class of quinazoline antifolates which act as inhibitors of thymidylate synthase and which are being evaluated for the treatment of human cancer. 19F images were obtained in vivo from the abdomen of mice following intravenous injection of CB3988 (500 mg/kg). Time resolutions of 4 and 20 min were achieved for two- and three-dimensional imaging, respectively. These images were consistent with the presence of high concentrations of drug (up to 26 mg/ml) in the gall bladder, urinary bladder, and small intestine, as confirmed ex vivo by extraction and HPLC analysis. The results indicate the potential value of 19F NMR imaging in pharmacokinetic studies.