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Biomedical subjects

F Lee

Publications and source records attributed to F Lee.

At least 325 records · Page 18Linked to original sources
PubMedDate not supplied

An alternating chemotherapy combination (MACOBLE) for intermediate and high-grade non-Hodgkin's lymphoma.

From June 1983 to February 1986, 48 patients with intermediate or high-grade non-Hodgkin's lymphomas (NHL) received a CHOP based combination with the addition of etoposide on days 1 and 2, bleomycin days 1 and 10 and methotrexate 1.5 g/m2 on day 10 (MACOBLE). Their median age was 59 years, 20 (42 per cent) had an ECOG performance status (PS) of 2 or 3, 24 (50 per cent) had stage IV disease, 25 (52 per cent) B symptoms and 21 (44 per cent) bulk (greater than 10 cm) disease. With a median follow-up of 62 months, 12 patients are alive, 10 of whom are disease-free. Median overall survival was 13 months (95 per cent confidence interval 6-23 months) with actuarial 5-year survival of 25 per cent (95 per cent confidence interval 13-37 per cent). Factors associated with inferior survival were ECOG PS 2 or 3 (P = 0.004), B symptoms (P = 0.013) and bulk disease (P = 0.017). These data suggest that, when treating an unselected patient population, attempts to increase the intensity of first-line chemotherapy may not improve the outcome.

Adult↗
PubMedDate not supplied

Methods determining phosphor imaging limits of quantitation in whole-body autoradiography rodent tissue distribution studies affect predictions of 14C human dosimetry.

INTRODUCTION: Radioluminography, or phosphor imaging, is often used in rodent quantitative whole-body autoradiography (QWBA) studies to determine the tissue distribution and pharmacokinetic (PK) parameters of new pharmaceutical entities in rodents. The rodent tissue pharmacokinetics information are then used to predict human radiation exposure to 14C or 3H during human radioisotope mass balance studies. The human dosimetry estimation can be biased by the method used to determine the lower limit of quantitation (LOQ) of the phosphor imager. A survey of autoradiographers revealed that at least five different methods are used to determine phosphor imager LOQ. The objective of this study is to compare and evaluate the human dosimetry estimates obtained by applying those five LOQ methods to a single set of WBA data. METHODS: Five different phosphor imager LOQ determination methods were applied to a single set of QWBA rodent tissue distribution data to produce five tissue concentration time profiles. Tissue PK parameters were determined for each profile and subsequently used to calculate the 14C exposure for a proposed human 14C mass balance study. RESULTS: A threefold difference was observed among the five predictions of human 14C exposure when the five different phosphor imager LOQ values were applied to the initial data set. DISCUSSION: The method chosen to determine the phosphor imaging LOQ for QWBA rodent tissue distribution study could impact the human 14C exposure estimates. The end result may either under- or overestimate the 14C-tissue exposure in humans during radioisotope studies, depending on the method used to determine LOQ. We recommend two approaches to reduce the variations in the determination of rodent tissue distribution pharmacokinetics: (1) Set more sampling time points to cover the terminal phase to obtain more accurate t 1/2 and (2) use Method 3 or the small sized sampling tool of Method 5 for LOQ determinations because it is a balanced approach for both simplicity and accuracy.

Animals↗
PubMedDate not supplied

Clinical pharmacokinetics of ganciclovir in patients with normal and impaired renal function.

The pharmacokinetics of ganciclovir was evaluated in 21 patients with life- or sight-threatening cytomegalovirus infections. Thirteen patients had normal renal function and eight patients had various degrees of renal insufficiency. Most patients received 5 mg of ganciclovir/kg as a 1-hour intravenous infusion twice daily for periods of up to 2 weeks. Quantification of ganciclovir was assessed by high-performance liquid chromatography and radioimmunoassay. In patients with normal renal function, a biexponential decay of ganciclovir from plasma was observed, with an initial distribution half-life (t1/2) of 0.76 +/- 0.67 hour and a terminal elimination t1/2 of 3.60 +/- 1.40 hours. A large fraction of the administered dose was excreted in urine, and total clearance of ganciclovir correlated well with creatinine clearance. In patients with renal insufficiency who were receiving 5 mg of ganciclovir/kg, the terminal elimination t1/2 of ganciclovir was markedly increased (11.50 +/- 3.90 hours), as compared with values obtained in patients with normal renal function. Hemodialysis efficiently reduced levels of ganciclovir in plasma by approximately 53.0% +/- 11.5%, a finding that indicates this drug should be administered after dialysis.

Acyclovir↗
PubMedDate not supplied

Restoration of alloreactivity of melanoma by transduction with B7.1.

Melanoma cells are unusual because, unlike most epithelial tumors, constitutive expression of human leukocyte antigen (HLA) class II molecules is common. To elucidate the role of HLA class II expression in the immunopathogenesis of melanoma, the authors compared HLA class II+ melanoma cells to autologous B cells with respect to their ability to stimulate primary (naïve) histoincompatible lymphocytes and T-cell clones (antigen experienced). Using primary lymphocytes (peripheral blood lymphocytes [PBLs]), melanoma cells were nonstimulatory when compared to autologous B cells. To determine whether this was caused by defective antigen processing, the authors used alloreactive T-cell clones, which require alloantigen presentation by a histocompatible stimulator cell but not costimulation. Melanoma cells stimulated the alloreactive T-cell clones in two of three clones tested, indicating that they processed and presented alloantigen. To determine whether the failure of melanoma cells to stimulate primary lymphocytes was caused by their inability to costimulate the T cells, the authors transduced the melanoma cells with B7.1 and achieved stable expression in more than 95% of the cells. The transduced cells were highly stimulatory, eliciting a 17- to 25-fold increase in proliferation by the peripheral blood lymphocytes compared with controls. Indeed, B7-expressing melanoma cells were more stimulatory than autologous B cells, which elicited an 11- to 15-fold increase compared with controls. These data indicate that melanoma cells fail to stimulate primary lymphocytes because they do not deliver costimulatory signals. Engineering HLA class II+ melanoma cells to express high levels of B7.1 may provide a way to elicit primary T-cell responses to melanoma-associated antigens.

Antibodies, Monoclonal↗
PubMedDate not supplied

Seroprevalence of and risk factors for antibodies to herpes simplex viruses, hepatitis B, and hepatitis C among southwestern Hispanic and non-Hispanic white women.

BACKGROUND AND OBJECTIVES: Few published data describe the seroprevalence of antibodies to herpes viruses and hepatitis viruses among Southwestern minority women. GOALS: To determine the prevalence of antibodies to herpes simplex virus type-1 and type-2, hepatitis B, and hepatitis C among 595 southwestern Hispanic and non-Hispanic white patients seeking gynecologic care; and to investigate risk factors associated with seropositivity. STUDY DESIGN: Analysis of serologic and interview data. Antibody assays were based on purified glycoprotein assays (herpes simplex virus), and commercial assays for hepatitis B virus and hepatitis C virus. RESULTS: Hispanic ethnicity was a risk factor for herpes simplex virus type-1 (age-adjusted odds ratio, 3.1; 95% confidence interval, 1.8-5.3) but was not associated with antibodies to herpes simplex virus type-2, hepatitis B virus, or hepatitis C virus. Risks associated with seropositivity to herpes simplex virus type-2 included a high lifetime number of sex partners, history of any sexually transmitted disease, and increasing age. Among all patients with herpes simplex virus type-2 antibodies, only 11.1% gave histories of genital herpes infection. For women with antibodies to hepatitis B virus, 31.1% gave histories of hepatitis during adulthood. CONCLUSIONS: The seroprevalence of antibodies to herpes simplex virus type-1 and herpes simplex virus type-2 was high in this clinic population; the prevalence of antibodies to herpes simplex virus type-1 was significantly higher in Hispanics than in non-Hispanic whites. Antibodies to herpes simplex virus type-2 and hepatitis B virus were associated with most indicator of sexual behavior. The high prevalence of antibodies to herpes simplex virus type-2 and the infrequent reporting of histories of genital herpes suggest that asymptomatic infection with herpes is common among these clinic patients.

Adult↗
PubMedDate not supplied

SIVrcm infection of macaques.

In a prior report, we described the isolation and characterization of SIVrcm, a distinct primate lentivirus found in a household pet Red-Capped Mangabey (RCM) in Gabon. SIVrcm is divergent from HIV-1 and HIV-2/SIV families of primate lentiviruses. In this report, additional in vitro replication studies and the results of SIVrcm infection in macaques are presented. SIVrcm causes little cytopathic effedct in Molt 4 Clone 8 cells and in rhesus and human PBMCs. In vivo, SIVrcm is non-pathogenic after 200 days in rhesus macaques and after one year in cynomolgous macaques, but does cause a chronic infection in both macaques.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Implementation of physician order entry: user satisfaction and self-reported usage patterns.

OBJECTIVES: To evaluate user satisfaction, correlates of satisfaction, and self-reported usage patterns regarding physician order entry (POE) in one hospital. DESIGN: Surveys were sent to physician and nurse POE users from medical and surgical services. RESULTS: The users were generally satisfied with POE (mean = 5.07 on a 1 to 7 scale). The physicians were more satisfied than the nurses, and the medical staff were more satisfied than the surgical staff; satisfaction levels were acceptable (more than 3.50) even in the less satisfied groups. Satisfaction was highly correlated with perceptions about POE's effects on productivity, ease of use, and speed. POE features directed at improving the quality of care were less strongly correlated with satisfaction. The physicians valued POE's off-floor accessibility most, and the nurses valued legibility and accuracy of POE orders most. Some features, such as off-floor ordering, were perceived to be highly useful and reported to be frequently used by the physicians; while other features, such as "quick mode'' ordering and personal order sets, received little self-reported use. CONCLUSIONS: Survey of POE users showed that satisfaction with POE was good. Satisfaction was more correlated with perceptions about POE's effect on productivity than with POE's effect on quality of care. Physicians and nurses constitute two very different types of users, underscoring the importance of involving both physicians and nonphysicians in POE development. The results suggest that development efforts should focus on improving system speed, adding on-line help, and emphasizing quality benefits of POE.

Attitude of Health Personnel↗
PubMedDate not supplied

Grappling with herpes: herpes gladiatorum.

Initial reports of herpes gladiatorum, a skin infection of wrestlers caused by herpes simplex virus (HSV), focused on case histories and clinical presentations of this disease. To more adequately address broader epidemiologic questions concerning this skin infection, we surveyed members of four southeastern college wrestling teams, sampled high school and college athletic trainers nationwide, and obtained serum specimens from members of one college wrestling team for HSV antibody studies. Nine of 48 (18.8%) college wrestlers in the southeastern athletic conference reported histories of herpes gladiatorum. Wrestlers with a prior history of oral HSV infection (cold sores) were less likely to report HSV skin infection than wrestlers without cold sores (RR = 0.25; 95% C.I. 0.03 to 1.8), while wrestlers with exposure to opponents with cutaneous HSV lesions were at high risk to develop herpes gladiatorum (RR = 9.4; 95% C.I. 2.2 to 40.0). The national survey of athletic trainers indicated that 7.6% of college wrestlers and 2.6% of high school wrestlers had HSV skin infection during the 1984-85 season. Herpes gladiatorum is a common problem among college wrestlers, and morbidity associated with this skin disease can be significant.

Adolescent↗
PubMedDate not supplied

The role of transrectal ultrasound in the early detection of prostate cancer.

Transrectal ultrasound allows tissue characterization of normal and abnormal internal anatomy of the prostate and therefore provides valuable information for the study of prostate cancer. In an early-detection program setting, the hypoechoic lesion proved to be twice as sensitive as a palpable abnormality in predicting the presence of cancer; for every two cancers detected by transrectal ultrasound, one was detected by digital rectal examination. When the presence of a hypoechoic lesion was the criterion for biopsy in a clinical setting, 41 percent proved to be cancer. Sixty-eight percent of these cancers were palpable; thus, for every four cancers detected by transrectal ultrasound, three were detected by digital rectal examination. Hence, in our diagnostic settings, transrectal ultrasound is more sensitive than digital rectal examination. Because transrectal ultrasound can measure tumor size and offer information regarding tumor spread, we recommend that transrectal ultrasound-guided biopsy be performed first on all palpable lesions. Up to 50 percent of negative biopsies guided by palpation have subsequently proved to be cancer with transrectal ultrasound-guided biopsy. If transrectal ultrasound-guided biopsy of a palpable lesion does not reveal cancer, however, a biopsy guided by palpation should be performed. Strategic transrectal ultrasound-guided biopsy for staging should be performed to obtain tissue from areas where microscopic extracapsular tumor extension is likely to be present. Based on presently available evidence, broader implementation and evaluation of transrectal ultrasound, a tool to be complemented by digital rectal examination and prostate-specific antigen, is advocated for the early detection of prostate cancer. It is hoped that the use of transrectal ultrasound will lead to increased survival, with good quality of life, in a cost-effective manner, for men at increasing risk from prostate cancer in the aging national population.

Aged↗
PubMedDate not supplied

Prostate cancer screening: current trends and future implications.

Screening for prostate cancer represents a clinical dilemma with no clear evidence to suggest decreased mortality from any diagnostic test. We now possess new knowledge regarding optimal combinations of DRE, TRUS, and PSA. While DRE and TRUS may be too subjective and PSA too nonspecific, their combined predictive values identify not only men at high risk but also those for whom continued frequent screening may not be cost effective. A monoclonal PSA decision level of no more than 4.0 ng/ml should be used, since 40 percent of cancers detected from 4.0 to 10.0 ng/ml already have extracapsular extension. Assuming that DRE is performed by experienced examiners, the combination of PSA and DRE should produce cost-effective early detection and minimize missed cancers below 4.0 ng/ml. TRUS should be reserved for those patients with either PSA elevations and/or DRE abnormalities. The use of TRUS gland volume data to further modify PSA decision levels, such as the "predicted" PSA concept, may also improve TRUS biopsy criteria and predictive values. Prostate cancer detection can then be objectively limited to a small percentage of the population and better selected for earlier, more localized disease. The ultimate decrease in mortality from screening remains to be demonstrated in randomized trials or observed only after decades of increased public awareness about prompt early detection combined with effective, definitive therapy.

Antigens, Neoplasm↗
PubMedDate not supplied

Violence in A&E: the role of training and self-efficacy.

AIM: To determine the amount of violence experienced by a sample of A&E staff during a three-month period, and to explore the effect of aggression management training and exposure to violence on their self-efficacy in dealing with aggressive patients. METHOD: A small-scale questionnaire survey was undertaken of 130 staff. RESULTS: 76 (58 per cent) responded. The findings suggested that verbal and physical violence were a common occurrence. The type and amount of aggression management training were variable. Greater self-efficacy in managing aggressive behaviour was observed in higher grades of staff, and in staff who had experienced higher levels of verbal aggression. CONCLUSION: Violence against nurses was widely reported. Their aggression management training did not appear to equip them with the skills required to manage this behaviour.

Attitude of Health Personnel↗