Non‐invasive estimation of 10B‐4‐borono‐L‐phenylalanine‐derived boron concentration in tumors by PET using 4‐borono‐2‐18F‐fluoro‐phenylalanine

In boron neutron capture therapy (BNCT), ¹⁰B‐4‐borono‐L‐phenylalanine (BPA) is commonly used as a ¹⁰B carrier. PET using 4‐borono‐2‐¹⁸F‐fluoro‐phenylalanine (¹⁸F‐FBPA PET) has been performed to estimate boron concentration and predict the therapeutic effects of BNCT; however, the association between tumor uptake of ¹⁸F‐FBPA and boron concentration in tumors remains unclear. The present study investigated the transport mechanism of ¹⁸F‐FBPA and BPA, and evaluated the utility of ¹⁸F‐FBPA PET in predicting boron concentration in tumors. The transporter assay revealed that 2‐aminobicyclo‐(2.2.1)‐heptane‐2‐carboxylic acid, an inhibitor of the L‐type amino acid transporter, significantly inhibited ¹⁸F‐FBPA and ¹⁴C‐4‐borono‐L‐phenylalanine (¹⁴C‐BPA) uptake in FaDu and LN‐229 human cancer cells. ¹⁸F‐FBPA uptake strongly correlated with ¹⁴C‐BPA uptake in 7 human tumor cell lines (r = .93; P < .01). PET experiments demonstrated that tumor uptake of ¹⁸F‐FBPA was independent of the administration method, and uptake of ¹⁸F‐FBPA by bolus injection correlated well with BPA uptake by continuous intravenous infusion. The results of this study revealed that evaluating tumor uptake of ¹⁸F‐FBPA by PET was useful for estimating ¹⁰B concentration in tumors.     

Evaluation of PCR for Detection of DNA Specific for Aspergillus Species in Sera of Patients with Various Forms of Pulmonary Aspergillosis

Pulmonary aspergillosis is classified into invasive, saprophytic, and allergic forms. In this study, we evaluated the usefulness of PCR for differentiating between different forms of aspergillosis or in monitoring disease activity during treatment by detecting DNA specific for Aspergillus species in the serum. Nested PCR was used to detect Aspergillus DNA in the sera of 30 patients with various forms of pulmonary aspergillosis. The results were compared with those of latex agglutination tests for detecting galactomannan antigen. We also examined the serial changes in the results of nested PCR during and after treatment of a subgroup of patients with invasive pulmonary aspergillosis with amphotericin B. The highest proportion of positive nested PCR results were in patients with invasive aspergillosis (10 of 12; 83%), while patients with pulmonary aspergilloma had the lowest frequency of positive tests (1 of 9; 11%). These results suggested that the sensitivity of the nested PCR depends on the extent of invasion by Aspergillus species. Serial assays showed that the results of nested PCR became negative shortly after commencement of antifungal treatment and that such changes did not correlate with clinical responsiveness to treatment. Our results indicate the potential usefulness of nested PCR with serum samples for the diagnosis of invasive aspergillosis and the detection of a shift in the status of infection from a noninvasive type to invasive aspergillosis. However, the results of the nested PCR did not correlate with the response to antifungal treatment.Pulmonary aspergillosis is classified into three types: invasive, saprophytic, and allergic. The type of disease caused by Aspergillus species is determined by the host immune activity and structural abnormalities of the bronchi and lung (2, 10, 17). Recently, Gefter et al. (8, 9) proposed a new type of semi-invasive pulmonary aspergillosis as an intermediate form between the invasive and saprophytic types. Binder et al. (3) later described a similar condition as chronic necrotizing pulmonary aspergillosis (CNPA). In spite of this classification, it is often difficult to differentiate among these disease forms, and intermediate or borderline cases often exist (1, 15).In a series of recent studies, we reported the usefulness of nested PCR for the detection of DNA specific for Aspergillus species in serum samples and for the diagnosis of invasive pulmonary aspergillosis (IPA) (11, 22). In the present study, we evaluated the usefulness of nested PCR for differentiating between different forms of pulmonary aspergillosis.     

Lower optimal dose of amrubicin for relapsed small-cell lung cancer: a retrospective study

International Journal of Clinical Oncology - Amrubicin (AMR) is one of the most active agents for small-cell lung cancer (SCLC). However, hematologic toxicity and infection at a commonly used dose...     

World Health Organization grade II–III astrocytomas consist of genetically distinct tumor lineages

Recent investigations revealed genetic analysis provides important information in management of gliomas, and we previously reported grade II–III gliomas could be classified into clinically relevant subgroups based on the DNA copy number aberrations (CNAs). To develop more precise genetic subgrouping, we investigated the correlation between CNAs and mutational status of the gene encoding isocitrate dehydrogenase (IDH) of those tumors. We analyzed the IDH status and CNAs of 174 adult supratentorial gliomas of astrocytic or oligodendroglial origin by PCR‐based direct sequencing and comparative genomic hybridization, respectively. We analyzed the relationship between genetic subclassification and clinical features. We found the most frequent aberrations in IDH mutant tumors were the combined whole arm‐loss of 1p and 19q (1p/19q codeletion) followed by gain on chromosome arm 7q (+7q). The gain of whole chromosome 7 (+7) and loss of 10q (?10q) were detected in IDH wild‐type tumors. Kaplan–Meier estimates for progression‐free survival showed that the tumors with mutant IDH, ?1p/19q, or +7q (in the absence of +7p) survived longer than tumors with wild‐type IDH, +7, or ?10q. As tumors with +7 (IDH wild‐type) showed a more aggressive clinical nature, they are probably not a subtype that developed from the slowly progressive tumors with +7q (IDH mutant). Thus, tumors with a gain on chromosome 7 (mostly astrocytic) comprise multiple lineages, and such differences in their biological nature should be taken into consideration during their clinical management.     

Anchored disc phenomenon with a normally positioned disc in the temporomandibular joint: characteristics and behaviour

We aimed to elucidate the pathogenesis and evaluate the therapeutic behaviour of patients with an anchored disc phenomenon but a normally positioned disc of the temporomandibular joint (TMJ). Fourteen patients with internal derangement including closed lock of one TMJ were examined. All had normally positioned discs. Synovial fluid was collected from the TMJ by arthrocentesis. Their symptoms, and the protein concentration in the synovial fluid, were evaluated. Their median duration of illness was 3 months (range 0.5-12), and the median protein concentration was low (343 microg/ml; range 36-791). Arthrocentesis was successful in nine. Arthroscopic findings in the five unsuccessful cases showed severe intra-articular adhesions of the TMJ. The main intra-articular pathological feature was the presence of adhesions, which might be affected by low protein concentrations in the synovial fluid. These findings may provide a new treatment in patients with normally positioned discs, despite the small number studied.     

Recent knowledge allowing diagnosis and treatment of deep-seated trichosporonosis]

Deep-seated trichosporonosis is a lethal opportunistic infection in immunocompromised patients. For the rapid diagnosis of this condition, we developed a novel nested-PCR assay that detects DNA specific for clinically important strains of Trichosporon in serum of patients with disseminated trichosporonosis. In this assay, two sets of oligonucleotide primers were derived from the sequence of 26 S ribosomal RNA genes of T. asahii. The specific fragment was amplified from T. asahii and T. mucoides but not from other microorganisms. In a retrospective study using serum samples of patients with disseminated trichosporonosis, the specific fragment was detected in 64% (7 of 11). To treat this infection, we studied the efficacy of rhG-CSF alone and in combination with antifungal agents against disseminated trichosporonosis in neutropenic mice. The results suggested that rhG-CSF might be a useful immunomodulator against Trichosporon infections and the therapeutic outcome might be better when used in combination with antifungal agents.     

Reliability of intensity-based physical activity measurement using an activity monitor in people with subacute stroke in the hospital setting: a cross-sectional study

Background Activity monitors are known to provide quantitative evaluation of physical activity in people with stroke. However, little evidence is available on the test–retest reliability and suitable measuring conditions for evaluating physical activity with an activity monitor in people with subacute stroke at a hospital setting.

Objectives To evaluate reliability of physical activity measurement using an activity monitor in different measuring conditions in hospitalized people with subacute stroke according to gait ability.

Methods Sixty-nine participants with subacute stroke were categorized based on their gait ability: group 1 (n = 22), could walk independently at sufficient gait speed (≥0.9 m/s); group 2 (n = 11), could walk independently with insufficient gait speed (<0.9 m/s); group 3 (n = 36), required assistance in walking. Physical activity (sedentary behavior, light-intensity physical activity, moderate-to-vigorous physical activity) was measured using an activity monitor (OMRON, HJA350-IT) for seven consecutive days. All physical activity variables were calculated in five conditions defined according to measurement periods (3, 5, or 7 days with or without weekends).

Results In groups 1 and 2, intraclass correlation coefficients were high across all measuring conditions in all physical activity variables (>0.7). In group 3, intraclass correlation coefficients were high in all measuring conditions (>0.7) except for three weekdays measuring condition (0.563–0.922).

Conclusions In hospitalized people with subacute stroke, the central tendency of intensity-based physical activity could be assessed with good reliability using an activity monitor. For reliable measurement, more measurement days are needed in those with dependent walking compared to those with independent walking.