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Biomedical subjects

T McCarty

Publications and source records attributed to T McCarty.

At least 19 recordsLinked to original sources
PubMed2001

Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer.

PURPOSE: To determine the safety, humoral immune response replication, and activity of multiple intratumoral injections of ONYX-015 (replication selective adenovirus) in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: This phase II trial enrolled patients with SCCHN who had recurrence/relapse after prior conventional treatment. Patients received ONYX-015 at a dose of 2 x 10(11) particles via intratumoral injection for either 5 consecutive days (standard) or twice daily for 2 consecutive weeks (hyperfractionated) during a 21-day cycle. Patients were monitored for tumor response, toxicity, and antibody formation. RESULTS: Forty patients (30 standard and 10 hyperfractionated) received 533 injections of ONYX-015. Standard treatment resulted in 14% partial to complete regression, 41% stable disease, and 45% progressive disease rates. Hyperfractionated treatment resulted in 10% complete response, 62% stable disease, and 29% progressive disease rates. Treatment-related toxicity included mild to moderate fever (67% overall) and injection site pain (47% on the standard regimen, 80% on the hyperfractionated regimen). Detectable circulating ONYX-015 genome suggestive of intratumoral replication was identified in 41% of tested patients on days 5 and 6 of cycle 1; 9% of patients had evidence of viral replication 10 days after injection during cycle 1, and no patients had evidence of replication > or = 22 days after injection. CONCLUSION: ONYX-015 can be safely administered via intratumoral injection to patients with recurrent/refractory SCCHN. ONYX-015 viremia is transient. Evidence of modest antitumoral activity is suggested.

Adenovirus E1B Proteins↗
PubMed2001

Uncertainty and opposition of medical students toward assisted death practices.

To explore medical students' views of assisted death practices in patient cases that describe different degrees and types of physical and mental suffering, an anonymous survey was administered to all students at one medical school. Respondents were asked about the acceptability of assisted death activities in five patient vignettes and withdrawal of life support in a sixth vignette. In the vignettes, actions were performed by four possible agents: the medical student personally; a referral physician; physicians in general; or non-physicians. Of 306 medical students, 166 (54%) participated. Respondents expressed opposition or uncertainty about assisted death practices in the five patient cases that illustrated severe forms of suffering which were secondary to amyotrophic lateral sclerosis, treatment-resistant depressive and somatoform disorders, antisocial and sexually violent behavior, or AIDS. Students supported the withdrawal of life support in the sixth vignette depicting exceptional futility secondary to AIDS. Students were especially opposed to their own involvement and to the participation of non-physicians in assisted death activities. Differences in views related to sex, religious beliefs, and personal philosophy were found. Medical students do not embrace assisted death practices, although they exhibit tolerance regarding the choices of medical colleagues. How these attributes of medical students will translate into future behaviors toward patients and peers remains uncertain. Medical educators must strive to understand the perspectives of physicians-in-training. Expanded, empirically informed education that is attuned to the attitudes of medical students may be helpful in fulfilling the responsibility of imparting optimal clinical care skills.

Adult↗
PubMed2000

Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: a phase II trial.

ONYX-015 is an E1B-55kDa gene-deleted adenovirus engineered to selectively replicate in and lyse p53-deficient cancer cells. To evaluate the selectivity of ONYX-015 replication and cytopathic effects for the first time in humans, we carried out a Phase II clinical testing of intratumoral and peritumoral ONYX-015 injection in 37 patients with recurrent head and neck carcinoma. Patients received ONYX-015 at a daily dose of 1 x 10(10) plaque-forming units (pfu) via intratumoral injection for 5 days during week 1 of each 3-week cycle (n = 30; cohort A), or 1 x 10(10) pfu twice a day for 10 days during weeks 1 and 2 of each 3-week cycle. Posttreatment biopsies documented selective ONYX-015 presence and/or replication in the tumor tissue of 7 of 11 patients biopsied on days 5-14, but not in immediately adjacent normal tissue (0 of 11 patients; P = 0.01). Tissue destruction was also highly selective; significant tumor regression (>50%) occurred in 21% of evaluable patients, whereas no toxicity to injected normal peritumoral tissues was demonstrated. p53 mutant tumors were significantly more likely to undergo ONYX-015-induced necrosis (7 of 12) than were p53 wild-type tumors (0 of 7; P = 0.017). High neutralizing antibody titers did not prevent infection and/or replication within tumors. ONYX-015 is the first genetically engineered replication-competent virus to demonstrate selective intratumoral replication and necrosis in patients. This agent demonstrates the promise of replication-selective viruses as a novel therapeutic platform against cancer.

Adenovirus E1B Proteins↗
PubMed2000

Accelerated development of neurochemical and behavioral deficits in LP-BM5 infected mice with targeted deletions of the IFN-gamma gene.

Mice homozygous for a germline deletion of the interferon-gamma gene (IFN-gamma (-/-)) were infected with the LP-BM5 (BM5) retrovirus mixture to determine if the inability to produce IFN-gamma reduces collateral CNS damage associated with chronic neuroinflammation. Virus burdens in spleens and brains of infected mice were comparable, but spatial memory deficits were manifested earlier and to a greater extent in BM5/IFN-gamma (-/-) mice. The mice with spatial memory deficits showed considerable degradation of axons and microtubules, along with apoptosis of striatal neurons. These lesions were accompanied by extensive infiltration of perivascular spaces and ventricles by iNOS-positive leukocytes, and a 17-fold increase in CSF glutamate levels. Despite high levels of VCAM and ICAM expression on cerebral vasculature endothelia, the serum levels of soluble ICAM-1 were significantly decreased in BM5/IFN-gamma (-/-) mice, which may contribute to the enhanced leukocyte infiltration and subsequent neuronal damage. These results suggest that the presence of IFN-gamma is necessary at some points in the inflammatory process to protect against neurodegeneration.

Animals↗
PubMed2000

Perceptions of the ethical acceptability of using medical examiner autopsies for research and education: a survey of forensic pathologists.

BACKGROUND: Forensic pathologists face difficult moral questions in their practices each day. Consistent ethical and legal guidelines for autopsy tissue use extending beyond usual clinical and legal imperatives have not been developed in this country. OBJECTIVE: To obtain the perceptions of medical examiners regarding the ethical acceptability of autopsy tissue use for research and education. METHOD: A written, self-report questionnaire was developed and piloted by a multidisciplinary team at the University of New Mexico, Albuquerque. All individuals who attended a platform presentation at the National Association of Medical Examiners Annual Meeting in September 1997 were invited to participate. RESULTS: Ninety-one individuals completed the survey (40% of all conference registrants and approximately 75% of presentation attendees). Sixty-three percent of respondents had encountered an ethical dilemma surrounding autopsy tissue use, and one third reported some professional ethics experience. Perspectives varied greatly concerning the ethical acceptability of using autopsy tissues to demonstrate or practice techniques (eg, intubation, brachial plexus dissection) and of fulfilling requests to supply varying kinds and quantities of tissues for research and education. Most respondents indicated that consent by family members was important in tissue use decisions. Respondents agreed on the importance of basic values in education and research, such as integrity, scientific or educational merit, and formal institutional approval of a project. Characteristics of the decedent did not influence decisions to release tissues, except when the individual had died from a mysterious or very rare illness. Attributes of medical examiners, with the exception of sex, also did not consistently predict responses. CONCLUSION: Significant diversity exists in beliefs among medical examiners regarding perceptions of the appropriate use of autopsy tissues for education and research. There is need for further inquiry and dialogue so that enduring policy solutions regarding human tissue use for education and research may be developed.

Attitude of Health Personnel↗
PubMed2000

Postoperative suppressive therapy for thyroid adenomas.

Thyroid adenoma is a common disease. If partial thyroidectomy is performed, postoperative suppression therapy is often given to avoid nodule development in the remaining thyroid. It is unclear whether this treatment is warranted. Patients who underwent a partial thyroidectomy with a histologic diagnosis of follicular thyroid adenoma from January 1985 until February 1998 were studied retrospectively. Patients were analyzed on the basis of postoperative therapy, new thyroid nodule growth, and costs. Seventy-six patients were identified with a recurrence rate of 4 per cent (3/76). Sixty-one per cent (46/76) were treated with postoperative thyroid suppression therapy, and no difference in new nodule development was noted with at least 6 months of follow-up (P = 0.274). No patients required reoperation. A large cost saving was shown for patients who were not treated with levothyroxine. We conclude that postoperative thyroid suppression may not be routinely indicated. A prospective, randomized study would be necessary to answer this question conclusively.

Adenoma↗
PubMed1999

Assessing medical students' competence in obtaining informed consent.

BACKGROUND: Medical schools increasingly place emphasis on preparing students to perform routine, ethically important clinical activities with sensitivity and acumen. A method for evaluating students' skills in obtaining informed consent that was created at our institution is described. METHODS: Formal assessment of medical students' professional attitudes, values, and ethics skills occurs in the context of three required and developmentally attuned comprehensive examinations. A videotaped station tested senior medical students' ability to obtain informed consent from a standardized patient who expresses concern about undergoing cardiac catheterization. Two checklists were completed by the patient. Videotapes were reviewed by a faculty member, and students' reactions to the assessment experience were documented. RESULTS: Seventy-one senior students participated, and all performed well. Mean scores of 6.3 out of 7 (range 5 to 7, SD = 0.5) on the informed consent checklist and 8.7 out of 9 (range 6 to 9, SD = 0.5) on the communication skills checklist were obtained. Students endorsed the importance of the skills tested. CONCLUSIONS: This method of examining medical students' abilities to obtain informed consent has several positive features and holds promise as an ethics competence assessment tool.

Adult↗
PubMed1999

STAT6-deficient mice exhibit normal induction of murine AIDS and expression of immunoglobulin E following infection with LP-BM5 murine leukemia viruses.

The unique Gag polyprotein of the replication-defective virus responsible for murine AIDS (MAIDS) induces B-cell activation, proliferation, and differentiation, including immunoglobulin class switch-recombination to immunoglobulin E (IgE). Secretion of IgE normally requires the serial induction of interleukin 4 (IL-4), engagement of the IL-4 receptor, activation of signal transducer and activator of transcription (STAT) 6, and induction of Iepsilon germline transcripts as a prelude to switching. Remarkably, expression of IgE is equivalent in normal and IL-4-deficient mice with MAIDS (Morawetz et al., J. Exp. Med. 184:1651-1661, 1996). To understand this anomaly, we studied mice with a null mutation of STAT6. Lymphoproliferation and immunodeficiency, the hallmarks of MAIDS, developed with comparable kinetics and degree in normal and mutant mice. In addition, serum IgE levels were indistinguishable in mice of either genotype. We conclude that B cells from mice with MAIDS activate unique IL-4- and STAT6-independent signaling pathways for B-cell activation and differentiation.

Animals↗
PubMed1997

Internal medicine, psychiatry, and emergency medicine residents' views of assisted death practices.

BACKGROUND: Although studies have revealed conflicting attitudes within the medical community regarding assisted death practices in the United States, the views of current resident physicians have not been described. OBJECTIVE: To investigate the perspectives of residents from 3 medical specialty fields regarding the acceptability of assisted suicide and euthanasia practices as performed by 4 possible agents (the resident personally, a referral physician, physicians in general, or nonphysicians in general) in 6 patient scenarios. METHODS: An anonymous survey exploring responses to 6 patient vignettes was conducted with a convenience sample of all residents in the internal medicine, psychiatry, and emergency medicine training programs. RESULTS: A total of 96 residents, 72% of those asked, participated in this study. Overall, residents expressed opposition or uncertainty regarding assisted suicide and euthanasia. The residents were disinclined to directly perform such practices themselves and did not support the conduct of assisted suicide practices by nonphysicians. Respondents were somewhat more accepting of other physicians' involvement in assisted death activities. Conflicting views were expressed by residents, with emergency medicine residents more likely to support assisted suicide practices in 4 of 6 patient vignettes than either internal medicine or psychiatry residents. Residents who reported being influenced by religious beliefs (21 respondents [22%]) did not support assisted death practices, whereas those influenced by personal philosophy (74 respondents [77%]) expressed less opposition. CONCLUSIONS: This study explores the uncertainty and differing views of residents from 3 fields about physician-assisted suicide practices. Study findings are considered within the larger literature on clinician attitudes toward assisted suicide and euthanasia.

Adult↗
PubMed1996

Urologic sequelae of childhood genitourinary trauma and abuse in men: principles of recognition with fifteen case illustrations.

Providing urologic care to men who have been traumatized during childhood may be especially challenging because of the extent, severity, and unusual character of their urogenital problems. Recognition of past trauma entails attentiveness to patients' background and behaviors. As illustrated through these 15 cases, patients who present with too many past surgeries, too many unremitting urologic complaints, too little sexual function and too few genital parts, sexual impulses that are too strong, sexualized conduct in clinical settings, and self-destructive behaviors surrounding sexuality may have experienced trauma in the past. While empirical studies are necessary to demonstrate the ultimate utility of these categories, appreciation of these clinical indications improves the urologic care provided to traumatized men in four ways: by elucidating unusual and unusually recalcitrant urologic complaints, thereby clarifying clinical decisions; by allowing for appropriate use of psychiatric consultation; by promoting a better understanding of the sequelae of trauma in men; and by alleviating the discomfort naturally felt by urologists and their staff when caring for these difficult, multiproblem patients.

Adult↗
PubMed1989

Thought disorder: current assessment, techniques, and future trends.

The early accounts of thought disorder were based primarily on abnormalities in the speech patterns of schizophrenic patients. Researchers have attempted to study and assess this phenomenon based on the verbal behaviors of individuals believed to experience disordered thinking. However, verbal dysfunction may not be the most accurate means of assessing thought disorder in psychiatric patients. A review of studies which have attempted to examine aspects of schizophrenic symptomatology suggests that the self-report technique may be a viable alternative for assessing disordered thought. Schizophrenic patients are able to give accurate accounts of experiences relating to their illness. We believe that the self-report technique may provide a reliable method for thought disorder assessment. Based on this assumption, we are currently in the process of developing a self-report scale which assess 13 constructs we believe to be associated with thinking. In a small sample of subjects, the questionnaire was able to differentiate schizophrenic subjects from normals.

Cognition Disorders↗