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At least 721 records · Page 40Linked to original sources
PubMed2004

Chromatin assembly factor-1, a marker of clinical value to distinguish quiescent from proliferating cells.

Histone synthesis and chromatin assembly are mainly associated with DNA replication and are thus intimately involved in cell cycle regulation. The expression of key components involved in these events in human cells was studied in relation to cell-proliferative status. Among several chromatin assembly factors, chromatin assembly factor (CAF)-1 stood out as the most discriminating marker of the proliferative state. We show, using both immunofluorescence and Western blot analysis, that the expression of both CAF-1 large subunits, p150 and p60, is massively down-regulated during quiescence in several cell lines. Upon exit from the quiescent state, the CAF-1 subunits are re-expressed early, before DNA replication. The amounts of either total or chromatin-associated pools of CAF-1 proteins correlate directly with cell proliferation. Regulation of CAF-1 expression is partly controlled at the RNA level, as shown by quantitative reverse transcription-PCR and Northern blot experiments. Biological material from benign and malignant human breast tumors analyzed by immunocytochemistry and immunohistochemistry exhibits a strong positive correlation between CAF-1 p60 expression and the following proliferation markers: S-phase fraction (r = 0.84, P < 0.0001); Ki-67 (r = 0.94, P < 0.0001); and proliferating cell nuclear antigen (r = 0.95, P = 0.0001). We discuss the advantages of using CAF-1 to assess cell proliferation. High CAF-1 p60 levels are also shown to be associated with various prognostic factors. Our data highlight the precise association of CAF-1 expression with the proliferative state and validate the use of this factor as a useful proliferation marker and prognostic indicator in malignant and benign breast lesions.

Biomarkers, Tumor↗
PubMed2006

Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer.

PURPOSE: This open-label study assessed the safety and immunogenicity of two doses and two routes of the anti-idiotypic monoclonal antibody abagovomab (formerly ACA125) in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. EXPERIMENTAL DESIGN: Eligible patients from the three participating institutions were any stage at diagnosis, had relapsed, and had complete or partial response to additional chemotherapy. Patients were randomized to receive abagovomab at 2.0 versus 0.2 mg and i.m. versus s.c. for four immunizations every 2 weeks and then monthly for two additional immunizations. Planned evaluation included interval physical examinations and laboratory assessments with immune assessment, including HLA typing, human anti-mouse antibody, ELISA, and enzyme-linked immunospot. Patients were required to remain on study until week 10 (the first post-baseline Ab3 determination) to be considered for immunologic assessment. The primary end points were safety and immunogenicity primarily determined by Ab3 response. RESULTS: Forty-two patients received at least one vaccination and were eligible for safety analysis. Thirty-three patients were available for Ab3 analysis (removed for progression of disease, 6; withdrawal of consent, 2; unrelated adverse event, 1). The most common adverse events were self-limited pain at injection site, myalgia, and fever. No hematologic or nonhematologic toxicity grade>2 related to immunization was seen. Ab3 was detectable in all patients (median, 236,794 ng/mL); none of route of administration (P=0.6268), dose (P=0.4602), or cohort (P=0.4944) was statistically significant in terms of effect on maximum post-baseline Ab3 titer. Human anti-mouse antibody was not detectable at baseline but was present in all patients at week 16 (range, 488-45,000 ng/mL). CONCLUSIONS: Immunization with abagovomab is well tolerated and induced robust Ab3 responses at the two doses and routes tested. A phase III randomized study with abagovomab (2.0 mg s.c.) is warranted.

Adult↗
PubMed2005

Colonic rupture in a patient on combination chemotherapy for metastasized carcinoma of the esophagogastric junction. Case report and review of the literature.

BACKGROUND: Cecal perforation due to neutropenic colitis is a known and described side effect of many chemotherapy regimens. We present a case of a patient with gastric adenocarcinoma who developed spontaneous cecal perforation during chemotherapy without the classic pattern of typhlitis. CASE REPORT: A 58-year-old woman was on chemotherapy for an adenocarcinoma of the gastric junction, when she developed a cecal perforation. There was neither evidence for leucopenia nor for typhlitis. Laparotomy was performed and cecostomy was established using the perforated bowel. Postoperative course was uneventful. The patient died from tumor progression 8 months after the diagnosis was made. CONCLUSION: There is no evidence for a connection between this event and chemotherapy treatment but neither can it be excluded. Even if unusual, colon toxicity could be a potential life-threatening complication associated with more drugs than usually thought.

Adenocarcinoma↗
PubMed2006

Congenital prothrombotic disorders in children with peripheral venous and arterial thromboses.

AIMS: To evaluate the prevalence of congenital prothrombotic disorders in children with peripheral venous and arterial thromboses. METHODS: Deficiencies in antithrombin (AT), proteins C (PC) and S (PS), and increased lipoprotein (a), and the presence of factor V (FV) G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) mutations were investigated. RESULTS: Forty-eight patients (mean age, 3.4 years) were investigated. Of these patients, 23 had venous thrombosis, 22 had arterial thrombosis, and 3 had both. No patients had AT, PC or PS deficiency. FV G1691A mutation was present in 2 (7.6%) and 3 (12%) patients with venous and arterial thromboses, respectively. The prothrombin G20210A mutation was present in 1 (4%) patient with arterial thrombosis. Homozygous MTHFR C677T mutation was detected in 4 (18%) and 2 (9%) patients with venous and arterial thromboses, respectively. Increased lipoprotein (a) was present in 2 (10%) and 1 (4.5%) patients with venous and arterial thromboses, respectively. Regarding acquired risk factors, 79% of all thrombotic events were related to catheter usage. An underlying disease was present in 96% of the patients. CONCLUSIONS: Compared to acquired risk factors, congenital prothrombotic disorders are rarely present in children with peripheral venous and arterial thromboses. These results do not support general screening of children with venous and arterial thromboses for congenital prothrombotic disorders.

Adolescent↗
PubMed2005

Young women as smokers and nonsmokers: a qualitative social identity approach.

The authors used a social identity perspective to explore young women's perceptions of smoking. They carried out 13 focus groups and 6 intercept interviews with women aged 16 to 28 years in regards to the social identities that might influence young women's smoking behavior. Three identities emerged: the cool smoker applied to the initiation of smoking; considerate smokers, who were older addicted smokers; and the actual and anticipated good mother identity, which applied to young women who quit smoking during pregnancy. These identities add to our understanding of the meaning of smoking within the lives of young women and might allow more focused initiatives with this group to prevent the progression to regular addicted smoking.

Adolescent↗
PubMed2005

Effect of donor selection on the early outcome of heart transplant recipients.

Recipients receiving heart transplants from 83 donors from 1995 to 2002 were analyzed to evaluate the effect of various donor factors on recipient outcomes. The 83 donors (13 women and 70 men; 2-51 years old) had cold ischemic times ranging between 55 and 287 minutes. Donor age, cause of death, inotropic support, and cold ischemic times of the hearts were compared to 1-year left ventricular ejection fraction, permanent pacemaker dependency, 30-day mortality, and 1-year survival in the recipients. Donors receiving low-dose inotropic support resulted in recipients with permanent pacemaker dependency in 14.8%, and 30-day mortality and 1-year survival rates of 7.4% and 70.3%, respectively. Donors not receiving inotropic support resulted in recipients with permanent pacemaker dependency in 3.5%, and 30-day mortality and 1-year survival of 3.5% and 83.9%, respectively. Cold ischemic times less than or equal to 120 minutes showed 30-day mortality and 1-year survival rates of 0% and 90.9%, respectively. Cold ischemic times equal to or more than 121 minutes showed 30-day mortality and 1-year survival rates of 8% and 76%, respectively. Increased donor age (P=.22) and cold ischemic time showed an increase in mortality without affecting mean ejection fraction in survivors. Use of inotropic support in donors (P=.95) showed an increase in mortality without affecting mean ejection fraction in survivors.

Adolescent↗
PubMed2006

Innovation in nursing education: a statewide grant initiative.

Meeting the challenges of the nursing shortage appears to be daunting for schools of nursing across the nation as they struggle to meet educational capacity needs with limited resources. A statewide grant program was developed and implemented through legislative initiatives providing opportunities for schools of nursing to respond to the need for innovation in nursing education. This article shares some of the successes and challenges identified through the process of implementing and evaluating this grant program. Insights into the political and regulatory process are provided as a model for other states to consider. Examples of educational strategies that were successful in improving the recruitment and retention of students and faculty are discussed. Nursing and other health care leaders across the nation should look to policy initiatives such as grant programs to infuse innovation into educational programs and to address educational capacity issues compounding the nursing shortage.

Education, Nursing↗
PubMed2002

The use of CAM by women suffering from nausea and vomiting during pregnancy.

BACKGROUND: Nausea and vomiting during pregnancy (NVP) affects two-thirds of pregnant women to varying degrees and over the years many modalities have been used to try to alleviate this often debilitating condition. There is a paucity of information in the literature about the use or efficacy of complementary and alternative medicine (CAM) for the treatment of this condition that affects so many women. Our primary objective was to examine the prevalence of CAM usage by women suffering from NVP. Our secondary objective was to ascertain if women had any supervision in the use of these treatments. METHODS: Women who called The Motherisk NVP helpline, were asked after the counseling session to complete a questionnaire, which included demographic data as well as information about their CAM use. RESULTS: Seventy women completed the questionnaire. 61% reported using CAM therapies, of which the three most popular were: ginger, vitamin B6 and acupressure. 21% of those who reported using CAM, had consulted CAM practitioners, 8% their physicians or pharmacists and 71% discussed the usage with family, friends and other allied health professionals. Women who did not use CAM stated they would probably use these modalities if there was more information about the safety in pregnancy. CONCLUSION: Pregnant women with NVP are mirroring the trend in the general population of the use of CAM. They are also using CAM therapies with little supervision from practitioners experienced in the use of these modalities.

Adult↗
PubMed2002

Advance directives for patients compulsorily admitted to hospital with serious mental illness. Randomised controlled trial.

BACKGROUND: An advance directive is a statement of a person's preferences for treatment, should he or she lose capacity to make treatment decisions in the future. AIMS: To evaluate whether use of advance directives by patients with mental illness leads to lower rates of compulsory readmission to hospital. METHOD: In a randomised controlled trial in two psychiatric services in inner London, 156 in-patients about to be discharged from compulsory treatment under the Mental Health Act were recruited. The trial compared usual psychiatric care with usual care plus the completion of an advance directive. The primary outcome was the rate of compulsory readmission. RESULTS: Fifteen patients (19%) in the intervention group and 16 (21%) in the control group were readmitted compulsorily within 1 year of discharge. There was no difference in the numbers of compulsory readmissions, numbers of patients readmitted voluntarily, days spent in hospital or satisfaction with psychiatric services. CONCLUSIONS: Users' advance instruction directives had little observable impact on the outcome of care at 12 months.

Adult↗
PubMed2004

Role of constitutively activated and insulin-like growth factor-stimulated ERK1/2 signaling in human hepatoma cell proliferation and apoptosis: evidence for heterogeneity of tumor cell lines.

Enhanced insulin-like growth factor II (IGF-II) and type I IGF receptor (IGF-IR) gene expression in liver tumors and the development of liver tumors in transgenic mice overexpressing IGF-II in the liver suggest that the IGFs and underlying signaling cascades may play auto/paracrine roles in the control of hepatocarcinoma (HCC) cell proliferation and in their protection against apoptosis. We have focused on the role of mitogen-activated protein kinase (ERK1/2) signaling on human HepG2 and Huh-7 hepatoma cell proliferation and on the protection of these cells against drug-induced apoptosis. Physiological concentrations of IGF-I stimulated DNA replication in HepG2 cells (1.5-fold) but not in Huh-7 cells, and this effect was abolished by PD98059 (MEK-1 inhibitor). Doxorubicin or cisplatin treatment induced apoptosis (caspase-dependent poly[ADP-ribose]polymerase cleavage) in both cell lines, but dose-dependent reversion of drug-induced apoptosis (57-84%) by IGF-I was only observed in HepG2 cells. The very low level of IGF-IR at the plasma membrane of Huh-7 cells may account for their unresponsiveness to IGF-I. We have shown that drug treatment enhanced (17-fold) or did not modify constitutive ERK1/2 activity in cultured HepG2 or Huh-7 cells, respectively. In both cell lines, inhibition of constitutive and drug-induced ERK1/2 activity by PD98059 yielded a complete inhibition of drug-induced apoptosis. Altogether, our data demonstrate the heterogeneous response of human hepatoma cells to an IGF stimulus and suggest (1) that auto/paracrine effects of IGF-I/-II might contribute to the proliferation of HCC cells and to their protection against apoptosis in vivo and (2) that drug-induced activation of ERK1/2 plays a role in drug-induced apoptosis in human hepatoma cells.

Apoptosis↗
PubMed2002

High-dose chemotherapy in poor-prognosis adult small round-cell tumors: clinical and molecular results from a prospective study.

PURPOSE: The prognosis of metastatic/high-risk localized small round-cell tumors (SRCTs) treated conventionally is dismal. In this phase II study, we explored a high-dose chemotherapy (HD-CT) approach and analyzed the clinical significance of fusion transcripts detection. PATIENTS AND METHODS: From June 1997 to November 1999, 28 SRCT patients (median age, 26 years; 14 peripheral primitive neuroectodermal tumors [pPNETs], seven rhabdomyosarcomas [RMSs], and seven desmoplastic small round-cell tumors [DSRCTs]) received induction chemotherapy with ifosfamide, epirubicin, and vincristine followed by HD-CT. Local treatment (radiotherapy and/or surgery) was performed when possible. Molecular analysis was performed on peripheral-blood and leukapheresis products by reverse-transcriptase polymerase chain reaction. RESULTS: Overall response (OR) was 65% (18 of 28), with 40% complete response and 25% partial response. According to histology, the OR rate was 86% in pPNET and 43% in both RMS DSRCT. With a median follow-up of 35 months, median overall survival was 16 months and median progression-free survival (PFS) was 10 months. PFS was statistically better in pPNET than other histologic types (P =.0045). No correlation was found between the fusion transcript and clinical outcome during follow-up. Furthermore, transcript detection in leukapheretic products was not of prognostic significance. CONCLUSION: Intensive HD-CT seems to enhance the response rate and survival when compared with conventional treatment in poor-prognosis pPNET. The poor results of this treatment in RMS and DSRCT do not support the inclusion of such an approach in these patient subsets. No definitive conclusions can currently be drawn concerning the clinical implications of the detection of fusion transcripts during treatment or follow-up.

Adolescent↗
PubMed2006

Formulas calculating creatinine clearance are inadequate for determining eligibility for Cisplatin-based chemotherapy in bladder cancer.

PURPOSE: Efficacy of formulas calculating creatinine clearance (CrCl) to determine renal function eligibility (CrCl > 60 mL/min) for cisplatin-based chemotherapy has not been examined adequately in the bladder cancer population. We hypothesize these formulas may underestimate measured CrCl, and therefore the eligibility for cisplatin-based chemotherapy. PATIENTS AND METHODS: A database of 208 patients with unresectable or metastatic bladder cancer treated on protocol at Memorial Sloan-Kettering Cancer Center (New York, NY) with cisplatin-based chemotherapy between 1983 and 1994 was examined retrospectively. The association between measured and calculated CrCl and the ability to complete three cycles (minimum therapeutic) of chemotherapy was examined. RESULTS: Baseline measured CrCl was less than 60 mL/min in 16% compared with 12% to 44% using various formulas. Concordance between calculated and measured CrCl less than 60 mL/min was poor (range of kappa, 0.14 to 0.38). In patients older than age 65, 22% had a measured CrCl less than 60 mL/min, compared with 10% to 63% calculated using various formulas. Overall, 80% completed at least three cycles of cisplatin-based chemotherapy. The ability to complete at least three cycles was statistically significantly related with a measured CrCl more than 60 mL/min (P = .02), but not with calculated CrCl more than 60 mL/min. CONCLUSION: Current formulas estimating CrCl tend to underestimate measured CrCl, especially in those older than 65 years. Depending on the formula used, up to 44% who actually received cisplatin-based chemotherapy based on measured CrCl would be deemed ineligible at present, potentially affecting survival outcomes. Methodology for determining CrCl and/or renal eligibility for cisplatin-based chemotherapy in patients with bladder cancer should be re-examined.

Adult↗
PubMed2006

Vascular endothelial and smooth muscle function relates to body mass index and glucose in obese and nonobese children.

CONTEXT: Endothelial and smooth muscle dysfunction are critical precursors of atherosclerosis. These can be detected in children at risk of cardiovascular disease. OBJECTIVE: The objective of this study is to evaluate endothelial and smooth muscle function and their determinants using flow-mediated dilatation (FMD) and glyceryl trinitrate-mediated dilatation (GTN) in obese, nonobese, and type 1 diabetes mellitus (T1DM) children. DESIGN: This is a cross-sectional study. SUBJECTS: The study subjects were 270 children [140 males, mean age 13.7 (2.8) yr] including 58 obese, 53 nonobese, and 159 T1DM children. MEASUREMENTS: Vascular function (FMD and GTN), body mass index (BMI) z-score, blood pressure, glucose, glycosylated hemoglobin, lipids, folate, homocysteine, and high sensitive C-reactive protein were measured. RESULTS: FMD and GTN were significantly lower in obese and T1DM compared with nonobese subjects (P < 0.001, P < 0.001). FMD and GTN were similarly reduced in obese and T1DM subjects (P = 0.22, P = 0.28). In all nondiabetic subjects (n = 111), both FMD and GTN were significantly and independently related to BMI z-score (r = -0.28, P = 0.003, beta = -0.36, P < 0.001) and weight z-score (beta = -0.31, P = 0.002; r = -0.52, P < 0.001). FMD related independently to total cholesterol (beta = -0.22, P = 0.02). GTN related independently to vessel diameter (beta = -0.49, P < 0.001). GTN related to glucose within the normal range (r = -0.34, P = 0.001). CONCLUSIONS: Children with obesity and T1DM have a similar degree of vascular dysfunction. BMI and weight adjusted for age and sex relate to endothelial and smooth muscle function in nonobese and obese children. Glucose relates to smooth muscle function in nonobese nondiabetic children. This suggests a continuum effect of BMI and glucose within the normal range on vascular function in childhood.

Adolescent↗
PubMed2006

The use of intrathecal morphine for postoperative pain relief after liver resection: a comparison with epidural analgesia.

An epidural catheter is used in some institutions for postoperative analgesia after liver surgery. However, anesthesiologists may not feel comfortable leaving a catheter in the epidural space because of concern about coagulation disturbances and possible bleeding complications caused by impaired liver function. In this study, we tested a single-shot intrathecal morphine technique and compared it to a continuous epidural naropine infusion for postoperative analgesia in liver surgery. Fifty patients were randomly assigned to an epidural analgesia group (EP group; n = 25) and an intrathecal analgesia group (IN group; n = 25). The quality of analgesia assessed by a visual analog scale (VAS), the side effects, and the additional IV analgesic requirements were recorded. We did not observe any signs of cord compression. Time to first pain drug requirement was longer in the EP group compared to the IN group (25 +/- 18.5 h versus 12 +/- 10.3 h; P < 0.05). In both groups, the VAS remained less than 30 mm throughout the 48-h follow-up period. Consumption of IV morphine with a patient-controlled analgesia device in the IN group was larger (mostly from 24 to 48 h after surgery) than the EP group (12.0 +/- 5.54 mg versus 3.1 +/- 2.6 mg, respectively; P < 0.01). The incidence of vomiting was 4% in both groups, whereas the incidence of pruritus (16% versus 0%) and nausea (16% versus 4%) was more frequent in the IN group. No postdural puncture headache and no spinal hematoma occurred. After liver resection, a single dose of intrathecal morphine followed by patient-controlled morphine analgesia can provide satisfactory postoperative pain relief. The quality of this treatment, according to the VAS, is not inferior to continuous epidural analgesia up to 48 h after surgery.

Analgesia, Epidural↗
PubMed2005

Cardiorespiratory adjustments of homing pigeons to steady wind tunnel flight.

We made detailed cardiorespiratory measurements from homing pigeons during quiet rest and steady wind tunnel flight. Our pigeons satisfied their 17.4-fold increase in oxygen consumption during flight with a 7.4-fold increase in cardiac output (Q) and a 2.4-fold increase in blood oxygen extraction. Q was increased primarily by increasing heart rate sixfold. Comparisons between our study and those from the only other detailed cardiorespiratory study on flying birds reveal a number of similarities and important differences. Although the avian allometric equations from this earlier study accurately predicted the flight Q of our pigeons, this was primarily due to due to compensating discrepancies in their heart rate and stroke volume predictions. Additionally, the measured heart mass (MH)-specific Q (Q/MH) of our pigeons during wind tunnel flight was about 22% lower than the estimated value. Compared to running mammals in previous studies, the 1.65-fold Q of our pigeons is consistent with their larger heart mass.

Animals↗
PubMedDate not supplied

Simplified therapy with zidovudine, lamivudine, and abacavir for very nonadherent, treatment-failing patients.

OBJECTIVE: To assess the effectiveness of a simplified therapy for very nonadherent patients who had previously failed with HAART. METHOD: We performed a prospective open-label study of antiretroviral-experienced patients. Dosing schedule comprised (co-formulated) zidovudine, lamivudine, and abacavir bid. Eligible patients had to have plasma HIV RNA >5000 copies/mL, previous therapy, and very poor adherence to the medication regimen. RESULTS: Eighty-five patients were included (mean viral load, 4.4 log/mL; mean CD4, 240 cells/mL; IDUs, 78%; methadone maintenance program, 42%; AIDS, 28%). Number of previous therapies: one, 53%; two, 28%; three or more, 19%. In the intent-to-treat analysis at 1 year, 38 patients (44.7%) achieved viral load below 500 copies/mL. Adherence greater than 90% of prescribed drugs was reported in 49% of patients, adverse events were reported in 17.6%, mortality in 6%, and lost to follow-up in 26%. The factors associated with virologic failure were nonadherence (odds ratio [OR], 4.4; 95% CI 1.5-12.3), baseline CD4 cell count <200 cells/mL (OR, 3.4; 95% CI 1.3-8.9; p =.01), and more than one previous treatment (OR, 2.7; 95% CI 1.1-6.9). CONCLUSION: Regarding previously very nonadherent patients, this simplified combination therapy containing three NRTIs obtained satisfactory results in ART-experienced patients. However, more aggressive interventions to enhance adherence are needed to improve results.

Adult↗