Echocardiographic caudal vena cava measurements in healthy cats and in cats with congestive heart failure and non-cardiac causes of cavitary effusions.

BACKGROUND: Echocardiographic indices of the inferior vena cava have been associated with elevated right atrial pressures in humans. HYPOTHESIS/OBJECTIVES: Describe caudal vena caval (CVC) sonographic dimensions in healthy cats compared to cats with cardiogenic cavitary effusion (CCE), cardiogenic pulmonary edema (CPE), or non-cardiac causes of cavitary effusion (NCE). ANIMALS: 30 healthy control cats and 52 client-owned cats with CCE, CPE, or NCE examined at two university hospitals. METHODS: Sagittal 2-dimensional (2D) and M-mode CVC dimensions were acquired from the subxiphoid view. Caudal vena cava collapsibility index (CVC-CI) was calculated. Variables were compared between study groups using Kruskal-Wallis and Dunn's Bonferroni testing. Receiver operating characteristic curves were used to assess sensitivity and specificity for diagnostic categories. RESULTS: Healthy cats had sagittal 2D and M-mode (median, interquartile range) CVC maximal dimensions of 2.4 mm (1.3-4.0) and 3.4 mm (1.5-4.9) and CVC-CI of 52% (45.2-61.8) and 55% (47.8-61.3), respectively. The CVC maximal dimensions in healthy controls were smaller than in cats with cavitary effusions or pulmonary edema (all P<0.05). CVC-CI was different between CCE and NCE (P<0.0001) with cutoffs of CVC-CI ≤38% (2D) or ≤29% (M-mode) being 90.5% and 85.7% sensitive, and 94.4% and 100% specific for diagnosis of CCE, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Caudal vena cava measurements are larger in cats with cavitary effusions and cats with CPE than healthy cats. In cats with cavitary effusion, decreased CVC-CI, ≤38% (2D) or ≤29% (M-mode), was helpful in distinguishing between cardiogenic and noncardiogenic etiology.

[Optic nerve morphology and vessel density in eyes with different phases of non-arteritic anterior ischemic optic neuropathy].

Objective: To compare the blood flow around the optic disc and related factors in patients with acute and chronic non-arteritic anterior ischemic optic neuropathy (NAION) and healthy volunteers with small disc cups under the same anatomical structure. Methods: This was a prospective case-control study. NAION patients with unilateral onset and healthy volunteers of the same phase were included in the study conducted at the Department of Ophthalmology of Peking Union Medical College Hospital between February 2017 and September 2018. Patients with a course of ≤ 3 months were categorized in the acute phase of NAION, and those with a course of >3 months were in the chronic phase of NAION. Healthy volunteers were in the control group. All subjects underwent the examination of best corrected visual acuity converted to logarithm of the minimum angle of resolution (LogMAR), measurement of non-contact intraocular pressure, slit lamp examination, small pupil fundus examination, and axial measurement. Optical coherence tomography was used to measure the thickness of retinal nerve fiber layers (RNFL) and retinal ganglion cell complex (GCC). Optical coherence tomography angiography was used to measure the vessel density around the optic disc. NAION patients underwent the visual field examination. Analysis of variance, non-parametric Mann-Whitney U test and Spearman coefficient was used for statistical analysis. Results: This study included 16 patients with acute phase of NAION, aged (57±9) years, 6 males and 10 females. There were 17 patients with chronic disease, aged (56±10) years, 7 males and 10 females. There were 15 healthy controls, aged (57±10) years old, 6 males and 9 females. There were no significant differences in age and gender between the groups (both P>0.05). The RNFL and the GCC in the NAION chronic phase group were significantly thinner than those in the acute phase group [(78±38) µm vs. (191±99) µm, (75±19) µm vs. (98±28) µm; t=4.389, 2.758; both P<0.05]. The cup/disc area ratio, cup/disc vertical diameter ratio and cup/disc horizontal diameter ratio in the chronic phase group were larger than those in the acute phase group [0.18 (0.11, 0.31) vs. 0.05 (0.01, 0.18), 0.45 (0.39, 0.56) vs. 0.22 (0.11, 0.41), 0.39 (0.28, 0.54) vs. 0.20 (0.07, 0.42)], and the difference was statistically significant (U=212.000, 208.000, 205.000; all P<0.05). Compared with the optic disc vessel density in the control group (53%±6%), there was a significant decrease in the acute phase group and the chronic phase group (45%±7%, 41%±8%; t=3.705, 4.940; both P<0.01). The blood vessel density in the nasal inferior of the chronic phase group was significantly lower than that in the acute phase group (36%±8% vs. 42%±7%, P=0.039), other sections didn't have significant difference (all P>0.05). There were tortuous capillaries in 8/16 of the acute phase cases, with a low blood flow density and visual field defect in relative positions. Correlation analysis showed that the whole density and peripapillary density in the NAION patients were negatively correlated with LogMAR, mean visual field defect, cup/disc area ratio, focal loss of volume of GCC and general loss of volume of GCC (r=-0.510, -0.733, -0.372, -0.532, -0.648; all P<0.01), but positively correlated with GCC and RNFL thickness (r=0.604, 0.508; both P<0.01). Conclusions: The optic disc vessel density in the acute phase and chronic phase of NAION is significantly reduced. The vessel density in the nasal area of the chronic phase is significantly reduced compared with the acute phase. The vessel density is correlated with visual acuity, visual field defect, disc indexes, thickness of RNFL and GCC. (Chin J Ophthalmol, 2019, 55: 677-686).

[Vessel density and structure in the macular region of non-arteritic anterior ischemic optic neuropathy patients].

Objective: To explore the correlation between the vessel density and the structure and visual function in patients with non-arteritic anterior ischemic optic neuropathy (NAION) in different stages. Methods: This case-control study included 25 NAION patients (28 eyes)of Peking Union Medical College Hospital from November 2017 to May 2018 and 25 healthy controls(HC) (25 eyes) of matched age and gender. General eye examination, visual field examination, and optical coherence tomography angiography were performed to obtain data of blood flow in the macular area and structure such as ganglion cell complex (GCC) and gross loss of volume (GLV), and focal loss of volume (FLV). All affected eyes were divided into the acute group (≤3 weeks), sub-acute group (4 to 12 weeks), and chronic group (>12 weeks) in line with the course of the disease. The group and regional analyses were made to carry out overall differences of blood flows and structures and the correlations with visual function. Results: There were 25 NAION patients with 28 eyes, 16 males and 9 females, aged (55±9) years. The acute group included 8 patients (8 eyes), and the sub-acute group included 10 patients (10 eyes), while the chronic group comprised 7 patients (10 eyes). The overall macular superficial vessel density of patients with NAION was significantly reduced compared with the HC(42.03%±5.70% vs.49.01%±3.34%, t=-5.546, P<0.01), but the deep vessel density was not significantly reduced (P>0.05). The superficial vessel density of the acute group, sub-acute group, and chronic group was significantly decreased(47.41%±3.51% vs. 41.68%±3.09% vs.38.06%±5.93%, all P<0.05). The GCC thickness in patients with NAION were significantly lower than the HC [(88.5±18.2) µm vs. (102.9±5.4)µm, P<0.05]. The GLV and FLV in patients with NAION were significantly higher than the HC (12.733%±11.216% vs. 0.941%±0.852%, 6.295%±4.291% vs. 0.596%±0.460%, both P<0.05). There was a correlation between the macular superficial vessel density and GCC thickness (r=0.606, P=0.001), FLV(r=-0.552, P=0.002), GLV (r=-0.685, P=0.000) and mean sensitivity (r=0.493, P=0.023). Conclusion: Compared with healthy controls, the macular superficial vessel density in NAION patients decreas along with the course of the disease, and its correlation with structural and visual function is revealed. (Chin J Ophthalmol, 2019, 55:195-202).

Electro-optically spectrum narrowed, multiline intracavity optical parametric oscillators.

We report on the first building of an active spectral narrowing mechanism in a pulsed, multiline optical parametric oscillator (OPO) based on a novel aperiodically poled lithium niobate (APPLN) device constructed using the aperiodic optical superlattice technique. The APPLN device functions simultaneously in the system as a multi-channel optical parametric down converter (OPDC) and an electro-optic (EO) gain spectral filter working on the corresponding (multiple) signal bands. When the APPLN OPO was installed in a diode pumped Nd:YVO4 laser system, highly narrowed dual-wavelength signal lines (at 1540 and 1550 nm) were observed at the output of the system through EO control of the APPLN. Correspondingly, an enhancement of the power spectral density of the source by a factor of ~7.8 with respect to the system operated in passive mode was found.

Puberty in the corpus callosum.

Adolescence is an important period for brain development. White matter growth is influenced by sex hormones such as testosterone, and the corpus callosum-the largest white matter structure in the human brain-may change structurally during the hormone-laden period of adolescence. Little is known about puberty's relationship to structural brain development, even though pubertal stage may better predict cognitive and behavioral maturity than chronological age. We therefore aimed to establish the presence and direction of pubertal effects on callosal anatomy. For this purpose, we applied advanced surface-based mesh-modeling to map correlations between callosal thickness and pubertal stage in a large and well-matched sample of 124 children and adolescents (62 female and 62 male) aged 5-18years from a normative database. When linking callosal anatomy to pubertal status, only positive correlations reached statistical significance, indicating that callosal growth advances with puberty. In tests of differences in callosal anatomy at different stages of puberty, callosal growth was concentrated in different locations depending on the pubertal stage. Changing levels of circulating sex hormones during different phases of puberty likely contributed to the observed effects, and further research is clearly needed. Direct quantification of sex hormone levels and regional fiber connectivity-ideally using fiber tractography-will reveal whether hormones are the main drivers of callosal change during puberty. These callosal findings may lead to hypotheses regarding cortical changes during puberty, which may promote or result from changes in inter-hemispheric connectivity.

The structure of the corpus callosum in obsessive compulsive disorder.

Abnormal brain connectivity has recently been reported in obsessive compulsive disorder (OCD). However, structural differences in the corpus callosum (CC), the primary structure connecting the two hemispheres, have not been extensively studied. In this case-control study, we recruited 30 patients with OCD and 30 healthy control subjects carefully matched for age, sex and handedness. Combining surface-based mesh-modeling and voxel-based morphometry (VBM), we compared callosal thickness and white matter (WM) density in patients and controls. We investigated associations between callosal structure and cortical gray matter (GM) density, and we related CC measures to neuropsychological performance in OCD. OCD patients showed small anterior and posterior callosal regions compared to healthy control subjects. In the OCD group, anterior callosal thickness was positively correlated with GM density of the right mid-dorso-lateral prefrontal (BA 9/46) area, while posterior callosal thickness was positively correlated with GM density in the left supramarginal gyrus (BA 40). Moreover, posterior callosal WM density was positively correlated with verbal memory, visuo-spatial memory, verbal fluency, and visuo-spatial reasoning performances. Callosal attributes were related to GM density in cortical areas innervated by the CC, and were also related to performance in cognitive domains impaired in the disorder. The CC may therefore be integrally involved in OCD.

WITHDRAWN: The structure of the corpus callosum in obsessive compulsive disorder.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Spermatic cord myxoid liposarcoma presenting as an incarcerated inguinal hernia: report of a case and review of literatures.

Incarcerated inguinal hernia is a common surgical indication in the emergency room. Delayed diagnosis can result in ischemic bowel or bowel perforation. The reported incarcerated contents include bowel loop, mesentery, omentum and, rarely, malignant lesions, such as lymphoma, metastatic tumors etc. We report a new case of primary spermatic cord liposarcoma presenting as emergent incarcerated inguinal hernia and review the related literature.

Generalized tensor-based morphometry of HIV/AIDS using multivariate statistics on deformation tensors.

This paper investigates the performance of a new multivariate method for tensor-based morphometry (TBM). Statistics on Riemannian manifolds are developed that exploit the full information in deformation tensor fields. In TBM, multiple brain images are warped to a common neuroanatomical template via 3-D nonlinear registration; the resulting deformation fields are analyzed statistically to identify group differences in anatomy. Rather than study the Jacobian determinant (volume expansion factor) of these deformations, as is common, we retain the full deformation tensors and apply a manifold version of Hotelling's $T(2) test to them, in a Log-Euclidean domain. In 2-D and 3-D magnetic resonance imaging (MRI) data from 26 HIV/AIDS patients and 14 matched healthy subjects, we compared multivariate tensor analysis versus univariate tests of simpler tensor-derived indices: the Jacobian determinant, the trace, geodesic anisotropy, and eigenvalues of the deformation tensor, and the angle of rotation of its eigenvectors. We detected consistent, but more extensive patterns of structural abnormalities, with multivariate tests on the full tensor manifold. Their improved power was established by analyzing cumulative p-value plots using false discovery rate (FDR) methods, appropriately controlling for false positives. This increased detection sensitivity may empower drug trials and large-scale studies of disease that use tensor-based morphometry.

Giant enhancement of band edge emission based on ZnO/TiO(2) nanocomposites.

Enhancement of band edge emission of ZnO nanorods up to a factor of 120 times has been observed in the composite consisting of ZnO nanorods and TiO(2) nanoparticles, while the defect emission of ZnO nanorods is quenched to noise level. Through a detailed investigation, it is found that the large enhancement mainly arises from fluorescence resonance energy transfer between the band edge transition of ZnO nanorods and TiO(2) nanoparticles. Our finding opens up new possibilities for the creation of highly efficient solid state emitters.

Enhancement of band gap emission stimulated by defect loss.

Defect radiation has been always considered as the most important loss for an emitter based on band gap emission. Here, we propose a novel approach which goes against this conventional wisdom. Based on the resonance effect between the surface plasmon of metal nanoparticles and defect emission, it is possible to convert the useless defect radiation to the useful excitonic emission with a giant enhancement factor. Through the transfer of the energetic electrons excited by surface plasmon from metal nanoparticles to the conduction band of the emitter, the band gap emission can be greatly enhanced, while the defect emission can be suppressed to noise level.

Differentiation of ovarian mucinous carcinoma and metastatic colorectal adenocarcinoma by immunostaining with beta-catenin.

AIMS: To investigate whether localization of beta-catenin is helpful in differentiating primary ovarian mucinous carcinoma and colorectal adenocarcinoma metastatic to the ovary. Extra-ovarian cancers which metastasize to the ovaries, especially from colorectal adenocarcinoma, frequently mimic primary ovarian carcinomas, particularly endometrioid and mucinous types. Distinguishing primary ovarian carcinoma from metastatic colorectal carcinoma is important for both therapeutic and prognostic reasons. Even after thorough histological examination, metastatic colorectal adenocarcinomas are still often mistaken for primary ovarian adenocarcinomas. Although some tumour makers have been advocated and are helpful in most cases, sometimes the distinction between primary mucinous carcinoma and metastatic colorectal carcinoma remains a problem. Activation of Wnt signalling through mutations of APC or beta-catenin is a key event in the development of colorectal cancer. These mutations lead to nuclear localization of beta-catenin, which can be demonstrated immunohistochemically. METHODS AND RESULTS: Formalin-fixed paraffin-embedded specimens from 43 primary ovarian mucinous carcinomas and 23 metastatic colorectal adenocarcinomas were included in this study. Sections were immunostained with antibodies to beta-catenin, cytokeratin (CK)7, CK20 and carcinoembryonic antigen (CEA). Nuclear localization of beta-catenin was found in 83% (19/23) of metastatic colorectal cancers and 9% (4/43) of ovarian mucinous carcinomas. Ovarian mucinous carcinomas were usually positive for CK7 (34/43, 79%). For comparison, 40 non-mucinous carcinomas of the ovary and 42 metastatic adenocarcinomas from other organs were also immunostained with antibodies against beta-catenin. Although nuclear localization of beta-catenin was occasionally seen in non-mucinous carcinoma of the ovary and metastatic adenocarcinoma from other organs, such tumours were usually distinguishable by their clinicopathological picture and rarely raised diagnostic problems. CONCLUSIONS: Immunostaining of beta-catenin is a useful marker for differentiating between ovarian mucinous carcinoma and metastatic colorectal adenocarcinoma.

An analysis of excitatory amino acids, nitric oxide, and prostaglandin E2 in the cerebrospinal fluid of pregnant women: the effect on labor pain.

UNLABELLED: It is still unclear which neurotransmitters are involved in labor pain. We measured the concentrations of excitatory amino acids, nitric oxide, and prostaglandin E2 in the cerebrospinal fluid (CSF) of pregnant women, particularly in those with labor pain. The patients included in the study consisted of women who underwent cesarean delivery either with labor pain (Labor Pain group, n = 40) or without labor pain (Nonlabor Pain group, n = 58). All patients received spinal anesthesia (intrathecal injection of 10-12 mg of bupivacaine) for the operation, and 2 mL of CSF was collected before bupivacaine injection. Concentrations of aspartate and glutamate (0.50 +/- 0.06 microM and 0.79 +/- 0.10 microM, respectively) were significantly larger in the Labor Pain group than in the Nonlabor Pain group (0.35 +/- 0.03 microM and 0.54 +/- 0.04 microM, P < 0.05). There were no significant differences in the concentrations of nitric oxide and prostaglandin E2 between the groups. A positive correlation was found between CSF concentrations of excitatory amino acids and labor pain. IMPLICATIONS: The excitatory amino acids, aspartate and glutamate, play a role in labor pain. N-methyl-D-aspartate receptor antagonists may be useful for labor pain and postlabor uterine contraction pain relief.

p53 and p21 expression in precancerous lesions and carcinomas of the uterine cervix: overexpression of p53 predicts poor disease outcome.

OBJECTIVES: Abnormal expression of the p53 and p21(waf1/cip1) tumor suppressor genes has been observed in a variety of human tumors, but little is known about its expression during cervical tumorigenesis. To identify the potential implications of both genes in the development of cervical carcinoma and explore the clinical importance of changes in gene expression, we assessed the levels of both proteins in precancerous lesions and carcinomas of the cervix. METHODS: In our study, 10 low-grade squamous intraepithelial lesions (LSIL), 35 high-grade squamous intraepithelial lesions (HSIL), 12 microinvasive carcinomas, and 103 invasive carcinomas were evaluated. The expression of p53 and p21 was studied by immunohistochemistry using monoclonal antibodies specific for these proteins. RESULTS: p21 was expressed in all samples of normal epithelium, LSIL, and HSIL, and the mean values of expression were 50.3, 42.5, and 44.5%, respectively. Conversely, the expression of p21 was significantly reduced in microinvasive (30.7%) and invasive carcinomas (9.9%). p53 nuclear staining was not detected in normal epithelium samples or LSILs, while 4 (11.4%) of 35 HSILs, 1 (8.3%) of 12 microinvasive carcinomas, and 38 (36.9%) of 103 invasive carcinomas were positive for p53. Compared with the results of the control group, precancerous lesions, and microinvasive carcinoma, the mean value of p53 expression (4.8%) in invasive carcinoma was significantly higher. Furthermore, p53 overexpression was significantly associated with advanced stage of the tumor (P < 0.001) [16/67 (23.9%) stage I, 15/28 (53.6%) stage II, and 7/8 (87.5%) stage III/IV]. In univariate analysis, p53 overexpression was a significant predictor of poor survival, whereas it had no independent influence on overall survival using the Cox regression method. Our data also revealed that no association between p53 immunostaining and p21 expression was found. CONCLUSIONS: The trend of reduced p21 expression in microinvasive and invasive carcinomas suggests that p21 may play a tumor-suppressor function in neoplastic transformation in cervical epithelium and inactivation of p21 may be an early event in cervical carcinogenesis. Our results indicated that p53 overexpression was a significant predictor of poor disease outcome in univariate analysis. Moreover, significantly increased expression of p53 in advanced-stage cervical carcinoma implies that inactivation of p53 is associated with tumor progression. Finally, this study further supports the notion that induction of p21 expression can be regulated in a p53-independent manner.

Isolated fetal and neonatal ascites: report of two cases.

Neonatal ascites is an uncommon problem that may be caused by a number of etiologies including diseases of genitourinary system and gastrointestinal system, cardiac disease, hepatic disease, systemic infection such as TORCH or parvovirus, chylous, ovarian cause, inborn error of metabolism and idiopathic. We reported two cases of neonatal ascites, one was caused by cytomegalovirus and no obvious causes could be detected in the second one. The ascites were diagnosed by prenatal ultrasound at the gestational age of 25 weeks and 37 weeks respectively and were resolved spontaneously after birth. One-year follow-up of both cases revealed normal growth and development. No recurrent ascites could be detected by abdominal sonography except for evidence of mild hepatomegaly that was noted in case 1. Thus, isolated fetal and neonatal ascites without other concomitant abnormalities were diagnosed, a separate entity from non-immune hydrops fetalis with excellent prognosis.

Intrathecal cyclooxygenase inhibitor administration attenuates morphine antinociceptive tolerance in rats.

Several lines of evidence suggest that the N-methyl-D-aspartate receptor (NMDA) and nitric oxide (NO) systems are involved in morphine tolerance. Cyclooxygenase (COX) inhibitors may also play a role in morphine tolerance by interacting with both systems. In the present study, we examined the effects of the COX inhibitors N-(2-cyclohexyloxy-4-nitrophenyl) methanesulphonamide (NS-398, selective COX2 inhibitor) and indomethacin (non-selective COX inhibitor) on the development of antinociceptive tolerance of morphine in a rat spinal model. The antinociceptive effect was determined by the tail-flick test. Tolerance was induced by injection of morphine 50 micrograms intrathecally (i.t.) twice daily for 5 days. The effects of NS-398 and indomethacin on morphine antinociceptive tolerance were examined after administering these drugs i.t. 10 min before each morphine injection. Neither NS-398 nor indomethacin alone produced an antinociception effect at doses up to 40 micrograms. NS-398 and indomethacin did not enhance the antinociceptive effect of morphine in naïve and morphine-tolerant rats. However, they shifted the morphine antinociceptive dose-response curve to the left when coadministered with morphine during tolerance induction, and reduced the increase in the ED50 of morphine (dose producing 50% of the maximum response) three- to four-fold. Collectively, these findings and previous studies suggest that COX may be involved in the development of morphine tolerance without directly enhancing its antinociceptive effect.

Morphine tolerance increases [3H]MK-801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord.

N-Methyl-D-aspartate (NMDA) receptor antagonists and nitric oxide synthase (NOS) inhibitors inhibit morphine tolerance. In the present study, a lumbar subarachnoid polyethylene (PE10) catheter was implanted for drug administration to study alterations in NMDA receptor activity and NOS protein expression in a morphine-tolerant rat spinal model. Antinociceptive tolerance was induced by intrathecal (i.t.) morphine infusion (10 micrograms h-1) for 5 days. Co-administered (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) (10 micrograms h-1 i.t.) with morphine was used to inhibit the development of morphine tolerance. Lumbar spinal cord segments were removed and prepared for [3H]MK-801 binding assays and NOS western blotting. The binding affinity of [3H]MK-801 was higher in spinal cords of morphine-tolerant rats (mean (SEM) KD = 0.41 (0.09) nM) than in control rats (1.50 (0.13) nM). There was no difference in Bmax. Western blot analysis showed that constitutive expression of neuronal NOS (nNOS) protein in the morphine-tolerant group was twice that in the control group. This up-regulation was partially prevented by MK-801. The results suggest that morphine tolerance affects NMDA receptor binding activity and increases nNOS expression in the rat spinal cord.

Atypical central neurocytoma: report of a case.

Central neurocytomas are rare, relatively benign intraventricular neoplasms composed of uniform round cells with neuronal differentiation. The majority of previously reported central neurocytomas did not recurr after tumor removal and the patients had favorable postoperative outcomes. Only a few cases with malignant histopathology or malignant behavior have been noted. Atypical central neurocytoma is a new entity that was first described in the literature in 1997. The tumors have been noted to exhibit a Ki-67 labeling index of 2% or more, or vascular proliferation, mitoses, and necrosis, or both. Atypical histologic findings are usually associated with a somewhat less favorable clinical course and requires postoperative radiotherapy. We report a unique case of a 33-year-old man with a large intraventricular central neurocytoma. The characteristic histopathologic picture, the immunoreactivity for both synaptophysin and neuron-specific enolase, and the ultrastructural features of neuronal differentiation distinguished it from ependymoma and oligodendroglioma. The mitotic activity (up to 3 mitoses/10 high power field) and the high percentage of Ki-67-staining tumor cells (labeling index, 5.0%) in our case were consistent with the atypical variant of central neurocytoma. The patient underwent craniotomy and partial resection of the tumor. Unfortunately, he died of hydrocephalus and brain edema, the next day.

Ultrastructural and biochemical characterization of catecholamine release mechanisms in cultured human pheochromocytoma cells.

OBJECTIVE: To characterize ultrastructurally and biochemically catecholamine release mechanisms of cultured human pheochromocytoma cells in the basal and stimulated states. METHODS: The cultured pheochromocytoma cells were prepared from human adrenal pheochromocytoma tumors. Biochemical determinations of catecholamine secretion from the cultured cells were carried out in the basal and stimulated states. Transmission electron microscopy was used to observe the modes of catecholamine release from the cells without and with stimulation by depolarization of the cells with the administration of 50 mmol/L KCl. RESULTS: Biochemical determinations consistently showed spontaneous secretion of catecholamines from the cultured cells in the basal state without stimulation. Catecholamine release in a calcium-dependent manner could be enhanced in the cells in response to high extracellular potassium concentration. A series of electron microscopic observations of the cultured cells consistently disclosed the classical exocytotic profiles on the cell surface in the basal state. In addition to abundant increase in the number of classical single exocytosis, compound exocytosis was frequently observed in the stimulated cells. Furthermore, other modes of catecholamine release mechanism involving the formation of pseudopodial and/or tubule-like structures, which were different from classical exocytosis, were often present in the intensely stimulation cells. CONCLUSIONS: Based on the biochemical and electron microscopic findings, we concluded: (1) classical single exocytosis is considered to be a primary mechanism responsible for spontaneous secretion of catecholamines from the cells in the basal state; (2) compound exocytosis is an essential mechanism for extruding large amounts of catecholamines in the stimulated cells; and (3) other modes of catecholamine release mechanism may operate in the cells in response to intense stimulation. These morphological data may be helpful in explanation of biochemical variability and extreme diversity of clinical manifestations in patients with pheochromocytoma tumor.

Pathogenetic mechanism of senile calcific aortic stenosis: the role of apoptosis.

OBJECTIVE: To investigate the pathogenetic mechanisms leading to the development of calcific degeneration of the aortic valve in the elderly patients with particular reference to the relationship between apoptosis and calcification in the aortic valve tissue. METHODS: High resolution scanning and transmission electron microscopic observations of the calcified aortic valves obtained during aortic valve replacement were carried out in 10 patients with senile calcific aortic stenosis. RESULTS: Various degrees of endothelial alterations from focal disruption of individual endothelial cells to extensive denudation of entire endothelium were observed particularly on the aortic side of the valve tissues. The apoptotic changes occurring in the nuclei of endothelial cells and fibroblasts were common findings in the calcified valve tissues. It was noteworthy that the severity of endothelial damage was closely related to apoptotic changes of the fibroblasts. Calcific deposits were frequently observed in association with the cellular fragments mainly derived from the apoptotic fibroblasts. CONCLUSIONS: Our results strongly indicate that apoptosis may play an important role in the alterations of endothelial integrity leading to the increased filtration of calcium into the deeper layer of the valve tissues. Then, the cellular degradation products and organelles extruded from the dead cells, mainly resulted from apoptosis provided the substrates for calcium binding with progressive development of calcification in the valve tissue. Although the role of apoptosis in contribution to the pathogenesis of senile calcific aortic stenosis is evident, further studies using modern molecular biotechnology are mandatory in order to clarify the mechanism for the initiation of apoptotic process in the endothelial cells and fibroblasts.