From child to adult: an exploration of shifting family roles and responsibilities in managing physiotherapy for cystic fibrosis.

Although chest physiotherapy is central to the management of cystic fibrosis many report problems with adherence. Research in other long-term conditions suggests that non-adherence may be exacerbated as the child grows older and self-care responsibilities are transferred to the young person. We explored the nature and variation in roles of family members, how responsibility was transferred from the parent/family to the child, and what factors aided or hindered this process.

Pharmacokinetics of dalbavancin in plasma and skin blister fluid.

Objectives: Dalbavancin is a novel lipoglycopeptide antibiotic in development for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria. The aim of the present study was to assess the penetration of dalbavancin into skin blister fluid.

Methods: Nine healthy subjects (five males; ranging in age from 26 to 57 years) were administered a single 30 min intravenous infusion of dalbavancin at a dose of 1000 mg.

Problems and solutions: accounts by parents and children of adhering to chest physiotherapy for cystic fibrosis.

Purpose: Although chest physiotherapy is central to the management of cystic fibrosis (CF), adherence among children is problematic. This study explores accounts by parents and children of the difficulties of adhering to chest physiotherapy for cystic fibrosis, and identifies strategies used by families to overcome these.

Methods: A qualitative study based on in-depth interviews with 32 children with a diagnosis of cystic fibrosis aged 7 - 17 years, and with 31 parents.

Distribution of radioactivity in bone and related structures following administration of [14C]dalbavancin to New Zealand white rabbits.

Penetration of dalbavancin into noninfected bone and joint tissues was assessed after an intravenous dose of 20 mg/kg (of body weight) [(14)C]dalbavancin given to rabbits. Drug-derived radioactivity, determined over 14 days by either liquid scintillation counting or autoradiography, remained above the MIC for common gram-positive pathogens that cause bone and joint infections.

A comparison of the pharmacokinetics and pharmacodynamics of docetaxel between African-American and Caucasian cancer patients: CALGB 9871.

Purpose: Increased clearance of drugs, such as oral cyclosporine, that are CYP3A and/or ABCB1 (P-gp/MDR1) substrates was reported in African-American compared with Caucasian patients. We hypothesized that the pharmacokinetics and pharmacodynamics of docetaxel, an i.v.

General practitioners' reasons for the failure of a randomized controlled trial (The TIGER Trial) to implement epilepsy guidelines in primary care.

Purpose: To explore reasons for the failure of a randomized controlled trial to influence implementation of epilepsy guidelines in primary care, and to generate theory about likely contexts in which guidelines would lead to changes in clinician behavior.

Methods: Qualitative study based on focus groups and a single in-depth interview. Participants included 47 primary health care staff selected from a purposive sample of 13 urban and rural general practices.

Anidulafungin does not require dosage adjustment in subjects with varying degrees of hepatic or renal impairment.

Two open-label studies assessed the effects of hepatic and renal impairment on anidulafungin pharmacokinetics. A single 50-mg dose was administered intravenously to subjects with varying degrees of hepatic or renal insufficiency or with end-stage renal disease; all were matched to normal healthy controls. Anidulafungin was well tolerated.

Lack of pharmacokinetic interaction between anidulafungin and tacrolimus.

The safety and pharmacokinetics of anidulafungin coadministered with tacrolimus were investigated using a single-sequence, open-label design. Healthy volunteers received 5 mg tacrolimus orally on days 1 and 13 of the study. Anidulafungin (200 mg) was administered intravenously on day 4, followed by 100-mg doses on days 5 through 13.

Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma.

Purpose: Recurrent grade III-IV gliomas have a dismal prognosis with minimal improvements in survival seen following currently available salvage therapy. This study was conducted to determine if the combination of a novel antiangiogenic therapy, bevacizumab, and a cytotoxic agent, irinotecan, is safe and effective for patients with recurrent grade III-IV glioma.

Experimental Design: We conducted a phase II trial of bevacizumab and irinotecan in adults with recurrent grade III-IV glioma.

Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas.

Purpose: Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG).

Patients And Method: Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule.

Expression of a mutant p193/CUL7 molecule confers resistance to MG132- and etoposide-induced apoptosis independent of p53 or Parc binding.

p193/CUL7 is an E3 ubiquitin ligase initially identified as an SV40 Large T Antigen binding protein. Expression of a dominant interfering variant of mouse p193/CUL7 (designated 1152stop) conferred resistance to MG132- and etoposide-induced apoptosis in U2OS cells. Immune precipitation/Western analyses revealed that endogenous p193/CUL7 formed a complex with Parc (a recently identified parkin-like ubiquitin ligase) and p53.

Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution.

Purpose: Allogeneic transplantation is typically limited to younger patients having a matched donor. To allow a donor to be found for nearly all patients, we have used a nonmyeloablative conditioning regimen in conjunction with stem cells from a related donor with one fully mismatched HLA haplotype.

Patients And Methods: Fludarabine, cyclophosphamide, and alemtuzumab were used as the preparatory regimen.

Rat neuropeptidomics by LC-MS/MS and MALDI-FTMS: Enhanced dissection and extraction techniques coupled with 2D RP-RP HPLC.

Recently developed sample preparation techniques employing microwave irradiation have enabled the comprehensive study of endogenous mammalian neuropeptides. These methods reduce interference from post-mortem protein degradation by deactivating proteases via heat denaturation. Alternatively, we have developed a protocol using cryostat dissection and a boiling extraction buffer to achieve a similar effect.

Telephone monitoring of distress in patients aged 65 years or older with advanced stage cancer: a cancer and leukemia group B study.

Background: Significant barriers to cancer patients receiving mental health treatment for distress have been reported in the literature. The objective of the current study was to determine whether distress in older patients (aged 65 years and older) would be reduced with educational materials (EM) supplemented by monthly telephone monitoring (TM) (TM + EM) compared with the use of EM alone because of more timely referrals to appropriate health professionals.

Methods: One hundred ninety-two older patients with breast, prostate, and colorectal cancers who had advanced disease and currently were receiving treatment were randomized to receive either TM + EM or EM alone.

What to do about medical students with unsatisfactory consultation skills?

If it is accepted that new doctors must be 'Fit to Practice' in a standard clinical house job, they should be competent in basic communication skills. Although these skills may be assessed as part of a routine OSCE-style exam in the course of the curriculum, the question is raised whether students who fail to demonstrate a minimal level of competence in this area should to be allowed to progress to the next stage of the course and eventually graduate. This paper describes our experiences with introducing 'barrier' stations in communication skills into the OSCE.

Evaluation of clinical pharmacy services in a hematology/oncology outpatient setting.

Background: The Veterans Affairs North Texas Health Care System in Dallas, TX, provides a unique opportunity for clinical pharmacists to work as providers. Even though clinical pharmacists are actively involved in patient care, many of their efforts remain undocumented, resulting in an underestimation of the importance of their services and missed opportunities for improvements and new directions.

Objective: To document and evaluate the services of a hematology/oncology clinical pharmacy in the outpatient setting.

Novel human IgG2b/murine chimeric antitenascin monoclonal antibody construct radiolabeled with 131I and administered into the surgically created resection cavity of patients with malignant glioma: phase I trial results.

Unlabelled: Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine the effect of these differences on the maximum tolerated dose (MTD), pharmacokinetics, dosimetry, and antitumor activity of (131)I-ch81C6 administered into the surgically created resection cavity (SCRC) of malignant glioma patients.

Methods: In this phase I trial, eligible patients received a single injection of (131)I-ch81C6 administered through a Rickham catheter into the SCRC.

Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme.

Purpose: More brain tumor markers are required for prognosis and targeted therapy. We have identified and validated promising molecular therapeutic glioblastoma multiforme (GBM) targets: human transmembrane glycoprotein nonmetastatic melanoma protein B (GPNMB(wt)) and a splice variant form (GPNMB(sv), a 12-amino-acid in-frame insertion in the extracellular domain).

Experimental Design: We have done genetic and immunohistochemical evaluation of human GBM to determine incidence, distribution, and pattern of localization of GPNMB antigens in brain tumors as well as survival analyses.

Epidermal growth factor receptor mutations in non-small cell lung cancer: a basic science discovery with immediate clinical impact.

A large body of preclinical work suggested that the epidermal growth factor receptor (EGFR) would be a successful target for therapy against non-small cell lung cancer (NSCLC), and this led to the development of oral, selective EGFR tyrosine kinase inhibitors (TKI) that improve symptoms and survival in patients with advanced NSCLC. However, not all patients benefit from this treatment, and there has been great interest in identifying the molecular correlates that predict for response to these agents. The recent detection of somatic mutations in EGFR that predict for response to the EGFR tyrosine kinase inhibitors has excited the scientific community.

Phase 1 trial of gefitinib plus sirolimus in adults with recurrent malignant glioma.

Purpose: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gefitinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent malignant glioma.

Patients And Methods: Gefitinib and sirolimus were administered on a continuous daily dosing schedule at dose levels that were escalated in successive cohorts of malignant glioma patients at any recurrence who were stratified based on concurrent use of CYP3A-inducing anticonvulsants [enzyme-inducing antiepileptic drugs, (EIAED)]. Pharmacokinetic and archival tumor biomarker data were also assessed.

Safety and pharmacokinetics of intravenous anidulafungin in children with neutropenia at high risk for invasive fungal infections.

Anidulafungin is an echinocandin with activity against Candida species and Aspergillus species. Adult dosages under study are 50 mg/day for esophageal candidiasis and 100 mg/day for invasive candidiasis and aspergillosis. Little is known, however, about the safety and pharmacokinetics of anidulafungin in children.

Analysis of micrometastatic disease in sentinel lymph nodes from resectable colon cancer: results of Cancer and Leukemia Group B Trial 80001.

Purpose: To determine whether sentinel lymph node (LN) sampling (SLNS) could reduce the number of nodes required to characterize micrometastatic disease (MMD) in patients with potentially curable colon cancer.

Patients And Methods: Cancer and Leukemia Group B 80001 was a study to determine whether SLNS could identify a subset of LNs that predicted the status of the nodal basin for resectable colon cancer and, therefore, could be extensively evaluated for the presence of micrometastases. Patients enrolled onto this study underwent SLNS after injection of 1% isosulfan blue, and both sentinel nodes (SNs) and non-SNs obtained during primary tumor resection were sectioned at multiple levels and stained using anti-carcinoembryonic antigen and anticytokeratin antibodies.

Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results.

Purpose: To assess the efficacy and toxicity of intraresection cavity iodine-131-labeled murine antitenascin monoclonal antibody 81C6 (131I-m81C6) among recurrent malignant brain tumor patients.

Patients And Methods: In this phase II trial, 100 mCi of 131I-m81C6 was injected directly into the surgically created resection cavity (SCRC) of 43 patients with recurrent malignant glioma (glioblastoma multiforme [GBM], n = 33; anaplastic astrocytoma [AA], n = 6; anaplastic oligodendroglioma [AO], n = 2; gliosarcoma [GS], n = 1; and metastatic adenocarcinoma, n = 1) followed by chemotherapy.

Results: With a median follow-up of 172 weeks, 63% and 59% of patients with GBM/GS and AA/AO tumors were alive at 1 year.