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Biomedical subjects

K T Luh

Publications and source records attributed to K T Luh.

At least 145 records · Page 8Linked to original sources

Intracellular pH regulation in cultured human pleural mesothelial cells.

The human pleural space is lined by a single layer of mesothelial cells, the intracellular pH (pH(i)) of which has never been investigated. In the present study, the intrinsic buffering power of H+ ions (beta(i)) and the pH(i) regulatory systems were investigated in primary cultures of human pleural mesothelial cells (PMCs) with microspectrofluorimetry. We found: (1) that at the resting pH(i), the beta(i) was low and increased as the pH(i) decreased; (2) that the pH(i) recovery was largely inhibited either with Na+-free medium or nominally HCO3 free medium containing ethyl-isopropyl amiloride (EIPA); (3) a 4-4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive, Na+/HCO3-dependent, but Cl(-)-independent acid extrusion mechanism in CO2/HCO3 buffer; and (4) that in the same buffer, a DIDS- sensitive but Na+-independent alkalosis was induced by intracellular Cl- depletion. We therefore conclude that at least three membrane pH(i) regulators are involved in regulating the pH(i) in PMCs, these being the EIPA-sensitive Na+-H+ exchanger; a novel electroneutral, DIDS-sensitive Na+-HCO3 cotransporter; and the DIDS-sensitive Cl(-)-HCO3 exchanger. Furthermore, under physiologic conditions, the Na+-HCO3 cotransporter plays a more important role in extrusion of excess intracellular H+ ions than does the Na+-H+ exchanger.

Amiloride↗

Sialomucin expression is associated with erbB-2 oncoprotein overexpression, early recurrence, and cancer death in non-small-cell lung cancer.

Mucin production, when heavily sialylated, can promote cancer cell invasion and metastasis, and modulate the immune recognition system of the host. To explore the prognostic implication of sialomucin expression in lung cancer, we studied 116 patients with non-small-cell lung cancer (NSCLC). Tumor specimens were stained immunohistochemically with monoclonal antibodies (mAbs) against mucin glycoprotein (17Q2, HMFG2, SM3), and histochemically with periodic acid-Schiff/alcian blue to differentiate neutral mucin from acid mucin, and with high-iron diamine/alcian blue to differentiate sialomucin from sulfomucin. The expression status of two established molecular prognostic factors, the p53 and erbB-2 oncoproteins, were evaluated immunohistochemically. The staining was performed on two separately archived, paraffin-embedded tumor blocks for each patient, with normal lung as a control. Correlations were subsequently made among stains and various clinicopathologic factors. All analyses were blinded, and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Associations were established among adenocarcinoma histotype and erbB-2 overexpression, sialomucin expression, and 17Q2 and HMFG2 immunohistochemical positivity (p < 0.05). Sialomucin expression was closely linked to erbB-2 overexpression (p = 0.01). Significant univariate predictors (p < 0.05) of recurrence and cancer death were surgical stage, p53 expression, erbB-2 overexpression, and sialomucin expression. These four factors remained as independent predictors of early recurrence (p < 0.05) after multivariate analysis. For cancer death prediction, p53 and sialomucin expression had a marginal effect. We concluded that sialomucin expression is also a poor indicator of prognosis, which is associated with erbB-2 oncoprotein overexpression, early postoperative recurrence, and cancer death in NSCLC.

Actuarial Analysis↗

Serodiagnosis of tuberculosis. A study comparing three specific mycobacterial antigens.

To compare the efficacy of different mycobacterial specific antigens and to assess the applicability of the combination of several different antigens in the diagnosis of tuberculosis, three ELISA tests derived by Antigen 60, 38kda, and Kp90 were evaluated in 594 Chinese patients (312 patients with active pulmonary tuberculosis and 282 control subjects). Quantified levels of sensitivity and specificity were compared with those in the nontuberculous control groups. Antigen 60 IgG (sensitivity and specificity, 80.77 and 88.4%) was more antigenic and more effective in its determination than was 38kda IgG (sensitivity and specificity, 64.21 and 80.74%) and Kp90 IgA (sensitivity and specificity, 62.58 and 66.3%). The clinical significance of the difference, however, was not striking: negative predictive value of Antigen 60, 38kda, and Kp90 was 93, 86 and 83%, respectively; positive predictive value of Antigen 60, 38kda, and Kp90 was 71, 54, and 39%, respectively. Combination of different antigens could improve the sensitivity and specificity by no more than 10%, with the sacrifice of the opposite parameter by no less than 20%. The same improvement in sensitivity could be easily achieved by adjusting the cutoff values in the ELISA test by a single antigen. We conclude that the sensitivity and specificity of presently available antigens for serodiagnosis of tuberculosis still remains limited at around 80%, which makes it a poor diagnostic tool for disease confirmation. In low incidence areas, its clinical value may be useful in disease exclusion. A combination of several different antigens provides no more improved diagnostic yield than what can be provided by cutoff value adjustment in a single antigen serologic test.

Adult↗

Empyema thoracis and lung abscess caused by viridans streptococci.

We retrospectively studied the bacteriology and clinical features of empyema thoracis and lung abscess caused by viridans streptococci in 72 patients seen from January 1984 to September 1996. A total of 76 strains of viridans streptococci were isolated, of which the most common isolates were Streptococcus constellatus (21 strains), S. intermedius (17), and S. sanguis (10). Species belonging to the S. milleri group accounted for the majority (68%) of isolates. In 38 (53%) patients these organisms were recognized as the sole pathogens. Of the 72 patients, 53 had empyema, 14 had lung abscesses, and five had both empyema and lung abscess. Forty-six (64%) patients had underlying diseases. Of these, malignancies were the most common (17 patients), followed by diabetes mellitus (12 patients) and central nervous system diseases (10 patients). Of the 48 patients who underwent chest-tube drainage, 27 (56%) received further treatments, including intrapleural streptokinase (18 cases), surgery (9), and both intrapleural streptokinase and surgery (3). Two (14%) of the patients with lung abscess alone underwent surgical treatment. Although all viridans streptococcal isolates were susceptible to penicillin, the patients in the study had a high mortality (21%). Univariate and multivariate analysis of data for patients with empyema alone (n = 53) showed a significantly increased risk of death in those with underlying malignancy (OR = 16.0, p = 0.023) and those with non-S. milleri-group isolates (OR = 3.72, p = 0.030). These data imply a strong clinical significance of viridans streptococci in the pathogenesis of empyema and lung abscess, as well as the need for species identification of viridans streptococci in patients with pleuropulmonary diseases.

Adult↗

Endobronchial lesions in a non-AIDS patient with disseminated Mycobacterium avium-intracellulare infection.

A 34 year old female developed Mycobacterium avium-intracellulare infection with generalized lymphadenopathy, hepatosplenomegaly, pulmonary infiltration, pleural effusion and endobronchial polypoid lesions. M. avium-intracellulare was identified by means of sputum cultures, pleural effusion culture and lymph node culture. The anti-human immunodeficiency virus (HIV) antibody was negative. The CD4+ cell count was normal. Bronchoscopic examination revealed multiple polypoid lesions, which had nearly occluded the right main bronchus, right middle lobe and left lower lobe bronchi. Neodymium yttrium aluminium garnet (Nd-YAG) laser and antimycobacterial therapy were used effectively to relieve the airway obstruction. The clinical symptoms and signs responded favourably to antimycobacterial therapy.

Adult↗

In vitro activity of ofloxacin against Mycobacterium tuberculosis.

For the past 3 years, ofloxacin has been widely used in treating patients with drug-resistant tuberculosis in Taiwan. To study its usefulness in treating these patients, 139 isolates of Mycobacterium tuberculosis from patients treated at the Taiwan Provincial Chronic Disease Control Bureau from September 1994 to September 1995 were tested to determine the in vitro antituberculosis activity of ofloxacin. Of these, 131 had not been previously exposed to ofloxacin, and 130 (99.2%) were susceptible to ofloxacin. Sixty-four isolates were found to be susceptible to all conventional antituberculosis drugs, and all of these were also susceptible to ofloxacin. Of the remaining 67 isolates that were resistant to one or more conventional antituberculosis drugs, 66 (98.5%) were susceptible to ofloxacin. There was no association between susceptibility to ofloxacin and susceptibility to conventional antituberculosis drugs among the isolates tested. Of the eight isolates of M. tuberculosis previously exposed to ofloxacin, seven (87.5%) were resistant. Our results indicate that patients with multidrug-resistant strains of M. tuberculosis who have not received prior ofloxacin treatment may be safely treated with ofloxacin even without knowing the result of pretreatment ofloxacin susceptibility tests. We also found that ofloxacin resistance emerges frequently. Therefore, an adequate combination of antituberculosis drugs, along with ofloxacin, should be prescribed to prevent the development of resistance to ofloxacin.

Anti-Infective Agents↗

Constitutive fatty acid and enzyme profiles of Mycobacterium species.

Sixty-one strains of Mycobacterium tuberculosis complex and 47 strains of nontuberculous mycobacteria were analyzed for fatty acids and enzyme profiles. Cellular fatty acids were extracted from bacteria, methylated and analyzed by gas liquid chromatography operated either manually (Perkin-Elmer) or by the automatic Microbial Identification System. The major cellular fatty acids in all mycobacterial species were C16:0 and C18:1. Tuberculostearic acid was found in all species with the exception of Mycobacterium gordonae. The fatty acids with a carbon-length longer than 20 could be detected only by conventional gas chromatography. Strains of M. tuberculosis had a high ratio of C26:0 to C24:0, and a relatively low ratio of C14:0 to C15:0. For determination of branched-chain fatty acids, the MIS provided more definitive results. The data indicated that the fatty acid profiles could provide rapid species identification. The results of the enzyme profile analysis using API-ZYM strips showed 39 different patterns from 59 strains of M. tuberculosis, and 41 different patterns from 46 nontuberculous mycobacteria strains, suggesting that enzyme profiles can also be used for strain characterization within the same species.

Chromatography, Gas↗

Microbiologic and histologic diagnosis of histoplasmosis in Taiwan.

Histoplasmosis is one of the most common opportunistic fungal infections in immunocompromised patients in endemic areas. We report the first two microbiologically documented cases of histoplasmosis in Taiwan. The first patient, with acquired immunodeficiency syndrome and a depleted CD4+ lymphocyte count, presented with a history of prolonged fever, papular skin rashes, pancytopenia and elevation of liver enzymes. He was diagnosed and treated initially for systemic toxoplasmosis, but the microbiologic and pathologic findings of the autopsied specimens disclosed disseminated infection caused by Histoplasma capsulatum. The second patient, an elderly man receiving corticosteroids for adrenal insufficiency, manifested with laryngeal histoplasmosis and was successfully treated with ketoconazole.

AIDS-Related Opportunistic Infections↗

Bacteremia caused by Helicobacter cinaedi in an AIDS patients.

Helicobacter cinaedi bacteremia has been infrequently described in homosexual patients with HIV infection. It may recur despite appropriate antimicrobial therapy. We report a bisexual patient with AIDS in whom H. cinaedi bacteremia developed and presented with prolonged fever and chronic diarrhea. The symptoms resolved without relapse after intravenous immunoglobulin therapy, which was administered for the treatment of concurrent parvovirus B19-associated anemia, and subsequent treatment with clarithromycin for 14 days.

AIDS-Related Opportunistic Infections↗

Nontuberculous mycobacteria isolates: clinical significance and disease spectrum.

The incidence of diseases caused by nontuberculous mycobacteria (NTM) is increasing worldwide. There has been no previous report regarding the clinical significance and disease spectrum of these bacteria in Taiwan. From January 1992 to June 1996, 201 isolates of NTM were recovered from clinical specimens from 143 patients at National Taiwan University Hospital. We retrospectively studied the clinical records and radiographs of these patients. A total of 86 isolates of NTM were considered clinically significant; they were cultured from 39 patients with soft-tissue infections and/or osteomyelitis (16 patients), isolated pulmonary infections (10), keratitis (6), disseminated infections (4), peritonitis, enteritis, and conjunctivitis. The most common organisms involved in these patients were Mycobacterium fortuitum complex, followed by Mycobacterium avium-intracellulare. Positive cultures of NTM were derived from respiratory sources (sputum, bronchial washing, and pleural effusion) from 111 patients; in 11 the isolates were associated with clinically significant disease, in two they were persistent colonizers, in 79 the isolates were considered to be contaminants, and for the remainder there were insufficient cultures to classify. The organisms involved in pulmonary diseases were M. avium-intracellular (4 patients), Mycobacterium chelonae (1), Mycobacterium abscessus (1), M. fortuitum (2), Mycobacterium gordonae (1), and unidentified scotochromogens (2), M. fortuitum complex (55%) was the most common pathogen of keratitis and soft-tissue infection. Three of the four cases of disseminated disease were caused by M. avium-intracellulare. The only isolate of Mycobacterium kansasii found in this study was a contaminant. The strains of clinically significant NTM isolates found in our hospital and their disease spectrum differ from those reported in other regions of the world.

Adult↗

Streptococcus adjacens endocarditis in a patient with nephrotic syndrome.

Streptococcus adjacens has never previously been reported as an etiologic organism of infective endocarditis in Taiwan. We describe a case of severe native valve endocarditis caused by S. adjacens, involving the mitral valve, the aortic valve, and the left atrium, in a 29-year-old woman with nephrotic syndrome on steroid therapy. Blood cultures yielded gram-positive cocci that grew poorly on blood agar but strongly on chocolate agar. Despite aggressive antibiotic treatment, the patients continued to have high fever and progressive congestive heart failure, which necessitated surgical intervention. Symptoms were alleviated after surgery; teicoplanin was continued for 4 weeks and the patient remained symptom-free at the 6 month follow up. To our knowledge, this is the first reported case of bacterial endocarditis involving the left atrium without preexisting myxoma.

Adult↗

Diagnostic role of endoscopy, stool culture, and toxin A in Clostridium difficile-associated disease.

This retrospective study was designed to assess the roles of stool culture for Clostridium difficile, detection of the presence of toxin A, and endoscopic examination in the diagnosis of Clostridium difficile-associated disease (CDAD). From January 1994 through September 1996, there were 213 patients with stool cultures positive for C. difficile in National Taiwan University Hospital. Of these, 126 had CDAD. There were 87 asymptomatic carriers of C. difficile in our study, 12 of whom were positive for toxin A. In addition, seven patients with pseudomembranous colitis (PMC), who were either culture-negative or not tested, were included in the study. The positive predictive values of stool cultures for CDAD and PMC were 59% and 32%, respectively. The positive predictive values of toxin A for CDAD and PMC were 41% and 43%, respectively. Seventy-eight patients (59%) improved with supportive treatment after discontinuing antibiotics. We concluded that stool culture for C. difficile and discontinuation of antibiotics should be the standard approach for patients with suspected CDAD. Endoscopic studies can eliminate some other possible causes of diarrhea such as inflammatory bowel disease, allow biopsies of suspicious lesions, and reveal the severity of CDAD. Toxin assay results need to be interpreted together with the clinical data.

Adolescent↗

Initial drug resistance of Mycobacterium tuberculosis in Taiwan.

The prevalence and mortality rate of pulmonary tuberculosis in adults are high in Taiwan. Because the emergence of drug-resistant tuberculosis is one of the major causes of this sustained high tuberculosis mortality, surveillance of initial drug resistance is important. We tested Mycobacterium tuberculosis isolates from 1,935 newly diagnosed tuberculosis patients from January 1990 through December 1995 at the Taiwan Provincial Chronic Disease Control Bureau. The overall initial drug resistance rate was 12.3%; 8.7% of isolates were resistant to only one drug, 2.6% to two drugs, 0.7% to three drugs, and 0.3% to four drugs. The resistance rates to individual drugs were: streptomycin, 5.7%; isoniazid, 9.2%; ethambutol, 0.7%; and rifampin, 1.5%. The frequency of multidrug-resistant M. tuberculosis (resistant to at least isoniazid and rifampin) was 1.2%. In view of the high initial isoniazid resistance rate and low initial ethambutol resistance rate, ethambutol should be added to the regimen for the initial treatment of tuberculosis in Taiwan. The emergence of multidrug-resistant M. tuberculosis is ominous and should be considered when treating patients in Taiwan.

Adolescent↗

Osteomyelitis and tenosynovitis due to Mycobacterium marinum in a fish dealer.

Osteomyelitis caused by nontuberculous mycobacteria is rarely reported. We describe a case of tenosynovitis and osteomyelitis of the right middle finger and metacarpal bone caused by Mycobacterium marinum in a fish dealer. This 52-year-old woman suffered progressive pain, numbness, tenderness, and erythematous swelling of the right middle finger over a 2-month period. A radiograph of the right hand disclosed osteolytic lesions at the third metacarpal bone and the third proximal phalanx. She was treated successfully with repeated surgical debridement and antimicrobial agents, including clarithromycin, ethambutol, rifampin, and doxycycline for 1 month, followed by ethambutol and clarithromycin. Pathologic examination of the debrided tissue disclosed epithelioid granuloma, caseous necrosis, and numerous acid-fast bacilli, which were later identified as M. marinum using conventional biochemical tests and by the characteristic gas-liquid chromatogram of esterified cellular fatty acid. The wound healed completely after 7 months of treatment. The patient is still under treatment, and clarithromycin and ethambutol will be given for a total of 18 months.

Animals↗

Burkholderia cepacia bacteremia: a retrospective analysis of 70 episodes.

Burkholderia cepacia, a widespread gram-negative environmental bacillus associated with nosocomial infections, is considered to be of relatively low virulence and rarely to cause invasive disease. We retrospectively analyzed the risk factors, clinical manifestations, antimicrobial susceptibilities, and prognostic factors of B. cepacia bacteremia cases. From 1982 through 1995, 70 episodes of bacteremia due to B. cepacia occurred in 52 patients at the National Taiwan University Hospital. The overall case fatality rate was 11%. Sixty-four episodes were nosocomial infections. The common predisposing conditions were stay in an intensive care unit (61%) and invasive procedures, including urinary catheter (54%), intravenous catheter (70%), and intubation (57%). Three episodes involved polymicrobial bacteremia. In 41 episodes in which the infectious focus was identified, the respiratory tract was the most common portal of entry (17/41) followed by intravascular catheters (11/41). Most strains tested were susceptible to ceftazidime (95%), piperacillin (93%), minocycline (85%), and cefotaxime (82%); but most were resistant to aminoglycosides, tetracycline, carbenicillin, and ticarcillin. For empirical therapy of B. cepacia bacteremia, ceftazidime or piperacillin should be the drug of choice.

Adolescent↗

Overexpression of MUC5 genes is associated with early post-operative metastasis in non-small-cell lung cancer.

Mucin glycoprotein can promote tumor-cell invasion metastasis and modulate the immune recognition of cancer. This study aimed to elucidate the clinical significance of mucin gene overexpression in lung cancer. We collected 60 lung cancer samples and paired non-tumorous lung portions of varying types and stages. Slot-blot analysis with specific anti-sense oligonucleotide probes derived from tandem repeat sequence of MUC1, -2, -3, -4, 5B and 5AC were utilized to compare the amount of mucin gene mRNA in tumor samples with that of the non-tumorous counterparts. A ratio higher than 1.5 for each specific mucin mRNA amount was considered to indicate mucin gene overexpression in tumors. Immunohistochemical staining of monoclonal antibodies against mature airway mucin (17Q2) and MUC1 mucin protein (HMFG2) were also used to analyze mucin protein. The study showed that overexpression of mucin genes frequently occurred in lung cancer (25 out of 60, 41.7%), but that there was no preferential expression of a particular mucin gene or a combination of mucin genes in these tumors. The overexpression of mucin genes and mucin protein had no correlation with tumor stage, nodal stage, histology or pathological differentiation grade. Tumors of smokers had higher MUC5B and MUC5AC mRNA expression ratios than those of non-smokers. Tumors with increased expression of mucin genes tended to be associated with post-operative relapse, especially when MUC5B and MUC5AC genes were overexpressed (p = 0.015 and 0.025, respectively). The study suggests that overexpression of novel tracheobronchial mucin genes may result in an increased likelihood of post-operative lung-cancer recurrence or metastases.

Adult↗

Bacteremia due to Citrobacter species: significance of primary intraabdominal infection.

From 1982 to 1994, 45 patients (1.22 episodes per 10,000 discharged patients) were treated for citrobacter bacteremia at National Taiwan University Hospital (Taipei). All patients had at least one underlying disease. Citrobacter bacteremia most commonly occurred in patients with malignancies (48.9%) or hepatobiliary stones (22.2%). Intraabdominal tumors comprised the majority (59.1%) of malignancies. Bacteremia commonly originated from sites such as the abdominal cavity (51.1%), urinary tract (20%), and lung (11.1%). Polymicrobial bacteremia was diagnosed in 15 patients (33.3%); for nine (60%) of these patients, the source of the infection was intraabdominal. Prior treatment with a third-generation cephalosporin was significantly associated (P < .01) with the development of multidrug resistance among the isolates. The mortality associated with citrobacter bacteremia was 17.8%. Poor prognostic factors included pneumonia, altered mental status on presentation, hypothermia, oliguria, septic shock, deterioration in mental status, hyperbilirubinemia, azotemia, and thrombocytopenia. Combination therapy, as compared with other regimens, improved the outcome of citrobacter bacteremia.

Adolescent↗

Flavobacterium indologenes bacteremia: clinical and microbiological characteristics.

To our knowledge, Flavobacterium indologenes has never been reported as a cause of bacteremia in humans. F. indologenes bacteremia was diagnosed in 12 patients at a tertiary referral center in southern Taiwan between 1 January 1992 and 31 December 1994. Six of these patients had ventilator-associated pneumonia, two had primary bacteremia, and one patient each had pyonephrosis, peritonitis, biliary tract infection, and surgical wound infection. Five patients (42%) had malignancies, and three (25%) had multiple burns. Polymicrobial bacteremia was diagnosed in eight patients (67%). Two (17%) of the patients in this study died; both had polymicrobial bacteremia. Antimicrobial susceptibility testing of the blood isolates from the 12 patients showed that > 90% of the isolates were susceptible to piperacillin, cefoperazone, ceftazidime, and minocycline. The chromatograms of esterified fatty acids for the isolates were identical. F. indologenes should be considered an etiologic agent of bloodstream infection, especially in hospitalized patients with severe underlying diseases.

Adult↗