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OBJECTIVE Gamma Knife radiosurgery (GKRS) is an established surgical option for the treatment of trigeminal neuralgia (TN), particularly for high-risk surgical candidates and those with recurrent pain. However, outcomes after three or more GKRS treatments have rarely been reported. Herein, the authors reviewed outcomes among patients who had undergone three or more GKRS procedures for recurrent TN. METHODS The authors conducted a multicenter retrospective analysis of patients who had undergone at least three GKRS treatments for TN between July 1997 and April 2019 at two different institutions. Clinical characteristics, radiosurgical dosimetry and technique, pain outcomes, and complications were reviewed. Pain outcomes were scored on the Barrow Neurological Institute (BNI) scale, including time to pain relief (BNI score ≤ III) and recurrence (BNI score > III). RESULTS A total of 30 patients were identified, including 16 women and 14 men. Median pain duration prior to the first GKRS treatment was 10 years. Three patients (10%) had multiple sclerosis. Time to pain relief was longer after the third treatment (p = 0.0003), whereas time to pain recurrence was similar across each of the successive treatments (p = 0.842). Complete or partial pain relief was achieved in 93.1% of patients after the third treatment. The maximum pain relief achieved after the third treatment was significantly better among patients with no prior percutaneous procedures (p = 0.0111) and patients with shorter durations of pain before initiation of GKRS therapy (p = 0.0449). New or progressive facial sensory dysfunction occurred in 29% of patients after the third GKRS treatment and was reported as bothersome in 14%. One patient developed facial twitching, while another experienced persistent lacrimation. No statistically significant predictors of adverse effects following the third treatment were found. Over a median of 39 months of follow-up, 77% of patients maintained complete or partial pain relief. Three patients underwent a fourth GKRS treatment, including one who ultimately received five treatments; all of them reported sustained pain relief at the extended follow-up. CONCLUSIONS The authors describe the largest series to date of patients undergoing three or more GKRS treatments for refractory TN. A third treatment may produce outcomes similar to those of the first two treatments in terms of long-term pain relief, recurrence, and adverse effects.

The left atrial appendage is thought to be responsible for the majority of embolic strokes, and has become an important target in the surgical management of atrial fibrillation. We present an original clip-and-loop technique using an AtriClip via a left minithoracotomy for post-stroke patients with atrial fibrillation. This procedure was performed in 43 cases between March 2018 and January 2020. No patient had a thrombus at the edge of the clip or communication into the left atrial appendage 3 months after surgery. Anticoagulant could be discontinued in all patients. Follow-up at 23 ± 10 months showed no recurrence of stroke.

Background We performed a clinical and pathological analysis of cases of acute vascular rejection (AVR), characterized by intimal arteritis and transmural arteritis (Banff v score) after kidney transplantation, in an attempt to clarify the mechanisms underlying the development and prognostic significance of AVR. Methods AVR (Banff score: v >0) was diagnosed in 31 renal allograft biopsy specimens (BS) obtained from 31 renal transplant patients receiving follow-up care at the Department of Urology, Tokyo Women's Medical University, between January 2010 and April 2016. Results AVR was diagnosed at a median of 124.6 days after transplantation. Among the 31 BS showing evidence of AVR, AVR was mild (v1 in Banff's classification) in 25 cases, moderate (v2) in 6, and severe (v3) in none. We classified the 31 BS with evidence of AVR by their overall histopathological features as follows: isolated v lesions were observed in 6 BS, acute antibody-mediated rejection (AAMR) in 7, acute T-cell–mediated rejection (ATCMR) in 12, and both ATCR and AAMR in 6. Loss of the renal allograft occurred during the observation period in 3 patients, and, of the remaining cases with functioning grafts, deterioration of renal allograft function after biopsy occurred in only 2 patients. Conclusions The results of our study suggest that ATCMR contributes to AVR in 40% to 60% of cases, AAMR in 20% to 40% of cases, and isolated v lesions in 20% of cases. The prognosis of the patient with the graft that had AVR was relatively good under the present immunosuppression protocol and current anti-rejection therapies.

The purpose of the present study is to assess the perioperative changes in the cognitive function of patients after cardiovascular surgery (CVS) and to find out risk factors for early postoperative cognitive decline. From December 2013 to March 2017, 291 patients underwent elective or urgent CVS with cardiopulmonary bypass in our institution. One hundred and fifteen patients, who agreed to an evaluation of their cognitive function, were included in this study. The cognitive function was evaluated by the HDS-R and MMSE at three time points: before surgery, in the early postoperative period and at discharge. The patients’ characteristics, perioperative data, HDS-R and MMSE scores were obtained by reviewing their medical records retrospectively. The patients were stratified into three age groups. In all of the age groups, the early postoperative cognitive functional scores were severely decreased in comparison to the preoperative values. However, by the time of discharge, the function had improved to the same level as before surgery in each of the groups. In addition, the similar tendency was observed in patients with preoperative cognitive dysfunction. Moreover, multiple regression analysis demonstrated that preoperative cognitive function and age were significant risk factors for early cognitive impairment. Although preoperative cognitive decline and patients’ age were the risk factors for early postoperative cognitive impairment after CVS, a significant recovery can be expected even in elderly patients or patients with low preoperative cognitive function by the time of discharge.

Summary Background Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barre syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barre syndrome. Methods This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barre syndrome were aged 18 years or older and could not walk independently (Guillain-Barre syndrome functional grade 3–5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ≤2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with ClinicalTrials.gov, number, NCT02493725. Findings Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ≤2) was 61% (90% CI 42–78; n=14) in the eculizumab group, and 45% (20–73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression). The possibility that anaphylaxis and intracranial abscess were related to eculizumab could not be excluded. No deaths or meningococcal infections occurred. Interpretation The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials. Funding The Japan Agency for Medical Research and Development, Ministry of Health, Labor and Welfare, and Alexion Pharmaceuticals.

Objectives Many pancreaticoduodenal artery (PDA) aneurysms are associated with celiac artery (CA) stenosis. The pathogenesis of PDA aneurysm may be associated with hemodynamic changes due to CA stenosis/occlusion. The aim of this study was to assess the hemodynamic changes of celiaco-mesenteric anastomosis in patients with PDA aneurysms concomitant with CA occlusion using four-dimensional flow-sensitive magnetic resonance imaging (4D-Flow). Methods 4D-Flow was performed preoperatively on five patients. Seven age- and sex-matched individuals were used as controls. Hemodynamic parameters such as flow volume and maximum flow velocity in PDAs, gastroduodenal arteries, common hepatic arteries, and superior mesenteric arteries were compared between both groups. Wall shear stress (WSS) and oscillatory shear index (OSI) were mapped in both groups. Results In the patient group, 4D-Flow identified retrograde flow of both gastroduodenal arteries and common hepatic arteries. Heterogeneous distribution patterns of both WSS and OSI were identified across the entire PDA in the patient group. OSI mapping showed multiple regions with extremely high OSI values (OSI > 0.3) in all patients. All PDA aneurysms, which were surgically resected, were atherosclerotic. Conclusions 4D-Flow identified hemodynamic changes in celiaco-mesenteric arteries in patients with PDA aneurysms with concomitant CA occlusion. These hemodynamic changes may be associated with PDA aneurysm formation.

Although the natural course of UIAs remains unclear, the risk of aneurysmal SAH due to small (10 mm) asymptomatic UIAs is low. Endovascular therapy for UIAs has increased because of device development and the need for less invasive treatment. We report the results, safety, and efficacy of endovascular therapy of small asymptomatic UIAs.A total of 457 patients with 500 small asymptomatic UIAs (maximum diameter10 mm) underwent endosaccular coil embolization at Juntendo University Hospital and affiliated hospitals. We retrospectively evaluated the technical feasibility, immediate and short-to-midterm follow-up anatomic results, procedure-related complications, and clinical outcomes.Endosaccular coil embolization was completed in 481 aneurysms (96.2%) and attempted in 19 (3.8%). Completed aneurysms were treated with the simple (39.5%), balloon-assisted (51.4%), and double-catheter (9.1%) techniques. Immediate angiographic outcomes were CO for 309 (64.2%) aneurysms, RN for 72 (15.0%), and RA for 100 (20.8%). Procedure-related complications occurred in 38 aneurysms (7.6%): 19 ischemic, 11 hemorrhagic, and 8 others. Permanent morbidity and mortality were 0.8% and 0.2%, respectively. Anatomic outcome of 427 aneurysms followed up for6 months with conventional catheter or MR angiographies showed recanalization in 72 (16.9%) aneurysms, necessitating retreatment in 9.9% (mean, 31.4 months). No patients had aneurysmal SAH during the clinical follow-up period (mean, 34.7 months).In this series, endovascular therapy of small asymptomatic UIAs was highly feasible with low morbidity and mortality rates.

BACKGROUND Hydroxyethyl starch (HES) solution is characterized by its mean molecular weight (MW), concentration, and degree of substitution (DS). This character varies worldwide. METHODS After binding fluorescein-isothiocyanate (FITC-HES), we evaluated the retention rate of three types of 6% HES in the A2 and V2 blood vessels of rat cremaster muscles using intravital microscopy in a mild hemorrhage model (10% of total blood volume). After blood withdrawal, we infused three types of FITC-HES: HES-A (MW 150-200 kDa, DS 0.6-0.68), HES-B (MW 175-225 kDa, DS 0.45-0.55), or HES-C (MW 550-850 kDa, DS 0.7-0.8) before determining the FITC-HES retention rate in the intravital microscope. RESULTS For V2, the FITC-HES retention rates 120 min after the start of the infusion were 27% +/- 7.2% of baseline values (HES-A), 65% +/- 9.1% (HES-B), and 86% +/- 9.6% (HES-C); for A2 they were 27% +/- 6.6%, 73% +/- 10.2%, and 89% +/- 8.7%, respectively. HES-B and HES-C were retained in the vessels longer than HES-A (P = 0.028 for V2, P = 0.038 for A2 between HES-B and HES-A; P = 0.022 for V2, P = 0.037 for A2 between HES-C and HES-A). There was no difference in the rate of disappearance from the vessels between HES-B and HES-C. CONCLUSIONS HES-B and HES-C are equally retained in the blood vessels. Middle-sized HES-B with low DS and middle substitution pattern stayed in the blood vessels as long as the large-sized HES. HES solutions of varying characters should be examined to optimize HES infusion.

Human leukemia cell lines are of great value in investigating basic and applied aspects of cell biology and clinical medicine. There have been 37 leukemia cell lines carrying 11q23 translocation and MLL rearrangements; however, cell lines harboring with t(1;11)(p32;q23) have not been established. We report here for the first time a new acute monocytic leukemia (AMoL) cell line with t(1;11)(p32;q23), designated TZ-1, and herein describe its biological characteristics. Mononuclear cells isolated from the ascites from a patient with AMoL (French-American-British classification; acute myeloid leukemia M5a) were isolated and passaged by liquid culture medium for a year. TZ-1 cells revealed typical monocytic features in morphology and had a t(1;11)(p32;q23) translocation. The immunoprofiling as determined by flow cytometry showed that TZ-1 cells are positive for myeloid and monocytic markers with lymphoid-associated markers. Fluorescence in situ hybridization and reverse transcription-polymerase chain reaction analyses revealed MLL-EPS15 fusion transcript and protein. Taken together, these results suggest that TZ-1 is a new monocytic leukemia cell line with t(1;11) translocation and fusion gene MLL-EPS15. The established cell line, TZ-1, could provide a valuable model in the analysis of the pathogenesis of MLL-EPS15-positive leukemia and in the development of new agents for this type of leukemia.

The purpose of this study was to investigate whether or not central noradrenergic neurons were involved in the time structure of circadian variation of heart rate (HR) in hypertension. We used spontaneously hypertensive rats (SHR(Izm)) and normotensive controls (Wistar Kyoto rats, WKY(Izm)). We selectively destroyed the noradrenergic neurons in the central nervous system (CNS) by administering noradrenergic neurotoxin, N-(2-chloroethy)-N-ethyl-2-bromobenzylamine (DSP4). Frequency domain measures of variation of HR (VHR) were obtained using the maximum entropy method. The 24-h time frame in VHR is usually dominant in both SHR(Izm) and WKY(Izm). Fourteen days after the administering of DSP4, the mean 24-h systolic arterial pressure (SAP) remained higher in SHR(Izm) than in WKY(Izm). After chemical lesion, ultradian rhythms (12-, 8-, 6-, and 4-h periods) in VHR became more remarkable in both SHR(Izm) and WKY(Izm) than before chemical lesion. Before chemical lesion, an inverse relationship existed between frequency and power spectral density in VHR, demonstrating 1/f(beta) characteristics. The slope of 1/f(beta) in VHR did not differ between SHR(Izm) and WKY(Izm). After the chemical lesion it did not also differ from that of each strain in control period (before lesion). Therefore, the noradrenergic neurons may not affect the time structure of HR in SHR(Izm) and WKY(Izm) for short-term time analysis. However, the intact noradrenergic neurons in CNS may be important to keep normal cardiac autonomic function in SHR(Izm) for long-term analysis.

We have experienced three cases of retroesophageal right subclavian artery. Two cases were cadavers, and one case was a live human. In the two cadavers of a 68-year-old and a 76-year-old, respectively Japanese and European males, the right subclavian artery originated from the aorta after the aorta branched the right carotid artery, the left carotid artery and the left subclavian artery. The right carotid artery immerged solely from the aorta. Where the right subclavian artery originated from the aorta, the artery took a dorsal direction. It passed between the esophagus and the vertebral column. The esophagus was compressed from the dorsal side by the right subclavian artery. The structural anomaly of the right subclavian artery accompanied the cephalad recurrence of the branch from the right vagal nerve toward the larynx. In the live human case, we obtained CT views. The patient was a 41-year-old Japanese, who complained of dysphagia lusoria. We found that the right subclavian artery was anomalous and originated from the aorta as the last cardinal branch in the thorax.

Fragile X syndrome (FXS) is the most common single gene (FMR1) disorder affecting cognitive and behavioral function in humans. This syndrome is characterized by a cluster of abnormalities including lower IQ, attention deficits, impairments in adaptive behavior and increased incidence of autism. Here, we show that young males with FXS have profound deficits in prepulse inhibition (PPI), a basic marker of sensorimotor gating that has been extensively studied in rodents. Importantly, the magnitude of the PPI impairments in the fragile X children predicted the severity of their IQ, attention, adaptive behavior and autistic phenotypes. Additionally, these measures were highly correlated with each other, suggesting that a shared mechanism underlies this complex phenotypic cluster. Studies in Fmr1-knockout mice also revealed sensorimotor gating and learning abnormalities. However, PPI and learning were enhanced rather than reduced in the mutants. Therefore, these data show that mutations of the FMR1 gene impact equivalent processes in both humans and mice. However, since these phenotypic changes are opposite in direction, they also suggest that murine compensatory mechanisms following loss of FMR1 function differ from those in humans.

SUMMARYPreviously, we have found that immunosuppressive macrophages (Mφs) induced by Mycobacterium intracellulare-infection (MI-Mφs) required cell contact with target T cells to express their suppressor activity against concanavalin A (Con A)-induced T cell mitogenesis. In this study, we examined the profiles of cell-to-cell interaction of MI-Mφs with target T cells. First, MI-Mφs displayed suppressor activity in an H-2 allele-unrestricted manner, indicating that MHC molecules are not required for cell contact. The suppressor activity of MI-Mφs was reduced markedly by paraformaldehyde fixation or treatment with cytochalasin B or colchicine, indicating that vital membrane functions are required for their suppressor activity. Secondly, the suppressor activity of MI-Mφs was independent of cell-to-cell interaction via CD40 ligand/CD40 and Mφ-derived indoleamine 2,3-dioxygenase, which causes rapid degradation of tryptophan in T cells. Thirdly, precultivation of splenocytes with MI-Mφs, allowing cell-to-cell contact, reduced Con A- or anti-CD3 antibody-induced mitogenesis but not phorbol myristate acetate/calcium ionophore A23187-elicited proliferation of T cells. In addition, co-cultivation of T cells with MI-Mφs caused marked changes in profiles of the tyrosine phosphorylation of 33 kDa, 34 kDa and 35-kDa proteins and, moreover, the activation of protein kinase C and its translocation to the cell membrane. It thus appears that suppressor signals of MI-Mφs, which are transmitted to the target T cells via cell contact, principally cross-talk with the early signalling events before the activation of PKC and/or intracellular calcium mobilization.

Objective Interferon alpha (IFN-α) is a key cytokine associated with systemic lupus erythematosus (SLE). IFN-α induces the expression of CD64 on monocytes (mCD64). Although enhanced mCD64 expression has been reported in patients with SLE, it has never been assessed quantitatively. The aim of this study was to investigate whether or not mCD64 expression correlates with SLE disease activity. Methods The mCD64 expression levels were assessed quantitatively in 40 patients with active or inactive SLE by using flow cytometry. The mCD64 expression levels were subsequently compared with the SLE disease activity index (SLEDAI) and levels of existing SLE activity biomarkers, such as anti-DNA antibody, complements, and so on. Results The mCD64 expression was significantly higher in active disease than in inactive disease SLE (median molecules/cell, interquartile range: 34,648, 8174–24,932 and 20,865, 6357–21,503, respectively; p Conclusion The mCD64 expression is a simple and useful biomarker for evaluating disease activity in patients with SLE.

Our previous studies have suggested that synthetic octacalcium phosphate (OCP) could be resorbed and replaced by newly formed bone if implanted in rat skull defects. We hypothesized that the implanted OCP is more resorbable than other commonly used bone graft substitutes of calcium phosphate compounds, such as hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP). To test the hypothesis, the present study was designed to compare histomorphometrically resorption of the implanted OCP, HA, and beta-TCP, which were kept in the experimental cranial defect of rats for a long term. A full thickness of standardized trephine defect was made in the rat parietal bone, and the same volume of granules of OCP, HA, and beta-TCP were implanted into the defect. Five specimens of each group were fixed 6 months after implantation. The percentage of remaining implants (r-Imp%) and newly formed bone (n-Bone%) in the defect was analyzed histomorphometrically. The statistical analysis showed that the r-Imp% of OCP was significantly lower than that of HA and beta-TCP. In contrast, the n-Bone% of OCP was significantly higher than that of HA and beta-TCP. The present study has shown that the implanted OCP in the rat cranial defect is more resorbable than the implanted beta-TCP and HA, whereas the implanted OCP enhances bone formation more than the implanted beta-TCP and HA.

Mammalian spermatozoa require a maturational event after ejaculation that allows them to acquire the capacity for fertilization. This process, known as capacitation, occurs spontaneously in simple defined medium implicating a potential role of autocrine induction. This study shows that the ether phospholipid 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphocholine (PAF) meets the criteria for an autocrine mediator of capacitation. Sperm released PAF after their dilution into capacitation medium and expressed a receptor for PAF on their membranes. PAF stimulated changes in the motility of sperm and enhanced fertilization in vitro. These actions were inhibited by a PAF receptor antagonist (UR-12519) and by extracellular recombinant PAF:acetylhydrolase (an enzyme that degrades PAF to a biologically inert form). Seminal plasma contained an acid-labile PAF:acetylhydrolase, whereas capacitation was inhibited by an acid-labile factor within seminal plasma, implicating this factor as a potential decapacitation factor within seminal plasma. Sperm from a PAF receptor knock-out mouse strain failed to express the receptor and displayed a significantly (p0.01) reduced rate of capacitation, as assessed by the spontaneous onset of the acrosome reaction in vitro. When used for in vitro fertilization, sperm from PAF receptor knock-out mice gave a significantly lower rate of fertilization (21.5%) than did wild-type sperm (66.7%). The study shows for the first time the operation of an autocrine loop that induces capacitation in sperm in vitro and shows that this loop acts in concert with other mediators of capacitation to promote efficient fertilization.

OBJECTIVES The impact of radical prostatectomy on the quality of life (QOL) of patients were evaluated. MATERIALS AND METHODS A total of 22 patients who underwent radical prostatectomy for clinically localized prostate cancer entered this study. Patients were asked to complete a questionnaire containing the general health questionnaire (GHQ) and a series of questions evaluating voiding function, incontinence and sexual dysfunction before and after the operation. In addition, the visual analogue scaled (VAS) questionnaire containing incontinence and sexual dysfunction was applied. RESULTS No significant differences in GHQ were found between pre- and post operative status, but disease-targeted QOL such as sexual function was affected after the radical prostatectomy. In the points of incontinence and sexual dysfunction, VAS questionnaire significantly correlated with those of categorical questionnaires. CONCLUSIONS There results suggest that GHQ is not affected, but disease-targeted QOL in some categories of sexual function is affected by radical prostatectomy, and that VAS questionnaires are not only useful for assessing the disease-targeted QOL but also easy to quantify QOL of the patients.

This study was conducted to clarify the relationship between long-term prognosis of functional status after stroke and the magnetic resonance imaging (MRI) findings as well as complications in the course. A total of 98 patients with initial cerebral thrombosis were enrolled, and 65 patients surviving 5 years after the event, were studied in terms of cognitive function and activity of daily living (ADL). Mean age at registration (3 months after the event) was 72.0 years-old and 44 were male. MRI findings were divided into eight categories including the size and laterality of infarction, in addition to six categories as previously described. The presence of dementia was identified according to the HDS-R and the DSM-III-R scales, and the extent of dementia, assessed with the CDR scale, was divided into 3 grades: none, mild, and severe. The extent of ADL status was also graded into 3 classes: independent, partially dependent, and completely dependent. Recurrence of stroke, pneumonia, and motor disorders (hip joint fracture) were counted as complications during the course. At baseline, dementia was identified in 44, consisting of 30 mild and 14 severe dementias. During 5 years, 11 cases with mild dementia showed deterioration, and 1 case without dementia developed mild dementia. At registration, there were 46 cases with partially dependent ADL status and 22 cases completely dependent, while deterioration of ADL was seen in 17 during 5 years. Multiple regression analyses showed that diffuse PVH and pneumonia were contributory factors to the development of dementia, while dementia, pneumonia and motor disorders were risk factors for deterioration of ADL. These findings suggested that in patients with cerebral thrombosis, especially in patients with diffuse PVH, pneumonia and motor disorders should be taken care of in order to prevent functional decline.

To ascertain the safety of repeat apheresis donation, hematological and biochemical tests were performed on 511 donors with a donation rate of over 6 times per year for a period of 12-19 months.Repeat donors who had apheresis more than 6 times in the previous year were chosen. Data for the repeat donors at the start of the experiments were compared with those at the end of the study. Blood samples were taken prior to donation. Serum protein, albumin, immunoglobulin G, A, and M, serum ferritin levels were determined by biochemical tests.When compared to prospective donors of 400 ml, WBC, lymphocytes, and serum ferritin levels were lower in a roughly frequency-dependent manner in female and male donor groups at the beginning of the study. All the data for the male group remained almost constant with increasing frequency of apheresis donation. However, in the female group, ferritin levels significantly decreased with over 21 donations.The present data showed that the serum ferritin level of the female donors decreased the most with increasing frequency of apheresis donation. The cumulative RBC left in the collecting chamber and for the laboratory test is discussed in relation to a possible cause of iron deficiency in frequent apheresis donors.

We examined the effects of an L-type Ca2+ channel blocker, nilvadipine (0.5 and 2.0 mg/kg), and that of a T-type Ca2+ channel blocker, flunarizine (10.0 and 40.0 mg/kg), on the hypnotic potency of both a benzodiazepine (BZ)-hypnotic, triazolam (1.0 mg/kg), and a non-BZ hypnotic, zolpidem (20.0 mg/kg), in rats. The polysomnogram was recorded for 6 h after administration of the vehicle solution alone, or after one of the Ca2+ channel blockers, with or without one of the hypnotics. Both Ca2+ channel blockers prolonged the increased total time of non-rapid eye movement (non-REM) sleep induced by either hypnotic. In the case of triazolam, however, the non-REM sleep-enhancing effect induced by nilvadipine was greater than that induced by flunarizine. These findings indicate that the hypnotic action of triazolam is potentiated more strongly by an L-type Ca2+ channel blocker than by a T-type Ca2+ channel blocker.

There is controversy regarding the initial pathology of tabes dorsalis. In a patient with early tabes dorsalis, tibial nerve somatosensory evoked potentials elicited normal P15, a delayed traveling peak in the lumbar bipolar leads, and absent subsequent components. Based on the comparison with normative data and stimulation at different intensities, the authors conclude that only the slower conducting antidromic motor volleys are preserved, whereas the dorsal root is damaged at its distal end.

The outer arm dynein of sea urchin sperm axoneme contains three intermediate chains (IC1, IC2, and IC3; M(r) 128,000, 98,000, and 74,000, respectively). IC2 and IC3 are members of the WD family; the WD motif is responsible for a protein-protein interaction. We describe here the molecular cloning of IC1. IC1 has a unique primary structure, the N-terminal part is homologous to the sequence of thioredoxin, the middle part consists of three repetitive sequences homologous to the sequence of nucleoside diphosphate kinase, and the C-terminal part contains a high proportion of negatively charged glutamic acid residues. Thus, IC1 is a novel dynein intermediate chain distinct from IC2 and IC3 and may be a multifunctional protein. The thioredoxin-related part of IC1 is more closely related to those of two redox-active Chlamydomonas light chains than thioredoxin. Antibodies were prepared against the N-terminal and middle domains of IC1 expressed as His-tagged proteins in bacteria. These antibodies cross-reacted with some dynein polypeptides (potential homologues of IC1) from distantly related species. We propose here that the three intermediate chains are the basic core units of sperm outer arm dynein because of their ubiquitous existence. The recombinant thioredoxin-related part of IC1 and outer arm dyneins from sea urchin and distantly related species were specifically bound to and eluted from a phenylarsine oxide affinity column with 2-mercaptoethanol, indicating that they contain vicinal dithiols competent to undergo reversible oxidation/reduction.

Introduction Due to the continuing shortage of cadaveric donors in Japan, ABO-incompatible living kidney transplantation (LKT) is being performed. It is well known that highly sensitized patients with positive panel reactive antibodies (PRA) often present with acute rejection. Therefore, we examined the impact of a positive PRA on the results of ABO-incompatible LKT. Materials and methods One hundred seventy-seven recipients underwent ABO-incompatible LKT between January 1989 and March 2003. Of these patients, 37 who had been examined for PRA before transplantation were included in this study. There were 25 men and 12 women of mean age 37.3 years. Plasmapheresis was performed to remove anti-ABO antibodies before transplantation. During the induction phase, methylprednisolone, azathioprine, or mycophenolate mofetil and cyclosporine or tacrolimus were used for immunosuppression. Splenectomy was performed at the time of kidney transplantation in all patients. PRA was measured using FlowPRA by flow cytometer. Results Eight of the 37 patients had a positive PRA before transplantation (class I, 5; class II, 1; class I and class II, 2). The incidence of acute rejection was 37.9% in the patients with a negative PRA and 37.5% in patients with a positive PRA. One patient with a negative PRA and one patient with a positive PRA lost grafts due to acute rejection. Conclusions Positive PRA may not increase the incidence of acute rejection in ABO-incompatible LKT because plasmapheresis and splenectomy are performed to eliminate anti-ABO antibody.

Introduction Due to the continuing shortage of cadaveric donors in Japan, ABO-incompatible living kidney transplantation is being performed. Our previous studies showed that the long-term graft survival in ABO-incompatible living kidney transplantation was comparable to that in ABO-compatible living kidney transplantation. However, the impact on HLA-identity on the results of ABO-incompatible living donor kidney transplantation had not been investigated previously. Materials and methods One hundred twenty-seven recipients underwent ABO-incompatible living kidney transplantation between January 1989 and December 2000. Five were grafted from HLA-identical sibling donors group (I). The remaining 122 recipients received grafts from an HLA-nonidentical donor (group N). Both groups were similar in terms of recipient age, donor age, warm ischemic time, and total ischemic time. Three or four sessions of plasmapheresis were performed prior to transplantation. Cyclosporine or tacrolimus, methylprednisolone, and azathioprine or mycophenolate mofetil were used for immunosuppression. Splenectomy was done at the time of kidney transplantation in all patients. Results Graft loss was seen in one of the five HLA-identical recipients due to chronic rejection. Five- and 10-year graft survival rates were 80.0% I vs 72.0% N, and 80.0% I vs 54.2% N, respectively. The incidence of acute rejection in the HLA-identical recipients was lower than that in the HLA-nonidentical recipients (20% I vs 67.2% N). In conclusion, long term graft survival among ABO-incompatible kidney transplants from HLA-identical sibling donors was much better than that from HLA-nonidentical sibling donors.

We investigated the effects of inhalation of tea catechin on MRSA in the 24 elderly in patients, who were known to carry MRSA in sputum. The patients in the catechin group (N=12) were administered an inhalation of tea catechin extracts (in saline/bromhexine) (3.7 g/L catechins, 43% of them are composed of epigallocatechin gallate), three times daily with hand nebulizer for four weeks. The clinical effects were compared with the control group (N=12) who were given an inhalation of saline/bromhexine alone. After a week of the course, the numbers of the patients with decreased or disappearance of MRSA in their sputum was significantly higher in the catechin group, compared with that in the control group (seven vs. no patients; P

Summary Background The development of antibiotic resistance by microorganisms is an increasing problem in medicine. In chronic wounds, bacterial colonization is associated with impaired healing. Cold atmospheric plasma is an innovative promising tool to deal with these problems. Objectives The 5‐min argon plasma treatment has already demonstrated efficacy in reducing bacterial numbers in chronic infected wounds in vivo. In this study we investigated a 2‐min plasma treatment with the same device and the next‐generation device, to assess safety and reduction in bacterial load, regardless of the kind of bacteria and their resistance level in chronic wounds. Methods Twenty‐four patients with chronic infected wounds were treated in a prospective randomized controlled phase II study with 2 min of cold atmospheric argon plasma every day: 14 with MicroPlaSter alpha device, 10 with MicroPlaSter beta device (next‐generation device) in addition to standard wound care. The patient acted as his/her own control. Bacterial species were detected by standard bacterial swabs and bacterial load by semiquantitative count on nitrocellulose filters. The plasma settings were the same as in the previous phase II study in which wounds were exposed for 5 min to argon plasma. Results Analysis of 70 treatments in 14 patients with the MicroPlaSter alpha device revealed a significant (40%, P

We investigated the responses of rapidly adapting pulmonary stretch receptors (RARs) and tracheal pressure (PT) to right atrial injections of the thromboxane A2 (TXA2) stable analogue STA2 (0.3, 1.0, and 3.0 microgram/kg) before and after administration of atropine sulfate (1 mg/kg), isoprenaline (200 micrograms/kg), indomethacin (1 mg/kg), or S-145 (0.5 mg/kg) in artificially ventilated, bilaterally vagotomized rabbits. The RARs increased their activity after STA2 administration, and the increase was dose-dependent. However, intraatrial injections of STA2 at all the doses examined had no significant effect on PT. The excitatory responses of RAR activity to STA2 (0.3-3.0 micrograms/kg) were not significantly altered by administration of atropine sulfate (anticholinergic agent), isoprenaline (bronchodilator), or indomethacin (cyclooxygenase inhibitor). However, S-145 treatment (TXA2 antagonist) blocked the STA2-induced RAR stimulation. To determine whether or not administration of STA2 causes release of acetylcholine (ACh), we also examined the effects of vagal efferent stimulation (10-15 V, 10 Hz, 1 ms), STA2 administration (3.0 micrograms/kg), and their combination on PT in rabbits associated with both artificial ventilation and bilateral vagotomy. The vagally mediated bronchoconstriction that led to an increase in PT was not enhanced by simultaneous administration of STA2 at 3.0 micrograms/kg in all of the tested animals. These results suggest that the stimulation of RARs by STA2 is not mediated by the release of ACh from the nerve endings but is probably due to a local inflammatory bronchoconstriction that does not significantly alter the value of PT.

The ex vivo release of leukotrienes B4 (LTB4) and C4 (LTC4) from the leukocytes of children with atopic dermatitis (AD) was evaluated after stimulation with Ca-ionophore and opsonized zymosan and compared with that of control children of similar ages. The blood eosinophil counts and total serum IgE levels in AD children were significantly higher than those in control children. The production of LTC4, but not LTB4, was significantly higher in AD children than in control children. There was a significant correlation between the relative blood eosinophil count and LTC4 generation after stimulation with both Ca-ionophore and opsonized zymosan in all subjects. Calculations of the amount of LTC4 produced per eosinophilic cell showed that there was no significant difference between cells from AD children and control children in terms of their ability to produce LTC4. These findings suggest that the enhanced LTC4 generation is due to increased numbers of eosinophils rather than to enhanced releasability of these cells.

To look into new potential indications for physical plasma and because some reports suggest plasma having antipruritic effects, we investigated the treatment of pruritus that often represents a therapeutic challenge.To assess the efficacy and safety of cold atmospheric argon plasma as add-on-therapy in pruritic diseases.We treated 46 patients with various pruritic diseases with cold plasma for 2 min daily in addition to standard treatment. All patients served as their own control, when their pruritic disease was treated with argon gas (placebo). The outcome measure was a long-term and short-term reduction in itching measured by means of a visual analogue score (VAS).The VAS scores at baseline were comparable (plasma 4.57, SD 2.38, argon 4.34, SD 2.35). We did not find any significant differences in VAS reduction between plasma and argon: long-term VAS difference of 1.97 (SD 1.33) for plasma and 1.74 (SD 2.37) for argon [P = 0.224, 95% CI: (-0.15; 0.60)], short-term VAS difference of 1.92 (SD 1.33) for plasma and 1.97 (SD 1.29) for argon [P = 0.544, 95% CI: (-0.21; 0.11)]. In both groups, patients experienced a significant reduction of pruritus at the end of therapy compared to baseline [plasma 1.97 (P0.0001), placebo 1.74 [P0.0001)]. No relevant side effects occurred, and treatment was well tolerated.Treatment with cold plasma did not result in higher pruritus reduction than treatment with placebo. A significant reduction of pruritus compared to no effect was found at the end of therapy in both groups. Both treatment options had similar safety profiles.

Hypotension is commonly reported in springtime when health changes, such as autonomic imbalance, are common and its symptoms may cause difficulties in daily activities. In this study, medical data from 101 outpatient clinic attendees (mean age 43.9 years; 16 males) making their first visit for hypotension symptoms, were compared with meteorological data from the clinic's location. The main symptom of hypotension was giddiness on standing. The most common coexisting conditions were gastrointestinal; e.g. gastro-oesophageal reflux disorder and irritable bowel syndrome. The 7-day moving average of total global solar radiation correlated significantly with the 7-day moving average of the number of patients with hypotension. Discriminant analysis revealed an increase in hypotension consultations in the total global solar radiation moving average range 11 – 19 MJ/m2 consistent with the local spring season. Guidance — such as wearing compression stockings during springtime — may help to reduce the occurrence of clinical hypotension in susceptible patients.

Pneumothorax in middle-aged and elderly patients has various different features from young patients. We set out to investigate the outcome and usefulness of video-assisted thoracic surgery (VATS) in this group.From January 1993 to August 2010, 168 patients underwent a total of 178 thoracoscopic surgeries. There were 160 men and 8 women with mean age of 67 (range, 50 to 85). The average duration of thoracic drainage before surgery was 7.4 days. We excised only responsible lesions as minimum degree of dissection as possible. When patients have intractable air leakage and chest computed tomography (CT) indicates severe pleural adhesions, pleurography should be performed to locate the site of air leakage and determine surgical approaches. One hundred and seventy patients were treated with the lateral approach, while 8 patients were successfully treated with the anterior approach. One hundred and fifty-one patients were treated with VATS alone, and 27 patients were treated with the combination of VATS and small thoracotomy. The duration of chest tube drainage, hospital stay, post-operative complication, outcome and recurrence were assessed.The air leakages stopped and all patients except for 2 patents were discharged without drainage tubes. Postoperative drainage time was 4.5 +/- 3.4 days. Postoperative hospital stay was 9.9 +/- 13.9 days. One patient died caused by perioperative myocardial infarction. Seventeen patients died of other diseases. Seven patients needed local hospital treatments and the recurrence rate was 3.9%.VATS for pneumothorax in patients over 50 years old is very useful by appropriate perioperative managements.

Gene expression is related to the pathogenesis of periodontitis and plays a crucial role in local tissue destruction and disease susceptibility. The aims of the present study were to identify the expression of specific genes and biological pathways in periodontitis-affected gingival tissue using microarray and quantitative real-time RT-PCR analyses.Healthy and periodontitis-affected gingival tissues were taken from three patients with severe chronic periodontitis. Total RNAs from six gingival tissue samples were used for microarray analyses. Data-mining analyses, such as comparisons, gene ontology and pathway analyses, were performed and biological pathways with a significant role in periodontitis were identified. In addition, quantitative real-time RT-PCR analysis was performed on samples obtained from 14 patients with chronic periodontitis and from 14 healthy individuals in order to confirm the results of the pathway analysis.Comparison analyses found 15 up-regulated and 13 down-regulated genes (all of which showed a change of more than twofold in expression levels) in periodontitis-affected gingival tissues. Pathway analysis identified 15 up-regulated biological pathways, including leukocyte transendothelial migration, and five down-regulated pathways, including cell communication. Quantitative real-time RT-PCR verified that five genes in the leukocyte transendothelial migration pathway were significantly up-regulated, and four genes in the cell communication pathway were significantly down-regulated, which was consistent with pathway analysis.We identified up-regulated genes (ITGB-2, MMP-2, CXCL-12, CXCR-4 and Rac-2) and down-regulated genes (connexin, DSG-1, DSC-1 and nestin) in periodontitis-affected gingival tissues; these genes may be related to the stimulation of leukocyte transendothelial migration and to the the impairment of cell-to-cell communication in periodontitis.

To evaluate the safety of cryopreserved and thawed peripheral blood stem cell (PBSC) autografts in children with active cancer, a toxicity assessment was made of 54 PBSC transfusions to 52 children (aged 1-16 years; median, 9 years). Patients were conditioned with high-dose chemotherapy without total body irradiation. The volume of PBSCs transfused varied from 46 to 500 mL (219.6 +/- 118.4 mL, mean +/- SD), with a mean of 0.91 g per kg of dimethyl sulfoxide. Insignificant and transient toxicities included hemoglobinuria in 40 patients (74%), headache in 38 (70%), nausea in 37 (69%), and vomiting in 25 patients (46%). Significant shock developed in 8 patients (15%), but they recovered quickly, whether they had supportive therapy or not. Vomiting and hyperbilirubinemia were the only toxicities that showed a correlation with the amount of PBSCs transfused. The data suggest that transient toxicity associated with PBSC autografts is rather common in children, and close observation of patients for possible serious morbidity is required.

1. Effects of prostaglandin E2 (PGE2) on ion transport were examined by observing the transmural (VT) and basolateral membrane voltage (VB) in the in vitro perfused rabbit connecting tubule (CNT) and the cortical collecting duct (CCD). 2. Addition of 1 microM PGE2 to the bath induced a biphasic response of transmural voltage (VT), with initial negative VT deflection followed by positive deflection in the CNT, but monophasic negative deflection in the CCD. Because PGE2 had no affect on the basolateral membrane voltage (VB), PGE2 mainly causes changes in the apical membrane voltage. 3. Elimination of Na+ from the lumen abolished the PGE2-induced VT response in the CNT. In the presence of 10 microM luminal amiloride, PGE2 caused only an initial negative deflection without causing later positive deflection. The positive VT deflection induced by PGE2 in the CCD was also blocked by luminal amiloride. 4. Addition of ouabain (0.1 mM) to the bath completely abolished the PGE2-induced VT changes in the CNT, indicating that an intact Na(+)-K+ pump is a prerequisite for the VT response to PGE2. 5. Addition of 2 mM Ba2+ to the lumen did not affect biphasic VT response to PGE2, indicating that Ba(2+)-sensitive K+ conductance is not involved. 6. Basolateral addition of 0.1 mM 8-(4-chlorophenylthio)-cAMP inhibited only the negative VT deflection induced by PGE2. 7. The positive VT deflection was blocked by basolateral addition of 50 microM 8-(N,N-diethylamino)octyl 3,4,5-trimethoxy benzoate hydrochloride (TMB-8), an inhibitor of intracellular Ca2+ release. But elimination of luminal Ca2+ did not affect the biphasic response to PGE2. 8. These findings suggest that the initial negative VT deflection is caused by an increase in Na+ influx across the luminal membrane through an amiloride-insensitive Na+ conductive pathway, whereas the later positive deflection is caused by the inhibition of Na+ influx through the amiloride-sensitive Na+ conductive pathway. The cAMP messenger system may be responsible for the initial negative deflection, whereas an increased intercellular Ca2+ release from the store is necessary for the later positive deflection caused by PGE2. The response in the CCD is comparable to the later response in the CNT.

Endogenous production of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-3 (IL-3), and interleukin-6 (IL-6) was investigated in 10 children who underwent a total of 12 courses of autologous peripheral blood stem cell transplant (PBSCT) by measuring their serum levels using immunoassay kits. The serum G-CSF level increased immediately following infusion of PBSC graft, peaked between days 3 and 7 posttransplant and then declined by the time the granulocyte count rose. No definitive association was found between the continuous high levels of G-CSF and infective episodes, the number of infused nucleated cells, monocytes, CFU-GM, or the number of days required to achieve greater than 0.5 x 10(9)/L granulocyte, greater than 1.0 x 10(9)/L leukocyte, or greater than 50 x 10(9)/L platelet counts. After PBSCT, IL-6 levels tended to be elevated. No detectable serum level of GM-CSF or IL-3 (< 50 pg/mL) was observed before PBSCT and 4 patients showed a transient increase in the GM-CSF level after PBSCT. No significant change was observed in the post-transplant serum levels of IL-3 or M- CSF. The role of endogenously secreted cytokines in early hematopoietic recovery after PBSCT needs further clarification, but, at present, routine use of exogenous G-CSF therapy is not recommended.

23Na MRI changes from the acute to chronic phase were investigated in seven patients with cerebral infarcts. They showed no signal increase during the first 13 h after the stroke and revealed a definite signal increase thereafter. This reached a maximum 45-82 h after stroke and became slightly less marked in the subacute and chronic phases, probably as a result of disappearance of cerebral oedema. In the early acute phase of stroke, 23Na MRI appears to fail to demonstrate Na+ increases in the ischaemic area, due presumably to the invisibility on MRI of intracellular 23Na in the intact brain. The increase more than 13 h after stroke, during which ischaemic cells are likely to die, is presumably because of increased visibility of intracellular 23Na in the dead cells. 23Na MRI is apparently insensitive to early ischaemic changes, but may be useful for assessing the cell viability in the ischaemic brain.

Interstitial lung disease (ILD) is a frequent manifestation of rheumatoid arthritis (RA), and it has a close bearing on the prognosis of RA patients. Computed tomography (CT) has been shown to be excellent for the diagnosis of diffuse lung disease. In this study chest radiographs and high-resolution CT (HRCT) scans were obtained in 91 patients with RA to evaluate their ILD precisely. By HRCT 43 patients could be diagnosed as having interstitial pneumonitis (IP), and 5 could be diagnosed as having bronchiolitis. The remaining 43 patients were normal by HRCT. Chest radiographic findings were consistent with the HRCT findings in approximately 50% of patients with IP. HRCT was superior to chest radiographs for the detection of early interstitial changes. The histogram of HRCT values might be a useful adjunct to HRCT diagnosis by adding some degree of objectivity. HRCT is useful for the diagnosis of ILD in patients with RA.

We report here the development of parkinsonian symptoms after carbamazepine discontinuation in two patients concurrently treated with risperidone. They had been receiving combined treatment of carbamazepine and risperidone for the control of aggressive behavior and psychotic symptoms. The parkinsonian symptoms had not occurred before carbamazepine discontinuation, and have achieved complete remission after the dose reduction of risperidone. These findings suggest that the development of parkinsonian symptoms may be associated with pharmacokinetic interaction between carbamazepine and risperidone.

St John's wort (SJW, Hypericum perforatum) is one of the most commonly used herbal antidepressants for treatment of mild to moderate depression. SJW enhances CYP3A4 activity and alters the pharmacokinetics of CYP3A4 substrates. This study investigated the effect of SJW on the pharmacokinetics of zolpidem in healthy subjects.A controlled, open-label, non-randomized, fixed-dose schedule design was used. Fourteen healthy male subjects received a single 10 mg oral dose of zolpidem followed by SJW administration (300 mg orally, three times a day) for 14 days; the last dose of SJW was coadministered with a single dose of zolpidem. Blood samples were obtained over a 24-h period after zolpidem administration. Pharmacokinetic data for zolpidem alone and in combination with SJW were analysed by high-performance liquid chromatography.After repeated administration of SJW, the mean values of AUC and C(max) for zolpidem significantly decreased (380.3 ± 181.4 vs. 265.4 ± 134.2 ng h/mL, P = 0.001; 83.1 ± 30.1 vs. 55.1 ± 24.8 ng/mL, P = 0.000 respectively) and the mean value of CL/F for zolpidem significantly increased (38.4 ± 31.5 vs. 56.9 ± 57.2 mL/min, P = 0.040). However, in three subjects, the AUC showed a small increase after SJW treatment.The effect of SJW on the pharmacokinetics of zolpidem has not previously been reported. Repeated administration of SJW decreases the plasma concentration of zolpidem, probably by enhancing CYP3A4 activity. Given the wide inter-subject variability observed, for personalized medicine, advice on the use of the combination should be individualized, based on the circumstances of the patient.

Bacterial colonization of chronic wounds slows healing. Cold atmospheric plasma has been shown in vitro to kill a wide range of pathogenic bacteria. Objectives To examine the safety and efficiency of cold atmospheric argon plasma to decrease bacterial load as a new medical treatment for chronic wounds.Thirty-eight chronic infected wounds in 36 patients were treated in a prospective randomized controlled phase II study with 5 min daily cold atmospheric argon plasma in addition to standard wound care. The patient acted as his or her own control. Bacterial species were detected by standard bacterial swabs and semiquantitative changes by nitrocellulose filters. Plasma setting and safety had been determined in a preceding phase I study.Analysis of 291 treatments in 38 wounds found a highly significant (34%, P10(-6)) reduction of bacterial load in treated wounds, regardless of the type of bacteria. No side-effects occurred and the treatment was well tolerated.Cold atmospheric argon plasma treatment is potentially a safe and painless new technique to decrease bacterial load of chronic wounds and promote healing.

The effects of prostaglandin (PG) E2 on cell swelling were studied in isolated perfused tubules of rabbit kidney. PGE2 (1 microM) added to the bath induced cell swelling by 13.4, 7.2, and 9.6% in the connecting tubule, distal convoluted tubule, and cortical collecting duct, respectively, but it had no effect on the proximal convoluted tubule and cortical thick ascending limb. The response was dose dependent in the range of 1 nM to 1 microM. PGI2 exerted a similar effect, but PGF2 alpha had no effect. The swelling was completely blocked by basolateral Na+ removal and was attenuated by bilateral Cl- removal, suggesting that the swelling was mediated by basolateral Na+ entry in association with Cl- entry. In all segments except proximal tubule, PGE2 caused an initial transient peak followed by a sustained increase in intracellular Ca2+. Intracellular Ca2+ chelation or inhibition of Ca2+ release from intracellular stores abolished the PGE2-induced cell swelling, but extracellular Ca2+ removal did not. An inhibitor of the Na(+)-Ca2+ exchanger (3',4'-dichlorobenzamil, 100 microM) in the bath completely inhibited PGE2-induced cell swelling. Neither furosemide (1 mM) nor amiloride (1 mM) added to bath abolished the response, indicating that neither Na(+)-K(+)-2Cl- cotransport nor Na(+)-H+ exchange is involved in the action of PGE2. The swelling response to PGE2 was observed even in the presence of ouabain, indicating that the effect of PGE2 is independent of Na(+)-K(+)-adenosinetriphosphatase inhibition. Nicardipine added to bath partially inhibited the swelling response.(ABSTRACT TRUNCATED AT 250 WORDS)

Minor endothelial injury was produced in pial arterioles by a laser-Evans blue technique. This technique previously has been shown to prevent relaxation of the arterioles by topical acetylcholine (ACh) or bradykinin, agonists whose actions are known to be endothelium dependent in most vascular beds. L-Arginine is thought to be the precursor of the endothelium-derived relaxing factor (EDRF) that mediates the response to ACh. To further test this hypothesis and to begin exploration of the intracellular effects of the laser injury, we used the laser to eliminate the response to ACh and then attempted to restore the responsivity by suffusing the arterioles with 10(-3) L-arginine for 10 min before testing with ACh. This treatment restored the response. In contrast, over the same time period, responses failed to recover in arterioles that were never exposed to L-arginine or in arterioles that were only exposed to L-arginine at the time of retest with ACh. D-Arginine failed to restore the response to ACh. L-Arginine failed to restore the response to bradykinin. The data support the hypothesis that L-arginine acts as a substrate for synthesis of “classical” EDRF in brain microvessels in vivo. The data suggest that laser-Evans blue injury either depletes the endothelium of L-arginine or interferes with conversion of L-arginine to EDRF. Increasing the substrate by exposing the vessels to L-arginine for 10 min permitted ACh to release sufficient EDRF to elicit dilatation. The data also support conclusions from earlier studies that in this vascular bed the dilations produced by ACh and bradykinin are mediated by different EDRF.

Thirty-eight cases of giant serpentine aneurysms (GSA), including 17 GSA of the middle cerebral artery (MCA), were reviewed in the literature. The treatment possibilities of GSA of the MCA are discussed together with our own case who was a 39-year-old male with a GSA of the right MCA and was treated only by STA-MCA anastomosis. The pathogenetic mechanism of progressive enlargement of the aneurysm is also discussed.

Four patients with cerebral hemorrhage were examined serially from the acute to chronic phase by 1H magnetic resonance imaging (MRI), 23Na MRI and computed tomography (CT). At 1-2 days after bleeding, the 23Na image revealed no visible signal change in the area of hemorrhage, although CT and 1H images clearly demonstrated the existence of a hematoma in the thalamus or putamen. At 4-7 days after the hemorrhage, the 23Na images began to exhibit a small increase in signal intensity at the hematoma site, while at 2-3 weeks, a marked increase in 23Na signal intensity was observed. These findings suggest that the hematoma consisted mainly of a corpuscular component, with a low Na+ concentration, with little serum component. Lack of signal from the corpuscular component on the 23Na image was confirmed by an in vitro study. In the late acute phase, Na+ accumulation may occur in the corpuscular component due to failure of the Na+ pump. The intracellular 23Na appears to be totally visible to MRI, resulting in an increase in signal intensity. In the subacute or chronic phase, the corpuscular component may be destroyed, leaving fluid in its place. A high Na+ concentration in this fluid may give markedly increased 23Na signal intensity on MRI. 23Na MRI appears to provide important information for understanding the evolution of cerebral hemorrhage and for estimating the viability of cells, although its value for diagnosis may not be great.