Application of image-recognition techniques to automated micronucleus detection in the in vitro micronucleus assay.

BACKGROUND: An in vitro micronucleus assay is a standard genotoxicity test. Although the technique and interpretation of the results are simple, manual counting of the total and micronucleus-containing cells in a microscopic field is tedious. To address this issue, several systems have been developed for quick and efficient micronucleus counting, including flow cytometry and automated detection based on specialized software and detection systems that analyze images. RESULTS: Here, we present a simple and effective method for automated micronucleus counting using image recognition technology. Our process involves separating the RGB channels in a color micrograph of cells stained with acridine orange. The cell nuclei and micronuclei were detected by scaling the G image, whereas the cytoplasm was recognized from a composite image of the R and G images. Finally, we identified cells with overlapping cytoplasm and micronuclei as micronucleated cells, and the application displayed the number of micronucleated cells and the total number of cells. Our method yielded results that were comparable to manually measured values. CONCLUSIONS: Our micronucleus detection (MN/cell detection software) system can accurately detect the total number of cells and micronucleus-forming cells in microscopic images with the same level of precision as achieved through manual counting. The accuracy of micronucleus numbers depends on the cell staining conditions; however, the software has options by which users can easily manually optimize parameters such as threshold, denoise, and binary to achieve the best results. The optimization process is easy to handle and requires less effort, making it an efficient way to obtain accurate results.

Calcium pyrophosphate crystal arthritis associated with immune checkpoint inhibitor successfully treated with intra-articular glucocorticoid: A case report.

Immune checkpoint inhibitors (ICIs) sometimes induce immune-related adverse events (irAEs), and arthritis is one of the irAE symptoms. Recently, crystal-induced arthritis, such as calcium pyrophosphate (CPP) crystal deposition disease and gout, has been reported to occur after ICI administration. However, the distinction between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis is difficult because their symptoms are similar. Besides, optimal treatment for ICI-associated crystal arthritis has not been established. Here, we report a patient who developed CPP crystal arthritis twice after pembrolizumab (ICI) administration and was successfully treated with intra-articular glucocorticoid injection. He suffered arthritis and acute interstitial nephritis simultaneously after ICI administration. Musculoskeletal ultrasound of his affected joint suggests that his arthritis was crystal-induced arthritis, and arthrocentesis detected CPP crystal in synovial fluid. Thus, we diagnosed his arthritis as ICI-associated cystal arthritis. Therefore, our case encourages the use of musculoskeletal ultrasound in patients with arthritis after treatment with ICI because it may distinguish between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis. Besides, ICI-associated crystal arthritis could be treatable by intra-articular glucocorticoid injection.

Benefits of amplification for unaided speech discrimination in age-related hearing loss with flat type audiogram.

OBJECTIVE: The present study aimed to investigate whether hearing aid use can induce improvement as acclimatization effect in unaided speech perception in patients with age-related hearing loss. METHODS: Fifty ears in 41 patients (age range: 65-91 years) diagnosed as age-related hearing loss were enrolled in this study. They used hearing aids for more than 8 hours per day. Unaided speech audiometry using 67-S Japanese monosyllabic word list was performed one or two years after the commencement of hearing aid use. The changes in the unaided speech discrimination score before and after the commencement of hearing aid use were analyzed. To investigate factors for improvement, the patients' backgrounds in terms of age, sex, pure tone average, unaided maximum speech discrimination score, fitting period (one year/two years), fitting ear (bilateral/unilateral), audiogram type (flat-type/other-type), and the level of amplification were also analyzed. RESULTS: Significant improvement in the unaided speech discrimination score after hearing aid use was seen only in the flat-type audiogram group. More than half of older patients in the flat-type audiogram group improved their unaided maximum speech discrimination score 10 % or more. The analysis of aided hearing thresholds revealed that the flat-type audiogram group had significantly lower thresholds of 3kHz and 4kHz than the other-type audiogram group. The age, sex, pure tone average, fitting period, fitting ear, functional gain were not influential factors for improvement. On the other hand, unaided maximum speech discrimination score before using hearing aid and aided hearing threshold at 4kHz had a negative correlation with improvement. CONCLUSION: The findings suggested that older patients with age-related hearing loss whose audiogram is a flat type can benefit from amplification as means of improving their unaided speech perception since flat-type audiogram can be more easily adjusted to sufficiently amplify speech sound at high frequencies. It should be considered that the potential for experience-dependent plasticity is retained even in older adults.

Septic arthritis induced by Streptococcus pneumoniae occurring in rheumatoid arthritis treated with abatacept and methotrexate: A case report.

Septic arthritis occurs more frequently in elderly patients with rheumatoid arthritis (RA), with Staphylococcus aureus being the most common aetiologic agent. Rarely, Streptococcus pneumoniae (pneumococcus) is the cause of septic arthritis. Biological disease-modifying antirheumatic drugs (bDMARDs) are widely used in RA, but it is unknown whether bDMARDs could be a risk factor for pneumococcal septic arthritis in such patients. Here, we report the case of a patient with RA treated with bDMARDs (abatacept) who developed pneumococcal septic arthritis. The patient is a 64-year-old female complicated with RA for >10 years. She was treated with abatacept and methotrexate and has been in remission for 2 years. She had not received any pneumococcal vaccination. She consulted at our hospital for left ankle arthralgia and fever. Blood culture and puncture of the left ankle joints detected pneumococcus, and the pneumococcal urine antigen test was positive. The patient was diagnosed with pneumococcal septic arthritis, and she recovered after the administration of antibiotics. This is the first case report discussing these circumstances, suggesting that bDMARDs may be a risk of pneumococcal septic arthritis in patients with RA. To prevent this, pneumococcal vaccination should be encouraged in such patients. Furthermore, if RA is in remission, we may consider the spacing or withdrawal of bDMARDs to avoid severe infection.

Prognosis of spontaneous pneumomediastinum occurring in dermatomyositis or polymyositis patients with interstitial lung disease according to antimelanoma differentiation-associated gene 5 antibody status: a retrospective cohort study.

OBJECTIVES: Spontaneous pneumomediastinum (SPNM) historically has been considered a poor prognostic factor in dermatomyositis/polymyositis patients complicated with interstitial lung disease (ILD). However, there is a lack of actual data regarding the association between SPNM occurrence and mortality in dermatomyositis/polymyositis patients. This study aimed to assess the association between SPNM occurrence and mortality in myositis patients with ILD according to antimelanoma differentiation-associated gene 5 (MDA5) antibody status. METHODS: Dermatomyositis/polymyositis patients with ILD who were hospitalised at five Japanese hospitals from 2016 to 2020 were included in this retrospective observational study. We collected data about baseline characteristics including myositis-specific autoantibodies, treatments, SPNM and death within 1 year from therapy initiation or strengthening. Baseline characteristics and outcomes were compared between patients with and without SPNM (the SPNM group and the non-SPNM group, respectively). RESULTS: A total of 119 patients were analysed. SPNM occurred in 23 patients, and 15 patients died. Fifteen patients with SPNM were anti-MDA5 antibody positive. The mortality rate was significantly higher in the SPNM group (34.8%) than in the non-SPNM group (7.3%) (p=0.001). All deaths in the SPNM group occurred in anti-MDA5 antibody-positive patients (8/15), whereas none of the anti-MDA5 antibody-negative patients in the SPNM group died (0/8). In anti-MDA5 antibody-positive patients, the mortality rate was significantly higher in patients with SPNM occurrence (53.3%) than in those without SPNM occurrence (4.0%) (p=0.001). CONCLUSION: SPNM occurred more frequently in anti-MDA5 antibody-positive than in anti-MDA5 antibody-negative myositis patients. SPNM occurrence was associated with higher mortality risk, especially in anti-MDA5 antibody-positive patients.

Efficacy and safety of dose escalation of tofacitinib in refractory anti-MDA5 antibody-positive dermatomyositis.

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is frequently complicated with rapidly progressive-interstitial lung disease (RP-ILD). The prognosis of MDA5-DM with RP-ILD is mostly poor despite intensive treatment with a combination of high-dose glucocorticoids and single conventional immunosuppressants. It was reported that the triple therapy (high-dose glucocorticoids, cyclophosphamide and tacrolimus) was more effective than a combination of high-dose glucocorticoids and stepwise addition of immunosuppressants. In addition, the efficacy of tofacitinib 10 mg/day for MDA5-DM with RP-ILD refractory to the triple therapy was suggested. However, the effect of those therapies was evaluated only in comparison to the historical control. Moreover, more importantly, there are still refractory patients even if treated with those therapies. In this case series, we report six MDA5-DM cases with RP-ILD in which the dose of tofacitinib was increased from 10 mg to 20 mg/day due to poor response to the triple therapy, followed by tofacitinib 10 mg/day. Four of six patients improved after dose escalation of tofacitinib, while two non-responders died. All six patients developed at least one infection including five cases of cytomegalovirus reactivation, one pulmonary aspergillosis, one herpes zoster and one herpes simplex keratitis. These cases suggest that the dose escalation of tofacitinib can be an option for MDA5-DM patients refractory to 10 mg/day of tofacitinib and other immunosuppressants although the risk of infection is a concern. The risk-benefit balance of the dose escalation of tofacitinib should be carefully assessed in each case.

[Effects of Phantom Factor on Shape Differences in Tomotherapy Water-equivalent Phantoms].

PURPOSE: The purpose of this study was to evaluate the effects of phantom factor on the verification of measured doses using cheese phantoms in tomotherapy. METHODS: Two plans for dose verification (plan classes and plan class phantom sets with a virtual organ at the risk set) were evaluated. The calculated and measured doses were compared with and without the phantom factor using cheese phantoms. Additionally, the phantom factor was evaluated for two conditions (TomoHelical/TomoDirect) in clinical cases (breast and prostate). RESULTS: When applying a phantom factor of 1.007, the deviation between the calculated and measured doses increased in Plan-Class and TomoDirect, decreased in TomoHelical, and increased in both clinical cases. CONCLUSION: When conducting dose verification, the effects of one phantom factor on measurement conditions may differ depending on when phantom factors were obtained (irradiation technique and irradiation field). It is therefore necessary to consider changes in measured doses due to changes in phantom scattering.

IL-21 is required for the maintenance and pathogenesis of murine Vγ4+ IL-17-producing γδT cells.

Murine IL-17-producing γδT (γδT17) cells are divided into two subsets: natural γδT17 (nγδT17) cells, whose development is restricted to the fetal thymus, and inducible γδT17 cells, which require antigen exposure for their IL-17 production and are presumed to develop from Rorc + Il17a - CCR9 + immature γδT17 cells in the adult thymus and whose T cell receptor (TCR) is biased toward Vγ4. Although IL-23 is known to be involved in developing γδT17 cells, the roles of other cytokines, such as IL-21, which is involved in developing Th17 cells like IL-23, in the development, maintenance, and pathophysiology of γδT17 cells remain unknown. Here, we show that IL-21 is dispensable for the fetal thymic development of nγδT17 cells but is required for the peripheral maintenance of Vγ4+nγδT17 cells. Upon stimulation with γδTCR, IL-1 plus IL-21 induces the proliferation of Vγ4+nγδT17 cells via STAT3 as effectively as IL-1 plus IL-23. Using bone marrow chimeric mice, we demonstrated that immature γδT17 cells are produced de novo in the adult mice from donor adult bone marrow cells and that IL-21 is dispensable for their development. Instead, IL-21 is required to expand newly induced Vγ4+γδT17 cells in the periphery upon immunization. Finally, using adoptive transfer experiments of γδT17 cells, we found that IL-21 receptors on γδT17 cells are involved in maintaining Vγ4+γδT17 cells, subsequent infiltration of Th17 cells into the spinal cord, and exacerbation of experimental autoimmune encephalomyelitis. Collectively, IL-21 plays a vital role in the maintenance and pathogenesis of Vγ4+γδT17 cells.

Immune checkpoint inhibitor-induced refractory polyarthritis rapidly improved by sarilumab and monitoring with joint ultrasonography: A case report.

RATIONALE: Immune checkpoint inhibitors (ICIs) have shown efficacy for the treatment of various kinds of malignant tumors. However, ICIs can cause immune-related adverse events, such as arthritis. Nevertheless, the treatment of ICI-induced arthritis has not been established yet. Here we report a case of ICI-induced polyarthritis successfully treated using sarilumab and monitored using joint ultrasonography. PATIENT CONCERNS: A 61-year-old man presented with polyarthritis. He had been treated with nivolumab for recurrent renal cell carcinoma 11 months before. He developed ICI-induced nephritis (proteinuria and elevated serum creatinine) 3 months before, which resolved after discontinuing nivolumab for 1 month. Two months after resuming nivolumab, he developed polyarthralgia and joint swelling, which were suspected to be associated with nivolumab administration, and hence we discontinued nivolumab again. Laboratory tests revealed elevated C-reactive protein level and erythrocyte sedimentation rate, but were negative for rheumatoid factor and anti-cyclic citrullinated peptide antibody. Joint ultrasonography revealed active synovitis in several joints, but a joint X-ray revealed no bone erosion. DIAGNOSES: We diagnosed polyarthritis as ICI-induced arthritis because the findings were not typical of rheumatoid arthritis (no bone erosion and seronegativity) and the patient had already developed other immune-related adverse events (ICI-induced nephritis). INTERVENTIONS: After discontinuation of nivolumab, we started treatment with 15 mg daily prednisolone and 1000 mg daily sulfasalazine, although it was ineffective. Hence, we initiated 200 mg biweekly sarilumab. OUTCOMES: Following sarilumab administration, polyarthritis improved rapidly, and joint ultrasonography confirmed the rapid improvement of synovitis. Hence, we tapered off the glucocorticoid treatment. No recurrence of renal cell carcinoma was noted for 2 years after the initiation of sarilumab despite no anti-tumor therapy. LESSONS: Sarilumab may serve as a good treatment option for treating refractory ICI-induced polyarthritis. Joint ultrasonography may contribute to the evaluation of ICI-induced polyarthritis and monitoring the effects of treatments.

Association of low-dose glucocorticoid use and infection occurrence in systemic lupus erythematosus patients: a prospective cohort study.

BACKGROUND: Infection is a major cause of mortality in patients with systemic lupus erythematosus (SLE). Therefore, minimizing the risk of infection is an important clinical goal to improve the long-term prognosis of SLE patients. Treatment with ≥7.5 mg prednisolone (PSL) or equivalent has been reported to increase the risk of infections. However, it remains unclear whether <7.5 mg PSL or equivalent dose affects the risk of infection in SLE patients. This study evaluated the association between the occurrence of infection in patients with SLE and low-dose glucocorticoid (GC) usage, especially <7.5 mg PSL or equivalent, to explore the GC dose that could reduce infection occurrence. METHODS: This prospective cohort study included patients from the Japanese multicenter registry of patients with SLE (defined as ≥4 American College of Rheumatology 1997 revised criteria) over 20 years of age. The PSL dose was categorized as PSL 0-2.5, 2.6-5.0, 5.1-7.5, and 7.6-15.0 mg. The primary outcome was infection requiring hospitalization. We conducted a multivariable analysis using time-dependent Cox regression analysis to assess the hazard ratio of infection occurrence compared with a dose of 0-2.5 mg PSL or equivalent in the other three PSL dose groups. Based on previous reports and clinical importance, the covariates selected were age, sex, and concurrent use of immunosuppressants with GC. In addition, two sensitivity analyses were conducted. RESULTS: The mean age of the 509 SLE patients was 46.7 years; 89.0% were female, and 77.2% used multiple immunosuppressants concomitantly. During the observation period, 52 infections requiring hospitalization occurred. The incidence of infection with a PSL dose of 5.0-7.5 mg was significantly higher than that in the PSL 0-2.5 mg group (adjusted hazard ratio: 6.80, 95% confidence interval: 2.17-21.27). The results of the two sensitivity analyses were similar. CONCLUSIONS: Our results suggested that the use of 5.0-7.5 mg PSL or equivalent could pose an infection risk in SLE patients. This finding indicates that PSL dose should be reduced to as low as possible in SLE patients to avoid infection.

New surgical procedure for laryngotracheal separation without a cannula or postoperative treatment.

OBJECTIVES: Laryngotracheal separation is a surgical procedure used in the treatment of intractable aspiration. As with total laryngectomy and laryngotracheal diversion, this procedure requires postoperative pressure above the suture location to prevent leakage at the anastomosis. To date, there have been no reports regarding laryngeal separation without postoperative treatment. The purpose of this study was to evaluate a new surgical procedure for laryngotracheal separation that is performed without a cannula and requires no postoperative treatment. METHODS: We performed the new surgical procedure in 7 patients. The mucosa of the cricoid cartilage was sutured to achieve tracheal closure. The closure was covered with a musculocutaneous flap of strap muscle; gauze was then tied over the skin and a 2-0 nylon suture was used to pierce the posterior part of the cricoid cartilage. In addition, a permanent tracheostoma was constructed without a tracheal cannula. RESULTS: No patients required a tracheal cannula or treatment after the operation. Additionally, aspiration pneumonia was prevented without complications in all patients. CONCLUSIONS: This new surgical procedure eliminates the need for a cannula and postoperative treatment. The effects of this method in terms of aspiration prevention are comparable to those of other surgical techniques.

Laryngotracheal separation procedure for elderly patients.

A procedure for laryngotracheal separation was performed on 5 elderly patients in poor general condition to prevent habitual aspiration pneumonia. Intractable aspiration was relieved in all the patients with no major postoperative complications. In this intervention, a modification of the procedure previously reported, the anterior part of the tracheal and cricoid cartilage was removed, and the subglottic mucosa was sutured to fashion a blind pouch. This procedure could be adjusted even in cases of severe laryngoptosis or after high tracheostomy. Laryngotracheal separation is likely to be useful as a simple and safe procedure even for older patients. If this comes to be, it will serve as a valuable intervention in today's aging society.

A Recurrent Case of Adult-onset Still's Disease with Concurrent Acalculous Cholecystitis and Macrophage Activation Syndrome/Hemophagocytic Lymphohistiocytosis Successfully Treated with Combination Immunosuppressive Therapy.

We herein report the case of 21-year-old female diagnosed with adult-onset Still's disease (AOSD) three years earlier who presented with fever and right upper abdominal pain. She was diagnosed with acute acalculous cholecystitis (AAC) based on hepatic dysfunction, elevated C-reactive protein, and gallbladder wall thickening on abdominal ultrasound. Based on the presence of pancytopenia, hyperferritinemia, and hemophagocytosis by a bone marrow examination, she was diagnosed with macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH) which was refractory to glucocorticoid pulse therapy. The combination of intravenous cyclosporine A with glucocorticoids was able to successfully control the disease activity of AOSD-related AAC and MAS/HLH.

Successful treatment of a patient with refractory immune thrombocytopenic purpura in systemic lupus erythematosus with rituximab.

Immune thrombocytopenic purpura (ITP) is one of the complications of systemic lupus erythematosus (SLE). Although corticosteroids are usually selected for initial therapy, some patients are corticosteroid-resistant and, therefore, require other immunosuppressants or splenectomy. However, the best treatment approach in such patients remains unknown, and there is little evidence regarding which immunosuppressive agent can provide best results. We report the case of a patient with corticosteroid-resistant SLE-associated ITP (SLE-ITP) who was successfully treated with rituximab (RTX). RTX might be a therapeutic option for corticosteroid-resistant SLE-ITP.

Regional left-ventricular diastolic wall motion assessed by a new program for ECG-gated myocardial perfusion SPECT in early-stage heart failure.

BACKGROUND: We developed a new program for gated single-photon emission computed tomography to estimate regional left-ventricular (LV) wall motion. We classified and graded diastolic wall motion, and compared its grading with global LV functions. METHODS AND RESULTS: Forty New York Heart Association functional class I (NYHA class I) patients and 15 control subjects were examined. The global time to peak filling and the regional diastolic wall motion synchrony, as estimated by the time lag between the earliest and latest regional peak filling, were evaluated. Using the control group's mean + 2 SD, diastolic wall motions were classified into four subsets: globally normal and regionally synchronous, globally normal but regionally dyssynchronous, globally prolonged and regionally dyssynchronous, and globally prolonged but regionally synchronous. These subsets were graded 0 to 3, respectively. Grade 0 was defined as normal. Grading was compared with global LV functions. Although 67.5% of patients demonstrated abnormal motion, the global diastolic parameter less frequently detected an abnormality (22.5% to 32.5%). Grading correlated with the first-third filling fraction (Spearman's rank correlation coefficient [rs] = -0.74, P = 3.8 x 10(-6)) and the first-third filling rate (rs = -0.49, P < .005). CONCLUSIONS: Regional diastolic wall motion abnormality was frequently detected even in early-stage heart failure. Grading reflected early diastolic dysfunction.

Relationship between left ventricular function and wall motion synchrony in heart failure assessed by ECG-gated myocardial perfusion SPECT.

OBJECTIVE: To confirm the relationship between left ventricular (LV) function and wall motion synchrony, and to identify the difference of synchrony between an ischemic heart disease (IHD) patient group and other heart disease (OHD) patient group among classified groups in heart failure, systolic, and diastolic parameters were compared using electrocardiograph-gated single-photon emission computed tomography. METHODS AND RESULTS: Twenty IHD and 30 OHD patient groups, comprised New York Heart Association functional class I-III (IHD1-3 and OHD1-3), and 15 controls were examined. The LV functions (ejection fraction, EF; peak-filling rate, PFR) and synchrony, which was estimated from the time lag between the earliest and latest regional systolic or diastolic temporal parameters (maximum difference of regional time to end-systole, MD-TES, or maximum difference of regional time to peak filling, MD-TPF), were compared. The LV function correlated with its synchrony in IHD and OHD (EF vs. MD-TES: r = -0.86, P = 1.3 x 10(-6) in IHD and r = -0.69, P = 2.8 x 10(-5) in OHD. PFR versus MD-TPF: r = -0.67, P < 0.002 in IHD and r = -0.63, P < 0.0002 in OHD). Dyssynchronous normal EF was observed in three IHD (15%) and six OHD (20%). Dyssynchronous normal PFR was observed in six IHD (30%) and six OHD (20%). MD-TES was significantly smaller in control group (CG) than in IHD3 and OHD3 (P < 0.005), and in IHD1 than in IHD3 and OHD3 (P < 0.05). MD-TPF was significantly smaller in CG than in IHD2, IHD3, and OHD3 (P < 0.05). However, there was no significant difference between LV synchrony in IHD and OHD, or among LV synchrony of the same functional classes between these two groups. CONCLUSIONS: This study confirms that LV function is correlated with wall motion synchrony. No statistically significant difference was confirmed in wall motion synchrony between IHD and OHD. However, dyssynchrony appears in the patients without apparent global LV dysfunction. This feature may facilitate identification of synchronous disorder in HF patients with preserved global LV function. It is expected that detection of such a disorder may lead to the initiation of appropriate treatments for early stage HF and prevent its progression.

[Effects of Serum Sodium Concentrations on Nausea and Vomiting after Moderately Emetogenic Chemotherapy].

Chemotherapy-induced nausea and vomiting (CINV) is the most unbearable adverse effect of chemotherapy. The antiemesis guidelines of the National Comprehensive Cancer Network indicate that hyponatremia is a risk factor for CINV, although the relationship between the incidence of CINV and hyponatremia has not been sufficiently studied. This two-center prospective observational study evaluated whether low serum sodium concentrations were a risk factor for CINV. The study included 34 patients who were scheduled to receive first-line carboplatin- or oxaliplatin-based chemotherapy for gynecological or colorectal cancers. Patient diaries were used to record the daily incidences of CINV events during a 5-day period. The patients were divided based on the median serum sodium concentration into a low Na+ group (<141 mEq/L) and a high Na+ group (≥141 mEq/L). The incidences of delayed nausea were 27.8% in the high Na+ group and 62.5% in the low Na+ group (p=0.042), with complete control rates (no vomiting, rescue medication, or grade 2 nausea) of 77.8% and 43.8%, respectively (p=0.042). The time to complete control failure in each group was analyzed using the Kaplan-Meier method, which revealed a significantly shorter time in the low Na+ group (p=0.03). Therefore, these results indicate that low serum sodium concentrations may increase the risk of CINV.

Isolation and characterization of a new 2,4-dinitrophenol-degrading bacterium Burkholderia sp. strain KU-46 and its degradation pathway.

A gram-negative bacterium, strain KU-46, was isolated from agricultural soil contaminated with pesticides and was found to utilize 2,4-dinitrophenol as the sole source of carbon and nitrogen. Based on 16S rRNA gene sequence analysis and its morphological, biochemical, and physiological characteristics, strain KU-46 was identified as a Burkholderia sp. Metabolite analyses by HPLC and liquid chromatography-MS indicated that 4-nitrophenol, 1,4-benzoquinone, and nitrite are the intermediates of 2,4-dinitrophenol metabolism, and 2,4-dinitrophenol is metabolized via 4-nitrophenol to 1,4-benzoquinone by strain KU-46. The 2,4-dinitrophenol degradation pathway enzymes are induced by both 2,4-dinitrophenol and 4-nitrophenol.

Global and regional evaluation of systolic and diastolic left ventricular temporal parameters using a novel program for ECG-gated myocardial perfusion SPECT--validation by comparison with gated equilibrium radionuclide angiography and speckle-tracking radial strain from echocardiography.

BACKGROUND: A newly developed program, named cardioGRAF, enabled the evaluation of left ventricular (LV) systolic and diastolic temporal parameters for the estimation of heart failure using ECG-gated myocardial perfusion SPECT (GMPS). OBJECTIVE: The feasibility of those global (g-) and regional (r-) parameters was validated to compare with gated equilibrium radionuclide angiography (ERNA) and speckle-tracking radial strain (STS) from echocardiography. METHODS: Thirty-three patients were studied using GMPS and ERNA (n=11) or GMPS and STS (n=22). The following g- or r-parameters obtained by cardioGRAF and ERNA or STS were compared: time to end systole (TES), time from end systole to peak filling rate (TPF1), time from 0 to peak filling rate (TPF2), time to peak radial strain (TPS), time from peak strain to peak negative strain rate (TP-SR1), and time from 0 to peak negative strain rate (TP-SR2). RESULTS: All g-parameters were successfully obtained by cardioGRAF and ERNA. The results demonstrated good correlations (g-TES: r = 0.79, p < 0.005; g-TPF1: r = 0.75, p < 0.02; TPF2: r = 0.83, p < 0.005). The differences were 11.9 +/- 31.8 ms in g-TES, 19.9 +/- 65.4 ms in g-TPF1, and 37.7 +/- 67.4 ms in g-TPF2. All r-parameters were successfully obtained by cardioGRAF. Eight patients and 12 segments were excluded because of the inadequate quality of routine echocardiography for STS analysis. However, r-parameters obtained by cardioGRAF were significantly correlated with those of STS (r-TES and r-TPS: r = 0.61, p = 1 x 10(-8); r-TPF1 and r-TP-SR1: r = 0.69, p = 3 x 10(-11); r-TPF2 and r-TP-SR2: r = 0.76, p = 2 x 10(-15)). The differences were 22.1 +/- 38.2 ms between r-TES and r-TPS, 7.0 +/- 123.4 ms between r-TPF1 and r-TP-SR1, and 38.1 +/- 111.5 ms between r-TPF2 and r-TP-SR2. CONCLUSION: The feasibility of evaluating systolic and diastolic temporal parameters by a new program was validated. This program has the potential to evaluate both diastolic and systolic heterogeneous wall motions which express dyssynchrony in heart failure.

Relationships among regional diastolic impairment, elongation of global time to peak filling rate, and global diastolic function using ECG-gated myocardial perfusion SPECT in heart failure.

OBJECTIVE: The relationships among regional diastolic impairment, the elongation of global time to peak filling rate (g-TPF), and global diastolic function were examined by a novel program using electrocardiography-gated myocardial perfusion single-photon emission computed tomography (SPECT) (GMPS) in heart failure (HF). METHODS: Fifteen control subjects and 70 HF patients, New York Heart Association functional classification I (N-1) 41 cases, classification II (N-II) 15 cases, and classification III (N-III) 14 cases, were examined by GMPS. Using the reference mean +2 SD (standard deviation) of g-TPF derived from control group (CG), HF patients were divided into a normal g-TPF group (NG) and elongated g-TPF group (EG). The distributions of g-TPF and regional (r-) TPF were estimated by histograms. The extension of regional diastolic impairment was estimated by the number of r-TPF elongated segments (NES). RESULTS: g-TPF and r-TPF mainly distributed from 100 ms to 220 ms and demonstrated a peak around 150 ms in CG and NG. g-TPF distributed from 240 ms to 560 ms, but r-TPF distributed from 90 ms to 690 ms and demonstrated two peaks around 150 ms and 350 ms in EG. NES significantly correlated with g-TPF (r=0.79, P=6x10(-10) in N-I; r=0.69 and P<0.005 in N-II; r=0.89, P=2x10(-5) in N-III). NES negatively correlated with first third filling fraction (1/3FF) (r=-0.83, P=3x10(-11) in N-I; r=-0.72, P<0.0005 in N-II) and first third filling rate (1/3FR) (r=-0.49, P=0.002 in N-I; r=-0.52, P=0.002 in N-II; r=-0.81, P<0.0005 in N-III). g-TPF significantly correlated with 1/3FF (r=-0.67, P=1.5x10(-6) in N-I; r=-0.69, P<0.005 in N-II) and 1/3FR (r=-0.41, P<0.01 in N-I; r=-0.69, P<0.01 in N-III). CONCLUSIONS: The development of regional early diastolic impairment makes g-TPF elongation and induces global dysfunction in early diastole.