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Biomedical subjects

M Michael

Publications and source records attributed to M Michael.

At least 55 records · Page 3Linked to original sources
PubMed2000

Efficiency of forensic mtDNA analysis. Case examples demonstrating the identification of traces.

The paper presents results of forensic mitochondrial DNA analyses which were aimed at typing the traces caused by touching or abrasion of skin cells. Five cases of strangulation tool investigation are summarised. Two cases of homicide could be cleared up by identifying the mtDNA of both the victim and the suspect on cables which had obviously been used as strangulation tools. In eight of 10 cases, weapons could be reliably assigned to their users. The mtDNA of the users could be even detected on cartridges after firing. In one case, evidence of a suicide could be provided by means of mtDNA sequencing of the wiping traces on a suicide note.

DNA Fingerprinting↗
PubMed2000

Initiating abstinence in cocaine abusing dually diagnosed homeless persons.

This study measured effectiveness of behavioral day treatment plus abstinence contingent housing and work therapy (DT+) versus behavioral day treatment alone (DT). A randomized controlled trial assessed participants at baseline, 2 and 6 months. Participants (N=110) met criteria for cocaine abuse or dependence, non-psychotic mental disorders, and homelessness. DT+ achieved greater abstinence at 2 and 6 months and more days housed at 6 months than DT. Effectiveness of DT+ was demonstrated, with greatest impacts on abstinence outcomes. Results replicated earlier work demonstrating effectiveness of behavioral day treatment and contingency management as an effective combination for cocaine abusing homeless persons.

Adult↗
PubMed2000

A phase I trial of docetaxel and gemcitabine in patients with advanced cancer.

BACKGROUND: Docetaxel and gemcitabine are active in a broad range of malignancies. The objective of this phase I trial was to determine the maximally tolerated doses of the combination of docetaxel and gemcitabine. PATIENTS AND METHODS: Patients with advanced cancer, WHO performance status 0-2, who had received up to one prior chemotherapy regimen were treated with gemcitabine on days 1 and 8 and docetaxel on day 8 repeated every 21 days. Prophylactic ciprofloxacin was commenced on day 11 of each cycle and continued until the neutrophil count reached 1.0 x 10(9)/l. G-CSF was not administered. Dose levels studied were docetaxel/gemcitabine: 60/800, 60/1000, 75/1000, 75/1200, 85/1200 and 100/1200 mg/m2. RESULTS: Thirty-nine patients were entered and all were assessable for toxicity. The highest administered dose level was 100 mg/m2 docetaxel and 1200 mg/m2 gemcitabine with dose limiting toxicities of febrile neutropenia, grade 4 neutropenia > or = 7 days, grade 4 thrombocytopenia, grade 3 stomatitis and/or grade 3 fatigue in three out of six patients. Treatment was well tolerated (40 cycles) in the 10 patients treated at the recommended dose level (85/1200) with only a single episode of febrile neutropenia and grade 3 or 4 non-hematologic toxicity was infrequent. There was no significant pulmonary toxicity. Responses were seen in a range of malignancies including non-small-cell lung cancer. CONCLUSIONS: The recommended dose level of 85 mg/m2 docetaxel and 1200 mg/m2 gemcitabine has a favourable toxicity profile and is suitable for further investigation in phase II trials. This non-platinum containing regimen warrants further investigation as a potential alternative to platinum containing regimens in non-small-cell lung cancer and other malignancies.

Adult↗
PubMed1999

Incidence of weapon injuries not related to interfactional combat in Afghanistan in 1996: prospective cohort study.

OBJECTIVE: To examine the descriptive epidemiology of weapon injuries not directly attributable to combat during armed conflict. DESIGN: Prospective cohort study. SETTING: Nangarhar region of Afghanistan, which experienced effective peace, intense fighting, and then peace over six months in 1996. SUBJECTS: 608 people admitted to Jalalabad hospital because of weapon injuries. MAIN OUTCOME MEASURES: Estimated incidence of injuries from combat or otherwise (non-combat injury) before, during, and after the fall of Kabul. RESULTS: Incidence of non-combat injury was initially 65 per 100 000. During the intense military campaign for Kabul the incidence declined dramatically, and then differentially increased dependent on injury subcategory-that is, whether injuries were accidental or intentional and whether they were inflicted by firearms or fragmenting munitions. Non-combat injuries accounted for 51% of weapon injuries observed over the study period. Civilians were more likely to have non-combat injuries than combat injuries. CONCLUSIONS: Weapon injuries that are not attributable to combat are common. Social changes accompanying conflict and widespread availability of weapons may be predictive of use of weapons that persists independently of conflict.

Accidents↗
PubMed1999

Loss of heteroplasmy in the displacement loop of brain mitochondrial DNA in astrocytic tumors.

The aim of this study was the determination of D-loop heteroplasmy in astrocytic brain tumors. DNA fragments corresponding to the hypervariable region 2 of the mitochondrial displacement loop (D-loop) from 12 astrocytic tumors and 2 corresponding brain samples were cloned into a plasmid vector. Heteroduplex analysis revealed high sequence variability in the brain samples and a subfraction of grade 2 and grade 3 tumors. Furthermore, the results were suggestive of a very low degree of heteroplasmy in all glioblastomas. This was confirmed by direct sequencing of 223 cloned DNA samples from nine individuals. Heteroplasmy was caused in most cases by a well-known length polymorphism of a homopolymeric c-tract. Heteroplasmy of the two reference brain samples was lost in the corresponding tumors. Genes Chromosomes Cancer 26:80-83, 1999.

Adult↗
PubMed1999

Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer.

PURPOSE: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in tumor development and progression. MMP expression has been correlated with advanced clinical stage and poor survival in some tumors, but data for small-cell lung cancer (SCLC) are lacking. The aim of this study was to assess the expression of MMPs and TIMPs in SCLC and to evaluate their importance relative to standard prognostic factors. PATIENTS AND METHODS: Expression of MMP-1, -2, -3, -9, -11, -13, and -14 and TIMP-1, -2, -3, and -4 was evaluated by immunohistochemistry (IHC). In situ hybridization was used to confirm expression of specific mRNAs. Clinical data collected included sex, tumor stage, performance status, weight loss, hematology (hemoglobin, WBC, platelets) and biochemistry (sodium, albumin, alkaline phosphatase, lactate dehydrogenase), treatment, and survival. RESULTS: Samples from 46 patients were evaluated: 30 males, 16 females; 29 limited, 17 extensive stage; 35 Eastern Cooperative Oncology Group performance status 0-1. Positive IHC staining was evident for MMP-1 and -9 in 60% to 70% of tumor cells, and for MMP-11, -13, and -14 and TIMP-2 and -3 in 70% to 100% of tumor cells. Stromal staining of TIMP-1 to -3 was present in less than 30% of specimens. On multivariate analysis, only stage and decreased tumoral expression of TIMP-1 were significant for response (P =.043). Significant factors for survival were tumor stage (P =.0021); weight loss (P =. 013); and high tumor cell expression of MMP-3 (P =.077), MMP-11 (P =. 031), and MMP-14 (P =.019). MMP and TIMP expression did not differ significantly between stages. CONCLUSION: MMPs and TIMPs are widely expressed in SCLC. Increased tumoral expression of MMP-3, -11, and -14 were independent negative prognostic factors for survival. The results support the evaluation of synthetic MMP inhibitors in patients with SCLC.

Carcinoma, Small Cell↗
PubMed1999

Compliance with post-hospitalization follow-up visits: rationing by inconvenience?

OBJECTIVES: Appointment-keeping after hospitalization is a poorly understood link between inpatient and outpatient care. We investigated how health care system and patient characteristics influence appointment-keeping after discharge from an acute care hospitalization. DESIGN: Prospective cohort study. SETTING: Urban public teaching hospital. SUBJECTS: All 372 consecutive eligible patients admitted over a 15 week period to medicine wards. METHODS AND MEASURES: We interviewed patients during hospitalization and after discharge, searched the hospital's electronic databases, and reviewed charts. We measured medication compliance, health care access and use, health status (SF-36), previous appointment compliance, and physician recommended follow-up appointments. Main outcome was appointment adherence after discharge. RESULTS: Patients were primarily African American (71%), uninsured (64%), female (53%), and had a mean age of 48 years; 64% of first appointments after discharge were kept. Adjusted odds ratios (95% confidence intervals) for appointment-keeping were 3.3 (1.7, 6.5) for receiving a written appointment at discharge, and 0.50 (0.27, 0.90) for previous difficulty with obtaining health care. Readmission rates were not associated with appointment adherence. CONCLUSION: Modifiable system, as well as patient, characteristics are associated with follow-up appointment-keeping. The practice of not giving patients written appointments at the time of discharge may constitute an implicit form of "rationing by inconvenience." Further studies should also evaluate potential associations between appointment-keeping and re-hospitalization.

Aftercare↗
PubMed1998

Measuring health-related quality of life in clinical trials that evaluate the role of chemotherapy in cancer treatment.

Quality of life is a subjective multidimentional concept that can be assessed by means of validated questionnaires completed by patients. The psychological effects of a diagnosis of cancer and the physical effects of the disease and its treating have a major impact on a patient's health-related quality of life. Much cancer treatment, especially chemotherapy for metastatic disease, is given for palliation. Palliation implies improvement in either the duration or quality of life remaining. However, treatment patients with common metastatic tumours to prolong life is generally unsuccessful, so improving quality of life is a more realistic goal. Most trials involve evaluating shrinkage of a tumour (i.e., tumour response), which does not imply a benefit to the patient. Few trials have assessed quality of life directly, although several validated instruments, described here, are available to quantify quality of life in cancer patients. These instruments represent a wide scope, from evaluating general health to assessing the quality of life of patients with specific types and stages of cancer. They respond to changes in clinical state and are strongly predictive of survival. Measures of quality of life should be incorporated in all clinical trials where treatment is palliative, and a simple, relevant measure of quality of life should be used as a (or the) primary outcome measure. Other measures of quality of life are important to ensure that gains in one area do not occur at the expense of others. A few large trials incorporating these principles have shown that chemotherapy can provide palliation for patients with advanced cancer.

Clinical Trials as Topic↗
PubMed1998

Development and characterization of new immortalized human breast cell lines

New human breast cell lines were developed from metastatic breast cancer tissues and normal breast tissues. Primary cultures were initiated from cellular outgrowths of explanted tissues or from mechanically isolated cells in two serum-free media. Cell cultures derived from both cancer and normal tissues were immortalized with pRSV-T plasmid to generate permanent breast cell lines that exhibited an epithelial morphology. Cell lines generated in this study were characterized with respect to morphology, growth rate, karyotype, presence of specific genes, and the expression of epithelial and breast markers. The cell lines expressed the epithelial cell markers, cytokeratins 8 and 18, and retained the capacity to produce human milk fat globulin. They also express the BRCA-1, erbB2, and EGF receptor genes and possess the H-ras, K-ras, and p53 genes. Preliminary data showed that one of the new cancer cell lines was highly sensitive to the cytotoxic action of taxol. It is envisioned that the new breast cell lines will be useful as targets for identification of therapeutic agents against breast cancer and as models for carcinogenesis studies.

Journal Article↗
PubMed1998

Adjuvant chemotherapy for high-risk urothelial transitional cell carcinoma: the Princess Margaret Hospital experience.

OBJECTIVE: To review the outcome of adjuvant systemic chemotherapy after surgery for patients with locally advanced urothelial transitional cell carcinoma (TCC) of the bladder and upper urinary tract who were at high risk for recurrence or metastatic spread. PATIENTS AND METHODS: Thirty-five patients (27 men and eight women, median age 59 years) received adjuvant chemotherapy and were followed for a median of 31 months from surgery (range 12-109). All patients had undergone surgery (cystectomy, nephrectomy, nephrouretectomy), with removal of all evident tumour from the following primary sites: bladder (29), renal pelvis (three) and ureter (three). Thirty patients had stage pT3 or greater, 22 had node-positive disease and 16 had vascular invasion. The median interval from surgery to chemotherapy was 2 months. Patients received a median of four courses of cisplatin, methotrexate and vinblastine (n = 23) or the same drugs with doxorubicin (n = 12). RESULTS: Toxicity included nine episodes of febrile neutropenia (one fatal) and six episodes of thromboembolism (one fatal). Eighteen patients (51%) remain alive and free of apparent disease with a median follow-up of 31 months. Actuarial overall and relapse-free survival were 64% and 57% at 2 years and 47% and 53% at 5 years, respectively. For the 22 node-positive patients, the median relapse-free survival and overall survival was 22 months and 33 months, respectively. CONCLUSIONS: Patients with urothelial TCC at high risk of relapse after radical surgery can have a reasonable chance of long-term survival with systemic adjuvant chemotherapy. Treatment is associated with toxicity. The benefits of treatment should be addressed in a large randomized controlled trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Phase I and pharmacologic study of 9-aminocamptothecin colloidal dispersion formulation given as a 24-hour continuous infusion weekly times four every 5 weeks.

PURPOSE: 9-Aminocamptothecin (9-AC) is a water-insoluble camptothecin (CMP) derivative that inhibits normal topoisomerase I function. Schedule dependency was noted, with the greatest activity seen in the setting of greater than 24 hours exposure to lactone (L) concentrations > or = 10 nmol/L. In this phase I study, 9-AC was given by a continuous intravenous infusion over 24 hours once weekly times four every 5 weeks. PATIENTS AND METHODS: Twenty patients, of whom 16 had fluorouracil-refractory colorectal cancer (CRC), entered the study. Dose levels were 0.7 mg/m2 (n = 4), 1.4 mg/m2 (n = 3), 1.9 mg/m2 (n = 6), and 1.65 mg/m2 (n = 7). Detailed pharmacokinetic (PK) measurements of 9-AC L and carboxylate (C) were performed on day 1 of cycles 1 and 2. RESULTS: At 1.9 mg/m2, dose-limiting toxicity (DLT) was reached, with three of six patients having grade 4 neutropenia. At 1.65 mg/m2, one of seven patients had grade 4 neutropenia. Nonhematologic toxicity was modest, with diarrhea > or = grade 3 in two patients and lethargy > or = grade 3 in eight. PK/pharmacodynamic (PD) analyses showed marked interpatient variability. Steady-state concentrations (Css) of 9-AC L > or = 10 nmol/L (3.6 microg/L) were seen in five of seven patients at 1.65 mg/m2 and five of six patients at 1.9 mg/m2. Using the sigmoidal maximal effect (Emax) model, 9-AC L area under the concentration-time curve (AUC) and Css correlated with day 15 decrease in neutrophils (R2 = .47), but not platelets. CONCLUSION: The recommended phase II dose of 9-AC colloidal dispersion (CD) given as a 24-hour continuous infusion weekly for 4 of every 5 weeks is 1.65 mg/m2.

Adult↗
PubMed1998

Assessing the impact of chemotherapy on tumor-related symptoms in advanced colorectal cancer.

In all patients with advanced colorectal cancer, disease eventually progresses following fluorouracil (5-FU) therapy, with a worsening of disease-related symptoms and quality of life (QOL). Irinotecan (CPT-11 [Camptosar]) has produced response rates of 16% to 27% in patients with 5-FU-refractory colorectal cancer, along with a modest survival gain and possible palliative benefit. Disease-related symptoms and QOL are major end points of palliation, although few studies have assessed them as primary end points of response. The concept of palliative response benefit has been applied successfully to randomized trials of systemic therapy in prostate and pancreatic cancers. This article will describe how this concept has been used in the design of a current phase II trial assessing the palliative benefit of irinotecan in patients with 5-FU-refractory colorectal cancer. This trial uses disease-related symptoms and performance status as primary end points. Palliative response was defined prospectively as one or more of the following; (1) 50% decrease in pain score; (2) 50% decrease in narcotic analgesic usage; or (3) 10-point increase in Karnofsky performance scale from baseline for 4 weeks, without deterioration of any of these parameters. The difficulties in using patient-oriented end points as response criteria in this trial and in the clinic will be addressed.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Australian multicentre phase II trial of paclitaxel in women with metastatic breast cancer and prior chemotherapy.

OBJECTIVE: To determine the efficacy and safety of paclitaxel given as a three-hour infusion in patients with metastatic breast cancer which had progressed despite hormonal therapy and/or chemotherapy. DESIGN AND SETTING: Multicentre phase it trial undertaken in five major centres or hospitals in Sydney, Melbourne and Adelaide. PATIENTS AND METHODS: 50 patients with clinically or radiologically measurable or evaluable metastatic breast cancer recruited between March and July 1993. All had received prior chemotherapy, with subsequent disease progression. INTERVENTION: Paclitaxel (Anzatax, Faulding) was given at a dose of 175 mg/m2 intravenously over three hours every three weeks for up to nine courses. MAIN OUTCOME MEASURES: Response rate (partial or complete); duration of progression-free survival; duration of survival; and adverse reactions. RESULTS: Patients had a median age of 51 years; 62% had received at least two prior drug regimens for metastatic breast cancer and 48% had anthracycline-resistant tumours. A median of six paclitaxel courses was given per patient. Overall response rate was 18% (95% confidence interval [95% CI], 9%-31%), with complete responses in four patients (8%). In patients with anthracycline-resistant tumours, response rate was 25% (95% CI, 10%-47%). Response was not influenced by extent of prior treatment. Estimated median progression-free survival was 4.1 months (95% CI, 3.2-6.0 months) and estimated median survival was 6.3 months (95% CI, 6.2-10.3 months). Treatment was well tolerated, with neutropenia the major toxic effect. CONCLUSIONS: Paclitaxel (three-hour infusion) has significant activity in heavily pretreated patients with metastatic breast cancer, including anthracycline-resistant tumours.

Adult↗