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Biomedical subjects

M H Nguyen

Publications and source records attributed to M H Nguyen.

At least 55 records · Page 3Linked to original sources

Candida infection of the arteriovenous fistula used for hemodialysis.

Arteriovenous fistula infection is an exceedingly rare manifestation of Candida infection, with only one case previously reported in the English literature. This report describes three cases of Candida arteriovenous fistula infection seen in a prospective study and reviews the previously reported case. All cases involved the polytetrafluoroethylene graft. The presentations can be either acute or subacute in onset, with drainage at the fistula site as the most common sign. The diagnosis of Candida arteriovenous fistula infection relies on the isolation of the organism from an intraoperative culture of the fistula. Candida was isolated from blood in three of four cases, and wound drainage in two of three cases. Antifungal therapy should be given, but complete removal of the arteriovenous fistula may be necessary for long-term cure.

Aged↗

Determinants of compliance with antiretroviral therapy in patients with human immunodeficiency virus: prospective assessment with implications for enhancing compliance.

Non-compliance with therapy is a significant problem, particularly when the disease process is chronic and therapeutic regimens are employed for prolonged periods. We assessed the prevalence and variables associated with compliance with antiretroviral therapy in patients with human immunodeficiency virus infection, by means of a longitudinal observational study of 46 patients aged 23 to 68 years, with human immunodeficiency virus infection, followed at the Pittsburgh VA Medical Center. Data on demographics, medical status, physical functioning (Karnofsky performance scores), CD4 lymphocyte count, depression (Beck depression inventory), coping (inventory of coping with illness scale scores), and psychological and emotional stress (profile of mood states scale scores), were prospectively assessed on all patients at baseline and every 6 months. Compliance was assessed at 6 and 12 months: patients taking > or = 80% of antiretroviral therapy were considered compliant. Overall, 63% of patients were compliant with antiretroviral therapy. Age, education, employment, religious support, and perceived quality of life did not correlate with compliance. By univariate analysis, lack of prior intravenous drug use was significantly associated with compliance (p = 0.01). Compliant patients had significantly better adaptive coping (p = 0.03), and less depression (p = 0.04). By multivariate analysis, black race was significantly associated with non-compliance independent of intravenous drug use and educational status. History of prior opportunistic infection (which presumably heightens the perceived severity of illness) (p = 0.02), and lesser psychological disturbance scores (p = 0.02) were associated with compliance. Compliance was observed despite the greater number of prescription medications taken by compliant patients (p = 0.04). At 12 months, Karnofsky scores were better in compliant patients (p = 0.02), although mortality was not different. Besides identifying predictors of compliance, our data suggest that symptoms of depression and psychological stress be sought in patients with non-adherence.

Activities of Daily Living↗

Candida prosthetic valve endocarditis: prospective study of six cases and review of the literature.

Candida prosthetic valve endocarditis (PVE) is a rare entity; however, its incidence is expected to increase given the recent increase in incidence of nosocomial bloodstream candida infection. This report reviews six cases of candida PVE studied prospectively plus 12 cases previously reported in the literature. Transesophageal echocardiography was more sensitive than transthoracic echocardiography in detecting vegetations. Valvular replacement combined with antifungal therapy has been the standard treatment. However, successful therapy with long-term administration of oral fluconazole has been reported for five patients. The mortality due to candida PVE was high, especially when PVE was complicated by congestive heart failure and persistent fungemia. For uncomplicated PVE, the mortality rate for patients receiving antifungal therapy alone (40%) was no worse than for those receiving combined medical and surgical therapy (33%).

Adult↗

Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that serves as a model for the human disease multiple sclerosis. We evaluated rolipram, a type IV phosphodiesterase inhibitor, for its efficacy in preventing EAE in the common marmoset Callithrix jacchus. In a blinded experimental design, clinical signs of EAE developed within 17 days of immunization with human white matter in two placebo-treated animals but in none of three monkeys that received rolipram (10 mg/kg s.c. every other day) beginning 1 week after immunization. In controls, signs of EAE were associated with development of cerebrospinal fluid pleocytosis and cerebral MRI abnormalities. In the treatment group, there was sustained protection from clinical EAE, transient cerebrospinal fluid pleocytosis in only one of three animals, no MRI abnormality, and marked reduction in histopathologic findings. Rolipram-treated and control animals equally developed circulating antibodies to myelin basic protein. Thus, inhibition of type IV phosphodiesterase, initiated after sensitization to central nervous system antigens, protected against autoimmune demyelinating disease.

3',5'-Cyclic-AMP Phosphodiesterases↗

Meningitis caused by Candida species: an emerging problem in neurosurgical patients.

Three cases of candida meningitis were encountered in a 3-year period in our hospital; all occurred in neurosurgical patients. We describe these three cases and review the 15 cases of neurosurgery-related candida meningitis previously reported in the English-language literature. Data regarding these 18 patients formed the basis for our review. Most patients with candida meningitis had recently received antibacterial agents, and it is notable that 50% of patients suffered from antecedent bacterial meningitis. The CSF analysis revealed neutrophilic pleocytosis that was indistinguishable from that of bacterial meningitis. The overall mortality was 11%. Administration of amphotericin B combined with flucytosine appeared to be the best therapeutic approach for candida meningitis.

Adult↗

In vitro evaluation of combination of fluconazole and flucytosine against Cryptococcus neoformans var. neoformans.

Amphotericin B and fluconazole are current acceptable therapies for cryptococcal meningitis; however, their effect remains suboptimal. The combination of fluconazole and flucytosine has yielded encouraging clinical results in human immunodeficiency virus patients with cryptococcal meningitis. To investigate the biological basis of this finding, we performed in vitro combination testing of fluconazole and flucytosine against 50 clinical strains of Cryptococcus neoformans var. neoformans. Synergy (fractional inhibitory concentration index of < 1.0) was observed in 62% of cases, while antagonism (fractional inhibitory concentration index of > 2.0) was not observed. For cases in which synergy was not achieved (autonomous or additive effects), the beneficial effect of the combination was still seen (i.e., there was still a decrease, although not as dramatic, in the MIC of one or both drugs when used in combination). The in vitro inhibitory action of flucytosine was greatly enhanced by the addition of fluconazole; the flucytosine MICs for Cryptococcus isolates were markedly decreased to concentrations which were severalfold lower than the achievable cerebrospinal fluid flucytosine concentration. On the other hand, the addition of flucytosine did not greatly enhance the in vitro activity of fluconazole if the initial fluconazole MIC for the isolate was > or = 8 micrograms/ml. Controlled clinical studies are warranted to further elucidate the potential utility of fluconazole-flucytosine combination therapy.

Antifungal Agents↗

Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate.

In the human disease multiple sclerosis (MS), the immune mechanisms responsible for selective destruction of central nervous system myelin are unknown. In the common marmoset Callithrix jacchus, a unique demyelinating form of experimental allergic encephalomyelitis resembling MS can be induced by immunization with whole myelin. Here we show that the MS-like lesion can be reproduced by immunization against the extracellular domain of a single myelin protein, myelin/oligodendrocyte glycoprotein (MOG). By contrast, immunization against the quantitatively major myelin proteins myelin basic protein or proteolipid protein results in inflammation but little or no demyelination. Furthermore, in the presence of encephalitogenic (e.g., disease-inducing) T cells, the fully demyelinated lesion is reconstructed by systemic administration of IgG purified from whole myelin-, or MOG-immunized animals, and equally by a monoclonal antibody against MOG, but not by control IgG. Encephalitogenic T cells may contribute to the MS-like lesion through disruption of the blood-brain barrier that permits access of demyelinating antibody into the nervous system. The identification of MOG as a major target antigen for autoimmune demyelination in a nonhuman primate should facilitate development of specific immunotherapies for human MS.

Animals↗

Listeria monocytogenes peritonitis in cirrhotic patients. Value of ascitic fluid gram stain and a review of literature.

Listeria monocytogenes has been increasingly implicated in spontaneous bacterial peritonitis in patients with cirrhosis. This bacterium can be mistaken for diphtheroids and gram-positive cocci if special attention is not paid to the motility pattern and specific biochemical tests. Although the sensitivity of ascitic fluid Gram stain is low, we describe a case in which the Gram stain of the ascites fluid was positive. This issue is now pertinent given recent recommendations of third-generation cephalosporin antibiotics as empiric therapy for spontaneous bacterial peritonitis; Listeria is resistant to cephalosporin agents. A positive Gram stain could affect the empiric antibiotic therapy. We review the clinical presentation and outcome in nine other cases of Listeria peritonitis occurring in cirrhotic patients.

Aged↗

Aspergillus peritonitis in a continuous ambulatory peritoneal dialysis patient. Case report and review of the literature.

Aspergillus peritonitis is a rare but treatable complication of continuous ambulatory peritoneal dialysis. We report a case of Aspergillus peritonitis in a continuous ambulatory peritoneal dialysis patient and review the nine other cases reported in the literature. The course was often insidious, and the clinical manifestation and laboratory findings were similar to those of bacterial peritonitis. The distinctive feature of these cases was the persistence of symptoms despite broad-spectrum antibiotics. Catheter removal is of crucial importance in the management of this disease.

Aged↗

Intraocular candidiasis in patients with candidemia. Clinical implications derived from a prospective multicenter study.

PURPOSE: Intraocular infection caused by Candida species can have devastating visual consequences. With the emergence of Candida as a major nosocomial pathogen, the authors investigated the prevalence of ocular lesions in patients with candidemia and evaluated risk factors for eye involvement. METHODS: This study is a prospective, multicentered, observational design. One hundred eighteen patients with candidemia were evaluated by the infectious disease service and received indirect ophthalmologic examination within 72 hours of a reported positive blood culture. Ocular findings were classified on the basis of objective, pre-determined criteria. Candida chorioretinitis was defined as the presence of focal, white, infiltrative chorioretinal lesions without vitreal involvement. Candida endophthalmitis was defined as chorioretinitis with extension into the vitreous or intravitreal "fluff balls." RESULTS: In contrast to previous studies of patients with candidemia citing prevalence rates of endophthalmitis approaching 40%, no patients were shown to have endophthalmitis. Candida chorioretinitis was seen in 9% of the patients, all of whom received antifungal agents. The observation that chorioretinitis never progressed to endophthalmitis suggests that systemic antifungal agents provided adequate ocular therapy. Risk factors for Candida chorioretinitis include fungemia with Candida albicans (versus nonalbicans species), multiple positive blood cultures, visual symptoms, and immunosuppression. Twenty percent of patients had nonspecific ocular lesions not directly related to infection. CONCLUSION: Patients with candidemia who have the risk factors noted above warrant formal ophthalmologic examination.

Adolescent↗

Meningitis due to Xanthomonas maltophilia: case report and review.

Xanthomonas maltophilia is being increasingly recognized as an opportunistic pathogen in debilitated patients. We report a case of postoperative meningitis due to X. maltophilia and review the cases of X. maltophilia meningitis reported in the literature. Because X. maltophilia is often resistant to multiple beta-lactam agents, including cephalosporins and imipenem, trimethoprim-sulfamethoxazole appears to be the drug of choice for treatment of X. maltophilia meningitis.

Cerebrospinal Fluid↗

Resistance of human immunodeficiency virus type 1 to acyclic 6-phenylselenenyl- and 6-phenylthiopyrimidines.

Acyclic 6-phenylselenenyl- and 6-phenylthiopyrimidine derivatives are potent and specific inhibitors of human immunodeficiency virus type 1 (HIV-1). The development of in vitro resistance to two derivatives, 5-ethyl-1-(ethoxymethyl)-(6-phenylthio)-uracil (E-EPU), was evaluated by serial passage of HIV-1 in increasing concentrations of inhibitor. HIV-1 variants exhibiting > 500-fold resistance to E-EPSeU and E-EPU were isolated after sequential passage in 1, 5, and 10 microM inhibitor. The resistant variants exhibited coresistance to related acyclic 6-substituted pyrimidines and the HIV-1-specific inhibitors (+)-(5S)-4,5,6,7-tetrahydro-5- pyrimidines and the HIV-1-specific inhibitors (+)-(5S)-4,5,6,7-tetrahydro-5- methyl-6-(3-methyl-2-butenyl)imidazo[4,5,1-jk]benzodiazepin-2(1H)- thione (TIBO R82150) and nevirapine, but remained susceptible to 3'-azido-3'-deoxythymidine, 2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and phosphonoformic acid. DNA sequence analysis of reverse transcriptase (RT) derived from E-EPSeU-resistant virus identified a Tyr (TAT)-to-Cys (TGT) mutation at either codon 188 (Cys-188; 9 of 15 clones) or codon 181 (Cys-181; 5 of 15 clones). The same amino acid changes were found in RT from E-EPU-resistant virus, but the Cys-181 mutation was more common (9 of 10 clones) than the Cys-188 mutation (1 of 10 clones). Site-specific mutagenesis and production of mutant recombinant viruses demonstrated that both the Cys-181 and Cys-188 mutations cause resistance to E-EPSeU and E-EPU. Of the two mutations, the Cys-188 substitution produced greater E-EPSeU and E-EPU resistance. The predominance of the Cys-188 mutation in E-EPSeU-resistant variants has not been noted for other classes of HIV-1 specific RT inhibitors. HIV-1 resistance is likely to limit the therapeutic efficacy of acyclic 6-substituted pyrimidines if they are used as monotherapy.

Antiviral Agents↗

In healthy primates, circulating autoreactive T cells mediate autoimmune disease.

A T cell response against myelin basic protein (MBP) is thought to contribute to the central nervous system (CNS) inflammation that occurs in the human demyelinating disease multiple sclerosis. To test whether MBP-reactive T cells that are normally retrieved from the circulation are capable of inducing CNS disease, MBP-reactive T cell clones were isolated from the peripheral blood of healthy, unimmunized Callithrix jacchus (C. jacchus) marmosets. This primate species is characterized by a natural chimerism of bone marrow elements between siblings that should make possible adoptive transfer of MBP-reactive T cells. We report that MBP-reactive T cell clones efficiently and reproducibly transfer CNS inflammatory disease between members of C. jacchus chimeric sets. The demyelination that is characteristic of experimental allergic encephalomyelitis induced in C. jacchus by immunization against human white matter did not occur after adoptive transfer of the MBP-reactive clones. It was noteworthy that encephalitogenic T cell clones were diverse in terms of their recognition of different epitopes of MBP, distinguishing the response in C. jacchus from that in some inbred rodents in which restricted recognition of MBP occurs. These findings are the first direct evidence that natural populations of circulating T cells directed against a CNS antigen can mediate an inflammatory autoimmune disease.

Animals↗

Antibiotic-resistant Acinetobacter meningitis in neurosurgical patients.

Acinetobacter anitratus has emerged as one of the common pathogens responsible for postneurosurgical meningitis at the authors' institution. Seven patients with Acinetobacter meningitis were identified during the 4-year period of this study, five of whom acquired organisms susceptible only to imipenem and amikacin. Acinetobacter bacteremia occurred concomitantly in five patients. Despite late institution of therapy as a result either of organism misidentification on Gram stain or of unexpected acquisition of a highly resistant organism, the patients' outcome was favorable after the initiation of appropriate antibiotic therapy. Imipenem and amikacin, with or without intrathecal aminoglycosides, were effective in patients with resistant strains of Acinetobacter.

Acinetobacter Infections↗

Differential migration of astrocytes grafted into the developing rat brain.

Fetal and neonatal astrocytes migrate in specific patterns when transplanted into the adult rat host brain. However, it is unclear whether these astrocytes demonstrate the same degree of mobility during early brain development. In the present study, neonatal cortical, hippocampal, and hypothalamic astrocytes were collected from the brains of 1- to 3-day-old rats and placed in tissue culture. After 14 to 21 days, cultures enriched in astrocytes were harvested and labelled with either the fluorescent dye Fast Blue or fluorescein-labelled latex beads. They were then transplanted into the right frontal cerebrum of neonatal rats at 2, 5, 8, and 11 days postpartum. Seven days after transplantation, animals were sacrificed and their brains were fixed by immersion in aldehydes, sectioned on a cryostat, and examined with fluorescence microscopy. Transplanted astrocytes migrated along the corpus callosum, internal capsule, glial limitans, ventricular linings, and hippocampal structure. Labelled cells were also found in the contralateral hemisphere in day 2 brains. Migration in a radial fashion from the injection site toward the periphery was a particularly obvious pattern, and was most pronounced in these younger hosts. In days 5 and 8 rat brains, astrocyte migration became more restricted to the hemisphere of implantation. In 11-day-old host brains, hemispheric restriction and other region-specific influences became manifest and specifically modulated migration. Radial migration was absent in the 11-day-old host group except for cells of cortical origin. The observed results demonstrate that neonatal cortical, hippocampal, and hypothalamic astrocytes transplanted into the neonatal cerebrum migrate in patterns that are more extensive than in the adult brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗