Glibenclamide attenuates brain edema associated with microglia activation after intracerebral hemorrhage.

OBJECTIVE: Glibenclamide, Sulfonylurea receptor 1 antagonist, reduces brain edema after cerebral hemorrhage. However, the effects of glibenclamide on microglial activation and inflammatory cell infiltration after cerebral hemorrhage are unclear. The present study investigated the effect of glibenclamide on microglial activation and inflammatory cell infiltration in a rat cerebral hemorrhage model. METHODS: A collagenase intracerebral injection model was used to cause cerebral hemorrhage in rats. After injury, glibenclamide was continuously administered at 1.0µL/h for 24hours. We evaluated hematoma volume, brain edema, expression of ABCC8, galectin-3 and CD11b, and anti-Iba-1 antibody staining. RESULTS: Glibenclamide significantly reduced water content. Meanwhile, glibenclamide significantly reduced expression of galectin-3 and CD11b in the cerebral cortex and putamen on the bleeding side. Immunohistochemical staining confirmed that glibenclamide attenuated activation of microglia around the hematoma. CONCLUSIONS: Glibenclamide reduced microglial activation and infiltration of inflammatory cells, resulting in amelioration of cerebral edema.

Oncological and Reproductive Outcomes of Abdominal Radical Trachelectomy.

Background/Aim: There is an increasing demand for preserving the fertility of young women impacted with early-stage cervical cancer. The aim of this study is to evaluate the oncological and reproductive outcomes of abdominal radical trachelectomy (ART). Patients and Methods: We retrospectively reviewed patients with FIGO stageIA2-IB1 cervical cancer who underwent ART from 2007 to 2018. We also compared the oncological prognosis between the patients who underwent ART and radical hysterectomy (RH). Results: A total of 42 patients underwent ART. During median follow-up 62.5 months, there were 4 (9.5%) recurrences and 1 (2.4%) death. As for tumors ≤2 cm, the 5-year recurrence-free survival (RFS) rate and overall survival (OS) rate for patients who underwent ART was similar to those who underwent RH (89.8% vs. 92.7%, p=0.42 and 97.3% vs. 95.0%, p=0.44, respectively). Nineteen patients attempted to conceive and seven of them were successful. There was one case of a first-trimester miscarriage, two cases of preterm delivery, three cases of full-term delivery and one ongoing pregnancy. Conclusion: ART could be a feasible alternative to RH for patients with tumors ≤2 cm with comparable oncological outcome.

Relationship Between Stress Coping Mechanisms and Depression in Kidney Transplant Recipients.

BACKGROUND: It has been reported that transplant recipients are exposed to physical and psychosocial stresses even after transplant surgery and exhibit psychological disorders such as depression. PURPOSE: In this study, we extracted trends concerning how recipients of kidney transplants cope with stress, and we also examined how they cope with depression and its countermeasures. METHOD: We administered questionnaire surveys to 109 kidney transplant recipients. These included items on personal attributes, medical information, depression, and stress-coping type scales. Statistical analysis was performed using factor analysis and multiple regression analysis. RESULTS: Fifteen out of 109 (13.8%) were found to be high-risk patients for depression based on responses to the questionnaire using the depression scale. We extracted 2 factors of stress-coping type, namely Factor 1, "Directly coping with the problem," of patients who try to directly resolve the problem in a positive manner and Factor 2, "Stress-release while avoiding the problem," for those who relieve their feelings in response to the stress without resolving the problem itself. When multiple regression analysis was conducted with the depression scale as the dependent variable and the stress-coping factor as the independent variable, Factor 1 tended to be associated with reduced depression and Factor 2 with increased depression. CONCLUSIONS: Results showed that to improve the mental health of those who receive kidney transplants, it is necessary to examine the depression and stress-coping types of such patients at an early stage and carry out education on stress-coping, focusing on resolving the actual problem.

Changes in resting-state brain networks after cognitive-behavioral therapy for chronic pain.

BACKGROUND: Cognitive-behavioral therapy (CBT) is thought to be useful for chronic pain, with the pathology of the latter being closely associated with cognitive-emotional components. However, there are few resting-state functional magnetic resonance imaging (R-fMRI) studies. We used the independent component analysis method to examine neural changes after CBT and to assess whether brain regions predict treatment response. METHODS: We performed R-fMRI on a group of 29 chronic pain (somatoform pain disorder) patients and 30 age-matched healthy controls (T1). Patients were enrolled in a weekly 12-session group CBT (T2). We assessed selected regions of interest that exhibited differences in intrinsic connectivity network (ICN) connectivity strength between the patients and controls at T1, and compared T1 and T2. We also examined the correlations between treatment effects and rs-fMRI data. RESULTS: Abnormal ICN connectivity of the orbitofrontal cortex (OFC) and inferior parietal lobule within the dorsal attention network (DAN) and of the paracentral lobule within the sensorimotor network in patients with chronic pain normalized after CBT. Higher ICN connectivity strength in the OFC indicated greater improvements in pain intensity. Furthermore, ICN connectivity strength in the dorsal posterior cingulate cortex (PCC) within the DAN at T1 was negatively correlated with CBT-related clinical improvements. CONCLUSIONS: We conclude that the OFC is crucial for CBT-related improvement of pain intensity, and that the dorsal PCC activation at pretreatment also plays an important role in improvement of clinical symptoms via CBT.

The longitudinal mental health impact of Fukushima nuclear disaster exposures and public criticism among power plant workers: the Fukushima NEWS Project study.

BACKGROUND: The Fukushima Daiichi and Daini Nuclear Power Plant workers experienced multiple stressors as both victims and onsite workers after the 2011 Great East Japan Earthquake and subsequent nuclear accidents. Previous studies found that disaster-related exposures, including discrimination/slurs, were associated with their mental health. Their long-term impact has yet to be investigated. METHOD: A total of 968 plant workers (Daiichi, n = 571; Daini, n = 397) completed self-written questionnaires 2-3 months (time 1) and 14-15 months (time 2) after the disaster (response rate 55.0%). Sociodemographics, disaster-related experiences, and peritraumatic distress were assessed at time 1. At time 1 and time 2, general psychological distress (GPD) and post-traumatic stress response (PTSR) were measured, respectively, using the K6 scale and Impact of Event Scale Revised. We examined multivariate covariates of time 2 GPD and PTSR, adjusting for autocorrelations in the hierarchical multiple regression analyses. RESULTS: Higher GPD at time 2 was predicted by higher GPD at time 1 (ß = 0.491, p < 0.001) and discrimination/slurs experiences at time 1 (ß = 0.065, p = 0.025, adjusted R 2 = 0.24). Higher PTSR at time 2 was predicted with higher PTSR at time 1 (ß = 0.548, p < 0.001), higher age (ß = 0.085, p = 0.005), and discrimination/slurs experiences at time 1 (ß = 0.079, p = 0.003, adjusted R 2 = 0.36). CONCLUSIONS: Higher GPD at time 2 was predicted by higher GPD and discrimination/slurs experience at time 1. Higher PTSR at time 2 was predicted by higher PTSR, higher age, and discrimination/slurs experience at time 1.

Applicability of buccal fat pad grafting for oral reconstruction.

This study evaluated the applicability of pedicled buccal fat pad grafting for the reconstruction of defects surgically created during oral surgery. A buccal fat pad graft was applied in 23 patients (5 males, 18 females; mean age 68.3 years) between 2003 and 2011. The graft was used to cover surgical defects of the palate, maxilla, upper gingiva, buccal mucosa, lower gingiva, oral floor, and temporomandibular joint region. Size of the surgical defects ranged from 15mm×12mm to 30mm×40mm; size of the buccal fat pad ranged from 15mm×12mm to 43mm×38mm. A pedicled buccal fat pad was prepared by incising the maxillary vestibule following primary surgery, and the surrounding connective tissue was preserved to supply nutrition to the pedicle during surgery. The buccal fat pad was placed on the raw surface of soft tissue or bone surface and sutured to the surrounding tissue of the defect. Complete epithelialization was observed within 4 weeks postoperatively. There were no complications or functional disorders during follow-up. Buccal fat pad grafting appears to be feasible for the reconstruction of surgically induced defects, and can be extended to the palate, mandible, mouth angle, and temporomandibular joint region.

Apoplexy accompanying pituitary adenoma as a complication of preoperative anterior pituitary function tests.

Pituitary apoplexy occurs as a very rare complication of the pituitary function test. We have experienced two cases of pituitary apoplexy following anterior pituitary function tests for preoperative assessment: a triple bolus test and a TRH test. To elucidate such a rare complication, we outline our two cases and review 28 cases from the literature. The clinical characteristics, etiology, pathophysiology, and diagnostic and therapeutic implications are also discussed. The combined data suggest that pituitary function tests have the potential to precipitate pituitary apoplexy, and its manifestations range from a clinically benign event to a catastrophic presentation with permanent neurological deficits or even death, although most patients may fortunately have a good outcome. We suggest that the pituitary function test should not be done as a routine test, and when such a test is planned, the patient should be observed with caution for any symptomatic changes for at least 2 hours following the test for appropriate treatment. Further, MRI, especially enhanced studies, may provide an earlier diagnosis of the pituitary apoplexy since CT scan images often fail to demonstrate either density changes or obvious enlargement of the pituitary adenoma at the acute stage.

Growth hormone therapy and scoliosis in patients with Prader-Willi syndrome.

Growth hormone (GH) therapy for short stature in patients with Prader-Willi syndrome (PWS) has started worldwide, and various favorable effects have been reported. However, the possibility of progression of scoliosis arises as a new problem of the GH therapy. In this study, we analyzed whether 72 patients who have been followed up in our hospital have such a problem. They included 46 males and 26 females (41 patients with the GH therapy and 31 without it) aged from one to 49 years. Consequently, 33 (45.8%) of 72 patients had scoliosis with the Cobb angle of >10 degrees. Twenty (48.8%) of forty-one patients who received a GH therapy and 13 (41.9%) of 31 patients without the therapy had scoliosis, the frequency of scoliosis between the two groups showing no statistical difference (P = 0.56). Height velocity of scoliotic and non-scoliotic patients during the first year of the therapy was 8.59 +/- 1.92 and 10.70 +/- 2.54 cm, respectively, showing a significant difference (P < 0.001). This shows that accelerated height velocity may not induce scoliosis. Comparison of starting age of a GH treatment revealed that non-scoliotic patients received the therapy earlier than scoliotic patients (P = 0.021). Among 20 scoliotic patients who received the GH therapy, the degree of scoliosis progressed during the therapy in six patients, improved in three and fluctuated in one. Many patients showed progression of scoliosis with age irrespective of the use of GH, and some patients improved their scoliosis during the GH therapy. These findings showed that a GH therapy increases height velocity of PWS patients but does not necessarily develop scoliosis, and early start of the therapy may not be an exacerbating factor of scoliosis.

Cause of sudden, unexpected death of Prader-Willi syndrome patients with or without growth hormone treatment.

Patients with Prader-Willi syndrome (PWS) are recognized to have a tendency of sudden, unexpected death (SED), but its exact cause is unknown because of paucity of such case reports. Since growth hormone (GH) treatment was applied to PWS patients worldwide, several cases of death have been reported. However, whether the therapy is directly related to their SED remains unknown, too. We collected 13 deceased PWS patients (Group A, aged 9 months to 34 years) who had never received GH therapy, and seven deceased patients (Group B, all boys aged 0.7-15 years) having received the therapy from the registration in PWS-patient-support associations and from the literature, respectively. We then compared the cause of SED between the two groups. Irrespective of GH therapy, SED of infants under age 1 year was associated with milk aspiration or hypothalamic dysregulation of respiration, while SED of patients in early childhood or adolescence occurred at sleeping in association with preceding viral infections. In contrast, SED of four adult (>20 years of age) patients who never received GH therapy was associated with complications, such as leg cellulites and pulmonary embolism, secondary to massive obesity and diabetes mellitus (DM). Two Group-B patients (aged 14 and 20 years) without any obesity-related or diabetes-related complications died of drowning in a bath tub, and their drowning death could be related to poor respiratory control. These findings indicated that the cause of SED is not essentially different between PWS patients with and without GH treatment. Deceased PWS patients may have had underlying respiratory dysregulation and hypothalamic dysfunction, and GH therapy might have led to certain obstructive respiratory disturbances that exacerbated the respiratory conditions. This will call clinicians' attention when using GH in PWS patients, for example, careful determination of the dose of GH and careful monitoring of patient's respiratory conditions, especially in male obese patients with respiratory problems.

Vanishing pituitary mass revealed by timely magnetic resonance imaging: examples of spontaneous resolution of nonfunctioning pituitary adenoma.

Spontaneous necrosis of a pituitary adenoma is not rare but represents a very unlikely way of curing a nonfunctioning pituitary adenoma. We report two cases of nonfunctioning pituitary adenoma, one of them with a family history of pituitary adenoma, in whom spontaneous complete resolution occurred through the necrosis of previously well-delineated adenoma. Sequential magnetic resonance imaging (MRI) scans provided clear evidence of the event, resulting in an empty sella. In the present cases, the pituitary necrosis was entirely asymptomatic with the exception of an initial atypical headache in one case, and cured the patients as well as a surgical procedure would have done. This exceptional curative process, however, should certainly not be relied on and does not rule out the possibility of recurrence.

Effects of musicokinetic therapy and spinal cord stimulation on patients in a persistent vegetative state.

We developed a method of musicokinetic therapy (MKT), employing a trampoline with live music performance (saxophone or electric piano), in an attempt to improve the clinical condition of patients in a persistent vegetative state (PVS). As an initial step for assessing the effect of MKT on PVS. we analyzed the changes in PVS score (range: 0-30) after MKT, which was continued for 3 months, in a consecutive series of 26 patients. These patients fulfilled the definition of PVS adopted by the Multi-Society Task Force on PVS. In this series, 7 patients were being treated by spinal cord stimulation at the same time. We, therefore, also had an opportunity to examine the effect of spinal cord stimulation on PVS. A greater or lesser improvement in PVS score (post-MKT score - pre-MKT score, mean +/- SD: 8.27 +/- 5.52) was observed in all patients except one. Among 12 patients who had been in PVS for 1 year or more before the initiation of MKT, 7 patients (56.3%) demonstrated improvement of their PVS score by 5 or more, and 4 patients (33.3%) reached a post-MKT score of greater than 20. The condition defined as PVS can never be scored better than 20. Since it is commonly felt that spontaneous improvement rarely occurs if PVS has continued for more than 6 months, the improvement after MKT appears to be better than that which could be observed spontaneously. The improvement in PVS score was often noted in patients with brain damage caused by trauma or SAH. There was no significant difference in improvement of the PVS score between patients who were treated by spinal cord stimulation and those who were not. Although the present study did not directly prove an effect of MKT on PVS, because no controls were involved, the results were consistent with the hypothesis that MKT is useful for improving the clinical condition of patients in PVS, especially those with severe brain damage caused by trauma or SAH.

Plasma orexin-A is lower in patients with narcolepsy.

Recently identified hypothalamic peptides called orexins (or hypocretins) have been implicated in the sleep-wake cycle and in sleep disorder narcolepsy. Neuropathological studies have shown that in patients with narcolepsy, global reduction in the expression of orexins occurs due to the loss of orexin neurons in the hypothalamus. Cerebrospinal fluid analysis has confirmed a reduced or undetectable level of orexin-A in most narcolepsy patients. In this study, measurement of plasma orexin showed significantly lower concentrations in patients with narcolepsy than in age- and gender-matched normal controls. These data suggest that low levels of orexin-A in plasma could serve as a biological marker for narcolepsy.

Dextran-magnetite complex: temperature dependence of its NMR relaxivity.

The NMR relaxivity of proton by dextran-magnetite (DM) complex was examined at temperatures from 20 to 80 degrees C. The decrease in T1 relaxivity with increasing temperature is due to the thermal activation of motion of water molecules in and/or surrounding DM particle. The decrease in magnetization of magnetite core is the secondary effect. The temperature dependence of T1 relaxivity was found to depend on molecular weight of dextran. The motion of dextran chains binding to core may affect the thermal activation of "heavy water" interacted with dextran. The Arrhenius plots of T1 relaxivity showed different slopes at 20-40 degrees C and 50-80 degrees C, while, no change in slope was observed for Fe(NO3)3, CuSO4 and Gd-DTPA solutions.

Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient.

BACKGROUND: Advanced glycation of proteins and their attendant advanced glycation end products (AGEs) contribute to the complications associated with diabetes mellitus or uremia. Regulatory mechanisms of AGE formation in vivo remain an issue of particular interest. We investigated a role of the glyoxalase detoxification system of precursor reactive carbonyl compounds (RCOs) in the in vivo AGE formation. METHODS: Plasma levels of AGEs [pentosidine and Nepsilon-carboxymethyllysine (CML)], their RCO precursors, d-lactate (the final product resulting from the glyoxalase detoxification pathway), as well as of various compounds known to generate AGE precursors and surrogate markers for oxidative stress (antioxidant enzymes and glutathione), were measured in both hemodialysis (HD) patients and normal subjects. The activity and protein expression of glyoxalase I, an enzyme essential for the detoxification of alpha-oxoaldehydes, in red blood cells (RBC) were also examined. RESULTS: In one 69-year-old lady who had been on hemodialysis (HD) for three years and had suffered from recurrent cardiovascular complications despite the absence of significant risk factors, plasma levels of pentosidine (77.3 +/- 2.4 pmol/mg protein) and CML (330.8 +/- 8.2 pmol/mg protein) were markedly elevated as compared to other HD patients (N = 20: 26.6 +/- 11.8 pmol/mg protein for pentosidine and 224.4 +/- 51.7 pmol/mg protein for CML). The plasma level of RCO precursors for pentosidine and CML was also higher in this patient than in other HD patients. Further investigation disclosed a very low activity in RBC of glyoxalase I (1.5 +/- 0.4 mU/106 RBC), as compared to other HD patients (3.9 +/- 0.6 mU/106 RBC) or normal subjects (4.0 +/- 0.6 mU/106 RBC). The glyoxalase I protein level, assessed in RBC by immunoblot analysis with a specific antibody, was markedly lower than that observed in HD patients and normal subjects. The causes of this deficiency remain unknown. Nucleotide sequencing of the products of reverse transcription-polymerase chain reaction from the patient's mononuclear cells revealed no genetic mutation within the coding region of the glyoxalase I gene. Plasma d-lactate level was also in the lower range (0.18 +/- 0.03 mg/dL) of the values measured in the other HD patients (0.27 +/- 0.09 mg/dL) and normal subjects (0.35 +/- 0.12 mg/dL). The plasma levels of various compounds known to generate AGE precursors (glucose, lipids and ascorbic acid) were either normal or low. The surrogate markers for oxidative stress such as antioxidant enzymes (glutathione peroxidases and superoxide dismutase) and glutathione were all within the range observed in the other HD patients. CONCLUSION: The unusually high levels of AGEs in this patient implicate a deficient glyoxalase detoxification of RCO precursors. The present clinical observation implicates, to our knowledge for the first time, the glyoxalase detoxification system and, in particular, glyoxalase in the actual level of AGEs in a uremic patient.

Telepsychiatry: assessment of televideo psychiatric interview reliability with present- and next-generation internet infrastructures.

OBJECTIVE: We assessed the reliability of remote video psychiatric interviews conducted via the internet using narrow and broad bandwidths. METHOD: Televideo psychiatric interviews conducted with 42 in-patients with chronic schizophrenia using two bandwidths (narrow, 128 kilobits/s; broad, 2 megabits/s) were assessed in terms of agreement with face-to-face interviews in a test-retest fashion. As a control, agreement was assessed between face-to-face interviews. Psychiatric symptoms were rated using the Oxford version of the Brief Psychiatric Rating Scale (BPRS), and agreement between interviews was estimated as the intraclass correlation coefficient (ICC). RESULTS: The ICC was significantly lower in the narrow bandwidth than in the broad bandwidth and the control for both positive symptoms score and total score. CONCLUSION: While reliability of televideo psychiatric interviews is insufficient using the present narrow-band internet infrastructure, the next generation of infrastructure (broad-band) may permit reliable diagnostic interviews.

Preliminary evaluation of volume-rendered three-dimensional display of time-of-flight MR angiography in the diagnosis of intracranial aneurysms.

We assessed the value of the volume-rendering method of displaying images of three-dimensional (3D) time-of-flight MR angiography (MRA) in the diagnosis of intracranial aneurysms. We obtained three-dimensional volume-rendered MRA from 21 patients with intracranial aneurysms. The images were evaluated in comparison with maximum-intensity-projection images (in 21 patients), conventional angiograms (in 21) and CT angiography (in nine). In 17 patients, 3D volume-rendered images were thought to show morphological features most clearly. They were superior to the other methods for demonstrating the precise location of the aneurysm in three patients and in showing the shape of the bleb in another three. 3D volume-rendered MRA can be effectively added to conventional imaging techniques for diagnosis of intracranial aneurysms.

Association study of serotonin transporter gene regulatory region polymorphism and alcoholism.

Previous studies have indicated associations between a functional biallelic repetitive element in the 5' regulatory region of the serotonin transporter gene (5-HTTLPR) and alcoholic subjects who have either dissocial personality disorder or severe withdrawal symptoms. To replicate these associations under the hypothesis that genetic polymorphism plays some role in the susceptibility or vulnerability of some subgroup of alcoholics, the associations between alcoholic subjects' genetic polymorphisms, clinical characteristics, and personality traits were examined. This case control study comprised 697 alcoholic and 270 control subjects. A questionnaire focusing on family and social background, history of drinking and alcohol withdrawal, DSM-III-R criteria for the evaluation of psychiatric conditions, and Feighner's criteria for the lifetime diagnosis and assessment of overall severity of alcoholism was administered to 373 alcoholic subjects. Temperament and Character Inventory (TCI) and Sensation Seeking Scale (SSS) were used to evaluate the other 324 alcoholics. The frequency of the homozygous short allele was significantly higher in alcoholic binge drinkers than in nonbinge drinking alcoholics. There were no significant differences in the frequencies of either the 5-HTTLPR genotype or the short vs. long allele in alcoholic and control subjects. The alcoholics' 5-HTTLPR genotype and allele frequencies did not differ significantly by the severity of withdrawal symptoms or by the number of positive Feighner's diagnostic criteria. Although these results indicate an association between 5-HTTLPR and a subgroup of alcoholics characterized by binge drinking, the authors found no differences in SSS and TCI subscale scores for alcoholics with different 5-HTTLPR genotypes. Future studies of the association in other alcoholic population should take into account personality traits.

Intraoperative wake-up procedure with propofol and laryngeal mask for optimal excision of brain tumour in eloquent areas.

This is the first thesis describing a new technique for awake craniotomy using a laryngeal mask. Awake craniotomy with propofol infusion has become increasingly popular for the optimal excision of brain tumours located in eloquent areas. During awake craniotomy, tracheal intubation is not performed and propofol infusion is limited to within doses which render the patient just sedated. This asleep-awake procedure is occasionally associated with difficulty in controlling brain volume, especially in patients with a significant mass effect of their brain tumours, since sufficient sedation with propofol tends to cause hypercapnea. We report an intraoperative wake-up procedure employing a laryngeal mask, which enables general anaesthesia to be performed at a sufficient dose of propofol and with control of the brain volume under mechanically assisted ventilation. Before the beginning of cortical mapping, propofol infusion is completely terminated, so allowing the patient to wake up within 5-15 min. Following completion of the tumour excision, general anaesthesia is re-induced at a sufficient dose of propofol. The laryngeal mask can be temporarily removed and repositioned with ease, if necessary. In our experience, this technique is applicable for the optimal excision of brain tumours, especially in patients who are very obese or those who have very large lesions.