Biomedical subjects

Robert Blum

Publications and source records attributed to Robert Blum.

16 recordsLinked to original sources

PubMed2026

Cognitive Behavior vs Bright Light Therapy for Insomnia in Women Undergoing Chemotherapy for Breast Cancer: A Randomized Clinical Trial.

IMPORTANCE: Women receiving chemotherapy for breast cancer experience insomnia and fatigue, which impair quality of life. To date, no randomized clinical trial (RCT) has evaluated the use of cognitive behavior therapy for insomnia (CBT-I) and bright light therapy (BLT) both alone and in combination, and few have evaluated the use of either during chemotherapy. OBJECTIVE: To determine the main effects of CBT-I and BLT on insomnia and fatigue symptoms in women undergoing chemotherapy for breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Sleep, Cancer, Rest (SleepCARE) was a 6-week, 2 × 2 factorial, superiority, parallel RCT conducted at 5 metropolitan and regional hospitals in Australia from January 22, 2021, to August 21, 2024. Participants were women (aged ≥18 years) receiving chemotherapy for early or metastatic breast cancer. INTERVENTIONS: Two brief interventions were administered: CBT-I and BLT alone (using light glasses at 1500 lux) and in combination, creating 4 groups (CBT-I alone, BLT alone, CBT-I plus BLT, and sleep hygiene education [SHE]). All interventions included SHE. The interventions lasted 6 weeks and included a 1:1 consultation session, emails sent once or twice per week, and a midpoint call for all groups, as well as light glasses for the BLT groups. MAIN OUTCOMES AND MEASURES: Dual primary outcomes were Insomnia Severity Index (ISI) scores and Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue T scores. Both are patient-reported outcome measures and measure insomnia and fatigue symptoms, respectively. Assessments occurred via surveys administered at baseline and at the midpoint (3 weeks), postintervention (6 weeks), and follow-up (3 months and 6 months) periods. Modified intention-to-treat analyses used latent growth models. RESULTS: Of the 219 women enrolled (mean [SD] age, 50.7 [10.8] years; 54 [26.9%] with metastatic cancer), 55 were randomized to CBT-I, 55 to BLT, 52 to CBT-I plus BLT, and 57 to SHE. A total of 208 women (95.0%) with any data at any time point were analyzed. Insomnia symptoms (ISI score mean difference [MD], -2.19 [95% CI, -3.33 to -1.05] points; P = .002) but not fatigue symptoms (PROMIS-Fatigue score MD, -0.90 [95% CI, -3.08 to 1.28] points; P = .52) improved more in the CBT-I groups compared with the non-CBT-I groups. The BLT groups (compared with the non-BLT groups) did not differ in insomnia symptoms (ISI score MD, -0.88 [95% CI, -2.02 to 0.26] points; P = .26) or fatigue symptoms (PROMIS-Fatigue score MD, -0.71 [95% CI, -2.89 to 1.47] points; P = .52). Comparable results emerged in the high-adherence subgroup and in the subgroups with high initial insomnia and fatigue symptoms. However, exploratory subgroup analyses in women with metastatic breast cancer showed that BLT (vs non-BLT) improved insomnia symptoms (ISI score MD, -2.87 [95% CI, -5.06 to -0.67] points; P = .01) and fatigue symptoms (PROMIS-Fatigue score MD, -5.16 [95% CI, -9.57 to -0.76] points; P = .02). CONCLUSIONS AND RELEVANCE: In the SleepCARE RCT of CBT-I and BLT administered for 6 weeks to women receiving chemotherapy for breast cancer, CBT-I improved insomnia but not fatigue compared with SHE or BLT. BLT did not produce greater improvements in fatigue or insomnia symptoms compared with non-BLT treatment. The study findings indicate that brief CBT-I, but not BLT, may reduce insomnia symptoms among women receiving chemotherapy for breast cancer. TRIAL REGISTRATION: ANZCTR Identifier: ACTRN12620001133921.

Humans↗

PubMed2006

Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects.

Sitagliptin (MK-0431) is an oral, potent, and selective dipeptidyl peptidase-IV (DPP-4) inhibitor developed for the treatment of type 2 diabetes. This multicenter, randomized, double-blind, placebo-controlled study examined the pharmacokinetic and pharmacodynamic effects of sitagliptin in obese subjects. Middle-aged (45-63 years), nondiabetic, obese (body mass index: 30-40 kg/m2) men and women were randomized to sitagliptin 200 mg bid (n = 24) or placebo (n = 8) for 28 days. Steady-state plasma concentrations of sitagliptin were achieved within 2 days of starting treatment, and >90% of the dose was excreted unchanged in urine. Sitagliptin treatment led to approximately 90% inhibition of plasma DPP-4 activity, increased active glucagon-like peptide-1 (GLP-1) levels by 2.7-fold (P < .001), and decreased post-oral glucose tolerance test glucose excursion by 35% (P < .050) compared to placebo. In nondiabetic obese subjects, treatment with sitagliptin 200 mg bid was generally well tolerated without associated hypoglycemia and led to maximal inhibition of plasma DPP-4 activity, increased active GLP-1, and reduced glycemic excursion.

Adenosine Deaminase↗

PubMed2005

Quantitative single-cell RT-PCR and Ca2+ imaging in brain slices.

We have established a quantitative reverse transcriptase-PCR (RT-PCR) approach for the analysis of RNA transcript levels in individual cells of living brain slices. Quantification is achieved by using rapid-cycle, real-time PCR protocols and high-resolution external cDNA standard curves for the gene of interest. The method consists of several procedures, including cell soma harvest, reverse transcription, and an optimized cDNA purification step, which allowed us to quantify transcripts in small types of neurons, like cerebellar granule cells. Thus, we detected in single granule cells an average of 20 transcript copies of the housekeeping gene glyceraldehyde-3-phosphate-dehydrogenase. We combined two-photon calcium imaging and quantitative RT-PCR in single Purkinje and granule cells, respectively, and identified distinct glutamate receptor-dependent Ca2+ responses in these two cell types. The approach was further tested by profiling the expression of the ionotropic glutamate receptor subunits NR2B and NR2C in the cerebellum. Our study revealed a developmental switch from an average of 15 NR2B copies/cell at postnatal day 8 (P8) to about five NR2C copies/cell after P26. Taken together, our results demonstrate that the new method is rapid, highly sensitive, provides reliable results in neurons of various sizes, and can be used in combination with Ca2+ imaging.

Animals↗

PubMed2005

Gold-tip electrodes--a new "deep lesion" technology for catheter ablation? In vitro comparison of a gold alloy versus platinum-iridium tip electrode ablation catheter.

Gold-tip electrodes. Radiofrequency (RF) catheter ablation is widely used to induce focal myocardial necrosis using the effect of resistive heating through high-frequency current delivery. It is current standard to limit the target tissue-electrode interface temperature to a maximum of 60-70 degrees C to avoid char formation. Gold (Au) exhibits a thermal conductivity of nearly four times greater than platinum (Pt-Ir) (3.17 W/cm Kelvin vs 0.716 W/cm Kelvin), it was therefore hypothesized that RF ablation using a gold electrode would create broader and deeper lesions as a result of a better heat conduction from the tissue-electrode interface and additional cooling of the gold electrode by "heat loss" to the intracardiac blood. Both mechanisms would allow applying more RF power to the tissue before the electrode-tissue interface temperature limit is reached. To test this hypothesis, we performed in vitro isolated liver and pig heart investigations comparing lesion depths of a new Au-alloy-tip electrode to standard Pt-Ir electrode material. Mean lesion depth in liver tissue for Pt-Ir was 4.33+/-0.45 mm (n=60) whereas Au electrode was able to achieve significantly deeper lesions (5.86+/-0.37 mm [n=60; P<0.001]). The mean power delivered using Pt-Ir was 6.95+/-2.41 W whereas Au tip electrode delivered 9.64+/-3.78 W indicating a statistically significant difference (P<0.05). In vitro pig heart tissue Au ablation (n=20) increased significantly the lesion depth (Au: 4.85+/-1.01 mm, Pt-Ir: 2.96+/-0.81 mm, n=20; P<0.001). Au tip electrode again applied significantly more power (P<0.001). Gold-tip electrode catheters were able to induce deeper lesions using RF ablation in vitro as compared to Pt-Ir tip electrode material. In liver and in pig heart tissue, the increase in lesion depth was associated with a significant increase in the average power applied with the gold electrode at the same level of electrode-tissue temperature as compared to platinum material.

Animals↗

PubMed2005

Neurotrophin-mediated rapid signaling in the central nervous system: mechanisms and functions.

Neurotrophins regulate growth, survival, and differentiation of central neurons. In addition to the "classical" effects that are relatively slow neurotrophins also elicit rapid signaling that modulates a variety of cellular functions such as membrane excitability, synaptic transmission, and activity-dependent synaptic plasticity. These rapid actions are mediated mainly through the interaction of Trk receptors with ion channels and ionotropic receptors in the plasma membrane.

Animals↗

PubMed2004

From modulator to mediator: rapid effects of BDNF on ion channels.

Neurotrophins (NTs) are [?AUTHOR] a family of structurally related, secreted proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons.1,2 Among these, BDNF (brain-derived neurotrophic factor) has drawn considerable interest because both its synthesis and secretion are increased by physiological levels of activity, indicating a unique role of this neurotrophin in coupling neuronal activity to structural and functional properties of neuronal circuits. In addition to its classical neurotrophic effects, which are evident within hours or days and which usually result from changes in cellular gene expression, BDNF exerts acute effects on synaptic transmission and is involved in the induction of long-term potentiation. Many of these rapid effects of BDNF are mediated by its modulation of ion channel properties following TrkB-mediated activation of intracellular second messenger cascades and protein phosphorylation. However, recent reports have shown that BDNF not only acts as a modulator of ion channels, but can also directly and rapidly gate a Na(+) channel, thereby assigning BDNF the properties of a classical excitatory transmitter. Thus, BDNF, in addition its role as a potent neuromodulator, emerges as an excitatory transmitter-like substance which acutely controls resting membrane potential, neuronal excitability, synaptic transmission and participates in the induction of synaptic plasticity.

Animals↗

PubMed2004

Impact of positron emission tomography on the management of patients with small-cell lung cancer: preliminary experience.

Accurate staging is important in small-cell lung cancer (SCLC). Patients with limited stage may benefit from chemoradiation, whereas those with extensive stage conventionally receive chemotherapy. Prophylactic cranial irradiation may benefit those attaining complete remission (CR). 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) enhances accuracy of staging in non-SCLC. Its role in SCLC remains unclear. We reviewed 36 consecutive SCLC patients who underwent 47 PET studies between December 1996 and January 2001, for either staging (n = 11), restaging after therapy (n = 21), or both (n = 4). Conventional imaging was also performed. Of 15 patients who had PET for staging, 5 (33%) were upstaged from limited to extensive disease and treated without thoracic radiotherapy. Twenty-five patients underwent 32 restaging PET scans, of which 20 (63%) were discordant with conventional imaging. In 8 cases PET showed more extensive disease than conventional imaging, and in 12 cases PET-apparent disease appeared less extensive. In 13 patients, 14 untreated discordant lesions were evaluable; PET was confirmed accurate in 11 (79%) sites by last follow-up. Restaging PET influenced management in 13 cases (52%). PET-CR conferred longer median time to progression (13.7 months) than no CR (9.7 months). FDG-PET for SCLC was often discordant with conventional assessment and frequently influenced management.

Aged↗

PubMed2004

Treatment of primary cutaneous follicular centre lymphoma with rituximab: a report of two cases.

Rituximab (anti-CD20 chimeric monoclonal antibody) has been demonstrated to have significant activity in nodal B-cell lymphomas, with very few associated adverse effects. Although primary cutaneous B-cell lymphomas (PCBCL) also express the CD20 antigen, relatively few reports of rituximab use in PCBCL have been published to date. We present two cases of primary cutaneous follicular centre lymphoma treated with rituximab (375 mg/m(2)/week intravenously for 4 weeks). Both cases responded to rituximab, with one partial response and one complete response seen. No adverse effects were observed. To date, disease progression has occurred in one case during overall follow up at 6 and 17 months. The potential role of rituximab in the treatment of these lymphomas is discussed.

Aged, 80 and over↗

PubMed2004

Characterization of pancreatic ERj3p, a homolog of yeast DnaJ-like protein Scj1p.

We have previously identified in the human EST sequence data base four overlapping clones that could be aligned with both a predicted protein sequence, deduced from the C. elegans genomic sequence, and partial amino acid sequences, obtained for a protein from canine pancreatic microsomes. We suggested that these proteins are homologs of yeast microsomal and DnaJ-like protein Scj1p and termed them ERj3p. Here we verified the predicted protein sequence of human ERj3p by sequence analysis of the corresponding cDNA. Multiple alignment of related sequences identified these proteins as true homologs of yeast Scj1p. Biochemical analysis of the canine protein characterized ERj3p as a soluble glycoprotein of the pancreatic endoplasmic reticulum. This pancreatic DnaJ-like protein was shown to interact with lumenal DnaK-like proteins, such as BiP. Furthermore, we found that ERj3p interacts with SDF2L1 protein that may be involved in protein O-glycosylation. We propose that ERj3p represents a cochaperone of DnaK-like chaperones of the mammalian endoplasmic reticulum and is involved in folding and maturation of newly synthesized proteins.

Amino Acid Sequence↗

PubMed2003

Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells.

The neurotrophin receptor TrkB is essential for normal function of the mammalian brain. It is expressed in three splice variants. Full-length receptors (TrkB(FL)) possess an intracellular tyrosine kinase domain and are considered as those TrkB receptors that mediate the crucial effects of brain-derived neurotrophic factor (BDNF) or neurotrophin 4/5 (NT-4/5). By contrast, truncated receptors (TrkB-T1 and TrkB-T2) lack tyrosine kinase activity and have not been reported to elicit rapid intracellular signalling. Here we show that astrocytes predominately express TrkB-T1 and respond to brief application of BDNF by releasing calcium from intracellular stores. The calcium transients are insensitive to the tyrosine kinase blocker K-252a and persist in mutant mice lacking TrkB(FL). By contrast, neurons produce rapid BDNF-evoked signals through TrkB(FL) and the Na(v)1.9 channel. Expression of antisense TrkB messenger RNA strongly reduces BDNF-evoked calcium signals in glia. Thus, our results show that, unexpectedly, TrkB-T1 has a direct signalling role in mediating inositol-1,4,5-trisphosphate-dependent calcium release; in addition, they identify a previously unknown mechanism of neurotrophin action in the brain.

Alternative Splicing↗

PubMed2003

Clinical study of primary cutaneous B-cell lymphoma using both the European Organization for Research and Treatment of Cancer and World Health Organization classifications.

Primary cutaneous B-cell lymphoma (PCBCL) is rare, with few series reported in the literature. Its classification and treatment remain controversial. Biopsy specimens of 13 patients with PCBCL were classified according to both the European Organization for Research and Treatment of Cancer (EORTC) and the new World Health Organization (WHO) classifications. Treatment and clinical outcomes were documented. Using the EORTC classification there were seven men and six women aged 32-85 years (mean = 51 years) with follicle centre cell (FCC) lymphoma (nine), immunocytoma (two) and primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg) (two). When the WHO classification was used, the nine patients with FCC were reclassified as follicle centre (five) and diffuse large B-cell lymphoma (four). Most patients had localized disease (12). Initial treatment consisted of radiotherapy alone (seven), combination chemotherapy alone (one), combined chemoradiotherapy (three) and surgery (two). Twelve patients achieved complete remission (median follow up 28 months, range 10-167 months). One patient with PCLBCL-leg died from progressive cutaneous disease. Most localized PCBCL lesions (except PCLBCL-leg) have a favourable prognosis. We recommend that clinicians be familiar with the important differences in the EORTC and WHO classifications. Further large prospective studies comparing the WHO and EORTC classifications are required to more clearly delineate the outcomes of the increasing number of patients who are classified as DLBCL by the WHO system.

Adult↗

PubMed2003

Pharmacokinetics of rosiglitazone in patients with varying degrees of renal insufficiency.

This study investigated the effect of varying degrees of renal insufficiency on the pharmacokinetics of rosiglitazone. Subjects were stratified by estimated creatinine clearance: normal (> 80 mL/min; n = 12), mild renal insufficiency (60-80 mL/min; n = 15), moderate renal insufficiency (30-59 mL/min; n = 18), and severe renal insufficiency not requiring dialysis (< or = 29 mL/min; n = 12). Plasma rosiglitazone concentrations and protein binding were determined after a single oral 8-mg dose of rosiglitazone. Total and unbound pharmacokinetic parameters were generated using noncompartmental methods. AUC, Cmax, and t1/2 data were analyzed separately by ANOVA to provide point estimates and corresponding 95% confidence intervals. The pharmacokinetics of rosiglitazone was not markedly affected by mild, moderate, or severe renal insufficiency. Slight increases (approximately 10%-20%) in mean unbound AUC0-infinity values were observed for each insufficiency group compared to the normal group but were not considered to be clinically relevant. Patients with severe insufficiency exhibited a 38% increase in mean fraction unbound, leading to an increase in total clearance, which resulted in a 19% to 24% lower mean total AUC0-infinity and Cmax values relative to the normal group. The rates of mild or moderate adverse events were similar for all groups; there were no severe adverse events. Impaired renal function does not markedly alter the pharmacokinetics of total or unbound rosiglitazone following a single dose of rosiglitazone. Therefore, the starting dose of rosiglitazone does not need to be adjusted in patients with renal impairment. Subsequent dose adjustments should be based on individual patient response.

Administration, Oral↗

PubMed2002

Neurotrophin-evoked depolarization requires the sodium channel Na(V)1.9.

Brain-derived neurotrophic factor (BDNF) and other neurotrophins are essential for normal brain function. Many types of neurons in the central nervous system are excited by BDNF or neurotrophin-4/5, an action that has recently been implicated in synaptic plasticity. The mechanisms involved in this transmitter-like action of neurotrophins remains unclear. Here, by screening candidate genes with an antisense messenger RNA expression approach and by co-expressing the receptor tyrosine kinase TrkB and various sodium channels, we demonstrate that the tetrodotoxin-insensitive sodium channel Na(V)1.9 underlies the neurotrophin-evoked excitation. These results establish the molecular basis of neurotrophin-evoked depolarization and reveal a mechanism of ligand-mediated sodium channel activation.

Animals↗

PubMed2002

Role of 18FDG-positron emission tomography scanning in the management of histiocytosis.

Diagnostic evaluation of histiocytic malignancies often involves a range of imaging studies to characterize skeletal and extraskeletal sites of involvement. Functional imaging with 18FDG PET provides a potential method for non-invasively detecting active disease. We report two cases where this modality was positive and facilitated therapeutic monitoring.

Adolescent↗

PubMed2002

Discordant response to chemotherapy detected by PET scanning: unveiling of a second primary cancer.

Positron emission Tomography (PET) is commonly used to stage malignancies and monitor response to treatment. This report describes two patients, one with metastatic breast cancer and the other with aggressive non-Hodgkin's lymphoma (NHL) whose responses to treatment were monitored by serial computed tomography and PET scans. In both cases after completion of systemic chemotherapy, repeat PET scanning revealed residual metabolically active tissue at the base of the neck. Because of differential therapeutic response, the possibility of different pathologic lesions was raised. In each case, further investigation with an ultrasound scan and needle biopsy revealed carcinoma of the thyroid. Both patients were subsequently treated with definitive surgery. In both described cases, a second primary malignancy was found that affected further management and in the second patient altered prognosis. This report concludes that residual metabolically active tissue on PET scans after treatment is not necessarily resistant primary disease. A mixed response requires further investigation, particularly in the case of persisting solitary abnormalities in the neck.

Adult↗

PubMed2001

Mannan Mucin-1 Peptide Immunization: Influence of Cyclophosphamide and the Route of Injection.

SUMMARY: The mucin MUC1 is greatly increased in breast cancer and is a potential target for immunotherapy. In mice, MUC1 conjugated to oxidized mannan (MUC1-mannan fusion protein [M-FP]) targets the mannose receptor and induces a high frequency of cytotoxic T lymphocytes and anti-tumor responses. On this basis, three phase I trials were performed in patients with adenocarcinoma to evaluate the tnxicity and the immunologic responses to mannan MUC1. Forty-one patients with metastatic or locally advanced carcinoma of the breast (trial 1), colon (trial 2), and various adenocarcinomas (trial 3) received increasing doses of M-FP (1 to 300 &mgr;g). The immunizations were given at weekly intervals (weeks 1 to 3) and repeated in weeks 7 to 9. Cyclophosphamide (to increase cellular immunity) was given on weeks 1 and 4. M-FP was given intramuscularly in trial 1 and intraperitoneally in trial 2. No toxic effects occurred, and delayed-type hypersensitivity responses were present only as a microscopic lymphocytic infiltration. Overall, approximately 60% of the patients had high-titer MUC1 immunoglobulin G1 antibody responses, with the intraperitoneal route yielding approximately 10-fold higher responses. Cellular responses (proliferation, cytotoxic T cells, or CD8 T cells secreting tumor necrosis factor-alpha alphand interferon-gamma in response to MUC1 stimulation in vitro) were found in 28% of the patients, which was similar to that seen without cyclophosphamide. In most patients, disease progressed, but in five it remained stable. In addition, there were no objective responses. M-FP is not toxic and induces immune responses that were amplified by the intraperitoneal route of immunization. Cyclophosphamide was of no benefit.

Journal Article↗