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Biomedical subjects

P Y Liu

Publications and source records attributed to P Y Liu.

At least 19 recordsLinked to original sources

Use of pulsed-field gel electrophoresis to investigate an outbreak of Serratia marcescens.

Pulsed-field gel electrophoresis (PFGE) typing was applied to the epidemiological investigation of 20 Serratia marcescens isolates collected from urine specimens of 17 patients and three urinals over a 2-month period. Twenty-five epidemiologically unrelated strains were also tested to determine the discriminatory power of PFGE. The PFGE fingerprints of each isolate were consistent in three different tests. The 20 outbreak isolates had an identical PFGE fingerprint pattern, while the epidemiologically unrelated strains demonstrated unique PFGE fingerprint patterns. The source of the outbreak was inadequately disinfected urinals. We conclude that PFGE served as a highly discriminatory and reproducible method for the epidemiological investigation of the outbreak of S. marcescens infection addressed by this study.

Disease Outbreaks

Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer.

BACKGROUND: Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer. METHODS: The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals. RESULTS: Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group. CONCLUSIONS: As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.

Adult

Intraperitoneal mitoxantrone or floxuridine: effects on time-to-failure and survival in patients with minimal residual ovarian cancer after second-look laparotomy--a randomized phase II study by theSouthwest Oncology Group.

A randomized phase II study of intraperitoneal (ip) mitoxantrone or floxuridine (FUDR) was performed for the treatment of minimal residual epithelial ovarian cancer found at second-look laparotomy after initial platinum-based chemotherapy. Entry was to take place within 30 days of reassessment laparotomies, with documentation of peritoneal metastases either microscopic or gross with cytoreduction to less than or equal to 1 cm in largest diameter. Patients were stratified by the site of the largest disease present (microscopic to 0.5 cm maximum diameter versus greater than 0.5 to 1 cm maximum diameter), by time of registration (< 14 days versus up to 30), and by serum CA-125 (< or = 35 versus >35 units/ml) prior to randomization to either ip mitoxantrone 10 mg/m2 every 2 weeks X 9 or ip floxuridine (FUDR) 3 g (total dose)/ day X 3 days every 3 weeks X 6 cycles. Implantable ip systems and 1.5-2 liters of normal saline were used to deliver the drugs of 83 patients registered between December 1988 and January 1994; there were 6 pathology exclusions and 9 surgical exclusions, and 1 nonevaluable patient for a total of 39 evaluable on mitoxantrone and 28 on FUDR being evaluable. FUDR is the choice for further study because of a progression-free survival exceeding 15% at 1 year over mitoxantrone and a median overall survival of 38 months. It should be emphasized again that the goal of a randomized phase II selection design is to select a winner for phase III testing should there be a substantial difference between the treatments with respect to the primary endpoint. Comparative conclusions between the treatment arms should not be attempted due to the inherently much smaller sample sizes. This should reemphasize the limitations in a comparison of efficacy; however, the toxicologic differences still emerge quite clearly.

Adult

The occurrence of cutaneous nerve endings and neuropeptides in vitiligo vulgaris: a case-control study.

Pioneering studies both in humans and animals have demonstrated an association between the peripheral nervous system and epidermal melanocyte destruction. The presence of certain neuropeptides and neuronal structural markers in peripheral nerve fibres was investigated in involved and uninvolved vitiligo skin and compared with normal healthy skin. A group of 18 vitiligo vulgaris patients and matched healthy volunteers participated in the investigation. The indirect immunofluorescence technique was employed. There was a tendency for a reduction in the number and intensity of low affinity (p75) nerve growth factor receptor immunoreactive (NGFr-IR) basal keratinocytes in involved vitiliginous skin (P < 0.06) compared with control skin, while the number of NGFr-IR nerve fibres was significantly increased (P < 0.01). The number of calcitonin gene-related peptide (CGRP)-IR nerve fibres in the epidermis and papillary dermis was dramatically increased in involved skin as compared with control skin (P < 0.01) and with uninvolved skin (P < 0.05). No clear difference could be found in the distribution of vasoactive intestinal polypeptide (VIP)- and neuropeptide tyrosine (NPY)-IR nerve fibres. A different structural appearance of the peripheral nervous system as well as a changed balance of neuropeptides in vitiliginous skin point to a critical role of the nervous system in the pathogenesis of vitiligo.

Adult

Use of restriction endonuclease analysis of plasmids and pulsed-field gel electrophoresis to investigate outbreaks of methicillin-resistant Staphylococcus aureus infection.

We used restriction endonuclease analysis of plasmids (REAP) and pulsed-field gel electrophoresis (PFGE) to investigate clusterings of methicillin-resistant Staphylococcus aureus (MRSA) infections in our orthopedic unit, neurosurgery unit, intensive care unit, and burn unit. Fourteen different strain types were identified by REAP and 10 different strain types were identified by PFGE among 25 MRSA isolates collected during these incidents of infection. Though neither technique was clearly superior to the other for typing MRSA isolates, REAP is recommended as a relatively simple and reproducible technique for the preliminary investigation of MRSA infection outbreaks in clinical settings.

Bacterial Typing Techniques

The addition of tamoxifen to dacarbazine and cisplatin in metastatic malignant melanoma. A phase II trial of the Southwest Oncology Group, (SWOG-8921).

Based on the reports of substantial improvement in the response rate w ith the addition of tamoxifen to a multiagent chemotherapy regimen for metastatic melanoma, Southwest Oncology Group (SWOG)-8921 was initiated. A prior regimen (SWOG-8804) of dacarbazine (DTIC) 750 mg/m(2) i.v. day 1 and cisplatin 100 mg/m(2) day 1 repeated every 3 weeks produced a 13% response rate in patients with metastatic melanoma without brain metastasis. SWOG-8921 using identical chemotherapy and schedule added tamoxifen 10 mg twice daily. There were 55 eligible patients registered, median age 52, with 37 men and 18 women. Fifty (91%) patients had evidence of visceral metastasis at registration. There were 10 responders (2 complete and 8 partial responses) for an 18% response rate (95% CI, 9-31%). The response rate in women was 28% (95% CI, 10-53%; in men, 14% (95% CI, 5-29%). Tamoxifen has produced a small increase in the response rate when added to the present combination and schedule of chemotherapy. Further Phase III trials will be necessary to assess whether there is a statistical advantage to the use of tamoxifen when combined with chemotherapy and whether there are statistical differences between men and women.

Adult

A phase II trial of piroxantrone in endometrial cancer: Southwest Oncology Group study 8918.

A phase II trial of the new anthrapyrazole piroxantrone was carried out by the Southwest Oncology Group in patients with advanced metastatic or recurrent endometrial cancer. A two-stage statistical design targeted accrual of 20 eligible patients. The starting dose of piroxantrone was 150 mg/m2 in patients without prior radiation therapy (RT) and 120 mg/m2 in patients with prior RT. There were 15 eligible patients, six of whom had received prior hormonal therapy while nine patients had not received prior hormonal therapy. Eight patients had received prior RT while seven patients had not received any prior RT. One to seven cycles of piroxantrone were administered. Dose escalation was feasible in four patients. No grade 5 toxicity was experienced by any patients. Most of the grade 4 (granulocytopenia in one) and grade 3 (leukopenia in three, granulocytopenia in three, anemia in two and thrombocytopenia in one) toxicity was related to myelosuppression. Grade 3 non-hematologic toxicities were nausea, fatigue and SGOT elevation. There was one partial response for a response rate of 7% (95% CI 0.2-32%) and median survival was 11 months (95% CI 3-13 months). The study was prematurely terminated due to lack of patient accrual.

Adult

Epidemiological typing of Flavimonas oryzihabitans by PCR and pulsed-field gel electrophoresis.

Flavimonas oryzihabitans has emerged as a potential nosocomial pathogen in recent years. The typing method for characterization of this species has never been reported before. Pulsed-field gel electrophoresis (PFGE) and enterobacterial repetitive intergenic consensus (ERIC)-based PCR were used to generate DNA fingerprints for 14F. oryzihabitans isolates obtained from eight episodes of nosocomial infections during a 2-year period. Both techniques successfully classified these clinical isolates into eight distinct genotypes, thus indicating that all of these episodes of infections were independent. In contrast, repeated isolates from the same patient were assigned to identical genotypes. The reproducibility of both techniques was good. Therefore, we conclude that both PFGE and ERIC-PCR have comparable reproducible and discriminatory powers for the typing of F. oryzihabitans and may be useful for clarifying the epidemiology of this species; however, ERIC-PCR has the advantages of both speed and simplicity.

Bacterial Typing Techniques

Epidemiological typing of isolates from an outbreak of infection with multidrug-resistant Enterobacter cloacae by repetitive extragenic palindromic unit b1-primed PCR and pulsed-field gel electrophoresis.

An outbreak of multidrug-resistant Enterobacter cloacae infection lasted for 4 months in a neonatal intensive care unit (NICU). Forty-six isolates from the NICU and 20 epidemiologically unrelated strains were characterized by pulsed-field gel electrophoresis (PFGE) and repetitive extragenic palindromic unit b1-primed PCR (REPUb1-PCR) typing. The PFGE patterns after XbaI restriction of the bacterial DNA were analyzed by computer software (Gelcompar) using the UPGMA (unweighted pair group method with arithmetic averages) clustering method and the Dice coefficient. The 46 isolates from the NICU were classified by PFGE typing into five clusters: A (further classified into 7 subtypes, A1 to A7), B, C, D, and E. This outbreak was attributed to multiple genetically related strains of cluster A which had a similarity of 85.8% +/- 4.6%. The minor band differences among strains of cluster A were probably due to minor genetic mutations. The type A1 and A3 strains were isolated from the clinical specimens of patients and hands of nurses. It was probable that these outbreak strains were transmitted among patients via the hands of personnel. REPUb1-PCR typing of the 46 isolates also demonstrated five types, in agreement with results obtained by the PFGE technique, but could not detect the minor mutations among the cluster A strains. Twenty epidemiologically unrelated strains were well distinguished by both PFGE and REPUb1-PCR typing. We conclude that PFGE is a highly discriminatory but time-consuming method for epidemiological typing of E. cloacae and that REPUb1-PCR is a more rapid method with good reproducibility and discriminatory power comparable to that of PFGE.

Bacterial Typing Techniques

The effectiveness of weekly iron supplementation regimen in improving the iron status of Chinese children and pregnant women.

It is evident that intermittent iron supplementation is better than daily supplementation in two aspects: iron absorption is more efficient and has insignificant side effects in contrast to the daily dose. The significantly higher daily iron loss observed in the daily iron supplemented groups rats also suggests alterations in total body iron metabolism. Based on serum ferritin distribution patterns, intermittent iron supplementation avoids temporary iron overload with daily iron supplemented. We conclude that weekly iron supplementation scheme is safer and easier to administer. This feasible strategy for the control of iron deficient anemia in pregnant women and children would be an effective iron-supplementation program (Baily et al., 1993).

Animals

A phase II trial of piroxantrone in advanced ovarian carcinoma after failure of platinum-based chemotherapy: Southwest Oncology Group Study 8904.

A phase II trial of the new anthrapyrazole piroxantrone was conducted by the Southwest Oncology Group in advanced ovarian carcinoma. The objective were to evaluate its response rate and toxicity in patients who had disease persistence, progression, or recurrence either during or after platinum-containing chemotherapy. A two-stage statistical design targeted accrual to 15 eligible patients if no responses were observed. The piroxantrone starting dose was 120 mg/m2, with the provision to escalate to 150 and 180 mg/m2. There were 16 eligible patients, all of whom had received either one (12 patients) or two (4 patients) prior platinum-containing regimens; one patient had received doxorubicin. Fourteen of the 16 patients were enrolled either at the time of disease persistence/progression during initial chemotherapy or with recurrence or progression within 6 months of the previous platinum-based remain. One to 5 cycles of piroxantrone were given. Dose escalation was feasible in 7 patients but was prevented in the other 9 by neutropenia. Maximum toxicity for all cycles was none or grade 1 in 2 patients; grade 2, 5; grade 3, 8; and grade 4, 1. All but one of the grade 3 or 4 events was from myelosuppression; there were no adverse cardiac events. No responses were observed. Thus, piroxantrone appears inactive in patients with persistent, progressive, or recurrent ovarian cancer who recently had received a platinum-based regimen.

Adult

Evaluation of merbarone (NSC 336628) in disseminated malignant melanoma. A Southwest Oncology Group study.

Merbarone, NSC 336628, is an investigational anticancer drug with activity against experimental animal tumors including melanoma. This paper presents results of a Phase II clinical study of merbarone in patients with biopsy proven stage IV malignant melanoma without prior chemotherapy and with no evidence of CNS involvement. Thirty-five patients with median age 58 (range 27-81), with performance status 0-2 were treated with merbarone 1000 mg/m2/day for five days by intravenous continuous infusion repeated every 3 weeks. All patients (21 males and 14 females) were evaluable for toxicity. Two patients were not evaluable for response having been removed from protocol treatment due to toxicity and received other treatment during the first course of chemotherapy. Among the evaluable patients there was one complete response in a supraclavicular lymph node lasting four months and one partial liver response lasting three months. The remaining thirty-one patients were non-responders. Of these one had a stable disease lasting 21 months. The overall objective response rate was 6% (2/35) with a 95% confidence interval of 1%-19%. Twenty-six of the 35 patients have died. The estimated median survival of the entire group was 9 months with a 95% confidence interval six to eleven months. Renal toxicity was dose-limiting and manifested as increasing serum creatinine (54% of patients), proteinuria (51%) and hematuria (9%). One patient experienced grade 4 creatinine increase, proteinuria and acute renal failure. Other toxicities included nausea (71%), vomiting (51%0, malaise (23%), weakness (20%), alopecia (17%), diarrhea (17), anorexia (14%) transaminase (SGOT, SGPT) increase (14%), constipation (14%), alkaline phosphatase or 5'nucleotidase increase (9%), and fever (9%). Hematologic toxicity (granulocytopenia, leukopenia, and anemia) was generally mild and infrequent (29%, only one patient had grade 4 granulocytopenia). Overall 9 patients (26%) had at least one grade 3 toxicity. We conclude that merbarone at this dose and schedule has detectable but minimal activity in the treatment of metastatic malignant melanoma and given the significant renal toxicity this schedule does not merit further evaluation in this disease.

Adult

A phase II trial of piroxantrone in disseminated malignant melanoma. A Southwest Oncology Group study.

Piroxantrone is one of the anthrapyrazoles developed in an effort to combine the broad antitumor activity of the anthracyclines with decreased myocardial toxicity. It has shown activity in metastatic melanoma during phase I trials. The Southwest Oncology Group (SWOG) conducted a phase II trial in disseminated malignant melanoma with piroxantrone administered at 150 mg/m2 intravenously over 1 h every 21 days, based upon the phase I experience. Forty-six eligible patients were registered to the trial and 44 were evaluable for response. Two partial responses, Wayne of 6 and 9 months duration were observed for an overall response rate of 5% (95% confidence interval 1%-15%). Thirty-six of 46 eligible patients have died with an estimated median survival of 5 months (95% confidence interval 3-8 months). Toxicities were tolerable with granulocytopenia being the predominant toxicity. Based upon the observed response rate, it is concluded that piroxantrone administered at this dose and schedule has detectable but minimal activity, and does not warrant further investigation in this disease.

Adult

DNA fingerprinting of Pseudomonas aeruginosa serotype O11 by enterobacterial repetitive intergenic consensus-polymerase chain reaction and pulsed-field gel electrophoresis.

We report the use of pulsed-field gel electrophoresis (PFGE) and enterobacterial repetitive intergenic consensus (ERIC)-based polymerase chain reaction (PCR) to characterize clinical isolates of Pseudomonas aeruginosa serotype O11 collected from an incident of hospital-acquired infection. Both typing techniques differentiated 20 different strain types among seven epidemiologically related isolates and 22 epidemiologically unrelated isolates. There was complete concordance between these two techniques. Our results indicate that the ERIC-based PCR technique represents a rapid and simple means for typing P. aeruginosa serotype O11 with a level of discrimination equivalent to that of PFGE.

Base Sequence

Design and analysis of multiarm clinical trials with survival endpoints.

The clinical trials literature has paid relatively little attention to the design and analysis of K-sample trials with survival endpoints where K is 3 or greater. Following the least-significant-difference approach proposed by Makuch and Simon [1], we derive sample size formulas by working with the logrank test and proportional hazards model directly. This approach ensures the type I error rate to be the nominal value when the global null hypothesis is true. For power considerations, planning the study based on the least favorable alternative is recommended. The resulting sample size requirements are presented in graphic form for K = 3 and 4. Assuming that there is a control group and considering only the alternative that the survival of the experimental treatments is at least as good as that of the control group, power investigations indicate that the proposed strategy has good power for detecting the difference between the control and the best treatment. The "overall power," defined as the chance of the global test and subsequent pairwise comparisons all being correct, is good when all treatments are similar to either the control or the best treatment. Overall power is poor when the hazards are more evenly spread out between the control and the best group because the sample size is inadequate to detect such differences.

Clinical Trials as Topic

Comparison of susceptibility to extended-spectrum beta-lactam antibiotics and ciprofloxacin among gram-negative bacilli isolated from intensive care units.

The in vitro activities of extended-spectrum beta-lactam antibiotics (including piperacillin, cefotaxime, ceftriaxone, ceftazidime, cefepime, imipenem, and meropenems) were assessed and compared with the activity of ciprofloxacin against 366 clinical Gram-negative bacilli isolates from the intensive care units of Taichung Veterans General Hospital. The most prevalent species isolated were Pseudomonas aeruginosa and Acinetobacter baumannii. The activities of ceftazidime, cefepime, imipenem, and meropenem against these isolates were comparable to that of ciprofloxacin. Meropenem was found to be the most potent extended-spectrum beta-lactam antibiotic tested and the MIC50s and MIC90s for most of these multiresistant strains were lower than those of imipenem, ceftazidime, and cefepime, except for Stenotrophomonas maltophilia. The extended-spectrum beta-lactam antibiotics that were still active against S. maltophilia were piperacillin and ceftazidime. More than 50% of Enterobacter spp. were resistant to third-generation cephalosporins and piperacillin, but they remained susceptible to carbapenems and cefepime.

Anti-Bacterial Agents