Relationship Between Cognitive Dysfunction and Systemic Metabolic Disorders in Elderly: Dementia Might be a Systematic Disease.

Vascular cognitive impairment (VCI) plays an important role in dementia in elderly people, and refers to the contribution of vascular pathology to the entire spectrum of cognitive disorders, ranging from mild cognitive impairment to severe dementia, as well as the pathological spectrum, from 'pure' Alzheimer disease through degrees of vascular comorbidity to 'pure' vascular dementia. In the present study, we investigated the relationship between cognitive dysfunction and systemic metabolic disorders, by employing deep learning (DL). We studied 202 patients (73.4 ± 13.0 years), 94.6% of whom were undergoing treatment for lifestyle diseases, and 68.8% of whom had a history of cerebrovascular disorder. We evaluated cognitive dysfunction by performing a Mini Mental State Examination (MMSE). We performed general blood examination, including Complete Blood Count and Basic Metabolic Panel, and measured cerebral blood oxygenation in the prefrontal cortex (PFC) using time-resolved near infrared spectroscopy (TNIRS). We then used deep neural networks to assess the MMSE scores of the subjects based on the TNIRS parameters and the blood examination data, independently. Next, we compared predicted MMSE scores based on the TNIRS and the blood examination. There was a significant positive correlation between the TNIRS parameters and the blood examination data (r = 0.6, p < 0.01). These observations suggest that cognitive dysfunction in patients with VCI may be caused by combinations of systemic metabolic disorders such as energy and oxygen metabolisms and cerebral circulatory disturbance due to arteriosclerosis resulting from lifestyle-related diseases.

Relationship Between Cerebral Blood Oxygenation and Electrical Activity During Mental Stress Tasks: Simultaneous Measurements of NIRS and EEG.

The incidence of stress-induced psychological and somatic diseases has been increasing rapidly, and it is important to clarify the neurophysiological mechanisms of stress response in order to establish effective stress management methods. We previously reported that the prefrontal cortex (PFC) plays an important role in stress response. In the present study, we employed near-infrared spectroscopy (NIRS) and electroencephalography (EEG) to investigate the characteristics of PFC activity during mental arithmetic tasks. A two-channel NIRS device was used to measure hemoglobin (Hb) concentration changes in the bilateral PFC during a mental arithmetic task (2 min) in normal adults. Simultaneously, EEG was used to also measure bilateral PFC activity during the same task. We evaluated concentration changes of oxy-Hb induced by the task while analyzing α wave changes using power spectrum analysis. It was observed that oxy-Hb in the bilateral PFC increased significantly during the task (p < 0.05), while α wave power in the PFC decreased significantly (p < 0.01). The present results indicate that mental stress tasks caused the activation of the bilateral PFC. Simultaneous measurements of NIRS and EEG are useful for evaluating the neurophysiological mechanism of stress responses in the brain.

Development of a Cuff-Less Blood Pressure Monitoring System and Its Application.

We present an unobtrusive cuff-less sphygmomanometer based on contact-type and optical pulse sensors for continuous and minimally invasive monitoring of blood pressure (BP). We developed a cuff-less sphygmomanometer that utilizes the pulse arrival time (PAT) to estimate continuous BP. To assess its accuracy, we recruited 10 healthy subjects in whom we carried out BP studies using the cuff-less sphygmomanometer compared with a standard cuff-type device in a stationary sitting patient. Preliminary results showed that the mean difference (MD) of estimated systolic blood pressure and diastolic blood pressure were 0.96 ± 9.6 (mean ± SD) mmHg and 1.14 ± 7.5 mmHg, respectively, compared to the control. The corresponding correlation between the estimated BP values and controls were 0.78 for systolic blood pressure (p < 0.01) and 0.69 for diastolic blood pressure (p < 0.01); thus, there were significant correlations. These results suggest that the developed cuff-less sphygmomanometer has the potential for continuous BP monitoring. Finally, we conducted a preliminary study of simultaneous monitoring of cuff-less BP and near-infrared spectroscopy to evaluate the potential for assessment of autonomic nervous system functions during mental stress tasks.

Differences in Tissue Oxygenation, Perfusion and Optical Properties in Brain Areas Affected by Stroke: A Time-Resolved NIRS Study.

Near infrared spectroscopy (NIRS) has been applied to measurements of cerebral blood oxygenation (CBO) in normal subjects and patients with various brain disorders including cerebrovascular diseases. However, it is not known whether NIRS allow us to measure CBO correctly in patients with abnormal cortices where optical characteristics such as optical pathlength (OP) may differ from those in normal cortex. In the present study, employing a time-resolved NIRS (TNIRS), we compared baseline hemoglobin (Hb) concentrations and OPs between normal and abnormal cortices in chronic stroke patients. We studied five patients with chronic cerebral infarction (two males, three females, age 59.0 ± 24.2 years) who were admitted to the University Hospital of Fukushima Prefectural Medical University. Employing TNIRS (TRS-20, Hamamatsu Photonics), we measured baseline Hb concentrations and OPs (760, 800, 830 nm) at various positions on the head. We observed that deoxy-Hb concentrations were significantly lower on the affected side (p < 0.01), and the tissue oxygen saturation was significantly higher than that on the affected side (p < 0.01), suggesting that oxygen consumption was reduced on the affected side. In addition, the OPs (760, 800 nm) were significantly longer on the affected side (p < 0.05); these changes might be caused by a possible increase of cerebrospinal fluid layer associated with brain tissue degeneration by ischemia. The present results suggest that NIRS should be performed on patients with abnormal cerebral cortices, giving special consideration to the possible difference in optical characteristics between normal and abnormal brain tissues.

Reliability of Wearable Two Channel CW-NIRS in Measurements of Brain Function.

Multi-channel NIRS, so-called optical topography (OT), allows functional mapping of the cortex; however, it takes a long time to set optodes on the head and is relatively expensive. Thus, OT is not suitable as a screening test of brain disorders evaluating many subjects. Recently, a wearable two-channel continuous wave NIRS (CW-NIRS) device has been developed. Such a simple NIRS device may be applicable as a screening test of brain disorders; however, its reliability in measurements of brain function is not yet clear. Here, we tested a two-channel CW-NIRS, which employs single LED (800 nm) for measurement of total hemoglobin (t-Hb) changes. We measured t-Hb changes in the bilateral prefrontal cortex (PFC) during mental arithmetic tasks, employing the CW-NIRS and time-resolve NIRS (TNIRS). The left-right asymmetry of the PFC activity was evaluated by calculating the laterality index (LI; (R-L)/(R + L) of t-Hb), which reflects mental stress. The interval between CW-NIRS and TNIRS measurements was 1-13 days. A significant positive correlation was observed between LI measured by CW-NIRS and TNIRS. These results suggest the reliability of the simple CW-NIRS, and it may be applicable to prevent stress-induced various diseases. Finally, it should be emphasized that the left-right asymmetry of PFC activity is relatively stable.

Inhibition of cerebellar granule cell turning by alcohol.

Ectopic neurons are often found in the brains of fetal alcohol spectrum disorders (FASD) and fetal alcohol syndrome (FAS) patients, suggesting that alcohol exposure impairs neuronal cell migration. Although it has been reported that alcohol decreases the speed of neuronal cell migration, little is known about whether alcohol also affects the turning of neurons. Here we show that ethanol exposure inhibits the turning of cerebellar granule cells in vivo and in vitro. First, in vivo studies using P10 mice demonstrated that a single intraperitoneal injection of ethanol not only reduces the number of turning granule cells but also alters the mode of turning at the EGL-ML border of the cerebellum. Second, in vitro analysis using microexplant cultures of P0-P3 mouse cerebella revealed that ethanol directly reduces the frequency of spontaneous granule cell turning in a dose-dependent manner. Third, the action of ethanol on the frequency of granule cell turning was significantly ameliorated by stimulating Ca(2+) and cGMP signaling or by inhibiting cAMP signaling. Taken together, these results indicate that ethanol affects the frequency and mode of cerebellar granule cell turning through alteration of the Ca(2+) and cyclic nucleotide signaling pathways, suggesting that the abnormal allocation of neurons found in the brains of FASD and FSA patients results, at least in part, from impaired turning of immature neurons by alcohol.

Cranial reshaping employing distraction and contraction in the treatment of sagittal synostosis.

We treated four patients with scaphocephaly using a combination of distraction and contraction techniques and achieved satisfactory results. Radial osteotomies in the frontal and occipital bones flattened these abnormal bossing bones and accelerated the disappearance of bony bumps created by distraction. This technique facilitates the achievement of the desired shape of the skull through fine adjustments of the distraction and contraction devices.

Prediction of tumor radiosensitivity in rectal carcinoma based on p53 and Ku70 expression.

The identification of predictive indicators of radiosensitivity is extremely useful in selecting patients suited for preoperative radiotherapy and avoiding unnecessary preoperative treatment. In this study, we evaluated the possible role of the immunohistochemical expression pattern of p53 and Ku70 protein in determining tumor radiosensitivity in rectal cancer before preoperative irradiation. We examined pretreatment biopsy materials from 111 patients by immunohistochemistry. The expression pattern of p53 and Ku70 was evaluated for association with tumor radiosensitivity, which was defined according to the criteria of the Japanese Research Society for Cancer of the Colon and Rectum. There was a significant correlation between the expression pattern of p53 and tumor radiosensitivity (P = 0.045); Ku70 and tumor radiosensitivity (P < 0.001); and the combination of p53 and Ku70, and tumor radiosensitivity (P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in both p53 and Ku70-positive cases for radioresistance were all superior to those of the group positive for p53 alone. In conclusion the examination of the combination of p53 and Ku70 may predict the radiosensitivity of rectal cancer before preoperative irradiation.

Tumor imprint cytology of ovarian ependymoma. A case report.

BACKGROUND: Ependymoma is a tumor that usually develops in the central nervous system and is extremely rare in the ovary. The first case of ovarian ependymoma was reported by Kleinman et al. (Kleinman GM, Young RH, Scully RE. Ependymoma of the ovary: report of three cases. Hum Pathol 1984;15:632-8.) in 1984, and only eight cases have been reported since then. Criteria for the histopathologic diagnosis of ependymoma are already established, but there has been no investigation of the cytologic diagnosis of ovarian ependymoma. METHODS: An imprint cytologic specimen was obtained from a recurrent ovarian ependymoma. The imprint cytologic features were compared with the findings of histologic examination, immunostaining, and electron microscopy. RESULTS: Imprint cytology revealed clusters of small cells with tapering cytoplasmic processes and a round nucleus. On the basis of these features, a neurogenic tumor could be included in the differential diagnosis. Furthermore, many rosette-like collections of cells that were suggestive of ependymal rosettes or perivascular pseudorosettes, characteristic of ependymoma, were found. The presence of ependymal rosettes and perivascular pseudorosettes also were confirmed by the histopathologic examination. Together with positive immunostaining for glial fibrillary acidic protein, this led to the diagnosis of ependymoma, which also was supported by the electron microscopic findings. CONCLUSIONS: Careful observation of the imprint cytologic specimen of an ovarian ependymoma should reveal numerous rosette-like collections of cells that were suggestive of ependymal rosettes or perivascular pseudorosettes. In addition, if we remember that ependymoma can develop in the ovary and find cells with tapering processes that suggest a neurogenic tumor, it may be possible to detect histologic features characteristic of ependymoma by the imprint cytology. To our knowledge, this is the first report on the imprint cytologic diagnosis of ependymoma originating in the ovary.

Paclitaxel and SN-38 overcome cisplatin resistance of ovarian cancer cell lines by down-regulating the influx and efflux system of cisplatin.

Cisplatin (DDP) is one of the key drugs used to treat patients with ovarian cancer, although resistance to DDP can occur. Paclitaxel and SN-38 (an active metabolite of irinotecan (CPT-11)) are two drugs that are effective in patients with DDP-resistant ovarian cancer. To study how these drugs may overcome the intrinsic and / or acquired resistance of cancer cells to DDP, we investigated the effect of a combination of DDP with paclitaxel and a combination of DDP with SN-38 on three ovarian cancer cell lines, RTSG (intrinsically resistant cell line), KF (DDP-sensitive cell line), and KFra (acquired resistant cell line obtained from KF). We found that these combinations showed additive to synergistic antitumor activity. A time-dependent platinum (Pt) accumulation was observed in the DDP-sensitive KF cell line, while a decrease occurred in the KFra cell line. Little accumulation was observed in RTSG. Intracellular Pt accumulation was increased in all three cell lines by exposure to paclitaxel or SN-38. Ouabain, a Na(+),K(+)-ATPase inhibitor, decreased Pt accumulation in KF and KFra cell lines and inhibited the paclitaxel- and SN-38-induced increases in Pt accumulation in these cell lines. When we assessed the mRNA levels of the multidrug resistance-associated protein (MRP), which may be an efflux pump for DDP, the combination of paclitaxel or SN-38 with DDP down-regulated these levels, which are up-regulated by DDP alone. These results suggest that paclitaxel and SN-38 overcome DDP resistance of ovarian cell lines by controlling intracellular accumulation of DDP via both the influx and efflux systems.

Primary ependymoma of the ovary, in which long-term oral etoposide (VP-16) was effective in prolonging disease-free survival.

BACKGROUND: Ovarian ependymoma is an extremely unusual teratoma of the ovary with only eight cases previously reported in the literature worldwide. CASE: A 26-year-old woman presented in 1992 with a sensation of abdominal fullness. The laparotomy revealed ovarian cancer (stage III), which proved to be an ependymoma pathologically. Three courses of the PVP regimen (cisplatin, vinblastine, peplomycin) and pelvic irradiation were administered postoperatively. Oral administration of etoposide (VP-16) was initiated after the residual tumor began to proliferate, and the tumor decreased in size and never regrew during etoposide administration for a total of 5 years and 8 months. The recurrent tumor was observed soon after the drug was discontinued. CONCLUSION: Oral administration of etoposide was effective in prolonging disease-free survival.

Case report of serous ovarian tumor of borderline malignancy (Stage Ic) in a pregnant woman.

We encountered a case of Stage Ic ovarian serous borderline malignancy in the first trimester of pregnancy. At laparotomy, spontaneous rupture of the capsule and a small amount of serous ascites was observed. Because of the laparotomy during pregnancy, correct staging of the tumor might not be performed. This case presented a major problem in deciding the treatment strategy, which are reported here together with some discussion of the literature on the preservation of fertility in borderline ovarian malignancy.

Intestinal perforation due to metastasis of breast carcinoma, with special reference to chemotherapy: a case report.

We report a case of small-bowel perforation due to metastatic carcinoma of the breast during chemotherapy. Partial resection of the small intestine and primary anastomosis were performed. Although the patient made a good recovery from panperitonitis, she died of the disease on the 55th postoperative day. Since perforation during chemotherapy results in an extremely poor prognosis, special caution during chemotherapy is needed for patients with possible gastrointestinal involvement with tumor.

Cisplatin sensitivity of ovarian cancer in the histoculture drug response assay correlates to clinical response to combination chemotherapy with cisplatin, doxorubicin and cyclophosphamide.

The histoculture drug sensitivity assay (HDRA) has been demonstrated to have high predictability for resistance, sensitivity, and survival for gastrointestinal cancer (Clin Cancer Res 1: 305-311, 1995; Clin Cancer Res 1: 1537-1543, 1995). In this report, we evaluated the clinical usefulness of the HDRA in ovarian cancer. HDRA was performed on tumors from patients with ovarian cancer. Eighty-five cases (97%) were evaluable. Tumor fragments were cultured on collagen-sponge gels. The cultures were incubated with cisplatin (CDDP) for seven days. Cell viability were assessed with the MTT end point. The optimal cut off concentration of CDDP was determined to be 25 micrograms/ml by correlation with the historical clinical response rate to CDDP. HDRA results were correlated to clinical response of 15 patients who received CDDP-based therapy that included doxorubicin and cyclophosphamide (CAP therapy). The true positive rate was 88%, the true negative rate was 86%, the sensitivity was 88%, the specificity was 86%, and the accurate prediction rate was 87% when HDRA results were compared to the response of the treated patients. The data suggest that the HDRA is capable of predicting the response to antitumor chemotherapy in patients with ovarian cancer and that measuring response to CDDP can be useful for optimization of CAP chemotherapy for patients with this disease.

Response of glassy-cell carcinoma of the cervix to cisplatin, epirubicin, and mitomycin C.

Among patients with uterine cervical cancer, glassy-cell carcinoma is very rare. The disease occurs mainly in younger patients, is rapidly progressive, and has a poor prognosis. We describe a case of glassy-cell carcinoma of the uterine cervix, in which preoperative intra-arterial chemotherapy was surprisingly effective.

"Face to face": a new method for the treatment of polydactyly of the thumb that maximises the use of available soft tissue.

Some patients with distal phalangeal polydactyly of the thumb have severe hypoplastic pulps that are difficult to make sufficiently large with either the fillet flap method or a symmetrical combination, the Bilhaut-Cloquet method. We have devised a new method to reconstruct the largest possible pulp by resecting only a minimum amount of soft dorsal skin tissue with one nail and not resecting any of the palmar skin of the thumbs. By contrast, other procedures require some resectioning of soft tissue of both the dorsal and the palmar skin. We have treated 13 cases with distal phalangeal polydactyly of the thumb since 1988 in this way. All the thumbs were successfully reconstructed with a sufficiently large pulp. The only problem was slight instability of the skin of the pulp after the operation, but this condition gradually improved during a five-year follow up. We think that this method facilitates the reconstruction of a sufficiently large pulp when both bifid pulps are hypoplastic.