In this study, we examined the efficacy and toxicity of S-1 with cisplatin as a second-line palliative chemotherapy for gemcitabine-refractory pancreatic cancer patients. Patients who had been previously treated with gemcitabine-based chemotherapy as palliative first-line chemotherapy received S-1/cisplatin [body surface area (BSA) <1.25 m2, S-1 40 mg/day; BSA ≤1.25 to <1.5 m2, 50 mg/day; BSA ≥1.5 m2 60 mg/day, orally, bid, daily on days 1–14 followed by a 7-day washout and cisplatin 60 mg/m2/day intravenously on day 1] every three weeks. The enrollment of 32 patients was planned, but the study was terminated early, prior to the first stage, following the enrollment of 11 patients. The median age of the patients was 56 (range, 42–74) years. Nine patients had a performance status (PS) of one. In total, there were 21 chemotherapy cycles and the median treatment duration was 21 (range, 7–96) days. Of the 11 patients, five could not be evaluated due to discontinuation prior to the response evaluation. One of the six evaluable patients achieved stable disease (9.1% in intention to treat analysis and 16.7% in per-protocol analysis), while five had progressive disease. Grade 3–4 hematological toxicities were anemia in one, neutropenia in one and thrombocytopenia in one cycle. Grade 3–4 nonhematological toxicities were fatigue in three, nausea in four, anorexia in two, diarrhea in one and peripheral neuropathy in two cycles. With a median follow-up period of 8.9 (range, 3.2–11.3) months, the median time to progression was 44 days [95% confidence interval (CI) 25.4–62.6] and the median overall survival was 81 days (95% CI 9.3–152.7). Combination chemotherapy with S-1 and cisplatin as applied in this study did not result in promising antitumor activity, a high degree of toxicity and poor compliance.
pancreatic cancer; S-1; cisplatin; gemcitabine-refractory
This study was designed to determine what acoustic elements are associated with musical perception ability in cochlear implant (CI) users; and to understand how acoustic elements, which are important to good speech perception, contribute to music perception in CI users. It was hypothesized that the variability in the performance of music and speech perception may be related to differences in the sensitivity to specific acoustic features such as spectral changes or temporal modulations, or both.
A battery of hearing tasks was administered to forty-two CI listeners. The Clinical Assessment of Music Perception (CAMP) was used, which evaluates complex-tone pitch-direction discrimination, melody recognition, and timbre recognition. To investigate spectral and temporal processing, spectral-ripple discrimination and Schroeder-phase discrimination abilities were evaluated. Speech perception ability in quiet and noise was also evaluated. Relationships between CAMP subtest scores, spectral-ripple discrimination thresholds, Schroeder-phase discrimination scores, and speech recognition scores were assessed.
Spectral-ripple discrimination was shown to correlate with all three aspects of music perception studied. Schroeder-phase discrimination was generally not predictive of music perception outcomes. Music perception ability was significantly correlated with speech perception ability. Nearly half of the variance in melody and timbre recognition was predicted jointly by spectral-ripple and pitch-direction discrimination thresholds. Similar results were observed on speech recognition as well.
The current study suggests that spectral-ripple discrimination is significantly associated with music perception in CI users. A previous report showed that spectral-ripple discrimination is significantly correlated with speech recognition in quiet and in noise (Won et al., 2007). The present study also showed that speech recognition and music perception are also related to one another. Spectral-ripple discrimination ability seems to reflect a wide range of hearing abilities in CI users. The results suggest that materially improving spectral resolution could provide significant benefits in music and speech perception outcomes in CI users.
cochlear implants; psychophysical abilities; music perception; speech perception
Choriocarcinoma in the testis is very rare, and it represents less than 1% (0.3%) of all the testicular germ cell tumors. It is a particularly aggressive variant of non-seminoma tumor, which is characterized by a high serum β-HCG level and multiple lung metastases. The optimal management for this disease remains undefined. We report here on a case of choriocarcinoma with multiple lung metastases, and the patient has achieved continuous remission for 2 years after combination chemotherapy of BEP (bleomycin, etoposide and cisplatin) and sequential high-dose chemotherapy with autologous peripheral stem cell rescue.
Neoplasms; Germ cell and embryonal; Testicular choriocarcinoma; High-dose chemotherapy
Leukemic promyelocytes have the unique ability to undergo differentiation after exposure to retinoic acid and both differentiation and apoptosis after exposure to arsenic trioxide (ATO). Recent studies have shown that inhibition of Src family kinases (SFKs) resulted in enhancement of retinoic acid-induced myeloid differentiation.
Materials and Methods
In this study, we investigated the question of whether the SFK inhibitor PP2 enhanced the differentiation of NB4 cells when combined with ATO as well as when combined with all-trans-retinoic acid (ATRA). In addition, we attempted to determine the difference in retinoic acid-induced gene expression between cells treated with PP2 in combination with ATRA and in combination with ATO.
SFK inhibitor PP2 induced significant enhancement of ATRA- or ATO-induced differentiation of NB4 cells. A significantly stronger synergistic effect was observed when PP2 was combined with ATRA than when combined with ATO. Flow cytometric analysis demonstrated a significant increase in CD11b-positive granulocytes up to 60.73% and 31.58%, respectively. These results were confirmed by nitroblue tetrazolium staining. These effects were not related to apoptosis. Results of Annexin-V-fluorescein staining revealed that PP2 combined with ATRA or PP2 combined with ATO did not induce apoptosis in NB4 cells. Retinoic acid-induced gene expression was different in both groups. Intercellular adhesion molecule-1 expression showed a significant increase in cells treated with PP2 in combination with ATRA, whereas cathepsin D expression showed a significant increase in cells treated with PP2 in combination with ATO.
Our data showed that SFK inhibitor PP2 enhanced acute promyelocytic leukemia cell differentiation when combined with either ATRA or ATO with difference in activation of retinoic acid-induced genes.
Acute promyelocytic leukemia; All-trans-retinoic acid; Arsenic trioxide; Src kinase; Cell differentiation
The number of pediatric cochlear implant (CI) recipients has increased substantially over the past 10 years, and it has become more important to understand the underlying mechanisms of the variable outcomes in this population. In this study, psychoacoustic measures of spectral-ripple and Schroeder-phase discrimination, the Clinical Assessment of Music Perception, and consonant-nucleus-consonant (CNC) word recognition in quiet and spondee reception threshold (SRT) in noise tests have been presented to 11 prelingually deafened CI users, aged 8–16 years with at least 5 years of CI experience. The children's performance was compared to the previously reported results of postlingually deafened adult CI users. The average spectral-ripple threshold (n = 10) was 2.08 ripples/octave. The average Schroeder-phase discrimination was 67.3% for 50 Hz and 56.5% for 200 Hz (n = 9). The Clinical Assessment of Music Perception test showed that the average complex pitch direction discrimination was 2.98 semitones. The mean melody score was at a chance level, and the mean timbre score was 34.1% correct. The mean CNC word recognition score was 68.6%, and the mean SRT in steady noise was −8.5 dB SNR. The children's spectral-ripple resolution, CNC word recognition, and SRT in noise performances were, within statistical bounds, the same as in a population of postlingually deafened adult CI users. However, Schroeder-phase discrimination and music perception were generally poorer than in the adults. It is possible then that this poorer performance seen in the children might be partly accounted for by the delayed maturation in their temporal processing ability, and because of this, the children's performance may have been driven more by their spectral sensitivity.
Cochlear implant; Prelingual hearing loss; Psychophysics; Music; Speech perception
Previous work showed that the Fidelity120 processing strategy provides better spectral sensitivity, while the HiResolution processing strategy can deliver more detailed temporal information for Advanced Bionics cochlear implant users. The goal of this study was to develop a new sound processing strategy by maximizing the spectral benefit of Fidelity120 and the temporal benefit of HiResolution to improve both aspects of hearing. Using acoustic simulations of Fidelity120 and HiResolution strategies, a dual-processing strategy was created by combining Fidelity120 in the low frequency channels and HiResolution in the high frequency channels. Compared to Fidelity120, the dual processing provided an improvement in performance for Schroeder-phase discrimination at 200-Hz and temporal modulation detection at 200-Hz with the cost of a slightly decreased performance for spectral-ripple discrimination relative to Fidelity120. Spectral-ripple discrimination was better with the dual processing than with HiResolution. However, no benefit for speech perception in noise was found for the dual processing strategy over Fidelity 120 or HiResolution in our preliminary tests. Some other more optimal combination of Fidelity120 and HiResolution may be required to maximize the spectral and temporal benefits to yield improved speech perception.
cochlear implant; spectral and temporal sensitivity; sound processing strategy
Previous studies have found a significant correlation between spectral-ripple discrimination and speech and music perception in cochlear implant (CI) users. This relationship could be of use to clinicians and scientists who are interested in using spectral-ripple stimuli in the assessment and habilitation of CI users. However, previous psychoacoustic tasks used to assess spectral discrimination are not suitable for all populations, and it would be beneficial to develop methods that could be used to test all age ranges, including pediatric implant users. Additionally, it is important to understand how ripple stimuli are processed in the central auditory system and how their neural representation contributes to behavioral performance. For this reason, we developed a single-interval, yes/no paradigm that could potentially be used both behaviorally and electrophysiologically to estimate spectral-ripple threshold. In experiment 1, behavioral thresholds obtained using the single-interval method were compared to thresholds obtained using a previously established three-alternative forced-choice method. A significant correlation was found (r = 0.84, p = 0.0002) in 14 adult CI users. The spectral-ripple threshold obtained using the new method also correlated with speech perception in quiet and noise. In experiment 2, the effect of the number of vocoder-processing channels on the behavioral and physiological threshold in normal-hearing listeners was determined. Behavioral thresholds, using the new single-interval method, as well as cortical P1-N1-P2 responses changed as a function of the number of channels. Better behavioral and physiological performance (i.e., better discrimination ability at higher ripple densities) was observed as more channels added. In experiment 3, the relationship between behavioral and physiological data was examined. Amplitudes of the P1-N1-P2 “change” responses were significantly correlated with d′ values from the single-interval behavioral procedure. Results suggest that the single-interval procedure with spectral-ripple phase inversion in ongoing stimuli is a valid approach for measuring behavioral or physiological spectral resolution.
spectral-ripple discrimination; behavioral and physiological measure; cochlear implant; auditory change response; auditory cortex
Arsenic trioxide (As2O3) is a well-known and effective treatment that can result in clinical remission for patients diagnosed with acute promyelocytic leukemia (APL). The biologic efficacy of As2O3 in APL and solid tumor cells has been explained through its actions on anti-proliferation, anti-angiogenesis, and apoptotic signaling pathways. We theorize that As2O3 activates a pathway that disrupts microtubule dynamics forming abnormal, nonfunctioning mitotic spindles, thus preventing cellular division. In this study, we investigated how As2O3 induces apoptosis by causing microtubule dysfunction.
Cultured NB4 cells were treated with As2O3, paclitaxel, and vincristine. Flow cytometric analysis was then performed. An MTT assay was used to determine drug-mediated cytotoxicity. For tubulin polymerization assay, each polymerized or soluble tubulin was measured. Microtubule assembly-disassembly was measured using a tubulin polymerization kit. Cellular microtubules were also observed with fluorescence microscopy.
As2O3 treatment disrupted tubulin assembly resulting in dysfunctional microtubules that cause death in APL cells. As2O3 markedly enhanced the amount of depolymerized microtubules. The number of microtubule posttranslational modifications on an individual tubulin decreased with As2O3 concentration. Immunocytochemistry revealed changes in the cellular microtubule network and formation of polymerized microtubules in As2O3-treated cells.
The microtubules alterations found with As2O3 treatment suggest that As2O3 increases the depolymerized forms of tubulin in cells and that this is potentially due to arsenite's negative effects on spindle dynamics.
Acute promyelocytic leukemia; Arsenic trioxide; Tubulin; Apoptosis; Antimitotic agents
Compare auditory performance of Hybrid and standard cochlear implant users with psychoacoustic measures of spectral and temporal sensitivity and correlate with measures of clinical benefit.
Tertiary academic medical center.
Hybrid cochlear implant users between 12 and 33 months post implantation. Hybrid recipients all had preservation of low-frequency hearing.
Administration of psychoacoustic, music perception, and speech reception in noise tests.
Main outcome measures
Performance on spectral-ripple discrimination, temporal modulation detection, Schroeder-phase discrimination, Clinical Assessment of Music Perception (CAMP), and speech reception in steady-state noise tests.
CAMP pitch performance at 262 Hz was significantly better in Hybrid users compared to standard implant controls. There was a near significant difference on speech reception in steady-state noise. Surprisingly, neither Schroeder-phase discrimination at two frequencies nor temporal modulation detection thresholds across a range of frequencies revealed any advantage in Hybrid users. This contrasts with spectral-ripple measures that were significantly better in the Hybrid group. The spectral-ripple advantage was preserved even when using only residual hearing.
These preliminary data confirm existing data demonstrating that residual low-frequency acoustic hearing is advantageous for pitch perception. Results also suggest that clinical benefits enjoyed by Hybrid recipients are due to improved spectral discrimination provided by the residual hearing. No evidence indicated that residual hearing provided temporal information beyond that provided by electrical stimulation.
electroacoustic; Hybrid cochlear implant; spectral; temporal
We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF-α, IFN-γ, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-α, IFN-γ, or IL-6 level was observed between groups, although leptin was significantly lower in cachectic patients than in the comparison group (15.3 ± 19.5 vs 80.9 ± 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia.
Adiponectin; Cachexia; Cytokines; Ghrelin; Leptin
The prognosis of gastric cancer patients with bone marrow metastases is extremely poor. The current study was conducted to evaluate the clinical outcomes of advanced gastric cancer patients with bone marrow metastases.
Materials and Methods
We retrospectively reviewed the medical records of 26 advanced gastric cancer patients with bone marrow metastases who were treated at Soonchunhyang University Hospital between September 1986 and February 2009.
The median age was 46 years (range, 24 to 61 years). All patients had poorly differentiated adenocarcinoma, including 17 signet ring cell carcinomas. The majority of the patients had thrombocytopenia, anemia, and elevated lactate dehydrogenase levels. Sixteen patients (61.5%) received palliative chemotherapy (median, 4 cycles; range, 1 to 13 cycles). The median overall survival after detection of bone marrow metastases for the cohort of patients was 37 days (95% confidence interval, 12.5 to 61.5 days). The median overall survival after detection of bone marrow involvement was 11 days in the best supportive care group (range, 2 to 34 days) and 121 days (range, 3 to 383 days) in the palliative chemotherapy group (p<0.001). The causes of death were tumor progression (11 patients, 45%), brain hemorrhage (6 patients, 25%), infection (5 patients, 21%), and disseminated intravascular coagulation (1 patient, 4%). There were no chemotherapy-related deaths.
Palliative chemotherapy could be considered in advanced gastric cancer patients with bone marrow metastases as a treatment option.
Stomach neoplasms; Bone marrow; Neoplasm metastasis; Drug therapy
Assessment of cochlear implant outcomes centers around speech discrimination. Despite dramatic improvements in speech perception, music perception remains a challenge for most cochlear implant users. No standardized test exists to quantify music perception in a clinically practical manner. This study presents the University of Washington Clinical Assessment of Music Perception (CAMP) test as a reliable and valid music perception test for English-speaking, adult cochlear implant users.
Forty-two cochlear implant subjects were recruited from the University of Washington Medical Center cochlear implant program and referred by two implant manufacturers. Ten normal-hearing volunteers were drawn from the University of Washington Medical Center and associated campuses. A computer-driven, self-administered test was developed to examine three specific aspects of music perception: pitch direction discrimination, melody recognition, and timbre recognition. The pitch subtest used an adaptive procedure to determine just-noticeable differences for complex tone pitch direction discrimination within the range of 1 to 12 semitones. The melody and timbre subtests assessed recognition of 12 commonly known melodies played with complex tones in an isochronous manner and eight musical instruments playing an identical five-note sequence, respectively. Testing was repeated for cochlear implant subjects to evaluate test-retest reliability. Normal-hearing volunteers were also tested to demonstrate differences in performance in the two populations.
For cochlear implant subjects, pitch direction discrimination just-noticeable differences ranged from 1 to 8.0 semitones (Mean = 3.0, SD = 2.3). Melody and timbre recognition ranged from 0 to 94.4% correct (mean = 25.1, SD = 22.2) and 20.8 to 87.5% (mean = 45.3, SD = 16.2), respectively. Each subtest significantly correlated at least moderately with both Consonant-Nucleus-Consonant (CNC) word recognition scores and spondee recognition thresholds in steady state noise and two-talker babble. Intraclass coefficients demonstrating test-retest correlations for pitch, melody, and timbre were 0.85, 0.92, and 0.69, respectively. Normal-hearing volunteers had a mean pitch direction discrimination threshold of 1.0 semitone, the smallest interval tested, and mean melody and timbre recognition scores of 87.5 and 94.2%, respectively.
The CAMP test discriminates a wide range of music perceptual ability in cochlear implant users. Moderate correlations were seen between music test results and both Consonant-Nucleus-Consonant word recognition scores and spondee recognition thresholds in background noise. Test-retest reliability was moderate to strong. The CAMP test provides a reliable and valid metric for a clinically practical, standardized evaluation of music perception in adult cochlear implant users.
Primary intestinal non-Hodgkin lymphoma (NHL) is a heterogeneous disease with regard to anatomic and histologic distribution. Thus, analyses focusing on primary intestinal NHL with large number of patients are warranted.
We retrospectively analyzed 581 patients from 16 hospitals in Korea for primary intestinal NHL in this retrospective analysis. We compared clinical features and treatment outcomes according to the anatomic site of involvement and histologic subtypes.
B-cell lymphoma (n = 504, 86.7%) was more frequent than T-cell lymphoma (n = 77, 13.3%). Diffuse large B-cell lymphoma (DLBCL) was the most common subtype (n = 386, 66.4%), and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) was the second most common subtype (n = 61, 10.5%). B-cell lymphoma mainly presented as localized disease (Lugano stage I/II) while T-cell lymphomas involved multiple intestinal sites. Thus, T-cell lymphoma had more unfavourable characteristics such as advanced stage at diagnosis, and the 5-year overall survival (OS) rate was significantly lower than B-cell lymphoma (28% versus 71%, P < 0.001). B symptoms were relatively uncommon (20.7%), and bone marrow invasion was a rare event (7.4%). The ileocecal region was the most commonly involved site (39.8%), followed by the small (27.9%) and large intestines (21.5%). Patients underwent surgery showed better OS than patients did not (5-year OS rate 77% versus 57%, P < 0.001). However, this beneficial effect of surgery was only statistically significant in patients with B-cell lymphomas (P < 0.001) not in T-cell lymphomas (P = 0.460). The comparison of survival based on the anatomic site of involvement showed that ileocecal regions had a better 5-year overall survival rate (72%) than other sites in consistent with that ileocecal region had higher proportion of patients with DLBCL who underwent surgery. Age > 60 years, performance status ≥ 2, elevated serum lactate dehydrogenase, Lugano stage IV, presence of B symptoms, and T-cell phenotype were independent prognostic factors for survival.
The survival of patients with ileocecal region involvement was better than that of patients with involvement at other sites, which might be related to histologic distribution, the proportion of tumor stage, and need for surgical resection.
intestine; non-Hodgkin lymphoma; prognosis; histopathology
Severe asthma is characterized by high medication requirements to maintain good disease control or by persistent symptoms despite high medication use. The transfer of bone marrow-derived mesenchymal stem cells (BMDMSCs) to the injured lungs is a possible treatment for severe asthma. This study investigated the therapeutic effects of BMDMSCs in airway remodeling and inflammation in an experimental toluene diisocyanate (TDI)-induced asthma animal model of severe asthma.
BMDMSCs were transferred into rats after TDI inhalation. Bronchoalveolar lavage (BAL) cell profiles, histological changes including an inflammatory index and goblet cell hyperplasia, and the airway response to methacholine using plethysmography were analyzed. Smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA) protein expression were observed in lung tissue using immunohistochemical staining. The collagen content was measured in lung tissue sections and lung extracts using Masson's trichrome staining and an immunoassay kit.
The numbers of inflammatory cells in BAL fluid, histological inflammatory index, airway response to methacholine, number of goblet cells, and amount of collagen were increased in TDI-treated rats compared with sham rats (P=0.05-0.002). BMDMSC transfer significantly reduced the TDI-induced increase in the inflammatory index and numbers of eosinophils and neutrophils in BAL fluid to levels seen in sham-treated rats (P<0.05). BMDMSC transfer significantly reduced the number of goblet cells, collagen deposition, and immune staining for SMA and PCNA with concomitant normalization of the airway response to methacholine.
The systemic transfer of BMDMSCs effectively reduced experimental TDI-induced airway inflammation and remodeling and airway hyperreactivity.
Airway remodeling; asthma; collagen; stem cells; TDI
We investigated the effects of mesenchymal stem cells (MSCs) on wound healing using a three-dimensional (3D) collagen gel scaffold. Three circular full-thickness skin defects were created on the back of Sprague-Dawley rats. One site was covered with a 3D collagen gel containing 2 × 106 MSCs (MSCs+/3D collagen+). Another site was replaced with a 3D collagen gel without MSCs and the third site was left empty. The wound size was significantly reduced in the MSCs+/3D collagen+ sites. MSCs+/3D collagen+ sites exhibited the most neovascularization. FISH showed that Y-chromosome possessing cells were found within the dermis of MSCs+/3D collagen+ sites. Gelatin zymography revealed that the most intense expression of MMP-9 was detected early in the MSCs+/3D collagen+ sites. Our results indicate that MSCs upregulate the early expression of MMP-9 which induces the early mobilization of VEGF. Thus, MSCs appear to accelerate significantly wound healing via early activation of MMP-9 and VEGF.
Mesenchymal Stem Cells; Wound Healing
Current chemotherapeutics for treating locally advanced or metastatic soft tissue sarcomas (STS) are limited. Accordingly, the present in vitro study was conducted to evaluate the effects of treatment of STS cells with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) applied as a single agent or in combination with a proteasome inhibitor, MG132.
Materials and Methods
Sensitivity to TRAIL and activity of TRAIL-induced apoptotic pathways were analyzed in four STS cell lines: HTB-82 (rhabdomyosarcoma), HT-1080 (fibrosarcoma), HTB-93 (synovial sarcoma), and HTB-94 (chondrosarcoma). Reduction of the dye dimethylthiazolyl 2,5 diphenyltetrazolium bromide (MTT) was used to evaluate cytotoxic activity; western blots were used to evaluate TRAIL-induced apoptosis.
TRAIL induced apoptosis in HTB-93 cells, but had little effect in HTB-82, HT-1080, or HTB-94 cells. Expression of TRAIL receptor-1 and -2 did not correlate with sensitivity to TRAIL. Co-incubation of cells with TRAIL and a proteasome inhibitor, MG132, augmented the apoptotic effect of TRAIL in both TRAIL-sensitive and TRAIL-resistant cells. This effect was due to up-regulation of TRAIL receptors and members of the pro-apoptotic BCL-2 family by MG132.
These data show that combining TRAIL with MG132 enhances apoptosis and overcomes TRAIL resistance. This restoration of TRAIL sensitivity occurs through an increase in the expression of death receptor 5 and of pro-apoptotic BCL-2 family members such as BAX.
TNF-related apoptosis-inducing ligand; MG 132; Soft tissue sarcoma; Apoptosis
Experienced users of the Clarion cochlear implant were tested acutely with the HiResolution (HiRes) and HiRes Fidelity120 (F120) processing strategies. Three psychophysically-based tests were used including spectral-ripple discrimination, Schroeder-phase discrimination and temporal modulation detection. Three clinical outcome measures were used including consonant-nucleus-consonant (CNC) word recognition in quiet, word recognition in noise and the clinical assessment of music perception (CAMP). Listener's spectral-ripple discrimination ability improved with F120, but Schroeder-phase discrimination was worse with F120 than with HiRes. Listeners who had better than average acuity showed the biggest effects. There were no significant effects of the processing strategy on any of the clinical abilities nor on temporal modulation detection. Additionally, the listeners' day-to-day clinical strategy did not appear to influence the result suggesting that experience with the strategies did not play a significant role. The results underscore the value of acoustic psychophysical measures through the sound processor as a tool in clinical research, because these measures are more sensitive to changes in the processing strategies than traditional clinical measures, e.g. speech understanding. The measures allow for the evaluation of sensitivity to specific acoustic attributes revealing the extent to which different processing strategies affect these basic abilities and could thus improve the efficiency of the development of processing strategies.
This study investigated the safety and effectiveness of each type of central venous catheters (CVC) in patients with cancer. We prospectively enrolled patients with cancer who underwent catherization involving a subclavian venous catheter (SVC), peripherally inserted central venous catheter (PICC), or chemo-port (CP) in our department. From March 2007 to March 2009, 116 patients underwent 179 episodes of catherization. A SVC was inserted most frequently (46.4%). Fifty-four complications occurred (30.1%): infection in 23 cases, malpositioning or migration of the tip in 18 cases, thrombosis in eight cases, and bleeding in five cases. Malpositioning or migration of the tip occurred more frequently with a PICC (P<0.001); infection occurred more often with a tunneled catheter (P=0.028) and was observed more often in young patients (P=0.023). The catheter life span was longer for patients with solid cancer (P=0.002) than for those with hematologic cancer, with a CP (P<0.001) than a PICC or SVC, and for an indwelling catheter with image guidance (P=0.014) than a blind procedure. In conclusion, CP is an effective tool for long term use and the fixation of tip is important for the management of PICC.
Catheterization, Central Venous; Complications; Neoplasms
Type B lactic acidosis is a rare condition in patients with solid tumors or hematological malignancies. Although there have been several theories to explain its mechanism, the exact cause of lactic acidosis remains to be discovered. Lactic acidosis is usually related to increased tumor burden in patients with malignancy. We experienced a case of lactic acidosis in a 39-year-old man who visited an emergency room because of dyspnea, and the cause of lactic acidosis turned out to be recurrent acute leukemia. Chemotherapy relieved the degree of lactic acidosis initially, but as the disease progressed, lactic acidosis became aggravated. Type B lactic acidosis can be a clinical presentation of acute exacerbation of acute leukemia.
Lactic acidosis; leukemia
Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoproliferative disorders associated with immunosuppression and Epstein-Barr virus infection. PTLD is classified into three major categories: early lesions, polymorphic PTLD, and monomorphic PTLD. The majority of monomorphic PTLD cases are non-Hodgkin's lymphoma of B-cell origin. This retrospective study was conducted to investigate the incidence, clinical manifestation, treatment, and outcomes of monomorphic PTLD among 5,817 recipients of solid organ or allogeneic hematopoietic stem cell transplantation from five institutions. Fourteen patients with monomorphic PTLD were identified (male:female 11:3; median age 42.6 yr, range 24-60). The overall incidence rate was 0.24%. The most common disease type was diffuse large B cell lymphoma (n=7). The median time between the transplant and diagnosis of PTLD was 85.8 months. However, all cases of PTLD after allogeneic hematopoietic stem cell transplantation occurred within 1 yr after transplantation. Ten of the 14 patients had EBV-positive tumor. Fourteen patients received combination systemic chemotherapy and four patients were treated with radiation therapy. Ten patients achieved a complete response (CR) and two patients a partial response (PR). The median follow-up period for surviving patients was 36.6 months. Nine patients remain alive (eight CR, one PR). Nine of 11 solid organ transplantations preserved graft function. The present study indicates a lower incidence rate and a longer median time before the development of PTLD than those of previous reports. Careful monitoring was needed after allogeneic hematopoietic stem cell transplantation for PTLD.
Monomorphic Post-transplant Lymphoproliferative Disorders
A 65-yr-old woman presented 17 yr status post-hysterectomy with bilateral ovarian salpingo-oophorectomy, attributable to ovarian cancer. She was admitted to our hospital, with multiple cystic liver masses and multiple large seeded masses in her abdomen and pelvic cavity. Histological examination of the pelvic masses demonstrated granulosa cell tumors. After two courses of systemic combination chemotherapy, with paclitaxel and carboplatin, the masses in the abdomen and pelvic cavity increased, and debulking surgery also failed because of peritoneal dissemination with severe adhesion. Finally, she underwent palliative radiotherapy for only the pelvic masses obstructing the urinary and GI tracts, and monthly hormonal therapy with a gonadotrophin-releasing hormone agonist; leuprorelin 3.75 mg IM. Subsequently, multiple masses beyond the range of the radiation as well as those within the radiotherapy field partially decreased. This partial response had been maintained for more than 8 months as of the last follow-up visit. Owing to its long and indolent course and the low metabolic rate of the tumors, advanced or recurrent granulosa cell tumor (GCT) requires treatment options beyond chemotherapy, surgery, and radiotherapy. Hormonal agents may provide another treatment option for advanced or recurrent GCT in those who are not candidates for surgery, chemotherapy, or radiotherapy.
Granulosa Cell Tumor; Hormone Therapy; Leuprolide
This study evaluated the maximal attainable performance of speech enhancement strategies based on coherent modulation filtering. An optimal adaptive coherent modulation filtering algorithm was designed to enhance known signals from a target talker in two-talker babble noise. The algorithm was evaluated in a closed-set, speech-recognition-in-noise task. The speech reception threshold (SRT) was measured using a one-down, one-up adaptive procedure. Five hearing-impaired subjects and five cochlear implant users were tested in three processing conditions: (1) original sounds; (2) fixed coherent modulation filtered sounds; and (3) optimal coherent modulation filtered sounds. Six normal-hearing subjects were tested with a 6-channel cochlear implant simulation of sounds processed in the same three conditions. Significant improvements in SRTs were observed when the signal was processed with the optimal coherent modulation filtering algorithm. There was no benefit when the signal was processed with the fixed modulation filter. The current study suggested that coherent modulation filtering might be a promising method for front-end processing in hearing aids and cochlear implants. An approach such as hidden Markov models could be used to generalize the optimal coherent modulation filtering algorithm to unknown utterances and to extend it to open-set speech.
Coherent modulation filter; speech enhancement; hearing aids; cochlear implants
Speech perception ability in noise is one of the most practical measures of success with a cochlear implant; however, with experience, this ability can change dramatically over time, making it a less than ideal tool for comparing performance among different processing strategies. This study examined performance on a spectral discrimination task and compared it to speech perception in noise. An adaptive procedure was used to determine the spectral-ripple density that subjects could discriminate. A closed-set, forced-choice adaptive procedure was used to determine speech reception thresholds for words in two-talker babble and in speech-shaped, steady-state noise. Spectral-ripple thresholds (ripples/octave) were significantly correlated with speech reception thresholds (dB SNR) in noise for 29 cochlear implant users (r = −0.55, p = 0.002 in two-talker babble; r = −0.62, p = 0.0004 in steady-state noise), demonstrating that better spectral resolution was associated with better speech perception in noise. A significant correlation was also found between the spectral-ripple discrimination ability and word recognition in quiet (r = 0.50, p = 0.009). In addition, test–retest reliability for spectral-ripple discrimination was good, and no learning was observed. The present study demonstrates that the spectral-ripple discrimination test, which is time efficient and nonlinguistic, would be a useful tool to evaluate cochlear implant performance with different signal processing strategies.
spectral resolution; speech perception in noise; cochlear implant
This study evaluated the role of temporal fine structure in the lateralization and understanding of speech in six normal-hearing listeners. Interaural time differences (ITDs) were introduced to invoke lateralization. Speech reception thresholds (SRTs) were evaluated in backgrounds of two-talker babble and speech-shaped noise. Two-syllable words with ITDs of 0 and 700 μs were used as targets. A vocoder technique, which systematically randomized fine structure, was used to evaluate the effects of fine structure on these tasks. Randomization of temporal fine structure was found to significantly reduce the ability of normal-hearing listeners to lateralize words, although for many listeners, good lateralization performance was achieved with as much as 80% fine-structure randomization. Most listeners demonstrated some rudimentary ability to lateralize with 100% fine-structure randomization. When ITDs were 0 μs, randomization of fine structure had a much greater effect on SRT in two-talker babble than in speech-shaped noise. Binaural advantages were also observed. In steady noise, the difference in SRT between words with 0- vs 700-μs ITDs was, on average, 6 dB with no fine-structure randomization and 2 dB with 100% fine-structure randomization. In two-talker babble this difference was 1.9 dB and, for most listeners, showed little effect of the degree of fine-structure randomization. These results suggest that (1) improved delivery of temporal fine structure would improve speech understanding in noise for implant recipients, (2) bilateral implant recipients might benefit from temporal envelope ITDs, and (3) improved delivery of temporal information could improve binaural benefits.
binaural hearing; fine structure; cochlear implant