Myelolipoma: A New Adrenal Finding in Carney's Complex?

Pigmented nodular cortical hyperplasia, a rare cause of Cushing’s syndrome, is characterized by resistance to inhibition with dexamethasone and normal sized adrenal glands with multiple, small pigmented nodules. The disorder may be a component of a syndrome inherited as an autosomal dominant pattern that includes intra- and extracardiac myxomas, lentiginous lesions, blue nevi, other functional endocrine tumors, and peripheral nerve tumors (Carney’s complex). We report a patient in whom bilateral myelolipomas were found, in addition to the usual features of this complex. A 29-yr-old man was admitted to the hospital for Cushing’s syndrome of probably more than 15 yr duration. Physical examination showed diffuse facial hyperchromatic macules, 0.2–0.5 cm, predominantly around the lips and on the palmar surfaces of the fingers. Results with dexamethasone suppression nocturnal testing (1 and 8 mg) were compatible with an adrenal adenoma. The computed tomography (CT) of the sella turcica was normal. Adrenal CT showed a tumor in the left gland with a double component: one solid and another suggestive of fat, consistent with an angiomyelolipoma. Following 5 wk treatment with ketoconazole, 800 mg per day po, serum cortisol decreased to 5.9 μg/dL, morning and evening, respectively. Bilateral adrenalectomy was performed. Pathologic examination revealed pigmented nodular cortical hypersplasia and a dominant myelolipoma in the left adrenal. A microscopic myelolipoma was identified in the right adrenal. An echocardiogram showed a mass on the posterior wall of the left ventricle which was a myxoma. Study of the patient's family disclosed two sisters with facial lentigines. Echocardiograms were performed on all available first degree relatives: all were normal. Nocturnal inhibition with dexamethasone revealed that one of the patient’s sisters with lentigines also had hypercortisolism. Myelolipoma has been reported in association to Cushing syndrome in humans and experimentally after pituitary extracts in animals. The relationship between this finding and the Carney’s complex remain elusive.     

Epidermal growth factor receptor expression correlates with poor survival in gastric adenocarcinoma from Mexican patients: a multivariate analysis using a standardized immunohistochemical detection system.

The aim of the study was to determine epidermal growth factor receptor (EGFR) expression in gastric adenocarcinoma by standardized immunohistochemistry and to correlate EGFR expression with clinical features and patient survival. EGFR expression was investigated in paraffin sections of resection specimens of 89 gastric carcinomas from Mexican Mestizo patients using standardized immunohistochemistry with antigen retrieval (Dako EGFRpharmDx assay detection system). Membrane staining of EGFR was evaluated in the neoplastic cells and graded using a semiquantitative score (0-3+). Of the 89 carcinomas examined, staining of neoplastic cells was weak in 17 (19.1%, score 1+), moderate in 16 (18.0%, score 2+), and strong in nine cases (10.1%, score 3+). EGFR reactivity was heterogeneous, frequently showing completely negative up to 3+ positive areas within an individual tumor. EGFR reactivity score correlated with distant metastases (P=0.002) and clinical stage (P=0.033). EGFR score 0/1+ was significantly associated with an increase in patient survival when compared to score 2+/3+ (P=0.0006). In a multivariate analysis, EGFR positive cells in muscularis or subserosa (P=0.004), distant metastases (P=0.016) and residual disease (P=0.039) were significantly correlated with decreased survival. The prognosis was associated with the EGFR reactivity score (P=0.003), distant metastases (P=0.0001) and residual disease (P=0.012) in a univariate analysis. EGFR reactivity in neoplastic cells is an independent prognostic factor in gastric adenocarcinoma. The relevance of the heterogeneity in EGFR expression with regard to tumor progression, metastasis and anti-EGFR therapy needs to be studied.     

The influence of the causes and contexts of medical errors on emergency medicine residents' responses to their errors: an exploration.

PURPOSE: To determine emergency medicine residents' emotional and behavioral responses to their medical errors and examine associations between residents' responses to medical error and perceptions of their training. METHOD: In 2003, 55 residents at two U.S. residency programs were asked to complete questionnaires about their errors and responses to their errors in three domains: emotional response, learning behavior, and disclosure. The questions were a mixture of free text, yes/no responses, and some were rated using a five-point Likert scale. Based on a conceptual framework, the authors constructed scales to describe the various domains and associations between the residents' responses to medical error and perceptions of their training were examined using Somers' D. RESULTS: A total of 43 residents returned questionnaires (80%); 40 of these residents described errors. Thirty-three (83%) residents discussed the error with someone; 27 (71%) with the attending and 10 (28%) with the patient/family. Negative emotions were common: 27 (68%) felt remorse, 21 (53%) guilt, 23 (58%) inadequacy, and 22 (55%) frustration. Residents' negative emotional responses were associated with their personal characteristics [26% (95% CI, 5-47%) association with lack of experience] and residents' perceptions of their training environment: 15% association with job overload (95% CI, -8-38%) and 23% association with lack of institutional support (95% CI, 5-41%). While 32 (81%) residents increased attention to detail, only 2 (5%) increased their use of evidence-based medicine. CONCLUSIONS: Errors committed by emergency medicine residents often resulted in negative emotions, limited constructive system-based improvements, and inadequate disclosure. Negative perceptions of the training environment are associated with negative emotional responses.     

Aromatic residues affecting permeation and gating in dSlo BK channels

 Structural determinants of permeation in large unit conductance calcium-activated potassium channels (BK channels) were investigated. Y293 and F294 in the P-region of dSlo were substituted by tryptophans. Compared to wild-type channels, Y293W channels displayed reduced inward unitary currents while F294W channels exhibited normal inward current amplitudes but flickery kinetics. Both mutations produced changes in current/voltage relations under bi-ionic conditions. Sensitivity to block by external tetraethylammonium (TEA) was affected in both channels, and the voltage dependence of TEA block was increased in F294W channels. Both mutations also affected gating by shifting the half-maximal activation voltage of macroscopic conductance/voltage relations to more positive potentials, and eliminating a slow component of deactivation. The double mutant did not produce ionic currents. These data are consistent with a model in which Y293 contributes to a potassium-binding site close to the outer mouth of the dSlo pore, while F294 contributes to an energy barrier near this site. Received: 16 September 1997 / Received after revision: 20 November 1997 / Accepted: 21 November 1997     

Phagocytosis in the colonial ascidian Botryllus schlosseri

Phagocytosis by Botryllus schlosseri hemocytes in influenced by temperature, pH, concentration, and physicochemical properties of the test particles and requires Ca²⁺ or Mg²⁺ ions to occur. Phagocytes recognized glucosyl or mannosyl residues on the surface of yeast cells, and a respiratory burst is associated with phagocytosis, as indicated by increased superoxide production. Factors that enhance phagocytosis of yeast, sheep red blood cells, and latex beads and reduce the uptake of yeast and sheep erythrocytes are present in the plasma.     

Extraarticular synovial chondromatosis: review of epidemiology, imaging studies, microscopy and pathogenesis, with a report of an additional case in a child

A rare benign condition of uncertain etiology and pathogenesis, Synovial Chondromatosis (SC) is most often seen intraarticularly in adults but only a handful of cases have been reported extraarticularly in children. Symptoms and physical signs consist of pain, swelling, and osteoarthritic changes related to a mass effect. Here we discuss the case of a 9-year-old boy with documented SC of the knee and critically review the Epidemiology, Clinical Presentation, Gross Anatomy and Microscopic Histopathologic Features as well as the role of Imaging Studies in Diagnosis. In addition, this paper reviews Current Pathogenetic Concepts including the infrequent but distinct possibility of malignant transformation.     

Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease

BACKGROUND: Reactive nitrogen species, formed via the reaction of nitric oxide (NO) with superoxide anion and via (myelo)peroxidase-dependent oxidation of NO(2)(-), have potent proinflammatory and oxidizing actions. Reactive nitrogen species formation and nitrosative stress are potentially involved in chronic obstructive pulmonary disease (COPD) pathogenesis. OBJECTIVES: To investigate the expression of markers of nitrosative stress, including nitrotyrosine (NT), inducible NO synthase (iNOS), endothelial NO synthase (eNOS), myeloperoxidase (MPO), and xanthine oxidase (XO) in bronchial biopsies and bronchoalveolar lavage from patients with mild to severe stable COPD compared with control groups (smokers with normal lung function and nonsmokers). METHODS: The expression of NT, iNOS, eNOS, MPO and XO in the bronchial mucosa and bronchoalveolar lavage of patients was measured by using immunohistochemistry, Western blotting, and ELISA and correlated with the inflammatory cell profile. RESULTS: Patients with severe COPD in stable phase had higher numbers of NT(+) and MPO(+) cells in their bronchial submucosa compared with mild/moderate COPD, smokers with normal lung function, and nonsmokers (P < .01). iNOS(+) and eNOS(+) but not XO(+) cells were significantly increased in smokers with COPD or normal lung function compared with nonsmokers (P < .05 and P < .01, respectively). In patients with COPD, the number of MPO(+) cells was significantly correlated with the number of neutrophils (r = +0.61; P < .0025) in the bronchial submucosa. Furthermore, the number of NT(+) and MPO(+) cells was negatively correlated with postbronchodilator FEV(1). CONCLUSION: These data suggest that nitrosative stress, mainly mediated by MPO and neutrophilic inflammation, may contribute to the pathogenesis of severe COPD.     

Laboratory diagnosis of thrombophilic states: where do we stand?

Until recently the laboratory diagnosis of thrombophilia consisted on investigation of the plasmatic anticoagulant pathways and the search for dysfibrinogenemia and antiphospholipid antibodies/lupus anticoagulants. More recently, the laboratory investigation has been expanded by including activated protein C (APC) resistance, due or not to the presence of the factor V Leiden mutation; hyperprothrombinemia, due to the presence of the prothrombin mutation G20210A and hyperhomocysteinemia, due to impairment of the relevant metabolic pathway because of enzymatic and/or vitamin deficiency. Testing for thrombophilia may be useful for many reasons. First, the results of testing may provide valuable information to assess the risk of recurrence in the proband. Second, testing family members is useful for prophylactic and diagnostic purposes. Third, the identification of patients bearing combined defect helps to identify those at increased risk for thrombosis. Testing is recommended for patients with a past history of thrombosis and should be extended to their first-degree family members. Since most of the tests are not reliable during anticoagulation, it is preferable to postpone laboratory testing until after discontinuation of the treatment. Whenever possible testing should be performed by means of functional assays. DNA analysis is required for the prothrombin mutation G20210A. Laboratory diagnosis for antiphospholipid antibodies/lupus anticoagulant should be performed by a combination of tests including phospholipid-dependent clotting assays and solid phase anticardiolipin antibodies. Hyperhomocysteinemia may be assessed by high-pressure liquid chromatography methods, or by fluorescence polarization immunoassays.     

Pathology of a new Toxic Syndrome caused by ingestion of adulterated oil in Spain

Summary The Toxic Syndrome (TS) caused by ingestion of adulterated rapeseed oil in Spain is a new disease of multisystemic character whose aetiology and pathogenesis remains unknown. The most prominent pathological feature is a peculiar non-necrotizing vasculitis, that affects mainly the intima and involves vessels of every type and size in practically every organ. The TS begins with an acute clinical picture with pleuropneumopathy, fever, headaches, exanthems and eosinophilia. In these early clinical phases the main pathological findings were observed in the lungs and consisted of intense pulmonary interstitial oedema with scanty inflammatory mononuclear infiltrates. Ultrastructural study revealed hydropic degeneration of pneumocytes types I and II with desquamation of type I. The patients in this phase died of respiratory failure, later deaths were due to thromboembolic complications. Later still the patients developped a neuromuscular syndrome, sclerodermiform skin lesions and severe weight loss and died predominantly of infectious complications and respiratory failure. The anatomopathological picture in the peripheral nerves was that of inflammatory neuropathy with a lymphocytic perineuritis that led to perineural fibrosis with secondary axonal degeneration. The muscle presented an interstitial inflammatory myopathy at first followed by a neurogenic muscular atrophy. The skin lesions in the late phases consisted in dermal or dermal and subdermal fibrosclerosis, with vasculitis of the small arteries in the lower dermis. The salivary glands and pancreas showed vasculitis and interstitial inflammation which progressed to interstitial fibrosis and parenchymal atrophy.