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Biomedical subjects

V L Yu

Publications and source records attributed to V L Yu.

At least 91 records · Page 5Linked to original sources

Assessment of enzyme immunoassay versus radioimmunoassay for detection of Legionella pneumophila serogroup 1 antigen in frozen urine specimens.

An enzyme immunoassay (EIA) was compared with a radioimmunoassay (RIA) for detection of Legionella pneumophila serogroup 1 antigen in 37 frozen urine samples. Among 18 samples positive by the RIA at the time of collection, 50% (9 of 18) of stored specimens retained positivity when retested by the RIA whereas 78% (14 of 18) of stored specimens retained positivity when retested by the EIA (P < 0.02). A false-negative result occurred after storage for 5 months or less if the original RIA result showed weak positivity.

Humans↗

Epitope-labeled soluble human interleukin-5 (IL-5) receptors. Affinity cross-link labeling, IL-5 binding, and biological activity.

The human receptor for the potent eosinophilopoietic cytokine interleukin-5 (IL-5) consists of two components: a 60-kDa ligand-binding alpha chain (IL-5 alpha R) and a 130-kDa beta chain (IL-5 beta R). Three ectodomain constructs of the alpha chain (alpha RED) bearing C-terminal epitope tags were engineered and expressed in baculovirus-infected Sf9 cells. Each recombinant alpha chain was secreted into the medium, maximum expression occurring 72 h post-infection. The various soluble alpha chains were shown by affinity cross-link labeling and competition with unlabeled IL-5 to bind recombinant human (rh) 125I-IL-5 specifically with an ED50 of 2-5 nM. The epitope tag provided a simple purification of the receptor from conditioned medium using immunoaffinity chromatography. The purified material had an apparent molecular mass of 43 kDa and was heterogeneously glycosylated. Sedimentation analysis revealed a 1:1 association of the purified epitope-tagged soluble receptor with its ligand, resulting in the formation of a 70-74-kDa complex. Circular dichroism analysis revealed that the soluble alpha chain existed with a significantly ordered structure consisting of 42% beta-sheet and 6% alpha-helix. Such analyses combined with fluorescence spectrometry suggested that ligand-receptor complex formation in solution resulted in minimal conformational changes, consistent with the suggestion that the membrane-associated form of the alpha chain itself has minimal signal transduction capability. Surface plasmon resonance studies of the interaction of the purified alpha RED with immobilized rhIL-5 revealed a specific, competable interaction with a dissociation constant of 9 nM. Preincubation of an IL-5-dependent cell line with the epitope-tagged alpha RED also dose-dependently neutralized rhIL-5-induced proliferation. These data demonstrate that biologically active epitope-tagged recombinant soluble IL-5 receptors are facile to produce in large quantities and may have therapeutic utility in the modulation of IL-5-dependent eosinophilia in man.

Amino Acid Sequence↗

Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases.

Cysteine proteases related to mammalian interleukin-1 beta-converting enzyme (ICE) and the nematode cell death abnormal ced-3 gene product have been implicated in the effector mechanism of apoptotic cell death. Two novel members of this new family of ICE/CED-3-related proteases, designated ICErel-II and ICErel-III, were cloned from human monocytic cells. Both were highly homologous to human ICE (52% identical) and CED-3 (25% identical) and both contained the absolutely conserved pentapeptide sequence Gln-Ala-Cys-Arg-Asp containing the catalytic cysteine residue. Other structural motifs that were comparable with ICE suggest that ICErel-II and ICErel-III are also synthesized as larger proenzymes which are proteolytically processed to form heterodimeric active enzymes. Pro-interleukin-1 beta processing activity could not be detected in cells transfected with ICErel-II or ICErel-III, but pro-domain-less truncated forms of ICErel-II and ICErel-III were capable of effectively inducing fibroblast apoptosis. ICErel-II and ICErel-III may, therefore, participate in proteolytic events culminating in the apoptotic death of human cells.

Amino Acid Sequence↗

Trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in cirrhosis: a randomized trial.

OBJECTIVE: To assess the efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis and ascites. DESIGN: A randomized controlled trial. SETTING: University-affiliated Veterans Affairs medical center. PATIENTS: 60 consecutive patients with cirrhosis and ascites. INTERVENTIONS: Consecutive patients were randomly assigned to receive either no prophylaxis or trimethoprim-sulfamethoxazole, one double-strength tablet daily, five times a week (Monday through Friday). Patient entry was stratified by serum bilirubin (> 51 mumol/L [> 3 mg/dL]), ascitic fluid protein (< 1 g/dL), and serum creatinine (> 177 mumol/L [> 2 mg/dL]) levels to ensure that high-risk patients would be similarly distributed in the two groups. The median duration of follow-up for the study patients was 90 days. MAIN OUTCOME MEASURES: Spontaneous bacterial peritonitis or spontaneous bacteremia as defined by objective criteria. RESULTS: Spontaneous bacterial peritonitis or spontaneous bacteremia developed in 27% (8 of 30) of patients who did not receive prophylaxis compared with 3% (1 of 30) of patients receiving trimethoprim-sulfamethoxazole (P = 0.025). Overall, infections developed in 9 of 30 patients (30%) not receiving prophylaxis and in 1 of 30 patients (3%) receiving trimethoprim-sulfamethoxazole (P = 0.012). Death occurred in 6 of 30 patients (20%) who did not receive prophylaxis and in 2 of 30 patients (7%) who received trimethoprim-sulfamethoxazole (P = 0.15). Side effects--particularly, hematologic toxicity--could not be attributed to trimethoprim-sulfamethoxazole in any patient. CONCLUSIONS: Trimethoprim-sulfamethoxazole was efficacious, safe, and cost-effective for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis.

Ascites↗

Herpes zoster-associated idiopathic thrombocytopenic purpura in a liver transplant recipient: a case report and overview.

Idiopathic (autoimmune) thrombocytopenic purpura has been previously reported as a rare complication in children and in a few adults following chickenpox. We report a case of varicella zoster virus-associated idiopathic thrombocytopenic purpura in an adult liver transplant recipient following dermatomal zoster. Idiopathic thrombocytopenic purpura developed 3 days after the onset of herpes zoster in our patient, with a nadir platelet count of 3000/mm3. The patient was treated with intravenous gamma globulin with recovery of thrombocytopenia after 3 weeks. Transplant clinicians need to be aware that this serious and potentially life-threatening complication may occur with herpes zoster in transplant recipients.

Acyclovir↗

Invasive gastrointestinal zygomycosis in a liver transplant recipient: case report and review of zygomycosis in solid-organ transplant recipients.

Zygomycosis is a rare but highly invasive fungal infection that occurs in transplant recipients. We report a case of invasive gastrointestinal zygomycosis that occurred in a heavily immunosuppressed liver transplant recipient 5 days after retransplantation and that presented as gastric perforation. Despite aggressive surgical and antifungal therapy, the patient died. We review 46 cases of invasive zygomycosis in solid-organ transplant recipients. The rhinocerebral form of zygomycosis occurred in 57% of cases; the pulmonary, cutaneous, and disseminated forms each occurred in 13%; the renal form occurred in 2%; and the gastrointestinal form occurred in 2%. The infection ensued a median of 2 months after transplantation (range, 5 days to 8 years). Seventy-six percent of the patients had diabetes or had received antirejection therapy, mainly in the form of corticosteroids, before the onset of zygomycotic infection. The mortality for patients who received antifungal therapy and/or who underwent surgery was 50% for those who had rhinocerebral zygomycosis, none for those who had pulmonary and cutaneous zygomycosis, and 100% for those who had disseminated zygomycosis. Knowledge of the diverse clinical manifestations (including gastrointestinal involvement, as is illustrated by our case) and predisposing factors in transplant recipients with zygomycosis can aid in early recognition of this disease in this patient population.

Adult↗

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↗

Comparison of culture methods for monitoring Legionella species in hospital potable water systems and recommendations for standardization of such methods.

A lack of standardization of environmental monitoring techniques for Legionella spp. complicates the interpretation of results and comparisons of results from different institutions. A comparative assessment of techniques recommended by the Centers for Disease Control and Prevention, the Hygiene Institute (Graz, Austria), and our laboratory was performed. Variables investigated were sampling method (swabbing and collection of water samples [250 ml] before and after swabbing), method of concentration (none, filtration, and centrifugation), acid buffer treatment (no acid treatment, treatment for 3 min, and treatment for 15 min), and choice of medium (five formulations of buffered charcoal yeast extract agar with glycine, vancomycin, polymyxin B, anisomycin, or cycloheximide). Thirty-three sites in seven hospital buildings were studied. Recovery by swab correlated with recovery from water after swabbing (P < 0.05). However, the quantity of Legionella spp. recovered from swab specimens (mean, 3.0 x 10(4) CFU per swab) was greater than that recovered from water (mean, 4.7 x 10(3) CFU/250 ml). Filtration resulted in recovery rates (mean, 5.2 x 10(3) CFU/250 ml) higher than those by centrifugation (mean, 2.3 x 10(3) CFU/250 ml). Three minutes of acid buffer treatment to reduce overgrowth by commensal flora did not improve selectivity or sensitivity for Legionella spp. if glycine-containing selective media were used. Fifteen minutes of acid buffer treatment reduced recovery compared with that after a 3-min treatment. All glycine-containing media tested effectively inhibited background flora, but one selective medium containing dyes, glycine, vancomycin, and polymyxin B (DGVP) resulted in the greatest quantitative recovery of Legionella pneumophila. Use of buffered charcoal yeast extract agar and the acid buffer treatment gave the greatest recovery of non-pneumophila species. A standardized protocol with an emphasis on the culturing of swab samples is presented.

Bacteriological Techniques↗

Necrotizing (malignant) external otitis: prospective comparison of CT and MR imaging in diagnosis and follow-up.

PURPOSE: To compare computed tomography (CT) and magnetic resonance (MR) imaging in the diagnosis and follow-up of necrotizing external otitis. MATERIALS AND METHODS: CT and MR imaging were performed in seven patients at diagnosis and at 6 and 12 months after initiation of therapy. Imaging findings were compared and correlated with the clinical course of the disease. RESULTS: Cortical bone erosion was best seen on CT scans (n = 5 vs n = 0 on MR images) and failed to normalize with cure. Subtemporal soft-tissue abnormalities (n = 7 with both modalities) were better appreciated with MR imaging and had low signal intensity on T1- and T2-weighted images. Soft-tissue changes improved but did not disappear completely with treatment. CONCLUSION: CT is preferred at initial diagnosis, as small cortical erosions are better seen. Either modality can be used to follow up soft-tissue evolution. MR imaging may be better for evaluation and follow-up of meningeal enhancement and changes within the osseous medullary cavity.

Aged↗

Infectious complications in liver transplant recipients on tacrolimus. Prospective analysis of 88 consecutive liver transplants.

This prospective study characterizes the incidence, etiology, timing, risk factors, and outcome of the infectious complications after 88 consecutive liver transplantations in 79 patients receiving tacrolimus (FK506) as primary immunosuppression with a median follow-up of 880 days. Infections occurred in 59% (47/79) of the patients, and 39% had major infections. Of the major infections, 55% were bacterial, 22% were viral, and 22% were fungal. Bacteremia accounted for 30% of major bacterial infections. Sixty percent of bacteremias occurring within the first 3 months were catheter related, while 75% of those occurring more than 3 months after transplant were of a biliary source. Patients with recurrent hepatitis C virus hepatitis and patients requiring dialysis after transplant had a significantly higher rate of infections as compared with other patients. Overall mortality was 18%, and 29% of all deaths were associated with infection. Only invasive aspergillosis was associated with infectious mortality. Our data suggest that the potent immunosuppressive agent FK506 is not associated with a higher incidence of infectious complications as compared with previous studies using CsA.

Adult↗

High-dose acyclovir compared with short-course preemptive ganciclovir therapy to prevent cytomegalovirus disease in liver transplant recipients. A randomized trial.

OBJECTIVE: To assess the efficacy of high-dose oral acyclovir therapy compared with preemptive, short-course ganciclovir therapy (administered only if cytomegalovirus [CMV] shedding occurred) to prevent CMV disease in liver transplant recipients. DESIGN: A randomized controlled trial. SETTING: Liver transplant center at a university-affiliated Veterans Affairs Medical Center. PATIENTS: 47 consecutive patients having liver transplantation. INTERVENTION: Patients were stratified by their CMV antibody status and the CMV antibody status of the donor and were randomly assigned to one of two treatment groups. Surveillance cultures for CMV (buffy coat and urine) were done every 2 to 4 weeks for 24 weeks in all patients. One group received high-dose oral acyclovir (800 mg four times daily). The experimental group received no acyclovir, but if surveillance cultures were positive, ganciclovir (5 mg/kg intravenously twice daily) was administered for 7 days. MEASUREMENTS: Cytomegalovirus shedding and CMV disease were measured in the two groups. RESULTS: Cytomegalovirus shedding before the onset of CMV disease occurred in 25% (6 of 24) of patients in the acyclovir group compared with 22% (5 of 23) in the experimental group. Cytomegalovirus disease developed in 29% (7 of 24) of the acyclovir group and in 4% (1 of 23) of the experimental group (P < 0.05). No hematologic toxicity occurred with ganciclovir. CONCLUSION: Oral acyclovir is ineffective prophylaxis against CMV in liver transplant recipients. Preemptive, short-course ganciclovir therapy in patients with CMV shedding was well tolerated and provided effective prophylaxis against subsequent CMV disease; this protocol targets the patients at risk for CMV disease and minimizes toxicity and expense.

Acyclovir↗

Decreased incidence of viral infections in liver transplant recipients. Possible effects of FK506?

Cytomegalovirus (CMV) is a major infectious complication of organ transplantation and its incidence is influenced by the type and intensity of immunosuppressive therapy employed. Using a new immunosuppressive agent FK506, CMV infection was observed in 30% and CMV disease in 15% of the 26 liver transplant recipients. Delayed onset of CMV disease was noted; the mean time to the occurrence of CMV disease being 137 days posttransplantation. No graft loss or mortality could be attributed to CMV infection. Mucocutaneous herpes simplex virus (HSV) infections were encountered in 19% of the patients, while no disease could be attributed to varicella zoster virus or Epstein-Barr virus (EBV). The contribution of FK506 to a decrease in viral morbidity and associated mortality bears further investigation.

Cytomegalovirus Infections↗

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↗

Prosthetic valve endocarditis: superiority of surgical valve replacement versus medical therapy only.

The objective of our study was to assess the long-term outcome of patients with prosthetic valve endocarditis. We used a multicenter, prospective, observational study design. Six university teaching hospitals with high volume cardiothoracic surgery participated. Seventy-four patients with prosthetic valve endocarditis as defined by explicit, objective criteria were selected for participation. All patients were followed up prospectively for 1 year. Thirty-one percent and 69% had development of endocarditis within 60 days of valve insertion ("early") and after 60 days ("late"), respectively. The most common causes were Staphylococcus epidermidis (40%), Staphylococcus aureus (20%), streptococcal species (18%), and aerobic gram-negative bacilli (11%). Physical signs of endocarditis (new or changing murmur, stigmata, emboli) were seen in 58%. At 6 months and 12 months, mortality was 46% and 47%, respectively. Surgical replacement of the infected valve led to significantly lower mortality (23%) as compared with medical therapy alone (56%), as assessed by both univariate and multivariate analyses (p < 0.05). Improved outcome was seen for the surgical group even when controlling for severity of illness at time of diagnosis. From these findings we conclude that accurate assessment of outcome in prosthetic valve endocarditis requires long-term follow-up of at least 6 months following diagnosis. Surgical therapy warrants greater scrutiny; evaluation in controlled clinical trials is appropriate.

Adult↗