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.

The gene encoding a newly discovered protein, chorein, is mutated in chorea-acanthocytosis.

Chorea-acanthocytosis is a neurodegenerative disorder with peripheral red cell acanthocytosis. Linkage of chorea-acanthocytosis to chromosome 9q21 has been found. We refined the locus region and identified a previously unknown, full-length cDNA encoding a presumably structural protein, which we called chorein. We found a deletion in the coding region of the cDNA leading to a frame shift resulting in the production of a truncated protein in both alleles of patients and in single alleles of obligate carriers.

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.

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.

[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.

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.

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.

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.

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.

A second-generation profiling system for quantitative methylation analysis of multiple gene promoters: application to lung cancer.

Cancer-specific gene promoter methylation has been described in many types of cancers, and various semi-quantified results have shown their usefulness. Here, we show a more sensitive and specific second-generation system for profiling the DNA methylation status. This method is based on bisulfite reaction of DNA and real-time PCR using two TaqMan MGB probes labeled with different fluorescence, followed by clustering analysis. Primers were designed with CpG-less sequences, and TaqMan MGB probes were designed to contain three or four CpG sites and to be shorter than conventional TaqMan probes. We have added new criteria for primer and probe design for further specificity. We confirmed the reliability of this system and applied it to analysis of lung cancers. Using 10 promoters, 90 primary lung cancers were clustered into six groups consisting of cases having similar smoking status and pathological findings. EGFR mutation and p16 promoter DNA methylation were exclusive, as previously reported; however, DNA methylation in other genes was unrelated to EGFR mutation. This system was also useful to distinguish double primary lung cancers from a single cancer with intrapulmonary metastasis. As above, our system has widespread availability in clinical use and biological research.

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.

Significance of human beta-defensins in the epithelial lining fluid of patients with chronic lower respiratory tract infections.

Human beta-defensins (hBDs) are the most abundant antimicrobial peptides in epithelial cells, and function in the host immune system. Respiratory epithelial cells express hBDs to inhibit bacterial proliferation during respiratory tract infections. The aim of this study was to investigate the release of hBDs into the respiratory tract and their benefit as a host defence system in chronic Pseudomonas aeruginosa infections. The levels of four hBD peptides (hBD-1-hBD-4) were measured in the bronchial epithelial lining fluid (ELF) of nine patients with chronic lower respiratory tract infection caused by P. aeruginosa. Eight patients with idiopathic pulmonary fibrosis and eight volunteers free of pulmonary disease were recruited as controls. ELF was obtained by bronchoscopic microsampling and hBD levels were measured by radioimmunoassays. The antimicrobial effects of hBDs were studied individually and in combination using an in-vitro colony count assay for P. aeruginosa. Concentrations of hBD-1 and hBD-3 tended to be higher in patients with chronic lower respiratory tract infection than in the controls. hBD-2 and hBD-4 were detected in ELF from five and four of nine patients, respectively, but the hBD levels in controls were all below the limits of detection. All patients with infection caused by mucoid P. aeruginosa had detectable hBD-2 and hBD-4 levels in ELF. In-vitro colony count assays showed a potential synergism between hBD-2 and hBD-4 in inhibiting bacterial proliferation. The findings indicate that hBDs, especially hBD-2 and hBD-4, are pathophysiologically important in infections caused by mucoid strains of P. aeruginosa.

[Pulmonary thromboembolism after lung resection in patients with schizophrenia; report of 2 cases].

We report 2 cases of pulmonary thromboembolism after lung resection in patients with schizophrenia. The first case is a 67-year-old woman. She underwent right lower lobectomy for primary lung cancer and suddenly felt dyspnea 2 days after the operation. She was diagnosed pulmonary thromboembolism by computed tomography (CT) and lung perfusion scintigram, and recoverd soon. The second case is a 42-year-old man. He underwent partial resection of the right lung for metastatic germ cell tumor. Six days after the operation, he fell into acute respiratory failure and died in spite of resuscitation. The autopsy showed that the cause of death was pulmonary thromboembolism. Because patients with schizophrenia have high-risk of pulmonary thromboembolism, extreme care must be exercised to avoid it.

[Posterior mediastinal hemangioma successfully resected with cardiopulmonary bypass; report of a case].

Mediastinal hemangioma is a rare tumor. We report a case of a 62-year-old woman with a posterior mediastinal hemangioma. She had a history of right breast cancer and a follow-up chest radiography revealed a mass located in the left posterior mediastinum. The size was about 80 mm in diameter. The tumor surrounded the descending thoracic aorta and involved intercostal arteries. Complete excision could be achieved by decompressing the descending aorta with the aid of partial cardiopulmonary bypass and the aortic cross-clamp. Histologically, the tumor was diagnosed as a benign hemangioma. It was reported that hemangioma would reccur after subtotal excision. To employ cardiopulmonary bypass was a very effective approach for the purpose of complete excision in our case.