Career advice for oncology trainees.
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Australia↗
Biomedical subjects
Mark Rosenthal
Publications and source records attributed to Mark Rosenthal.
Reproducibility of cardioventilatory measurements using a respiratory mass spectrometer.
The aim of this study was to assess the within subject reproducibility of cardioventilatory measurements and the maximum permitted 'normal' variability over time at rest and exercise using the respiratory mass spectrometer (RMS). Ten subjects underwent an incremental exercise test on three separate occasions utilising rebreathing (RB) and helium dilution mixed expired gas analysis (HME) functions of the RMS. Measurements included heart rate (HR), oxygen consumption (V(O2)), carbon dioxide excretion (V(VO2)), effective pulmonary blood flow (Q(eff)), stroke volume (SV), arteriovenous oxygen content difference (AVO), transfer factor (Dl(CO)), functional residual capacity (FRC), minute ventilation (VE), tidal volume (VT) and respiratory quotient (RQ). The coefficients of variation for each variable for the 10 subjects were calculated. At rest, the 90th centile variability for measured cardiopulmonary variables (RB only) was <35%. During exercise, the 90th centile for variability for measured cardiopulmonary variables for HME and RB were < or =20 and <40%, respectively. These measurements in healthy adults should inform sample size in research studies.
Adult↗
Bronchoscopy following diagnosis with cystic fibrosis.
We recently changed our practice to perform bronchoscopy following diagnosis with cystic fibrosis. On a retrospective review of 25 children, Pseudomonas aeruginosa was detected in bronchoalveolar lavage for the first time in five children (20%) and Staphylococcus aureus in four (16%). Lavage culture was positive in eight of 18 children without respiratory symptoms. This highlights the potential of bronchoscopy following diagnosis, even in asymptomatic children.
Bronchoscopy↗
Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients.
Treatment of Alzheimer's disease (AD) is difficult due to ignorance of its pathogenesis. AD patients have defects in phagocytosis of amyloid-beta (1-42) (Abeta) in vitro by the innate immune cells, monocyte/macrophages and in clearance of Abeta plaques [5]. The natural product curcuminoids enhanced brain clearance of Abeta in animal models. We, therefore, treated macrophages of six AD patients and 3 controls by curcuminoids in vitro and measured Abeta uptake using fluorescence and confocal microscopy. At baseline, the intensity of Abeta uptake by AD macrophages was significantly lower in comparison to control macrophages and involved surface binding but no intracellular uptake. After treatment of macrophages with curcuminoids, Abeta uptake by macrophages of three of the six AD patients was significantly (P<0.001 to 0.081) increased. Confocal microscopy of AD macrophages responsive to curcuminoids showed surface binding in untreated macrophages but co-localization with phalloidin in an intracellular compartment after treatment. Immunomodulation of the innate immune system by curcuminoids might be a safe approach to immune clearance of amyloidosis in AD brain.
Aged↗
Voriconazole therapy in children with cystic fibrosis.
BACKGROUND: There is increasing evidence for the efficacy of the antifungal voriconazole, particularly in immunosuppression. We describe our experience of using voriconazole in children with CF. METHODS: We performed a retrospective case note review of children with CF treated with voriconazole in a single centre over an 18 month period. RESULTS: A total of 21 children aged 5 to 16 years (median 11.3) received voriconazole for between 1 and 50 (22) weeks. Voriconazole was used as monotherapy in 2 children with recurrent allergic bronchopulmonary aspergillosis (ABPA); significant and sustained improvements in clinical and serological parameters for up to 13 months were observed, without recourse to oral steroids. Voriconazole was used in combination with an immunomodulatory agent in a further 11 children with ABPA, with significant improvement in pulmonary function and serology. 8 children without ABPA but who had recurrent Aspergillus fumigatus isolates and increased symptoms also received voriconazole; this group did not improve with treatment. Adverse effects occurred in 7 children (33%: photosensitivity reaction 3, nausea 2, rise in hepatic enzymes 1, hair loss 1). CONCLUSIONS: Voriconazole may be a useful adjunctive therapy for ABPA in CF. Voriconazole monotherapy appears to be an alternative treatment strategy when oral corticosteroids may not be suitable.
Adolescent↗
The Accutrend sensor glucose analyzer may not be adequate in bedside testing for neonatal hypoglycemia.
UNLABELLED: The aim of this prospective observational study was to compare a bedside test with the reference laboratory method in routine postnatal glucose monitoring. Term newborns with increased risk or clinical signs of hypoglycemia were screened with a bedside test. In case of a glucose value below 2.25 mmol/L, a second blood sample was taken and a duplicate glucose measurement done in the laboratory using a bedside test (Accutrend sensor) and the reference laboratory method (hexokinase method) at the same time and from the same sample. From 110 term newborns, 122 blood samples were obtained for duplicate measurements (median 1.69 mmol/L, SD 0.45 mmol/L). Of these 122, Accutrend correctly identified 97% as being <2.25 mmol/L by the laboratory method. A Bland-Altman plot revealed a mean underestimation of the Accutrend of only -0.09 mmol/L. However, due to high scattering, the maximal over- and underestimation was 0.89 and 1.39 mmol/L, respectively. Only 75% of the results from the Accutrend were within +/-20% of the result of the laboratory method. If the cut-off for low glucose concentrations was set 0.6 mmol/L higher for the bedside test as compared to the laboratory method, all patients except one would have been correctly identified as hypoglycemic. CONCLUSION: When using the Accutrend sensor, single infants with even marked hypoglycemia might be missed. Some delay in receiving accurate measurements might be more helpful for clinical decisions and long-term outcome than immediate but potentially misleading results.
Blood Glucose↗
A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy.
PURPOSE: To determine whether recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) can prevent or ameliorate the development of chemotherapy-induced peripheral neuropathy (CIPN) after treatment with carboplatin (AUC 6) and paclitaxel (175 mg/m(2) over 3 hours). EXPERIMENTAL DESIGN: Randomized double-blind placebo-controlled phase II clinical trial. Eligible patients had solid tumors for which treatment with carboplatin/paclitaxel was appropriate. The primary end point was a standardized composite peripheral nerve electrophysiology (CPNE) score, based on nerve velocities and amplitudes, measured at baseline and after four cycles of chemotherapy. Secondary efficacy end points included CPNE score at last cycle and at exit evaluation, vibration perception threshold, H-reflex latency, symptom scores, and quantitative assessment of neurologic signs. Study drug was given s.c. daily for 7 days starting the day before chemotherapy. Patients were randomized to receive low-dose rhuLIF (2 microg/kg), high-dose rhuLIF (4 microg/kg), or placebo. RESULTS: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 microg/kg), 39 received high dose rhuLIF (4 microg/kg) and 42 received placebo. rhuLIF was well tolerated with 95% compliance and no adverse effects on quality of life. No differences between groups in CPNE or any of the individual neurologic testing variables were observed between baseline and cycle 4 or by the secondary efficacy variables. CONCLUSIONS: rhuLIF is not effective in preventing CIPN caused by carboplatin and paclitaxel. CPNE is a reliable and valid tool that was sensitive to the onset and progression of CIPN.
Adult↗
Results of strontium-89 therapy in patients with prostate cancer resistant to chemotherapy.
PURPOSE: Strontium-89 (Sr-89) chloride is an effective palliative treatment of the bone metastases of prostate cancer. Chemotherapy has also been shown to have a palliative benefit in this disease. We aimed to determine the benefits and complications of Sr-89 therapy in patients with prostate cancer who had become refractory to chemotherapy. We conducted a retrospective review of 14 treatments administered to 13 patients with chemotherapy-resistant and hormone-resistant prostate cancer. RESULTS: Of the 14 administered treatments, 8 (57%) resulted in improved pain control, with 2 patients able to stop analgesia. The median duration of response was 56 days. No prostate-specific antigen response was seen in the 8 patients tested. There was significant and prolonged bone marrow toxicity, with 6 patients requiring red blood cell transfusion. Prolonged thrombocytopenia was seen, with platelet counts remaining below baseline levels after treatment in all but one patient. Leukopenia was generally mild and not associated with infection. CONCLUSIONS: Sr-89 is an effective treatment of patients with chemotherapy-refractory prostate cancer, but careful and prolonged monitoring of hematologic parameters after therapy is required.
Adult↗
What to do for prostate cancer patients with a rising PSA?--A survey of Australian practice.
PURPOSE: To document current Australian management of asymptomatic prostate cancer patients with prostate-specific antigen (PSA) relapse after radical treatment or considered unsuitable for radical treatment. MATERIALS AND METHODS: Four case scenarios-postprostatectomy PSA relapse, postradiotherapy (RT) with a slow or a rapidly rising PSA level, or no radical treatment-were presented. Management preferences, including (where relevant) RT, androgen ablation either immediate or delayed until a PSA rise or symptomatic progression, and other approaches, were identified. The preferred methods of androgen ablation were noted. RESULTS: One hundred eighteen informative replies out of 324 e-mailed surveys were received. For postprostatectomy PSA relapse, 59% of respondents favored salvage RT. For post-RT with a slow or a rapidly rising PSA level and treatment of nonradical patients, there was no clear consensus of opinion, with respondents divided among the different options. A diverse range of PSA levels was cited for delayed intervention, with values ranging from 0.8 to 100 ng/mL. PSA doubling time proved a more consistent criterion for determining intervention. Most respondents favored the use of a luteinizing hormone-releasing hormone agonist as first-line androgen ablation, although patient choice was recognized as important in all decision making. CONCLUSIONS: A lack of available evidence underlies the diversity of opinion regarding the management of asymptomatic prostate cancer patients with a rising PSA. The need for randomized controlled trials in this area is highlighted.
Androgen Antagonists↗
Re: A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma.
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Androgens↗
Bronchoscopy and infection.
Bronchoscopy can be useful to diagnose respiratory infections in the immunocompromised and those with problematic cystic fibrosis or with focally abnormal chest X-rays. Its role in paediatric tuberculosis is controversial with scanty objective evidence. As it is an invasive procedure, the following should be asked: what question am I trying to answer by bronchoscopy? Will the answer justify the risks of the procedure?
Bronchoalveolar Lavage Fluid↗
Subcutaneous terbutaline in children with chronic severe asthma.
A continuous subcutaneous infusion of terbutaline (CSIT) was used to treat 8 children with chronic severe asthma who continued to experience frequent symptoms, despite treatment with regular oral prednisolone. Five patients experienced a symptomatic improvement from CSIT, leading to a reduction in regular medication. Three patients did not experience any lasting benefit from CSIT. The most common side effects were related to the infusion site (bruising and local infection). CSIT may lead to an improvement in symptoms and a reduction in oral steroid dose in selected children with chronic severe asthma. These initial findings support the need for further controlled studies to evaluate the use of CSIT in severe childhood asthma.
Adolescent↗
Bone marrow stem cells do not repopulate the healthy upper respiratory tract.
Recent studies reported differentiation of both bone marrow and tissue-specific stem cells into cells of other organs. The demonstration that bone marrow stem cells differentiate into human hepatocytes in vivo has raised the possibility of new therapeutic approaches for liver disease. For diseases such as cystic fibrosis (CF), correction of the respiratory epithelium is being attempted by gene therapy. Differentiation of bone marrow stem cells into epithelium of the lung and airway was recently reported in an animal model, and would provide an alternative approach. We examined the nasal epithelium of female patients up to 15 years after gender-mismatched bone marrow transplantation. Donor-derived epithelial cells were sought with a combination of Y-chromosome fluorescence in situ hybridization and anti-cytokeratin antibody. In nasal brushing samples from 6 transplant-recipients, a median of 2.5% (range, 0.7-18.1%) of nuclei was male and identified as being of donor-origin. However, a complete absence of staining with anti-cytokeratin antibodies confirmed that these were not epithelial cells, but were likely to be either intraepithelial lymphocytes or mesenchymal cells. Following whole bone marrow transplantation, bone marrow progenitor cells do not differentiate into respiratory epithelium of the healthy upper airway. The differences between this and other studies could relate to the cells transplanted, to differential rates of turnover, or to the requirement for specific triggers to stimulate migration and differentiation. In the absence of such conditions, whole bone marrow transplantation is unlikely to provide a route for correction of the CF airway.
Adolescent↗
Macrolides in the respiratory tract in cystic fibrosis.
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Anti-Bacterial Agents↗
Differential diagnosis of asthma.
Asthma tends to be diagnosed too easily by clinicians without sufficient consideration being given to alternative possibilities. Most asthma is obvious, mild and easy to treat. Deviations from this typical picture should be a signal to consider carefully other diagnoses. Age of onset, pattern of symptoms, sputum production, diurnal variations or the lack thereof, associated upper respiratory symptoms, abnormal physical signs, poor control on standard inhaler therapy and unusual flow volume loops are all pointers to non-asthma diagnoses.
Asthma↗
Treatment of primary pulmonary hypertension with oral sildenafil.
Sildenafil, a selective phosphodiesterase-5 inhibitor, was administered orally to a 14-year-old girl with primary pulmonary hypertension (PPH) at a dose of 0.5 mg/kg/4 h on a daily basis, increased to doses of 1 and 2 mg/kg at monthly intervals. Following therapy, oxygen saturation increased and exercise capacity improved significantly, but with no change in pulmonary haemodynamics. No side-effects were noted. Sildenafil may be beneficial in children with PPH, but the mechanism of benefit is unclear.
Administration, Oral↗