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Biomedical subjects

J E Edwards

Publications and source records attributed to J E Edwards.

At least 109 records · Page 6Linked to original sources
PubMed1994

A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute.

BACKGROUND: Amphotericin B has long been the standard treatment for candidemia, but its use is complicated by its toxicity. More recently, fluconazole, a water-soluble triazole with activity against candida species and little toxicity, has become available. We conducted a multicenter randomized trial that compared amphotericin B with fluconazole as treatment for candidemia. METHODS: To be eligible, patients had to have a positive blood culture for candida species, a neutrophil count > or = 500 per cubic millimeter, and no major immunodeficiency. Patients were randomly assigned to receive either amphotericin B (0.5 to 0.6 mg per kilogram of body weight per day) or fluconazole (400 mg per day), each continued for at least 14 days after the last positive blood culture. Outcomes were assessed by a group of investigators blinded to treatment assignment. RESULTS: Of the 237 patients enrolled, 206 met all entry criteria. The most common diagnoses were renal failure, nonhematologic cancer, and gastrointestinal disease. There was no statistically significant difference in outcome: of the 103 patients treated with amphotericin B, 81 (79 percent) were judged to have been treated successfully, as were 72 of the 103 patients treated with fluconazole (70 percent P = 0.22; 95 percent confidence interval for the difference, -5 to 23 percent). The bloodstream infection failed to clear in 12 patients in the amphotericin group and 15 in the fluconazole group; the species most commonly associated with failure was Candida albicans. There were 41 deaths in the amphotericin group and 34 deaths in the fluconazole group (P = 0.20). Intravascular catheters appeared to be the most frequent source of candidemia. There was less toxicity with fluconazole than with amphotericin B. CONCLUSIONS: In patients without neutropenia and without major immunodeficiency, fluconazole and amphotericin B are not significantly different in their effectiveness in treating candidemia.

Amphotericin B↗
PubMed1994

Efficacy of a home-based training program for older adults using elastic tubing.

The purpose of this study was to investigate the efficacy of, and the adherence to, a 12-week home-based progressive resistance training program for older adults utilizing elastic tubing. Sixty-two adults (mean age, 71.2 years) qualified to participate in the study. Subjects were randomly assigned to either the exercise (E) (n = 31) or non-exercise (NE) group (n = 31). Pre- and post-testing included isokinetic (1.05 rad.s-1) concentric/eccentric knee extension/flexion strength testing and flexibility measures of the hip, knee, and ankle. The E group trained three times per week, performing one to three sets of 10-12 repetitions for each of 12 resistance exercises. The exercises involved muscles of both the lower and upper body. Within the E group, 25 of the 31 subjects (80.6%) completed the study. Of the E subjects completing the study adherence to the three training sessions per week was 90% (range 72%-100%). Training resistances used during workouts increased significantly with the average estimated increase being 82% (P < 0.001). The E group also demonstrated significant (P < 0.05) increases in isokinetic eccentric knee extension (12%) and flexion (10%) strength. No other significant changes were observed between E and NE groups. These results suggest that home-based resistance training programs utilizing elastic tubing can serve as a practical and effective means of eliciting strength gains in adults over the age of 65.

Aged↗
PubMed1994

Clozapine in the treatment of a young adolescent with schizophrenia.

Although recent reports have suggested that clozapine may be efficacious in the treatment of adolescents with schizophrenia, few studies have examined the use of clozapine in patients younger than 17 years of age. We describe highly successful trials of clozapine conducted in a 13-year-old girl and her cousin, both of whom developed severe symptoms of schizophrenia, which were refractory to neuroleptic medication, at the ages of 11 and 13 years, respectively. The pharmacology of and clinical experience with clozapine are reviewed.

Adolescent↗
PubMed1994

Alopecia areata and increased prevalence of psychiatric disorders.

BACKGROUND: The relationship between psychiatric disorders and alopecia areata has not been well studied. Although previous reports have been unable to correlate psychiatric illness with hair loss, a recent study determined that 74% of patients with alopecia areata (AA) under evaluation had one or more lifetime psychiatric diagnoses. METHODS: Two hundred and ninety-four community-based patients with alopecia areata responded to a detailed questionnaire distributed by Help Alopecia International Research, Inc. The prevalence of psychiatric disorders was determined using diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IIIR). RESULTS: Major depression, generalized anxiety disorder, social phobia, and paranoid disorder were all present in patients with alopecia areata at rates significantly higher than in the general population. CONCLUSIONS: Alopecia areata patients are at a higher risk of developing psychiatric comorbidity during their clinical course.

Alopecia Areata↗
PubMed1994

Fluconazole and platelet microbicidal protein inhibit Candida adherence to platelets in vitro.

Adherence to vascular endothelium is considered an essential step in the pathogenesis of hematogenously disseminated candidiasis. Platelets have been shown to promote Candida adherence to vascular endothelium in vitro. In contrast, recent studies indicate that platelets may also play a role in the primary host defense against endovascular infection by secretion of alpha granule-derived platelet microbicidal protein (PMP), which possesses both bactericidal and fungicidal activities as well as antiadherence properties. We examined the influences of PMP and the antifungal agent fluconazole on the adherence of Candida albicans to rabbit platelets, as measured by quantitative flow cytometry. In the absence of PMP and fluconazole, adherence of C. albicans to platelets was rapid (complete within 1 min), saturable, and reversible. Following 2 h of exposure to fluconazole at 10x the MIC, platelet binding of C. albicans was substantially reduced (mean reduction, 32.1%; P = 0.08). Similarly, exposure of C. albicans to PMP (range, 0.5 to 5 micrograms/ml) for 2 h (but not 30 min) significantly reduced candidal adherence to platelets 43.1 to 62.1%; (reduction range, P < 0.05). Moreover, exposure of C. albicans to PMP (5 micrograms/ml for 30 min) and then fluconazole (10x the MIC for 2 h) further decreased candidal adherence to platelets in comparison with the adherence after exposure to either agent alone (mean reduction, 57.2%; P = 0.02 and 0.05, respectively). These data demonstrate that PMP and fluconazole individually reduce the ability of C. albicans to bind to platelets in vitro and that the antiadherence activities of fluconazole are augmented by PMP.

Animals↗
PubMed1994

Sterol composition of Cryptococcus neoformans in the presence and absence of fluconazole.

Analysis of the sterol compositions of 13 clinical isolates of the pathogenic yeast Cryptococcus neoformans obtained from five patients with recurring cryptococcal meningitis showed that, unlike Candida albicans, the major sterols synthesized by this yeast were obtusifoliol (range, 21.1 to 68.2%) and ergosterol (range, 0.0 to 46.5%). There was considerable variation in the sterol contents among the 13 isolates, with total sterol contents ranging from 0.31 to 5.9% of dry weight. The isolates from the five patients who had relapses had different total sterol contents and compositions in comparison with those of the pretreatment isolates, indicating either that the sterols had been changed by therapy or that the patients were infected with new isolates with different sterol compositions. Growth of the cryptococcal isolates in the presence of subinhibitory concentrations of fluconazole (0.25x the MIC) significantly altered the sterol content and pattern. The total sterol content decreased in nine isolates and increased in four isolates in response to pretreatment with fluconazole. Fluconazole had no consistent effect on ergosterol levels. In contrast, fluconazole caused a decrease in obtusifoliol levels and an increase in 4,14-dimethylzymosterol levels in all isolates. These results indicate extensive diversity in sterol content, sterol composition, and sterol synthesis in response to subinhibitory concentrations of fluconazole in C. neoformans strains. We propose that fluconazole inhibits the sterol synthesis of C. neoformans by interfering with both 14 alpha-demethylase-dependent and -independent pathways. No correlation between the sterol compositions of C. neoformans isolates and their susceptibilities to fluconazole was found.

Cholestadienols↗
PubMed1994

Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis.

One strategy for improving resistance to opportunistic pathogens is to determine host cellular responses during the invasion process and upregulate those responses that are relevant to host defense mechanisms. Within this context, we have shown previously that invasion of endothelial cells by Candida albicans in vitro causes increased production of prostaglandins. As a prerequisite for modulating endothelial cell prostaglandin production, we now characterize the mechanisms through which this process occurs. Endothelial cell invasion by C. albicans appeared to stimulate the conversion of arachidonic acid into prostaglandins by upregulating the synthesis of endothelial cell cyclooxygenase and increasing the activity of the endothelial cell phospholipase. The enhanced activities of these two enzymes were independent of calphostin C-sensitive protein kinase C and resulted in the increased production and extracellular secretion of prostaglandin I2 (PGI2), PGF2 alpha, and PGE2. The secretion of these prostaglandins had no effect on the amount of endothelial cell injury induced by C. albicans. The role of the increased prostaglandin secretion by endothelial cells is likely related to modulation of the leukocyte response at the candida-leukocyte-endothelial cell interface.

Candida albicans↗
PubMed1993

Long distance transport of lambs and the time needed for subsequent recovery.

The effects of nine and 14 hours of road transport and the subsequent recovery in lairage of 392 hill lambs were studied in August and November. The gathering and the handling of the lambs were stressful, both physically and psychologically, and the journey imposed further psychological and metabolic stress. The levels of noise in the trailer were high (90db[A]). There were no measurable differences between the responses of the lambs transported for nine or 14 hours and there appeared to be three stages in their recovery after transport. After the first 24 hours of lairage changes in the blood components usually associated with short term stress and dehydration had recovered; after 96 hours there had been a well defined recovery of liveweight and the levels of most of the metabolites measured appeared to have stabilised and after 144 hours the lambs had recovered almost completely, most of the creatine phosphokinase had been cleared from the plasma and their plasma protein levels had stabilised.

Animals↗
PubMed1993

Aberrant right subclavian artery with left aortic arch: associated cardiac anomalies.

Anomalous origin of the right subclavian artery (ARSA) from the aorta distal to the normally positioned left subclavian artery is a relatively frequent congenital anomaly in subjects with left aortic arch. The purpose of this study was to determine the relative frequency of associated cardiovascular anomalies in individuals with this anomaly. From the records of approximately 11,000 pathologic specimens in the Registry of Cardiovascular Disease of United Hospital (St. Paul, MN, USA), we found 128 (1.2%) with ARSA. Of the 128 ARSA, 117 (2.9%) occurred among 4102 instances of congenital heart disease. The 117 cases with congenital heart disease and ARSA were conotruncal anomalies in 38%, septal defects in 28%, obstructive anomalies of the left side of the heart in 21%, right heart anomalies in 5%, and miscellaneous conditions in the other 8%. Down syndrome existed in 14 (12%) of the 117 specimens with ARSA and some congenital cardiac anomaly; nine of the latter had an atrioventricular canal (AVC) malformation.

Adolescent↗
PubMed1993

Familial interruption of the aortic arch.

Interruption of the aortic arch (IAA) is an important congenital cardiac malformation occurring in 1.4% of cases with a congenital cardiac malformation. Only two reports have described IAA in siblings, each with type B and an anomalous right subclavian artery. We report the occurrence of IAA type B with an anomalous right subclavian artery in two siblings and their half-sibling, each of whom had additional conotruncal cardiac malformations. Recent evidence suggests that conotruncal cardiac malformations, including IAA type B, are related to abnormalities of neural crest cell migration. Thus, the family reported herein may manifest a syndrome related to alterations in mesenchymal tissue/neural crest cell migration.

Aorta, Thoracic↗
PubMed1993

Severe candidal infections in neutropenic patients.

The incidence of candidal infections in patients with cancer is increasing, and drug-resistant fungi are being isolated more frequently. Diagnosis of hematogenously disseminated candidiasis remains difficult. Characteristic clinical presentations, such as endophthalmitis and chronic hematogenously disseminated candidiasis, are inconstant and may not develop until after neutrophil recovery. Blood cultures are insensitive for detecting candidemia. Growth of Candida species in even one blood culture is strongly suggestive of hematogenously disseminated candidiasis. Serological tests to diagnose this disease remain experimental. Whenever feasible, central venous catheters should be removed from patients with candidemia. Amphotericin B is the treatment of choice for acute and chronic hematogenously disseminated candidiasis. The roles of azoles and liposomal amphotericin B in treating these diseases are currently undefined. Prophylactic use of antifungal agents decreases the incidence of documented fungal infections in neutropenic patients but does not improve overall survival and may increase the likelihood of infections by resistant fungi.

Amphotericin B↗
PubMed1993

The effect of a 12-week dynamic resistance strength training program on gait velocity and balance of older adults.

This study tested whether a 12-week dynamic resistance strength training program can change gait velocity and improve measures of balance among adults age 65 and older. Fifty-five community-dwelling adults (mean age = 71.1) were randomized into an exercise (n = 25) or control (n = 30) group. The exercisers were requested to complete three bouts of strength training per week for 12 weeks using elastic tubing. At posttest the exercisers demonstrated slower gait velocity, enhanced balance, and an improved ability to walk backward, although none of these posttest measures was significantly different from the control group.

Age Factors↗
PubMed1993

Interferon-gamma protects endothelial cells from damage by Candida albicans.

Endothelial cells activated with interferon-gamma (IFN-gamma) have been shown to inhibit the replication of Toxoplasma gondii. To determine if this cytokine protects endothelial cells from damage by Candida albicans, human umbilical vein endothelial cells were pretreated with IFN-gamma and infected with C. albicans; endothelial cell damage was measured by the release of 51Cr. Pretreatment with IFN-gamma decreased the extent of endothelial cell injury caused by C. albicans by up to 100% +/- 8.2%. This diminution of endothelial cell damage was confirmed by scanning electron microscopy. The degree of protection was dependent on the concentration of IFN-gamma, with maximum protection occurring at 13 units/mL. Higher concentrations of IFN-gamma were toxic to the endothelial cells. Pretreating the endothelial cells with this cytokine had no effect on candidal germination and growth, suggesting that IFN-gamma stimulates endothelial cells to become resistant to or inhibit the action of candidal virulence factors.

Candida albicans↗
PubMed1993

Fungicidal properties of defensin NP-1 and activity against Cryptococcus neoformans in vitro.

Defensin NP-1, derived from the neutrophils of rabbits, was tested for its fungistatic and fungicidal activity against strains of Cryptococcus neoformans. The MICs for the encapsulated strains tested ranged from 3.75 to 15.0 micrograms of NP-1 per ml. The minimum fungicidal concentrations for these strains were similar to the MICs. An acapsular strain, however, had a lower MIC of 0.93 and minimum fungicidal concentration of 1.88 micrograms/ml. NP-1 demonstrated time-dependent and concentration-dependent killing of C. neoformans. Killing occurred rapidly in the first 20 min of exposure to NP-1 and was maximum at 90 to 120 min. Killing of C. neoformans by NP-1 was concentration dependent with 31% +/- 9% survival at 25 micrograms/ml, 13% +/- 4% survival at 50 micrograms/ml, 9% +/- 5% survival at 75 micrograms/ml, and 5% +/- 3% survival at 100 micrograms/ml. NP-1's fungicidal effect on C. neoformans was also inoculum dependent, with increased activity observed at 10(4) versus 10(5) or 10(6) cells per ml. In addition, stationary-phase C. neoformans was less susceptible to NP-1 killing than yeast cells in the logarithmic phase. Subinhibitory concentrations of both NP-1 (0.25 x MIC) and fluconazole (0.25 x MIC) acted synergistically in inhibiting growth of C. neoformans. Similar combinations of NP-1 and amphotericin B, however, did not yield synergy.

Amphotericin B↗
PubMed1993

Thrombin-induced rabbit platelet microbicidal protein is fungicidal in vitro.

Platelet microbicidal protein (PMP) is released from platelets in response to thrombin stimulation. PMP is known to possess in vitro bactericidal activity against Staphylococcus aureus and viridans group streptococci. To determine whether PMP is active against other intravascular pathogens, we evaluated its potential fungicidal activity against strains of Candida species and Cryptococcus neoformans. Anionic resin adsorption and gel electrophoresis confirmed that the fungicidal activity of PMP resided in a small (approximately 8.5-kDa), cationic protein, identical to previous studies of PMP-induced bacterial killing (M.R. Yeaman, S.M. Puentes, D.C. Norman, and A.S. Bayer, Infect. Immun. 60:1202-1209, 1992). When assayed over a 180-min period in vitro, the susceptibilities of these fungi to PMP varied considerably. Generally, Candida albicans strains (mean survival, 33.5% +/- 6.9% [n = 6]) as well as isolates of Candida glabrata (mean survival, 50.8% +/- 2.9% [n = 2]) were the most susceptible to killing by PMP, while Candida guillermondii and Candida parapsilosis were relatively resistant to PMP-induced killing. Compared with C. albicans, C. neoformans was relatively resistant to the fungicidal activity of PMP, with a mean survival among the isolates studied of 77.4% +/- 12.4% (n = 6). Against C. albicans, PMP-induced fungicidal activity was time dependent (range, 0 to 180 min), PMP concentration dependent (range, 10 to 150 U/ml), and inversely related to the fungal inoculum (range, 5 x 10(3) to 1 x 10(5) CFU/ml). Scanning electron microscopy of PMP-exposed C. albicans and C. neoformans cells revealed extensive surface damage and collapse, suggesting that the site of PMP fungicidal action may directly or indirectly involve the fungal cell envelope.

Amphotericin B↗