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C Phillips

Publications and source records attributed to C Phillips.

At least 19 recordsLinked to original sources
PubMed2000

Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials.

OBJECTIVE: To summarise the effect of primary prevention with lipid lowering drugs on coronary heart disease events, coronary heart disease mortality, and all cause mortality. DESIGN: Meta-analysis. IDENTIFICATION: Systematic search of the Medline database from January 1994 to June 1999 for English language studies examining drug treatment for lipid disorders (use of the MeSH terms "hyperlipidemia" and "anticholesteremic agents," keyword searches for individual drug names, and a search strategy for identifying randomised trials to capture relevant articles); identification of older studies through systematic reviews and hand search of bibliographies. INCLUSION CRITERIA: All randomised trials of at least one year's duration that examined drug treatment for patients with no known coronary heart disease, cerebrovascular disease, or peripheral vascular disease and that measured clinical end points, including all cause mortality, coronary heart disease mortality, and non-fatal myocardial infarctions. DATA EXTRACTION: Review of the articles and extracted relevant data by two authors separately, with disagreements resolved by consensus. RESULTS: Four studies met eligibility criteria. Drug treatment reduced the odds of a coronary heart disease event by 30% (summary odds ratio 0.70, 95% confidence interval 0.62 to 0.79) but not the odds of all cause mortality (0.94, 0.81 to 1.09). When statin drugs were considered alone, no substantial differences in results were found. CONCLUSIONS: Treatment with lipid lowering drugs lasting five to seven years reduces coronary heart disease events but not all cause mortality in people with no known cardiovascular disease.

Cause of Death↗
PubMed2000

TB and husbandry.

Explore the source record for details and available documents.

Animal Husbandry↗
PubMed2000

Improved metabolic control reduces the number of postprandial apolipoprotein B-48-containing particles in type 2 diabetes.

Postprandial lipoproteins are raised in diabetes and there is increasing evidence for the atherogenicity of the chylomicron remnant. Increased postprandial cholesteryl ester transfer has also been demonstrated in diabetes and may contribute to the atherogenic lipoprotein profile. The present study examined the effect of improving metabolic control on postprandial lipoproteins in 13 Type 2 diabetic patients. Blood was taken fasting and at 2-h intervals following a high fat, 1100 kcal meal. Patients were brought into good control by intensified dietary advice and oral hyperglycaemic agents or insulin if blood glucose failed to respond. Fasting and postprandial cholesteryl ester transfer protein (CETP) and lecithin:cholesteryl acyltransferase (LCAT) were determined in six patients. Lipoproteins were isolated by sequential ultracentrifugation. Chylomicron and very low density lipoprotein (VLDL) apolipoprotein B-48 and apolipoprotein B-100 were isolated by polyacrylamide gradient gel electrophoresis and quantified by densitometric scanning. CETP and LCAT were determined by an endogenous method which determined cholesterol esterification and transfer between the patients' lipoproteins. There was a significant reduction in postprandial chylomicron apo B-48 (P<0.005), apo B-100 (P<0.0005) and chylomicron cholesterol (P<0.001) following improved diabetic control. The chylomicron lipid/apo B ratio increased with improved control (P<0.01). Postprandial CETP and LCAT were significantly reduced in good control (P<0.01 and P<0.05, respectively) and there were significant changes in HDL composition. The study shows that improvement in metabolic control in Type 2 diabetic patients leads to a reduction in postprandial chylomicron particles and less transfer of cholesterol to apo B-containing lipoproteins.

Aged↗
PubMed2000

Acute tubulointerstitial nephritis attributable to indinavir therapy.

Indinavir sulfate has been reported to cause asymptomatic crystalluria and nephrolithiasis in patients with human immunodeficiency virus (HIV) infection. Patients taking indinavir may present with asymptomatic crystalluria, nephrolithiasis with frank renal colic and obstruction, flank pain in the absence of nephrolithiasis, and dysuria or urgency. Asymptomatic crystalluria has been described as benign. Discontinuation of the drug has not been recommended in the absence of nephrolithiasis. We report two HIV-positive patients receiving indinavir who developed acute interstitial nephritis with foreign body giant cell reaction on renal biopsies. Both patients had asymptomatic crystalluria, although crystals were associated with clumps of white blood cells (WBCs) on urinalysis in one patient. Both cases show that the inflammatory response was significant enough to lead to tubular injury and acute renal impairment. Our findings suggest that asymptomatic crystalluria attributable to indinavir may illicit an inflammatory response with acute renal insufficiency, warranting monitoring of renal function, especially in patients with crystalluria.

Adult↗
PubMed2000

Effects of intrathecal administration of ziconotide, a selective neuronal N-type calcium channel blocker, on mechanical allodynia and heat hyperalgesia in a rat model of postoperative pain.

Ziconotide (SNX-111), a selective blocker of neuronal N-type voltage-sensitive calcium channels, is antinociceptive when it is administered intrathecally. It is currently under clinical investigation for the treatment of malignant and non-malignant pain syndromes. The present study was undertaken to compare and contrast antinociceptive properties of ziconotide, morphine and clonidine in a rat model of post-operative pain. Post-operative pain was produced by making a longitudinal incision through the skin, fascia, and muscle of the plantar aspect of the left hindpaw. This procedure produced immediate (0.5 h after surgery) and long-lasting (4-7 days post-surgery) heat hyperalgesia and mechanical allodynia in the injured hindpaw. Pain thresholds in the contralateral hindpaw were unaffected. Administered one day after incisional surgery, intrathecal ziconotide blocked established heat hyperalgesia in the injured hindpaw in a dose-dependent manner yielding an ED(50)4 h) but reversible (<24 h) blockade of established mechanical allodynia. Administered one day after surgery, intrathecal bolus injection of morphine dose-dependently blocked heat hyperalgesia in the injured hindpaw with an ED(50) of 1.6 microg (2.1 nmol) and heat nociceptive responses in the normal hindpaw with an ED(50) of 2.7 microg (3.6 nmol). The effects were immediate and short-lasting (</=1 h). Intravenous bolus injection of 3 mg/kg (1.1 micromol/kg) ziconotide, administered either before or after incisional surgery, had no effect on thermal pain thresholds measured in either the injured or normal hindpaw. In contrast, intraperitoneal injections of 2 mg/kg (2.6 micromol/kg) morphine and 2.5 mg/kg (9.4 micromol/kg) clonidine blocked heat hyperalgesia in the injured hindpaw; morphine, but not clonidine, also elevated thermal (heat) nociceptive response thresholds in the normal hindpaw. The results of this study show that intrathecal ziconotide is antinociceptive in a rat incisional model of post-operative pain and is more potent, longer acting, and more specific in its actions than intrathecal morphine.

Analgesics↗
PubMed2000

Interactions of intrathecally administered ziconotide, a selective blocker of neuronal N-type voltage-sensitive calcium channels, with morphine on nociception in rats.

Ziconotide is a selective, potent and reversible blocker of neuronal N-type voltage-sensitive calcium channels (VSCCs). Morphine is an agonist of mu-opioid receptors and inhibits N-type VSCC channels via a G-protein coupling mechanism. Both agents are antinociceptive when they are administered intrathecally (spinally). The present study investigated the acute and chronic (7-day) interactions of intrathecally administered ziconotide and morphine on nociception in several animal models of pain. In the acute study, intrathecal bolus injections of morphine and ziconotide alone produced dose-dependent inhibition of formalin-induced tonic flinch responses and withdrawal responses to paw pressure. The combination of ziconotide and morphine produced an additive inhibition of formalin-induced tonic flinch responses and a significant leftward shift of the morphine dose-response curve in the paw pressure test. After chronic (7-day) intrathecal infusion, ziconotide enhanced morphine analgesia in the formalin test. In contrast, chronic intrathecal morphine infusion produced tolerance to analgesia, but did not affect ziconotide antinociception. Antinociception produced by ziconotide alone was the same as that observed when the compound was co-administered with morphine to morphine-tolerant rats. In the hot-plate and tail immersion tests, chronic intrathecal infusion of morphine lead to rapid tolerance whereas ziconotide produced sustained analgesia with no loss of potency throughout the infusion period. Although ziconotide in combination with morphine produced an apparent synergistic analgesic effects during the initial phase of continuous infusion, it did not prevent morphine tolerance to analgesia. These results demonstrate that (1) acute intrathecal administrations of ziconotide and morphine produce additive or synergistic analgesic effects; (2) chronic intrathecal morphine infusion results in tolerance to analgesia but does not produce cross-tolerance to ziconotide; (3) chronic intrathecal ziconotide administration produces neither tolerance nor cross-tolerance to morphine analgesia; (4) intrathecal ziconotide does not prevent or reverse morphine tolerance.

Analgesics, Opioid↗
PubMed2000

The health status of diabetic patients receiving orthotic therapy.

Diabetes has a major impact on the quality of life and those with related foot ulcers are among those most affected. The main aim of the study, which was carried out over an 18-month time period, was to compare the self-reported health status of a group of diabetic patients receiving orthotic therapy with that of other groups who did not receive the therapy. A sample of 280 was recruited from patients with type I and type II diabetes. The study group comprised four groups of patients: those receiving orthotic therapy (insoles) for pedal complications as a result of their diabetes; those with diabetes mellitus, without complications of the disease affecting their foot; those with unilateral lower limb amputation and those with active ulceration who had not been prescribed footwear. The specialised orthotic intervention resulted in statistically significant improvements in health status (p < 0.05), (measured using the SF-36) both physically and mentally, for patients with at-risk feet and should become an integral part of the treatment regime for diabetics with at-risk feet.

Chi-Square Distribution↗
PubMed2000

Experience-dependent changes in cerebral activation during human REM sleep.

The function of rapid-eye-movement (REM) sleep is still unknown. One prevailing hypothesis suggests that REM sleep is important in processing memory traces. Here, using positron emission tomography (PET) and regional cerebral blood flow measurements, we show that waking experience influences regional brain activity during subsequent sleep. Several brain areas activated during the execution of a serial reaction time task during wakefulness were significantly more active during REM sleep in subjects previously trained on the task than in non-trained subjects. These results support the hypothesis that memory traces are processed during REM sleep in humans.

Adult↗
PubMed2000

Cytokine upregulation of the antigen presenting function of acute myeloid leukemia cells.

Acute myeloid leukemia (AML) cells are malignant counterparts of normal myeloid pathway progenitors. Myeloid progenitors differentiate into professional antigen presenting cells (APC) under the essential influence of GM-CSF along with additional cytokines. Twelve cases of human AML were tested for ability to be differentiated toward a professional APC phenotype in short-term culture with addition of GM-CSF and the following recombinant proteins: TNFalpha, IL-4, CD40 ligand, Flt3 ligand and SCF. Significant upregulation of CD80 (B7-1) and enhancement of alloantigen presentation was seen with the addition of GM-CSF and TNFalpha alone or with additional cytokines. The combination of GM-CSF and TNFalpha, either alone or in combination with an additional cytokine, resulted in enhancing alloantigen presentation by at least two-fold over the media control group in 10/12 patients studied, and resulted in CD80 expression of greater than 15% in 11/12 patients studied. In AML cultures with GM-CSF and TNFalpha, coexpression of CD80 and either CD34 or an aberrant surface marker (CD56) was seen. In one case, sorted CD80, cells retained a characteristic cytogenetic marker and CD34 expression, proving their derivation from an AML precursor. These studies verify other reports of in vitro differentiation of human AML precursors into enhanced APC, suggesting that this phenomenon could be utilized for immunotherapy strategies aimed at enhancing presentation of leukemia antigens to T cells.

Acute Disease↗
PubMed2000

Long-term stability of surgical open-bite correction by Le Fort I osteotomy.

Skeletal changes greater than those observed in untreated adults have been noted beyond 1 year post-surgery in adult patients who had surgical correction of a long face deformity. The stability of skeletal landmarks and dental relationships from 1 to >3 years post-surgery was examined in 28 patients who had undergone surgery of the maxilla only, and in 26 patients who had undergone 2-jaw surgery to correct >2 mm anterior open bite. Although the average changes in almost all landmark positions and skeletal dimensions were less than 1 mm, point B moved down >2 mm and face height increased >2 mm in one-third of the maxilla-only group and in 40% of the 2-jaw group (>4 mm in 10% and 22% respectively). Overbite decreased 2-4 mm in only 7% of the maxilla-only and 12% of the 2 groups, with no changes >4 mm, because in three-fourths of the patients with an increase in anterior face height, further eruption of the incisors maintained the overbite relationship. In the maxilla-only group, mandibular length (Co-Pg) showed >2 mm long-term change in 45% of the patients, two-thirds of whom showed an increase rather than a decrease in length. In the 2-jaw group, no patients showed a decrease in Co-Pg length and one-third had an increase. For both groups, changes in overjet were smaller and less frequent than changes in mandibular length.

Adaptation, Physiological↗
PubMed2000

Association of involvement in psychological self-regulation with longer survival in patients with metastatic cancer: an exploratory study.

There have been numerous anecdotal claims that when patients are dedicated users of a variety of psychological self-regulation strategies, including relaxation, mental imaging, cognitive restructuring and meditation, such dedication may have a life-prolonging effect. Our aim was to test this possibility more rigorously, in patients with metastatic cancer.A prospective, longitudinal, correlative study was carried out on 22 patients with varying kinds of medically incurable metastatic cancer. The intervention was one year of weekly group psychological therapy. Extensive verbal data (patients' written homework and therapists' notes) were collected over the year. The extent of each patient's involvement with psychological work was estimated following a qualitative analysis of these data. Patients were classed as showing high, moderate, or low involvement on the basis of a quantitative rating of categories defined by the analysis. These three subgroups did not differ significantly in their expected median survival duration as estimated from independent quantitative predictions by a large panel of oncologists who analyzed the patients' medical charts at time of study entry.A significant relationship was found between degree of involvement in psychological work and survival duration. Results are presented as Kaplan-Meier survival curves (Fig. 2;P = 0. 006, Log Rank test) and as a graphic display of the median survival of each of the three groups (Fig. 3). The main likely confounders (medical status, age, quality of life, and attendance at therapy) were similar across subgroups and did not change the relation between psychological work and survival duration. Limitations in the design are discussed. However, the strong effects observed support clinical observations that dedicated involvement in psychological self-regulation may prolong the life of some patients with metastatic cancer.

Adult↗
PubMed2000

Development of a minimum data set-based depression rating scale for use in nursing homes.

BACKGROUND: depression is common but under-diagnosed in nursing-home residents. There is a need for a standardized screening instrument which incorporates daily observations of nursing-home staff. AIM: to develop and validate a screening instrument for depression using items from the Minimum Data Set of the Resident Assessment Instrument. METHODS: we conducted semi-structured interviews with 108 residents from two nursing homes to obtain depression ratings using the 17-item Hamilton Depression Rating Scale and the Cornell Scale for Depression in Dementia. Nursing staff completed Minimum Data Set assessments. In a randomly assigned derivation sample (n = 81), we identified Minimum Data Set mood items that were correlated (P < 0.05) with Hamilton and Cornell ratings. These items were factored using an oblique rotation to yield five conceptually distinct factors. Using linear regression, each set of factored items was regressed against Hamilton and Cornell ratings to identify a core set of seven Minimum Data Set mood items which comprise the Minimum Data Set Depression Rating Scale. We then tested the performance of the Minimum Data Set Depression Rating Scale against accepted cut-offs and psychiatric diagnoses. RESULTS: a cutpoint score of 3 on the Minimum Data Set Depression Rating Scale maximized sensitivity (94% for Hamilton, 78% for Cornell) with minimal loss of specificity (72% for Hamilton, 77% for Cornell) when tested against cut-offs for mild to moderate depression in the derivation sample. Results were similar in the validation sample. When tested against diagnoses of major or non-major depression in a subset of 82 subjects, sensitivity was 91% and specificity was 69%. Performance compared favourably with the 15-item Geriatric Depression Scale. CONCLUSION: items from the Minimum Data Set can be organized to screen for depression in nursing-home residents. Further testing of the instrument is now needed.

Adult↗
PubMed2000

Specialized dementia programs in residential care settings.

The authors conducted a telephone survey in 7 states to determine the prevalence of residential care specialized dementia programs (RC-SDPs) and to identify a sample of homes (n = 56) for more detailed study. The 56 homes were site visited, and data were gathered on facility administration, therapeutic environment, and characteristics of 259 randomly selected residents. Comparison data from 138 nursing home Special Care Units (NH-SCUs) and 1,340 of their residents were obtained from 4 studies conducted in the same 7 states. RC-SDPs were smaller, provided a more homelike environment, and had a higher proportion of residents paying privately, compared with NH-SCUs. Mean levels of cognitive and physical impairment among residents were higher in NH-SCUs; prevalences of psychotropic medication use and problem behaviors were similar. Among RC facilities, small homes were more homelike, provided fewer structured activities, and charged less than larger facilities. RC-SDPs include 5 types: small, independently operated homes; multiple small homes with joint administration; larger, all-dementia facilities; SDPs operated within larger, exclusively RC facilities; and RC-SDPs in multilevel facilities.

Aged↗
PubMed2000

Active life expectancy from annual follow-up data with missing responses.

Active life expectancy (ALE) at a given age is defined as the expected remaining years free of disability. In this study, three categories of health status are defined according to the ability to perform activities of daily living independently. Several studies have used increment-decrement life tables to estimate ALE, without error analysis, from only a baseline and one follow-up interview. The present work conducts an individual-level covariate analysis using a three-state Markov chain model for multiple follow-up data. Using a logistic link, the model estimates single-year transition probabilities among states of health, accounting for missing interviews. This approach has the advantages of smoothing subsequent estimates and increased power by using all follow-ups. We compute ALE and total life expectancy from these estimated single-year transition probabilities. Variance estimates are computed using the delta method. Data from the Iowa Established Population for the Epidemiologic Study of the Elderly are used to test the effects of smoking on ALE on all 5-year age groups past 65 years, controlling for sex and education.

Aged↗
PubMed2000

Mechanisms of gastrointestinal copper absorption in the African walking catfish: copper dose-effects and a novel anion-dependent pathway in the intestine.

In mammals, copper (Cu) absorption occurs mostly in the small intestine, and some of the Cu transporters involved in its uptake have been characterised. In fish, however, the regions of the gut involved in Cu absorption and the membrane transport mechanisms responsible for gastrointestinal Cu uptake are unknown. Everted gut sacs and isolated perfused intestine of Clarias gariepinus were used to explore Cu absorption (at 22 degrees C). Gut sacs exposed to 100 micromol l(-1) mucosal solution Cu ([Cu](m)) showed that Cu was mostly (70 %) absorbed in the middle and hind intestine. Most of the accumulated Cu was located in the mucosa. In perfused intestines, cumulative Cu absorption from the mucosal solution to the serosal perfusate was greatest at 10 micromol l(-1) [Cu](m) and decreased at higher values of [Cu](m), while tissue accumulation of Cu showed a dose-dependent elevation. Absorption efficiency therefore declined with increasing Cu dose, and basolateral transport was the limiting factor in Cu uptake. Serosal applications of the P-type ATPase inhibitor vanadate (100 micromol l(-1)) or the anion transport inhibitor DIDS (100 micromol l(-1)) caused threefold increases in net Cu uptake (at [Cu](m)=10 micromol l(-1)). The vanadate effect was explained by a reduction in transepithelial potential rather than inhibition of Cu-ATPase, but the DIDS effect was not. Transepithelial potential, water transport and tissue [Cu] were not affected by DIDS, but tissue [K(+)] was elevated. Removal of Cl(-) simultaneously from both the mucosal and serosal solutions caused a 10-fold reduction in the rate of Cu uptake, while removal of Cl(-) from the mucosal solution only completely abolished Cu absorption to the serosal perfusate. Transepithelial potential effects are discussed. We conclude that Cu absorption occurs mostly in the intestine and is normally driven by a basolateral Cu/anion symport that prefers Cl(-).

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

Distribution of glucocorticoid and mineralocorticoid receptors and 11beta-hydroxysteroid dehydrogenases in human and rat ocular tissues.

PURPOSE: The administration of glucocorticoids as topical or systemic medications may lead to the development of ocular hypertension through the induction of morphologic and biochemical changes in the trabecular meshwork leading to a reduction in the facility of aqueous outflow. Glucocorticoids exert their physiological effects by binding to and activating glucocorticoid and mineralocorticoid receptors. The activity of glucocorticoids is critically regulated at a prereceptor level by the two isozymes of 11beta-hydroxysteroid dehydrogenase. The purpose of this study was to determine the distribution of glucocorticoid target receptors and the isozymes of 11beta-hydroxysteroid dehydrogenase (11 beta-HSD) that regulate the activity of glucocorticoids at a prereceptor level in human and rat ocular tissues. METHODS: Horizontal sections of normal adult human and rat eyes were cut and hybridized with 35S-labeled cRNA probes specific for the glucocorticoid receptor, mineralocorticoid receptor, and 11beta-HSD types 1 and 2 using in situ hybridization. Immunohistochemical analysis of glucocorticoid and mineralocorticoid receptors using monoclonal antibodies was carried out on rat eye tissue sections. Whole rat eyes were homogenized and the activity of 11beta-HSD types 1 and 2 in the eye assessed as the percentage conversion of tritiated corticosterone to tritiated 11-dehydrocortico-sterone when corticosterone was added to the homogenate. RESULTS: In the rat ocular tissues mRNAs encoding glucocorticoid receptor, mineralocorticoid receptor, and 11beta-HSD types 1 and 2 were detected in nonpigmented ciliary epithelium, trabecular meshwork, corneal epithelium and endothelium, and anterior lens epithelium. Immunohistochemistry confirmed the presence of glucocorticoid and mineralocorticoid receptors at these sites. Activity of both isozymes of 11beta-HSD was demonstrated in homogenized rat eyes (percentage conversion of tritiated corticosterone to 11-dehydrocorticosterone; mean +/- SD, 11beta-HSD 1 = 15% +/- 5.3%, 11beta-HSD 2 = 7.9% +/- 2.8%). In both human and rat eyes, expression of mRNAs encoding glucocorticoid receptor and 11beta-HSD type 1 was high in the trabecular meshwork and lens epithelium, whereas expression of mRNAs encoding the mineralocorticoid receptor and 11beta-HSD type 2 was high in nonpigmented ciliary epithelium and corneal epithelium and endothelium. CONCLUSIONS: Glucocorticoid target receptors and the enzymes regulating glucocorticoid activity at these receptors are present in mammalian ocular tissues, which regulate aqueous humor formation and outflow. Alteration in the number or affinity of receptors or in the activity of regulatory enzymes may alter the susceptibility of certain individuals to the effects of glucocorticoids on intraocular pressure.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Identification of a stem-loop structure important for polyadenylation at the murine IgM secretory poly(A) site.

We have previously shown that a distal GU-rich downstream element of the mouse IgM secretory poly(A) site is important for polyadenylation in vivo and for polyadenylation specific complex formation in vitro. This element can be predicted to form a stem-loop structure with two asymmetric internal loops. As stem-loop structures commonly define protein RNA binding sites, we have probed the biological activity of the secondary structure of this element. We show that mutations affecting the stem of the structure abolish the biological activity of this element in vivo and in vitro at the level of cleavage and polyadenylation specificity factor/cleavage stimulation factor complex formation and that both internal loops contribute to the enhancing effect of the sequence in vivo. Lead (II) cleavage patterns and RNase H probing of the sequence element in vitro are consistent with the predicted secondary structure. Furthermore, mobility on native PAGE suggests a bent structure. We propose that the secondary structure of this downstream element optimizes its interaction with components of the polyadenylation complex.

Animals↗