Biomedical subjects
Publications and source records attributed to R Murphy.
Through a work redesign project, one hospital focuses on the root of the nursing care delivery system. The premise was simple--a return to the basics to redefine barriers, needed system changes, and role responsibilities. Successful outcomes include improved recruitment and retention as well as increased patient, staff and community satisfaction.
BACKGROUND: Prolonged infusional 5-fluorouracil (5-FU) and bolus 5-FU modulated by leucovorin are associated with higher response rates than bolus 5-FU alone. Cisplatin enhances 5-FU cytotoxicity in some preclinical models. METHODS: The authors tested the feasibility of combining concurrent infusional leucovorin (500 mg/m2/d) with protracted infusional 5-FU (200 mg/m2/d) and weekly bolus cisplatin (20 mg/m2) in 22 patients with metastatic colorectal cancer. RESULTS: Four partial responses (PR) were noticed among 21 evaluable patients (19%). The median time to treatment failure and median survival were 6 months and 11 months, respectively. All but two patients required 5-FU dose reduction after a median of 2 weeks because of mucositis. However, severe mucositis and diarrhea occurred in only 18% and 5% of the patients, respectively. Palmar-plantar erythrodysesthesia of mild to moderate severity occurred in 55% of patients. Megaloblastic changes were evident in the peripheral blood during therapy, and may reflect prolonged DNA-directed toxicity of 5-FU. The median tolerated dose level of 5-FU was 113 mg/m2/d (range, 64-150 mg/m2/d). Mean steady-state plasma concentrations (Cpss) of 5-FU appeared to increase linearly from 0.19 microM to 0.39 microM over the dose range 64 to 200 mg/m2/d. Patients with grade 2 gastrointestinal toxicity had significantly higher 5-FU Cpss than patients with grade 0 or 1 toxicity. CONCLUSIONS: The early onset of toxicity with this regimen of protracted infusional 5-FU/high-dose leucovorin and weekly cisplatin required marked attenuation of the 5-FU dose intensity, and the results were no better than that expected with infusional 5-FU alone.
OBJECTIVE: To assess the efficacy and safety of itraconazole in preventing relapse of histoplasmosis after induction therapy with amphotericin B in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. DESIGN: A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks. SETTING: Tertiary care hospitals participating in a clinical investigation sponsored by the National Institutes of Allergy and Infectious Diseases (AIDS Clinical Trial Group and Mycoses Study Group). PATIENTS: Forty-two patients with AIDS who had successfully completed induction therapy for disseminated histoplasmosis amphotericin B, at least 15 mg/kg body weight given over 4 to 12 weeks. INTERVENTIONS: Itraconazole, 200 mg given orally twice daily. MAIN OUTCOME MEASURES: Response to therapy, specifically prevention of histoplasmosis relapse, was the main outcome measure. Secondary end points were survival and the effect of therapy on Histoplasma capsulatum variety capsulatum antigen levels in urine and serum. Plasma itraconazole concentrations were measured to document drug absorption and compliance with therapy. RESULTS: The median follow-up was 109 weeks, and median survival was 98 weeks. Two relapses occurred (5%; 95% CI, 0.5% to 16%), one in a patient withdrawn from the study 18 weeks earlier and one in a patient who did not comply with the study therapy. Patients with elevated antigen levels at study entry showed clearance of antigen from urine and serum; urine specimens became negative in 43% of patients (CI, 26% to 59%), and serum specimens became negative in 75% of patients (CI, 56% to 94%). Only one patient discontinued treatment because of itraconazole toxicity (hypokalemia). CONCLUSIONS: Itraconazole, 200 mg twice daily, is safe and effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. Antigen clearance from blood and urine correlates with clinical efficacy.
It has been suggested that the thymic polypeptide thymopoietin interacts with skeletal muscle nicotinic acetylcholine receptors (nAChRs) and brain nicotinic receptors labeled by alpha-bungarotoxin (alpha-BuTX). In this study, the effects of neonatal thymectomy on the density of skeletal muscle nAChRs and the density of brain alpha-BuTX binding sites at 7 and 45 days postnatal were investigated. In addition, the densities of receptors in the skeletal muscle and brain of the athymic nu/nu mouse at 42 days postnatal were measured. We found little evidence that the absence of the thymus alters the density of nicotinic receptors in either skeletal muscle or brain.
The ergogenic effect of aspartate salts on performance during prolonged exercise is still controversial. Potential mechanisms of the suggested ergogenic effect of aspartate on exercise performance are a sparing of muscle glycogen stores or its faster resynthesis during exercise. The purpose of this study was to determine whether aspartate causes a sparing of muscle glycogen during exercise. Six groups of rats were studied: one group received a single injection of aspartate (1 g.kg-1, IP) and was then sacrificed at rest, a second group of aspartate-treated rats was sacrificed after a 60-min swim. The third and fourth groups were given an injection of physiological saline and then sacrificed respectively at rest and after a 60-min swim. The fifth and sixth groups were given an aspartate or a saline injection and then sacrificed after swimming to exhaustion. The exhaustion times after saline (178.9 +/- 38.2 min) and aspartate (174.4 +/- 45.2 min) were not significantly different. Results did not confirm an ergogenic effect of a single dose of aspartate on swimming endurance in the rat. Aspartate-treated rats had a significantly lower plasma FFA concentration after swimming to exhaustion when compared to control rats (respectively, 0.70 +/- 0.25 vs. 1.16 +/- 0.45 mM). Also, the results of the present study do not support the hypothesis of a sparing of muscle or liver glycogen with aspartate, because a similar content of glycogen remained in the muscles and liver of control rats after a 60-min swim or after swimming to exhaustion.
It is well known that diabetic patients are at an increased risk of the earlier development of significant atherosclerotic disease. We wish to report the case of a young insulin-dependent diabetic with an 18 months history of rapidly progressing 'diabetic' retinopathy who presented with right-sided weakness and was found to have severe carotid artery disease. We suggest that the sudden proliferation in his retinopathy was due to retinal ischaemia secondary to the carotid artery stenosis and we wish to present this as a case of ocular ischaemic syndrome in a young diabetic patient.
To evaluate the use of human immunodeficiency virus type 1 (HIV-1) tat mRNA quantification as a marker for antiretroviral therapy, 10 zidovudine-naive, p24 antibody-positive subjects (Centers for Disease Control classes III and IV) were studied at the start of zidovudine treatment. HIV-1 proviral DNA content and tat mRNA levels were monitored for 20 weeks from the initiation of therapy. Levels of tat mRNA were quantified using an engineered tat cRNA internal control under conditions of linear amplification. Proviral DNA levels increased in 2 patients and decreased in 8 during 20 weeks of therapy. In each case, tat mRNA levels exhibited similar but much more pronounced changes. Results indicate that quantitative measurement of tat mRNA levels is extremely useful for monitoring antiretroviral therapy.
Ten patients with AIDS and progressive cytomegalovirus disease were treated with ganciclovir and foscarnet concurrently. The patients had received ganciclovir and foscarnet monotherapy a median of 330 days before receiving combination therapy for a median of 80 days. Nine of the 10 patients responded to the combination. No electrolyte abnormalities were noted during combination therapy, but rates of neutropenia (relative rate, combination vs. ganciclovir, 1.99; P = .229) and thrombocytopenia (relative rate, combination vs. ganciclovir, 1.53; P = .616) were higher with combination therapy than with either drug alone. The relative rate of anemia was significantly increased with combination therapy compared with monotherapy (relative rate, combination vs. ganciclovir, 2.69; P = .025). These data suggest that combination ganciclovir and foscarnet therapy after failure of either alone appears to be as effective as standard therapy with single agents. The rate of anemia with combination therapy was significantly greater than either agent alone, but no significant difference was noted among the other parameters of toxicity studied.
BACKGROUND: Socioeconomic status (SES) indicators including education, income, and occupation are associated with coronary heart disease (CHD) risk factors, morbidity, and mortality. In most industrialized nations, individuals with less education, lower income, and blue collar occupations have the highest CHD rates. It is suggested by some that these differences by SES are increasing even as age-adjusted CHD mortality declines. METHODS AND RESULTS: The Minnesota Heart Survey includes measurement of CHD risk factors and behaviors in population-based samples of Minneapolis-St. Paul adults aged 25 to 74 years in 1980 to 1982 (N = 3243) and 1985 to 1987 (N = 4538). Education was significantly and inversely related to blood pressure, cigarette smoking, body mass index, and a summary risk score for both men and women. Serum cholesterol was inversely related to education in women but not in men. Education was positively associated with leisure physical activity and health knowledge. Associations with household income were less consistent in magnitude and direction. Risk characteristics improved significantly between the 1980 to 1982 and 1985 to 1987 surveys. These changes were similar across education and household income levels. CONCLUSIONS: Improvement in CHD risk factors over time unrelated to education or income suggests that population-wide factors such as improved health knowledge, availability of healthy food items, hypertension treatment, and restrictions on cigarette smoking are operating beneficially in all SES groups. Although the SES gradient in risk factors is not increasing, it remains substantial and indicates directions for future prevention efforts.
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We have previously reported that (a) fetal fibroblasts migrate into 3-dimensional collagen matrices to a significantly greater extent that do adult cells, (b) this difference in migratory behaviour results from the secretion by fetal fibroblasts of a "migration stimulating factor" (MSF), and (c) adult fibroblasts retain responsiveness to MSF, this providing the basis of a bioassay for monitoring factor activity. Using a recently modified purification protocol, MSF isolated from fetal fibroblast conditioned medium elutes as a single activity peak in the penultimate Mono Q anion exchange chromatography step. Analysis of this material by SDS-PAGE indicates that it consists of three proteins, one with an apparent molecular mass of 119 kDa and a doublet with molecular masses of approximately 43 and 33 kDa, respectively. Our data suggest that the two proteins comprising the doublet result from the degradation of the larger molecule during the purification procedure. Both the 119 kDa species and lower molecular weight doublet stimulate fibroblast migration (with half maximal activity in the region of 1-10 pg/ml) and contain a structural domain exhibiting significant amino acid sequence homology with the gelatin-binding fragment (GBF) of fibronectin. Bona fide preparations of GBF, obtained by the limited proteolysis of plasma fibronectin, also stimulate the migration of adult fibroblasts in a similar dose-dependent manner to that of MSF. In spite of this similarity, MSF and GBF differ in terms of a number of biological and biochemical parameters, thereby suggesting that MSF is a distinct gene product and not a proteolytic degradation fragment of fibronectin. MSF stimulates the synthesis of a high molecular weight species of hyaluronic acid (HA). Our current data suggest that the observed effect of MSF on cell migration is actually a secondary consequence of the accumulation of this HA in the collagen matrix. TGF-beta is a potent inhibitor of MSF, both in terms of its effects on cell migration and HA synthesis. As MSF is present in wound fluid, we have suggested that the inhibition of MSF activity by TGF-beta may reflect the antagonistic interaction of these two cytokines in the control of the wound healing process. Our recent data indicate that discrete minority subpopulations of MSF-secreting fibroblasts are also present at specific sites in the healthy adult and that these may undergo a transient and local expansion during wound healing.(ABSTRACT TRUNCATED AT 400 WORDS)
We investigated the long-term health effects of HIV-1 infection in homosexual men not close to developing AIDS by comparing 916 HIV-1-seropositive (SP) men at least 1.67-3.67 years prior to a clinical AIDS diagnosis to 2,161 HIV-1-seronegative (SN) controls. The SP group reported a higher total of 12 distinct symptoms (fatigue, shortness of breath, night sweats, rash, cough, diarrhea, headache, thrush, skin discoloration, fever, weight loss, and sore throat/mouth) than did the SN group (p < 0.0001), corresponding to at least 5.6 more days/year of such symptoms. The SP group had lower body mass index (p < 0.0001) and lower hemoglobin (p < 0.0001). The SP group was more depressed, as measured by CES-D score (p = 0.047), before knowledge of one's serostatus was likely, and became even further depressed (p = 0.038 for increase in depression) after the HIV-1 serostatus test was accessible to high-risk groups. These associations remained unchanged in multivariate models, incorporating other covariates.
Studies of the enteric nervous system have proved to be important in the development of new concepts of the chemical nature of transmission from neurons. In particular, they have revealed the multiplicity of influences that peptides can have on transmission, such as their action as primary transmitters, and the fact that they often act as co-transmitters in enteric neurons. However, in other cases no roles can be attributed to neuropeptides in enteric neurons, and their involvement in short-term changes in excitability seems minor.
The antimicrobial activity of 2,2'-bipyridine, an iron-binding agent, was investigated by incorporating this agent into Scotchbond dental adhesive resin. The growth of Streptococcus mutans on the surface of resin, media and culture vessel was determined by optical density measurements. It was observed that 2,2'-bipyridine exhibited excellent antimicrobial properties.
Lumbar disc prolapse with urinary dysfunction is an uncommon condition. The clinical, pathological and follow-up details of 30 patients are presented. Detrusor recovery is rare and most patients are left with an areflexic bladder. Female patients with lumbar disc prolapse and an areflexic detrusor who strain to empty their bladders are likely to develop genuine stress incontinence. This may be managed by the early institution of intermittent self-catheterisation, which may reduce the need for incontinence surgery.
Using a case-control study of untreated men, we investigated the physical, mental, and economic effects of human immunodeficiency virus (HIV-1) infection prior to the diagnosis of acquired immunodeficiency syndrome (AIDS). Beginning 2 to 2.5 years prior to AIDS, case subjects reported more of 12 HIV-1 related symptoms and during the year prior to AIDS, at least 30.6 extra days of these symptoms than did control subjects. Within the 6 months preceding AIDS, case subjects' unemployment rose to 9% (P < or = .05) and depression to 34.2% (P < or = .001). At 6 to 12 months and within 6 months before AIDS, 17.1% and 31.5%, respectively, were anemic, while 37.7% and 64.7% had CD4+ counts less than 200 x 10(6)/L. Diagnosing AIDS at CD4+ counts less than 200 x 10(6)/L could significantly reduce pre-AIDS morbidity. Other implications of these findings are discussed.
This study examines the risk of developing cytomegalovirus (CMV) retinitis as a function of the duration and degree of CD4+ lymphocyte depletion. A retrospective analysis of 135 persons infected with the human immunodeficiency virus (HIV) was performed. Kaplan-Meier estimates for the percentage of patients developing CMV retinitis during the 27-month study period were calculated. Twenty-six patients were diagnosed as having CMV retinitis. In 14 of these patients, T cell phenotyping was done within the 3 months preceding diagnosis. The mean CD4+ lymphocyte count for these patients was 15.6 cells/mm3 (range, 2-33/mm3). At 27 months, the percentage of patients developing CMV retinitis with baseline CD4+ lymphocyte counts of 0-50, 51-100, and 101-250 cells/mm3 was 41.9%, 26.3%, and 14.7%, respectively (log-rank test, p = 0.003). The odds ratio for developing CMV retinitis for those with baseline CD4+ lymphocyte counts of 0-50 cells/mm3 compared with those with CD4+ lymphocyte counts of 101-250 cells/mm3 was 4.62 (p = 0.002). Twenty-four patients had CD4+ lymphocyte counts of < or = 50 cells/mm3 for an average of 13.1 months prior to diagnosis. Twenty-two patients had an acquired immune deficiency syndrome (AIDS)-defining illness diagnosed for an average of 18.0 months prior to the onset of retinitis. CMV retinitis is most likely to develop in patients with AIDS when the CD4+ lymphocyte count is < or = 50 cells/mm3.
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