Acute effects of low-intensity one-legged electrical muscle stimulation on arterial stiffness in experimental and control limbs.

The aim of this study was to examine the acute effects of low-intensity one-legged electrical muscle stimulation (EMS) for skeletal muscle on arterial stiffness in EMS and non-EMS legs. Eighteen healthy subjects received two different protocols (Control (CT) and Experimental (ET) trials) in random order on separate days. EMS was applied to the left lower limb at 4 Hz for 20 min at an intensity corresponding to an elevation in pulse rate of approximately 15 beats/min (10.9 ± 5.1% of heart rate reserve). Before and after the experiment, arterial stiffness parameters in the control right leg (CRL) and control left leg (CLL) in CT and non-EMS leg (NEL) and EMS leg (EL) in ET were assessed by pulse wave velocity (baPWV, faPWV) and cardio-ankle vascular index (CAVI). No significant changes in all parameters were observed in either leg in CT. Conversely, in ET, low-intensity, single-leg EMS significantly reduced CAVI, baPWV, and faPWV in the EL, but not in the NEL. Acute, low-intensity single-leg EMS reduces arterial stiffness only in the EL. These data support our idea that physical movement-related regional factors rather than systematic factors are important for inducing acute reductions in arterial stiffness.

Development and implementation of an aspiration pneumonia cause investigation algorithm.

The diagnostic criteria of aspiration pneumonia have not been established, and it remains an underdiagnosed entity. Diagnosis and cause investigation is essential in improving the management of aspiration pneumonia. The Japanese Respiratory Society Guidelines for the Management of Pneumonia in Adults (JRS Guidelines) show a list of risk factors for aspiration pneumonia. We developed an algorithm to aid physicians in evaluating these possible underlying factors and guide their management with a focus on aspiration pneumonia. The algorithm was developed based on the JRS Guidelines. The algorithm suggested dysphagia screening, pneumococcal and influenza vaccination, and other preventative measures for pneumonia. The algorithm was implemented in the acute setting of a general hospital among older patients admitted with pneumonia. Their outcomes were compared with a historical control group constituting similar patients from the previous year. Forty patients with pneumonia were assessed with the algorithm group, and 44 patients were included in the control group. In the algorithm group, significantly more cases (95.0% vs. 15.9%, p < 0.01) underwent early screening for a swallowing disorder. Two patients in the algorithm group were diagnosed with a new condition causing aspiration pneumonia, as opposed to none in the control group. Drugs with a potential risk for aspiration were identified and discontinued in 27.5% of the patients in the algorithm group and 4.5% in the control group. In conclusion, an aspiration pneumonia cause investigation algorithm translating the JRS guideline approach into practice enhanced the rate of swallow screening and preventative measures for aspiration.

Acute Effects of Low-Intensity Electrical Stimulation on Segmental Arterial Stiffness.

Electrical muscle stimulation (EMS) has traditionally been employed to improve muscle strength and glucose uptake. EMS may also reduce arterial stiffness, but little is known about whether low-intensity EMS reduces systemic and/or regional arterial stiffness. This study aimed to examine the effects of low-intensity EMS of the lower limbs on segmental arterial stiffness. Fourteen healthy subjects participated in experiments under two different protocols (control resting trial (CT) and electrical stimulation trial (ET)) in random order on separate days. The EMS was applied to the lower limbs at 4 Hz for 20 min at an intensity corresponding to an elevation of approximately 15 beats/min in pulse rate (10.7 ± 4.7% of heart rate reserve). Arterial stiffness was assessed by cardio-ankle vascular index (CAVI), CAVI0, heart-ankle pulse wave velocity (haPWV), brachial-ankle pulse wave velocity (baPWV), heart-brachial pulse wave velocity (hbPWV), and carotid-femoral pulse wave velocity (cfPWV). In both trials, each parameter was measured at before (Pre) and 5 min (Post 1) and 30 min (Post 2) after trial. After the experiment, CT did not cause significant changes in any arterial stiffness parameters, whereas ET significantly reduced CAVI (from Pre to Post 1: -0.8 ± 0.5 unit p < 0.01), CAVI0 (from Pre to Post 1: -1.2 ± 0.8 unit p < 0.01), haPWV (from Pre to Post 1: -47 ± 35 cm/s p < 0.01), and baPWV (from Pre to Post 1: -120 ± 63 cm/s p < 0.01), but not hbPWV or cfPWV. Arm diastolic blood pressure (BP) at Post 2 was slightly but significantly increased in the CT compared to Pre or Post 1, but not in the ET. Conversely, ankle diastolic and mean BPs at Post 1 were significantly reduced compared to Pre and Post 2 in the ET (p < 0.01). These findings suggest that low-intensity EMS of the lower limbs reduces arterial stiffness, but only in sites that received EMS.

Limb-Specific Features and Asymmetry of Nerve Conduction Velocity and Nerve Trunk Size in Human.

This study aimed to simultaneously examine the differences of human nerve conduction velocity (NCV) and nerve cross-sectional area (nCSA) between the upper and lower limbs and between different regions of the upper and lower limbs. Thirty healthy subjects volunteered for the study. NCV and nCSA of the ulnar and tibial nerves were measured with the dominant and non-dominant arms and the supporting and reacting legs using supramaximal electric stimulation and peripheral nerve ultrasonography at three regions for ulnar and tibial nerves, respectively. Supramaximal electric stimulation was superficially applied to the ulnar and tibial nerves at each point. These action potentials were recorded from the digiti minimi and soleus muscles for the ulnar and tibial nerves, respectively. Our results clearly showed that the NCV, nCSA, and circumference of the ulnar and tibial nerves were higher and greater in the lower limbs than in the upper limbs. The greater the circumference, the greater the nCSA for both the upper and lower limbs. However, unlike the upper limbs, the supporting leg did not have higher NCV than the reacting leg despite its greater circumference. Therefore, nCSA can be related to the circumference but not necessarily function for NCV developments of the lower limbs. These various aspects between the upper and lower limbs suggest that NCV does not depend on the nCSA sizes or upper and lower limb circumference; the results indicate the existence of limb-specific NCV but not nCSA developments.

The epidemiology of minor surgical problems during specialists' absence: Single center, descriptive study.

BACKGROUND: In Japan, even if physicians have not experienced surgical training, they face many instances in which they must provide initial surgical treatment, especially during off-hours. This study aimed to identify the frequency and fields of commonly encountered problems in a Japanese emergency department. METHODS: A retrospective review was performed to identify walk-in outpatients with exogenous problems visiting during off-hours in the Japanese educational hospital providing primary to tertiary emergency care between January 1 and December 31, 2014. Diseases were aggregated according to International Classification of Primary Care (Second Edition; ICPC-2). RESULTS: During the study period, 33 424 patients visited and 7476 were classified into the "exogenous" group. We analyzed the data of 7421 patients after excluding 55 who were deemed undiagnosable based on reviews of the charts. The median age of patients who visited the ED during off-hours was 29 years (range: 0-101 years, IQR: 8-60 years). Altogether, 226 types of problems included in ICPC-2 were identified during the study period. The majority fields of exogenous problems were 'skin,' 'Musculoskeletal,' and 'eye.' The 15 problems with the highest frequencies accounted for 50.2% of the total problems. CONCLUSIONS: We identified surgical problems with high treatment frequencies among patients visiting the ED during off-hours. Providing education focusing on these frequent surgical problems can help to improve the initial treatment quality and reduce the anxiety for those doctors who provide initial surgical treatment.

Development of a 2-h suicide prevention program for medical staff including nurses and medical residents: A two-center pilot trial.

BACKGROUND: Suicide is a crucial global health concern and effective suicide prevention has long been warranted. Mental illness, especially depression is the highest risk factor of suicide. Suicidal risk is increased in people not only with mental illness but also with physical illnesses, thus medical staff caring for physically-ill patients are also required to manage people with suicidal risk. In the present study, we evaluated our newly developed suicide intervention program among medical staff. METHODS: We developed a 2-h suicide intervention program for medical staff, based on the Mental Health First Aid (MHFA), which had originally been developed for the general population. We conducted this program for 74 medical staff members from 2 hospitals. Changes in knowledge, perceived skills, and confidence in early intervention of depression and suicide-prevention were evaluated using self-reported questionnaires at 3 points; pre-program, immediately after the program, and 1 month after program. RESULTS: This suicide prevention program had significant effects on improving perceived skills and confidence especially among nurses and medical residents. These significant effects lasted even 1 month after the program. LIMITATIONS: Design was a single-arm study with relatively small sample size and short-term follow up. CONCLUSIONS: The present study suggests that the major target of this effective program is nurses and medical residents. Future research is required to validate the effects of the program with control groups, and also to assess long-term effectiveness and actual reduction in suicide rates.

Efficacy of hormonal and mental treatments with MMPI in FtM individuals: cross-sectional and longitudinal studies.

BACKGROUND: Cross-sex hormone treatment (CSHT) is an important option for gender dysphoria (GD) individuals to improve the quality of life. However, in Japan, sex reassignment surgery (SRS) and CSHT for GD had been discontinued until 1998 (over 30 years). After resumption, the number of GD individuals wishing treatment rapidly increased. On the other hand, the number of medical institutions available for evaluation was limited. For this reason, hormonal treatment has been administered to GD individuals requiring the prompt start of CSHT in the absence of mental health assessment by specialists. In this study, we examined the efficacy of CSHT and psychotherapy. METHODS: The participants were 155 female-to-male (FtM) individuals who consulted our gender identity clinic, and were definitively diagnosed. A cross-sectional study was conducted by dividing them into two groups: groups with and without CSHT on the initial consultation (Group CSHT: n = 53, Group no-CSHT: n = 102). In all participants, Minnesota Multiphasic Personality Inventory (MMPI) and blood hormone tests were performed on the initial consultation. In addition, CSHT was combined with psychotherapy for a specific period in Group no-CSHT, and FtM individuals in whom an additional MMPI test could be conducted (Group combined treatment (CT), n = 14) were enrolled in a longitudinal study. RESULTS: In the cross-sectional study, there was no significant difference on the MMPI test. In the longitudinal study, there were improvements in the clinical scales other than the Mf scale on the MMPI test. In Group CT, the D, Sc, and Si scale scores on the initial consultation were significantly higher than in Group CSHT. However, there was no clinical scale with a significantly higher value after the start of treatment. The Pd scale score was significantly lower. CONCLUSIONS: CSHT improved mental health. Psychotherapy-combined CSHT may further improve it. TRIAL REGISTRATION: The study was reviewed and approved by the Ethics Committee of Kansai Medical University (A comprehensive treatment for gender dysphoria: No. 0314 registered date 10th December 2003), and was approved at UMIN000028102 on 6th July 2017 as retrospectively registered.

Cross calibration of 123I-meta-iodobenzylguanidine heart-to-mediastinum ratio with D-SPECT planogram and Anger camera.

BACKGROUND: Cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake is quantified using the heart-to-mediastinum ratio (HMR) with an Anger camera. The relationship between HMR determined using D-SPECT with a cadmium-zinc-telluride detector and an Anger camera is not fully understood. Therefore, the present study aimed to define this relationship using images derived from a phantom and from patients. METHODS: Cross-calibration phantom studies using an Anger camera with a low-energy high-resolution (LEHR) collimator and D-SPECT, and clinical 123I-MIBG studies proceeded in 40 consecutive patients (80 studies). In the phantom study, a conversion coefficient (CC) was defined based on phantom experiments and applied to the Anger camera and the D-SPECT detector. The HMR was calculated using anterior images with the Anger camera and anterior planograms with D-SPECT. First, the HMR from D-SPECT was cross-calibrated to the Anger camera, and then, the HMR from both cameras were converted to the medium-energy general-purpose collimator condition (CC 0.88; ME88 condition). The relationship between HMR and corrected and uncorrected methods was examined. A 123I-MIBG washout rate was calculated using both methods with and without background subtraction. RESULTS: Based on the phantom experiments, the CC of the Anger camera with an LEHR collimator and of D-SPECT using an anterior planogram was 0.55 and 0.63, respectively. The original HMR from the Anger camera and D-SPECT was 1.76 ± 0.42 and 1.86 ± 0.55, respectively (p < 0.0001). After D-SPECT HMR was converted to the Anger camera condition, the corrected D-SPECT HMR became comparable to the values under the Anger camera condition (1.75 ± 0.48, p = n. s.). When the HMR measured using the two cameras were converted under the ME88 condition, the average standardized HMR from the Anger camera and D-SPECT became comparable (2.21 ± 0.65 vs. 2.20 ± 0.75, p = n. s.). After standardization to the ME88 condition, a systematic difference in the linear regression lines disappeared, and the HMR from both the Anger (StdHMRAnger) and D-SPECT (StdHMRDSPECT) became comparable. Additional correction using a regression line further improved the relationship between both HMR [StdHMRDSPECT = 0.09 + 0.98 × StdHMRAnger (R 2 = 0.91)]. The washout rate closely correlated with and without background correction between both methods (R 2 = 0.83 and 0.65, respectively). CONCLUSION: The phantom-based conversion method is applicable to D-SPECT and enables the common application of HMR irrespective of D-SPECT and the Anger camera.

The impact of delirium on outcomes in acute, non-intubated cardiac patients.

BACKGROUND: Because of progress in cardiovascular management, many critically ill geriatric patients undergo various procedures and intensive cardiovascular care treatments. Although delirium frequently affects geriatric patients post-procedurally and after intensive cardiovascular care, the impact of delirium on acute cardiac patients has not been well understood. The objective of this study was to investigate the impact of delirium on outcomes in acute, non-intubated cardiac patients. METHODS: This was a prospective cohort study including non-surgical cardiac patients aged 65 years or older admitted to the intensive care unit or intensive cardiac care unit. We excluded mechanically ventilated patients. Delirium was evaluated using the confusion assessment method for the intensive care unit. The primary outcome analysed was 60-day mortality. The secondary outcomes analysed were risk and precipitating factors for delirium development. RESULTS: Of 163 patients, 35 (21.5%) developed delirium. Patients with delirium had higher 60-day mortality rates than those without delirium (22.9% versus 3.9%, P<0.001) and spent an average of 10 days longer in the hospital (32±20 versus 22±16 days, P=0.002). On the multivariable Cox analysis, delirium was independently associated with 60-day mortality (adjusted hazard ratio 3.91; 95% confidence interval 1.06-17.36; P=0.04), which was also confirmed by the propensity score-matched analysis. Dementia, history of cerebrovascular disease, and higher sequential organ failure assessment score were significantly associated with delirium development. CONCLUSIONS: Acute delirium is common and predicts mortality in non-intubated cardiac patients. Cardiac critical care providers should be aware of this neurological condition.

Neuromechanical Modulation of the Achilles Tendon During Bilateral Hopping in Patients with Unilateral Achilles Tendon Rupture, Over 1 Year After Surgical Repair.

BACKGROUND: Patients who have had an Achilles tendon (AT) rupture repaired are potentially at higher risk for re-rupture than those without previous rupture. Little attention has been given to the neuromechanical modulation of muscle-tendon interaction and muscle activation profiles during human dynamic movements after AT rupture repair. OBJECTIVE: The purpose of this study was to examine muscle-tendon behavior and muscle activation during bilateral hopping. METHODS: We enrolled nine subjects who had undergone surgical repair of unilateral AT rupture within the past 1-2 years. Subjects performed bilateral hopping while we took ultrasound, kinematic, and electromyogram recordings and measurements. AT behaviors were also recorded. We then compared responses between values obtained from the ruptured AT leg (LEGATR) and non-ruptured AT leg (LEGNOR). RESULTS: During hopping, the AT stretching amplitudes were greater in the LEGATR than in the LEGNOR, although the peak AT force and stiffness were smaller in the LEGATR than in the LEGNOR. The AT negative mechanical work did not show any significant differences between both legs. However, positive works were significantly lower in the LEGATR than in the LEGNOR. Electromyogram patterns in both soleus and tibialis anterior muscles clearly differed after ground contact for the LEGATR and the LEGNOR. CONCLUSIONS: These results suggest that the repaired ruptured AT can be compliant and have insufficient Young's modulus, which can influence mechanical responses in muscle activities. The modulation of agonist-antagonist muscle activities corresponding to the different levels of stiffness between the LEGATR and the LEGNOR may not be fully functioning during the pre-activation phase.

Profile comparison revealed deviation from structural constraint at the positively selected sites.

The amino acid substitutions at a site are affected by mixture of various constraints. It is also known that the amino acid substitutions are accelerated at sites under positive selection. However, the relationship between the substitutions at positively selected sites and the constraints has not been thoroughly examined. The advances in computational biology have enabled us to divide the mixture of the constraints into the structural constraint and the remainings by using the amino acid sequences and the tertiary structures, which is expressed as the deviation of the mixture of constraints from the structural constraint. Here, two types of profiles, or matrices with the size of 20 x (site length), are compared. One of the profiles represents the mixture of constraints, and is generated from a multiple amino acid sequence alignment, whereas the other is designed to represent the structural constraints. We applied the profile comparison method to proteins under positive selection to examine the relationship between the positive selection and constraints. The results suggested that the constraint at a site under positive selection tends to be deviated from the structural constraint at the site.

Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events.

OBJECTIVE: Comprehensive profiling of gene expression in peripheral blood leucocytes (PBLs) in patients with acute coronary syndrome (ACS) as a prognosticator is needed. We explored the specific profile of gene expression in PBLs in ACS for long-term risk stratification. METHODS: 30 patients with ACS who underwent primary percutaneous coronary intervention (PCI) and 15 age-matched adults who participated in medical check-ups were enrolled from three centres. Peripheral blood samples were collected to extract RNA for microarray analyses. RESULTS: During the 5-year follow-up, 36% of this cohort developed the expected non-fatal coronary events (NFEs) of target lesion revascularisation (TLR) and PCI for a de novo lesion. Class comparison analysis (p<0.005) demonstrated that 83 genes among 7785 prefiltered genes (41 upregulated vs 42 downregulated genes) were extracted to classify the patients according to the occurrence of NFE. Pathway analysis based on gene ontology revealed that the NFEs were associated with altered gene expression regarding the T-cell receptor signalling pathway in ACS. Univariate t test showed that the expression level of death-associated protein kinase1 (DAPK1), known to regulate inflammation, was the most significantly negatively regulated gene in the event group (0.61-fold, p<0.0005). Kaplan-Meier curve analysis and multivariate analysis adjusted for baseline characteristics or clinical biomarkers demonstrated that lower DAPK1 expression in PBL emerged as an independent risk factor for the NFEs (HR: 8.73; CI 1.05 to 72.8, p=0.045). CONCLUSIONS: Altered gene expression in T-cell receptor signalling in PBL in ACS could be a prognosticator for secondary coronary events. TRIAL REGISTRATION NUMBER: UMIN000001932; Results.

[Constructing a multicenter collaboration system].

Providing medical care for Gender Identity Disorder (GID) poses enormous challenges and difficulties. The one obstacle to overcome is building a pluralistic treatment system in collaboration with experts from various fields of medicine as outlined in "Guidelines for Treatment and Diagnosis of GID version 3rd" established by the Japanese Society of Psychiatry and Neurology. Another obstacle includes the multilayered decision tree in deployment of physical as well as psychiatric treatment. Offering continuous supports of the pluralistic treatment system following the multilayered decision tree poses a major obstacle. In this report, we examined these obstacles from a perspective of the actually accessible healthcare resources and came up with a proposal of constructing a multicenter collaboration system. As one of concrete example of a solution to these obstacles, we demonstrated our activity of "Kansai GID network." By sustaining these activities, many obstacles posed in the treatment of GID could be overcome. We hope substantial and comprehensive treatment systems for GID shall be promptly established in Japan.

Successful endoscopic ultrasound-guided fine-needle aspiration of the pelvic lesion through the sigmoid colon.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a useful modality when the target is a lymph node located in the mediastinum, perigastric area or perirectum. Although it is difficult to carry out EUS-FNA of the colon using an oblique view linear scope, we report two cases of successful EUS-FNA of the lesions via the proximal sigmoid colon using a recently available new convex type EUS scope. Case 1 was a 77-year-old Japanese woman noted to have multiple lymph node swelling in the para-aortic area and in the pelvis. Case 2 was a 60-year-old Japanese woman noted to have a large mass in the left lower abdomen. In case 1, oral EUS showed no lymph node swelling. In both cases, EUS with forward-viewing radial echoendoscope was carried out via the anus, and multiple lymph-node swelling or a large mass was observed near the proximal sigmoid colon. In the EUS-FNA for these cases, we used a new convex-type EUS scope that has an oblique view, but with a wide-angled optical device giving a view similar to a forward one. EUS-FNA was successfully carried out on the lesions. The pathological specimen revealed diffuse large B-cell lymphoma in case 1 and gastrointestinal stromal tumor (GIST) in case 2.

Effect of the oral absorption of benzenesulfonanilide-type cyclooxygenase-1 inhibitors on analgesic action and gastric ulcer formation.

A benzensulfonanilide-type cyclooxygenase-1 (COX-1)-selective inhibitor, ZXX2-77: 4-amino-4'-chloro-N-methylbenzenesulfonanilide (4a), has been reported as a novel analgesic that does not cause gastric damage. This compound has a weak analgesic effect but has potent in vitro COX-1 inhibitory activity. Since the reason for the weak analgesic effect in vivo was thought to be the low rate of oral absorption, the blood concentration of ZXX2-77 (4a) was measured in rats. It was found that the C(max) value (1.2 microM) of ZXX2-77 (4a) at a dose of 30 mg/kg did not reach the COX-1 IC(50) value (3.2 microM). On the other hand, ZXX2-79 (4b) (SO(2)NH derivative of ZXX2-77 (4a); 4-amino-4'-chlorobenzenesulfonanilide), which shows less potent COX inhibitory activities (COX-1 IC(50) = 12 microM, COX-2 IC(50) = 150 microM) than those of ZXX2-77 (4a) in vitro, was found to be more absorbable (C(max) = 16 microM at a dose of 30 mg/kg in rats) than ZXX2-77 (4a). Furthermore, ZXX2-79 (4b) not only showed a potent analgesic effect in a formalin test but also caused little gastric damage. These findings indicate that demethylated sulfonamide compounds are more easily absorbed than are N-methylated sulfonamide compounds and suggest that COX-1-selective inhibitors will be useful as analgesics that do not cause gastric damage.

Cyclooxygenase-1-selective inhibitors are attractive candidates for analgesics that do not cause gastric damage. design and in vitro/in vivo evaluation of a benzamide-type cyclooxygenase-1 selective inhibitor.

Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable to COX-1-inhibitory activity or other bioactivities. Here, we report that N-(5-amino-2-pyridinyl)-4-(trifluoromethyl)benzamide ( 18f, TFAP), which has a structure clearly different from those of currently available COX-1-selective inhibitors, is a potent COX-1-selective inhibitor (COX-1 IC 50 = 0.80 +/- 0.05 microM, COX-2 IC 50 = 210 +/- 10 microM). This compound causes little gastric damage in rats even at an oral dose of 300 mg/kg, though it has an analgesic effect at as low a dose as 10 mg/kg. Our results show that COX-1-selective inhibitors can be analgesic agents without causing gastric damage.

[Crime prevention in high-functioning pervasive developmental disorders with paraphilia].

Paraphilia refers to occasional concomitant disorders of pervasive developmental disorder (PDD). When a restricted interest of PDD is focused on a sexual object, paraphilia may be develop as a problematic symptom. However, having this concomitant disorder does not always result in criminal behavior. When the social interactivity of a particular patient with PDD is severely impaired, paraphilia could lead to a sex crime. Because pedophilia targets sacrifice innocent and defenseless children, it is critical to prevent such sex crimes by understanding the psychopathology of PDD with paraphilia, especially pedophilia. Two cases of male adolescents with high-functioning PDD and pedophilia were reported; one ended up committing a serious crime, and the other controlled his sexual impulse. The psychopathology of these two cases was similar; however, the outcome turned out to be quite different. The similarity and dissimilarity of these two cases were analyzed. We came to a conclusion that early intervention could be a key to prevent the development of criminal sexual behavior in PDD with paraphilia (pedophilia). Both patients became aware of pedophilia during adolescence and developed a depressive state at the time of consulting our clinic. In the first case, the patient stabbed a woman with a knife. He could not respect other people, including women he was sexually interested in and has always been preoccupied with his own peculiar ideas. He did not listen to other people's opinions and his abnormal thoughts had never been corrected because of his lack of ability to form interpersonal relationships. The second patient could control his sexual impulse. He has an ability to sympathize with the child he is sexually interested in and has confronted his sexual impulses. He could build interpersonal relationship with others and listen to other people's opinions. He made an effort to manage his sexual impulses positively through individual psychotherapy. He was diagnosed at the age of two years and started rehabilitation training soon after. He had some experiences of consulting people when he was in trouble. In the treatment and correctional education of pedophilia, some sort of special care regarding the characteristics of PDD is indispensable; e.g., pointing-out and explaining unacceptable behavior repeatedly, teaching the correct action concretely, and changing the pathological sexual preference into a constructive one, etc. These therapeutic approaches are quite different from controlling paraphilia without PDD. PDD adolescents with impaired social interactivity could be further helper if they are diagnosed at an earlier stage of their lives and managed appropriately. A sense of being accepted by others and also experiences of mutual interaction with others are particularly important for them. Professionals should be aware that an early and proper intervention method could prevent the later development of criminal behavior in PDD adolescents who suffer from a sense of incompatibility with others because of concomitant paraphilia.

Analgesic agents without gastric damage: design and synthesis of structurally simple benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors.

In order to create novel analgesic agents without gastric disturbance, structurally simple cyclooxygenase-1 (COX-1) inhibitors with a benzenesulfonanilide skeleton were designed and synthesized. As a result, compounds 11f and 15a, which possess a p-amino group on the benzenesulfonyl moiety and p-chloro group on the anilino moiety, showed COX-1-selective inhibition. Moreover compound 11f, which is the most potent compound in this study showed more potent analgesic activity than that of aspirin at 30 mg/kg by po. The anti-inflammatory activity and gastric damage, however, were very weak or not detectably different from aspirin. Since the structure of our COX-1 inhibitors are very simple, they may be useful as lead compounds for superior COX-1 inhibitors as analgesic agents without gastric disturbance.

[Outcome of treatment with surgical resection of the remaining tumor after modified M-VAC treatment for advanced urothelial carcinoma].

We retrospectively evaluated the effect of the surgical resection of the remaining tumor after modified M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) (m-M-VAC) treatment for locally advanced or metastatic urothelial carcinoma. In m-M-VAC therapy, methotrexate and vinblastine on 15 and 22 days were omitted from the classical M-VAC to avoid the discontinuation and the dose reduction, and duration of 1 course was shortened to 21 days from 28 days of the classical M-VAC. Seven patients with locally invasive or metastatic carcinoma of the renal pelvis, ureter, and bladder, 6 males and 1 female, with a median age 64.1 years, ranging from 49 to 77 years received m-M-VAC chemotherapy without severe side effects. In all patients, the residual viable carcinoma was completely resected and they achieved complete remission. The median survival time was 20 months (range, 7 to 61). Five of these 7 patients were still alive. Two patients had no recurrence and achieved long-term survival (survival duration; 61 and 39 months). Although further studies and long-term follow up are required, these results suggest that patients who present with locally advanced or metastatic urothelial carcinoma may benefit from surgical resection after m-M-VAC.