Size-adapted microcalcification segmentation in mammography utilizing scale-space signatures

The purpose of this study is size-adapted segmentation of individual microcalcifications in mammography, based on microcalcification scale-space signature estimation, enabling robust scale selection for initialization of multiscale active contours. Segmentation accuracy was evaluated by the area overlap measure, by comparing the proposed method and two recently proposed ones to expert manual delineations. The method achieved area overlap of 0.61 ± 0.15 outperforming statistically (p < 0.001) the other two methods (0.53 ± 0.18, 0.42 ± 0.16). Only the proposed method performed equally for both small (<460 μm) and large (≥460 μm) microcalcifications. Results indicate an accurate method, which could be utilized in computer-aided diagnosis schemes of microcalcification clusters.     

The expression of matrix metalloproteinase-11 protein in various types of glomerulonephritis.

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated to play important roles in a number of pathological processes such as inflammation. In human glomeruli, the mesangial matrix turnover is controlled by a dynamic equilibrium between synthesis and degradation to which metalloproteinases are known to contribute. Metalloproteinase-11 (MMP-11) was originally discovered as a gene whose expression was associated with tissue remodelling. The aim of this study was to investigate whether MMP-11 protein is expressed in various types of glomerulonephritis and to elucidate the role of this expression. METHODS: Using standard immunohistochemistry, we analysed MMP-11 expression in renal biopsies from 95 patients with primary glomerulonephritis (n = 44) and secondary, either lupus-associated glomerulonephritis (n = 22) or pauci-immune, ANCA-associated glomerulonephritis due to small vessel vasculitis (n = 23) or Wegener's granulomatosis (n = 6). The examined cases were divided into two groups (proliferative and non-proliferative). Anti-Ki67 and -CD68 immunostaining was also performed in order to estimate cell proliferation and number of macrophages, respectively. RESULTS: MMP-11 immunopositivity was detected in the glomeruli of the majority of pathological samples. The highest incidence of MMP-11 immunopositivity (26.3%) was noticed in glomerulonephritides associated with microscopic polyangiitis and Wegener's granulomatosis. Generally, MMP-11 was often expressed in segmental areas of sclerosis, microadhesions, cellular and fibrocellular crescents. Fibrotic crescents and fibrotic glomeruli were constantly MMP-11-immunonegative. In MMP-11 immunoreactive glomeruli, increased numbers of macrophages were often detected in the mesangium (P = 0.001), while no such observation could be made with regard to proliferating cells (P = 0.170). CONCLUSIONS: MMP-11, like an inflammatory mediator, may exert a chemotactic influence on macrophages which aggregate in the mesangium; MMP-11 is not likely to have a parallel mitogenic or antifibrotic effect in diseased glomeruli.     

Genetics: Familial blepharophimosis with ovarian dysfunction

Three cases including two sisters and one brother with blepharophimosisare described. Their father also had blepharophimosis. Moreover,the elder sister initially presented with resistant ovary syndromeand thereafter true premature menopause, while the younger onepresented with resistant ovary syndrome. The explanation forthe association of blepharophimosis with primary ovarian dysfunctionis unknown, but the possibility of a microdeletion of geneticmaterial containing two geographically associated, but independentgenes could not be confirmed or excluded. All families affectedby blepharophimosis should be counselled about the high incidenceof ovarian dysfunction and female infertility, at least in oneform of the syndrome.     

Unintentional injury mortality in the European Union: how many more lives could be saved?

AIMS: The wide variation of unintentional (accidental) injury mortality rates in the European Union (EU) member states suggests that there is high potential for prevention. This paper attempts to quantify the potential for saving lives in this part of the world if all 25 member states were to learn from the experience of countries with advanced injury prevention records. METHODS: Unintentional injury mortality data (latest three available years), including denominator population estimates, were obtained from the World Health Organization (WHO) mortality database for all 22 EU countries with a population of more than one million. Annual average age-adjusted injury mortality rates were used to derive the potential for saving of lives under two scenarios: (a) if all EU member states matched the country with the lowest unintentional rate for all causes of injury combined; (b) if the benchmark was alternatively the country with the lowest unintentional injury cause-specific rate. Separate calculations were performed for children (0-14), adults (15-64), and the elderly (65 and over). RESULTS: Under the first scenario, over 73,000 lives could have been saved in the EU 25 in a single year, notably nearly half (47.4%) fewer unintentional injury deaths could be observed in children, over half in adult (54%), and two-fifths (38%) in the elderly. Under the second, more optimistic, scenario 59% of childhood and adult and 75% of unintentional injury deaths among the elderly would have been avoided. CONCLUSIONS: A substantial proportion of lives lost due to unintentional injury might be saved if all countries were to achieve the lowest unintentional injury mortality rates in the EU. The above calculations are based on a simple theoretical model but there is increasing evidence on the array of existing effective preventive interventions and improved trauma care calls for public health action in each member state that could in practice halt, to the extent possible, the unintentional injury epidemic.     

Airway obstruction and acute respiratory failure due to Aspergillus tracheobronchitis

OBJECTIVE: To report a patient with lymphoma who developed Aspergillus tracheobronchitis resulting in airway obstruction and acute respiratory failure. DESIGN: Case report. SETTING: Intensive care unit of a tertiary care hospital. PATIENT: A 22-yr-old female with lymphoma who developed a respiratory infection 3 months after completing immunosuppressive therapy. She was treated empirically with broad spectrum antibiotics and subsequently received a supplementary chemotherapeutic course. Soon afterward she developed severe respiratory failure. Chest radiograph showed atelectasis of the right upper and lower lobes. INTERVENTIONS: Emergent mechanical ventilation; fiberoptic bronchoscopy. MEASUREMENTS AND MAIN RESULTS: Fiberoptic bronchoscopy revealed extensive obstruction of both main and subsegmental bronchi with a solid mass strongly adhered to the bronchial wall; both histologic examination and culture of that mass revealed Aspergillus. The patient died of refractory hypoxemia a few days later. CONCLUSIONS: Aspergillus tracheobronchitis should be considered in immunocompromised patients with suspected lung infection even when the main radiographic finding is atelectasis. Bronchoscopy and histologic examination of identified intraluminal material should be performed as soon as possible.     

Sepsis severity is the major determinant of circulating thrombopoietin levels in septic patients

OBJECTIVE: To measure serum thrombopoietin levels and to investigate their relationship with platelet counts and other potential determinants in septic patients. DESIGN: Prospective study comparing septic patients and healthy volunteers. SETTING: General intensive care units in two tertiary university hospitals. PATIENTS: A total of 152 consecutive septic patients (69 with sepsis, 24 with severe sepsis, and 59 with septic shock). Twenty-two healthy volunteers served as control subjects. Sepsis severity was determined by grading septic patients in those having sepsis, severe sepsis, and septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After blood sampling, platelet counts, and serum thrombopoietin, interleukin-6 and C-reactive protein levels were measured. Platelets did not decrease in patients with sepsis, but they significantly decreased in patients with severe sepsis and septic shock (p <.01 vs. controls and sepsis). In contrast, thrombopoietin levels (median [range]) increased in patients with sepsis (159 [34-1272] pg/mL) compared with controls (57 [33-333] pg/mL, p <.001), exhibiting further significant increase in patients with severe sepsis and septic shock (461 [73-1550] and 522 [45-2313] pg/mL, respectively, p <.001 vs. sepsis). In multiple regression analysis, thrombopoietin levels were independently related only to sepsis severity (higher in patients with increased sepsis severity, p <.001) and platelet counts (higher in patients with lower platelet counts, p =.004). Sepsis severity accounted for most of the variance explained by the model. Thrombopoietin was significantly related to interleukin-6 (r =.26) and C-reactive protein (r =.37, p <.001 for both). In serial measurements, interleukin-6 peak values constantly preceded those of thrombopoietin, whereas peaks in thrombopoietin levels coincided with clinical episodes of septic shock. CONCLUSIONS: Sepsis severity is the major determinant of elevated thrombopoietin levels in septic patients, whereas platelet count is a secondary determinant. Thrombopoietin represents a potential marker of sepsis severity.     

Determinant of HIV-1 mutational escape from cytotoxic T lymphocytes

CD8+ class I-restricted cytotoxic T lymphocytes (CTLs) usually incompletely suppress HIV-1 in vivo, and while analogous partial suppression induces antiretroviral drug-resistance mutations, epitope escape mutations are inconsistently observed. However, escape mutation depends on the net balance of selective pressure and mutational fitness costs, which are poorly understood and difficult to study in vivo. Here we used a controlled in vitro system to evaluate the ability of HIV-1 to escape from CTL clones, finding that virus replicating under selective pressure rapidly can develop phenotypic resistance associated with genotypic changes. Escape varied between clones recognizing the same Gag epitope or different Gag and RT epitopes, indicating the influence of the T cell receptor on pressure and fitness costs. Gag and RT escape mutations were monoclonal intra-epitope substitutions, indicating limitation by fitness constraints in structural proteins. In contrast, escape from Nef-specific CTL was more rapid and consistent, marked by a polyclonal mixture of epitope point mutations and upstream frameshifts. We conclude that incomplete viral suppression by CTL can result in rapid emergence of immune escape, but the likelihood is strongly determined by factors influencing the fitness costs of the particular epitope targeted and the ability of responding CTL to recognize specific epitope variants.     

Photoregulation of Biological Activity by Photochromic Reagents, IV. A Model for Diurnal Variation of Enzymic Activity

Levels of acetylcholinesterase activity can be made to vary in response to the presence or absence of sunlight in a system that can be considered as a model for photoperiodic processes found in nature. The enzyme is rendered photosensitive by the presence of a photochromic inhibitor, N-p-phenylazophenylcarbamyl choline, which changes from a trans to a cis isomer under the influence of the light of the sun and reverts back to the trans isomer in the dark. The two isomers differ in their ability acetylcholinesterase, thus rendering the enzyme system responsive to sunlight. The relationship of this system to photoresponsive processes in nature is discussed, and a possible role in photoregulation is suggested for naturally occurring carotenoids.     

High-resolution CT findings in mild pulmonary fat embolism

OBJECTIVE: The aim of this article is to describe the high-resolution CT (HRCT) findings in mild cases of fat embolism syndrome (FES). MATERIAL AND METHODS: Nine patients with FES were examined with HRCT of the lungs (collimation, 1 mm/edge-enhancement algorithm). The median age of the patients was 26 years (range, 17 to 35 years). Five cases were included prospectively, and four cases were reviewed retrospectively. Of the major clinical criteria for FES, respiratory signs were present in six patients, CNS signs were present in two patients, and petechiae was present in six patients. HRCT patterns were recorded and analyzed. The type of injury and FES-associated clinical findings were also recorded. RESULTS: HRCT findings included ground-glass opacities in seven patients, associated with thickened interlobular septa in five patients and a patchy distribution resulting in a geographic appearance in four patients. A nodular pattern was observed in two patients. Resolution of the abnormalities occurred within 16.4 days (range, 7 to 25 days). CONCLUSION: The HRCT findings of mild fat embolism consist of bilateral ground-glass opacities and thickening of the interlobular septa. Centrilobular nodular opacities are present in some patients.     

Incidental MRI finding of a pons tuberculoma in a patient with so-far-undiagnosed multisystemic tuberculosis infection

Tuberculomas are routinely included in the differential diagnosis of newly detected intracranial lesions in patients with known systemic tuberculosis, but are rarely considered in patients without systemic disease. We report a 49-year-old patient without any neurological symptoms whose magnetic resonance imaging examination showed a lesion in the pons that was suspected of being an opportunistic, DD granulomatous lesion, which prompted further laboratory examinations revealing systemic tubercle bacillus (TB) infection. Tuberculosis should be included in the differential diagnosis of an intracranial solitary lesion even in atypical locations and in asymptomatic patients without prior diagnosis of a TB.