Biomedical subjects

T C Hsu

Publications and source records attributed to T C Hsu.

At least 19 recordsLinked to original sources

PubMed2006

4-Nitroquinoline-1-oxide-induced mutagen sensitivity and risk of nonmelanoma skin cancer: a case-control analysis.

The UV radiation-mimetic chemical 4-nitroquinoline-1-oxide (4-NQO) is thought to induce squamous cell carcinoma (SCC) similar to those induced by UV radiation in animals. Therefore, we tested the hypothesis that cellular sensitivity to 4-NQO is associated with risk of developing skin cancer in a case-control study of 191 patients with nonmelanoma skin cancer (NMSC; 81 SCC and 110 basal cell carcinoma (BCC)) and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10 microM for 24 hours and scored for chromatid breaks in 50 well-spread metaphases. We found that the mean frequency of chromatid breaks per cell (b/c) was significantly higher in the cases (mean+/-SD, 0.46+/-0.43 for SCC and 0.43+/-0.38 for BCC) than in the controls (0.25+/-0.25; P<0.001 for both comparisons) and were associated with more-than-twofold increased risk for both SCC and BCC after adjustment for known risk factors. Therefore, our findings support the notion that sensitivity to 4-NQO reflects susceptibility to UV-induced NMSC. However, there is a lack of correlation between UVB-induced b/c and 4-NQO-induced b/c in this study population. Therefore, these findings need to be verified by additional studies.

4-Nitroquinoline-1-oxide↗

PubMed2005

Mutagen-induced chromatid breakage as a marker of cancer risk.

Risk assessment is now recognized as a multidisciplinary process, extending beyond the scope of traditional epidemiologic methodology to include biological evaluation of interindividual differences in carcinogenic susceptibility. Modulation of environmental exposures by host genetic factors may explain much of the observed interindividual variation in susceptibility to carcinogenesis. These genetic factors include, but are not limited to, carcinogen metabolism and DNA repair capacity. This chapter describes a standardized method for the functional assessment of mutagen sensitivity. This in vitro assay measures the frequency of mutagen-induced breaks in peripheral lymphocytes. Mutagen sensitivity assessed by this method has been shown to be a significant risk factor for tobacco-related malignancies, especially those of the upper aerodigestive tract. Mutagen sensitivity may therefore be a useful member of a panel of susceptibility markers for defining high-risk subgroups for chemoprevention trials. This chapter describes methods for and discusses results from studies of mutagen sensitivity as measured by quantifying chromatid breaks induced by chromosome breaking agents, such as the gamma-radiation radiomimetic DNA crosslinking agent bleomycin and chemicals that form so-called bulky DNA adducts, such as 4-NQO and the tobacco smoke constituent, benzo[a]pyrene, in short-term cultured peripheral blood lymphocytes.

Animals↗

PubMed2002

Genetic instability of specific chromosomes associated with a family history of cancer.

This study evaluated the association between family history of cancer and bleomycin-induced mutagen breaks at specific chromosomes. The authors' hypothesis was that individuals exhibiting mutagen-induced specific chromatid breaks might have genetic instability and thus be more likely to report a family history of cancer. The study included 78 healthy individuals. All subjects completed a personal interview to collect epidemiologic information, including a detailed family history of cancer, and donated a 10-mL blood sample. Bleomycin-induced mutagen sensitivity on specific chromosomes was quantified by counting the bleomycin-induced specific chromosomal breaks with Q-banding techniques. We found that chromosome 4 breaks were significantly associated with a positive family history of cancer in first-degree relatives with an odds ratio of 3.18 and 95% confidence interval of 1.05-9.61. However, none of the other chromosomes showed significantly increased risk with family cancer history. In addition, the mutagen-induced chromosome 4 breaks were not associated with age, sex, ethnicity, or smoking status. These findings suggested that chromosome 4 mutagen sensitivity might be a predictor of familial susceptibility to cancer.

Aged↗

PubMed2001

Transformation nonresponsive cells owe their resistance to lack of p65/nuclear factor-kappaB activation.

Clonal variants of mouse epidermal JB6 cells that are genetically susceptible (P+) or resistant (P-) to tumor promoter-induced neoplastic transformation exhibit differential activator protein-1 (AP-1) response. Transactivation of AP-1 appears to be necessary but not sufficient to promote transformation in JB6 cells. Inhibition of AP-1 is invariably accompanied by inhibition of nuclear factor-kappaB (NF-kappaB) when transformation is suppressed, suggesting that NF-kappaB may also play a role in neoplastic transformation. We report here that transactivation of NF-kappaB is inducible by tumor promoters in P+ but not in P- JB6 cells. Inhibition of NF-kappaB using a nondegradable mutant of IkappaBalpha suppressed inducible anchorage-independent transformation of P+ JB6 cells, suggesting that NF-kappaB activation is required for tumor promotion. Induced degradation of IkappaBalpha occurred in both P+ and P- JB6 cells, indicating that failure to activate NF-kappaB in P- JB6 cells cannot be attributed to failure to degrade IkappaBalpha. Slightly higher levels of nuclear p65 were seen in P+ than in P- JB6 cells. The p65-specific DNA binding activity was also higher in P+ cells upon induction by tumor necrosis factor-alpha, suggesting that differential NF-kappaB activation may be attributable to changes in p65 activity. Transactivation of p65 protein was substantially higher in P+ than in P- JB6 cells, as determined by assay of Gal4-p65 fusion constructs. Thus activated, p65 may be a limiting factor for NF-kappaB activation and transformation responses. Stable expression of p65 in P- JB6 cells conferred not only inducible NF-kappaB and AP-1 activation but also transformation response to tumor promoters. Therefore, p65/NF-kappaB appears to be not only necessary for but also sufficient to confer tumor promotion response. Although stable expression of p65 in P- cells produced p65 increases in whole cell extracts, only the transfectants exhibiting increased nuclear p65 showed transformation response. Thus, elevation of nuclear p65 appears to be a necessary step for a transformation response. The P-/p65 transfectants showing acquired transformation response also showed elevated p65-specific transactivation response, thus recapitulating the NF-kappaB phenotypes seen in P+ cells. Expression of a transactivation-deficient mutant of Jun or dominant-negative extracellular signal-regulated kinase suppressed both AP-1 activation and p65-specific transactivation in JB6 cells, suggesting that AP-1 activity is needed for p65 transactivation and consequently for NF-kappaB activation. Thus, the transformation nonresponsive P- JB6 cells owe their resistance to lack of NF-kappaB activation and p65 transactivation that appears in turn to be attributable to insufficient AP-1 activation.

Animals↗

PubMed2001

Comparative efficacy as antioxidants between ascorbic acid and epigallocatechin gallate on cells of two human lymphoblastoid lines.

Both ascorbic acid and epigallocatechin gallate, which is one of the key polyphenols contained in green tea leaves, have been considered excellent antioxidants. The present study compared the efficacy as antioxidants between the two agents on an equimolar basis. Cells of two lymphoid lines were used as test material to determine the reduction of chromosome damage induced by the radiomimetic antibiotic bleomycin. Without bleomycin, both agents, at concentrations of 10(-7), 10(-6), 10(-5), and 10(-4) M, showed chromosome damage similar to the untreated controls. With bleomycin, the weakest concentration of both showed no protective effect. At concentrations of 10(-6) and 10(-5) M, especially the latter, a significant reduction in frequencies of chromatid breaks was recorded. However, at the highest concentration, 10(-4) M, the chromatid break frequencies rose to the same level as that of cells treated with bleomycin alone, suggesting that both behaved like pro-oxidants.

Antioxidants↗

PubMed2001

Heterochromatin and interstitial telomeric DNA homology.

The purpose of this investigation was twofold. The first objective was to demonstrate that, in most of ten mammalian species commonly used in biomedical research, not all constitutive heterochromatin (C-bands) represents telomeric DNA. For example, the C-bands in human chromosomes, the long arm of the X and the entire Y chromosome of Chinese hamster, and most of the short arms of Peromyscus and Syrian hamster chromosomes are not telomeric DNA. In addition to the usual terminal telomeric DNA in the chromosomes of these mammalian species, the pericentromeric regions of seven or eight Syrian hamster chromosomes and all Chinese hamster chromosomes except pair one have pericentromeric regions that hybridize with telomeric DNA, some in C-bands and some not. The second objective was to describe a simple fluorescence in situ hybridization (FISH) reverse-printing procedure to produce black-and-white microphotographs of metaphase and interphase cells showing locations of telomeric DNA with no loss of resolution. Thus, at least three different types of heterochromatin (telomeric heterochromatin, nontelomeric heterochromatin and a combination of both) are present in these mammalian species, and this simple black-and-white reverse printing of telomeric FISH preparations can depict them economically without sacrificing clarity.

Animals↗

PubMed2001

Early genes responsive to abscisic acid during heterophyllous induction in Marsilea quadrifolia.

The aquatic fern Marsilea quadrifolia produces different types of leaves in response to changes in natural environment and culture conditions. When the conditions are in favor of producing the submerged-type leaves, exogenous application of the plant hormone abscisic acid (ABA) induces the formation of aerial-type leaves. Tissues responsive to ABA were localized to the shoot apical meristem and the associated organ primordia. From these tissues, at least two tiers of ABA-regulated early genes were identified, including seven primary genes and seventeen secondary genes. These genes, designated ABRH for ABA-responsive heterophylly, showed diverse expression patterns during the course of heterophyllous induction. Changes in the transcript level of ABRH genes started early, within 0.5-1.0 h after the addition of ABA to the culture medium. Some changes were transient while the others were persistent. The ABRHs contain extensive sequence homology to known genes, including those encoding transcription factors, protein kinases, membrane transporters, metabolic enzymes, structural proteins and those encoded by the chloroplast genome. Identification of these ABRHs is a first step toward the understanding of the regulation mechanisms of heterophylly, and the results suggest the involvement of novel metabolic and regulatory pathways in ABA-controlled morphogenesis.

Abscisic Acid↗

PubMed2001

Epitope mapping of factor VIII inhibitor antibodies of Chinese origin.

Epitopes recognized by factor VIII (FVIII) inhibitors of Chinese origin were analysed by immunoblotting with full-length recombinant FVIII (rFVIII), thrombin-activated FVIII (FVIIIa) and 16 FVIII fusion proteins synthesized by bacteria. Twenty-eight patients, 12 with haemophilia A and 16 with autoimmune diseases, were recruited. Antibodies from 22 patients showed reactivity with rFVIII, 20 with FVIIIa, and one reacted only with FVIII fusion proteins. Of these 22 cases, most were reactive with A2-a2 and A3-C1-C2 of FVIII(a). Of the nine cases that depicted binding to the fusion proteins, three were reactive with the A domains, three with only the B domain, and the other three with both the A and B (or C) domains. An epitope for a neutralizing antibody of a haemophilia A patient, designated TWN-112, was localized to residues 323-390, specified by FVIII fusion proteins. The same epitope also appeared on an FVIII-expression phage library screening. Immunoabsorption of antibodies from TWN-112 with the epitope reduced the neutralizing activity of the inhibitor by 33%. The incidence of a1 of FVIII is higher, and that of a3 is lower, than previously reported. Two novel epitopes, reported for the first time in this paper, were localized on the 8B2 (amino acid residues 1022-1204) and 8A2(V) (residues 673-740) fusion proteins. These two epitopes were able to reduce inhibitory antibody activity by 24% and 25% respectively. Changes of FVIII fragment specificity were also observed in one of six patients for whom multiple samples, collected at different times, were available. Our initial finding showed that the FVIII inhibitors in these Chinese patients shared epitopes with those of patients from very different genetic backgrounds, suggesting a common mechanism for the development of FVIII inhibitors.

Adolescent↗

PubMed2001

Human parvovirus B19 infection in patients with systemic lupus erythematosus.

OBJECTIVE: The clinical significance of the presence of B19 DNA in patients with SLE was studied. METHODS: Sera from 72 patients with systemic lupus erythematosus (SLE), 23 patients with rheumatoid arthritis (RA), 18 patients with Sjögren's syndrome (SS), eight patients with Raynaud's phenomenon (RP), five patients with primary biliary cirrhosis (PBC), five patients with polymyositis (PM), four patients with erythema infectiosum (EI) and 22 normal controls were examined for parvovirus B19 (B19) infection by serological assays, nested PCR and Southern blotting. RESULTS: Parvovirus B19 DNA was detected in 17 of 72 patients with SLE and in three of four patients with EI, but not in patients with other systemic rheumatic diseases. Of the 17 patients with B19 DNA, only one had IgG anti-B19 antibody and two had IgM anti-B19 antibodies, whereas IgG and IgM anti-B19 antibodies were detected in 27 (49.1%) and 21 (38.2%) of 55 SLE patients without B19 DNA respectively. All sera from the patients with EI contained both IgG and IgM anti-B19 antibodies. B19 DNA was found more commonly in sera from SLE patients without anti-B19 antibodies than in those with anti-B19 antibodies (P<0.05). CONCLUSIONS: B19 infection in patients with SLE may be due to lack of anti-B19 antibodies because of either the immunocompromised nature of the host or the use of immunosuppressive drugs. There was a higher prevalence of hypocomplementaemia and RP in patients with parvovirus B19 viraemia than in those without parvovirus B19 viraemia.

Adult↗

PubMed2001

Antigenic specificity of anti-neutrophil cytoplasmic antibody.

PURPOSE: To determine the antigens recognized by sera containing classic anti-neutrophil cytoplasmic antibodies (c-ANCAs) and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCAs). METHODS: A total of 160 serum samples (all from a reference laboratory) that were originally collected from different clinics for ANCA tests were examined for c-ANCA and p-ANCA by indirect immunofluorescence (IIF). All positive sera were further tested for reactivity to proteinase 3 (PR3), myeloperoxidase (MPO), lactoferrin (LF), and lysozyme (LZ) by enzyme-linked immunosorbent assay (ELISA). In addition, sera from 110 patients with systemic lupus erythematosus (SLE), 51 patients with rheumatoid arthritis (RA), and 40 healthy subjects were also tested for reactivity to these antigens. RESULTS: HF detected ANCA in 81 (51%) of the 160 clinical serum samples. Of these 81 serum samples, 21 (26%) contained c-ANCA and 60 (74%) contained p-ANCA. P-ANCA was more commonly found in antinuclear antibody (ANA)-positive sera than in ANA-negative sera (p < 0.01). Of the 21 serum samples positive for c-ANCA, 12 (57%) reacted to PR3, four (19%) to LF, four (19%) to LZ, and three (14%) to MPO on ELISA. By contrast, of the 60 sera positive for p-ANCA, 15 (25%) reacted to MPO, 13 (22%) to PR3, eight (13%) to LF, and four (7%) to LZ. The prevalence of ANCA specificities in serum samples from SLE patients were as follows: anti-PR3, 0%; anti-MPO, 1%; anti-LF, 27%; and anti-LZ, 29%. The prevalence of ANCA specificities in serum samples from RA patients were as follows: anti-PR3, 6%; anti-MPO, 2%; anti-LF, 8%; anti-LZ, 4%. CONCLUSION: Sera positive for c-ANCA and p-ANCA reacted to diverse cytoplasmic antigens from neutrophils. P-ANCA was found in 55% of ANA-positive serum samples. LF and LZ were most commonly found in serum samples from patients with SLE.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2001

Characteristics and potency of an acellular pertussis vaccine composed of pertussis toxin, filamentous hemagglutinin, and pertactin.

In an attempt to develop a safer pertussis vaccine, we successfully purified 3 pertussis protective antigens-pertussis toxin, filamentous hemagglutinin, and a 69-kDa outer membrane protein (also named pertactin), from Bordetella pertussis strain ATCC 9340. The toxicity of pertussis toxin could be effectively reduced by the treatment with formaldehyde 0.07% while preserving of a high degree of immunogenicity. By mixing purified pertussis antigens with diphtheria and tetanus toxoids (DT), we have formulated a DT acellular pertussis (DTaP) vaccine. Toxicity studies on body-weight gain in mouse, histamine sensitization, lymphocyte promoting, and Chinese hamster ovary cell clustering tests suggested that this DTaP vaccine is safer than a whole cell vaccine produced in France (DTP[F]). The formulated vaccine elicited high levels of anti-pertussis toxin antibodies in both mice and monkeys. In mice, a 2-fold neutralization of anti-pertussis toxin antibodies was produced by DTaP compared with DTP(F) vaccine and an acellular vaccine manufactured in Japan (DTaP[J]). More importantly, in intracerebral challenge assay in mouse, this vaccine also provided a better protection than DTaP(J).

Bacterial Outer Membrane Proteins↗

PubMed2000

Activator protein 1 (AP-1)- and nuclear factor kappaB (NF-kappaB)-dependent transcriptional events in carcinogenesis.

Generation of reactive oxygen species (ROS) during metabolic conversion of molecular oxygen imposes a constant threat to aerobic organisms. Other than the cytotoxic effects, many ROS and oxidants are also potent tumor promoters linking oxidative stress to carcinogenesis. Clonal variants of mouse epidermal JB6 cells originally identified for their differential susceptibility to tumor promoters also show differential reduction-oxidation (redox) responses providing a unique model to study oxidative events in tumor promotion. AP-1 and NF-kappaB, inducible by tumor promoters or oxidative stimuli, show differential protein levels or activation in response to tumor promoters in JB6 cells. We further demonstrated that AP-1 and NF-kappaB are both required for maintaining the transformed phenotypes where inhibition of either activity suppresses transformation response in JB6 cells as well as human keratinocytes and transgenic mouse. NF-kappaB proteins or extracellular signal-regulated kinase (ERK) but not AP-1 proteins are shown to be sufficient for conversion from transformation-resistant to transformation-susceptible phenotype. Insofar as oxidative events regulate AP-1 and NF-kappaB transactivation, these oxidative events can be important molecular targets for cancer prevention.

Animals↗

PubMed2000

Assessment of intragastric pH value changes after early nasogastric feeding.

Studies have suggested that early feeding after injury decreases morbidity and mortality. Few reports, however, have focused on the change in pH inside the stomach after early tube feeding. The aim of the present study was the assessment of 1) the change in intragastric pH after surgery, and 2) the effect of early nasogastric tube feeding on intragastric pH value. From April 1997 to February 1998, 80 patients who underwent colon resection for colorectal cancer by a single surgeon entered the study and were randomized into four groups. Twenty patients (group I) were kept on NPO for 1 wk, and 20 patients per group (groups II, III, and IV) were fed through a nasogastric tube from the second to the seventh postoperative day with low-residual (Osmolite HN), high-fat (Pulmocare), and glutamine-containing (AlitraQ) enteral formulas. Feeding started at 500 kcal/500 cc/d. If the patient tolerated the formula well, feeding increased to 1500 kcal/1500 cc(-1)/d(-1) the following day. Intragastric pH was measured preoperatively and then twice daily until the sixth postoperative day. The pH value of intragastric juice increased significantly once feeding started (3. 67 +/- 1.33 on the third postoperative day; 4.28 +/- 1.26 on the six postoperative day). The pH value seemed only mildly affected by the patient's tolerance for tube feeding (poorly tolerated group, pH 3. 52 +/- 1.75 versus 3.75 +/- 1.21 in the well-tolerated group on the third postoperative day; poorly tolerated group, pH 3.67 +/- 1.02 versus 4.45 +/- 1.27 in the well-tolerated group on the sixth postoperative day). The pH value of intragastric juice was higher in group II than in groups III and IV (4.51 +/- 1.57, 3.90 +/- 1.20, 4. 42 +/- 0.89 respectively, on the sixth postoperative day). This series suggests that early nasogastric feeding can significantly elevate the intragastric pH value in patients after resection of colorectal cancer. Nasogastric feeding may decrease the incidence of stress ulceration by elevating the pH value of intragastric juice.

Carbohydrates↗

PubMed2000

Effect of high ambient temperature on contamination and physical stability of one-liter ready-to-hang enteral delivery systems.

The effect of high ambient temperature on the physical stability and bacterial contamination of 1-L, prefilled, closed enteral feeding systems was examined under simulated clinical conditions. One hundred Jevity Ready-to-Hang enteral feeding systems (Abbott Park, IL, USA) were placed in a 37 degrees C incubator for 24 h. The Ready-to-Hang formula containers were visually inspected at 0 and 24 h. Formula samples were collected from the containers at 24 h and plated on trypticase soy agar. Two samples had insignificant bacterial growth of one colony-forming unit per milliliter that was not demonstrated in repeat culture. No growth was observed for any other sample. Additional samples collected from the two apparently contaminated delivery sets showed no growth. No set showed signs of formula instability, such as coagulation, clumping, or curdling. These findings suggest that, even at a high ambient temperature of 37 degrees C, the risk of bacterial contamination or compromised physical integrity is very low with the use of 1-L, prefilled, closed enteral feeding systems.

Bacteria↗

PubMed2000

Altered heel-pad mechanical properties in patients with Type 2 diabetes mellitus.

AIMS: To compare the heel-pad mechanical properties in patients with Type 2 diabetes mellitus with forefoot ulceration, without forefoot ulceration and age-matched healthy subjects. METHODS: Heel-pad mechanical properties in 40 heels of 20 healthy subjects (group I) age-matched with the other groups, 42 heels of 21 diabetic patients without forefoot ulceration (group II), and 14 heels of 12 diabetic patients with active forefoot ulceration (group III) were assessed using a self-constructed loading-unloading device and a 10-MHz linear-array ultrasound transducer. RESULTS: There were no differences in the unloaded heel-pad thickness, compressibility index and elastic modulus between the three groups. When compared with group I subjects (mean +/- SD, 27.9 +/- 6.1%), a significant increase (P < 0.001) was found in both group II (36.1 +/- 8.7%) and group III patients (43.2 +/- 6.6%) for the energy dissipation ratio. This ratio was also significantly different (P = 0.003) between groups II and III. CONCLUSIONS: The higher impact energy dissipated in the heel-pad may put patients with Type 2 diabetes at higher risk for developing foot ulceration.

Adult↗

PubMed2000

Treatment of proximal plantar fasciitis with ultrasound-guided steroid injection.

OBJECTIVE: To investigate the efficacy of ultrasound-guided steroid injection for the treatment of proximal plantar fasciitis and to evaluate mechanical properties of the heel pad after steroid injection. DESIGN: Proximal plantar fascia and heel pad were assessed with a 10-MHz linear array ultrasound transducer. Pain intensity was quantified with a tenderness threshold (TT) and visual analog scale (VAS). The transducer was incorporated into a specially designed device to measure mechanical properties of the heel pad. Evaluations were performed before injection and at 2 weeks and 3 months after injection. SETTING: An outpatient clinic of a tertiary care center. PATIENTS: Fourteen consecutive patients with unilateral proximal plantar fasciitis. INTERVENTION: Ultrasound-guided injection of 7 mg betamethasone and 0.5 mL of 1% lidocaine into the inflamed proximal plantar fascia. MAIN OUTCOME MEASURES: VAS, TT, heel pad and plantar fascia thickness, and echogenicity of the proximal plantar fascia on sonogram were assessed. Mechanical properties included unloaded heel pad thickness, compressibility index, and energy dissipation ratio. RESULTS: Both VAS score +/- standard deviation (SD; 5.43 +/- 2.03, 1.39 +/- 2.19, 0.57 +/- 1.40 at the 3 measurements, respectively) and TT +/- SD (5.05 +/- 1.42, 9.34 +/- 1.84, 9.93 +/- 1.98 kg/cm2 at the 3 measurements, respectively) improved significantly (p < .001) after steroid injection. The mean thickness of the plantar fascia was greater in the symptomatic side than in the asymptomatic side before treatment (0.58 +/- 0.13 cm vs 0.40 +/- 0.11 cm, p < .001). The thickness had decreased significantly 3 months after injection (0.46 +/- 0.12 cm at 2 weeks, 0.42 +/- 0.10 cm at 3 months, p < .001). The hypoechogenicity at the proximal plantar fascia disappeared after steroid injection (p < .001). Mechanical properties of the heel pad did not change 3 months after steroid injection (p > .05). CONCLUSION: Ultrasound offers an objective measurement of the therapeutic effect on proximal plantar fasciitis. Accurate steroid injection under ultrasound guidance can effectively treat proximal plantar fasciitis without significant deterioration of the mechanical properties of the heel pads.

Adult↗

PubMed2000

Phase II study of oral tegafur-uracil and folinic acid as first-line therapy for metastatic colorectal cancer: Taiwan experience.

BACKGROUND: Tegafur-uracil has become an important regimen in the treatment of metastatic colorectal cancer. Tegafur is a prodrug that is converted to 5-fluorouracil (5-FU) and has been reported to be less toxic and to have a higher therapeutic index. The additional advantage of tegafur is oral administration, an important consideration to improve the quality of life in these patients. Tegafur in combination with uracil is thought to have greater anti-tumor activity due to the inhibitory effect of uracil on the degradation of 5-FU by hepatic dihydropyrimidine dehydrogenase. Tegafur with folinic acid has been reported with modest efficacy and acceptable toxicity. The purpose of this study was to evaluate the effectiveness and toxicity profile of oral tegafur-uracil plus folinic acid in Chinese patients with metastatic colorectal cancer. METHODS: Between May 1998 and August 1999, 40 patients with metastatic colorectal carcinoma were enrolled in this study. All the patients had to have measurable lesions. The initial dose of tegafur-uracil was 300 mg/m2/day for 28 days, followed by a 7-day rest period. Folinic acid was administered orally at a dose of 60 mg/day concurrently with tegafur-uracil. For patients with neutrophil count <1500/microl or a platelet count <100,000/microl after treatment, the treatment was postponed for a maximum of 2 weeks. After that time, if the neutrophil count was 1000-1500/microl and the platelet count was 70,000-100,000 microl, the dose of tegafur-uracil was reduced by 50%, and if lower values resulted, the treatment was discontinued. RESULTS: Forty patients received a total of 318 courses of treatment and a response rate of 32.5% (95% CI, 18-47%), including five complete remissions and eight partial remissions, was achieved. Toxicity was mild and generally tolerable. Gastrointestinal toxicities, including diarrhea, nausea and vomiting, were the major side effects. Seven incidences (17.5%) of grade 3-4 gastrointestinal toxicity were observed. Hematological toxicities were minimal with no evidence of severe (grade 3 or 4) leukopenia and thrombocytopenia. No episode of hepatic, renal, cardiac or neurological toxicity occurred. Two patients (5%) developed transient painful fissuring erythroderma over their palms and soles (the hand-foot syndrome). CONCLUSIONS: The data from our study indicate that oral tegafur-uracil plus folinic acid is an active and tolerable first-line treatment for Chinese patients with metastatic colorectal cancer, with the additional advantage of being easily administered at home.

Adenocarcinoma↗

PubMed2000

Parvovirus B19 infection associated with the production of anti-neutrophil cytoplasmic antibody (ANCA) and anticardiolipin antibody (aCL).

We described four patients who had clinical diagnosis of erythema infectiosum and presented with skin rash, polyarthralgia, polyarthritis, and mild fever. Anti-parvovirus B19 IgM and IgG antibodies were found in all four patients and parvovirus B19 DNA was detected in three of the four patients by polymerase chain reaction (PCR) in sera using standard methods. Anticardiolipin antibody (aCL) was positive in three of the four patients included three with anti-beta2 glycoprotein I (beta2GPI). The immunoglobulin isotype of aCL was found to be IgM. Anti-neutrophil cytoplasmic antibody (ANCA) included three p-ANCA and one c-ANCA was detected in all four patients by indirect immunofluoresence (IIF). Both anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) antibodies were found in two patients whom had polyarthritis for more than 6 months. These data indicate parvovirus B19 may be linked to the induction of an autoimmune response.

Adult↗