Effects of a walking program in patients with chronic unilateral vestibular hypofunction.

[Purpose] Patients with chronic unilateral vestibular hypofunction show decreased postural stability and low levels of physical activity and also experience much anxiety. Physical activity is known to improve these symptoms; however, no study has reported any positive effects of physical activity, such as symptom reduction or improvement in function in these patients. In this study, we investigated the role of a walking program in improvement of dizziness, anxiety, and postural stability in this patient population. [Participants and Methods] This study included 21 patients with unilateral vestibular hypofunction and chronic dizziness. Patients were instructed to walk 30 min daily for 3 months. Physical activity levels and questionnaires for clinical symptoms, anxiety, and postural stability were evaluated before and after intervention. [Results] We observed significant differences in the amount of moderate-to-vigorous physical activity, clinical symptoms, and self-perceived handicap before and after the intervention. Additionally, anxiety levels were significantly reduced and postural stability was significantly improved in these patients. [Conclusion] A walking program improved physical activity levels, clinical symptoms, and postural stability and reduced self-perceived handicap and anxiety in patients with chronic unilateral vestibular hypofunction. These results highlight the effectiveness of a walking program for these patients and emphasize its role as a complementary vestibular rehabilitation strategy.

In vitro analysis of mechanism of pulsed-laser thrombolysis.

Thrombolytic therapy in the treatment of cardiogenic acute cerebral embolism caused by coagulated blood carries the risk of hemorrhagic complications, and there is a need to develop safer and more reliable treatment methods. Laser thrombolysis therapy, which utilizes the difference in energy absorption between the thrombus and the arterial wall, has shown promise as a new treatment method because it can selectively act only on the thrombus. It has not been applied clinically, however, and one of the main reasons for this is that its underlying mechanism has not been elucidated. We developed a pulse laser thrombolysis system for treating cerebral blood vessels that consists of a diode-pumped solid-state neodymium-yttrium aluminum garnet laser, which has excellent stability and maintainability and is suitable for clinical applications coupled to a small-diameter optical fiber. Moreover, we analyzed the mechanisms that occur during pulsed laser irradiation of transparent glass tubes and gelatin phantoms. We found that bubbles form as a thermal effect in addition to ablation of the pulsed laser irradiation. Furthermore, we detected no shock waves or water jets associated with the bubbles. We analyzed the bubbles' dynamics and growth rate, and their effect on a rabbit blood clot phantom. We concluded that the bubbles generated by the laser irradiation physically cut the thrombus and thereby had a thrombectomy effect. We believe that this study will clarify the mechanism of laser thrombolysis therapy and contribute greatly to the realization of its clinical application.

Stable tissue-simulating phantoms with various water and lipid contents for diffuse optical spectroscopy.

We introduced a method for producing solid phantoms with various water-to-lipid ratios that can simulate the absorption, and to some extent the scattering characteristics of human breast tissue. We also achieved phantom stability for a minimum of one month by solidifying the emulsion phantoms. The characteristics of the phantoms were evaluated using the six-wavelength time-domain diffuse optical spectroscopy (TD-DOS) system we developed to measure water and lipid contents and hemoglobin concentration. The TD-DOS measurements were validated with a magnetic resonance imaging system.

Hemodynamic Measurements of the Human Adult Head in Transmittance Mode by Near-Infrared Time-Resolved Spectroscopy.

Using a near-infrared time-resolved spectroscopy (TRS) system, we measured the human head in transmittance mode to obtain the optical properties and the hemodynamic changes of deep brain tissues in seven healthy adult volunteers during hyperventilation. For six out of seven volunteers, we obtained the optical signals with sufficient intensity within 10 sec. of sampling. We confirmed that it is possible to non-invasively measure the hemodynamic changes of the human head during hyperventilation, even in the transmittance measurements by the developed TRS system. These results showed that the level of deoxygenated hemoglobin was significantly increased, and the level of oxygenated and total hemoglobin and tissue oxygen saturation were also significantly decreased during hyperventilation. We expect that this TRS technique will be applied to clinical applications for measuring deep brain tissues and deep biological organs.

Effect of the chest wall on the measurement of hemoglobin concentrations by near-infrared time-resolved spectroscopy in normal breast and cancer.

BACKGROUND: Optical imaging and spectroscopy using near-infrared light have great potential in the assessment of tumor vasculature. We previously measured hemoglobin concentrations in breast cancer using a near-infrared time-resolved spectroscopy system. The purpose of the present study was to evaluate the effect of the chest wall on the measurement of hemoglobin concentrations in normal breast tissue and cancer. METHODS: We measured total hemoglobin (tHb) concentration in both cancer and contralateral normal breast using a near-infrared time-resolved spectroscopy system in 24 female patients with breast cancer. Patients were divided into two groups based on menopausal state. The skin-to-chest wall distance was determined using ultrasound images obtained with an ultrasound probe attached to the spectroscopy probe. RESULTS: The apparent tHb concentration of normal breast increased when the skin-to-chest wall distance was less than 20 mm. The tHb concentration in pre-menopausal patients was higher than that in post-menopausal patients. Although the concentration of tHb in cancer tissue was statistically higher than that in normal breast, the contralateral normal breast showed higher tHb concentration than cancer in 9 of 46 datasets. When the curves of tHb concentrations as a function of the skin-to-chest wall distance in normal breast were applied for pre- and post-menopausal patients separately, all the cancer lesions plotted above the curves. CONCLUSIONS: The skin-to-chest wall distance affected the measurement of tHb concentration of breast tissue by near-infrared time-resolved spectroscopy. The tHb concentration of breast cancer tissue was more precisely evaluated by considering the skin-to-chest wall distance.

Influence of cerebral white matter lesions on the activities of daily living of older patients with mild stroke.

AIM: Neurological symptom severity is a prognostic factor for post-stroke activities of daily living (ADL). Recently, it has been reported that white matter lesions indicate poor functional prognosis in patients with stroke. The present study investigated the influence of white matter lesions on the ADL of older patients with stroke who have mild neurological symptoms. METHOD: We investigated ADL at discharge in 44 patients with stroke (men, n = 27; women, n = 17; mean age 78 years [range 71-85 years]) aged ≥65 years with National Institutes of Health Stroke Scale scores of ≤5 (cerebral infarction, n = 37; cerebral hemorrhage, n = 7). We used single correlation analysis and multiple regression analysis to investigate factors that correlated with ADL at discharge. ADL at discharge was also evaluated on the basis of white matter lesion severity (Fazekas classification, grades 0-3). RESULTS: Single correlation analysis showed that age (r = -0.36, P = 0.016), male sex (r = 0.362, P = 0.016), neurological symptom severity (r = -0.361, P = 0.016), ADL on starting rehabilitation (r = 0.685, P < 0.001) and white matter lesion severity (r = -0.361, P = 0.016) significantly correlated with ADL at discharge. Multiple regression analysis showed that ADL on starting rehabilitation (ß = 0.519, t = 4.723, P < 0.001) and white matter lesion severity (ß = -0.309, t = -3.057, P < 0.01) were statistically significant prognostic factors for ADL at discharge. ADL at discharge score was significantly lower in the group with high white matter lesion severity (Fazekas, grade 2) than in the other two groups (Fazekas, grade 0, P < 0.01; Fazekas, grade 1, P < 0.05). CONCLUSION: Severe white matter lesions are a prognostic factor for poor ADL at discharge in older patients with stroke who have mild neurological symptoms. Geriatr Gerontol Int 2016; 16: 942-947.

Sensitivity correction for the influence of the fat layer on muscle oxygenation and estimation of fat thickness by time-resolved spectroscopy.

Near-infrared spectroscopy (NIRS) has been used for noninvasive assessment of oxygenation in living tissue. For muscle measurements by NIRS, the measurement sensitivity to muscle (S(M)) is strongly influenced by fat thickness (FT). In this study, we investigated the influence of FT and developed a correction curve for S(M) with an optode distance (3 cm) sufficiently large to probe the muscle. First, we measured the hemoglobin concentration in the forearm (n=36) and thigh (n=6) during arterial occlusion using a time-resolved spectroscopy (TRS) system, and then FT was measured by ultrasound. The correction curve was derived from the ratio of partial mean optical path length of the muscle layer 〈L(M)〉 to observed mean optical path length 〈L〉. There was good correlation between FT and 〈L〉 at rest, and 〈L〉 could be used to estimate FT. The estimated FT was used to validate the correction curve by measuring the forearm blood flow (FBF) by strain-gauge plethysmography (SGP_FBF) and TRS (TRS_FBF) simultaneously during a reactive hyperemia test with 16 volunteers. The corrected TRS_FBF results were similar to the SGP_FBF results. This is a simple method for sensitivity correction that does not require use of ultrasound.

Optical imaging of tumor vascularity associated with proliferation and glucose metabolism in early breast cancer: clinical application of total hemoglobin measurements in the breast.

BACKGROUND: Near-infrared optical imaging targeting the intrinsic contrast of tissue hemoglobin has emerged as a promising approach for visualization of vascularity in cancer research. We evaluated the usefulness of diffuse optical spectroscopy using time-resolved spectroscopic (TRS) measurements for functional imaging of primary breast cancer. METHODS: Fifty-five consecutive TNM stage I/II patients with histologically proven invasive ductal carcinoma and operable breast tumors (<5 cm) who underwent TRS measurements were enrolled. Thirty (54.5%) patients underwent 18F-fluoro-deoxy-glucose (FDG) positron emission tomography with measurement of maximum tumor uptake. TRS was used to obtain oxyhemoglobin, deoxyhemoglobin, and total hemoglobin (tHb) levels from the lesions, surrounding normal tissue, and contralateral normal tissue. Lesions with tHb levels 20% higher than those present in normal tissue were defined as "hotspots," while others were considered "uniform." The findings in either tumor type were compared with clinicopathological factors. RESULTS: "Hotspot" tumors were significantly larger (P= 0.002) and exhibited significantly more advanced TNM stage (P=0.01), higher mitotic counts (P=0.01) and higher levels of FDG uptake (P=0.0004) compared with "uniform" tumors; however, other pathological variables were not significantly different between the two groups. CONCLUSIONS: Optical imaging for determination of tHb levels allowed for measurement of tumor vascularity as a function of proliferation and glucose metabolism, which may be useful for prediction of patient prognosis and potential response to treatment.

[A case in which dihydropyrimidine dehydrogenase deficiency was strongly suspected during adjuvant chemotherapy with capecitabine for colon cancer].

Severe toxicity in patients with a deficiency of dihydropyrimidine dehydrogenase(DPD), an enzyme that reduces fluoropyrimidine, is very rare, and reports on this condition are few. Accordingly, diagnosis is very difficult. The patient was 70-year-old man who was admitted for adjuvant chemotherapy with capecitabine(3,600mg/day)for rectal cancer. He was admitted to our hospital because of severe oral mucositis(grade 3)and hand-foot syndrome(grade 3). After hospitalization, he experienced complications with neutropenia(grade 4)and thrombocytopenia(grade 4). The patient died 25 days after the onset of chemotherapy. Despite the measurement of the DPD value in mononuclear cells of peripheral blood and urophanic uracil and dihydrouracil, we were unable to diagnose DPD deficiency. However, we suspected a partial deficiency of DPD on the basis of the clinical course.

[A case of primary adenocarcinoma of small intestine responding to XELOX chemotherapy and leading to a partial metabolic response].

We report a case of adenocarcinoma of the small intestine responding to XELOX chemotherapy, leading to a partial metabolic response(PMR). The patient was a 58-year-old male with multiple peritoneal dissemination of adenocarcinoma of the small intestine. Chemotherapy with XELOX(L-OHP 130 mg/m² on day 1 , and capecitabine 1,000 mg/m2 on days 1-14)was performed. After 4 courses, a significant tumor reduction was obtained. This case suggests that chemotherapy with XELOX is a potential regimen for small intestinal adenocarcinoma.

[A case of resected rectal cancer with hepatic node and multiple liver metastases effectively treated by preoperative modified FOLFOX6 and sLV5FU2 chemotherapy].

A 55-year-old male had complained of melena.Colonoscopy revealed a type 2 tumor at the rectum.CT demonstrated hepatic lymph nodes and multiple liver metastases(stage IV).Low anterior resection was performed(tub2, RsRa, circ, type 2, pSS, pN1, sH3, cHN1, sP0, cM0: fstage IV).The patient was treated with mFOLFOX6 and sLV5FU2 after operation.CT revealed a partial response after 14 courses of systemic chemotherapy.sLV5 FU2 therapy was converted to capecitabine because he experienced bone marrow suppression.CT showed that the liver metastases had enlarged but the hepatic lymph nodes disappeared.Right portal vein embolization was performed.After 4 weeks, right hepatectomy and hepatic lymph node dissection were performed.Preoperative chemotherapy with mFOLFOX6 seems beneficial as a neoadjuvant chemotherapy for hepatic lymph node-positive advanced colorectal cancer.

Label-free imaging of intracellular motility by low-coherent quantitative phase microscopy.

The subject study demonstrates the imaging of cell activity by quantitatively assessing the motion of intracellular organelles and cell plasma membranes without any contrast agent. The low-coherent interferometric technique and phase-referenced phase shifting technique were integrated to reveal the depth-resolved distribution of intracellular motility. The transversal and vertical spatial resolutions were 0.56 µm and 0.93 µm, respectively, and the mechanical stability of the system was 1.2 nm. The motility of the cell was assessed by mean squared displacement (MSD) and we have compensated for the MSD by applying statistical noise analysis. Thus we show the significant change of intracellular motility after paraformaldehyde treatment in non-labeled cells.

Changes of evoked cerebral blood oxygenation and optical pathlength in the frontal lobe during language tasks: a study by multi-channel, time-resolved near-infrared spectroscopy and functional MRI.

To determine the alterations in optical characteristics and cerebral blood oxygenation (CBO) in the frontal lobe during language tasks, we evaluated the changes in mean optical pathlength (MOP) and CBO induced by a verbal fluency task (VFT) in the right and left frontal lobes in normal adults (n = 9, mean age = 29.6 +/- 4.8 years). We employed a newly developed 8-channel time-resolved near-infrared spectroscopy (TRS) instrument. The results demonstrated differences in MOP in the fronto-temporal areas with subject and wavelength; however, there was no significant difference between the right and left sides (p > 0.05). Also, the VFT did not affect the MOP significantly as compared to that before the tasks (p > 0.05). In all of the recording regions, the VFT caused increases in concentration of oxyhemoglobin and total hemoglobin associated with a decrease in deoxyhemoglobin concentration, indicating that these cortical areas were activated by the VFT. However, the mean concentration changes of oxyhemoglobin and total hemoglobin on the left side were larger than those on the right side. In addition, functional MRI demonstrated that the inferior frontal gyrus on the left side was activated in the subjects who exhibited increases in oxyhemoglobin concentration in these areas. These results suggest that TRS may be useful to study language function and to assess hemispheric dominance for language.

Bedside assessment of cerebral vasospasms after subarachnoid hemorrhage by near infrared time-resolved spectroscopy.

We examined the usefulness of near infrared time-resolved spectroscopy (TRS) for detection of vasospasm in subarachnoid hemorrhage (SAH). We investigated seven aneurysmal SAH patients with poor clinical conditions (WFNS grade V) who underwent endovascular coil embolization. Employing TRS, we measured the oxygen saturation (SO(2)) and baseline hemoglobin concentrations in the cortices. Measurements of TRS and transcranial Doppler sonography (TCD) were performed repeatedly for 14 days after SAH. In four of the seven patients, the SO(2) and hemoglobin concentrations measured in the brain tissue of the middle cerebral artery territory remained stable after SAH. However, in three patients, TRS revealed abrupt decreases in SO(2) and total hemoglobin between 5 and 9 days after SAH. Cerebral angiography performed on the same day revealed severe vasospasms in these patients. Although TCD detected the vasospasm in two of three cases, it failed to do so in one case. TRS could detect vasospasms after SAH by evaluating the cortical blood oxygenation.

[A case of early poorly-differentiated neuroendocrine carcinoma of stomach].

A 45-year-old male was admitted to our hospital complaining of anemia. Gastric endoscopy showed a type IIa+IIc tumor at the anterior wall of the gastric angle. Based on the pathology of the biopsy specimen, poorly-differentiated adenocarcinoma was diagnosed. Computed tomography scans showed regional lymph node swelling. Distal gastrectomy with a D2 lymph node dissection was performed. On pathology, the tumor was immunohistochemically positive for chromogranin A and synaptophysin. The Ki67 index was 70%. The tumor was diagnosed as poorly-differentiated neuroendocrine carcinoma of the stomach. He was treated with S-1 and CPT-11. Neuroendocrine cell carcinoma of the stomach is rare and usually has a very poor prognosis. Thus, we are reporting this case of early poorly-differentiated neuroendocrine carcinoma of the stomach that was curatively resected and had 12-month survival without recurrence.

[A case of gastric cancer with peritoneal dissemination who achieved long survival by successive treatments with S-1 in combination with CDDP, paclitaxel and irinotecan].

The patient was a 63-year-old male with multiple peritoneal disseminations of advanced gastric cancer. He underwent chemotherapy with a combination of S-1 120 mg/day (3 weeks administration and 2 weeks rest) and cisplatin (CDDP) 60 mg/m(2) (day 8). After 3 courses of this regimen, CT revealed no evidence of ascites. He then underwent laparatomy. Peritoneal dissemination appeared, and the findings were sT3, N0, H0, P1, CY1, M1(PLE), sStage IV. A bypass operation was performed. As second-line chemotherapy, he received combination chemotherapy with S-1 and paclitaxel (PTX) 60 mg/m(2) (div), 20 mg/m(2) ( ip) (day 1, 8). However, he complained of ascites after 16 courses. We tried weekly administration of PTX and tri-weekly administration of irinotecan (50 mg/m(2)) with S-1. This treatment was successfully continued for 20 courses. The adverse effect was anemia (grade 2). He died two years eight months after surgery. The chemotherapy with S-1/CDDP, S-1/PTX, and S-1/PTX/irinotecan was thought to be effective for advanced gastric cancer with peritoneal dissemination.

[A case of stage IV AFP producing cecal cancer responding to mFOLFOX6 leading to a partial response].

We report a case of stage IV AFP producing cecal cancer responding to mFOLFOX6 leading to a partial response. The patient was a 72-year-old female with multiple liver metastases of cecal cancer. She underwent a right hemicolectomy and right salpingo-oophorectomy in a non-curative resection. Final findings revealed cecal cancer, type 3, 60 x 55 mm, pSI (right ovary), pN3, sH3, sP0, cM0, fStage IV, respectively. After surgery, chemotherapy with mFOLFOX6 was performed. After 4 courses, a significant tumor reduction (PR) was obtained. She died 1 year 2 months after surgery. This case suggests that chemotherapy with mFOLFOX6 is a potential regimen for AFP producing colon cancer.

Low-coherent quantitative phase microscope for nanometer-scale measurement of living cells morphology.

We have developed a Linnik-type interference microscope provided with a low-coherent light source to obtain topographic images of an intact cellular membrane on a nanometer scale. Our technique is based on measurement of the interference between light reflected from the cell surface and a reference beam. The results show full field surface topography of cultured cells and reveal an intrinsic membrane motion of tens of nanometers.

Ultrastructural changes at the myotendinous junction induced by exercise.

BACKGROUND: Although exercise is believed to reduce the risk of rupture of the myotendinous junction, exercise-induced structural changes in this region have not been studied. We examined exercise-induced ultrastructural changes in the myotendinous junction of the lower legs in rats. METHODS: Ten adult male LETO rats were used. Five rats were randomly placed in the Exercise group; the remaining five were used as controls and placed in the non-Exercise group. Running exercise was performed every day for 4 weeks. The tibialis anterior and gastrocnemius muscles were then removed from both legs from each animal in the two groups. The specimens were subsequently examined by transmission electron microscopy (TEM). Numerous finger-like processes were observed at the myotendinous junction. The changes in frequency of branching of the finger-like process (the number of times one finger-like process branched) and the direction of the processes (the angle of the major axis of a finger-like process to the longitudinal direction of the muscle fiber) were studied. To evaluate the two indicators above, each 10 fingerlike process was randomly and separately selected from the tibialis anterior and gastrocnemius muscles of rats, providing 50 finger-like processes of both muscles for evaluation per group. RESULTS: In terms of the frequency of branching of the fingerlike processes, the mean values obtained in the non-Exercise group were 0.04 and 0.18 times, respectively, in the tibialis anterior and gastrocnemius muscles and were 0.38 and 1.16 times, respectively, in these two muscles in the Exercise group. Regarding the direction of the finger-like processes, the values were 4.1 degrees and 3.6 degrees, respectively in the non-Exercise group and 10.4 degrees and 14.5 degrees , respectively in the Exercise group. The differences between the two animal groups were significant. CONCLUSIONS: Morphological changes in the myotendinous junction occurred as an adaptation to tension increased by exercise.

Presumed primary malignant melanoma of the liver: a case report.

A 55-year-old woman was hospitalized with a palpable and painful mass in her upper abdomen. Abdominal computed tomography revealed a 10 × 7-cm tumor extending into the abdominal cavity from the left hepatic lobe and multiple metastatic lesions in the right hepatic lobe. A left hepatic lobectomy was performed for debulking and palliative resection. Histopathological examination of the resected specimen diagnosed the large hepatic tumor in the left hepatic lobe as a malignant melanoma. Physical and radiological examinations were performed on dermatological, ophthalmic, gynecological, and central nervous system areas, and endoscopic examinations were performed on the upper digestive tract and colon. No other lesions were disclosed as possible primary tumors for the disease. This result suggested that the tumor might arise from the left hepatic lobe.