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Biomedical subjects

Shan-Chwen Chang

Publications and source records attributed to Shan-Chwen Chang.

At least 55 records · Page 3Linked to original sources

Neutralizing antibody response and SARS severity.

Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. With a linear mixed model, neutralizing antibody titer was shown to peak between week 5 and week 8 after onset and to decline thereafter, with a half-life of 6.4 weeks. Patients with a longer illness showed a lower neutralizing antibody response than patients with a shorter illness duration (p = 0.008). When early responders were compared with most patients, who seroconverted on and after week 3 of illness, the small proportion (17.4%) of early responders (antibody detectable within 2 weeks) had a higher death rate (29.6% vs. 7.8%) (Fisher exact test, p = 0.004), had a shorter survival time of <2 weeks (Fisher exact test, p = 0.013), and were more likely to be > 60 years of age (Fisher exact test, p = 0.01). Our findings have implications for understanding the pathogenesis of SARS and for SARS vaccine research and development.

Adult↗

Cryptococcus neoformans peritonitis in two patients with liver cirrhosis.

Cryptococcus neoformans is an important pathogen in immunocompromised patients. We report 2 cases of spontaneous C. neoformans peritonitis in patients with liver cirrhosis, a condition not previously reported in Taiwan. Patient 1, a 59-year-old man with alcoholic liver cirrhosis, had primary C. neoformans peritonitis with fungemia. The patient recovered completely after prolonged fluconazole therapy without relapse. Patient 2, a 51-year-old woman with liver cirrhosis due to Budd-Chiari syndrome, had C. neoformans isolated from ascites, cerebrospinal fluid, and blood culture. In spite of adequate antifungal treatment, the patient died of fulminant sepsis. Information about the interaction and relation between liver cirrhosis and cryptococcal peritonitis is rare in the literature. The experience of these cases may help facilitate the diagnosis and treatment of cryptococcal peritonitis.

Cryptococcosis↗

Dose reduction for the management of indinavir-related toxicity in human immunodeficiency virus type 1-infected patients in Taiwan: clinical and pharmacokinetic assessment.

This study evaluated the feasibility of reducing the indinavir (IDV) dosage in Taiwanese patients receiving the standard IDV/ritonavir (RTV) dosage of 800/100 mg twice a day who had undetectable plasma human immunodeficiency virus type 1 (HIV-1) RNA but had developed IDV-related toxicities. After dosage reduction to IDV/RTV 600/100 mg twice a day, the dose-related toxicity decreased and plasma HIV RNA remained undetectable at 24 weeks post-switch in all patients. The maximal plasma concentration (Cmax) and area under the plasma concentration-time curve of IDV decreased significantly (median, 6.3 vs 4.3 microg/mL and 1892 vs 1292 microg.min/mL, p=0.01 and 0.001, respectively) but the minimal plasma concentration remained at a similar level (median, 1.0 vs 0.8 microg/mL, p=0.12). This study found that the reduction in the dosage of IDV in HIV-1 infected patients receiving the standard IDV/RTV regimen guided by therapeutic drug monitoring decreased the Cmax, dose-related toxicity and medical cost without compromising viral control.

Acquired Immunodeficiency Syndrome↗

Impact of nosocomial infections on medical costs, hospital stay, and outcome in hospitalized patients.

BACKGROUND AND PURPOSE: Nosocomial infections have been shown to be associated with increased attributable mortality, length of hospital stay, and health care costs in studies mainly conducted in western populations. However, the health care system in Taiwan differs from the typical situation in western countries, with longer hospitalization times and lower daily costs. The purpose of this study was to understand the economic and clinical impacts of nosocomial infections in Taiwan. METHODS: Between June 1, 2001 and December 31, 2001, every hospitalized patient (age >/= 16 years) with nosocomial infections (case group) and matched control patients without nosocomial infections of the same age, gender, underlying medical illness, clinical diagnosis at admission and disease severity (control group) were recruited. Demographic characteristics, length of hospitalization, costs and final outcomes of both groups were collected for analysis. RESULTS: A total of 482 patient-pairs with median age of 68 years were studied. The median length of hospital stay was 40 days for the case group and 22 days for the control group (p < 0.0001). The median hospital cost for the case group was 363,425 New Taiwan Dollars (NTD) and 165,965 NTD for the control group (p < 0.0001). The median additional hospital stay for patients with nosocomial infection was 15 days, which amounted to 127,354 NTD. The extra hospital costs were not only associated with accommodation but also fees for materials, and costs relating to pharmacy, laboratory tests and diet. Patients with nosocomial infections were more likely to have shock, organ failure and death (all p < 0.0001). Additional hospital stay and costs were not related to various infection sites and bacterial pathogens causing nosocomial infections; however, medical costs attributable to nosocomial fungal infection were higher than that of bacterial infections. CONCLUSIONS: Nosocomial infections have a significant impact on the length of hospital stay and medical care cost. Extra costs of nosocomial infections resulted not only from prolongation of hospital stay, but also other medical costs. Infection control for preventing nosocomial infections may play an important role in reducing medical costs, hospital stay, and mortality in hospitalized patients.

Aged↗

Community-acquired anaerobic bacteremia in adults: one-year experience in a medical center.

A prospective observational study was conducted to evaluate the clinical characteristics and outcome of community-acquired anaerobic bacteremia. From June 1 2001 through May 31 2002, 52 patients with community-acquired anaerobic bacteremia were enrolled at the emergency department in a teaching hospital. There were 19 patients (34%) with polymicrobial bacteremia and Escherichia coli was the most common copathogen (n = 6). Of 62 anaerobic isolates, species of the Bacteroides fragilis group were the most common isolates (n = 28, 45%), followed by Clostridium spp. (n = 11, 18%). Among the 52 patients enrolled, up to 27% had underlying malignancy and the gastrointestinal tract accounted for 48% of the sources of infection. Clinical manifestations suggesting anaerobic infections were common and three-quarters (n = 39) of 52 patients received adequate empirical antimicrobial treatment. Documentation of anaerobic bacteremia seldom influenced antimicrobial treatment. The 30-day mortality was 25%. Although univariate analysis revealed that underlying malignancy (p=0.003), leukopenia (p=0.044) and absence of fever (p=0.047) were associated with mortality, only malignancy (p=0.007) was an independent risk factor in the multivariate analysis.

Academic Medical Centers↗

Clinical manifestations and inflammatory cytokine responses in patients with severe acute respiratory syndrome.

BACKGROUND AND PURPOSE: Severe acute respiratory syndrome (SARS) is a highly transmissible disease with significant morbidity and mortality. Death from SARS is most often due to rapidly progressive respiratory compromise (acute respiratory distress syndrome, ARDS) and subsequent multi-organ dysfunction. However, the mechanisms evoking respiratory distress and a fulminant systemic response remain unclear. In order to elucidate the pathogenic mechanisms of SARS, we analyzed clinical manifestations and levels of serum cytokines of SARS patients. METHODS: Fourteen hospitalized patients with a diagnosis of SARS-associated coronavirus infection at National Taiwan University Hospital from March to May 2003 were included. Data on clinical manifestations, parameters of laboratory tests, complications and final outcomes of patients were collected retrospectively. Serial plasma inflammatory cytokines, including interleukin (IL)-1beta (IL-1beta), IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) of preserved serum were measured by enzyme immunoassay. RESULTS: All 14 patients had fever, dry cough and dyspnea. Twelve were intubated during hospitalization. The median duration from onset of fever to the nadir level or most severe condition was 9 days for hypoxia, 7 days for lymphocytopenia, 6.5 days for thrombocytopenia, 9.5 days for maximal pulmonary infiltrates; to peak serum levels was 9 days for C-reactive protein (CRP), 10.5 days for IL-6, 13.5 days for IL-8 and 12 days for TNF-alpha; to defervescence was 13 days. There was no significant elevation of serum IL-1beta levels in any of the 14 patients. There were no significant differences in peak levels of IL-6, IL-8 and TNF-alpha between patients with and without ARDS. The 8 patients who died tended to have higher peak levels of serum TNF-alpha compared to those who survived (14 vs 9.1 pg/mL; p = 0.06). CONCLUSION: Rapid elevation of inflammatory cytokines-IL-6, IL-8 and TNF-alpha might play a role in the development of SARS-related ARDS. The timing of elevations in inflammatory cytokines and CRP is correlated with progression of pulmonary infiltrates of SARS patients. The peak level of serum TNF-alpha tends to be higher in patients who die of SARS than in those who survive. Our results indicate that CRP and TNF-alpha might be used as prognostic markers of SARS.

Adult↗

Meningitis due to Histoplasma capsulatum and Mycobacterium tuberculosis in a returned traveler with acquired immunodeficiency syndrome.

Histoplasmosis has rarely been reported in Taiwan, and its clinical manifestations may be similar to those of tuberculosis. With increasing international travel, physicians need to be aware of the possibility of this disease when caring for patients with advanced human immunodeficiency virus (HIV) infection who have traveled to endemic areas. A 55-year-old Chinese male from Burma presented with concurrent histoplasmosis and tuberculous meningitis as the initial opportunistic infection of acquired immunodeficiency syndrome. Fever, altered mentation, pancytopenia, splenomegaly and marked elevations of serum lactate dehydrogenase (3601 U/L) and ferritin (>10(6) ng/mL) were noted. Despite treatment with amphotericin B and antituberculous therapy, the patient died on the 25th day of hospitalization. This case illustrates the complexity and challenges of management of opportunistic infections in travelers returning from Southeast Asia who are in the advanced stage of HIV infection.

AIDS-Related Opportunistic Infections↗

Impact of highly active antiretroviral therapy on incidence and management of human immunodeficiency virus-related opportunistic infections.

We review the changes in incidences of HIV-related opportunistic infections and the safety of discontinuation of primary and secondary prophylaxis for HIV-related opportunistic infections in patients achieving immune restoration after the introduction of highly active antiretroviral therapy (HAART). HIV-related opportunistic infections continue to occur in patients who are newly diagnosed with HIV infection, those in the early course of HAART or non-adherent to HIV care and HAART, and those in whom non-HIV-related infections have emerged as a significant cause of morbidity and mortality in the post-HAART era. Clinical studies of patients with tuberculosis and HIV co-infection are reviewed to provide appropriate regimen combinations of rifamycins and antiretrovirals, which have varying degrees of drug-drug interactions that have posed challenges in the management of tuberculosis as well as HIV infection.

AIDS-Related Opportunistic Infections↗

Temporal relationship of viral load, ribavirin, interleukin (IL)-6, IL-8, and clinical progression in patients with severe acute respiratory syndrome.

Although viral replication and overwhelming immune responses are believed to contribute to the progression of severe acute respiratory syndrome (SARS), little is known about the temporal relationship between viral load, ribavirin, proinflammatory cytokines, and clinical progression. We report that ribavirin was not effective in reducing the SARS coronavirus load in 3 of 8 probable cases studied and that elevated levels of interleukin (IL)-6 and IL-8 subsequent to the peak viral load were found in 8 and 6 cases, respectively. The nadir lymphocyte count during lymphopenia, the peak level of lactate dehydrogenase, and the peak density of pulmonary infiltrates lag further behind the peak viral load by a median of 4, 5, and 3.5 days, respectively. These findings provide important information for therapeutic strategies to treat SARS.

Adult↗

Clinical experience of the 23-valent capsular polysaccharide pneumococcal vaccination in HIV-1-infected patients receiving highly active antiretroviral therapy: a prospective observational study.

To assess the impact of vaccination with 23-valent pneumococcal polysaccharide vaccine on the risks for development of pneumococcal disease, all-cause community-acquired pneumonia, HIV progression, and mortality and immunologic and virologic responses among HIV-1-infected patients treated with highly active antiretroviral therapy (HAART), we conducted a 2-year prospective observational cohort study at a university hospital in Taiwan. A total of 305 HIV-1-infected patients who received 23-valent pneumococcal vaccine (vaccinees) and 203 patients who did not (non-vaccinees) were prospectively observed between 1 June 2000 and 31 October 2002. Changes of CD4+ and plasma viral load (PVL) from baseline to week 4 of vaccination were assessed in 31 randomly selected vaccinees. The incidence of pneumococcal disease and bacteremia of vaccinees was 2.1 per 1000 patient-years (PY) (95% confidence interval (95% CI), 1.7-2.5 per 1000 PY) over the median observation of 641 days (range, 37-832 days) following vaccination while that of non-vaccinee was 21.8 per 1000 PY (95% CI, 20.1-23.7 per 1000 PY) and 7.3 per 1000 PY (95% CI, 7.0-7.6 per 1000 PY), respectively, over the observation of 500 days (range, 32-851 days), with an adjusted odds ratio (AOR) for developing pneumococcal disease of 0.085 (95% CI, 0.010-0.735) and for bacteremia of 0.22 (95% CI, 0.018-2.561). The median CD4+ count increased by 45 x 10(6) l(-1) (P = 0.01) and median PVL change was 0 log(10) copies/ml (range of decrease, -0.74 to 2.47 log(10) copies/ml) after 1 month of pneumococcal vaccination among the subgroup of 31 vaccinees receiving HAART. The median CD4+ count increase from baseline to the end of study was 149 x 10(6) l(-1) for vaccinees and 107 x 10(6) l(-1) for non-vaccinees (P = 0.21). The AOR of developing all-cause community-acquired pneumonia and new AIDS-defining opportunistic illnesses (OI) of vaccinees as compared to non-vaccinees was 1.876 (95% CI, 0.785-4.485) and 0.567 (95% CI, 0.217-1.484), respectively. Death rate of vaccinees and non-vaccinees was 17.7 per 1000 PY (95% CI, 16.5-18.9 per 1000 PY) and 80.5 per 1000 PY (95% CI, 77.1-83.9 per 1000 PY), respectively. Adjusted hazard ratio for death of vaccinees as compared with non-vaccinees was 0.733 (95% CI, 0.236-2.274). Our data suggested that vaccination with 23-valent pneumococcal polysaccharide vaccine and receipt of HAART were associated with reduced risks for pneumococcal disease among HIV-1-infected patients receiving HAART. Vaccination did not increase the risks of all-cause community-acquired pneumonia, HIV progression, and mortality. Vaccination did not increase PVL or decrease CD4+ among HIV-1-infected patients receiving HAART.

Adult↗

Impact of chronic hepatitis B virus (HBV) infection on outcomes of patients infected with HIV in an area where HBV infection is hyperendemic.

Between June 1994 and February 2003, a total of 111 human immunodeficiency virus (HIV)-infected patients with chronic hepatitis B virus (HBV) coinfection and 387 HIV-infected patients without HBV or hepatitis C virus coinfection were prospectively observed to assess the impact of HBV infection on outcomes of HIV-infected patients. After a median duration of observation of 25 months, coinfected patients were more likely to develop hepatitis (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [CI], 1.69-3.82) and hepatic decompensation (adjusted odds ratio [AOR], 9.94; 95% CI, 1.89-52.35). Although similar proportions of the 2 patient groups had an increase in the CD4 count by > or =100x10(6) cells/L (AOR, 0.78; 95% CI, 0.45-1.36) and development of new opportunistic illnesses (AOR, 0.94; 95% CI, 0.53-1.66), HBV-infected patients had an increased risk for virologic failure (AOR, 1.76; 95% CI, 1.03-2.99) and death (AHR, 1.71; 95% CI, 1.19-2.47) after highly active antiretroviral therapy was initiated.

Adolescent↗

A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications.

Primary Klebsiella pneumoniae liver abscess complicated with metastatic meningitis or endophthalmitis is a globally emerging infectious disease. Its pathogenic mechanism remains unclear. The bacterial virulence factors were explored by comparing clinical isolates. Differences in mucoviscosity were observed between strains that caused primary liver abscess (invasive) and those that did not (noninvasive). Hypermucoviscosity correlated with a high serum resistance and was more prevalent in invasive strains (52/53 vs. 9/52; P < 0.0001). Transposon mutagenesis identified candidate virulence genes. A novel 1.2-kb locus, magA, which encoded a 43-kD outer membrane protein, was significantly more prevalent in invasive strains (52/53 vs. 14/52; P < 0.0001). The wild-type strain produced a mucoviscous exopolysaccharide web, actively proliferated in nonimmune human serum, resisted phagocytosis, and caused liver microabscess and meningitis in mice. However, magA- mutants lost the exopolysaccharide web and became extremely serum sensitive, phagocytosis susceptible, and avirulent to mice. Virulence was restored by complementation using a magA-containing plasmid. We conclude that magA fits molecular Koch's postulates as a virulence gene. Thus, this locus can be used as a marker for the rapid diagnosis and for tracing the source of this emerging infectious disease.

Animals↗

Nutritionally variant streptococcal infections at a University Hospital in Taiwan: disease emergence and high prevalence of beta-lactam and macrolide resistance.

From January 1993 to December 2002, 28 patients with nutritionally variant streptococci (NVS) infections were treated at a university hospital in Taiwan. Twelve (43%) of these patients had various underlying malignancies, and 7 (25%) had underlying valvular heart diseases. Nine patients (32%) had infective endocarditis, and 9 (32%) had primary bacteremia. The deaths of 7 patients (25%) were directly related to NVS infection. Among the 28 isolates recovered from these patients, 50% were not susceptible to penicillin, 33% were not susceptible to cefotaxime, and 93% were not susceptible to azithromycin.

Adolescent↗

Neuromuscular disorders in severe acute respiratory syndrome.

OBJECTIVE: To delineate and clarify neuromuscular disorders in patients with probable severe acute respiratory syndrome (SARS). DESIGN: Case series with follow-up ranging from 3 weeks to 2 months. SETTING: National Taiwan University Hospital, Taipei. PATIENTS: We investigated 4 patients with SARS who had concomitant neuromuscular problems. A diagnosis of SARS was based on the demonstration of serum coronavirus antibodies. Clinical presentations, laboratory results, electrophysiologic findings, and follow-up conditions were determined. RESULTS: Patients developed neuromuscular problems approximately 3 weeks after the onset of SARS. Two women experienced motor-predominant peripheral nerve disorders. A man developed myopathy and a third woman experienced neuropathy and myopathy. Cerebrospinal fluid obtained from 2 patients with neuropathy disclosed normal protein content and the absence of pleocytosis and SARS coronavirus antibodies. Both patients with myopathy had elevated serum creatine kinase levels. A rapid clinical and electrophysiologic improvement was evident during follow-up examinations, with a good prognosis. CONCLUSIONS: The neuromuscular problems in patients with SARS are considered to be critical-illness polyneuropathy or myopathy, possibly coexistent. Further pathological and microbiological studies are necessary to determine the relationship between SARS coronavirus and neuromuscular problems.

Adult↗

Evaluation of antibody responses against SARS coronaviral nucleocapsid or spike proteins by immunoblotting or ELISA.

Severe acute respiratory syndrome (SARS)-CoV is a newly emerging virus that causes SARS with high mortality rate in infected people. To study the humoral responses against SARS-CoV, we evaluated nucleocapsid (N) and spike (S) proteins-specific antibodies in patients' sera by Western blotting and enzyme-linked immunosorbent assay (ELISA). Recombinant N and S proteins of SARS-CoV were purified from transformed E. coli. Serum specimens from 40 SARS-CoV-infected patients in the convalescent phase were analyzed by Western blotting using the purified antigens. Serial serum specimens from 12 RT-PCR-confirmed SARS patients were assayed by ELISA using the recombinant N protein as coated antigen. By Western blotting, 97.5% of the SARS patients were positive for N protein-specific antibodies whereas only 47.5% of the samples were positive for S protein-specific antibodies. Using N protein-based ELISA, 10 out of the 12 patients were positive for N protein-specific antibodies and 6 of them showed seroconversion at mean of 16 days after onset of fever. Immunoblotting was useful for detecting the humoral immune response after SARS-CoV infection. Antibodies against SARS-CoV N protein appear at the early stage of infection, therefore, N protein-based ELISA could serve as a simple, sensitive, and specific test for diagnosing SARS-CoV infection.

Amino Acid Sequence↗