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J Sullivan

Publications and source records attributed to J Sullivan.

At least 37 records · Page 2Linked to original sources
PubMed2001

A phase I study of irinotecan in pediatric patients: a pediatric oncology group study.

A Phase I trial of irinotecan was performed to determine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), and the incidence and severity of other toxicities in children with refractory solid tumors. Thirty-five children received 146 courses of irinotecan administered as a 60-min i.v. infusion, daily for 5 days, every 21 days, after premedication with dexamethasone and ondansetron. Doses ranged from 30 mg/m2 to 65 mg/m2. An MTD was defined in heavily pretreated and less-heavily pretreated (i.e., two prior chemotherapy regimens, no prior bone marrow transplantation, and no radiation to the spine, skull, ribs, or pelvic bones) patients. Myelosuppression was the primary DLT in heavily pretreated patients, and diarrhea was the DLT in less-heavily pretreated patients. The MTD in the heavily pretreated patient group was 39 mg/m2, and the MTD in the less-heavily pretreated patients was 50 mg/m2. Non-dose-limiting diarrhea that was well controlled and of brief duration was observed in approximately 75% of patients. A partial response was observed in one patient with neuroblastoma, and in one patient with hepatocellular carcinoma. Stable disease (4-20 cycles) was observed in seven patients with a variety of malignancies including neuroblastoma, pineoblastoma, glioblastoma, brainstem glioma, osteosarcoma, hepatoblastoma, and a central nervous system rhabdoid tumor. In conclusion, the recommended Phase II dose of irinotecan administered as a 60-min i.v. infusion daily for 5 days, every 21 days, is 39 mg/m2 in heavily treated and 50 mg/m2 in less-heavily treated children with solid tumors.

Adolescent↗
PubMed2001

Racial variation in prostate specific antigen in a large cohort of men without prostate cancer.

Several studies have reported racial variation in serum prostate specific antigen (PSA) levels. Many of these studies, however, have included a significant number of men without a documented digital rectal examination (DRE) result or without prostate biopsies if abnormalities in PSA or DRE were detected. Thus, it is not clear that men with prostate cancer have been excluded in these analyses. In this report, data from 9,162 men (3,786 African-American men and 5,376 white men) are reviewed. All men had both serum PSA and DRE testing. Every man in this study had either a documented normal DRE and PSA (< 4 ng/mL) (3,422 African-American men and 4,795 white men) or a negative prostate biopsy (364 African-American men and 581 white men). Data were analyzed in age-matched decades. African-American men and white men had no difference in serum PSA levels between 30 and 39 years of age. At 40-49, 50-59, 60-69 and 70-79 years of age, African-American men had a statistically higher serum PSA level than white men. From these data, we conclude that racial variation in serum PSA is present in all decades above 40 years of age. Our data are unique in that this cohort included a substantial number of men between 30 and 39 years of age. In this group of young men, no racial differences in serum PSA were detected. These studies indicate, for the first time, that the onset of racial variation in PSA occurs after the fourth decade of life.

Adult↗
PubMed2001

Surviving uncertainty and projecting recovery: a qualitative study of patients' and family members' experiences with acute spinal cord injury.

The purpose of this grounded theory study (Glaser & Strauss, 1967) was to explore, identify, and describe patients' and family members' experiences during the acute phase of spinal cord injury (SCI). The study sample consisted of 14 patients with acute spinal cord injury and 11 associated family members. Data sources included: unstructured interviews, participant observation, document analysis, and field notes. Level I (substantive), Level II (categorical), and Level III (theoretical constructs) codes were developed during data analysis. The substantive grounded theory generated in this study described how patients and family members defined and managed physiological and psychological uncertainty of acute SCI by mobilizing family resources and projecting recovery in the sociocultural context of the acute hospital environment.

Adaptation, Psychological↗
PubMed2000

Why do cytotoxic T lymphocytes fail to eliminate hepatitis C virus? Lessons from studies using major histocompatibility complex class I peptide tetramers.

Hepatitis C virus (HCV) infection is a major public health problem, affecting an estimated 3% of the world's population, and over 10% in some countries. Infection in most cases becomes persistent, and can lead to hepatic inflammation, fibrosis and liver failure. The T lymphocyte reponse, in particular that mediated by cytotoxic T lymphocytes (CTLs), is likely to be involved in determining the outcome of infection, although its overall role is not clear. The use of major histocompatibility complex (MHC) class I peptide tetrameric complexes (tetramers) to study antiviral CTL responses has revolutionized our approach to the study of human infection. We have used a panel of MHC class I tetramers to analyse immune responses in HCV-infected individuals at various stages of disease. We find that the CTL response against HCV is vigorous in its early phases but dwindles over time both in terms of lymphocyte number and function. A number of potential explanations for this 'CTL failure' are discussed.

Adult↗
PubMed2000

HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors.

A unique cohort of HIV-1-infected long term nonprogressors (LTNP) with normal CD4(+) T cell counts and <50 copies/ml of plasma were prospectively recruited for study. HLA typing revealed a dramatic association between the HLA B*5701 class I allele and nonprogressive infection [85% (11 of 13) vs. 9.5% (19 of 200) in progressors; P < 0. 001]. Antigen-specific CD8(+) T cells were enumerated by flow cytometric detection of intracellular IFN-gamma in response to HIV antigens and HLA B*57-gag tetramer staining. No quantitative differences in the total HIV-specific CD8(+) T cell responses were observed between B*57(+) LTNP and five B*57(+) progressors (P = 0.4). Although similar frequencies of peptide specific CD8(+) T cells were also found, the gag-specific CD8(+) T cell response in the LTNP group was highly focused on peptides previously shown to be B*57-restricted. These findings indicate that, within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease. They also strongly suggest a mechanism of virus specific immunity that directly operates through the B*5701 molecule. Further characterization of qualitative differences in the virus-specific responses that distinguish HLA B*57(+) LTNP from progressors may ultimately define mechanisms of effective immune mediated restriction of virus replication.

Alleles↗
PubMed2000

Time acts as a conditioned stimulus to control behavioral sensitization to amphetamine in rats.

Repeated exposure to the psychostimulant drug, amphetamine, results in a persistent increase in the ability of the drug to elicit behavioral activation.(14,19) The development of sensitized responses to amphetamine involves long-lasting neuroadaptations within defined circuitry.(3,6,12,15,23) The behavioral expression of sensitization, however, can come under the control of specific environmental cues. Thus, the sensitized locomotor response to a challenge injection of amphetamine is greater if the drug is given in the environment previously associated with intermittent injections than if given in a different environmental context.(2,13,16,18,20,21) Contrary to the wealth of information on the significance of contextual cues, little is known about the importance of time cues in the expression of sensitized responding to amphetamine. In the present study we, therefore, asked whether time of injection might influence the expression of amphetamine sensitization. We found that time can readily act as a conditioned stimulus to control the expression of behavioral sensitization to amphetamine in rats. This finding is important for understanding the mechanisms underlying sensitization to psychostimulant drugs and its impact on behavior.

Amphetamine↗
PubMed2000

Nursing scripts and the organizational influences on critical thinking: report of a study of neonatal nurses' clinical reasoning.

During 1995-1997 a study was undertaken to explore the extent to which theoretical knowledge acquired through a distance education programme in neonatal nursing was brought to bear in the real-world clinical reasoning of course participants. The study utilized a think aloud technique and included both concurrent (on-the-job) and retrospective verbal reports at 0, 6 and 12 months into the programme. Participants (n=4) were also interviewed individually on completion of the study. Results indicated that important inconsistencies existed between participants' theoretical knowledge and their practice; they also pointed to some organizational influences on these theory-practice inconsistencies. Script (or schema) theory provided a useful explanatory framework for these results. The paper includes a brief description of data collection and analysis techniques; its main emphasis, however, is on these theory-practice inconsistencies and their explanation in terms of the nature and acquisition of nursing practice scripts. The implications of nursing scripts for the promotion of critical thinking and evidence-based practice are discussed.

Adult↗
PubMed2000

Phylogeography of Peromyscus furvus (Rodentia; muridae) based on cytochrome b sequence data.

We conducted phylogenetic analyses of cytochrome b sequence data to assess genetic variation within and among the three allopatric segments of the distribution of Peromyscus furvus from the Sierra Madre Oriental in eastern Mexico. We identified 24 unique haplotypes among the 54 individuals examined and genetic distances ranged up to 0.078 substitutions per site. Populations from the central portion of the range formed a monophyletic unit, whereas samples from the southern distributional unit were polyphyletic. Furthermore, the southernmost population sampled may represent a distinct species. This high degree of genetic differentiation among populations, currently recognized as conspecific, mirrors the result of other genetic studies of highland rodents in Mesoamerica. Together these studies indicate that the region, already considered hyperdiverse on the basis of species diversity and endemism, may contain considerably greater diversity than is currently appreciated.

Animals↗
PubMed2000

Role of stored iron in atherosclerosis.

Myocardial infarction remains the No. 1 killer of American men and women, with a death rate of 225,000 per year, and stroke, the third leading cause of death in the United States, afflicts about 600,000 per year. The combined financial burden of these diseases is approximately $134 billion per year. Therefore, interventions that reduce mortality and suffering will have a significant impact on the health care system. This article summarizes research conducted during the last 2 decades that addresses the idea that stored iron plays a role in the pathogenesis of atherosclerosis and that iron reduction through phlebotomy may play a role in the treatment or prevention of atherosclerosis. Body iron stores rise after adolescence in men and menopause in women. This rise has been linked to the pathogenesis of atherosclerosis through iron-induced oxidation of low-density lipids and foam cell formation. However, the available evidence on the iron hypothesis remains circumstantial. Reduction of body iron stores in the setting of a controlled, prospective intervention trial is necessary to determine whether the amount of stored iron is related to clinically meaningful vascular disease. Such a study is feasible because reduction in iron stores can be achieved safely and predictably without induction of iron deficiency by graded phlebotomy. The Iron and Atherosclerosis Study (FeAST), a Veteran's Administration Cooperative Study, is under way to test this concept.

Arteriosclerosis↗
PubMed2000

Positioning of patients with severe traumatic brain injury: research-based practice.

Traumatic brain injuries (TBIs) are the most common disabling injuries in the United States, accounting for 44% of all deaths due to trauma. Once inflicted, primary cerebral injury is immutable and irreversible. Consequently, initial critical care of TBI patients focuses on prevention of secondary cerebral injury through the treatment of intracranial hypertension, systemic resuscitation, and multisystem stabilization. Relationships exist between therapeutic positioning, multisystemic stability, and prevention of secondary cerebral injury in severe TBI. A critical review and synthesis of current research literature on multisystem responses to positioning led to development of clinical recommendations based on currently available evidence and generated best practices for positioning patients with severe TBI.

Bed Rest↗
PubMed2000

Evaluating the role of physical and radiographic examinations in assessing bullet tract termination for gunshot victims.

Knowledge of the path of a bullet and how it terminates is critical for expeditious assessment and optimal management of patients with gunshot wounds. To assess the accuracy of physical examination and X-rays in these patients, a prospective study was undertaken for all gunshot victims seen for a 1-year period on a single trauma service. The paramedics and trauma surgeons' physical examinations were evaluated for whether a bullet tract could be accurately categorized as 1) through and through, 2) graze, 3) palpable under dermis, or 4) retained (ie, not palpable). The impact of X-rays was assessed with regard to how it affected the trauma surgeons' categorization. A total of 78 patients were seen with a total of 120 bullet tracts. Seventy-seven per cent were injured by assault, and 64 per cent were shot with a 9-mm or .38-caliber handgun. Twenty of 60 (33%) bullet tracts on the torso terminated with a missile that was palpable under dermis, but only 2 of 10 neck (20%), 1 of 28 extremity (4%), and 1 of 22 head/face (5%) did so. Paramedics evaluated 15 torso bullet tracts that ended palpable under dermis, of which they detected 5 (33%). Upon initial examination, the trauma surgeon detected 11 of 20 torso bullet tracts that ended palpable under dermis (55%), and detected 14 of the 20 after X-rays were done (70%). Overall, obtaining X-rays changed the categorization for 15 of 111 bullet tracts (13%). We conclude that bullet tracts on the torso result in a subcutaneously palpable bullet one-third of the time, much more frequently than in other body regions. Paramedics only detect one-third of subcutaneously palpable missiles on the torso. X-rays change the categorization of bullet tracts infrequently. We recommend that a careful examination of the skin of the torso to detect palpable missiles be incorporated into the secondary survey of patients with wounds to that body region.

Allied Health Personnel↗
PubMed2000

Transurethral resection of the prostate: failure patterns and surgical outcomes in patients with symptoms refractory to alpha-antagonists.

BACKGROUND: alpha-Antagonists (AAs) are ineffective in some men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Transurethral resection of the prostate (TURP) may be required. Reasons for AA failure and surgical outcomes in these patients have not been reported. METHODS: We retrospectively reviewed cases of TURP for LUTS due to bladder outlet obstruction from 1995 to 1998. The TURP patients in whom AA therapy had failed (group 1) were compared with those who had symptomatic BPH but were not taking AAs (group 2). Comorbid conditions that might influence treatment results were considered, as were sizes of resection and pathologic results. RESULTS: No differences occurred between groups 1 (n = 38) and 2 (n = 25) in age, length of postoperative follow-up, or resection size. However, outcomes were poorer in group 1 than in group 2. A trend toward greater comorbidity that might lead to voiding dysfunction, though not statistically significant, was seen in group 1. CONCLUSIONS: Postoperative results of TURP may be less successful after AA therapy failure. This may be due to preoperative risk factors that affect voiding function rather than to prostatic size.

Adrenergic alpha-Antagonists↗
PubMed1999

Identification of a new recipient in the Sydney Blood Bank Cohort: a long-term HIV type 1-infected seroindeterminate individual.

We have reported previously a cohort of long-term survivors of HIV-1 infection, known as the Sydney Blood Bank Cohort, who received HIV-1-positive blood from a common infected donor. A new recipient, C135, has been identified. This recipient became infected after receiving blood donated during the presumed time of seroconversion of the donor in February 1981. C135 has been infected for more than 18 years without signs of disease progression. The virus load in this recipient has remained below the detectable level (<20 RNA copies/ml of plasma) and repeated Western blot analyses have given an indeterminate result. By booster PCR techniques we have demonstrated that this individual is infected with HIV-1 and have characterized the viral nef and nef/LTR region sequences present. The strain of HIV-1 identified contains deletions of 88 bp from the nef alone region and a total of 139 bp deleted from the nef/LTR overlap and LTR regions. The LTR contains three wild-type Sp1 transcription factor-binding sites, the 3' wildtype NF-kappaB site, and a duplicated Sp1 and NF-kappaB region. A truncated Nef protein of only 19 amino acids is encoded. The deletions and rearrangements in the nef gene and LTR sequences are characteristic of Sydney Blood Bank Cohort strains of virus. The identification of C135 increases the Sydney Blood Bank Cohort size to nine individuals and represents a rare example of a genuine, long-term HIV-1 infection accompanied by indeterminate anti-HIV-1 serology.

Amino Acid Sequence↗
PubMed1999

In rats, odor-induced Fos in the olfactory pathways depends on the phase of the circadian clock.

We used immunostaining for Fos to study the effect of circadian clock phase on odor-induced neuronal activation in the olfactory system in rats. Brief presentation of cedar odor to rats housed in constant darkness stimulated Fos expression in the main olfactory bulb, anterior olfactory nucleus, piriform cortex, and several other odor-responsive structures, both in the subjective day and subjective night phases of the cycle. Fos expression in response to odor, but not basal expression, was greatly enhanced in the subjective night in all structures examined. These findings are consistent with the idea that odor-induced neuronal activation in the olfactory pathways is modulated by the phase of the circadian clock.

Animals↗