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Biomedical subjects

E Smith

Publications and source records attributed to E Smith.

At least 73 records · Page 4Linked to original sources
PubMed2001

Tandem-cycle high-dose melphalan and cisplatin with peripheral blood progenitor cell support in patients with breast cancer and other malignancies.

We evaluated the feasibility of tandem-cycle high-dose chemotherapy (HDCT) with cisplatin, melphalan, and peripheral blood progenitor cells (PBPCs). Fifty patients with high-risk primary (n = 17) or stage IV breast cancer (n = 29) or other malignancies (n = 4) received 2 cycles of intravenous melphalan, 20 to 151.8 mg/m2, and cisplatin, 200 mg/m2, followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF. Starting at 40 mg/m2 of melphalan, patients also received PBPCs. Delayed platelet recovery defined the maximum tolerated dose (MTD) for melphalan at 101.2 mg/m2 per cycle. There were no treatment-related deaths. Cycle 2 was delivered at a median of 1.7 months after cycle 1; 72% of patients treated at the MTD received both cycles. Cycle 2 was omitted when patients refused it or had disease progression or toxicities, primarily prolonged thrombocytopenia. Complete response rates in stage IV breast cancer patients increased from 28% pre-HDCT to 55% after cycle 2. At a median follow-up of 4.6 years (range, 1.5-8.1 years), 11 of 29 patients with stage IV breast carcinoma were alive with 5-year projected progression-free and overall survival rates of 19% (95% confidence interval [CI], 7%-41%) and 39% (95% CI, 20%-62%), respectively. Five-year projected progression-free and overall survival rates for patients with stage IV breast cancer in complete response following HDCT versus all others were 35% (95% CI, 15%-70%) versus 0% (P = .01) and 61% (95% CI, 35%-91%) versus 10% (95% CI, 2%-60%) (P = .003; log-rank test), respectively. Estrogen-receptor positivity was predictive of reduced risk of progression (relative risk [RR], 0.25; 95% CI, 0.10-0.65; P = .003) and death (RR, 0.27; 95% CI, 0.10-0.72; P = .009) after adjusting for response status. Five-year projected relapse-free and overall survival rates were 71% (95% CI, 43%-96%) and 82% (95% CI, 56%-100%), respectively, for the 17 patients with high-risk primary breast cancer. Tandem-cycle high-dose melphalan and cisplatin with PBPCs is feasible. Preliminary data suggest significant activity in selected patients with stage IV responding breast carcinoma.

Adult↗
PubMed2001

Clinical trials in a rural population: professional education aspects.

BACKGROUND: While the majority of cancer patients in rural New Hampshire and Vermont are treated in community hospitals, few have entered clinical trials. This report describes a rural hospital consortium as a single Cancer and Leukemia Group B (CALGB) affiliate that used local cancer teams and itinerant oncologists to develop a clinical trials program. METHOD: Grafted onto an existing oncology outreach program, educational programs were developed to help identify patients and recruit them to cooperative group clinical trials. Outcomes included the number of patients accrued to clinical trials, and a comparison of the quality of audited research records with those of affiliated institutions of the CALGB. The consequences of the program were to measure changes in patterns of care of breast, prostate, colorectal, and lung cancers during the study period. These included diagnostic, staging, and treatment changes that occurred over time. RESULTS: 3.3% of incident cases were accrued to clinical trials during the study period, more often for breast and colorectal than for lung and prostate cancers. Reasons that were identified for low accrual were lack of clinical trials for the majority of cases, including the elderly. More than 65% of the patients in the outreach population were older than 65, compared with 50% at the cancer center. Patterns of care did change for breast and prostate cancers, but were similar to national trends.

Adult↗
PubMed2001

Pharmacokinetics of nelfinavir in human immunodeficiency virus-infected infants.

BACKGROUND: Nelfinavir dosed at approximately 20 to 30 mg/kg three times a day (TID) in older children provides exposure similar to 750 mg TID in adults. However, the pharmacokinetics (PK) of nelfinavir in infants who are < 2 years of age is not well-described. The objective of this study was to determine the pharmacokinetics of nelfinavir in infants < 2 years of age. METHODS: Nelfinavir concentrations were evaluated in 22 HIV-infected infants between 15 days and 2 years of age receiving nelfinavir as part of Pediatric ACTG Study 356. Nelfinavir therapy was initiated at approximately 25 mg/kg TID (n = 18) or approximately 55 mg/kg twice a day (n = 4) and given in combination with nevirapine, stavudine and lamivudine. PK samples were obtained predose and 1.5 and 4 h postdose at approximately 6-month intervals. Eight infants (all < or = 3 months of age) also had intensive PK samples collected at Week 1. RESULTS: The median apparent clearance in the infants with intensive pharmacokinetic sampling was 2.7 liters/h/kg (range, 1.8 to > or = 10) and was similar between twice a day and TID dosing cohorts. Overall nelfinavir concentrations at all collection times were lower in these infants than previously reported in older pediatric patients. CONCLUSIONS: Nelfinavir concentrations in infants are highly variable and lower than those seen in adult or older pediatric populations receiving labeled dosing. Therefore it is necessary to further evaluate nelfinavir safety, effectiveness and pharmacokinetics at higher doses than used among other pediatric populations.

Anti-HIV Agents↗
PubMed2001

Estimates of the health risk reductions associated with attainment of alternative particulate matter standards in two U.S. cities.

As part of its periodic re-evaluation of particulate matter (PM) standards, the U.S. Environmental Protection Agency estimated the health risk reductions associated with attainment of alternative PM standards in two locations in the United States with relatively complete air quality data: Philadelphia and Los Angeles. PM standards at the time of the analysis were defined for particles of aerodynamic diameter less than or equal to 10 microm, denoted as PM-10. The risk analyses estimated the risk reductions that would be associated with changing from attainment of the PM-10 standards then in place to attainment of alternative standards using an indicator measuring fine particles, defined as those particles of aerodynamic diameter less than or equal to 2.5 microm and denoted as PM-2.5. Annual average PM-2.5 standards of 12.5, 15, and 20 microg/m3 were considered in various combinations with daily PM-2.5 standards of 50 and 65 microg/m3. Attainment of a standard or set of standards was simulated by a proportional rollback of "as is" daily PM concentrations to daily PM concentrations that would just meet the standard(s). The predicted reductions in the incidence of health effects varied from zero, for those alternative standards already being met, to substantial reductions of over 88% of all PM-associated incidence (e.g., in mortality associated with long-term exposures in Los Angeles, under attainment of an annual standard of 12.5 microg/m3). Sensitivity analyses and integrated uncertainty analyses assessed the multiple-source uncertainty surrounding estimates of risk reduction.

Air Pollutants↗
PubMed2001

Placebo-controlled study of divalproex sodium for agitation in dementia.

The authors assessed the efficacy, tolerability, and safety of divalproex sodium for the treatment of agitation associated with dementia in a 6-week, randomized study of 56 nursing home patients with agitation and dementia treated with either placebo or individualized doses of divalproex sodium. Participants were blinded to treatment except for a physician-monitor and a pharmacist. When several covariates were taken into account, the drug/placebo difference in Brief Psychiatric Rating Scale Agitation scores became statistically significant (P=0.05). Sixty-eight percent of patients on divalproex were rated as showing reduced agitation on the Clinical Global Impression scale, vs. 52% on placebo (P=0.06 in the adjusted analysis). Side effects occurred in 68% of the divalproex group vs. 33% of the placebo group (P=0.03) and were generally rated as mild. This placebo-controlled study, despite some limitations, suggests possible short-term efficacy, tolerability, and safety of divalproex for agitation in dementia and supports further placebo-controlled studies.

Aged↗
PubMed2001

Hydrocarbon humps in the marine environment: synthesis, toxicity, and aqueous solubility of monoaromatic compounds.

A recent study has shown that some monoaromatic hydrocarbon constituents of the so-called unresolved complex mixtures (UCMs) or gas chromatographic humps, which are widespread in the marine environment, are toxic to the mussel Mytilus edulis. Here we describe the synthesis and toxicological assessment of 6-cyclohexyltetralin, 7-cyclohexyl-1-methyltetralin, and 7-cyclohexyl-1-n-propyltetralin, which contain structural features consistent with some monoaromatic UCM hydrocarbons. The compounds were all toxic to M. edulis when measured in the assay used previously to determine the toxicity of a monoaromatic UCM. The aqueous solubilities of the hydrocarbons in fresh and seawater at different temperatures were determined and found to range from about 10 to 110 microg/L (10-60 microg/L in seawater at 15 degrees C). Further studies of the aromatic UCM composition of a wide range of oils and oil residues are required to determine whether such alkylated compounds as 7-cyclohexyl-1-methyltetralin and 7-cyclohexyl-1-n-propyltetralin or their analogues are widespread in oils. If these aromatic compounds prove to be important in UCMs, toxicity experiments should be conducted with other biological end points and monitoring studies of pollutant hydrocarbons should probably include measurement of aromatic UCM hydrocarbons.

Animals↗
PubMed2001

Child maltreatment and the early onset of problem behaviors: can a program of nurse home visitation break the link?

This study investigated the relationship between child maltreatment and the early onset of problem behaviors in the Elmira Nurse Home Visitation Program. Participants were predominantly low-income and unmarried mothers and their first-born children who were randomized either to receive over 2 years of home-visitation services by nurses or to be placed in a comparison group. Data were drawn from a follow-up study that took place when the children were 15 years of age. Results demonstrated that, in the comparison group. child maltreatment was associated with significant increases in the number of early onset problem behaviors reported by the youth. For the youth in the nurse-visited group there was no relationship between maltreatment and early onset problem behaviors. We suggest that this finding was due to the effects of the intervention in reducing the number as well as the developmental timing of the maltreatment incidents. Results suggest that prenatal and infancy home visiting by nurses can moderate the risk of child maltreatment as a predictor of conduct problems and antisocial behavior among children and youth born into at-risk families.

Adolescent↗
PubMed2000

Cross section for b-Jet production in &pmacr;p collisions at radicals = 1.8 TeV

Bottom-quark production in &pmacr;p collisions at sqrt[s] = 1.8 TeV is studied with 5 pb(-1) of data collected in 1995 by the D0 detector at the Fermilab Tevatron Collider. The differential production cross section for b jets in the central rapidity region ( | y(b)|<1) as a function of jet transverse energy is extracted from a muon-tagged jet sample. Within experimental and theoretical uncertainties, D0 results are found to be higher than, but compatible with, next-to-leading-order QCD predictions.

Journal Article↗
PubMed2000

[Sexually transmitted infections among immigrants in Denmark. Is it a problem?].

INTRODUCTION: The aim of the study was to assess the incidence of sexually transmitted infections (STIs) in immigrants in Denmark. MATERIAL AND METHODS: Analysis of surveillance data from 1.8.1990-31.5.2000 for HIV infection and from 1.1.1994-31.5.2000 for gonorrhoea and syphilis. National data on the population mainly per 1.1.1998 were used. RESULTS: Overall, 28% of the notified, newly diagnosed HIV-infected persons were foreigners, a proportion which was 18% for both cases with gonorrhoea and syphilis; 488 (64%) were from Africa, whereas 110 (14%) were from Europe. The estimated annual incidence of first-time diagnosed HIV infection was five times higher in immigrants than in native Danes (22.3 vs 4.1 per 10(5)), namely 161.8 per 10(5) in Africans and 5.6 per 10(5) in Europeans. Similar differences were found for gonorrhoea (6.87 vs 2.14 per 10(5)) and syphilis (1.66 vs 0.16 per 10(5)). In addition, the annual incidence of newly diagnosed HIV was three times higher in male and 16 times higher in female immigrants than in Danes. The incidence of both gonorrhoea and syphilis in Danes was five times higher in men than in women, which was also found for gonorrhoea in immigrants. In immigrants, no real difference in the incidence of HIV and syphilis was found between the two genders. CONCLUSION: The incidence of diagnosed HIV infection, gonorrhoea, and syphilis in Denmark is generally low, but fairly high in certain groups of immigrants. Information, early diagnosis and treatment are central elements in the prevention of STIs and should be adapted for new sub-populations.

Denmark↗
PubMed2000

Restoration of positioning control following Disabled-2 expression in ovarian and breast tumor cells.

The physical interaction of epithelial cells with the basement membrane ensures correct positioning and acts as a survival factor for epithelial cells. Cells that detach from the basement membrane often undergo apoptosis; however, in carcinomas, this positional control is absent, permitting disorganized cell proliferation. In the majority of breast and ovarian carcinomas (85-90%), the expression of a candidate tumor suppressor, Disabled-2 (Dab2), is frequently lost. The Dab2-negative tumor cells are no longer in contact with an intact basement membrane, as indicated by the absence of collagen IV (in about 90% of cases). However, in the subset (10-15%) of ovarian tumors in which Dab2 expression is positive, the presence of a basement membrane-like structure around tumor cells was observed. Recombinant adenovirus-mediated expression of Dab2 was used in Dab2-negative ovarian and breast cancer cells, and re-expression of Dab2 was found to lead to cell death or growth arrest. Dab2 expression suppressed MAPK activation and c-fos expression. Plating the infected cells on a basement membrane matrigel rescued the cells from death and growth arrest. Thus, Dab2 exhibits a negative activity for cell growth and survival, which can be countered by attachment of the cells to basement membrane matrix. We conclude that Dab2 functions in cell positioning control and mediates the exigency for basement membrane attachment of epithelial cells. Loss of Dab2 may contribute to the basement membrane-independent, disorganized proliferation of tumor cells in ovarian and breast carcinomas.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Use of hormone replacement therapy (Hrt) And detection of human papillomavirus (Hpv) Dna in postmenopausal women.

PURPOSE: This study investigated the association between detection of HPV DNA among current and past HRT users compared to never HRT users, duration of HRT use, and type of HRT (estrogen, estrogen/progestin).METHODS: Postmenopausal women (n = 390) were recruited from a university hospital and completed a questionnaire regarding 1) HRT use, duration, and type, 2) reproductive and sexual history, 3) smoking and alcohol use, and 4) HPV-related diseases. Cervical specimens were obtained for Pap smears, and for the presence of HPV using PCR/dot blot and DNA sequencing, and Southern blot or SSCP. Age-adjusted odds ratios (OR), 95% confidence intervals (CI), and logistic regression examined the association between HRT use and risk of HPV detection.RESULTS: The frequency of HPV was 10%, with 2.8% oncogenic types. Compared to Never Users, Current (adj. OR = 1.50, 95% CI = 0.55, 4.07) and Past (OR = 1.96, CI = 0.56, 6.86) HRT users had an elevated risk of HPV detection. Although HRT duration among Current Users was not statistically significant (OR = 1.01, 95% CI = 0.95, 1.07), duration among Past Users was significantly associated with an increased risk of HPV detection (OR = 1.30, CI = 1.06, 1.61). In addition, Past Users of estrogen/cyclic progestin HRT regimens were significantly more likely to be detected with HPV (OR = 1.82, CI = 1.11, 2.97) compared to Never Users.CONCLUSIONS: These findings indicate that risk of HPV detection is increased among users of HRTs, particularly among Past Users associated with longer duration and among those taking HRT regimens that included a progestin. Results suggest a latency or duration effect may be important in elevating the risk. They also support previous in vitro studies of progestin effects on HPV gene regulation.

Journal Article↗
PubMed2000

Preventing child abuse and neglect with a program of nurse home visitation: the limiting effects of domestic violence.

CONTEXT: Home visitation to families with young children has been promoted as an effective way to prevent child maltreatment, but few studies have examined the conditions under which such programs meet this goal. OBJECTIVE: To investigate whether the presence of domestic violence limits the effects of nurse home visitation interventions in reducing substantiated reports of child abuse and neglect. DESIGN: Fifteen-year follow-up study of a randomized trial. SETTING: Semirural community in upstate New York. PARTICIPANTS: Of 400 socially disadvantaged pregnant women with no previous live births enrolled consecutively between April 1978 and September 1980, 324 mothers and their children participated in the follow-up study. INTERVENTIONS: Families were randomly assigned to receive routine perinatal care (control group; n = 184 participated in follow-up), routine care plus nurse home visits during pregnancy only (n = 100), or routine care plus nurse home visits during pregnancy and through the child's second birthday (n = 116). MAIN OUTCOME MEASURES: Number of substantiated reports over the entire 15-year period involving the study child as subject regardless of the identity of the perpetrator or involving the mother as perpetrator regardless of the identity of the child abstracted from state records and analyzed by treatment group and level of domestic violence in the home as measured by the Conflict Tactics Scale. RESULTS: Families receiving home visitation during pregnancy and infancy had significantly fewer child maltreatment reports involving the mother as perpetrator (P =. 01) or the study child as subject (P =.04) than families not receiving home visitation. The number of maltreatment reports for mothers who received home visitation during pregnancy only was not different from the control group. For mothers who received visits through the child's second birthday, the treatment effect decreased as the level of domestic violence increased. Of women who reported 28 or fewer incidents of domestic violence (79% of sample), home-visited mothers had significantly fewer child maltreatment reports during the 15-year period than mothers not receiving the longer-term intervention (P =.01). However, this intervention did not significantly reduce child maltreatment among mothers reporting more than 28 incidents of domestic violence (21% of sample). CONCLUSIONS: The presence of domestic violence may limit the effectiveness of interventions to reduce incidence of child abuse and neglect. JAMA. 2000;284:1385-1391.

Child Abuse↗
PubMed2000

The right person? the right place? the right time? a pilot study of the appropriateness of nursing home placements.

The appropriate use of health services is a key challenge for the NHS. Older people have been consistently identified as being disproportionately represented amongst those defined as 'inappropriately' located within the acute health sector. Prior to the introduction of community care it was hypothesised that older people were entering nursing home care inappropriately. With the requirement for assessment prior to entry into nursing homes now a feature of the system such 'inappropriate' admissions should not occur. This pilot study investigates the feasibility of determining inappropriate admissions and the extent of this phenomenon in nursing homes used by three inner London Boroughs. To determine the number of 'inappropriate' placements in nursing homes in three London Boroughs (Lambeth, Southwark & Lewisham). Retrospective audit of nursing home case notes using standardised data collection method. New local authority funded admissions to nursing homes from LSL during the period 1 April 1993-31 March 1995. One hundred and fifty seven people entered the 25 nursing homes identified. For 65% nursing home placement was appropriate, 14% were apparently more suited to residential care and 17% for community care. Documentation concerning clients held by the nursing homes was generally poor. Despite the introduction of the Community Care Act and the clear requirement for assessment before entry into nursing home care, approximately one-third of the placements reviewed were inappropriate and did not meet the individual's care needs. Further research is underway to determine if these findings apply nationally.

Journal Article↗
PubMed2000

Universal slow dynamics in granular solids

Experimental properties of a new form of creep dynamics are reported, as manifest in a variety of sandstones, limestone, and concrete. The creep is a recovery behavior, following the sharp drop in elastic modulus induced either by nonlinear acoustic straining or rapid temperature change. The extent of modulus recovery is universally proportional to the logarithm of the time after source discontinuation in all samples studied, over a scaling regime covering at least 10(3) s. Comparison of acoustically and thermally induced creep suggests a single origin based on internal strain, which breaks the symmetry of the inducing source.

Journal Article↗
PubMed2000

Neuroserpin reduces cerebral infarct volume and protects neurons from ischemia-induced apoptosis.

Neuroserpin, a recently identified inhibitor of tissue-type plasminogen activator (tPA), is primarily localized to neurons within the central nervous system, where it is thought to regulate tPA activity. In the present study neuroserpin expression and its potential therapeutic benefits were examined in a rat model of stroke. Neuroserpin expression increased in neurons surrounding the ischemic core (ischemic penumbra) within 6 hours of occlusion of the middle cerebral artery and remained elevated during the first week after the ischemic insult. Injection of neuroserpin directly into the brain immediately after infarct reduced stroke volume by 64% at 72 hours compared with control animals. In untreated animals both tPA and urokinase-type plasminogen activator (uPA) activity was significantly increased within the region of infarct by 6 hours after reperfusion. Activity of tPA then decreased to control levels by 72 hours, whereas uPA activity continued to rise and was dramatically increased by 72 hours. Both tPA and uPA activity were significantly reduced in neuroserpin-treated animals. Immunohistochemical staining of basement membrane laminin with a monoclonal antibody directed toward a cryptic epitope suggested that proteolysis of the basement membrane occurred as early as 10 minutes after reperfusion and that intracerebral administration of neuroserpin significantly reduced this proteolysis. Neuroserpin also decreased apoptotic cell counts in the ischemic penumbra by more than 50%. Thus, neuroserpin may be a naturally occurring neuroprotective proteinase inhibitor, whose therapeutic administration decreases stroke volume most likely by inhibiting proteinase activity and subsequent apoptosis associated with focal cerebral ischemia/reperfusion. (Blood. 2000;96:569-576)

Animals↗
PubMed2000

Glucocorticoids inhibit developmental stage-specific osteoblast cell cycle. Dissociation of cyclin A-cyclin-dependent kinase 2 from E2F4-p130 complexes.

Unique cell cycle control is instituted in confluent osteoblast cultures, driving growth to high density. The postconfluent dividing cells share features with cells that normally exit the cell cycle; p27(kip1) is increased, p21(waf1/cip1) is decreased, free E2F DNA binding activity is reduced, and E2F4 is primarily nuclear. E2F4-p130 becomes the predominant E2F-pocket complex formed on E2F sites, but, unlike the complex that typifies resting cells, cyclin A and CDK2 are also present. Administration of dexamethasone at this, but not earlier stages, results in reduction of cyclin A and CDK2 levels with a parallel decrease in the associated kinase activity, dissociation of cyclin A-CDK2 from the E2F4-p130 complexes, and inhibition of G(1)/S transition. The glucocorticoid-mediated cell cycle attenuation is also accompanied by, but not attributable to, increased p27(kip1) and decreased p21(waf1/cip1) levels. The attenuation of osteoblast growth to high density by dexamethasone is associated with severe impairment of mineralized extracellular matrix formation, unless treatment commences in cultures that have already grown to high density. Both the antimitotic and the antiphenotypic effects are reversible, and both are antagonized by RU486. Thus, glucocorticoids induce premature attenuation of the osteoblast cell cycle, possibly contributing to the osteoporosis induced by these drugs in vivo.

3T3 Cells↗