Screening for colorectal cancer: which test is best?
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Colonoscopy↗
Biomedical subjects
J Bond
Publications and source records attributed to J Bond.
Administering amphotericin B--a practical approach.
Despite the introduction in recent years of novel antifungal agents, the potency and broad spectrum of activity of amphotericin B have ensured that it remains the treatment of choice for most deep-seated mycoses. However, this agent is not without significant toxicity, particularly in patients who are already seriously ill and/or who are receiving other potentially nephrotoxic drugs. We review the various routes by which amphotericin B can be administered, focusing mainly on the intravenous route. The use of more rapid infusion rates, lipid-complexed preparations, sodium supplementation in salt-depleted patients and strategies to reduce the incidence of infusion-related reactions and nephrotoxicity are also considered. Finally, detailed recommendations for the administration of amphotericin B are provided.
Amphotericin B↗
Studies on the effects of growth hormone administration in vivo on the rates of glucose transport and utilization in rat skeletal muscle.
The effects of growth hormone (GH) administration to rats in vivo on the sensitivity of the rate of glucose utilization to insulin were studied in soleus muscles isolated from these rats. A single injection of GH did not increase the rate of glucose transport within 1-2 h. However, 12 h after, the rate of glucose transport was increased at 10 mU insulin l-1 and was accompanied by a similar increase in the rate of lactate formation but no change in the rate of glycogen synthesis. Prolonged treatment with GH decreased the rate of glucose transport and glycogen synthesis and increased the content of glucose 6-phosphate at physiological levels of insulin but did not affect the rate of lactate formation. These results suggest that: (a) GH does not increase the rate of glucose transport acutely; however, after several hours, the sensitivity of glucose transport and glycolysis to insulin are increased; (b) prolonged elevations of the level of GH in plasma decrease the sensitivity of the rate of glucose transport and glycogen synthesis to insulin. However, redirection of glucose residues away from the pathway of glycogen synthesis towards that of glycolysis and a possible increase in the rate of glycogenolysis maintain a normal rate of lactate formation, although the rate of glucose transport is decreased.
Animals↗
Who goes to the hospital? An investigation of high users of hospital days.
Hospital morbidity data are useful for administrative purposes, but because Canadian data are based on the number of hospital visits for a given diagnosis rather than the number of patients with the diagnosis, they have historically been ineffective in determining how many people have been hospitalized with a given condition. Now, by linking computerized patient data, the records of the same patient can be combined. Linked records can be used to estimate disease prevalence, examine health care utilization, and evaluate the effectiveness of medical treatments, procedures and programs. Hospital morbidity records for the fiscal year 1989/90 were linked by person to study hospital utilization in New Brunswick and Saskatchewan. Approximately 11% and 12% of their populations, respectively, were admitted to hospital in the study period. The percentage of the population that was hospitalized increased with age from 50 onwards. About one in four hospital patients were admitted to hospital more than once in 1989/90, and approximately 4% were admitted four or more times. Cancer diagnoses were associated with the highest hospital re-admission rates. About half of hospitalized patients spent five days or less in hospital over the period studied. At the other extreme, 10% of patients, referred to as "high users," accounted for about half of the hospital days--but only 1% of the population in these two provinces. Typically, high users are patients with chronic conditions or illnesses severely affecting cognitive or physical abilities. This profile of high users suggests that high medical costs are due not so much to intensive care of terminally ill patients, but to ordinary medical and palliative care of chronically and seriously ill patients. Restructuring health care data so that all of the records for one patient could be linked would help identify problem areas in the health care system and help evaluate new ways of delivering health care.
Adolescent↗
Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup.
BACKGROUND: The identification and removal of adenomatous polyps and post-polypectomy surveillance are considered to be important for the control of colorectal cancer. In current practice, the intervals between colonoscopies after polypectomy are variable, often a year long, and not based on data from randomized clinical trials. We sought to determine whether follow-up colonoscopy at three years would detect important colonic lesions as well as follow-up colonoscopy at both one and three years. METHODS: Patients were eligible if they had one or more adenomas, no previous polypectomy, and a complete colonoscopy and all their polyps had been removed. They were randomly assigned to have follow-up colonoscopy at one and three years or at three years only. The two study end points were the detection of any adenoma, and the detection of adenomas with advanced pathological features (defined as those > 1 cm in diameter and those with high-grade dysplasia or invasive cancer). RESULTS: Of 2632 eligible patients, 1418 were randomly assigned to the two follow-up groups, 699 to the two-examination group and 719 to the one-examination group. The percentage of patients with adenomas in the group examined at one and three years was 41.7 percent, as compared with 32.0 percent in the group examined at three years (P = 0.006). The percentage of patients with adenomas with advanced pathological features was the same in both groups (3.3 percent). CONCLUSIONS: Colonoscopy performed three years after colonoscopic removal of adenomatous polyps detects important colonic lesions as effectively as follow-up colonoscopy after both one and three years. An interval of at least three years is recommended before follow-up colonoscopy after both one and three years. An interval of at least three years is recommended before follow-up examination after colonoscopic removal of newly diagnosed adenomatous polyps. Adoption of this recommendation nationally should reduce the cost of post-polypectomy surveillance and screening.
Adenoma↗
Direct growth stimulation of normal human epithelial cells by mutant p53.
We developed a high-titer amphotropic retroviral vector that expresses mutant (Ala143) human p53 to test directly the response of genetically normal human epithelial cells to p53 mutation. Contrary to our prediction, we found that in pancreatic epithelium (whose tumors display a high frequency of p53 mutation) but not in thyroid (whose tumors show an exceptionally low mutation frequency), expression of mutant p53 induced a dramatic, though self-limiting, proliferative response. This result questions the assumption that p53 mutation is relevant only to the later stages of tumorigenesis.
Cell Division↗
Toxicity of phorbol esters for human epithelial cells expressing a mutant ras oncogene.
Phorbol esters and related compounds provide a promising source of potential anticancer agents. The mechanism of their toxicity, however, is unclear, and interpretation has been complicated by the conflicting responses exhibited by different transformed cell lines. Previously we showed that in primary thyroid follicular cells, expression of mutant p21ras conferred a striking sensitivity to the toxic effects of phorbol esters. We have now extended this work using a thyroid cell line with an inducible mutant ras gene to exclude the possibility that this result was a trivial consequence of the marked growth stimulation induced in these cells by mutant p21ras. Furthermore, by assessing the action of a panel of phorbol esters and a potential chemotherapeutic agent, bryostatin, we demonstrated that this phenomenon was only a function of biologically active phorbol esters. These results provide a molecular rationale for the development of phorbol ester analogues as chemotherapeutic agents.
Antineoplastic Agents↗
Effect of serum growth factors and phorbol ester on growth and survival of human thyroid epithelial cells expressing mutant ras.
We previously demonstrated a high incidence of ras mutation in thyroid follicular (epithelial) cell neoplasms and showed that expression of mutant ras is a potent mitogenic stimulus for normal human follicular cells in culture. Here we show that induction of cell proliferation in primary follicular cells by a mutant human Ha-ras (val 12) expressed from a retroviral vector was absolutely dependent on the presence of serum growth factors. Induction of DNA synthesis showed partial dependence. Mutant ras-induced growth was also inhibited by exposure to phorbol ester at concentrations sufficient to downregulate protein kinase C. More importantly, we observed an unexpected toxic effect of phorbol ester in this system that was specific to cells expressing mutant ras. This has potential significance both for elucidating the basic mechanism of ras action in epithelial cells and also as a pointer to a novel therapeutic strategy.
Animals↗
Development of a measure of professional collaboration in primary health care.
STUDY OBJECTIVE: The aim was to develop indices of the degree of collaboration between district nurses, general practitioners, and health visitors. DESIGN: Semistructured interviews were conducted with each member of a pair of professionals who had patients in common. In each district a stratified random sample of six general practitioners and six community nurses was drawn, and for each a "partner" of the other profession was sampled. SETTING: A stratified random sample of 20 district health authorities in England. PARTICIPANTS: Complete interviews were obtained with 148 doctor-nurse and 161 doctor-health visitor pairs. MAIN RESULTS: Only 27% of general practitioners and district nurses with patients in common and 11% of general practitioners and health visitors collaborate. Stepwise logistic discriminant analysis was used to develop measures of collaboration between general practitioners and district nurses and between general practitioners and health visitors. The indices of collaboration were calculated from the responses of the community nurse to at most 10 questions. CONCLUSIONS: The indices developed here might be used as a measure of one aspect of the quality of service offered by a primary health care team or to assess the effect of changes in working patterns or the degree of collaboration within the organisation.
Community Health Nursing↗
The inhibitory effects of cromakalim and its active enantiomer BRL 38227 against various agonists in guinea pig and human airways: comparison with pinacidil and verapamil.
The effects of the potassium channel activators, cromakalim, BRL 38227 and pinacidil, and the calcium antagonist, verapamil, have been compared against various spasmogens on airway responses in vitro and in vivo in the guinea pig and also in human isolated bronchi. In guinea pig tracheal spirals, potassium channel activators generally had a greater inhibitory effect than verapamil against tone induced by a wide range of spasmogens (spontaneous, 5-hydroxytryptamine, leukotriene D4, prostaglandin E2). The potassium channel activators had very little effect against potassium chloride- and carbachol-induced tone in guinea pig tracheal spirals [e.g., cromakalim (20 microM) induced relaxations of 0.21 +/- 0.03 (relative to an isoprenaline maximum = 1.0, mean +/- S.E.M.) against carbachol, compared to 0.77 +/- 0.03 against histamine]. In vivo, the potassium channel activators prevented histamine and 5-hydroxytryptamine-induced bronchoconstrictions, but had little inhibitory effect against acetylcholine. In contrast, in human bronchi, cromakalim was capable of inducing powerful concentration-dependent relaxations against carbachol-induced tone [cromakalim (20 microM) induced relaxations of 0.77 +/- 0.09 (relative to isoprenaline = 1.0, mean +/- S.E.M.) against carbachol, compared to 0.95 +/- 0.04 against histamine]. In human bronchi, all the inhibitory agents were more potent and more effective, except that verapamil did not have an increased maximum response. We conclude that potassium channel activators should be effective at relaxing contractions induced by a wide range of spasmogens in man.
Animals↗
Physiological glucocorticoid levels regulate glutamine and insulin-mediated glucose metabolism in skeletal muscle of the rat. Studies with RU 486 (mifepristone).
This study examined the effects of antagonism of the peak level of glucocorticoids in vivo, which occurs as rats enter the feeding/activity (dark) period on glucose and glutamine metabolism in incubated isolated rat soleus muscle preparations. Thus the rats were treated with the potent glucocorticoid antagonist RU 486 2 h before and 1 and 2 h into the dark period. Both the content of glutamine in skeletal muscle in vivo and plasma glucose and glutamine concentrations were elevated midway through the dark period, compared with the beginning of the period. RU 486 prevented the increases in plasma glucose and glutamine and caused a significant decrease in both the rate of release of glutamine in soleus muscle in vitro and the content of glutamine in gastrocnemius muscle. The sensitivity of soleus muscle to insulin in vitro is markedly decreased when isolated midway through the dark period (i.e. at 03:00 h) [Leighton, Kowalchuk, Challiss & Newsholme (1988) Am. J. Physiol. 255, E41-E45]. We now show that the concentrations of insulin required to stimulate lactate formation and glycogen synthesis half-maximally were 95 and 250 muunits/ml respectively, and treatment of rats with RU 486 decreased these values to 55 and 90 muunits of insulin/ml respectively. Thus antagonism of the action of the normal circadian rise in the level of glucocorticoids in rats reverses insulin insensitivity in soleus muscles in vitro.
Alanine↗
The effect of tumour bearing on skeletal muscle glutamine metabolism.
1. The effects of tumour bearing on glutamine metabolism in rat skeletal muscle were examined using the Walker 256 carcinosarcoma. 2. There was a rapid and marked decrease in skeletal muscle glutamine content, which was correlated with the size of the tumour, and a decrease in plasma glutamine concentration. 3. The rate of release of glutamine from EDL muscle in vitro was increased in cachectic, tumour bearing animals, but was unaffected from the soleus muscle of the same animals. 4. It is hypothesized that the increase in the rate of muscle glutamine release during cachexia represents a response of this tissue in order to satisfy the demand for glutamine by the tumour or by cells of the immune system.
Animals↗
Experience and preparation of community nursing staff for work associated with HIV infection and AIDS.
Some of the findings from a national survey of 3754 community nursing staff in England regarding their experience of and preparation for working with HIV infection and AIDS are reported. The current absence of confidence to deal with HIV infection is explained and suggestions made regarding the content of educational developments.
Acquired Immunodeficiency Syndrome↗
In vitro assembly of gap junctions.
Gap junction structures were assembled in vitro from octyl-beta-D-glucopyranoside-solubilized components of lens fiber cell membranes. Individual pore structures (connexons), short double-membrane structures, and other amorphous material were evident in the solubilized mixture. Following the removal of the detergent by dialysis, these connexons associated to form single- and double-layered, two-dimensional hexagonal arrays (unit cell size a = b = 8.5 nm). The formation of larger arrays was dependent on the lipid-to-protein ratio and the presence of Mg2+ ions. Crystallographic analysis of electron micrographs revealed that lens junctional connexons consisted of six subunits surrounding a stain-filled channel. Upon further detergent treatment, in vitro assembled gap junctions were insoluble and formed three-dimensional stacks while other components were solubilized. SDS-PAGE and mass data from scanning transmission electron microscopy strongly suggest that a 38-kDa polypeptide, which is a processed form of the lens specific gap junction protein MP70, is a major component of the arrays. The in vitro assembly of gap junctions opens new avenues for the structural analysis of gap junctions and for the study of the intermolecular interactions of connexons during junctional assembly.
Animals↗
The effect of catecholamines on the metabolism of glutamine by skeletal muscle of the rat.
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Animals↗
Cost of continuing-care facilities in the evaluation of experimental national health service nursing homes.
In this paper the costing method and results from the UK evaluation of National Health Service (NHS) nursing-home and continuing-care hospital accommodation for elderly people are presented. Results demonstrate that, in deciding on the relative efficiency of NHS nursing-home and hospital accommodation, it should be possible to provide NHS nursing-home care at a cost which is no greater than its hospital counterpart. Cost implications of future developments should be monitored in the possible event that they are set up differently from the NHS nursing homes discussed in this paper. Despite being more costly than private-sector nursing-home accommodation, NHS nursing homes cater for a less able group of people, although some overlap exists. The implications of such results are discussed in the light of the UK Government's recent proposals to reform both the NHS and community care.
Costs and Cost Analysis↗
National Health Service nursing homes again.
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Homes for the Aged↗
Evolutionary aspects of superoxide dismutase: the copper/zinc enzyme.
Copper/zinc superoxide dismutase is typically an enzyme of eukaryotes. The presence of the enzyme in the ponyfish symbiont Photobacterium leiognathi and some free living bacteria does not have an immediate explanation. Amino acid sequence alignment of 19 Cu/Zn superoxide dismutases shows 21 invariant residues in key positions related to maintenance of the beta-barrel fold, the active site structure including the electrostatic channel loop, and dimer contacts. Nineteen other residues are invariant in 18 of the 19 sequences. Thirteen of these nearly invariant residues show substitutions in Photobacterium Cu/Zn superoxide dismutase. Copper/zinc superoxide dismutase from the trematode Schistosoma mansoni shows an N-terminal sub-domain with a hydrophobic leader peptide, as in human extracellular superoxide dismutase which is a Cu/Zn enzyme. The latter also has a C-terminal sub-domain with preponderance of hydrophilic and positively charged residues. The amino acid sequence of this superoxide dismutase between the N-terminal and C-terminal regions shares many features of cytosolic Cu/Zn superoxide dismutase, including 20 of the 21 invariant residues found in 19 Cu/Zn enzymes, suggesting a similar type of beta-barrel fold and active site structure for the extracellular enzyme.
Amino Acid Sequence↗