Preclinical Cushing's syndrome in adrenal incidentalomas

Adrenal tumors are usually diagnosed by clinical symptoms of hormone excess. The increasing use of ultrasound and computed tomography results in the detection of a substantial number of incidentally discovered adrenal tumors. Most of these tumors are nonfunctional adrenocortical adenomas, but a few cases of subclinical cortisol production in "incidentalomas" have been reported. We investigated prospectively the prevalence of autonomous cortisol production in 68 patients (44 females and 24 males, aged 25-90 yr) with adrenal incidentalomas at our institution. As a screening procedure all patients with incidentalomas underwent an overnight dexamethasone suppression test (1 mg). Patients who failed to suppress serum cortisol below 140 nmol/L (5 micrograms/dL) underwent more comprehensive studies (prolonged dexamethasone suppression test, determination of the diurnal rhythm of cortisol secretion in saliva, and CRH stimulation test). Eight patients (12% of all patients with incidentalomas; 5 females and 3 males, aged 25-71 yr) were finally identified as having cortisol- producing tumors, and the findings in these patients were compared with those of overt Cushing's syndrome in 8 patients (8 females, aged 26-50 yr) suffering from cortisol-producing adrenal adenomas. The tumor size of patients with cortisol-producing incidentalomas ranged from 2-5 cm. No specific signs and symptoms of hypercortisolism were present, but arterial hypertension (seven of eight subjects), diffuse obesity (four of eight subjects), and noninsulin-dependent diabetes mellitus (NIDDM; two of eight subjects) were frequently observed. Baseline cortisol levels were in the normal to upper normal range, whereas baseline ACTH levels were suppressed in five of the eight patients. In none of the patients was serum cortisol suppressible by low dose or high dose dexamethasone. The ACTH and cortisol responses to CRH were normal in two, blunted in one, and suppressed in four patients. Unilateral adrenalectomy was performed in seven patients and resulted in temporary adrenal insufficiency in four of them. After surgery, improvement of arterial hypertension, a permanent weight loss in obese subjects, and a better metabolic control of NIDDM were noted in the majority of patients. The following conclusions were reached. Incidentally diagnosed adrenal tumors with pathological cortisol secretion in otherwise clinically asymptomatic patients are more frequently observed than previously assumed. Adrenocortical insufficiency is a major risk in these patients after adrenalectomy. After surgery, hypertension, obesity, and NIDDM may improve. Patients with asymptomatic adrenal incidentalomas, therefore, should be screened for cortisol production by means of an overnight dexamethasone suppression test

Control of Biological Exposure to UV Radiation in the Arctic Ocean: Comparison of the Roles of Ozone and Riverine Dissolved Organic Matter

Reports of severe stratospheric ozone depletion over the Arctic have heightened concern about the potential impact of rising ultraviolet-B (UV-B) radiation on north polar aquatic ecosystems. Our optical measurements and modelling results indicate that the ozone-related UV-B influence on food web processes in the Arctic Ocean is likely to be small relative to the effects caused by variation in the concentrations of natural UV-absorbing compounds, known as chromophoric dissolved organic matter(CDOM), that enter the Arctic basin via its large river inflows. The aim of our present study was to develop and apply a simple bio-optical index that takes into account the combined effects of attenuation by atmospheric ozone and water column CDOM, and photobiological weighting for high-latitude environments such as the Arctic Ocean. To this end, we computed values for a biologically effective UV dose rate parameter ('weighted transparency' or T*) based on underwater UV measurements in highlatitude lakes and rivers that discharge into the Arctic Ocean; measured incident UV radiation at Barrow, Alaska; and published biological weighting curves for UV-induced DNA damage and UV photoinhibition of photosynthesis. The results underscore how strongly the Arctic Ocean is influenced by riverine inputs: shifts in CDOM loading (e.g., through climate change, land-use practices, or changes in ocean circulation) can cause variations in biological UV exposure of much greater magnitude than ozone related effects

Penilaian Risiko Adanya Total Koliform pada Air Produksi IPA X Menggunakan Metode Failure Mode And Effect Analysis

Risiko terbesar sistem penyediaan air minum adalah kegagalan menyediakan air minum yang aman bagi masyarakat. Berdasarkan laporan hasil pengujian sampel air produksi IPA X bulan Maret 2016 untuk pemeriksaan parameter wajib diketahui bahwa sampel melebihi baku mutu Permenkes RI No. 492 Tahun 2010 untuk parameter total koliform. Total koliform sebagai indikator pencemaran air oleh patogen menyebabkan air tidak aman dikonsumsi. Proses disinfeksi berperan penting dalam menyisihkan patogen. Kinerjanya dipengaruhi oleh suhu, pH, kekeruhan, dan zat organik. Salah satu cara pengendalian kualitas air produksi melalui pendekatan manajemen risiko menggunakan metode Failure Modes and Effect Analysis (FMEA). Risiko potensial harus terukur agar dapat ditentukan risiko penyebab permasalahan dan tindakan pengurangan risiko yang tepat. Penilaian risiko berdasarkan skala Risk Priority Number (RPN) dijadikan dasar penentuan prioritas tindakan perbaikan. Berdasarkan hasil analisis, risiko kegagalan terbesar yaitu penentuan dosis klor dan zat organik (level risiko tinggi); sisa klor (level risiko sedang); kekeruhan dan pH (level risiko sangat rendah). Usulan perbaikan untuk mengurangi risiko tersebut yaitu dilakukan penentuan dosis klor setiap hari, pengendalian pembentukan disinfectant by products (DBPs) akibat adanya zat organik dalam air dengan menurunkan konsentrasi zat oganik menggunakan granular activated carbon (GAC) atau teknologi aerasi, mengurangi pembentukan DBPs dengan menurunkan dosis disinfektan, menyisihkan DBPs setelah senyawa tersebut terbentuk menggunakan GAC, meningkatkan sisa klor menjadi 0,6 mg/l, melakukan pemantauan kekeruhan dan pH pada sistem pengoperasian filter

Diagnostik und Therapie asymptomatischer Nebennierentumoren

Bei 23 Frauen und neun Männern im mittleren Alter von 54 (25-73) Jahren wurde bei der Klärung anderer Beschwerden zufällig ein asymptomatischer Nebennierentumor entdeckt. In allen Fällen ließen sich die Tumoren computertomographisch darstellen. Achtmal waren sie beidseits lokalisiert, in je 12 Fällen rechts- oder linksseitig. Der durchschnittliche Tumordurchmesser betrug 3 (1-9) cm. Vier Tumoren (12,5 %) wiesen eine endokrine Aktivität auf (ein Phäochromozytom, drei cortisolproduzierende Tumoren). Acht Patienten wurden adrenalektomiert, dabei ergaben sich sechs Nebennierenadenome, ein benignes Phäochromozytom und ein Ganglioneurom. Eine Feinnadelbiopsie wurde bei zwei Patienten vorgenommen, der zytologische Befund war benigne. Computertomographische Verlaufskontrollen bei elf (34,4 %) der nicht-operierten Patienten 6-48 Monate (im Mittel 14 Monate) später zeigten bei keinem der Patienten eine Größenzunahme des Tumors. Daher erscheint es bei zufällig diagnostizierten Nebennierentumoren gerechtfertigt, zunächst einmal den Verlauf zu beobachten, da gutartige Prozesse offensichtlich weitaus häufiger sind als maligne. Bei einem Tumordurchmesser von mehr als 6 cm ist jedoch wegen des Malignitätsrisikos eine Adrenalektomie durchzuführen

Wnt1 promotes cementum and alveolar bone growth in a time-dependent manner

The WNT/β-catenin signaling pathway plays a central role in the biology of the periodontium, yet the function of specific extracellular WNT ligands remains poorly understood. By using a Wnt1-inducible transgenic mouse model targeting Col1a1-expressing alveolar osteoblasts, odontoblasts, and cementoblasts, we demonstrate that the WNT ligand WNT1 is a strong promoter of cementum and alveolar bone formation in vivo. We induced Wnt1 expression for 1, 3, or 9 wk in Wnt1Tg mice and analyzed them at the age of 6 wk and 12 wk. Micro–computed tomography (CT) analyses of the mandibles revealed a 1.8-fold increased bone volume after 1 and 3 wk of Wnt1 expression and a 3-fold increased bone volume after 9 wk of Wnt1 expression compared to controls. In addition, the alveolar ridges were higher in Wnt1Tg mice as compared to controls. Nondecalcified histology demonstrated increased acellular cementum thickness and cellular cementum volume after 3 and 9 wk of Wnt1 expression. However, 9 wk of Wnt1 expression was also associated with periodontal breakdown and ectopic mineralization of the pulp. The composition of this ectopic matrix was comparable to those of cellular cementum as demonstrated by quantitative backscattered electron imaging and immunohistochemistry for noncollagenous proteins. Our analyses of 52-wk-old mice after 9 wk of Wnt1 expression revealed that Wnt1 expression affects mandibular bone and growing incisors but not molar teeth, indicating that Wnt1 influences only growing tissues. To further investigate the effect of Wnt1 on cementoblasts, we stably transfected the cementoblast cell line (OCCM-30) with a vector expressing Wnt1-HA and performed proliferation as well as differentiation experiments. These experiments demonstrated that Wnt1 promotes proliferation but not differentiation of cementoblasts. Taken together, our findings identify, for the first time, Wnt1 as a critical regulator of alveolar bone and cementum formation, as well as provide important insights for harnessing the WNT signal pathway in regenerative dentistry