Mesenchymal chondrosarcoma of the temporal bone

A 64-year-old patient with mesenchymal chondrosarcoma of the temporal bone is described. CT and MRI showed an extensive mass with calcification involving the temporal bone and extending into the middle cranial fossa and nasopharynx. The tumor was ill-defined from surrounding normal bone, and a subtotal petrosectomy was carried out. The nasopharyngeal extension was removed secondarily using an endoscope. The clinical and diagnostic aspects and management of this rare lesion are discussed.     

Genotype-phenotype correlations for EPM2A mutations in Lafora's progressive myoclonus epilepsy: exon 1 mutations associate with an early-onset cognitive deficit subphenotype

Mutations in the EPM2A gene encoding a dual-specificity phosphatase (laforin) cause an autosomal recessive fatal disorder called Lafora's disease (LD) classically described as an adolescent-onset stimulus-sensitive myoclonus, epilepsy and neurologic deterioration. Here we related mutations in EPM2A with phenotypes of 22 patients (14 families) and identified two subsyndromes: (i) classical LD with adolescent-onset stimulus-sensitive grand mal, absence and myoclonic seizures followed by dementia and neurologic deterioration, and associated mainly with mutations in exon 4 (P = 0.0007); (ii) atypical LD with childhood-onset dyslexia and learning disorder followed by epilepsy and neurologic deterioration, and associated mainly with mutations in exon 1 (P = 0.0015). To understand the two subsyndromes better, we investigated the effect of five missense mutations in the carbohydrate-binding domain (CBD-4; coded by exon 1) and three missense mutations in the dual phosphatase domain (DSPD; coded by exons 3 and 4) on laforin's intracellular localization in HeLa cells. Expression of three mutant proteins (T194I, G279S and Y294N) in DSPD formed ubiquitin-positive cytoplasmic aggregates, suggesting that they were folding mutants set for degradation. In contrast, none of the three CBD-4 mutants showed cytoplasmic clumping. However, CBD-4 mutants W32G and R108C targeted both cytoplasm and nucleus, suggesting that laforin had diminished its usual affinity for polysomes. Our data, thus, represent the first report of a novel childhood syndrome for LD. Our results also provide clues for distinct roles for the CBD-4 and DSP domains of laforin in the etiology of two subsyndromes of LD.     

Optical bioimaging: from living tissue to a single molecule: calcium imaging in blood vessel in situ employing two-photon excitation fluorescence microscopy

Recent developments in optoelectronics permit real-time Ca(2+) imaging of thin planes within cells utilizing laser scanning confocal microscopy (LSCM). However, a major complication associated with this imaging system involves increased phototoxicity with improved spatiotemporal resolution. Two-photon excitation microscopy (TPEM) helps to minimize phototoxicity due to the restriction of this technique to the volume proximal to the geometric focus of the light. In this study, the capability of Ca(2+) imaging was investigated employing recently developed real-time TPEM, RTS2000MP (Bio-Rad, Tokyo) with a mode-locked Ti-sapphire laser. Z-axis resolution of RTS2000MP with high NA objectives defined as full-width at half maximum (FWHM) with a 0.5-microm fluorescent bead provided values nearly identical to those obtained with LSCM at a small pinhole (0.2 mm) (approximately 0.6 microm). When serial sectioning of 21 sequential images at 0.3-microm intervals in cultured endothelial cells loaded with calcein and tetramethyl-rhodamine methylester were performed with TPEM, the z-axis resolution was higher than that observed with LSCM; moreover, the photobleaching rate was significantly lower than that obtained with LSCM. Maximum fluorescence intensities were detected at 780 nm in excitation spectra of fluo-3 and fluo-4 Ca(2+)-sensitive probes with TPEM. Fluorescence images in mouse arterial endothelial cells loaded with fluo-4 could be clearly visualized by TPEM in situ. Application of acetylcholine caused oscillatory increase in [Ca(2+)](i) of endothelial cells; subsequently, relaxation along the major axis of smooth muscle cells was evident. Furthermore, consecutive long-lasting experiments could be repeated with identical response in the same microscopic field. In conclusion, fluorescence imaging employing TPEM is useful for Ca(2+) imaging in blood vessels in situ.     

Lysophosphatidic acid enhances in vivo infiltration and activation of guinea pig eosinophils and neutrophils via a Rho/Rho-associated protein kinase-mediated pathway

Lysophosphatidic acid (LPA) has been shown to be a chemoattractant in in vitro studies. The present study was carried out to determine whether LPA enhances infiltration of inflammatory cells in in vivo studies with guinea pigs. LPA (1 - 10 microg/ml), when by guinea pigs for 5 min, substantially increased the numbers of eosinophils and neutrophils in the bronchoalveolar lavege fluid (BALF), which was recovered at over 4 h after the inhalation of LPA. Infiltration in BALF was significantly inhibited by inhalation of Y-27632, an inhibitor of Rho-associated protein kinase (ROCK). LPA also increased superoxide production of eosinophils and neutrophils. In contrast, Y-27632 inhibited superoxide production. These findings suggest that LPA may contribute to infiltration and activation of inflammatory cells in bronchial asthma; furthermore, the Rho/ROCK-mediated pathway may be involved.     

Allogenic blood transfusion is an independent risk factor for infective complications after less invasive gastrointestinal surgery

BACKGROUND: The present study aimed to clarify the predisposing factors for postoperative infectious complications after less invasive surgery. METHODS: A total 150 surgical patients were placed in either group H (operative blood loss > or = 500 mL) or group L (<500 mL). The patients' background factors and postoperative inflammatory responses were assessed. RESULTS: The operating time was an independent risk factor for infectious complication in group H. In contrast, allogenic blood transfusion was the only significant risk factor for infection in group L. In the patients who received blood transfusion, exaggerated postoperative interleukin-6 response was found in group H, whereas an increased consumption of interleukin-6 soluble receptor with resultant induction of immunosuppressive acidic protein (IAP) were found in group L. CONCLUSIONS: Perioperative blood transfusion may predominantly contribute to increased susceptibility to infection after less invasive surgery through increased affinity of interleukin-6 soluble receptor and enhanced IAP response.     

Three-dimensional stereotactic surface projection of brain perfusion SPECT improves diagnosis of Alzheimer’s disease

OBJECTIVES: Alzheimer's disease (AD) is diagnosed by either inspection of the brain perfusion SPECT, or three-dimensional stereotactic surface display (3D-SSP). The purpose was to compare diagnostic performances of these methods. METHODS: Sixteen nuclear medicine physicians independently interpreted 99mTc-ECD SPECT in one session and SPECT with 3D-SSP in another session without clinical information for 50 studies of AD patients and 40 studies of healthy volunteers. Probabilities of AD were reported according to a subjective scale from 0% (normal) to 100% (definite AD). Receiver operating characteristics curves were generated to calculate areas under the ROC curves (Az's) for the inspection as well as for an automated diagnosis based on a mean Z value in the bilateral posterior cingulate gyri in a 3D-SSP template. RESULTS: Mean Az for visual interpretation of SPECT alone (0.679 +/- 0.058) was significantly smaller than that for visual interpretation of both SPECT and 3D-SSP (0.778 +/- 0.060). Az for the automated diagnosis (0.883 +/- 0.037) was significantly greater than that for both modes of visual interpretation. CONCLUSIONS: 3D-SSP enhanced performance of the nuclear medicine physicians inspecting SPECT. Performance of the automated diagnosis exceeded that of the physicians inspecting SPECT with and without 3D-SSP.     

Mechanism of QT interval prolongation induced by sevoflurane in guinea-pig ventricular myocyte

BACKGROUND: Sevoflurane causes QT interval prolongation clinically, but its precise mechanism has not been clarified. We examined the mechanism of QT interval prolongation induced by sevoflurane by means of electrophysiological technique in guinea-pig ventricular myocyte. METHODS: Electrocardiogram was recorded in guinea-pig and effect of sevoflurane (1, 2, 4%) was examined. Action potential (AP), delayed rectified potassium current (IKr), and L-type calcium channel current (ICa) were monitored as whole-cell current and by voltage clamp techniques in guinea-pig single ventricular myocytes. Sevoflurane was applied by bubbling into the bathing solution. RESULTS: Sevoflurane (1, 2, 4%) increased QTc value. Sevoflurane prolonged the duration of AP at 2%, but shortened it at 6%. IKr was reduced to 35% of control in the presence of 2% sevoflurane, but a higher concentration (6%) did not show further inhibition. ICa was reduced only to 87% of control in the presence of 2% sevoflurane and the reduction was dose-dependent (4, 6%). CONCLUSIONS: Sevoflurane 2% inhibited IKr, but it showed only slight inhibition on ICa. Because the duration of AP is regulated by ICa (plateau phase) and IKr (repolarization), greater inhibition of IKr than ICa could result in prolongation of AP. It is suggested that this mechanism may play a role in QT interval prolongation under sevoflurane anesthesia.     

Anesthetic management for electroconvulsive therapy (ECT) in a patient with primary aldosteronism

A 68-year-old male with primary aldosteronism who was scheduled for electroconvulsive therapy (ECT). We used propofol and suxamethonium to induce anesthesia, and measured plasma levels of aldosterone to evaluate the influence of ECT during anesthesia. Although plasma levels of aldosterone increased gradually after ECT, there were no complications including severe hypertension or arrhythmia perioperatively.     

Induction of immunologic tolerance to cardiac allograft by simultaneous blockade of inducible co-stimulator and cytotoxic T-lymphocyte antigen 4 pathway

BACKGROUND: Inducible co-stimulator (ICOS) is one of the most recently described members of the CD28 family, and it plays an important role in immune responses. To investigate the role of ICOS in allograft rejection, the authors studied graft survival after cardiac transplantation in mice. METHODS: Hearts from BALB/c mice were transplanted into C3H/He mice. Immunohistochemical staining and flow cytometry were performed. Monoclonal antibody to ICOS or ICOS-immunoglobulin (Ig) was injected intraperitoneally. The authors performed mixed lymphocyte reaction (MLR). RESULTS: ICOS was expressed strongly by graft-infiltrating cells during rejection of the allograft. Blockade of the ICOS pathway with anti-ICOS antibody and ICOSIg significantly prolonged graft survival time relative to that in untreated mice; however, all cardiac allografts were eventually rejected by a single treatment. Treatment with both ICOSIg and cytotoxic T-lymphocyte antigen 4 (CTLA4) Ig induced not only long-term acceptance of the cardiac allograft but also donor-specific tolerance, which was shown by acceptance of donor but not third-party skin. Graft arterial intimal hyperplasia in these cardiac allografts was remarkably less than that in cardiac allografts treated with tacrolimus. Addition of anti-ICOS antibody or ICOSIg to MLR resulted in inhibition of T-cell proliferation. CONCLUSIONS: Inhibition of T-cell proliferation with ICOSIg and CTLA4Ig was more effective than that with ICOSIg alone. Thus, ICOS appears to be an important regulator of T-cell activation, and may be an effective therapy in clinical cardiac transplantation.