South Africa: a fragile miracle.
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Health Expenditures↗
Biomedical subjects
R J Maxwell
Publications and source records attributed to R J Maxwell.
Proton NMR observation of the antineoplastic agent Iproplatin in vivo by selective multiple quantum coherence transfer (Sel-MQC).
We have noninvasively detected the proton signal of an antineoplastic agent Iproplatin in vivo by selective multiple quantum coherence transfer (Sel-MQC). Without isotopic labeling or chemical modification, the Sel-MQC method labels Iproplatin by its intrinsic proton multiple quantum coherences and, hence, differentiates the Iproplatin signal from the intensive overlapping resonances of lipid and lactate. This proton NMR method should also be applicable to study other drugs with appropriate spin coupling patterns.
Animals↗
Pharmacokinetics of the 13C labeled anticancer agent temozolomide detected in vivo by selective cross-polarization transfer.
The anticancer agent temozolomide labeled with 13C (8-Carbamoyl-3-13C-methylimidazo-[5,1-d]-1,2,3,5-tetrazin-4-(3H)-o ne), was noninvasively detected in subcutaneous RIF-1 tumors by a selective cross polarization 13C NMR method, at a field strength of 9.4T. Pharmacokinetics of the drug, at a dose of 150 mg/kg, were determined for intravenous and intraperitoneal models of administration (three animals per mode). The half-life of the drug in the tumors was approximately 60 min. The uptake and clearance of the drug, however, varied significantly between individual hosts, for both modes of administration. These results demonstrate the feasibility of obtaining pharmacokinetics of anticancer agents for individual tumors without the need for a label that might modify drug activity (e.g., fluorine). The variability of the in vivo measurements, even within the same tumor model, demonstrates the necessity of directly monitoring the tumor to evaluate drug pharmacokinetics.
Animals↗
Why rationing is on the agenda.
The National Health Service Act of 1946 set out to provide a comprehensive health service, free at the point of use, to the whole population of the UK. The purpose-as Nye Bevan, then Minister of Health, put it-was to ensure that nobody should be denied, on the grounds of lack of means, 'the best that medical skill can provide'. Among the many fears about the Act voiced at the time, the idea that the State would not be able to afford it was not one. Indeed, that wise man William Beveridge had even mistakenly assumed, in the wartime White Paper on Social Security, that good health care would ultimately save money for the State, once an initial backlog of neglect had been made good, and that the cost of health insurance would then fall.
Child↗
Can we do better?
In the introductory chapter, I claimed that rationing is a fact of life in the NHS, and that the rationing dilemma is worsening over time, primarily because what medicine can offer becomes vastly more sophisticated and in aggregate more expensive. What is implied in Nye Bevan's intent that every citizen should receive 'the best that medical skill can provide' is very different now from what it was in 1946 when the NHS Act was passed. And the going will be ever harder in the years ahead, since medical possibilities, offering genuine benefit for some, will continue to increase faster than national wealth.
Decision Making↗
Significance of systemic endotoxaemia in inflammatory bowel disease.
Quantitative and qualitative disturbances in faecal flora suggest a role for enteric bacteria and their products in the pathogenesis of inflammatory bowel disease (IBD). This study investigated the hypothesis that systemically circulating endotoxins are of pathogenic significance in IBD by measuring antibody, cytokine, and acute phase protein responses. Systemic endotoxaemia was found in 88% patients with ulcerative colitis (n = 25) and 94% with Crohn's disease (n = 31) during clinical relapse. Systemic endotoxaemia correlated positively with anatomic extent and clinical activity of ulcerative colitis. Circulating tumour necrosis factor (TNF) was detected in 40% of patients with ulcerative colitis and 45% with Crohn's disease. Plasma TNF concentrations correlated with clinical and laboratory measures of disease activity and were associated with a surgical outcome to the disease episode. Plasma soluble TNF receptor p55 concentration correlated positively with disease activity and endotoxin core antibody concentrations. Plasma IgG endotoxin core antibody concentrations were significantly increased in patients with Crohn's disease and correlated with systemic endotoxaemia. The presence of systemic endotoxaemia, its correlation with disease activity, disease extent, and endotoxin core antibody concentration and the detection of circulating TNF and soluble TNF receptors all support a pathogenic role for endotoxins in IBD.
Adolescent↗
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.
Animals↗
Health care in cities.
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Delivery of Health Care↗
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.
Adsorption↗
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.
Colitis, Ulcerative↗
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%.
Carbon Dioxide↗
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.
Antineoplastic Agents↗
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.
Adenoma↗
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.
Animals↗
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.
Aging↗
Western donors and the former Soviet Union.
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Europe↗