Clinical characteristics and outcomes of pheochromocytoma crisis: a literature review of 200 cases.

PURPOSE: Pheochromocytoma crisis is a life-threatening endocrine emergency that requires prompt diagnosis and treatment. Because of its rarity, sudden onset, and lack of internationally uniform and validated diagnostic criteria, pheochromocytoma crisis remains to be fully clarified. Therefore, we aimed to describe the clinical characteristics and outcomes of pheochromocytoma crisis through a literature review. METHODS: We performed a systematic literature search of PubMed/MEDLINE database, Igaku-Chuo-Zasshi (Japanese database), and Google Scholar to identify case reports of pheochromocytoma crisis published until February 5, 2021. Information was extracted and analyzed from the literature that reported adequate individual patient data of pheochromocytoma crisis in English or Japanese. Cases were also termed as pheochromocytoma multisystem crisis (PMC) if patients had signs of hyperthermia, multiple organ failure, encephalopathy, and labile blood pressure. RESULTS: In the 200 cases of pheochromocytoma crisis identified from 187 articles, the mean patient age was 43.8 ± 15.5 years. The most common symptom was headache (39.5%). The heart was the most commonly damaged organ resulting from a complication of a pheochromocytoma crisis (99.0%), followed by the lungs (44.0%) and the kidney (21.5%). PMC accounted for 19.0% of all pheochromocytoma crisis cases. After excluding 12 cases with unknown survival statuses, the mortality rate was 13.8% (26/188 cases). Multivariable logistic regression analysis revealed that nausea and vomiting were significantly associated with a higher mortality rate. CONCLUSION: Pheochromocytoma can present with different symptomatology, affecting different organ systems. Clinicians should be aware that patients with nausea or vomiting are at a higher risk of death because of pheochromocytoma crisis.

Preoperative prediction for regaining ambulatory ability in paretic non-ambulatory patients with metastatic spinal cord compression.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To analyze the predictive factors for postoperative ambulatory recovery in paretic non-ambulatory patients with metastatic spinal cord compression (MSCC). SETTING: Japan. METHODS: Eighty-two consecutive patients (74.4% men; mean age, 66.2 years) who could not walk before surgery due to cervical or thoracic MSCC and underwent posterior decompressive surgery between 2003 and 2014 were included. Patients were divided into two groups according to ambulatory status at 6 weeks after surgery: recovery (group R) and non-recovery (group NR). To evaluate the speed of progression of motor deficits, we assessed the period from onset of neurological symptoms to gait inability (T1). RESULTS: Fifty patients (61.0%) regained the ability to walk (group R). The period of T1 demonstrated a positive correlation with probability of ambulatory recovery (P=0.00; Kendall's tau-b=0.38), and a receiver operating characteristic curve analysis showed that the cutoff value of T1 was 5 days (area under the curve=0.72; P=0.001). In multivariate analysis, <6 days of T1 was one of the independent risk factors for failing to regain ambulatory ability (odds ratio, 8.74; P=0.00). CONCLUSIONS: The speed of progression of motor deficits can independently and powerfully predict the chance of postoperative ambulatory recovery as well as previously identified predictors. Since information about the speed of progression can be obtained easily by interviewing patients or family members, even if the patient is in an urgent state, our results will be helpful in clinical decision-making.

Paracoccidioides brasiliensis and P. lutzii antigens elicit different serum IgG responses in chronic paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis (S1, PS2, and PS3) and by the new species, P. lutzii. Considering that genetic differences in the Paracoccidioides genus could elicit distinct immune responses by the host, current research investigated serum IgG levels to antigens from P. brasiliensis B339 (S1), P. brasiliensis LDR3 (PS2), and atypical strain LDR2 (P. lutzii), in patients with chronic PCM from the northern and west regions of Paraná, Brazil (n = 35). Cell-free antigen (CFA) and high molecular mass fraction (hMM) were produced from each strain. Samples were analyzed by ELISA and immunodiffusion (ID). ELISA positivity using CFA: B339-100 %, LDR3-83 %, and LDR2-74 %. Response to CFA from B339 was more intense (p < 0.05), while there was no difference between LDR3-LDR2. IgG anti-hMM was higher for antigens from B339 or LDR3, when compared with LDR2 (p < 0.05). There was a positive correlation for each strain between CFA-hMM and for hMM between B339-LDR3 and LDR3-LDR2. ID positivity with CFA: B339-63 %, LDR3-66 %, and LDR2-60 %. We conclude that the intensity of reaction of the patients' sera varies with the strain used; hMM influences tests that use CFA, independently of strain; using ID, positive rates were very similar, but there was a large number of false negative results; ELISA tests using antigens from P. brasiliensis S1 were able to detect a larger number of patients than PS2 and P. lutzii (which had a considerable number of false negative results), and therefore, its use may be more appropriate in this region of Brazil.

Phasic synaptic incorporation of GluR2-lacking AMPA receptors at gonadotropin-releasing hormone neurons is involved in the generation of the luteinizing hormone surge in female rats.

Reproductive success depends on a robust and appropriately timed preovulatory luteinizing hormone (LH) surge, which is induced by the activation of gonadotropin-releasing hormone (GnRH) neurons in response to positive feedback from increasing estrogen levels. Here we document an increase in postsynaptic GluR2-lacking Ca2+ -permeable AMPA-type glutamate receptors (CP-AMPARs) at synapses on GnRH neurons on the day of proestrus in rats, coincident with the increase in estrogen levels. Functional blockade of CP-AMPARs depressed the synaptic responses only on the day of proestrus and concomitantly attenuated the LH surge. Thus, the phasic synaptic incorporation of postsynaptic CP-AMPARs on GnRH neurons is involved in the generation of the LH surge.

Epithelial to mesenchymal transition in murine tracheal allotransplantation: an immunohistochemical observation.

BACKGROUND: Aberrant epithelial repair is a crucial event in the airway remodeling that characterizes obliterative bronchiolitis (OB) in transplanted lungs. Recent data from experiments using epithelial cell lines and human airway tissues from lung transplant recipients suggest that epithelial to mesenchymal transition (EMT) plays an important role in OB. The aim of this study was to clarify whether EMT is involved in airway remodeling in an animal model. METHODS: We performed orthotopic tracheal transplantation from BALB/c to C57BL/6 mice with from BALC/c to BALB/c mouse grafts as controls. Five allogeneic and 3 syngeneic recipients were humanely killed at predetermined postoperative days 2-12 as well as 14 and 21. Histology was evaluated using hematoxylin-eosin (H&E) staining. We studied the expression of specific markers, including E-cadherin, an epithelial marker; α-smooth muscle actin (SMA), and S100A4, mesenchymal markers, and zinc finger E-box-binding homeobox 1 (ZEB1), an EMT-related transcription factor. RESULTS: Histologic assessment of serial H&E stains of allogeneic grafts showed remarkable pseudostratified respiratory epithelium with subepithelial inflammatory cell infiltration, as well as denuded and flattened epithelium and subepithelial fibrosis. The dynamic epithelial changes occurred earlier than the subepithelial fibrosis. Immunohistochemical evaluation indicated the emergence of α-SMA- positive epithelial cells that were most prominent on day 7. The expression of E-cadherin was attenuated in α-SMA-positive epithelial cells. S100A4 was also expressed in epithelial cells. A few days before the intraepithelial expression of α-SMA, ZEB1 emerged in the nuclei of epithelial cells. CONCLUSIONS: We observed expression of an EMT-related transcription factor and mesenchymal markers along with the attenuation of epithelial marker expression in epithelial cells, several days before prominent subepithelial fibrosis formation, results that suggest epithelial cells to play an important fibrosis role in airway remodeling during epithelial to mesenchymal transition.

A mechanical coil insertion system for endovascular coil embolization of intracranial aneurysms.

Like other fields of medicine, robotics and mechanization might be introduced into endovascular coil embolization of intracranial aneurysms for effective treatment. We have already reported that coil insertion force could be smaller and more stable when the coil delivery wire is driven mechanically at a constant speed. Another background is the difficulty in synchronizing operators' minds and hands when two operators control the microcatheter and the coil respectively. We have therefore developed a mechanical coil insertion system enabling a single operator to insert coils at a fixed speed while controlling the microcatheter. Using our new system, the operator manipulated the microcatheter with both hands and drove the coil using foot switches simultaneously. A delivery wire force sensor previously reported was used concurrently, allowing the operator to detect excessive stress on the wire. In vitro coil embolization was performed using three methods: simple mechanical advance of the coil; simple mechanical advance of the coil with microcatheter control; and driving (forward and backward) of the coil using foot switches in addition to microcatheter control. The system worked without any problems, and did not interfere with any procedures. In experimental coil embolization, delivery wire control using the foot switches as well as microcatheter manipulation helped to achieve successful insertion of coils. This system could offer the possibility of developing safer and more efficient coil embolization. Although we aim at total mechanization and automation of procedures in the future, microcatheter manipulation and synchronized delivery wire control are still indispensable using this system.

Indications for and limits of conservative surgery in breast cancer.

Improvements in diagnostic techniques and, above all, breast cancer screening campaigns - essential for early diagnosis - have enabled the objectives of conservative surgery to be pursued: disease control, no or low incidence of recurrences and an excellent esthetic result. However, to reach these objectives, it is essential to ensure a careful evaluation of the medical history of every patient, a detailed clinical examination and the correct interpretation of imaging. Particular attention should be paid to all factors influencing the choice of treatment and/or possible local recurrence: age, site, tumor volume, genetic predisposition, pregnancy, previous radiotherapy, pathological features, and surgical margins. The decision to undertake conservative treatment thus requires a multidisciplinary approach involving pathologists, surgeons and oncological radiologists, as well, of course, as the patient herself.

Non-genomic inhibitory effect of glucocorticoids on activated peripheral blood basophils through suppression of lipid raft formation.

We investigated the non-genomic effects of glucocorticoids (GCs) on inhibition of plasma membrane lipid raft formation in activated human basophils. Human basophils obtained from house dust mite (HDM)-sensitive volunteers were pretreated with hydrocortisone (CORT) or dexamethasone (Dex) for 30 min and then primed with phorbol 12-myristate 13-acetate (PMA, 10 ng/ml) or HDM (10 µg/ml). The expression of CD63, a basophil activation marker, was assessed by flow cytometry. Membrane-bound GC receptors (mGCRs) were analysed by flow cytometry and confocal laser microscopy. Lipid rafts were assessed using a GM1 ganglioside probe and visualization by confocal laser microscopy. Pretreatment of basophils with CORT (10(-4) M and 10(-5) M) and Dex (10(-7) M) significantly inhibited CD63 expression 20 min after addition of PMA or HDM. The inhibitory effects of GCs were not altered by the nuclear GC receptor (GCR) antagonist RU486 (10(-5) M) or the protein synthesis inhibitor cycloheximide (10(-4) M) (P < 0·05). CORT coupled to bovine serum albumin (BSA-CORT) mimicked the rapid inhibitory effects of CORT, suggesting the involvement of mGCRs. mGCRs were detectable on the plasma membrane of resting basophils and formed nanoclusters following treatment with PMA or HDM. Pretreatment of cells with BSA-CORT inhibited the expression of mGCRs and nanoclustering of ganglioside GM1 in lipid rafts. The study provides evidence that non-genomic mechanisms are involved in the rapid inhibitory effect of GCs on the formation of lipid raft nanoclusters, through binding to mGCRs on the plasma membrane of activated basophils.

Erosion bleeding as a late complication of chest wall reconstruction with a Dacron mesh silicone prosthesis.

A 71-year-old man who had undergone chest wall resection and reconstruction with a Dacron mesh silicone prosthesis for chondrosarcoma 23 years previously presented with a chest wall hematoma. Since the hematoma was found to increase in size over time, we performed an operation to achieve hemostasis. Operative findings showed that the prosthesis had separated into three sheets.

Cyclosporin A treatment and decreased fungal load/antigenemia in experimental murine paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb). The cyclosporin A (CsA) is an immunosuppressant drug that inhibits calcineurin and has been described as a potential antifungal drug. The present study investigated the effect of CsA on the immune response, fungal load/antigenemia in experimental murine PCM. It was used four groups of BALB/c mice: (a) infected with 1 x 105 Pb18 yeast cells (Pb), (b) infected and treated with CsA every other day 10 mg/kg of CsA (s.c.) during 30 days (Pb/CsA), (c) treated with CsA (CsA) and (d) no infected/treated (PBS). The immune response was evaluated by lymphocyte proliferation, DTH assays to exoAgs, ELISA for IgG anti-gp43 (specific immune responses) and cytokine serum levels (IFN-γ, TNF-α, IL-4 and IL-10). Fungal load was determined by lung colony-forming units (CFU) counts, lung and liver histopathology analysis and antigenemia determined by inhibition-ELISA. As expected, CsA was able to inhibit the specific cellular and humoral immune response (P < 0.05), with decrease in serum IFN-γ, TNF-α and IL-4 levels (P < 0.05). Cyclosporin A treatment also resulted in significantly decreased lung Pb CFU (P < 0.05) as well as a lower number of yeasts in the lung and liver (P < 0.05) by histopathology. In concordance, the decreased antigenemia was observed in Pb/CsA group (P < 0.05). In conclusion, even with immunosuppressive action, treatment with CsA results in decreased lung fungal load/antigenemia in experimental PCM in BALB/c mice. Further study is required to determine whether this represents less severe disease or protection by CsA.

[Thymoma with synchronous pulmonary metastasis; report of a case].

We report a resected case of thymoma with a solitary pulmonary metastasis. A 63-year-old woman had pointed out a solitary nodule in right lung field on chest X-ray. Computed tomography (CT) scan showed an anterior mediastinal tumor and a solitary lung nodule in the right lower lobe. Extended thymectomy and partial resection of right lung was performed. Pathological diagnosis showed an invasive thymoma (type B3) and a pulmonary metastasis. Post operative radiotherapy was administered and she is doing well 19 months following the resection. Thymoma with a solitary synclonous pulmonary metastasis is rare and is classified into Masaoka stage IVb. Generally, thymoma cases with distant metastasis are not indication for operation. But, if radical resection is possible, operation is recommended for good prognosis.

Disturbance of rapid eye movement sleep in senescence-accelerated mouse prone/8 mice is improved by retinoic acid receptor agonist Am80 (Tamibarotene).

Senescence-accelerated mouse prone/8 (SAMP8) mice are known to exhibit age-related deterioration in sleep-wake architecture compared with senescence-accelerated mouse resistant/1 (SAMR1) mice. We investigated whether treatment with Am80 (Tamibarotene), a retinoic acid receptor agonist, would improve sleep in 9-10-month-old SAMP8 mice. One week of Am80 administration improved the decrease in rapid eye movement (REM) sleep shown by SAMP8 mice. Real-time RT-PCR analysis demonstrated an impairment in the hippocampal retinoid cascade (retinoic acid receptor alpha and transthyretin) in SAMP8 in comparison to SAMR1 mice. Am80 treatment induced an increase in mRNA expression in the vesicular acetylcholine transporter in the brainstem and transthyretin in the hippocampus. Furthermore, decreased cortical acetylcholine content in SAMP8 was improved by Am80 administration. Decreased non-REM sleep and delta oscillation were also observed in SAMP8 mice; however, this was not improved by Am80 administration. These results partially support the hypothesis that the effects of aging on sleep-wake architecture are improved by the activation of retinoic acid receptors. The improvement may be induced by the activation of the cholinergic pathway.

Soluble components of Histoplasma capsulatum var. capsulatum have hemagglutinin activity and induce syngeneic hemophagocytosis in vitro.

Histoplasma capsulatum var. capsulatum is a thermally dimorphic fungus that causes histoplasmosis. Fungal hemagglutination activity and cases of reactive hemophagocytic syndrome (RHS) have been reported in the disseminated form of disease. In the present study, soluble components of H. capsulatum var. capsulatum have been investigated for hemagglutinin activity and the capacity to induce hemophagocytosis in the mouse system. To analyze hemagglutinating activity, mouse red blood cells (RBC) (1% v/v in PBS) were incubated (37 degrees C, 1 h) with cell-free antigen (CFAg) from H. capsulatum var. capsulatum (isolate IMT/HC128) (RBC-CFAg) or previously heated CFAg (56 degrees C, 30 min) (RBC-hCFAg) or as control with PBS (RBC-PBS). Hemophagocytosis was analyzed by incubating BALB/c mouse peritoneal phagocytic cells (5 x 10(6) cells) with syngeneic RBC, sensitized or not with CFAg. In addition, mouse polyclonal antibodies were raised against syngeneic RBC-CFAg (anti-RBC-CFAg) and used to analyze CFAg chromatographic fractions (Sephadex G75/120) by immunoenzymatic assay (ELISA). Hemagglutinin activity was observed with RBC-CFAg, but not with RBC-hCFAg or RBC. Also, hemophagocytosis was observed with RBC-CFAg, but not with RBC. The anti-RBC-CFAg antibodies reacted with CFAg fractions corresponding to a molecular mass (MM) higher than 150 kDa. In conclusion, the yeast form of H. capsulatum var. capsulatum releases thermolabile soluble components with hemagglutinin activity and it has been demonstrated for the first time that soluble components of the same fungus induce syngeneic hemophagocytosis in the in vitro mouse system. Also, indirect analysis with antibodies suggests that high-MM components (>150 kDa) are responsible for the interaction with RBC.

Exophiala xenobiotica infection in cultured striped jack, Pseudocaranx dentex (Bloch & Schneider), in Japan.

This report describes Exophiala infection in cultured striped jack, Pseudocaranx dentex, in Japan in 2005. One hundred out of 35,000 fish died per day and mortalities continued for 1 month. Diseased fish showed swelling of the abdomen and kidney distension. Numerous septate hyphae, pale brown in colour, were seen in kidney in squash preparations. Histology revealed abundant fungal hyphae and conidia in gill, heart and kidney. Fungal hyphae were accompanied by cell necrosis and influx of inflammatory, mainly mononuclear cells. The fungus isolated from the diseased fish had septate hyphae, pale brown in colour and 1.8-3.0 microm in diameter. Conidiogenous cells were conspicuous annellides, short or cylindrical or fusiform in shape. Conidia were one-celled, ellipsoidal with smooth walls, accumulated in balls at the apices of annellides that tended to slide down, 1.5-2.0 microm in width and 3.0-5.0 microm in length. The fungus was classified into the genus Exophiala based on its morphology and as Exophiala xenobiotica based on the sequences of the ITS 1-5.8S-ITS 2 regions of rDNA. This is the first record of this fungus in a marine fish.

Movement-related cortical evoked potentials using four-limb imagery.

We compared the electroencephalographic changes during actual and imaginary movements with four limbs and classified optimally the responses during four-limb imagery. Evoked potentials in imagery exhibited lower and delayed peaks compared to actual-movement responses, but activations in the primary and the supplementary motor area were similar. Source-modeling analysis revealed that the motor and the parietal cortex were activated similarly, but several dipole sources were active in the frontal cortex for imagery. We compared thirteen classification methods and a combination of template matching and time-frequency methods showed the highest average of 70% classification rate for all limbs.

Detection of Paracoccidioides brasiliensis gp43 gene in sputa by loop-mediated isothermal amplification method.

The fungus Paracoccidioides brasiliensis is the pathogen of paracoccidioidomycosis (PCM), a systemic mycosis prevalent in Latin America. The loop-mediated isothermal amplification method (LAMP) was used in this study to detect the presence of P. brasiliensis in sputa samples from patients with chronic PCM, suspected PCM, and a negative control. The target P. brasiliensis gp43 gene was amplified in less than 4 hr in 11 of 18 sputa samples tested. The LAMP method had the advantage of speed and simplicity compared with the classic diagnostic methods such as the histopathological test or biological material culture and did not require sophisticated technical apparatus. It would be an important aid in cases where immediate treatment would mean patient survival, especially in immune-suppressed patients.

Granulomatous pericarditis associated with systemic Mucormycosis in a finless porpoise (Neophocaena phocaenoides).

An adult male finless porpoise (Neophocaena phocaenoides) kept in an aquarium in Japan displayed loss of appetite and reduced body weight over several months. Necropsy examination revealed the presence of lesions in the pericardium, lung, and mediastinal and pancreatico-duodenal lymph nodes. Microscopically, these comprised regions of necrotizing granulomatous inflammation with multinucleated giant cells and surrounding fibrosis. Fungal hyphae were identified within macrophages and the extracellular tissue. Immunohistochemical labelling determined that these organisms were of the order Mucorales. A diagnosis of granulomatous pericarditis associated with systemic mucormycosis was made.

Generalized hyperkeratosis caused by Scopulariopsis brevicaulis in a Japanese Black calf.

A 6-month-old Japanese Black female calf became gradually emaciated over a 40-day period and was humanely killed. At necropsy, hyperkeratotic nodules were seen to have spread over almost the entire body surface. Scopulariopsis brevicaulis was isolated from the skin and identified morphologically and by gene sequence analysis of the D1/D2 domain of large subunit ribosomal RNA. Numerous periodic acid-Schiff-positive, lemon-shaped conidia were detected histologically in the keratinized layer and the hair follicles. The distribution of the fungal elements in the skin corresponded to that of the hyperkeratotic lesions. This is the first report of a disease caused by S. brevicaulis in animals. Previously reported human infections have not included generalized hyperkeratosis.