Hereditary Trichodysplasia: Marie Unna'S Hypotrichosis

This is a study of eight members of one family with Marie Unna hypotrichosis occurring in five generations. All affected individuals were born with widespread facial “milia”, sparse scalp hair and decreased body hair. Laboratory studies including urinary amino acids and plasma testosterone were normal. On histologic examination the hair follicles of the scalp showed proliferation of the internal root sheath and horn pearl formation in the lower third of the follicle. Abnormal hairs were flat and ribbon-like and twisted at irregular intervals. Extensive peeling of the cuticle was demonstrated by scanning electron microscopy. Electron microscopy of the hair shafts revealed intracellular fractures of the cuticular cells, increased interfibrillar matrix and fractures of the cortical cell fibrils and fractures of the medullary cells. X-ray diffraction studies were normal. On amino acid analysis of affected hairs a small decrease in cysteine-cystine and an increase in methionine content was noted. Since the hair shafts are clearly abnormal in this disorder, the name hereditary trichodysplasia is suggested. The condition is inherited as an autosomal dominant trait

Non-prominal adverbs with spatial meaning in modern Russian and Serbian languages

Предмет ове дисертације представља комплексна анализа просторних значења незаменичких прилога у савременом руском и српском језику. У раду су обрађене оне категорије прилога које сматрамо најрелевантнијим, ослањајући се на претходна истраживања. Представљене су сличности и разлике у употреби незаменичких прилога у савременом руском и српском језику, док је, поред тога, пружен опис подсистема незаменичких прилога са просторним значењем, као и принцип и начин функционисања наведеног подсистема. Како се подсистеми са просторним значењем у руском и српском језику често преплићу, размотрени су и парадигматски и синтагматски односи између тих подсистема, тамо где је то могуће. Основне хипотезе односе се на тврдње да је подсистем незаменичких прилога са просторним значењем организован у виду хијерархизованих семантичких опозиција; затим, да се према оријентационом и кинетичком аспекту незаменички прилози са просторним значењем у руском и српском језику у великој мери подударају; те да се специфичност српског језика манифестује ређом употребом незаменичких прилога са просторним значењем у односу на руски језик, а која се компензује употребом других врста речи; на крају, да се локализатор не именује незаменичким прилогом са просторним значењем, већ се може установити из ужег или ширег контекста. Дакле, у дисертацији смо тежили да опишемо просторна значења сваког разматраног прилога у раду према оријентационом и кинетичком аспекту, дамо схематски приказ разматраних прилога, упоредимо прилоге са сличним просторним значењем у ова два језика, као и да упоредимо прилоге са сличним просторним значењем у једном језику...The subject of this dissertation is a complex analysis of spatial meanings of non-pronominal adverbs in modern Russian and Serbian languages. The paper processed those categories of adverbs that we consider to be the most relevant, relying on previous research. Similarities and differences were presented in use of non-pronominal adverbs in modern Russian and Serbian languages, while, apart from this, the description of subsystem of non-pronominal adverbs with spatial meaning was given, together with the principle and method of functioning of the stated subsystem. Given that subsystems with spatial meaning in the Russian and Serbian languages often interlace, paradigmatic and syntagmatic relations between these subsystems were examined where possible. Basic hypotheses relate to assertions that the subsystem of non-pronominal adverbs with spatial meaning is organized in the form of hierarchized semantic oppositions; then, that according to orientation aspect and static/dynamic aspect non-pronominal adverbs with spatial meaning in the Russian and Serbian languages largely correspond; that specificity of the Serbian language is manifested in rarer use of non-pronominal adverbs with spatial meaning compared to the Russian language, which is compensated by the use other word classes; that, finally, the localizer is not named using non-pronominal adverb with spatial meaning, but it can be established on the basis of narrower or broader context. Hence, we aimed in this dissertation to describe spatial meanings of each adverb examined in the paper according to orientation aspect and static/dynamic aspect, to give a schematic view of examined adverbs, to cross-reference adverbs with similar spatial meaning in these two languages, as well as to compare adverbs with similar spatial meaning within one language..

Anatomy of the feeding arteries of the cerebral arteriovenous malformations

Background: Identification and anatomic features of the feeding arteries of the arteriovenous malformations (AVMs) is very important due to neurologic, radiologic, and surgical reasons.   Materials and methods: Seventy-seven patients with AVMs were examined by using a digital subtraction angiographic (DSA) and computerised tomographic (CT) examination, including three-dimensional reconstruction of the brain vessels. In addition, the arteries of 4 human brain stems and 8 cerebral hemispheres were microdissected.   Results: The anatomic examination showed a sporadic hypoplasia, hyperplasia, early bifurcation and duplication of certain cerebral arteries. The perforating arteries varied from 1 to 8 in number. The features of the leptomeningeal and choroidal vessels were presented. The radiologic examination revealed singular (22.08%), double (32.48%) or multiple primary feeding arteries (45.45%), which were dilated and elongated in 58.44% of the patients. The feeders most often originated from the middle cerebral artery (MCA; (23.38%), less frequently from the anterior cerebral artery (ACA; 12.99%), and the posterior cerebral artery (PCA; 10.39%). Multiple feeders commonly originated from the ACA and MCA (11.69%), the MCA and PCA (10.39%), the ACA and PCA (7.79%), and the ACA, MCA and PCA (5.19%). The infratentorial feeders were found in 9.1% of the AVMs. Contribution from the middle meningeal and occipital arteries was seen in 3.9% angiograms. Two cerebral arteries had a saccular aneurysm. The AVM haemorrhage appeared in 63.6% of patients.   Conclusions: The knowledge of the origin and anatomic features of the AVMs feeders is important in the explanation of neurologic signs, and in a decision regarding the endovascular embolisation, neurosurgical and radiosurgical treatments

Clinical assessment of skin phototypes: watch your words!

Fitzpatrick skin phototype classification is widely used to assess risk factors for skin cancers. This skin type evaluation is easy to use in clinical practice but is not always applied as initially described, nor practiced in a standardised way. This can have implications on the results of relevant dermato-epidemiological studies. To demonstrate, in a large multinational setting, that the phrasing of questions on sun sensitivity can have a strong impact on the perception and reporting of skin phototype, as well as the importance of a standardised procedure for phototype assessment. Using data collected from 48,258 screenees of the Euromelanoma campaign in six European countries from 2009 to 2011, we analysed the impact of change in the question phrasing on phototype classification in each country. Changing the wording of a question to assess the phototype of a person also significantly influenced the classification of phototypes in different countries (p<0.001 for each country). The difference essentially corresponded to a shift towards a less sun-sensitive skin type when a shorter question that did not include skin colour description was used. The only exception was Portugal where phototype was not patient-assessed and classification shifted towards a more sun-sensitive phototype. Results were statistically significant and highly consistent, irrespective of gender. The phrasing of questions on skin type is important and substantially influences reporting. A standardized procedure to classify phototypes should be used in order to obtain comparable data between studies

Physicochemical Factors Governing the Partition of Pramipexole and Its Five Impurities in Microemulsion Liquid Chromatographic Systems

Microemulsions when used as mobile phases represent a very powerful chromatographic tool due to their polyphase structure. The aim of this study was to investigate the influence of the mobile phase composition and resulting microemulsion droplet's properties, as well as the stationary phase lipophilicity on the chromatographic behavior of pramipexole and its five impurities. Investigation was carried out according to the experimental plan defined by a full factorial design 2(4) with four central point replications. While the most affected by column characteristics was the last eluting, most lipophilic substance, the composition and characteristics of microemulsion droplets were equally important, so the partition system microemulsion droplets/stationary phase proved to be the most significant. Stationary phase lipophilicity did not affect the most hydrophilic component and only the partition system microemulsion droplets/bulk of the eluent impacted its behavior. For the separation of the critical pair, almost equal effects of the microemulsion droplets/stationary phase and bulk of the eluent/stationary phase partition systems were noted

Enhanced diagnostic immunofluorescence using biopsies transported in saline

BACKGROUND: The demonstration of tissue-bound immunoreactants by direct immunofluorescence microscopy (DIF) is a valuable parameter in the diagnosis of various autoimmune and immunecomplex-mediated skin diseases. For preservation of tissue-bound immunoreactants, biopsies are usually fresh-frozen in liquid nitrogen or transported in Michel's fixative. But even optimally preserved tissue specimens are no guarantee for the correct diagnosis by DIF, especially when weak to moderate IgG fluorescence of the epidermal basement membrane zone is involved. In such cases false negative results are easily obtained due to the relatively high dermal "background" fluorescence produced by polyclonal anti-human IgG fluorescein conjugates. METHODS: In the present study we have compared the use of normal saline (0.9% NaCl) with liquid nitrogen and Michel's fixative as transport medium for skin biopsies. From 25 patients with an autoimmune skin disease (pemphigus, pemphigoid, lupus erythematosus and vasculitis) four matched skin biopsies were obtained and transported in either saline for 24 and 48 hours, liquid nitrogen, or Michel's fixative for 48 hours. RESULTS: Direct IF microscopy showed significant reduction of background fluorescence (p < 0.01) and relatively enhanced desired specific (IgG, IgA) staining in biopsies transported in saline. A conclusive or tentative IF diagnosis was reached in 92% after 24 h saline, 83% after 48 h saline, 68% after freezing in liquid nitrogen, and 62% after 48 h Michel's medium (n = 25). CONCLUSIONS: We conclude that transporting biopsies without freezing in normal saline for 24 hours is an adequate and attractive method for routine IF diagnosis in autoimmune and immune complex-mediated dermatoses. The superior results with saline incubation are explained by washing away of IgG background in dermis and epidermis

Brn2 Is a Transcription Factor Regulating Keratinocyte Differentiation with a Possible Role in the Pathogenesis of Lichen Planus

Terminal differentiation of skin keratinocytes is a vertically directed multi-step process that is tightly controlled by the sequential expression of a variety of genes. In this study, we investigated the role of the POU domain-containing transcription factor Brn2 in keratinocyte differentiation. Immunohistochemical analysis showed that Brn2 is expressed primarily in the upper granular layer. Consistent with its epidermal localization, Brn2 expression was highly induced at 14 days after calcium treatment of cultured normal human epidermal keratinocytes. When Brn2 was overexpressed by adenoviral transduction, Brn2 led to increased expression of the differentiation-related genes involucrin, filaggrin, and loricrin in addition to inhibition of their proliferation. Chromatin immunoprecipitation demonstrated that Brn2 bound to the promoter regions of these differentiation-related genes. We injected the purified Brn2 adenovirus into rat skin, which led to a thickened epidermis with increased amounts of differentiation related markers. The histopathologic features of adenovirus-Brn2 injected skin tissues looked similar to the features of lichen planus, a human skin disease showing chronic inflammation and well-differentiated epidermal changes. Moreover, Brn2 is shown to be expressed in almost all cell nuclei of the thickened epidermis of lichen planus, and Brn2 also attracts T lymphocytes. Our results demonstrate that Brn2 is probably a transcriptional factor playing an important role in keratinocyte differentiation and probably also in the pathogenesis of lichen planus lesions

Microbiological testing of adults hospitalised with community-acquired pneumonia: An international study

This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines. This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015. In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p&lt;0.01), while ERS concordance was higher in North America than in Europe (33.5% versus 19.5%; p&lt;0.01). Testing practices of adults hospitalised with CAP varied significantly by geography and disease severity. There was a wide discordance between real-life testing practices and IDSA/ATS/ERS guideline recommendations

Atypical pathogens in hospitalized patients with community-acquired pneumonia: A worldwide perspective

Background: Empirical antibiotic coverage for atypical pathogens in community-acquired pneumonia (CAP) has long been debated, mainly because of a lack of epidemiological data. We aimed to assess both testing for atypical pathogens and their prevalence in hospitalized patients with CAP worldwide, especially in relation with disease severity. Methods: A secondary analysis of the GLIMP database, an international, multicentre, point-prevalence study of adult patients admitted for CAP in 222 hospitals across 6 continents in 2015, was performed. The study evaluated frequency of testing for atypical pathogens, including L. pneumophila, M. pneumoniae, C. pneumoniae, and their prevalence. Risk factors for testing and prevalence for atypical pathogens were assessed through univariate analysis. Results: Among 3702 CAP patients 1250 (33.8%) underwent at least one test for atypical pathogens. Testing varies greatly among countries and its frequency was higher in Europe than elsewhere (46.0% vs. 12.7%, respectively, p &lt; 0.0001). Detection of L. pneumophila urinary antigen was the most common test performed worldwide (32.0%). Patients with severe CAP were less likely to be tested for both atypical pathogens considered together (30.5% vs. 35.0%, p = 0.009) and specifically for legionellosis (28.3% vs. 33.5%, p = 0.003) than the rest of the population. Similarly, L. pneumophila testing was lower in ICU patients. At least one atypical pathogen was isolated in 62 patients (4.7%), including M. pneumoniae (26/251 patients, 10.3%), L. pneumophila (30/1186 patients, 2.5%), and C. pneumoniae (8/228 patients, 3.5%). Patients with CAP due to atypical pathogens were significantly younger, showed less cardiovascular, renal, and metabolic comorbidities in comparison to adult patients hospitalized due to non-atypical pathogen CAP. Conclusions: Testing for atypical pathogens in patients admitted for CAP in poorly standardized in real life and does not mirror atypical prevalence in different settings. Further evidence on the impact of atypical pathogens, expecially in the low-income countries, is needed to guidelines implementation

Prevalence and etiology of community-acquired pneumonia in immunocompromised patients

Background. The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia. Methods. We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor. Results. At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non\u2013community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001). Conclusions. Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses