Mass producible, robust SERS substrates based on metal film on nanosphere (MFON) on an adhesive substrate for detection of surface-adsorbed molecules and their evaluation by helium ion microscopy.

We have developed a SERS stamp that can be pressed directly onto a solid surface for characterization of surface-adsorbed target molecules. The stamp was fabricated by transfer of a dense monolayer of SiO2 nanospheres from a glass surface onto a piece of adhesive tape and subsequent evaporation of silver. The performance of the resulting SERS stamps was evaluated by their exposure to methyl mercaptan vapor, and immersion in rhodamine 6G and ferbam solutions. It was found that beside the nanosphere diameter and metal deposition thickness, the extent of burial of the nanospheres into the adhesive tape, dictated by the pressure during the nanosphere transfer process, had a significant effect. We carried out FDTD calculations of the near field. Models are based on morphological information obtained from helium ion microscopy, which can provide high-resolution images of poor electrical conductors such as our SERS stamp. While one of our main eventual goals is detection of pesticides on agricultural produce, we have begun to take a careful step by testing our SERS stamp on better characterized surfaces such as a porous gel surface, having been immersed in fungicides such as ferbam. We also present our preliminary results with ferbam on oranges. It is expected that our well-characterized SERS stamp will play a role in shedding light on the poorly studied transfer process of target molecules onto a SERS surface as well as serving as a new SERS platform.

Efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for lupus nephritis: a prospective, single-arm, single-centre, open label pilot study in Japan.

Background Pulsed cyclophosphamide or mycophenolate mofetil for lupus nephritis has limited efficacy. We previously reported a case of mixed-class IV + V lupus nephritis successfully treated with cyclophosphamide and tacrolimus. This study assessed the efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for the treatment of lupus nephritis. Methods In a prospective, single-arm, open label pilot study, we recruited 15 patients aged 18-64 years with active lupus nephritis who met the American College of Rheumatology criteria for a diagnosis of systemic lupus erythematosus (1997). The treatment protocol was a starting dose of prednisolone of 0.6-1.0 mg/kg/day for 2 weeks and then tapered to a maintenance dose, intravenous cyclophosphamide (500 mg biweekly for 3 months) and tacrolimus (3.0 mg/day). Tacrolimus was continued as maintenance therapy. Complete remission was defined as a spot urine protein/creatinine ratio of < 0.5 g/gCr with no active urine casts and a serum creatinine level that was either normal or within 30% of a previously abnormal baseline level. We retrospectively compared results for the study patients with those of 18 historical controls conventionally treated with cyclophosphamide and prednisolone. Results At baseline, the mean patient age was 41.5 ± 14.6 years (male:female ratio 2:13), urine protein/creatinine ratio 3.9 ± 2.3 g/gCr and serum creatinine 84.6 ± 34.6 µmol/L. Lupus nephritis classifications included classes IV ( n = 8), III + V ( n = 1), IV + V ( n = 5) and unclassified ( n = 1). Eleven patients completed the treatment protocol and four withdrew. At 6 months, 12 of 15 (80.0%) had achieved complete remission using intention-to-treat analysis, significantly more than historical controls (seven of 18 patients, 38.9%). A transient increase in serum creatinine and gastric symptoms occurred in three cases. One patient withdrew due to cytomegalovirus antigenemia and severe diabetes, and one patient died of thrombotic microangiopathy. Conclusions Multitarget therapy with cyclophosphamide and tacrolimus can be a therapeutic option for lupus nephritis. Clinical trials registration Combination therapy of tacrolimus and intravenous cyclophosphamide for remission induction of lupus nephritis, UMIN: 000004893, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000005830&language=E . Date of registration: 18 January 2011.

Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological features with other lobular carcinoma variants.

OBJECTIVE: Pleomorphic lobular carcinoma (PLC) is a subtype of breast cancer with unique morphological features, but it remains controversial whether PLC should be considered an independent disease entity. The aim of this study was to illustrate cytopathological characteristics of PLC in comparison with other lobular carcinoma variants. METHODS: We investigated clinicopathological features of PLC (n = 11) compared with those of other variants of invasive lobular carcinoma (ILC, non-PLC) (n = 32). Histological variants of the non-PLC group consisted of classic (n = 25), solid (n = 2), alveolar (n = 1) and a tubulolobular type (n = 4). A review of cytological reports and fine needle aspiration (FNA) smear samples was performed for the PLC (n = 9) and non-PLC (n = 27) groups. RESULTS: Patients with PLC were older, and had a higher nuclear grade and a higher incidence of axillary lymph node metastasis and triple negative phenotype than non-PLC patients (P = 0.007, P < 0.001, P = 0.02 and P < 0.001, respectively). Cytological findings in PLC included medium- to large-sized nuclei, prominent nucleoli, a moderate-to-severe degree of pleomorphism, apocrine change and background necrosis, none of which were evident in the smears of the non-PLC group (P < 0.001, P = 0.002, P < 0.001, P < 0.001, and P = 0.03, respectively). Despite these differences, patients with PLC and non-PLC showed similar clinical outcomes in our follow-up period. CONCLUSIONS: Based on our results, a cytological diagnosis of PLC should be proposed if there are moderate- to large-sized nuclei, prominent nucleoli, a moderate-to severe degree of nuclear pleomorphism, apocrine change and necrosis in the background in FNA biopsy samples.

Development of array-type atmospheric-pressure RF plasma generator with electric on-off control for high-throughput numerically controlled processes.

An array-type atmospheric-pressure radio-frequency (RF) plasma generator is proposed for high-precision and high-throughput numerically controlled (NC) processes. We propose the use of a metal-oxide-semiconductor field-effect transistor (MOSFET) circuit for direct RF switching to achieve plasma on-off control. We confirmed that this type of circuit works correctly using a MOSFET with a small parasitic capacitance between its source and gate. We examined the design method for the distance between adjacent electrodes, which corresponds to the parasitic capacitance between adjacent electrodes and is very important in the individual on-off control of each electrode. We developed a prototype array-type plasma generator apparatus with 19 electrodes and the same number of MOSFET circuits; we then confirmed that each electrode could control its plasma on-off state individually. We also demonstrated that the thickness uniformity of the surface Si layer of a silicon-on-insulator wafer could be processed to less than 1 nm peak to valley by the NC sacrificial oxidation method using the apparatus.

Mucinous carcinoma of the breast: a comparative study on cytohistological findings associated with neuroendocrine differentiation.

OBJECTIVE: Mucinous carcinoma (MCA) may show neuroendocrine differentiation (ND), but the cytological features characteristic of ND remains elusive. We compared fine needle aspiration (FNA) findings of MCA between cases with high and low degrees of ND. METHODS: Histological sections of 37 MCA cases were immunohistochemically evaluated for expression of chromogranin A and synaptophysin, and were graded as 0 to 3+ degrees of ND. They were divided into low ND (grade 0 and 1+) and high ND (grade 2+ and 3+) groups. Pre-operative FNA samples of each group were assessed for cytological features. RESULTS: The mean age of the high ND group (n = 18) was higher than the low ND group (n = 19, P = 0.01). In FNA samples of the high ND group, 17 cases showed moderate to severe degrees of discohesiveness, but low ND cases mainly showed no or only mild discohesiveness (P < 0.001). Nine of the low ND cases displayed overlapped, cohesive cell clusters, whereas, in the high ND cases, the cells were arranged in a loose, flat and monolayered pattern (P = 0.045). Fourteen of the high ND cases had round nuclei, but oval nuclei were predominant in the low ND cases (P = 0.027). The nuclei were eccentrically located in 12 of the high ND cases but were centrally located in 14 of the low ND cases (P = 0.01). CONCLUSIONS: Mucinous carcinoma with high ND may be diagnosed by the presence of discohesiveness, a flat, monolayered pattern, and round or eccentrically located nuclei. Features of ND in carcinomas in other organs, such as intracytoplasmic granules and coarse chromatin, may not be reliable cytological features of ND in MCA.

Presynaptic cell type-dependent regulation of GABAergic synaptic transmission by nitric oxide in rat insular cortex.

Nitric oxide (NO) is a key retrograde messenger that regulates synaptic transmission in the cerebral cortex. However, little is known about NO-induced modulatory effects and their mechanisms relative to inhibitory synaptic transmission. The present study aimed to examine the effects of NO on unitary inhibitory postsynaptic currents (uIPSCs) and to postulate the synaptic location of NO action. We performed multiple whole-cell patch-clamp recordings from rat insular cortex and divided recorded cells into three subtypes: pyramidal cells (Pyr), fast-spiking interneurons (FS), and non-FS GABAergic interneurons. In the connections from FS to Pyr (FS→Pyr), the application of S-nitroso-N-acetyl-dl-penicillamine (SNAP, 100 µM), an NO donor, suppressed uIPSC amplitudes in 31% of the connections, whereas 39% of the connections showed uIPSC facilitation. The remaining FS→Pyr connections showed little effect of SNAP on uIPSCs. An analysis of paired-pulse ratio (PPR) implied the involvement of presynaptic mechanisms in SNAP-induced effects on uIPSCs. Similar effects of SNAP were observed in FS→FS/non-FS connections; 33%, 54%, and 13% of the connections were facilitated, suppressed, and unchanged, respectively. In contrast, non-FS→Pyr or FS/non-FS showed constant uIPSC suppression by SNAP. PPR analysis supports the hypothesis that these SNAP-induced effects are mediated by presynaptic mechanisms in FS→FS/non-FS and non-FS→Pyr/FS/non-FS connections. The NO scavenger, 2-phenyl-4,4,5,5-tetramethylimidazolineoxyl-1-oxyl-3-oxide (PTIO), or the inhibitor of guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), abolished the SNAP-induced uIPSC modulation. These results suggest that NO regulation of inhibitory synaptic transmission is dependent on presynaptic cell subtypes and that, at least in part, the effects are mediated by presynaptic mechanisms.

Microfocus x-ray imaging of traceable pointlike (22)Na sources for quality control.

PURPOSE: The purpose of this study is to propose a microfocus x-ray imaging technique for observing the internal structure of small radioactive sources and evaluating geometrical errors quantitatively, and to apply this technique to traceable pointlike (22)Na sources, which were designed for positron emission tomography calibration, for the purpose of quality control of the pointlike sources. METHODS: A microfocus x-ray imaging system with a focus size of 0.001 mm was used to obtain projection x-ray images and x-ray CT images of five pointlike source samples, which were manufactured during 2009-2012. The obtained projection and tomographic images were used to observe the internal structure and evaluate geometrical errors quantitatively. Monte Carlo simulation was used to evaluate the effect of possible geometrical errors on the intensity and uniformity of 0.511 MeV annihilation photon pairs emitted from the sources. RESULTS: Geometrical errors were evaluated with sufficient precision using projection x-ray images. CT images were used for observing the internal structure intuitively. As a result, four of the five examined samples were within the tolerance to maintain the total uncertainty below ±0.5%, given the source radioactivity; however, one sample was found to be defective. CONCLUSIONS: This quality control procedure is crucial and offers an important basis for using the pointlike (22)Na source as a basic calibration tool. The microfocus x-ray imaging approach is a promising technique for visual and quantitative evaluation of the internal geometry of small radioactive sources.

The effect of exemestane, anastrozole, and tamoxifen on lipid profiles in Japanese postmenopausal early breast cancer patients: final results of National Surgical Adjuvant Study BC 04, the TEAM Japan sub-study.

BACKGROUND: In this Tamoxifen Exemestane Adjuvant Multinational Japan sub-study, we evaluated the time course of changes in serum lipids in postmenopausal women with hormone-sensitive early breast cancer treated with exemestane, anastrozole, or tamoxifen for postoperative adjuvant therapy. PATIENTS AND METHODS: A total of 154 breast cancer patients were assigned to receive exemestane, anastrozole, or tamoxifen in this randomized open-label study. Serum lipid parameters including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured during 1 year of treatment. RESULTS: TC and LDL-C rapidly decreased in patients treated with tamoxifen at 3 months. Compared with anastrozole and exemestane patients, TC and LDL-C were significantly lower at all assessment time points in tamoxifen patients (P < 0.05). TG increased in tamoxifen patients; it was significantly higher compared with exemestane patients at all assessment time points (P < 0.05). HDL-C slightly decreased in exemestane patients; it was significantly lower compared with anastrozole patients at 3 months and 1 year (P = 0.0179 and 0.0013, respectively). CONCLUSION: Changes of lipid profiles in Japanese postmenopausal women treated with tamoxifen were relatively favorable, while exemestane and anastrozole had no clinically significant effect on the serum lipids.

Insulin facilitates repetitive spike firing in rat insular cortex via phosphoinositide 3-kinase but not mitogen activated protein kinase cascade.

The insular cortex (IC) processes gustatory and visceral information, which functionally correlate to feeding behavior. Insulin, a well-known hormone controlling glucose metabolism, is released by elevation of blood glucose concentration following feeding behavior. The IC expresses dense insulin receptors and receives projection from the hypothalamus, which monitors changes in glucose concentration. Therefore, it is likely that insulin modulates neural properties in the IC. However, little is known about the effects of insulin on electrophysiological properties of the neocortex including the IC. To explore the effects of insulin on subthreshold responses and action potential properties in the IC, intracellular recording with sharp glass electrodes was performed from IC pyramidal cells using slice preparations. Although application of insulin (100 nM) had little effect on the resting membrane potential, input resistance and rheobase, insulin significantly increased the frequency of repetitive spike firing in response to a long depolarizing current pulse injection: the slope of the frequency-current curve was increased from 23.7±2.3 Hz/nA to 29.5±3.4 Hz/nA. Insulin slightly decreased the action potential threshold without affecting the amplitude of medium-duration and slow afterhyperpolarization (sAHP) s. The insulin-induced facilitation of repetitive spike firing was dose-dependent and blocked by pre-application of 200 nM lavendustin A, a tyrosine kinase inhibitor. Moreover, when combined with 200 nM wortmannin, a phosphoinositide 3-kinase (PI3-K) inhibitor, or 500 nM deguelin, an inhibitor of protein kinase B (PKB/Akt) downstream of PI3-K, insulin failed to increase the frequency of repetitive spike firing. In contrast, co-application of insulin and (10 µM) PD 98059, an inhibitor of mitogen activated protein kinase (MAPK), exerted facilitation of repetitive spike firing. These results suggest that acute insulin-induced facilitation of firing frequency is at least partially induced by hyperpolarizing effects on the action potential threshold, and that this facilitation is induced by activation of PI3-K but not MAPK cascade.

A combinatorial approach toward fabrication of surface-adsorbed metal nanoparticles for investigation of an enzyme reaction.

We are presenting a combinatorial approach for the preparation of surface-adsorbed metal nanoparticles for investigation of biological phenomena. Metal nanoparticles, in particular noble metal nanoparticles, have become increasingly recognized for their importance in studies of biological systems. An intense near-field associated with these particles can be exploited to improve the performance of various spectroscopic techniques. In this paper, we combine the metal nanoparticle with a colorimetric enzyme reaction and explore spectral changes of the metal nanoparticle dependent on the extent of the reaction, alkaline phosphatase acting on nitro-blue tetrazolium chloride. Changing the shape of the gold particle has a clear effect on the extent of the spectral shift. Furthermore, we demonstrate that the method we employ for preparation of metal particles, vacuum evaporation of a metal on a monolayer of surface-adsorbed monodisperse polystyrene or silica nanospheres, is supremely suited for a combinatorial approach. By depositing two different metals on nanospheres as multi-layers while varying the ratio as well as absolute thicknesses, it is possible to produce a large variety of metal particles in parallel. We show the potential of such a combinatorial approach for rapidly producing metal nanoparticles of choice.

Effects of exemestane, anastrozole and tamoxifen on bone mineral density and bone turnover markers in postmenopausal early breast cancer patients: results of N-SAS BC 04, the TEAM Japan substudy.

BACKGROUND: Use of aromatase inhibitors in women with postmenopausal breast cancer accompanies risks of bone loss. We evaluated changes in bone mineral density (BMD) and bone turnover markers in patients treated with exemestane, anastrozole or tamoxifen for hormone-sensitive postmenopausal early breast cancer. PATIENTS AND METHODS: Sixty-eight patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational Japan bone substudy were randomly assigned to receive tamoxifen, exemestane or anastrozole. During a 2-year study period, lumbar spine BMD was measured using dual-energy X-ray absorptiometry, and urinary type I collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP) were also measured. RESULTS: BMD at 2 years of treatment was higher in tamoxifen patients compared with exemestane and anastrozole patients; however, the intergroup difference was not significant (p = 0.2521 and p = 0.0753, respectively). BMD was higher in exemestane patients compared with anastrozole patients; however, the intergroup difference was not significant (p = 0.7059 and p = 0.8134, respectively). NTX and BAP were significantly lower in tamoxifen patients compared with exemestane and anastrozole patients at 1 and 2 years of treatment (p < 0.05). CONCLUSION: Tamoxifen may provide better bone protection compared with exemestane or anastrozole. The effect of exemestane and anastrozole on bone loss may be comparable in Japanese postmenopausal women.

Early recurrence after surgical resection in patients with pathological stage I non-small cell lung cancer.

INTRODUCTION: Early recurrence is observed even in patients who undergo complete resection and had pathological (p-) stage I. Therefore, we focused on early recurrence, and attempted to elucidate the relationship between early recurrence and clinicopathological factors. METHODS: Between May 1993 and December 2005, 1201 patients with non-small cell lung cancer (NSCLC) underwent surgical treatment at our institution. Of these, 402 patients who underwent complete resection and had p-stage I NSCLC were retrospectively analyzed for clinicopathological factors. Patients were divided into four groups according to the period between surgery and recurrence (R): no recurrence (NR, n = 331), late recurrence (LR, n = 28, R > 2 years), intermediate recurrence (IR, n = 22, 1 year < R < or = 2 years), and early recurrence (ER, n = 21, R < or = 1 year). RESULTS: The overall 5-year survival rate for patients with p-stage I was 79.9 %. The overall 5-year survival rates were 91.0 %, 55.6 %, 17.1 %, and 7.5 % for the NR, LR, IR, and ER group, respectively. Preoperative high CEA level, lymphatic permeation, and pleural invasion were proven to be independent factors for overall recurrence. Moreover, multivariate analysis showed that preoperative CEA level, pathological T factor, lymphatic permeation, vascular invasion, and pleural invasion influenced early recurrence within one year. CONCLUSIONS: The present study demonstrated that preoperative CEA level, pathological T-factor, lymphatic permeation, vascular invasion, and pleural invasion were independent prognostic factors for early recurrence within one year, even in patients with pathological stage I. In patients with these factors, adjuvant therapy may be indicated since this may improve their survival.

Rosenthal fiber-rich glioblastoma: a case report.

BACKGROUND: Rosenthal fibers (RFs) are thick, elongated, brightly eosinophilic structures occurring within astrocytic processes. Although the presence of abundant RFs within brain tumors is most closely associated with a low-grade astrocytoma, particularly pilocytic astrocytoma (PA), a few RFs are recognized to occur, although rarely, in glioblastoma (GBM). We report a very rare case of GBM with abundant RFs. CASE REPORT: A 60-year-old woman presented with a 6-month history of difficulty coordinating her right hand, occasional intermittent diplopia, and occasional dizzy spells. An MRI showed a heterogeneously enhancing, infiltrating mass lesion with a cystic component involving the left midbrain, thalamus, and posterior basal ganglia. Biopsy was performed. Cytologic touch imprints revealed fibrillary astrocytic cells possessing oval nuclei and long delicate processes with abundant RFs. Histologic sections showed diffusely infiltrating astrocytoma with prominent RFs diffusely distributed throughout the tumor, brisk mitotic activity, vascular proliferation, and small areas of necrosis, as seen in a GBM. The Ki-67 (MIB-1) labeling index was 7.1%. P53 immunoreactivity was not seen. A follow-up MRI study performed 3 months after the biopsy showed a considerable tumor progression with extension into the left superior cerebellar peduncle and progressive hydrocephalus. DISCUSSION: This is a case of RF-rich GBM (primary or de novo type). The differential diagnosis includes PA and anaplastic PA. For the histological diagnosis, infiltrating astrocytoma with abundant RFs should be carefully examined in light of clinical information (e.g., patient age, evolution of the symptoms) and neuroimaging studies.

Morbidity in video-assisted thoracoscopic lobectomy for clinical stage I non-small cell lung cancer: is VATS lobectomy really safe?

OBJECTIVE: The objective of this study was to compare video-assisted thoracoscopic lobectomy (VATS lobectomy) with standard thoracotomy in terms of morbidity and mortality. PATIENTS AND METHODS: Two-hundred and forty-nine consecutive patients with clinical (c) stage I non-small cell lung cancer who underwent surgery between 1999 and 2003 were retrospectively analyzed. All of the patients underwent surgical resection that was at least as extensive as lobectomy. VATS lobectomy was performed in 73 patients, and thoracotomy in 176 patients. RESULTS: The clinical stages were stage IA in 151 (60.6 %), and stage IB in 98 (39.4 %), and the pathological stages were I in 206 (82.7 %), II in 16 (6.4 %), and III in 27 (10.9 %). The mean operation time was 291 minutes for VATS and 215 minutes for thoracotomy ( P = 0.0 042). The mean blood loss was 160 ml and 191 ml ( P = 0.2 738), respectively. Mortality was 1.4 % (1/73) in the VATS group, and 2.3 % (4/176) in the thoracotomy group ( P = 0.6 438). Morbidity was 19.2 % (14/73), and 24.4 % (44/176), respectively ( P = 0.1 315). Air leakage was the most frequent complication. Anastomotic leakage was found in four patients who underwent thoracotomy. The incidence of pulmonary vessel injury was 8.2 % in the VATS group and 1.7 % in the thoracotomy group ( P = 0.0 361). While pulmonary vessel injury was observed frequently in the intermediate part of the study period, the incidence decreased in the late period. CONCLUSIONS: Pulmonary vessel injury, longer operation times, and greater blood loss have been frequently observed with VATS lobectomy. Proficiency is required to perform VATS lobectomy, and the procedure should be performed by a well-trained surgeon as indicated by the results of this study.

[Risk factors of recurrence in resected stage I non-small cell lung cancer].

We reviewed risk factors of recurrence in resected pathological stage I non-small cell lung cancer (I NSCLC). Objective is 229 complete resected I NSCLC in our department. Risk factors of recurrence were carcinoembryonic antigen (CEA), histology, differentiation, lymphatic invasion, blood vessel invasion, pleural invasion and tumor size. By univariate analysis, lymphatic invasion (p=0.009), blood vessel invasion (p=0.008), pleural invasion, p1 (p=0.013), p2 (p=0.001), and tumor size (value of cut off was 2 cm) were significant risk factors of recurrence. By multivariate analysis, blood vessel invasion (p=0.004), pleural invasion (p1 or p2) [p=0.001], were significantly risk factors of recurrence. It was suggested that I NSCLC presenting pathological blood vessel invasion and/or pleural invasion should be recognized as cases with a high risk of recurrence, and a strict follow-up and adjuvant therapy should be in consideration.

Cerebral phaeohyphomycosis caused by ladophialophora bantiana and Fonsecaea monophora: report of three cases.

Three cases of cerebral phaeohyphomycosis are described. Two cases (Cases 1, 2) are caused by highly neurotropic fungi, Cladophialophora bantiana, and the other one (Case 3) is the first reported case in the United States, caused by the newly defined Fonsecaea monophora. (Case 1): A 65-year-old woman had been treated for a presumed diagnosis of Guillain-Barré syndrome and was found to have a ring-enhancing, fluid-filled lesion in the right frontal lobe. The lesion was aspirated twice and then resected completely. (Case 2): A 45-year-old woman with a history of severe dermatomyositis presented with subacute ischemia in the left brainstem. Approximately 2 months later, she developed acute obstructive hydrocephalus and was found to have small cystic lesions in the left ambient cistern, fourth ventricle and cerebral aqueduct, which had probably caused the previous ischemic symptoms due to emboli/ thrombi. (Case 3): A 62-year-old, post livertransplant woman developed multiple brain and bone abscesses. Cultures from these lesions grew the same fungi. Histologically, all three cases revealed multiple epithelioid and giant cell granulomata with groups of golden-brown yeast-like cells as well as chains of budding cells. In Case 3, scattered muriform cells, characteristic of chromoblastomycosis, were present. In Cases 2 and 3, the fungi were easily identified on frozen sections, which may be considered useful in determining post-operative therapy.

Fatal Epstein-Barr virus meningitis: an autopsy report.

A 3-year-old Asian female presented with fever for 1 week and neck swelling for 1 day. Serology revealed a recent Epstein-Barr virus (EBV) infection. Late on the evening of admission, she developed confusion and would not follow commands. A CT scan showed diffuse cerebral edema and a cerebral flow scan demonstrated no blood flow to the brain. She was declared brain dead and expired on the following day. At autopsy, the brain weighted 1175 grams and grossly showed significant edema. Microscopically, the entire neuraxis revealed extensive leptomeningeal infiltrate of mainly CD8+ T lymphocytes, the majority of which expressed activated markers, HLA-DR and/or CD45RO, and monocytes/macrophages with intermixed numerous apoptotic/karyorrhectic nuclear fragments. These nuclear fragments were considered to be due to apoptosis of the expanded population of CD8+ T lymphocytes. Focal venulitis was noted. EBV-encoded small nuclear RNA in situ hybridization revealed positivity in the occasional lymphocytes. Interestingly, most intraparenchymal as well as leptomeningeal vascular endothelium showed HLA-DR immunoreactivity. This finding has been reported primarily in the acute inflammatory/demyelinating conditions, not in the viral meningitis/meningoencephalitis, and was thought to be related to cytokines due to widespread inflammation in our case. Massive edema secondary to severe EBV-meningitis can be fatal.

[Castleman's disease in the interlobar fissure resected by video-assisted thoracoscopic surgery; report of a case].

An abnormal shadow was detected on the chest X-ray of a 33-year-old man in a medical check-up. Chest computed tomography (CT) showed a 2 x 2 x 3 cm tumor which was enhanced, round, homogeneous, and adjacent to the pulmonary artery in the right interlobar fissure. Video-assisted thoracoscopic surgery was performed in August 2002 for diagnosis and treatment. The tumor was surgically removed and grossly round, elastic and hard. The histopathological diagnosis was hyaline vascular type of Castleman's disease. Postoperative course was uneventful, and the patient was discharged on the third postoperative day. Interlobar Castleman's disease successfully resected by video-assisted thoracoscopic surgery is rare.

The herbal medicine Toki-shakuyaku-san improves the hypertension and intrauterine growth retardation in preeclampsia rats induced by Nomega-nitro-L-arginine methyl ester.

The chronic inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME) induces a preeclampsia-like syndrome including hypertension and intrauterine growth retardation (IUGR) in pregnant rats. We tested the traditional herbal medicine Toki-shakuyaku-san (TS) for beneficial effects in this model. L-NAME was infused subcutaneously into pregnant rats from day 14 of gestation. TS (1 g/kg, 2 g/kg) was administered by gavage from day 14 to 20. Systolic blood pressure was measured on day 19. On day 20, rats were sacrificed and serum NO levels, placental weight, fetal body weight, fetal cerebrum weight and the thickness of the cerebral cortex were analyzed. TS (1 g/kg, 2 g/kg) inhibited L-NAME-induced hypertension. The decrease in fetal body weight, cerebrum weight and thickness of the cerebral cortex was abrogated by TS (2 g/kg). The effect of TS on blood pressure was found only in the rats that were both pregnant and infused with L-NAME. L-arginine, at the amount equivalent to that contained in TS, showed no effect. Further, the change in serum NO levels induced by TS was only marginal. TS thus improved the hypertension and IUGR in preeclampsia rats induced by L-NAME in a NO-independent manner. These data suggested that TS may be beneficial for the treatment and prevention of preeclampsia.

Staple line coverage with absorbable mesh after thoracoscopic bullectomy for spontaneous pneumothorax.

BACKGROUND: Thoracoscopic simple bullectomy for primary spontaneous pneumothorax (PSP) has a relatively high postoperative recurrence rate and sometimes results in postoperative air leakage. One of the reasons for postoperative recurrence is the regrowth of bullae around the staple line. Therefore, reinforcement of the visceral pleura around the staple line is a reasonable way to prevent postoperative air leaks and recurrence. This study was done to determine the efficacy in preventing postoperative air leak and recurrent pneumothorax of widely covering the staple line with absorbable mesh after thoracoscopic bullectomy. METHODS: Wide coverage of the staple line with absorbable mesh was performed on 114 patients with PSP. These patients were retrospectively compared with 126 patients who underwent thoracoscopic simple bullectomy alone. RESULTS: The postoperative duration of chest drainage in the coverage group (mean, 1 day; range, 0-5) was significantly shorter than that in the simple bullectomy group (mean, 3 days; range 0-20). A prolonged air leak (>7 days) occurred in six patients in the simple bullectomy group, but there were no such leaks in the coverage group. Recurrent pneumothorax occurred in three patients (2.6%) in the coverage group and 12 patients (9.5%) in the simple bullectomy group. CONCLUSION: Wide coverage of the staple line with absorbable mesh is effective in preventing postoperative air leak and in decreasing the recurrence rates of PSP.