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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

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

Dry, moist, and wet skin wound repair.

Effects of wet (saline in a vinyl chamber), moist (hydrocolloid dressing), and dry (sterile gauze dressing) environments on wound repair were studied in a porcine partial-thickness wound model. Chambers were exchanged and refilled daily with normal saline containing penicillin G (100 U/ml) and streptomycin (100 micrograms/ml). Hydrocolloid and gauze dressings were kept in place until biopsy of the wound site. Wounds in wet, moist, and dry environments were completely epithelialized on days 6, 7, and 8, respectively. Thickness of the epidermis in wet, moist, and dry wounds was 204 +/- 23, 141 +/- 12, and 129 +/- 18 (mean +/- SEM), respectively. Moist wounds had more subepidermal inflammatory cells than wet wounds. In comparison to dry wounds, the moist or the wet healing environment resulted in less necrosis and faster and better quality of healing in the formation of the newly regenerated epidermis.

Animals

Analysis of clonal relationships among isolates of Shigella sonnei by different molecular typing methods.

Shigella sonnei is a major cause of diarrheal disease in developed as well as in developing countries. Epidemiologic studies of this organism have been limited by the lack of a simple and effective method for comparing strains. In this study, we have compared different molecular typing methods, i.e., plasmid profile analysis, restriction endonuclease analysis of plasmids, rRNA gene restriction analysis (ribotyping), pulsed-field gel electrophoresis (PFGE), and enterobacterial repetitive intergenic consensus (ERIC) sequence-based PCR (ERIC-PCR) for typing 20 clinical isolates of S. sonnei collected from six incidents of infection. PFGE and ERIC-PCR fingerprintings had the highest discriminatory power for discrimination of epidemiologically related isolates from epidemiologically unrelated strains of S. sonnei, and both gave seven distinct strain types among these isolates and the type strain of the species. Plasmid study and ribotyping produced only six and typing techniques demonstrated two distinct patterns, respectively, among these strains. All of these molecular an identical fingerprint for eight temporally related sporadic isolates. It is possible that these temporally related isolates belonged to a single bacterial clone and circulated obscurely through the community. Our results indicate that the ERIC-PCR technique represents a rapid and simple means for typing S. sonnei with a level of discrimination equivalent to that of PFGE but greater than those of plasmid profile analysis, restriction endonuclease analysis of plasmids, and ribotyping.

Bacterial Typing Techniques

Phase II trial of didemnin-B in advanced epithelial ovarian cancer. A Southwest Oncology Group study.

A Phase II study of Didemnin-B, a marine cyclic depsipeptide, was undertaken in patients with progressive epithelial ovarian cancer. The starting dose was 2.6 mg/m2. Fifteen patients received the drug, of whom twelve were evaluable. There were no responses observed in the twelve patients. The two most frequent toxicities were nausea and vomiting and anemia. On the basis of this trial, Didemnin-B is not felt to have significant effect with epithelial ovarian cancer.

Aged

Prognostic factors in clinical trials.

Prognostic factors define the study population, help formulate the study objectives, and influence the treatment strategies. They must be accounted for in the study analysis to obtain valid estimates of the treatment differences and to evaluate results across studies. The causal relationship between a prognostic factor and the study endpoint can only be established through prospective randomized study designs. Potential factors discovered through retrospective analysis must be verified to establish their validity. Using such factors prematurely to select patient population and treatment strategy for a new study will not establish the validity of the potentially important factor.

Clinical Trials as Topic

Phase II trial of amonafide in previously treated patients with advanced ovarian cancer: a Southwest Oncology Group study.

Twenty-three patients with metastatic or recurrent Stage III or IV epithelial ovarian cancer who were refractory to or relapsed following previous chemotherapy with cisplatin or a cisplatin analog were entered into a phase II study of amonafide. The starting dose of amonafide was 300 mg/m2 delivered daily over 1 hr by intravenous infusion. In the absence of myelosuppression, the dose of amonafide was escalated by increments of 75 mg/m2 to a maximum of 450 mg/m2. There were 19 eligible and 17 fully evaluable patients. Grade 3 or 4 leukopenia occurred in 14 (74%) patients and grade 3 or 4 thrombocytopenia in 6 (32%) patients. No objective complete or partial responses were observed. Four patients had stable disease for 3, 4, 4.5, and 6 months, respectively. Therefore, amonafide in the doses used in the present trial does not have significant activity in previously treated patients with ovarian cancer.

Adenine

A randomized phase II trial of trimetrexate or didemnin B for the treatment of metastatic or recurrent squamous carcinoma of the uterine cervix: a Southwest Oncology Group trial.

Patients with measurable metastatic or recurrent squamous carcinoma of the uterine cervix who had failed prior surgery or radiation therapy were enrolled on this randomized phase II study. Twenty-seven eligible patients were assigned to receive didemnin B at either 2.6 mg/m2 iv every 28 days (sixteen patients) or at 5.6 mg/m2 (eleven patients). Sixteen patients were assigned to receive 12 mg/m2/day iv trimetrexate for 5 days, repeated every 21 days. Toxicity for didemnin B was characterized by nausea and vomiting (78% of patients), anemia (59%), mild diarrhea (11%), and episodic hypersensitivity (three patients). Toxicity for trimetrexate included nausea and vomiting (69%), leukopenia (51%), mild thrombocytopenia (38%), anemia (63%), and diarrhea (31%). No antitumor responses were observed for either agent. Neither trimetrexate nor didemnin B at these doses and schedules is recommended for the treatment of advanced squamous carcinoma of the uterine cervix.

Antineoplastic Agents

Survey of the prevalence of beta-lactamases amongst 1000 gram-negative bacilli isolated consecutively at the Royal London Hospital.

beta-Lactamase expression was examined in 1000 consecutive Gram-negative bacilli isolated from urine, wound swab, sputum or blood specimens received at the Microbiology Laboratory of the Royal London Hospital. This survey, performed between January and April, 1991, followed a similar study undertaken in early 1982. The distribution of species was similar in the two surveys, except that the proportion of Pseudomonas aeruginosa isolates had increased from 11% in 1982 to 17.5% in the present study. This increase was balanced by a decreased proportion of enterobacteria. Amongst plasmid-mediated beta-lactamases, TEM-1 (especially), TEM-2, SHV-1 and OXA types continued to predominate in enterobacteria. Their frequency in Escherichia coli was unchanged (46% in 1991 compared with 43% in 1982), but had increased from 5 to 22% amongst Proteus mirabilis isolates. An apparent decrease in their frequency amongst Enterobacter cloacae isolates, from 48% in 1982 to 17% in 1991, probably reflected changes to strain prevalence rather than enzyme prevalence. Plasmid type beta-lactamases were present in fewer than 2% of P. aeruginosa isolates in both surveys. In the present study, chromosomal beta-lactamase derepression (constitutive hyperproduction) was detected in 10/76 isolates of E. cloacae, Enterobacter aerogenes, Citrobacter freundii, Serratia spp. and Morganella morganii, and in 2/170 P. aeruginosa isolates. These proportions were increased, compared with those seen the 1982 survey, though the significance was borderline (P approximately 0.05; chi 2 test). Extended-spectrum plasmid mediated beta-lactamases, unknown in 1982, were found in 11/70 Klebsiellae pneumoniae isolates in the present study. Ten of these organisms, representing at least five distinct strains, produced TEM-10 enzyme, encoded by a plasmid of c. 90 kb; the remaining organism had an unidentified SHV-derived enzyme.

Anti-Bacterial Agents

Evaluation of amonafide in cervical cancer, phase II. A SWOG study.

The Southwest Oncology Group conducted a Phase II study of amonafide in patients with metastatic or recurrent squamous cell cervical cancer. Twelve of the 15 patients were fully evaluable for response and toxicity. There were no clinical responses seen; 2 patients had stable disease while 13 had progressive disease. The major complication of this therapy was myelosuppression. Four patients had life-threatening granulocytopenia (less than 500/microliters), 3 patients had life-threatening leukopenia (less than 1000/microliters), while 2 patients had life-threatening thrombocytopenia (less than 25,000/microliters). Amonafide has significant toxicity but appears to be an inactive drug in metastatic or recurrent squamous cell cancer of the cervix.

Adenine

The relationship of serum IL-6 levels to acute graft-versus-host disease and hepatorenal disease after human bone marrow transplantation.

The potential involvement of cytokines in acute graft-versus-host disease led us to analyze interleukin-6 in serial serum sets from 22 allogeneic marrow recipients who developed either grade 3 or 4 GVHD (n = 10), grade 2 GVHD (n = 6), or grade 1 or no diagnosed GVHD (n = 6). A total of 279 serial serum samples taken three times weekly before day 35 were analyzed. Maximum IL-6 levels were greater than 40 U/ml (range, 40-1536 U/ml), 11-40 U/ml, and less than or equal to 10 U/ml for six, eleven, and five patients, respectively. Serum IL-6 peaks were temporally related to onset of GVHD, onset of a syndrome of hepatorenal dysfunction (HRD), or bilateral lung infiltration. Eight of ten patients who developed grade 3 or 4 GVHD overall had IL-6 maxima of greater than 10 U/ml an average of 1.5 +/- 1.8 days before the clinical onset. Fifteen of 17 patients with peak IL-6 levels greater than 10 U/ml developed symptoms of hepatic and renal dysfunction within three days of the peak, while none of five patients with less than or equal to 10 U/ml of Il-6 developed HRD. Regression analysis demonstrated a linkage between the log magnitudes of the serum IL-6 peaks and onset of either GVHD or HRD within three days (P = 0.001). Furthermore, IL-6 peaks tended to precede GVHD onset for the 10 patients whose GVHD onset and IL-6 peak were within three days of each other (P = 0.02). These results, confirmed by both specific bioassay and by IL-6 ELISA, support the idea that acute GVHD in humans involves a cytokine cascade that includes production of IL-6 in addition to the previously reported involvement of tumor necrosis factor alpha and interferon-gamma.

Acute Disease

Effects of an Asian client-therapist language, ethnicity and gender match on utilization and outcome of therapy.

The purpose of this study was to examine the relationship of Asian client-therapist ethnicity, language and gender match on two measures of utilization: number of sessions with primary therapist and dropout from therapy; and one measure of client outcome: admission-discharge difference in Global Assessment Scale (GAS) scores. The sample consisted of 1746 Asian client episodes in Los Angeles County mental health facilities between January 1983 and August 1988. Various types of multiple regression analyses were used to investigate the relationship of language, ethnicity, and gender match to the three dependent variables and to eight socio-demographic variables. Either client-therapist language match or ethnic match significantly increased the number of client sessions with the primary therapist. However, only ethnicity match had a significant effect on dropout rate. Gain in GAS admission-discharge score was not affected by either a client-therapist ethnicity or language match. Gender match had no consistent effect on the dependent variables. Of the covariates examined, only therapist discipline (social worker) had a consistent effect on the dependent variables. It was concluded that both client-therapist language and ethnicity match are important variables affecting the utilization of treatment. Further research will be needed to separate the effects of language and ethnicity on therapy utilization.

Adolescent

Influence of therapist ethnicity and language on therapy outcomes of Southeast Asian clients.

The purpose of this study was to examine the relationship of Southeast Asian client-therapist ethnicity and language match on three therapy outcomes: number of sessions with primary therapist, dropout from therapy and admission-discharge difference in Global Assessment Scale (GAS) scores. The sample consisted of 543 Southeast Asian client episodes in Los Angeles County mental health facilities between January 1983 and August 1988. Various types of multiple regression analyses were used to investigate the relationship of language and ethnicity match to the three outcome variables and to eight sociodemographic variables. Either therapist-client language or ethnicity match significantly increased the number of client sessions with the primary therapist. Dropout from therapy was significantly affected by a language match in the Cambodian sample only but the effect was to increase dropout. Neither ethnicity nor language match was significantly related to GAS score gain. Several possible explanations for these findings and their clinical significance were explored.

Adult

Child abuse disposition: concurrences and differences between a hospital team, child protection agency and the court.

Ninety-six children admitted to a pediatric ward for maltreatment are described statistically using variables characterizing the child, the family and the type of abuse. Recommendations of the hospital's child protection team in 81 cases are compared to those of the county childrens Services Board and the court. Multiple regression analysis is used to identify which variables influenced the decisions of these three agencies.

Adolescent

[Observation on immunogenic effect of intradermal inoculation of small dose of hepatitis B vaccine].

The immunogenic effect of intradermal inoculation of small dose of HB vaccine was evaluated in 120 seronegative villagers (men: 55, women: 65) whose ages were from 3 to 70. These participants were randomly divided into subcutaneous group (I) and intradermal group (II). The results showed that the anti-HBs seroconversion rates and P/N ratios of those who showed the seroconversion for group I, II were 98.4%, 98.3% and 88.0, 89.4, respectively after the third injection. There was no significant difference between the groups in the seroconversion rates and their P/N ratios (P greater than 0.05). It is concluded that in these two groups small doses of HB vaccine have stimulated high immune responses. Intradermal small dose regimen is safe, more economic and will make the HB vaccine available to more people.

Adolescent

Inhibition by diphosphonate compounds of calcification of porcine bioprosthetic heart valve cusps implanted subcutaneously in rats.

Calcification limits the long-term success of heart valve bioprostheses fabricated from glutaraldehyde cross-linked porcine aortic valves. The pathophysiology of calcification of bioprostheses has been studied experimentally with subcutaneous implants of the valve cusps in rats; in this preparation, the accumulation of calcific deposits is biochemically and morphologically identical to that occurring in clinical specimens. The objective of the present study was to determine whether mineralization of bioprosthetic valve cusps (BC) subcutaneously implanted in 3-week-old male rats could be inhibited through the use of diphosphonate compounds. Ethanehydroxydiphosphonate (EHDP), administered by daily subcutaneous injection (25 mg/kg/24 hr) for 21 days inhibited calcification (BC Ca++ = 154.9 +/- 4.1), but caused somatic growth retardation and disruption of epiphyseal development. However, local administration of EHDP by osmotic pump (5 mg/kg/24 hr) implanted in direct contact with the cuspal tissue for 14 days prevented BC calcification (BC CA++ = 4.3 +/- 0.7) without adverse effects. Furthermore, EHDP given by osmotic pump had a prolonged effect on reducing calcification, as demonstrated by implants harvested 21 days (BC CA++ = 12.2 +/- 6.4) after the drug supply was exhausted. Finally, BC preincubated in aminopropanehydroxydiphosphonate for 24 hr before 21 day implantation underwent less calcification (CA++ = 24.2 +/- 7.4) than control valves (BC CA++ 126.6 +/- 7.5) with no adverse effects. We conclude that diphosphonates inhibit BC calcification, and that adverse effects of systemic therapy can be avoided by local administration.

Animals