Biomedical subjects

William Fisher

Publications and source records attributed to William Fisher.

17 recordsLinked to original sources

PubMed2006

Hoosier Oncology Group randomized phase II study of docetaxel, vinorelbine, and estramustine in combination in hormone-refractory prostate cancer with pharmacogenetic survival analysis.

PURPOSE: To determine the safety and efficacy of two docetaxel doublets in hormone-refractory prostate cancer (HRPC) patients and to examine the prognostic role of polymorphisms in host genes important to docetaxel metabolism and transport. EXPERIMENTAL DESIGN: Sixty-four chemotherapy-naive patients with HRPC were randomized to docetaxel and vinorelbine (D, 20 mg/m2 i.v. days 1 and 8; V, 25 mg/m2 i.v. days 1 and 8) or docetaxel and estramustine phosphate (D, 60-70 mg/m2 i.v. day 1; E, 280 mg oral thrice daily days 1-5) administered q21d. Primary end point was clinically significant toxicity. A pharmacogenetic analysis of host genes was done in patients who received at least one cycle of docetaxel therapy. RESULTS: Grade 3/4 toxicity occurred in 15.6% of DV patients and in 28.6% DE patients. Neither arm exceeded the threshold of clinically significant toxicity. In the DV arm, objective response rate was 33%, prostate-specific antigen response rate was 20%, and median survival was 16.2 months. In the DE arm, objective response rate was 67%, prostate-specific antigen response rate was 43%, and median survival was 19.7 months. Pharmacogenetic analyses showed a significant association between survival beyond 15 months and the ABCG2 421 C > A (Q141K) polymorphism compared with the wild-type (C/C) genotype (66% versus 27%; P = 0.05). CONCLUSIONS: DV and DE doublets are active with a tolerable toxicity profile in patients with HRPC; however, efficacy does not seem superior to standard single-agent docetaxel. The ABCG2 421 C > A (Q141K) polymorphism may be an important predictor of response and survival in HRPC patients treated with docetaxel-based chemotherapy.

Adult↗

PubMed2006

A population-based and longitudinal study of sexual behavior and multidrug-resistant HIV among patients in clinical care.

BACKGROUND: Population-based and longitudinal information regarding sexual risk behavior among patients with multidrug resistant (MDR) HIV and their sexual partners is of great public health and clinical importance. OBJECTIVE: To characterize the HIV sexual risk behaviors of patients with and without drug-resistant HIV in the clinical care setting over time. MEASUREMENTS: 393 HIV-positive patients completed questionnaires of self-reported sexual risk behaviors at approximate 6-month intervals extending over 24 months. HIV viral load and genotypic drug resistance obtained during the same time points were matched to the behavioral data. Multidrug resistance was defined as having resistance to 2 or 3 antiretroviral (ARV) drug classes. RESULTS: In serial cross-sectional analyses, 393 patients (44% female and 79% heterosexual) contributed 919 matched behavioral and virologic results over the 24 months of data collection. Of these, 250 patients (64%) reported having sex during at least 1 survey period resulting in greater than 10,000 sexual events with more than 1000 partners. Unprotected sexual behavior was reported by 45% of sexually active patients, resulting in 34% of all sex events that exposed 29% of all partners. Of these patients with unprotected sexual events, 31% had HIV drug resistance--11.6% with resistance to 2 classes of ARVs (2-class), and 1.8% with 3-class ARV resistance at the time of a sexual risk event. Close to 1000 or 28% of all unprotected sexual events involved resistant strains (11% of these with resistance to 2 classes and 0.2% with 3-class resistance, exposing 20% of unprotected sexual partners to resistant HIV (8% to 2-class and 0.6% to 3-class resistance). In longitudinal analysis among the 78 patients who reported a cumulative total of 12 months of sexual history and had resistance testing, 38% reported engaging in unprotected sexual behavior. There was substantial and complex variation in the distribution of unprotected sexual events and in the detection of resistance over time. CONCLUSION: In this study of HIV sexual risk and resistance over time among HIV-infected patients in clinical care, a substantial proportion engaged in unprotected sex and had drug-resistant HIV, frequently exposing partners to 1- or 2-class resistant HIV strains. However, relatively few exposures involved 3-class resistance. The dynamics of sexual risk behavior and HIV drug resistance are complex and vary over time and urgently require both general and targeted interventions to reduce transmission of resistant HIV.

Adult↗

PubMed2006

A national survey of state mental health authority programs and policies for clients who are parents: a decade later.

This study presents a survey of State Mental Health Authorities' (SMHA) programs and policies addressing the needs of adult clients in their role as parent. Six program and policy areas (parent status identification, parent-focused residential programs, parent functioning assessment, outpatient services for parents, policies for hospitalized parents, and policies for hospitalized pregnant women) are examined. Results of the most recent 1999 survey are compared with results from a similar 1990 survey. This comparison reveals that the majority of SMHAs continue to overlook adult clients in their parenting role, and few SMHA programs and policies address issues of parenting.

Adult↗

PubMed2005

HIV drug resistance and HIV transmission risk behaviors among active injection drug users.

HIV(+) injection drug users in clinical care may harbor and transmit drug-resistant HIV. We performed a retrospective study of HIV drug resistance and risk behavior among HIV(+) injection drug users in care to determine the number of needle-sharing events that involved and the proportion of sharing partners exposed to drug-resistant HIV. Among 180 HIV injection drug users, 55 (31%) reported injecting drugs in the previous month, and 22 of these (40%) shared needles and/or works 148 times with 296 partners, of whom 271 (92%) were thought to be HIV(-) or status unknown. Further, 55 (31%) drug users harbored resistant HIV, including 5 (3% of total) who also shared needles and/or works a total of 27 times with 44 partners (18% of all sharing events and 15% of all exposed partners). A small proportion of injection drug users receiving clinical care engage in injection risk behavior and carry resistant HIV; however, because of multiple partners and needle-sharing events, they expose a substantial number of individuals to drug-resistant HIV. Strategies to reduce injection drug use risk behaviors among patients in clinical care are needed to reduce the transmission of sensitive and resistant HIV.

Anti-HIV Agents↗

PubMed2005

Roles of cyclophilins in cancers and other organ systems.

Cyclophilins are originally identified as cellular binding proteins for the immunosuppressive drug cyclosporin A. Many cyclophilins, including CypA, CypB, CypC, CypD, and Cyp40, have been discovered and shown to be ubiquitously distributed in many types of cells and organ systems. Recent investigations have uncovered many important properties and functions for cyclophilins including peptidyle-prolyl-isomerase activity and protein folding/repair; maintaining mitochondrial functions and involvement in apoptosis; roles in regulation of T-cell function and inflammation; interaction with CD147; and pathogenesis of vascular disease, human immunodeficiency virus infection, and rheumatoid arthritis. Furthermore, the expression and functions of cyclophilins may be correlated with tumor biology of several types of cancers including pancreatic carcinoma. Molecular mechanisms of cyclophilin-mediated biologic events and future directions of research are discussed in this review. Understanding the roles of cyclophilins in cancers and other organ systems will be crucial in determining clinical applications for the treatment or diagnosis of human diseases.

Antigens, CD↗

PubMed2005

Roles of thymosins in cancers and other organ systems.

Thymosins are small peptides, originally identified from the thymus, but now known to be more widely distributed in many tissues and cells. Thymosins are divided into three main groups, alpha-, beta-, : and gamma-thymosins, based on their isoelectric points. alpha-thymosins (ProTalpha, Talphal) have nuclear localization and are involved in transcription and/or DNA replications; whereas beta-thymosins (Tbeta4, Tbeta10, Tbetal5) have cytoplasmic localization and show high affinity to G-actin for cell mobility. Furthermore, it is well known that both alpha- and beta-thymosins play important roles in modulating immune response, vascular biology, and cancer pathogenesis. More importantly, thymosins may have significant clinical applications. They may serve as molecular markers for the diagnosis and prognosis of certain diseases. In addition, they could be molecular targets of certain diseases or be used as therapeutic agents to treat certain diseases. However, the molecular mechanisms of action of thymosins are largely unknown. This review not only presents recent advances of basic science research of thymosins and their clinical applications but provides thoughtful views for future directions of investigation on thymosins.

Animals↗

PubMed2005

A phase II study of single agent gemcitabine in relapsed or refractory follicular or small lymphocytic non-Hodgkin lymphomas: a Hoosier Oncology Group Study.

Gemcitabine is a pyrimidine analog that is active in patients with aggressive lymphomas and Hodgkin disease. This study assessed tumor response in patients with previously treated follicular or small lymphocytic non-Hodgkin lymphoma. This was a 2-stage phase II trial with the first stage requiring 2 of 13 responses to proceed to the second stage. Gemcitabine was given as a single agent to patients with previously treated follicular or small lymphocytic lymphomas. Gemcitabine was administered at 1250 mg/m2 over 30 minutes on days 1 and 8 of a 21-day cycle for a maximum of 6 cycles. Thirteen patients were treated with 1 to 6 cycles of chemotherapy. Two patients experienced grade 4 toxicity with neutropenia. No grade 4 nonhematologic toxicity was seen. There was 1 partial response and 8 patients (61%) had either minimal response or stable disease. Single-agent gemcitabine administered at this dose and schedule produced 1 partial remission and half the patients had stable disease. However, the study had to be stopped early because of lack of meaningful response.

Aged↗

PubMed2005

Impact of referral source and study applicants' preference for randomly assigned service on research enrollment, service engagement, and evaluative outcomes.

OBJECTIVE: The inability to blind research participants to their experimental conditions is the Achilles' heel of mental health services research. When one experimental condition receives more disappointed participants, or more satisfied participants, research findings can be biased in spite of random assignment. The authors explored the potential for research participants' preference for one experimental program over another to compromise the generalizability and validity of randomized controlled service evaluations as well as cross-study comparisons. METHOD: Three Cox regression analyses measured the impact of applicants' service assignment preference on research project enrollment, engagement in assigned services, and a service-related outcome, competitive employment. RESULTS: A stated service preference, referral by an agency with a low level of continuity in outpatient care, and willingness to switch from current services were significant positive predictors of research enrollment. Match to service assignment preference was a significant positive predictor of service engagement, and mismatch to assignment preference was a significant negative predictor of both service engagement and employment outcome. CONCLUSIONS: Referral source type and service assignment preference should be routinely measured and statistically controlled for in all studies of mental health service effectiveness to provide a sound empirical base for evidence-based practice.

Adult↗

PubMed2004

Antiretroviral resistance and high-risk transmission behavior among HIV-positive patients in clinical care.

BACKGROUND: HIV-positive patients receiving antiretroviral therapy (ART) who engage in HIV transmission behaviors may harbor and transmit drug-resistant HIV. However, little is known about the risk behaviors of these patients, potential partners exposed and the relationship of these to ART resistance. OBJECTIVE: To determine the relationship of HIV drug resistance and continuing HIV transmission risk behavior among HIV-positive patients in care. METHODS: A retrospective, cross-sectional study of HIV transmission risk behavior and HIV drug resistance data from 333 HIV-positive patients. RESULTS: Among a diverse population of 333 HIV-positive patients, 75 (23%) had unprotected sex during the previous 3-months, resulting in 1126 unprotected sexual events with 191 partners of whom 155 were believed by patients to be HIV-negative or of unknown status. Eighteen of the 75 (24%) had resistant HIV and 207 unprotected sexual events, exposing 18% of the HIV- or status unknown partners. There was no difference in the proportion of patients engaging in unprotected sex who had undetectable viral load (VL) (22%): VL > 400 copies/ml without resistance (20%) and VL > 400 copies/ml with resistance (26%). Resistance and risk behavior was predicted only by lower mental health scores (odds ratio, 10.3; 95% confidence interval, 1.7-18.6). CONCLUSION: A substantial minority (23%) of patients in clinical care engaged in HIV sexual transmission risk behavior. A small subset of these also had ART-resistant HIV. However, this core group (approximately 5% of all patients) accounted for a large number of high-risk HIV transmission events with resistant virus, exposing a substantial number of partners.

Adult↗

PubMed2004

Cell-specific cytotoxicity of human pancreatic adenocarcinoma cells using rat insulin promoter thymidine kinase-directed gene therapy.

The formation of a normal pancreas and the activation of insulin production are, in part, dependent on the expression and activation of the pancreatic duodenal homeobox gene 1 (PDX-1). The expression of PDX-1 also has been detected in various human pancreatic ductal adenocarcinoma (PDA) cell lines. This has made it possible to generate a cancer cell-specific gene expression system to treat human pancreatic cancer. In this study, we have developed a cell-specific cytotoxic model of PDA cells using the expression of herpes simplex virus thymidine kinase (TK) under the control of the rat insulin promoter (RIP-TK). We have shown that the cell-specific cytotoxicity in human PDA cells depends on the presence of PDX-1. Our results also demonstrate that in vivo PDA-specific cytotoxicity can be achieved with RIP-TK using an intraperitoneal liposomal gene delivery method followed by a short period of ganciclovir treatment in severe combined immunodeficient (SCID) mice. Furthermore, PDX-1 protein was found in all six freshly isolated human pancreas cancer specimens and two liver metastasis samples that were group-tested, suggesting the feasibility of using RIP-TK gene therapy in humans. This study may provide an alternative strategy for the future treatment of pancreatic cancer.

Animals↗

PubMed2004

The 2002 Canadian Contraception Study: part 1.

OBJECTIVES: To investigate the contraception and sexual health-related awareness, attitudes, and practices of a representative sample of Canadian women of childbearing age. METHODS: A self-report survey was mailed to a national sample of 3345 women, aged 15 to 44 years, who were members of a pre-recruited market research panel. Survey questions and methodology were similar to 3 previous Canadian Contraception Studies, allowing for description of current patterns of behaviours and beliefs and comparison of trends over time. RESULTS: Of 3345 women contacted, 1582 returned completed surveys, for a response rate of 47.3%. Responses were weighted to represent Canadian women by region, age, and marital status on the basis of current census data. Eighty-six percent of women sampled had ever had sexual intercourse and 78% were currently sexually active. Women's familiarity with oral contraceptives and condoms as methods of contraception was high (96% and 93%, respectively), but familiarity with other methods was much lower (sterilization, 62%; withdrawal, 59%; the morning-after pill, 57%; intrauterine devices, 50%; depot [injectable] medroxyprogesterone acetate, 38%). A very favourable opinion was held by 63% of respondents concerning oral contraceptives, by 38% concerning condoms, and by 39% and 28% concerning male and female sterilization, respectively. Among respondents who have ever had sexual intercourse, the most frequently used current methods were oral contraceptives (32%), condoms (21%), male sterilization (15%), female sterilization (8%), and withdrawal (6%). Nine percent of these respondents reported using no method of contraception at all. The currently reported rate of female sterilization is the lowest ever recorded in Canada. Survey results show that adherence to contraceptive methods is a challenge for many women and their partners, and that risk of sexually transmitted disease is an ongoing concern. CONCLUSION: This study provides a wide-ranging examination of contraception awareness, beliefs, and use among Canadian women that may provide guidance for clinical and public health practice. Part 1 of this report describes the methodology of the 2002 Canadian Contraception Study and the overall results of this study; Part 2 considers results pertaining specifically to adolescent women and women in their later reproductive years, reports on indicators of women's sexual function and reproductive health history, describes approaches to addressing challenges in contraception counselling, and presents data concerning trends in Canadian women's awareness and use of contraception over the past 2 decades.

Adolescent↗

PubMed2004

The 2002 Canadian Contraception Study: Part 2.

The 2002 Canadian Contraception Study investigated the contraception and sexual health-related knowledge, attitudes, and practices of a representative sample of Canadian women of childbearing age. In Part 2 of the report of this research, the authors focus on the contraceptive attitudes and practices of adolescent women and women in their later reproductive years, provide data on sexual and reproductive health indicators of Canadian women, describe 2-decade trends in the awareness, opinion, and utilization of contraceptive methods among Canadian women, and describe contraception counselling strategies that may be used to improve patient choice and adherence to method. This report closes with an overall discussion of the findings of the 2002 Canadian Contraception Study.

Adolescent↗

PubMed2004

Service quality as measured by service fit and mortality among public mental health system service recipients.

Service fit, defined as consistency between mental health services judged needed and services received was measured for a random sample of service recipients in a public mental health system (N = 6588). A variant of small area analysis was used to measure the relationship between catchment area mortality rates from natural causes, suicide, and medicolegal causes and area fit scores for a variety of services. We tested the theory-based hypothesis that service fit would predict interarea variations in mortality better than simple measures of amount of service prescribed and received. We also tested the hypothesis that, controlling for relevant demographic and clinical factors, fit would be protective for mortality from all causes. Findings supported the first hypothesis. With respect to the second, service fit for only certain services was protective. Housing and clubhouses services were particularly protective, suggesting the importance of services providing social support.

Adult↗

PubMed2004

Relationship between race and ethnicity and forensic clinical triage dispositions.

OBJECTIVE: Racial and ethnic disparities in the criminal justice system have been widely reported, as have racial and ethnic disparities in diagnoses and certain aspects of clinical management. This study examined the association between race and ethnicity and dispositions for pretrial defendants who were referred for forensic mental health evaluations. METHODS: Available data were reviewed for all defendants in Massachusetts who were referred to a Massachusetts court clinic from 1994 to 2001 for a screening evaluation of their competence to stand trial, their criminal responsibility, or both. Logistic regression models were developed to assess the relationship between defendants' race and ethnicity and the likelihood that they would be referred for inpatient evaluation and the likelihood that they would be evaluated within a strict-security facility. Race or ethnicity of the pretrial defendants was identified by clinicians. RESULTS: Blacks, but not Hispanics, were significantly more likely than whites to be referred for an inpatient evaluation after an outpatient forensic screening evaluation. Among male defendants, both Hispanics and blacks were more likely than whites to be referred for an inpatient evaluation in a strict-security facility, regardless of diagnoses and the level of severity of the criminal charges. CONCLUSIONS: Racial and ethnic disparities in disposition decisions exist within the forensic mental health system. These disparities, however, likely reflect numerous clinician and nonclinician variables.

Adult↗

PubMed2002

Etoposide, ifosfamide and cisplatin (VIP) plus concurrent radiation therapy for previously untreated limited small cell lung cancer (SCLC): a Hoosier Oncology Group (HOG) phase II study.

Results of a previous Hoosier Oncology Group (HOG) study revealed a small survival advantage for VIP versus etoposide and cisplatin (EP) for patients with extensive stage small cell lung cancer (SCLC). This phase II study evaluated VIP with concurrent thoracic radiotherapy in patients with limited stage SCLC. Eligible patients had a Karnofsky Performance Score > or = 50, no prior chemotherapy or radiotherapy, and adequate end organ function. Fifty-three patients were entered. Radiotherapy was given as a daily fraction of 1.8 Gy, five fractions per week for 5 weeks for a total dose of 45 Gy, beginning on day 1 of VIP. The first 13 patients received etoposide 75 mg/m(2), cisplatin 20 mg/m(2), and ifosfamide 1.2 g/m(2) on days 1-4 with Mesna every 3 weeks for four cycles unless the patient demonstrated disease progression or undue toxicity. Excessive toxicity was seen in the first 13 patients; therefore, VIP was modified by deleting the 4th day for all subsequent patients. The major toxicity in this trial was myelosuppression. Grade 3/4 anemia, granulocytopenia, and thrombocytopenia occurred in 38, 75, and 34% of patients, respectively. There were four treatment-related deaths [three patients (23%) on the 4-day regimen and one patient (2.5%) on the 3-day regimen]. Twenty-five patients (47.2%) achieved a CR and 11 patients (20.8%) had a PR for an overall response rate of 68%. Minimum follow up for all patients is 5 years. Overall, 46 of 53 patients have died. Median, 1, 2 and 5 year overall survival for the entire group is 15.1 months, 69.8, 35.9, and 13.2, respectively. The results of this phase II trial of VIP with concurrent early thoracic radiotherapy failed to demonstrate a superior response rate over other series utilizing EP. In addition, treatment-related morbidity and mortality appears to be unacceptably high with the VIP regimen.

Adult↗

PubMed2002

Using state administrative and pharmacy data bases to develop a clinical decision support tool for schizophrenia guidelines.

Administrative and pharmacy data bases represent a largely untapped resource for clinical decision support and quality improvement. In this study, we examined the feasibility of using New York State Office of Mental Health (NYSOMH) data bases to develop an automated clinical report to support implementation of schizophrenia guidelines. First we reviewed the structure of existing data bases for capacity and limitations in supporting guideline implementation. Second, we identified schizophrenia guideline recommendations and adherence measures that would be the focus of our implementation. Third, a preliminary report was programmed, based on operational definitions of the guideline recommendations. Finally, we developed user groups to define content and format of new reports, through an iterative process of field testing, feedback, and revision. Our experience suggests that administrative and pharmacy data bases, despite their limitations, can be used to develop guideline-based clinical decision support tools for schizophrenia with high physician acceptability.

Antipsychotic Agents↗

PubMedDate not supplied

Longitudinal patterns of offending during the transition to adulthood in youth from the mental health system.

Arrest rates among the population of youth who have been served in child mental health systems are known to be high during adolescence and young adulthood, but individual longitudinal patterns have not been examined. The present study used developmental trajectory modeling, a contemporary method used widely in criminology, to examine clusters of individual criminal justice involvement patterns at ages 8 through 25, from database records of 131 individuals in public adolescent mental health services. Three groups of particular concern emerged: one with increasingly high offense rates and two with moderate to high violent offense rates that did not desist. Offense patterns in these groups indicate that early intervention should occur before age 15. Some risk factors were identified. Peak offending for most groups occurred between ages 18 and 20. Implications of these findings for mental health services during the transition to adulthood are offered.

Adolescent↗