[Basic thoughts on psychopharmacological interventions through psychotherapy of severe forms of post-traumatic stress disorder: a case study].

PubMed

Joksimovic, Ljiljana; Wöller, Wolfgang; Kunzke, Dieter

2013-01-01

The present paper focuses on clinical issues concerning the psychopharmacological treatment of severe forms of post-traumatic stress disorder (PTSD).Using a case study, we discuss problems in this field against the background of psychodynamic and psychotraumatological theories. We also present strategies for the appropriate use of psychotropic drugs in the psychotherapy of PTSD.

Swiss cheese striatum: clinical implications.

PubMed

Burnett, Melinda S; Witte, Robert J; Ahlskog, J Eric

2014-06-01

Markedly enlarged Virchow-Robin spaces throughout the striatum appear occasionally on magnetic resonance imaging (MRI) scans of the elderly, and this type of striatum is known as the Swiss cheese striatum (SCS); however, its clinical impact is unknown. To determine the clinical features associated with SCS detected on MRI scans. A blinded, retrospective case-control study using medical records from 2000 to 2007 obtained from an MRI database at the Mayo Clinic in Rochester, Minnesota, of residents 40 years of age or older of Olmsted County, Minnesota, who had extensive Mayo Clinic medical records and MRI reports suggestive of SCS. Cases with a severe form of SCS (n = 27) were randomly selected for comparison with age-, sex-, and examination year-matched controls (n = 52) with a minimal form of SCS or no SCS. Magnetic resonance imaging. Associations of clinical and imaging features with the presence of a severe form of SCS. Medical records were reviewed for clinical features such as parkinsonism, dementia, and vascular risk factors. The MRI scans were visually scored for degree of leukoaraiosis, central atrophy, and cortical atrophy. No significant differences were found between those with a severe form of SCS and controls in rates of parkinsonism (19% vs 17%; odds ratio, 1.09 [95% CI, 0.28-4.16]) or dementia of any type (30% vs 21%; odds ratio, 1.57 [95% CI, 0.48-5.13]). Vascular risk factors were not significantly different between groups. Swiss cheese striatum correlated with degree of leukoaraiosis (P < .001). Potential associations with visualized cortical atrophy (P = .01), nonobstructive urinary incontinence (18.5% vs 3.9%; P = .04), and syncope (37% vs 9.6%; P = .01) did not hold up after correction for the false discovery rate. Our study suggests that marked cribriform change in the striatum was not associated with the development of extrapyramidal clinical disorders, including parkinsonism. The association of SCS with leukoaraiosis suggests that it is part of a more generalized cerebrovascular process. Skepticism is called for when attributing clinical symptoms to this MRI finding.

'Refeeding syndrome' in a Kuwaiti child: clinical diagnosis and management.

PubMed

Al Sharkawy, Ibrahim; Ramadan, Dina; El-Tantawy, Amira

2010-01-01

To report a case of refeeding syndrome in a Kuwaiti child, its clinical presentation and management. A 13-month-old Kuwaiti boy presented with acute severe malnutrition in the form of marasmic kwashiorkor. On admission, blood sugar and serum electrolytes were normal but on the 3rd day he developed typical biochemical features of refeeding syndrome in the form of hyperglycemia, severe hypophosphatemia, hypokalemia, hypocalcemia and hypomagnesemia. The child then received treatment appropriate for refeeding syndrome in the form of lower calorie intake with gradual increase, as well as supplementation of electrolytes, thiamine and vitamins and he eventually made a safe recovery. This case showed that during rehabilitation of a malnourished child, a severe potentially lethal electrolyte disturbance (refeeding syndrome) can occur. Careful monitoring of electrolytes before and during the refeeding phase was needed and helped to detect this syndrome early. We suggest that slow and gradual calorie increase in the 'at-risk' patient can help prevent its occurrence. Copyright (c) 2010 S. Karger AG, Basel.

Evaluation of the Psychometric Properties of the Asian Adolescent Depression Scale and Construction of a Short Form: An Item Response Theory Analysis.

PubMed

Lo, Barbara Chuen Yee; Zhao, Yue; Kwok, Alice Wai Yee; Chan, Wai; Chan, Calais Kin Yuen

2017-07-01

The present study applied item response theory to examine the psychometric properties of the Asian Adolescent Depression Scale and to construct a short form among 1,084 teenagers recruited from secondary schools in Hong Kong. Findings suggested that some items of the full form reflected higher levels of severity and were more discriminating than others, and the Asian Adolescent Depression Scale was useful in measuring a broad range of depressive severity in community youths. Differential item functioning emerged in several items where females reported higher depressive severity than males. In the short form construction, preliminary validation suggested that, relative to the 20-item full form, our derived short form offered significantly greater diagnostic performance and stronger discriminatory ability in differentiating depressed and nondepressed groups, and simultaneously maintained adequate measurement precision with a reduced response burden in assessing depression in the Asian adolescents. Cultural variance in depressive symptomatology and clinical implications are discussed.

Phenotype-genotype correlations in X linked retinitis pigmentosa.

PubMed Central

Kaplan, J; Pelet, A; Martin, C; Delrieu, O; Aymé, S; Bonneau, D; Briard, M L; Hanauer, A; Larget-Piet, L; Lefrançois, P

1992-01-01

Retinitis pigmentosa (RP) represents a group of clinically heterogeneous retinal degenerations in which all modes of inheritance have been described. We have previously found two different clinical profiles in X linked RP as a function of age and mode of onset. The first clinical form has very early onset with severe myopia. The second form starts later with night blindness with mild myopia or none. At least two genes have been identified in X linked forms, namely RP2 (linked to DXS7, DXS255, and DXS14) and RP3 (linked to DXS84 and OTC) on the short arm of the X chromosome. In order to contribute to phenotype-genotype correlations in X linked RP, we tested the hypothesis that the two clinical profiles could be accounted for by the two different gene loci. The present study provides evidence for linkage of the clinical form with early myopia as the onset symptom with the RP2 gene (pairwise linkage to DXS255: Z = 3.13 at theta = 0), while the clinical form with later night blindness as the onset symptom is linked to the RP3 gene (pairwise linkage to OTC: Z = 4.16 at theta = 0). Images PMID:1357178

Personality Assessment Use by Clinical Neuropsychologists

ERIC Educational Resources Information Center

Smith, Steven R.; Gorske, Tad T.; Wiggins, Chauntel; Little, Jessica A.

2010-01-01

The present study is an exploration of the personality assessment practices of clinical neuropsychologists. Professional members of the National Academy of Neuropsychology and the International Neuropsychological Society (N = 404) were surveyed to examine use of several forms of personality, behavior, and emotional function measures. Results…

Clinical investigation on Theileria equi and Babesia caballi infections in Italian donkeys.

PubMed

Laus, Fulvio; Spaterna, Andrea; Faillace, Vanessa; Veronesi, Fabrizia; Ravagnan, Silvia; Beribé, Francesca; Cerquetella, Matteo; Meligrana, Marina; Tesei, Beniamino

2015-04-28

Interest in the welfare and diseases of donkeys is constantly increasing in several countries. Despite this, clinical research into donkeys needs to be in continual development since they show different reactions compared to horses in many conditions, including infectious diseases, and need specific clinical and therapeutic approaches. No reports are currently available on clinical and clinical pathology data regarding donkeys with natural piroplasms infection. Venous blood samples were taken from one hundred and thirty eight donkeys and underwent indirect fluorescent antibody test (IFAT) to detect IgG antibodies against Theileria equi and Babesia caballi and real-time polimerase chain reaction (PCR) to detect Babesia spp. and Theileria spp. Clinical examinations, haematological analyses and serum bilirubin evaluation were also performed and compared with positive or negative status. A seroprevalence of 40.6% and 47.8% was found for T. equi and B. caballi, respectively; double positivity was detected in 19.6% of the animals. PCR results showed that 17.4% of the animals tested positive for T.equi and 3.6% for B. caballi with no double positivity. Twelve donkeys (8.7%) had clinical signs consistent with chronic forms of the disease and no acute forms were detected. Fifty-eight donkeys had haematological and serum bilirubin alterations and 56 (96.6%) of them were IFAT and/or PCR positive. Changes in erythrocyte number, packed cell volume, hemoglobin concentration, mean corpuscular hemoglobin, platelets number and total bilirubin were significantly associated with positive and symptomatic animals. Nonspecific clinical presentation seems to be very common in donkeys and several clinical pathology alterations persist after natural infection. Therefore, apparently healthy donkeys can have masked but severe clinical pathology alterations. Acute forms are very seldom observed in donkeys. Clinical monitoring of chronically infected donkeys is recommended since such animals represent a risk both for transmission to other animals and for their own health; furthermore, their production performances could be reduced. The study should also be intended as a contribution for veterinary practitioners because it describes the most usual clinical presentations and laboratory findings of equine piroplasmosis in naturally infected donkeys in endemic areas.

Analysis of risk factors in the development of retinopathy of prematurity.

PubMed

Knezević, Sanja; Stojanović, Nadezda; Oros, Ana; Savić, Dragana; Simović, Aleksandra; Knezević, Jasmina

2011-01-01

Retinopathy of prematurity (ROP) is a multifactorial disease that occurs most frequently in very small and very sick preterm infants, and it has been identified as the major cause of childhood blindness. The aim of this study was to evaluate ROP incidence and risk factors associated with varying degrees of illness. The study was conducted at the Centre for Neonatology, Paediatric Clinic of the Clinical Centre Kragujevac, Serbia, in the period from June 2006 to December 2008. Ophthalmologic screening was performed in all children with body weight lower than 2000 g or gestational age lower than 36 weeks. We analyzed eighteen postnatal and six perinatal risk factors and the group correlations for each of the risk factors. Out of 317 children that were screened, 56 (17.7%) developed a mild form of ROP, while 68 (21.5%) developed a severe form. Univariate analysis revealed a large number of statistically significant risk factors for the development of ROP, especially the severe form. Multivariate logistical analysis further separated two independent risk factors: small birth weight (p = 0.001) and damage of central nervous system (p = 0.01). Independent risk factors for transition from mild to severe forms of ROP were identified as: small birth weight (p = 0.05) and perinatal risk factors (p = 0.02). Small birth weight and central nervous system damage were risk factors for the development of ROP, perinatal risk factors were identified as significant for transition from mild to severe form of ROP.

A Scoring System to Predict the Severity of Hirschsprung Disease at Diagnosis and its Correlation with Molecular Genetics.

PubMed

Núñez-Ramos, Raquel; Fernández, Raquel M; González-Velasco, Miguel; Ruiz-Contreras, Jesús; Galán-Gómez, Enrique; Núñez-Núñez, Ramón; Borrego, Salud

2016-01-27

Hirschsprung disease (HSCR) has a wide range of severity. There are non-severe forms treated conservatively until surgery and severe forms that require an early stoma and prolonged hospitalization. Our objective was to establish a clinical scoring system to predict the severity of HSCR and to evaluate the possible existence of a clinical-genetic correlation. We carried out a retrospective observational study including all HSCR cases treated in our hospital. The sample was divided into severe and non-severe disease according to the number of surgical procedures, hospitalization time and episodes of enterocolitis. The proposed score was applied at diagnosis, and the sensitivity, specificity and optimal cut-point were determined. We conducted a prospective molecular study of RET, EDNRB and EDN3 on all patients, as well as SOX10 in Waardenburg Syndrome type 4 forms. Among the 42 patients treated between 1983 and 2013, 15 met the severe disease criteria. This group had a higher mean score (13.15±2.36) than the non-severe group (8.15±2.13; p<0.001). A score {greater than or equal to}11 had a sensitivity of 87% and a specificity of 81% in detecting the severe cases. Causative mutations were identified in 12 patients, 8 of them in the severe group (p=0.015). Most of these mutations (75%) were located in the RET proto-oncogene. The proposed scoring system enables the early selection of patients with severe behaviour of HSCR. A value {greater than or equal to}11 showed good sensitivity and specificity for this purpose. Causative mutations were identified in more than 50% of patients who met the criteria for severe disease.

Pelizaeus-Merzbacher disease in patients with molecularly confirmed diagnosis.

PubMed

Mierzewska, H; Jamroz, E; Mazurczak, T; Hoffman-Zacharska, D; Szczepanik, E

2016-01-01

Pelizaeus-Merzbacher disease (PMD) is X-linked hypomyelinating leukodystrophy caused by mutations of the PLP1 gene, which codes the proteolipid protein 1. The result of mutations is abnormal myelination - hypomyelination and dysmyelination of cerebral white matter, and in some form of the disease hypomyelinating peripheral neuropathy. DNA samples from 68 patients suspected of PMD due to the clinical course and hypomyelination at magnetic resonance imaging (MRI) were analyzed. Medical history and detailed clinical course of PMD patients were also analyzed. Different mutations of the PLP1 gene were detected in 14 boys from 11 families (~20%). Amongst the molecularly confirmed patients, 13 presented classical PMD forms but clinical phenotypes varied in the severity even amongst siblings. One patient presented a severe connatal form. One mother, obligate carrier, presented complicated SPG2 (spastic paraparesis). There was no phenotype-genotype correlation in our material. In many cases PMD was suspected with a delay of many years, sometimes only after birth of another affected child in the family. Pelizaeus-Merzbacher disease was most frequently misdiagnosed as cerebral palsy.

α-Globin as a molecular target in the treatment of β-thalassemia

PubMed Central

Mettananda, Sachith; Gibbons, Richard J.

2015-01-01

The thalassemias, together with sickle cell anemia and its variants, are the world’s most common form of inherited anemia, and in economically undeveloped countries, they still account for tens of thousands of premature deaths every year. In developed countries, treatment of thalassemia is also still far from ideal, requiring lifelong transfusion or allogeneic bone marrow transplantation. Clinical and molecular genetic studies over the course of the last 50 years have demonstrated how coinheritance of modifier genes, which alter the balance of α-like and β-like globin gene expression, may transform severe, transfusion-dependent thalassemia into relatively mild forms of anemia. Most attention has been paid to pathways that increase γ-globin expression, and hence the production of fetal hemoglobin. Here we review the evidence that reduction of α-globin expression may provide an equally plausible approach to ameliorating clinically severe forms of β-thalassemia, and in particular, the very common subgroup of patients with hemoglobin E β-thalassemia that makes up approximately half of all patients born each year with severe β-thalassemia. PMID:25869286

Prospective, Multicentre, Nationwide Clinical Data from 600 Cases of Acute Pancreatitis

PubMed Central

Párniczky, Andrea; Kui, Balázs; Szentesi, Andrea; Balázs, Anita; Szűcs, Ákos; Mosztbacher, Dóra; Czimmer, József; Sarlós, Patrícia; Bajor, Judit; Gódi, Szilárd; Vincze, Áron; Illés, Anita; Szabó, Imre; Pár, Gabriella; Takács, Tamás; Czakó, László; Szepes, Zoltán; Rakonczay, Zoltán; Izbéki, Ferenc; Gervain, Judit; Halász, Adrienn; Novák, János; Crai, Stefan; Hritz, István; Góg, Csaba; Sümegi, János; Golovics, Petra; Varga, Márta; Bod, Barnabás; Hamvas, József; Varga-Müller, Mónika; Papp, Zsuzsanna; Sahin-Tóth, Miklós; Hegyi, Péter

2016-01-01

Objective The aim of this study was to analyse the clinical characteristics of acute pancreatitis (AP) in a prospectively collected, large, multicentre cohort and to validate the major recommendations in the IAP/APA evidence-based guidelines for the management of AP. Design Eighty-six different clinical parameters were collected using an electronic clinical research form designed by the Hungarian Pancreatic Study Group. Patients 600 adult patients diagnosed with AP were prospectively enrolled from 17 Hungarian centres over a two-year period from 1 January 2013. Main Results With respect to aetiology, biliary and alcoholic pancreatitis represented the two most common forms of AP. The prevalence of biliary AP was higher in women, whereas alcoholic AP was more common in men. Hyperlipidaemia was a risk factor for severity, lack of serum enzyme elevation posed a risk for severe AP, and lack of abdominal pain at admission demonstrated a risk for mortality. Abdominal tenderness developed in all the patients with severe AP, while lack of abdominal tenderness was a favourable sign for mortality. Importantly, lung injury at admission was associated with mortality. With regard to laboratory parameters, white blood cell count and CRP were the two most sensitive indicators for severe AP. The most common local complication was peripancreatic fluid, whereas the most common distant organ failure in severe AP was lung injury. Deviation from the recommendations in the IAP/APA evidence-based guidelines on fluid replacement, enteral nutrition and timing of interventions increased severity and mortality. Conclusions Analysis of a large, nationwide, prospective cohort of AP cases allowed for the identification of important determinants of severity and mortality. Evidence-based guidelines should be observed rigorously to improve outcomes in AP. PMID:27798670

Revisiting metatropic dysplasia: presentation of a series of 19 novel patients and review of the literature.

PubMed

Geneviève, D; Le Merrer, M; Feingold, J; Munnich, A; Maroteaux, P; Cormier-Daire, V

2008-04-15

Metatropic dysplasia (MD-OMIM: 156530 and 250600) is a rare chondrodysplasia characterized by short limbs with limitation and enlargement of joints and usually severe kyphoscoliosis, first described in 1893. Up until now, 81 other patients have been reported. The phenotypic variability of MD has led to a classification based on radiological anomalies dividing into three different types: a lethal autosomal recessive form, an autosomal recessive non-lethal form and a non-lethal autosomal dominant form with less severe radiographs manifestations and a better clinical outcome. Here, we report on clinical and radiological features of 19 novel MD patients. We describe new radiological features, including precocious calcification of hyoid and cricoid cartilage, irregular and squared-off calcaneal bones and severe hypoplasia of the anterior portion of first cervical vertebrae. In addition, the observation of an overlap between the autosomal recessive non-lethal form and the non-lethal autosomal dominant form, the rarity of sibship recurrences and the observation of vertical transmissions of MD in the literature argue in favor of an autosomal dominant mode of inheritance for all MD types. This hypothesis is reinforced by the use of the statistical single ascertainment method that rejects the hypothesis of an autosomal recessive mode of inheritance responsible for MD. Therefore, we propose that recurrence in sibs is due to gonadal mosaicism. Copyright 2008 Wiley-Liss, Inc.

The Spectrum of Intermediate Syndrome Following Acute Organophosphate Poisoning: A Prospective Cohort Study from Sri Lanka

PubMed Central

Jayawardane, Pradeepa; Dawson, Andrew H; Weerasinghe, Vajira; Karalliedde, Lakshman; Buckley, Nicholas A; Senanayake, Nimal

2008-01-01

Background Intermediate syndrome (IMS) is a major cause of death from respiratory failure following acute organophosphate poisoning. The objective of this study was to determine repetitive nerve stimulation (RNS) predictors of IMS that would assist in patient management and clinical research. Methods and Findings Seventy-eight consenting symptomatic patients with organophosphate poisoning were assessed prospectively with daily physical examination and RNS. RNS was done on the right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. The study was conducted as a prospective observational cohort study in the Central Province, Sri Lanka. IMS was diagnosed in ten out of 78 patients using a priori clinical diagnostic criteria, and five of them developed respiratory failure. All ten patients showed progressive RNS changes correlating with the severity of IMS. A decrement-increment was observed at intermediate and high frequencies preceding the onset of clinical signs of IMS. As the patient developed clinical signs of IMS, decrement-increment was progressively noted at low and intermediate frequencies and a combination of decrement-increment and repetitive fade or severe decrement was noted at high frequencies. Severe decrement preceded respiratory failure in four patients. Thirty patients developed forme fruste IMS with less severe weakness not progressing to respiratory failure whose RNS was characterized by decrement-increment or a combination of decrement-increment and repetitive fade but never severe decrements. Conclusions Characteristic changes in RNS, preceding the development of IMS, help to identify a subgroup of patients at high risk of developing respiratory failure. The forme fruste IMS with the characteristic early changes on RNS indicates that IMS is a spectrum disorder. RNS changes are objective and precede the diagnosis and complications of IMS. Thus they may be useful in clinical management and research. PMID:18630983

A Scoring System to Predict the Severity of Hirschsprung Disease at Diagnosis and Its Correlation With Molecular Genetics.

PubMed

Núñez-Ramos, Raquel; Fernández, Raquel M; González-Velasco, Miguel; Ruiz-Contreras, Jesús; Galán-Gómez, Enrique; Núñez-Núñez, Ramón; Borrego, Salud

2017-01-01

Objectives Hirschsprung disease (HSCR) has a wide range of severity. There are nonsevere forms treated conservatively until surgery and severe forms that require an early stoma and prolonged hospitalization. Our objective was to establish a clinical scoring system to predict the severity of HSCR and to evaluate the possible existence of a clinical-genetic correlation. Methods We carried out a retrospective observational study including all HSCR cases treated in our hospital. The sample was divided into severe and nonsevere disease according to the number of surgical procedures, hospitalization time, and episodes of enterocolitis. The proposed score was applied at diagnosis, and the sensitivity, specificity, and optimal cut-point were determined. We conducted a prospective molecular study of RET, EDNRB, and EDN3 on all patients, as well as SOX10 in Waardenburg Syndrome type 4 forms. Results Among the 42 patients treated between 1983 and 2013, 15 met the severe disease criteria. This group had a higher mean score (13.15 ± 2.36) than the nonsevere group (8.15 ± 2.13; p < 0.001). A score ≥11 had a sensitivity of 87% and a specificity of 81% in detecting the severe cases. Causative mutations were identified in 12 patients, 8 of them in the severe group ( p = 0.015). Most of these mutations (75%) were located in the RET proto-oncogene. Conclusion The proposed scoring system enables the early selection of patients with severe behavior of HSCR. A value ≥11 showed good sensitivity and specificity for this purpose. Causative mutations were identified in more than 50% of patients who met the criteria for severe disease.

Sialidosis: A Review of Morphology and Molecular Biology of a Rare Pediatric Disorder.

PubMed

Khan, Aiza; Sergi, Consolato

2018-04-25

Sialidosis (MIM 256550) is a rare, autosomal recessive inherited disorder, caused by α- N -acetyl neuraminidase deficiency resulting from a mutation in the neuraminidase gene ( NEU1 ), located on 6p21.33. This genetic alteration leads to abnormal intracellular accumulation as well as urinary excretion of sialyloligosaccharides. A definitive diagnosis is made after the identification of a mutation in the NEU1 gene. So far, 40 mutations of NEU1 have been reported. An association exists between the impact of the individual mutations and the severity of clinical presentation of sialidosis. According to the clinical symptoms, sialidosis has been divided into two subtypes with different ages of onset and severity, including sialidosis type I (normomorphic or mild form) and sialidosis type II (dysmorphic or severe form). Sialidosis II is further subdivided into (i) congenital; (ii) infantile; and (iii) juvenile. Despite being uncommon, sialidosis has enormous clinical relevance due to its debilitating character. A complete understanding of the underlying pathology remains a challenge, which in turn limits the development of effective therapeutic strategies. Furthermore, in the last few years, some atypical cases of sialidosis have been reported as well. We herein attempt to combine and discuss the underlying molecular biology, the clinical features, and the morphological patterns of sialidosis type I and II.

Rapid execution of fan beam image reconstruction algorithms using efficient computational techniques and special-purpose processors

NASA Astrophysics Data System (ADS)

Gilbert, B. K.; Robb, R. A.; Chu, A.; Kenue, S. K.; Lent, A. H.; Swartzlander, E. E., Jr.

1981-02-01

Rapid advances during the past ten years of several forms of computer-assisted tomography (CT) have resulted in the development of numerous algorithms to convert raw projection data into cross-sectional images. These reconstruction algorithms are either 'iterative,' in which a large matrix algebraic equation is solved by successive approximation techniques; or 'closed form'. Continuing evolution of the closed form algorithms has allowed the newest versions to produce excellent reconstructed images in most applications. This paper will review several computer software and special-purpose digital hardware implementations of closed form algorithms, either proposed during the past several years by a number of workers or actually implemented in commercial or research CT scanners. The discussion will also cover a number of recently investigated algorithmic modifications which reduce the amount of computation required to execute the reconstruction process, as well as several new special-purpose digital hardware implementations under development in laboratories at the Mayo Clinic.

Epidemiological and clinical features of leptospirosis in a highly endemic area over three time periods.

PubMed

Mišić-Majerus, Ljiljana; Habuš, Josipa; Štritof, Zrinka; Bujić, Nevenka; Mađarić, Vesna; Kolaric-Sviben, Gordana; Vince, Silvijo; Peršić, Zdenka; Turk, Nenad

2017-11-01

To present the features of human leptospirosis over three time periods (1970-1975; 2000-2005; 2010-2015), to compare the collected data and to determine whether the incidence, seasonal and spatial distribution, prevalence of presumptive infective serogroups and clinical features have changed over the last 50 years. Epidemiological and clinical data obtained from patients hospitalised and treated in a well-known endemic focus of leptospirosis, Koprivnica-Križevci County in Croatia, were analysed. We observed a steady decline in the overall incidence of leptospirosis and a change in the patient age distribution, with the age ratio changing in favour of middle-aged and older patients. Although leptospirosis was most frequently diagnosed in August in all time periods, the number of cases increased in autumn. The most prevalent serogroup during the first and the second time period was Icterohaemorrhagiae, while in the third time period, the serogroup Australis prevailed. We also noted an increase in the number of severe clinical manifestations. This retrospective research demonstrates a continuous decline in the incidence of human leptospirosis in Croatia. The pattern of disease has changed from predominantly mild clinical forms observed in children to more severe clinical forms observed in middle-aged to older patients, especially those working in agriculture. Additional epidemiological changes included an increase in the number of cases during the autumn months and changes in prevailing serogroups. Statistical analysis revealed a significant relationship between the severity of the clinical picture, patient age and presumed sources of infection. © 2017 John Wiley & Sons Ltd.

The Forms and Functions of Impulsive Actions: Implications for Behavioral Assessment and Therapy

ERIC Educational Resources Information Center

Farmer, Richard F.; Golden, Jeannie A.

2009-01-01

Impulsivity is a central defining feature of several psychiatric disorders and a frequent correlate of many forms of psychopathology and maladjustment. Despite recognition of the importance of impulsivity to an understanding of a wide variety of clinically-relevant behaviors, this multifaceted construct remains ill-defined and not well understood.…

Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E.

PubMed

Semplicini, Claudio; Vissing, John; Dahlqvist, Julia R; Stojkovic, Tanya; Bello, Luca; Witting, Nanna; Duno, Morten; Leturcq, France; Bertolin, Cinzia; D'Ambrosio, Paola; Eymard, Bruno; Angelini, Corrado; Politano, Luisa; Laforêt, Pascal; Pegoraro, Elena

2015-04-28

To determine the clinical spectrum of limb-girdle muscular dystrophy 2E (LGMD2E) and to investigate whether genetic or biochemical features can predict the phenotype of the disease. All LGMD2E patients followed in participating centers were included. A specific clinical protocol was created, including quantitative evaluation of motor, respiratory, and cardiac function. Phenotype was defined as severe or mild if the age at loss of ambulation occurred before or after 18 years. Molecular analysis of SGCB gene and biochemical features of muscle biopsies were reviewed. Thirty-two patients were included (16 male, 16 female; age 7-67 years; 15 severe, 12 mild, and 5 unknown). Neurologic examination showed proximal muscle weakness in all patients, but distal involvement was also observed in patients with severe disease early in the disease course. Cardiac involvement was observed in 20 patients (63%) even before overt muscle involvement. Six patients had restrictive respiratory insufficiency requiring assisted ventilation (19%). Seventeen different mutations were identified, and 3 were recurrent. The c.377_384dup (13 alleles) was associated with the severe form, the c.-22_10dup (10) with the milder form, and the c.341C>T (9) with both. The entire sarcoglycan complex was undetectable by muscle immunohistochemistry or Western blot in 9/10 severe cases and reduced in 7/7 mild cases. The residual amount of sarcoglycan in muscle resulted a predictor of age at loss of ambulation. This study expands the spectrum of phenotype in β-sarcoglycanopathy and provides strong evidence that severity of clinical involvement may be predicted by SGCB gene mutation and sarcoglycan protein expression. © 2015 American Academy of Neurology.

Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E

PubMed Central

Semplicini, Claudio; Vissing, John; Dahlqvist, Julia R.; Stojkovic, Tanya; Bello, Luca; Witting, Nanna; Duno, Morten; Leturcq, France; Bertolin, Cinzia; D'Ambrosio, Paola; Eymard, Bruno; Angelini, Corrado; Politano, Luisa

2015-01-01

Objective: To determine the clinical spectrum of limb-girdle muscular dystrophy 2E (LGMD2E) and to investigate whether genetic or biochemical features can predict the phenotype of the disease. Methods: All LGMD2E patients followed in participating centers were included. A specific clinical protocol was created, including quantitative evaluation of motor, respiratory, and cardiac function. Phenotype was defined as severe or mild if the age at loss of ambulation occurred before or after 18 years. Molecular analysis of SGCB gene and biochemical features of muscle biopsies were reviewed. Results: Thirty-two patients were included (16 male, 16 female; age 7–67 years; 15 severe, 12 mild, and 5 unknown). Neurologic examination showed proximal muscle weakness in all patients, but distal involvement was also observed in patients with severe disease early in the disease course. Cardiac involvement was observed in 20 patients (63%) even before overt muscle involvement. Six patients had restrictive respiratory insufficiency requiring assisted ventilation (19%). Seventeen different mutations were identified, and 3 were recurrent. The c.377_384dup (13 alleles) was associated with the severe form, the c.-22_10dup (10) with the milder form, and the c.341C>T (9) with both. The entire sarcoglycan complex was undetectable by muscle immunohistochemistry or Western blot in 9/10 severe cases and reduced in 7/7 mild cases. The residual amount of sarcoglycan in muscle resulted a predictor of age at loss of ambulation. Conclusions: This study expands the spectrum of phenotype in β-sarcoglycanopathy and provides strong evidence that severity of clinical involvement may be predicted by SGCB gene mutation and sarcoglycan protein expression. PMID:25862795

Suspected postpartum endometritis: a controlled clinical trial of single-agent antibiotic therapy with Amox-CA (Augmentin) vs. ampicillin-metronidazole +/- aminoglycoside.

PubMed

Fernandez, H; Claquin, C; Guibert, M; Papiernik, E

1990-01-01

Endometritis is the commonest postpartum complication and is one of the leading causes of maternal morbidity, if not mortality. The object of the present clinical trial was to assess the efficiency of single-agent therapy with Amox-CA (Augmentin) (formulation which includes a beta-lactamase inhibitor), against standard treatment which necessarily combines two or three antibiotics depending on the clinical severity of the case. 101 patients were evaluated in this comparative prospective randomized study. The mild forms were defined by a temperature between 37.9 and 38.4 degrees C and the severe forms by a temperature of more than 38.5 degrees C (which alone required treatment with three antibiotics). The time until the return of apyrexia and the clinical cure rate, as well as duration of treatment, were identical in both groups. Tolerance was good: no side effect requiring discontinuation of treatment occurred. In the population value, the use of a single-agent therapy with amoxycillin/clavulanic acid is not significantly different from a double or triple-agent regimen, and the convenience is increase.

Development of an enzyme-linked immunosorbent assay for the serodiagnosis of several clinical forms of sporotrichosis.

PubMed

Bernardes-Engemann, A R; Costa, R C Orofino; Miguens, B R; Penha, C V L; Neves, E; Pereira, B A S; Dias, C M P; Mattos, M; Gutierrez, M C; Schubach, A; Oliveira Neto, M P; Lazéra, M; Lopes-Bezerra, L M

2005-09-01

We performed a serological study with sera from 92 patients with confirmed sporotrichosis registered between 1999 and 2004 in two hospitals in Rio de Janeiro State, Brazil. The clinical presentation of sporotrichosis was distributed as follows: lymphocutaneous, 67%; fixed cutaneous, 23%; disseminated cutaneous, 8%; and extracutaneous, 2%. Sera were assayed by ELISA against a cell wall antigen of Sporothrix schenckii, SsCBF, that we have previously described. The cross-reactivity was determined with 77 heterologous sera. The serological test showed a sensitivity of 90% and a global efficiency of 86%. A group of 55 patients with several clinical presentations of sporotrichosis was clinically and serologically followed-up for at least 6 months. We observed by ELISA data a decrease in the antibody serum titers which correlated with the progress in healing. An HIV-positive patient with meningeal sporotrichosis was serologically followed-up for over 2 years. Serum and cerebrospinal fluid specimens were examined and significant antibodies levels against the antigen SsCBF were detected. Our results strongly suggest that this serological test is valuable for the differential diagnosis and follow-up of all clinical forms of sporotrichosis.

Prevalence of clinically important traumatic brain injuries in children with minor blunt head trauma and isolated severe injury mechanisms.

PubMed

Nigrovic, Lise E; Lee, Lois K; Hoyle, John; Stanley, Rachel M; Gorelick, Marc H; Miskin, Michelle; Atabaki, Shireen M; Dayan, Peter S; Holmes, James F; Kuppermann, Nathan

2012-04-01

To determine the prevalence of clinically important traumatic brain injuries (TBIs) with severe injury mechanisms in children with minor blunt head trauma but with no other risk factors from the Pediatric Emergency Care Applied Research Network (PECARN) TBI prediction rules (defined as isolated severe injury mechanisms). Secondary analysis of a large prospective observational cohort study. Twenty-five emergency departments participating in the PECARN. Children with minor blunt head trauma and Glasgow Coma Scale scores of at least 14. Treating clinicians completed a structured data form that included injury mechanism (severity categories defined a priori). Clinically important TBIs were defined as intracranial injuries resulting in death, neurosurgical intervention, intubation for more than 24 hours, or hospital admission for at least 2 nights. We investigated the rate of clinically important TBIs in children with either severe injury mechanisms or isolated severe injury mechanisms. Of the 42,412 patients enrolled in the overall study, 42,099 (99%) had injury mechanisms recorded, and their data were included for analysis. Of all study patients, 5869 (14%) had severe injury mechanisms, and 3302 (8%) had isolated severe injury mechanisms. Overall, 367 children had clinically important TBIs (0.9%; 95% CI, 0.8%-1.0%). Of the 1327 children younger than 2 years with isolated severe injury mechanisms, 4 (0.3%; 95% CI, 0.1%-0.8%) had clinically important TBIs, as did 12 of the 1975 children 2 years or older (0.6%; 95% CI, 0.3%-1.1%). Children with isolated severe injury mechanisms are at low risk of clinically important TBI, and many do not require emergent neuroimaging.

[Clinical and monitoring experience of isotretinoin in Italy].

PubMed

Cavicchini, S; Bottoni, A; Caputo, R

1989-01-01

We report the results of a multicentric evaluation on effectiveness and safety of isotretinoin in severe acne, recalcitrant to traditional treatments. 208 patients, suffering especially from cystic acne, have been enrolled in a post-marketing clinical trial in 11 Dermatological Italian Departments. The clinical effectiveness of isotretinoin has been very good in 77% of patients, good in 16% and sufficient in 4%. The tolerability of the drug was considered good in 90% of patients. Finally, isotretinoin might be considered as one of the most effective drugs in the therapy of severe forms of acne, resistant to usual treatment, and often affecting patients on the physical and psychological side.

The Clinical Approach to Encephalitis.

PubMed

Piquet, Amanda L; Cho, Tracey A

2016-05-01

Encephalitis has various etiologies, but viral infections and autoimmune disorders are the most commonly identified. Clinical signs, geographical clues, and diagnostic testing-including cerebrospinal fluid abnormalities and magnetic resonance imaging abnormalities-can be helpful in identifying the cause. Certain forms of encephalitis have specific treatments; hence, establishing a diagnosis rapidly and accurately is crucial. Here, we describe the clinical approach to diagnosing several common etiologies of encephalitis as well as treatment strategies.

A Review of Progress in Clinical Photodynamic Therapy

PubMed Central

Huang, Zheng

2005-01-01

Photodynamic therapy (PDT) has received increased attention since the regulatory approvals have been granted to several photosensitizing drugs and light applicators world-wide. Much progress has been seen in basic sciences and clinical photodynamics in recent years. This review will focus on new developments of clinical investigation and discuss the usefulness of various forms of PDT techniques for curative or palliative treatment of malignant and non-malignant diseases. PMID:15896084

Wechsler Adult Intelligence Scale-IV Dyads for Estimating Global Intelligence.

PubMed

Girard, Todd A; Axelrod, Bradley N; Patel, Ronak; Crawford, John R

2015-08-01

All possible two-subtest combinations of the core Wechsler Adult Intelligence Scale-IV (WAIS-IV) subtests were evaluated as possible viable short forms for estimating full-scale IQ (FSIQ). Validity of the dyads was evaluated relative to FSIQ in a large clinical sample (N = 482) referred for neuropsychological assessment. Sample validity measures included correlations, mean discrepancies, and levels of agreement between dyad estimates and FSIQ scores. In addition, reliability and validity coefficients were derived from WAIS-IV standardization data. The Coding + Information dyad had the strongest combination of reliability and validity data. However, several other dyads yielded comparable psychometric performance, albeit with some variability in their particular strengths. We also observed heterogeneity between validity coefficients from the clinical and standardization-based estimates for several dyads. Thus, readers are encouraged to also consider the individual psychometric attributes, their clinical or research goals, and client or sample characteristics when selecting among the dyadic short forms. © The Author(s) 2014.

Congenital Neonatal Hyperthyroidism Caused by Germline Mutations in the TSH Receptor Gene: Case Report and Review of the Literature

PubMed Central

Chester, Jeremy; Rotenstein, Deborah; Ringkananont, Usanee; Steuer, Guy; Carlin, Beatrice; Stewart, Lindsay; Grasberger, Helmut; Refetoff, Samuel

2018-01-01

Neonatal hyperthyroidism, a rare and serious disorder occurs in two forms. An autoimmune form associated with maternal Graves’ disease, resulting from transplacental passage of maternal thyroid-stimulating antibodies, and a nonautoimmune form, resulting from mutations in the stimulatory G protein or the thyrotropin receptor (TSHR) causing constitutive activation of intracellular signaling cascades. To date, 29 separate cases of thyrotoxicosis caused by germline mutations of the TSHR have been documented. These cases have expressed themselves in a range of clinical consequences. This report describes a new case of a newborn with nonautoimmune hyperthyroidism secondary to a constitutively active TSHR mutation (S281N) whose clinical course was complicated by severe respiratory compromise. Typical clinical findings in this disorder are discussed by a review of all previously published cases. PMID:18655531

[Depersonalization and déjà vu experiences: prevalences in nonclinical samples].

PubMed

Probst, P; Jansen, J

1991-01-01

According to the relevant psychological and psychiatric literature, depersonalization and déjà vu experiences are usually viewed as symptoms of severe psychiatric or neurological disorders, especially in schizophrenia, depression and epilepsy. Studies of these phenomena in non-clinical populations are rate. In this article we present the results of several epidemiological investigations. On the basis of survey and interview research, quantitative and qualitative aspects of both phenomena were assessed, as well as the relations with personality variables like emotionality. The results indicate prevalence rates up to 80 percent in non-clinical populations. Based on epidemiological considerations, the question of differentiation between clinical and non-clinical forms of depersonalization and déjà vu is discussed.

Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism.

PubMed

de Oliveira, Amanda Priscila; Bernardo, Cássia Rubia; Camargo, Ana Vitória da Silveira; Ronchi, Luiz Sérgio; Borim, Aldenis Albaneze; de Mattos, Cinara Cássia Brandão; de Campos Júnior, Eumildo; Castiglioni, Lílian; Netinho, João Gomes; Cavasini, Carlos Eugênio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos

2015-01-01

The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.

Factors influencing the severity of acute viral hepatitis A

PubMed Central

Kim, Joo Il; Jung, Young Kul; Kwon, Oh Sang; Kim, Yeon Suk; Ku, Yang Suh; Choi, Duck Joo; Kim, Ju Hyun

2010-01-01

Background/Aims Most patients with acute viral hepatitis A have a favorable course, but a few of them suffer from severe forms of hepatitis such as fulminant hepatitis. This study was carried out to identify the factors influencing the severity of acute viral hepatitis A. Methods We retrospectively reviewed the medical records of 713 patients with acute hepatitis A, who were divided into two groups: severe hepatitis A (N=87) and non-severe hepatitis A (N=626). Severe hepatitis was defined as fulminant hepatitis or prolongation of prothrombin time (INR≥1.5). Clinical variables were compared between the two groups. Results The incidence of fulminant hepatitis was 1.4% (10/713) in patients with acute hepatitis A. Thirty-three (4.6%) cases exhibited HBsAg positivity. In multivariate analyses, significant alcohol intake and the presence of HBsAg were significant predictive factors of fulminant hepatitis A, and significant alcohol intake and age were significant predictive factors of severe hepatitis A. HBeAg and HBV-DNA status did not affect the clinical course of hepatitis A in chronic hepatitis B carriers. Conclusions While most patients with acute hepatitis A have an uncomplicated clinical course, our data suggest that a more-severe clinical course is correlated with being older, significant alcohol intake, and chronic hepatitis-B-virus infection. PMID:20924212

Up to Four Distinct Polypeptides Are Produced from the γ34.5 Open Reading Frame of Herpes Simplex Virus 2

PubMed Central

Korom, Maria; Davis, Katie L.

2014-01-01

ABSTRACT The herpes simplex virus 1 (HSV-1) ICP34.5 protein strongly influences neurovirulence and regulates several cellular antiviral responses. Despite the clinical importance of HSV-2, relatively little is known about its ICP34.5 ortholog. We found that HSV-2 produces up to four distinct forms of ICP34.5 in infected cells: a full-length protein, one shorter form sharing the N terminus, and two shorter forms sharing the C terminus. These forms appeared with similar kinetics and accumulated in cells over much of the replication cycle. We confirmed that the N-terminal form is translated from the primary unspliced transcript to a stop codon within the intron unique to HSV-2 γ34.5. We found that the N-terminal form was produced in a variety of cell types and by 9 of 10 clinical isolates. ICP27 influenced but was not required for expression of the N-terminal form. Western blotting and reverse transcription-PCR indicated the C-terminal forms did not contain the N terminus and were not products of alternative splicing or internal transcript initiation. Expression plasmids encoding methionine at amino acids 56 and 70 generated products that comigrated in SDS-PAGE with the C1 and C2 forms, respectively, and mutation of these sites abolished C1 and C2. Using a recombinant HSV-2 encoding hemagglutinin (HA)-tagged ICP34.5, we demonstrated that the C-terminal forms were also produced during infection of many human and mouse cell types but were not detectable in mouse primary neurons. The protein diversity generated from the HSV-2 γ34.5 open reading frame implies additional layers of cellular regulation through potential independent activities associated with the various forms of ICP34.5. IMPORTANCE The herpes simplex virus 1 (HSV-1) protein ICP34.5, encoded by the γ34.5 gene, interferes with several host defense mechanisms by binding cellular proteins that would otherwise stimulate the cell's autophagic, translational-arrest, and type I interferon responses to virus infection. ICP34.5 also plays a crucial role in determining the severity of nervous system infections with HSV-1 and HSV-2. The HSV-2 γ34.5 gene contains an intron not present in HSV-1 γ34.5. A shorter N-terminal form of HSV-2 ICP34.5 can be translated from the unspliced γ34.5 mRNA. Here, we show that two additional forms consisting of the C-terminal portion of ICP34.5 are generated in infected cells. Production of these N- and C-terminal forms is highly conserved among HSV-2 strains, including many clinical isolates, and they are broadly expressed in several cell types, but not mouse primary neurons. Multiple ICP34.5 polypeptides add additional complexity to potential functional interactions influencing HSV-2 neurovirulence. PMID:25031346

Catastrophic antiphospholipid syndrome and pregnancy. Clinical report.

PubMed

Khizroeva, J; Bitsadze, V; Makatsariya, A

2018-01-08

We have observed the development of a catastrophic antiphospholipid syndrome (CAPS) in a pregnant woman hospitalized at 28 weeks of gestation with a severe preeclampsia. On the same day, an eclampsia attack developed, and an emergency surgical delivery was performed. On the third day, multiorgan failure developed. Examination showed a persistent circulation of lupus anticoagulant, high level of antibodies to cardiolipin, b2-glycoprotein I, and prothrombin. The usual diagnosis of the severe preeclampsia masked a catastrophic antiphospholipid syndrome, exacerbated by the coincident presence of several types of antiphospholipid antibodies. The first pregnancy resulted in a premature birth at 25 weeks, possibly also due to the circulation of antiphospholipid antibodies. The trigger of the catastrophic form development was the pregnancy itself, surgical intervention, and hyperhomocysteinemia. CAPS is the most severe form of antiphospholipid syndrome, manifested in multiple microthrombosis of microcirculation of vital organs and in the development of multiorgan failure against the background of the high level of antiphospholipid antibodies. CAPS is characterized by renal, cerebral, gastrointestinal, adrenal, ovarian, skin, and other forms of microthrombosis. Thrombosis recurrence is typical. Thrombotic microvasculopathy lies at the heart of multiorgan failure and manifests clinically in central nervous system lesions, adrenal insufficiency, and ARDS development. CAPS is a life-threatening condition, therefore, requires an urgent treatment. Optimal treatment of CAPS is not developed. CAPS represent a general medical multidisciplinary problem.

Social Functioning in Youth with Anxiety Disorders: Association with Anxiety Severity and Outcomes from Cognitive-Behavioral Therapy

ERIC Educational Resources Information Center

Settipani, Cara A.; Kendall, Philip C.

2013-01-01

Social functioning was assessed using the Child Behavior Checklist and Teacher Report Form for children with anxiety disorders who participated in a randomized clinical trial (N = 161, aged 7-14). Significant relationships were found between severity of children's principal anxiety disorder and most measures of social functioning, such that poorer…

Validation of modified forms of the PedsQL generic core scales and cancer module scales for adolescents and young adults (AYA) with cancer or a blood disorder.

PubMed

Ewing, Jane E; King, Madeleine T; Smith, Narelle F

2009-03-01

To validate two health-related quality of life (HRQOL) measures, the PedsQL Generic Core and Cancer Module adolescent forms (13-18 years), after modification for 16-25-year-old adolescents and young adults (AYA) with cancer or a blood disorder. AYA patients and nominated proxies were recruited from three Sydney hospitals. Modified forms were administered by telephone or in clinics/wards. Analyses included correlations, factor analysis, and analysis of variance of known-groups (defined by the Memorial Symptom Assessment Scale). Eighty-eight patients and 79 proxies completed questionnaires. Factor structures consistent with those of the unmodified forms confirmed construct validity. Cronbach's alpha ranged 0.81-0.98. Inter-scale correlations were as hypothesized, confirming discriminant validity. Statistically significant differences between groups with mild, moderate, and severe symptoms (P < 0.05) confirmed clinical validity. These modified forms provide reliable and valid measures of HRQOL in AYA with cancer or a blood disorder, suitable for clinical trials, research, and practice.

Examining Concurrent Validity and Predictive Utility for the Addiction Severity Index and Texas Christian University (TCU) Short Forms

PubMed Central

PANKOW, JENNIFER; SIMPSON, D. DWAYNE; JOE, GEORGE W.; ROWAN-SZAL, GRACE A.; KNIGHT, KEVIN; MEASON, PAUL

2012-01-01

Treatment providers need tools which are designed to identify risk, treatment needs, and monitor client engagement. These are essential components in substance abuse treatment for offender populations. This study evaluated a flexible set of 1-page modular assessments known as the TCU Short Forms and compared them with the measures of global domains contained in the Addiction Severity Index (ASI). The sample was based on 540 adult males and females in corrections-based substance abuse treatment services located in Arkansas and Missouri. Results suggest the set of TCU forms and ASI both reliably represent core clinical domains, but TCU Short Forms explained more variance in therapeutic engagement criteria measured during treatment. Similarities and differences of the assessment tools are discussed, along with applications PMID:23087588

Anti-Idiotypic Antibodies in Patients with Different Clinical Forms of Paracoccidioidomycosis

PubMed Central

Souza, A. R.; Gesztesi, J.-L.; del Negro, G. M. B.; Benard, G.; Sato, J.; Santos, M. V. B.; Abrahão, T. B.; Lopes, J. D.

2000-01-01

Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America. Patients with PCM show a wide spectrum of clinical and pathological manifestations depending on both host and pathogen factors. Two clinical forms of the disease are recognized: the acute or juvenile form and the chronic or adult form. The major antigenic component of the parasite is a glycoprotein of 43 kDa (gp43). All patient sera present antibodies against gp43 (anti-gp43) and, as demonstrated before by our group, spontaneous anti-idiotypic (anti-Id) antibodies (Ab2) can be detected in patient sera with high titers of anti-gp43. Since it has been postulated that anti-Id antibodies may have a modulating function, we decided to purify and characterize anti-Id antibodies in this system. The possible correlation of Ab2 titers with different clinical forms of disease was also verified. Results showed that purified human anti-Id antibodies (human Ab2) recognized specifically the idiotype of some murine monoclonal anti-gp43 (17c and 3e) but not others (40.d7, 27a, and 8a). Spontaneous anti-Id antibodies were found in all clinical forms of disease. The majority of patients (88%, n = 8) with the acute form of PCM had high titers of Ab2. However, among patients with the multifocal chronic form of the disease, only 29% (n = 14) had high titers of Ab2; 70% (n = 10) of patients with the unifocal chronic form had low titers of Ab2. A correlation between Ab2 titers and anti-gp43 titers was observed before and during antimycotic treatment. Our results suggest that titers of anti-Id antibodies correlate with the severity of PCM in humans. PMID:10702489

[Clinical and genetic special features of Niemann-Pick disease, type C].

PubMed

Zakharova, E Iu; Mikhaĭlova, S V; Proshliakova, T Iu; Rudenskaia, G E

2012-01-01

Niemann-Pick disease, type C is a rare hereditary disorder of the group of lisosomal storage diseases, caused by mutations in the genes NPC1 or NPC2. Depending on the onset age, several clinical forms of this disease, which differs by manifestation age, main clinical signs and clinical course, are distinguished. Niemann-Pick disease type C can imitate other hereditary and acquired diseases, which complicates its early diagnostics. Clinical and genetic diversity of this disorder, considered on the clinical cases diagnosed at the FSI "RCMG" of RAMS, are discussed in this review.

A Clinical Review of the Treatment of Catatonia

PubMed Central

Sienaert, Pascal; Dhossche, Dirk M.; Vancampfort, Davy; De Hert, Marc; Gazdag, Gábor

2014-01-01

Catatonia is a severe motor syndrome with an estimated prevalence among psychiatric inpatients of about 10%. At times, it is life-threatening especially in its malignant form when complicated by fever and autonomic disturbances. Catatonia can accompany many different psychiatric illnesses and somatic diseases. In order to recognize the catatonic syndrome, apart from thorough and repeated observation, a clinical examination is needed. A screening instrument, such as the Bush-Francis Catatonia Rating Scale, can guide the clinician through the neuropsychiatric examination. Although severe and life-threatening, catatonia has a good prognosis. Research on the treatment of catatonia is scarce, but there is overwhelming clinical evidence of the efficacy of benzodiazepines, such as lorazepam, and electroconvulsive therapy. PMID:25538636

Myxomatosis.

PubMed

Bertagnoli, S; Marchandeau, S

2015-08-01

Myxomatosis, a major disease of European rabbits (Oryctolagus cuniculus), is enzootic on several continents. The disease is infectious, virulent and contagious. The pathogen is a virus of the family Poxviridae, genus Leporipoxvirus. In its classic form the disease is often fatal, characterised by severe immunosuppression and the appearance of skin pseudotumours (myxomas); it is conducive to effective mechanical transmission by many biting arthropods. Atypical clinical forms, referred to as amyxomatous, of variable severity and with an apparent preference for direct transmission, have recently emerged in Europe. Virus-host interactions have been particularly well studied since the voluntary introduction of the myxoma virus into Australia and Europe, revealing a remarkable process of co-evolution. Molecular analysis has recently demonstrated the extraordinary evolutionary capacity of the myxoma virus.

Clinical spectrum of botulism.

PubMed

Cherington, M

1998-06-01

Botulism is a paralyzing disease caused by the toxin of Clostridium botulinum. The toxin produces skeletal muscle paralysis by producing a presynaptic blockade to the release of acetylcholine. Recent studies have pinpointed the site of action of the several types of botulinum neurotoxin at the nerve terminal. Since the discovery of the toxin about 100 years ago, five clinical forms of botulism have been described: 1) classic or foodborne botulism; 2) wound botulism; 3) infant botulism; 4) hidden botulism; 5) inadvertent botulism. A clinical pattern of descending weakness is characteristic of all five forms. Almost all human cases of botulism are caused by one of three serotypes (A, B, or E). Classic and wound botulism were the only two forms known until the last quarter of this century. Wound botulism was rare until the past decade. Now there are increasing numbers of cases of wound botulism in injecting drug users. Infant botulism, first described in 1976, is now the most frequently reported form. In infant botulism spores of Clostridium botulinum are ingested and germinate in the intestinal tract. Hidden botulism, the adult variant of infant botulism, occurs in adult patients who usually have an abnormality of the intestinal tract that allows colonization by Clostridium botulinum. Inadvertent botulism is the most recent form to be described. It occurs in patients who have been treated with injections of botulinum toxin for dystonic and other movement disorders. Laboratory proof of botulism is established with the detection of toxin in the patient's serum, stool, or wound. The detection of Clostridium botulinum bacteria in the stool or wound should also be considered evidence of clinical botulism. Electrophysiologic studies can provide presumptive of botulism in patients with the clinical signs of botulism. Electrophysiologic testing can be especially helpful when bioassay studies are negative. The most consistent electrophysiologic abnormality is a small evoked muscle action potential in response to a single supramaximal nerve stimulus in a clinically affected muscle. Posttetanic facilitation can be found in some affected muscles. Single-fiber EMG studies typically reveal increased jitter and blocking, which become less marked following activation. The major treatment for severe botulism is advance medical and nursing supportive care with special attention to respiratory status.

Evaluation of a New Grading System for Clinical Skills in Dental Student Clinics.

PubMed

Bodenmann, Aurel D; Bühler, Julia M; Amato, Mauro; Weiger, Ronald; Zitzmann, Nicola U

2017-05-01

Several evaluation systems for clinical exams have been suggested over the years, but no systematic analysis of checklists or criteria-based exam forms has yet been undertaken. The aims of this study were to analyze criteria-based evaluation forms and to identify areas in the teaching process potentially requiring improvements. All evaluation forms introduced in 2012 at the Clinic for Periodontology, Endodontology, and Cariology at the University Center of Dental Medicine in Basel, Switzerland, and applied over a three-year period (n=1,093 in 2015) were analyzed using predefined criteria. The authors investigated how well clinical tasks were examined with the given criteria and which criteria were preferably evaluated with a grading system (0-2) or a yes/no choice. The average final grades ranged from 0.89 (n=92) for gold inlay preparation to 1.76 (n=46) for periodontal treatment. Comments were made in 38.5% (n=356) of all exams, mainly highlighting specific aspects of existing criteria. Overall, 13 criteria out of 66 should be checked instead of graded. This methodological analysis of exam forms assessing tasks in operative dentistry yielded valuable information on areas with potential for improvement in the dental curriculum and the evaluation process. Aspects that require more theoretical background and/or hands-on recommendations from experienced clinicians were identified, and ways of further refining and redesigning the evaluation forms were proposed.

Complete Genome Sequences of Two Geographically Distinct Legionella micdadei Clinical Isolates

PubMed Central

Jose, Bethany R.; Perry, Jasper; Smeele, Zoe; Aitken, Jack; Gardner, Paul P.

2017-01-01

ABSTRACT Legionella is a highly diverse genus of intracellular bacterial pathogens that cause Legionnaire’s disease (LD), an often severe form of pneumonia. Two L. micdadei sp. clinical isolates, obtained from patients hospitalized with LD from geographically distinct areas, were sequenced using PacBio SMRT cell technology, identifying incomplete phage regions, which may impact virulence. PMID:28572318

Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism

PubMed Central

de Oliveira, Amanda Priscila; Bernardo, Cássia Rubia; Camargo, Ana Vitória da Silveira; Ronchi, Luiz Sérgio; Borim, Aldenis Albaneze; Brandão de Mattos, Cinara Cássia; de Campos Júnior, Eumildo; Castiglioni, Lílian; Netinho, João Gomes; Cavasini, Carlos Eugênio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos

2015-01-01

The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region—rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD. PMID:26599761

Comprehensive comparison of self-administered questionnaires for measuring quantitative autistic traits in adults.

PubMed

Nishiyama, Takeshi; Suzuki, Masako; Adachi, Katsunori; Sumi, Satoshi; Okada, Kensuke; Kishino, Hirohisa; Sakai, Saeko; Kamio, Yoko; Kojima, Masayo; Suzuki, Sadao; Kanne, Stephen M

2014-05-01

We comprehensively compared all available questionnaires for measuring quantitative autistic traits (QATs) in terms of reliability and construct validity in 3,147 non-clinical and 60 clinical subjects with normal intelligence. We examined four full-length forms, the Subthreshold Autism Trait Questionnaire (SATQ), the Broader Autism Phenotype Questionnaire, the Social Responsiveness Scale2-Adult Self report (SRS2-AS), and the Autism-Spectrum Quotient (AQ). The SRS2-AS and the AQ each had several short forms that we also examined, bringing the total to 11 forms. Though all QAT questionnaires showed acceptable levels of test-retest reliability, the AQ and SRS2-AS, including their short forms, exhibited poor internal consistency and discriminant validity, respectively. The SATQ excelled in terms of classical test theory and due to its short length.

Determinants of impaired quality of life in patients with fibrous dysplasia.

PubMed

Majoor, Bas C J; Andela, Cornelie D; Bruggemann, Jens; van de Sande, Michiel A J; Kaptein, Ad A; Hamdy, Neveen A T; Dijkstra, P D Sander; Appelman-Dijkstra, Natasha M

2017-04-27

Fibrous dysplasia is a rare bone disorder, commonly associated with pain, deformity and fractures, which may significantly impact on quality of life. In this study we evaluate quality of life in patients with fibrous dysplasia using the Short Form-36 and the Brief Pain Inventory questionnaires. Data were compared with those of the general Dutch population. Out of 138 patients from a cohort of 255 patients with fibrous dysplasia that were sent questionnaires assessing quality of life and pain, the response rate was 70.3%, with 97 patients, predominantly female (65%), completing the questionnaires. Monostotic fibrous dysplasia was predominant (n = 62, 64%). Fibrous dysplasia patients had significantly lower quality of life outcome scores than the general Dutch population for all tested domains of the Short Form-36 except for the "Mental health" and the "Role emotional" domains. More severe forms of fibrous dysplasia, had the more severe Short-Form-36 quality of life outcomes, but there was no significant difference in Brief Pain Inventory domains between different subtypes of fibrous dysplasia. Quality of life was lower in patients with higher disease burden, as reflected by high skeletal burden scores (p = 0.003) and high levels of P1NP (p = 0.002). We demonstrate impairments in all domains of quality of life, except for 'Mental health' and 'Role emotional' domains, across the wide spectrum of fibrous dysplasia including its milder forms. We identified high skeletal burden scores, reflecting disease severity, as the most consistent predictor of impaired quality of life. Our findings hold significant clinical implications as they draw attention to the clinically unmet need to address quality of life issues in the management of patients with all subtypes of fibrous dysplasia, including its milder forms.

Mitochondrial cytopathies and the kidney.

PubMed

Emma, Francesco; Salviati, Leonardo

2017-04-01

Mitochondrial cytopathies include a heterogeneous group of diseases that are characterized by impaired oxidative phosphorylation. Current evidence suggests that renal involvement is probably more frequent than originally suspected but remains subclinical in a significant number of patients or is underestimated due to the severity of other clinical manifestations. Until recently, these diseases were thought to develop primarily in pediatric patients but patients that become symptomatic only in adulthood are now well recognized. From a renal standpoint, many patients with severe systemic disease and several patients with oligo-symptomatic clinical pictures have tubular defects, ranging from isolated tubular wasting of electrolytes to complete forms of renal Fanconi syndrome. Aside from rare cases of tubulo-interstitial and cystic diseases, other patients present with glomerular diseases that correspond in the majority of cases to focal segmental glomerulosclerosis lesions. Two specific entities should be singled out, namely the 3243 A>G mutation in the gene encoding for the mitochondrial leucine tRNA because it represents the most frequent form of mitochondrial glomerulopathy, and defects in the biosynthesis of coenzyme Q10 because they represent one of the few treatable forms of mitochondrial cytopathies. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

AGXT gene mutations and their influence on clinical heterogeneity of type 1 primary hyperoxaluria.

PubMed

Amoroso, A; Pirulli, D; Florian, F; Puzzer, D; Boniotto, M; Crovella, S; Zezlina, S; Spanò, A; Mazzola, G; Savoldi, S; Ferrettini, C; Berutti, S; Petrarulo, M; Marangella, M

2001-10-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder that is caused by a deficiency of alanine: glyoxylate aminotransferase (AGT), which is encoded by a single copy gene (AGXT). Molecular diagnosis was used in conjunction with clinical, biochemical, and enzymological data to evaluate genotype-phenotype correlation. Twenty-three unrelated, Italian PH1 patients were studied, 20 of which were grouped according to severe form of PH1 (group A), adult form (group B), and mild to moderate decrease in renal function (group C). All 23 patients were analyzed by using the single-strand conformation polymorphism technique followed by the sequencing of the 11 AGXT exons. Relevant chemistries, including plasma, urine and dialyzate oxalate and glycolate assays, liver AGT activity, and pyridoxine responsiveness, were performed. Both mutant alleles were found in 21 out of 23 patients, and 13 different mutations were recognized in exons 1, 2, 4, and 10. Normalized AGT activity was lower in the severe form than in the adult form (P < 0.05). Double heterozygous patients presented a lower age at the onset of the disease (P = 0.025), and they were more frequent in group A (75%) than in the group B (14%; P = 0.0406). The T444C mutation was more frequent in the severe form (P < 0.05), and the opposite was observed for G630A (P < 0.05). G630A mutation homozygotes had a higher AGT residual activity (P = 0.00001). This study confirms the allelic heterogeneity of the AGXT, which could to some extent be responsible for the phenotypic heterogeneity in PH1.

Leishmania (Viannia) guyanensis in tegumentary leishmaniasis.

PubMed

Borges, Arissa Felipe; Gomes, Rodrigo Saar; Ribeiro-Dias, Fátima

2018-06-01

Leishmania (Viannia) guyanensis is a causal agent of American tegumentary leishmaniasis (ATL). This protozoan has been poorly investigated; however, it can cause different clinical forms of ATL, ranging from a single cutaneous lesion to severe lesions that can lead to destruction of the nasopharyngeal mucosa. L. (V.) guyanensis and the disease caused by this species can present unique aspects revealing the need to better characterize this parasite species to improve our knowledge of the immunopathological mechanisms and treatment options for ATL. The mechanisms by which some patients develop a more severe form of ATL remain unclear. It is known that the host immune profile and parasite factors may influence the clinical manifestations of the disease. Besides intrinsic parasite factors, Leishmaniavirus RNA 1 (LRV1) infecting L. guyanensis can contribute to ATL immunopathogenesis. In this review, general aspects of L. guyanensis infection in humans and mouse models are presented.

Thalassaemia.

PubMed

Taher, Ali T; Weatherall, David J; Cappellini, Maria Domenica

2018-01-13

Inherited haemoglobin disorders, including thalassaemia and sickle-cell disease, are the most common monogenic diseases worldwide. Several clinical forms of α-thalassaemia and β-thalassaemia, including the co-inheritance of β-thalassaemia with haemoglobin E resulting in haemoglobin E/β-thalassaemia, have been described. The disease hallmarks include imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic haemolytic anaemia, compensatory haemopoietic expansion, hypercoagulability, and increased intestinal iron absorption. The complications of iron overload, arising from transfusions that represent the basis of disease management in most patients with severe thalassaemia, might further complicate the clinical phenotype. These pathophysiological mechanisms lead to an array of clinical manifestations involving numerous organ systems. Conventional management primarily relies on transfusion and iron-chelation therapy, as well as splenectomy in specific cases. An increased understanding of the molecular and pathogenic factors that govern the disease process have suggested routes for the development of new therapeutic approaches that address the underlying chain imbalance, ineffective erythropoiesis, and iron dysregulation, with several agents being evaluated in preclinical models and clinical trials. Copyright © 2018 Elsevier Ltd. All rights reserved.

Behavioral aspects of clinical trials. An integrated framework from behavior theory.

PubMed

Morrow, G R; Hickok, J T; Burish, T G

1994-11-01

A less-than-optimal proportion of patients with cancer are entered into National Cancer Institute-sponsored clinical trials. This article reviews the literature on accrual in oncology clinical trials to characterize the extent of the problem, identify reasons for low accrual, and suggest ways to promote accrual. Four well known theories of health behavior (the Health Belief Model, Subjective Expected Utility Theory, Protection Motivation Theory, and the Theory of Reasoned Action) point to central concepts involved in understanding patient health-related behavior: (1) the probability that an unwelcomed health event will happen to a patient, (2) the severity of that event if it does occur, (3) the effectiveness of a particular behavior (such as taking part in a clinical trial) to modify the severity, and (4) the cost of adopting that behavior. These concepts form a framework for integrating the available information about accrual to clinical oncology trials. Patient and physician factors previously related to clinical trials suggest specific recommendations for increasing accrual to clinical oncology trials.

[Therapeutic bacterial vaccine Immunovac in complex treatment of patients with chronic pyoderma].

PubMed

Sorokina, E V; Masiukova, S A; Kurbatova, E A; Egorova, N B

2010-01-01

Assessment of therapeutic effect and immunologic parameters during use of Immunovac vaccine for complex treatment of chronic forms of pyoderma. Ninety-five patients with different clinical forms of chronic pyoderma (furunculosis, hydradenitis, chronic ulcerative and ulcerative-vegetans pyoderma, folliculitis, impetigo etc.) were studied. Fifty-nine patients received immunotherapy with Immunovac vaccine together with basic therapy and 36 patients comprised control group treated only with basic therapy. Studied immunologic parameters were as follows: assessment of functional activity of lymphocytes, determination of lymphocyte subpopulations by flow cytometry, total immunoglobulins classes A, G, M by radial immunoduffusion, affinity of antibodies by enzyme immunoassay, levels of IFNalpha and IFNgamma. Use of Immunovac vaccine in complex treatment of patients with chronic forms of pyoderma enhanced clinical effect of basic therapy, which expressed in decrease of severity and frequency of disease relapses irrespective to clinical form and severity of pyoderma. Therapeutic effect during use of Immunovac vaccine amounted 84.7%, whereas in control group it was 41.6% after 12 months of follow-up. Increase of functional activity of neutrophils, subpopulation of lymphocytes with markers CD4+, CD8+, CD72+, affinity of antibodies as well as induced production of IFNalpha and IFNgamma was revealed. Correction of immunologic parameters correlated with positive results of patients treatment. Inclusion of bacterial polycomponent vaccine Immunovac in complex treatment of patients with chronic pyoderma promotes enhancement of therapeutic effect of basic therapy and correction of immunologic parameters.

Next-Generation of Allergen-Specific Immunotherapies: Molecular Approaches.

PubMed

Curin, Mirela; Khaitov, Musa; Karaulov, Alexander; Namazova-Baranova, Leyla; Campana, Raffaela; Garib, Victoria; Valenta, Rudolf

2018-06-09

The aim of this article is to discuss how allergen-specific immunotherapy (AIT) can be improved through molecular approaches. We provide a summary of next-generation molecular AIT approaches and of their clinical evaluation. Furthermore, we discuss the potential of next generation molecular AIT forms for the treatment of severe manifestations of allergy and mention possible future molecular strategies for the secondary and primary prevention of allergy. AIT has important advantages over symptomatic forms of allergy treatment but its further development is limited by the quality of the therapeutic antigen preparations which are derived from natural allergen sources. The field of allergy diagnosis is currently undergoing a dramatic improvement through the use of molecular testing with defined, mainly recombinant allergens which allows high-resolution diagnosis. Several studies demonstrate that molecular testing in early childhood can predict the development of symptomatic allergy later on in life. Clinical studies indicate that molecular AIT approaches have the potential to improve therapy of allergic diseases and may be used as allergen-specific forms of secondary and eventually primary prevention for allergy.

Inverse association between CSF Aβ 42 levels and years of education in mild form of Alzheimer's disease: the cognitive reserve theory.

PubMed

Dumurgier, Julien; Paquet, Claire; Benisty, Sarah; Kiffel, Claire; Lidy, Claude; Mouton-Liger, François; Chabriat, Hugues; Laplanche, Jean-Louis; Hugon, Jacques

2010-11-01

In Alzheimer's disease (AD), the cognitive reserve theory predicts that at any level of assessed clinical severity, the underlying brain pathology is more advanced in patients with more cognitive reserve. Recent evidences suggest that cerebrospinal fluid (CSF) biomarkers may reflect the brain pathology in AD. We investigated the relationship between education level and CSF concentrations of β-amyloid, total tau and phosphorylated tau (ptau-181) in a cohort of 70 subjects newly diagnosed with AD. We report that CSF concentration of β-amyloid was inversely associated with years of education, after adjustment for age, sex, and severity of the disease. We further demonstrate in stratified analysis that this relation was mainly present in mild form of the disease (CDR1), and was attenuated in more advanced forms of the disease. These results are consistent with the cognitive reserve theory, and suggest that cognitive reserve may be protective against amyloid related cognitive impairment at the onset of the clinical dementia. Copyright © 2010 Elsevier Inc. All rights reserved.

Osteomalacia with low alkaline phosphatase: a not so rare condition with important consequences.

PubMed

Belkhouribchia, Jamal; Bravenboer, Bert; Meuwissen, Marije; Velkeniers, Brigitte

2016-01-28

Hypophosphatasia is a genetic disorder, characterised by a dysfunctional tissue-non-specific isoenzyme of alkaline phosphatase that impacts bone metabolism and predisposes to osteomalacia or rickets. The clinical presentation is very diverse, depending on the age of onset and the severity of the disease. Several forms of hypophosphatasia are recognised. We present a case of a 50-year-old woman with low impact fractures and loss of teeth at a young age. She also had a low alkaline phosphatase and was diagnosed with adult hypophosphatasia. Although the severe forms of hypophosphatasia are rather rare, the adult form is thought to occur quite frequently. As this condition is not well known by healthcare professionals, the time to diagnosis and initiation of adequate treatment is often postponed. When encountering a patient with low alkaline phosphatase, low bone density or a history of bone fractures, the possibility of hypophosphatasia should be considered. 2016 BMJ Publishing Group Ltd.

Platelet-rich plasma and plantar fasciitis.

PubMed

Monto, Raymond R

2013-12-01

Plantar fasciitis is the most common cause of heel pain and can prove difficult to treat in its most chronic and severe forms. Advanced cases of plantar fasciitis are often associated with ankle stiffness, heel spurs, and other conditions and can lead to extensive physical disability and financial loss. Most available traditional treatments, including orthoses, nonsteroidal anti-inflammatory drugs, and steroid injections have a paucity of supportive clinical evidence. More invasive treatments, ranging from corticosteroid and botulinum-A toxin injections to shockwave therapy and plantar fasciotomy, have demonstrated varying clinical success in severe cases but carry the potential for serious complication and permanent disability. Platelet-rich plasma has recently been demonstrated to be helpful in managing chronic severe tendinopathies when other techniques have failed. This review examines the pathophysiology, diagnostic options, nonoperative treatment modalities, and surgical options currently used for plantar fasciitis. It also focuses on the clinical rationale and available evidence for using autologous platelet-rich plasma to treat severe refractory chronic plantar fasciitis.

Isolated p.H62L Mutation in the CYP21A2 Gene in a Simple Virilizing 21-Hydroxylase Deficient Patient

PubMed Central

Fernández, Cecilia; Belli, Susana; Buzzalino, Noemi; Dain, Liliana

2013-01-01

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency accounts for 90%–95% of cases. This autosomal recessive disorder has a broad spectrum of clinical forms, ranging from severe or classical, which includes the salt-wasting and simple virilizing forms, to the mild late onset or nonclassical form. Most of the disease-causing mutations described are likely to be the consequence of nonhomologous recombination or gene conversion events between the active CYP21A2 gene and its homologous CYP21A1P pseudogene. Nevertheless, an increasing number of naturally occurring mutations have been found. The change p.H62L is one of the most frequent rare mutations of the CYP21A2 gene. It was suggested that the p.H62L represents a mild mutation that may be responsible for a more severe enzymatic impairment when presented with another mild mutation on the same allele. In this report, a 20-year-old woman carrying an isolated p.H62L mutation in compound heterozygosity with c.283-13A/C>G mutation is described. Although a mildly nonclassical phenotype was expected, clinical signs and hormonal profile of the patient are consistent with a more severe simple virilizing form of 21-hydroxylase deficiency. The study of genotype-phenotype correlation in additional patients would help in defining the role of p.H62L in disease manifestation. PMID:23936690

Isolated p.H62L Mutation in the CYP21A2 Gene in a Simple Virilizing 21-Hydroxylase Deficient Patient.

PubMed

Taboas, Melisa; Fernández, Cecilia; Belli, Susana; Buzzalino, Noemi; Alba, Liliana; Dain, Liliana

2013-01-01

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency accounts for 90%-95% of cases. This autosomal recessive disorder has a broad spectrum of clinical forms, ranging from severe or classical, which includes the salt-wasting and simple virilizing forms, to the mild late onset or nonclassical form. Most of the disease-causing mutations described are likely to be the consequence of nonhomologous recombination or gene conversion events between the active CYP21A2 gene and its homologous CYP21A1P pseudogene. Nevertheless, an increasing number of naturally occurring mutations have been found. The change p.H62L is one of the most frequent rare mutations of the CYP21A2 gene. It was suggested that the p.H62L represents a mild mutation that may be responsible for a more severe enzymatic impairment when presented with another mild mutation on the same allele. In this report, a 20-year-old woman carrying an isolated p.H62L mutation in compound heterozygosity with c.283-13A/C>G mutation is described. Although a mildly nonclassical phenotype was expected, clinical signs and hormonal profile of the patient are consistent with a more severe simple virilizing form of 21-hydroxylase deficiency. The study of genotype-phenotype correlation in additional patients would help in defining the role of p.H62L in disease manifestation.

Mercury Toxicity and Treatment: A Review of the Literature

PubMed Central

Bernhoft, Robin A.

2012-01-01

Mercury is a toxic heavy metal which is widely dispersed in nature. Most human exposure results from fish consumption or dental amalgam. Mercury occurs in several chemical forms, with complex pharmacokinetics. Mercury is capable of inducing a wide range of clinical presentations. Diagnosis of mercury toxicity can be challenging but can be obtained with reasonable reliability. Effective therapies for clinical toxicity have been described. PMID:22235210

[Radon therapy in medical rehabilitation of patents with seronegative spondyloatrthritis. An open controlled study].

PubMed

Barnatskiĭ, V V

2009-01-01

A differential approach to the use of selected methods of radon therapy (including dry air and water baths with different radon concentrations) is proposed for the treatment of different nosological forms of seronegative spondyloarthritis taking into consideration their varying clinical manifestations (arthritis, enthesitis, spondylitis), the degree of general clinical activity, functional state, and severity of inflammation (based on laboratory analyses).

IL-1β, IL-6, and RANTES as Biomarkers of Chikungunya Severity

PubMed Central

Sun, Yong-Jiang; Kwek, Dyan J. C.; Lim, Poh-Lian; Dimatatac, Frederico; Ng, Lee-Ching; Ooi, Eng-Eong; Choo, Khar-Heng; Her, Zhisheng; Kourilsky, Philippe; Leo, Yee-Sin

2009-01-01

Background Little is known about the immunopathogenesis of Chikungunya virus. Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity. Methods and Findings Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study. Plasma fractions were analyzed using a multiplex-microbead immunoassay. Among the patients, the most common clinical features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis (40%). Profiles of 30 cytokines, chemokines, and growth factors were able to discriminate the clinical forms of Chikungunya from healthy controls, with patients classified as non-severe and severe disease. Levels of 8 plasma cytokines and 4 growth factors were significantly elevated. Statistical analysis showed that an increase in IL-1β, IL-6 and a decrease in RANTES were associated with disease severity. Conclusions This is the first comprehensive report on the production of cytokines, chemokines, and growth factors during acute Chikungunya virus infection. Using these biomarkers, we were able to distinguish between mild disease and more severe forms of Chikungunya fever, thus enabling the identification of patients with poor prognosis and monitoring of the disease. PMID:19156204

The functional consequences of mis-sense mutations affecting an intra-molecular salt bridge in arylsulphatase A.

PubMed Central

Schestag, Frank; Yaghootfam, Afshin; Habetha, Matthias; Poeppel, Peter; Dietz, Frank; Klein, Roger A; Zlotogora, Joel; Gieselmann, Volkmar

2002-01-01

Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulphatase A. We describe the functional consequences of three mis-sense mutations in the arylsulphatase A gene (Asp-335-Val, Arg-370-Trp and Arg-370-Gln), affecting an apparent intramolecular Asp-335 to Arg-370 salt bridge, and interpret the effects and clinical consequences on the basis of the three-dimensional structure of arylsulphatase A. Asp-335-Val and Arg-370-Trp substitutions each cause a complete loss of enzyme activity and are associated with the most severe form of the human disease, whereas the Arg-370-Gln-substituted enzyme retains some residual activity, being found in a patient suffering from the milder juvenile form of the disease. Detailed analysis reveals that formation of the apparent salt bridge depends critically on the presence of aspartic acid and arginine residues at positions 335 and 370, respectively. Substitution by various other amino acids, including glutamic acid and lysine, affects enzyme function severely. Biosynthesis and immunoprecipitation studies indicate that the Asp-335-Val substitution affects folding of arylsulphatase A more severely than either the Arg-370-Trp or Arg-370-Gln substitutions. In vitro mutagenesis data show that clinical severity correlates with the space occupied by residue 370. The combination with structural data suggests that the bulky tryptophan residue broadens the cleft held together by the apparent salt bridge, whereas the smaller glutamine residue still allows the cleft to close, yielding a less severely affected enzyme. The position of residue 370 in the three-dimensional structure of the enzyme provides a plausible explanation for the differing severities in loss of enzyme function caused by the mutations and thus the clinical phenotype. PMID:12086582

What Does the Term "Clinical Depression" Mean?

MedlinePlus

... more-severe form of depression, also known as major depression or major depressive disorder. It isn't the same as depression caused ... many doctors use the symptom criteria for major depressive disorder in the Diagnostic and Statistical Manual of Mental ...

[Osteogenesis imperfecta. Clinical, functional and multidisciplinary evaluation of 65 patients].

PubMed

Fano, V; Rodríguez Celin, M; Del Pino, M; Buceta, S; Obregón, M G; Primomo, C; García, H; Miscione, H; Lejarraga, H

2010-05-01

Osteogenesis Imperfecta (OI) is a genetic disease, in which the main clinical features are increased bone fragility, pathological fractures, blue sclera, dentinogenesis imperfecta and conductive or mixed hearing loss. Clinical variability is wide. Although there is no curative treatment, there are several therapeutic tools capable of improving the course of the condition and patient quality of life. Sixty-five children seen in a Paediatric Hospital during six months in 2007 were evaluated. Thirty-five were type I OI, and thirty were types III-IV. Median age was 7.8 years (range 1.9-19.2); mean length of follow up was 4.7 years. The majority of children attended regular school for their corresponding age. Mean height was -1.4 sDS and -5.64 sDS in types I and III-IV respectively. Nineteen percent of patients were overweight and 11% were obese. Mean age at first orthopaedic surgery inserting telescopic rods was 6.5 years. Scoliosis was present in 44.6% of patients and was directly related to severity. Bleck's motor scale showed that 93% of patients with mild forms and 29% of severe forms had a sustainable walking ability. A wheelchair was used by 25% of patients. Family inheritance was confirmed in 65% of cases. Integral care using a multidisciplinary approach is required due to the complexity and clinical variability of the condition. Copyright 2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Third wave of African swine fever infection in Armenia: Virus demonstrates the reduction of pathogenicity

PubMed Central

Sargsyan, M. A.; Voskanyan, H. E.; Karalova, E. M.; Hakobyan, L. H.; Karalyan, Z. A.

2018-01-01

Aim: First cases of clinically uncommon African swine fever (ASF), caused by virus genotype II are described in this article. These cases occurred in Armenia, Tavush region, Dilijan municipality in 2011. The aim of this study was to identify and describe the new pathogenic forms of ASF in Armenia. Materials and Methods: The isolation and identification of ASF virus (ASFV) were carried out using conventional techniques. Clinical signs of infection were recorded daily. Gross anatomical pathology characteristics were observed during routine postmortem examinations. Blood and serum were obtained by puncture of the jugular vein using a vacutainer system. Results: The presence of ASFV DNA in the spleens was confirmed by polymerase chain reaction. Sequenced sections of p72 showed phylogenetic identity to genotype 2. The pathology exhibits unusual manifestations of the main disease. The unusual form of ASF demonstrates characteristics of a subacute form of the disease, with the possibility of conversion to a chronic form. Decreased lethality, low level of hemorrhages, and absence of severe pancytopenia in smears from spleen, lymph nodes, and blood are common features of the new form of ASF. Unlike severe thrombocytopenia in the typical ASF, the unusual form exhibited moderate or minor decrease of this feature. Despite a moderate decrease in hemadsorption titers, the unusual pattern of the disease was characterized by viremia and the presence of the virus in the visceral organs, including the brain. Conclusion: Our data allow assuming that new nosological form of ASF (genotype II) may present as a transitional form of the disease with the possibility of chronization. PMID:29479149

Validity and Reliability of the Turkish version of DSM-5 Social Anxiety Disorder Severity Scale- Child Form.

PubMed

Yalin Sapmaz, Şermin; Ergin, Dilek; Şen Celasin, Nesrin; Karaarslan, Duygu; Öztürk, Masum; Özek Erkuran, Handan; Köroğlu, Ertuğrul; Aydemir, Ömer

2017-12-01

This study aimed to assess the validity and reliability of the Turkish version of the Diagnostic and statistical manual of Mental Disorders. (5 th ed.) (DSM-5) Social Anxiety Disorder Severity Scale- Child Form. The scale was prepared by carrying out the translation and back translation of the DSM-5 Social Anxiety Disorder Severity Scale - Child Form. The study group consisted of 31 patients that had been treated in a child psychiatry unit and diagnosed with social anxiety disorder and 99 healthy volunteers that were attending middle or high school during the study period. For the assessment, the Screen for Child Anxiety and Related Emotional Disorders (SCARED) was also used along with the DSM-5 Social Anxiety Disorder Severity Scale - Child Form. Regarding reliability analyses, Cronbach's alpha internal consistency coefficient was calculated as 0.941, while item-total score correlation coefficients were measured between 0.566 and 0.866. A test-retest correlation coefficient was calculated as r=0.711. As for construct validity, one factor that could explain 66.0 % of the variance was obtained. As for concurrent validity, the scale showed a high correlation with the SCARED. It was concluded that the Turkish version of the DSM-5 Social Anxiety Disorder Severity Scale - Child Form could be utilized as a valid and reliable tool both in clinical practice and for research purposes.

Use of biologics in severe food allergies.

PubMed

Fiocchi, Alessandro; Pecora, Valentina; Valluzzi, Rocco L; Fierro, Vincenzo; Mennini, Maurizio

2017-06-01

Severe cases of food allergy account for the majority of the burden in terms of risks, quality of life, and resource expenditure. The traditional approach to these forms has been strict avoidance. More recently, Oral ImmunoTherapy (OIT) has gained a role in their management. However, in severe food allergies OIT is often infeasible. Case reports, observational, and prospective studies have recently proposed different approaches to severe food allergy. The majority of them include the use of biologics. Omalizumab has been the most studied drug for severe food allergies, and its role as adjuvant treatment to OIT is well established. Interest has been raised on other biologics, as dupilumab, reslizumab, and mepolizumab. Toll-like receptor agonists, and gene therapy using adeno-associated virus coding for Omalizumab are promising alternatives. The recent studies are deeply influencing the clinical practice. We review the modifications of the clinical approach to severe food allergies so far available. We indicate the possible evolutions of treatment with biologics in severe food allergies.

Clinical outcomes of isolated renal failure compared to other forms of organ failure in patients with severe acute pancreatitis.

PubMed

Gougol, Amir; Dugum, Mohannad; Dudekula, Anwar; Greer, Phil; Slivka, Adam; Whitcomb, David C; Yadav, Dhiraj; Papachristou, Georgios I

2017-08-07

To assess differences in clinical outcomes of isolated renal failure (RF) compared to other forms of organ failure (OF) in patients with severe acute pancreatitis (SAP). Using a prospectively maintained database of patients with acute pancreatitis admitted to a tertiary medical center between 2003 and 2016, those with evidence of persistent OF were classified to renal, respiratory, cardiovascular, or multi-organ (2 or more organs). Data regarding demographics, comorbidities, etiology of acute pancreatitis, and clinical outcomes were prospectively recorded. Differences in clinical outcomes after development of isolated RF in comparison to other forms of OF were determined using independent t and Mann-Whitney U tests for continues variables, and χ 2 test for discrete variables. Among 500 patients with acute pancreatitis, 111 patients developed persistent OF: mean age was 54 years, and 75 (67.6%) were male. Forty-three patients had isolated OF: 17 (15.3%) renal, 25 (21.6%) respiratory, and 1 (0.9%) patient with cardiovascular failure. No differences in demographics, etiology of acute pancreatitis, systemic inflammatory response syndrome scores, or development of pancreatic necrosis were seen between patients with isolated RF vs isolated respiratory failure. Patients with isolated RF were less likely to require nutritional support (76.5% vs 96%, P = 0.001), ICU admission (58.8% vs 100%, P = 0.001), and had shorter mean ICU stay (2.4 d vs 15.7 d, P < 0.001), compared to isolated respiratory failure. None of the patients with isolated RF or isolated respiratory failure died. Among patients with SAP per the Revised Atlanta Classification, approximately 15% develop isolated RF. This subgroup seems to have a less protracted clinical course compared to other forms of OF. Isolated RF might be weighed less than isolated respiratory failure in risk predictive modeling of acute pancreatitis.

The Staff Observation Aggression Scale - Revised (SOAS-R) - adjustment and validation for emergency primary health care.

PubMed

Morken, Tone; Baste, Valborg; Johnsen, Grethe E; Rypdal, Knut; Palmstierna, Tom; Johansen, Ingrid Hjulstad

2018-05-08

Many emergency primary health care workers experience aggressive behaviour from patients or visitors. Simple incident-reporting procedures exist for inpatient, psychiatric care, but a similar and simple incident-report for other health care settings is lacking. The aim was to adjust a pre-existing form for reporting aggressive incidents in a psychiatric inpatient setting to the emergency primary health care settings. We also wanted to assess the validity of the severity scores in emergency primary health care. The Staff Observation Scale - Revised (SOAS-R) was adjusted to create a pilot version of the Staff Observation Scale - Revised Emergency (SOAS-RE). A Visual Analogue Scale (VAS) was added to the form to judge the severity of the incident. Data for validation of the pilot version of SOAS-RE were collected from ten casualty clinics in Norway during 12 months. Variance analysis was used to test gender and age differences. Linear regression analysis was performed to evaluate the relative impact that each of the five SOAS-RE columns had on the VAS score. The association between SOAS-RE severity score and VAS severity score was calculated by the Pearson correlation coefficient. The SOAS-R was adjusted to emergency primary health care, refined and called The Staff Observation Aggression Scale - Revised Emergency (SOAS-RE). A total of 350 SOAS-RE forms were collected from the casualty clinics, but due to missing data, 291 forms were included in the analysis. SOAS-RE scores ranged from 1 to 22. The mean total severity score of SOAS-RE was 10.0 (standard deviation (SD) =4.1) and the mean VAS score was 45.4 (SD = 26.7). We found a significant correlation of 0.45 between the SOAS-RE total severity scores and the VAS severity ratings. The linear regression analysis showed that individually each of the categories, which described the incident, had a low impact on the VAS score. The SOAS-RE seems to be a useful instrument for research, incident-recording and management of incidents in emergency primary care. The moderate correlation between SOAS-RE severity score and the VAS severity score shows that application of both the severity ratings is valuable to follow-up of workers affected by workplace violence.

A Heads-Up Display for Diabetic Limb Salvage Surgery

PubMed Central

Rankin, Timothy M.; Giovinco, Nicholas A.; Mills, Joseph L.; Matsuoka, Yoky

2014-01-01

Although the use of augmented reality has been well described over the past several years, available devices suffer from high cost, an uncomfortable form factor, suboptimal battery life, and lack an app-based developer ecosystem. This article describes the potential use of a novel, consumer-based, wearable device to assist surgeons in real time during limb preservation surgery and clinical consultation. Using routine intraoperative, clinical, and educational case examples, we describe the use of a wearable augmented reality device (Google Glass; Google, Mountain View, CA). The device facilitated hands-free, rapid communication, documentation, and consultation. An eyeglass-mounted screen form factor has the potential to improve communication, safety, and efficiency of intraoperative and clinical care. We believe this represents a natural progression toward union of medical devices with consumer technology. PMID:24876445

Metabolomic changes in serum of children with different clinical diagnoses of malnutrition

USDA-ARS?s Scientific Manuscript database

Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and ...

Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry

PubMed Central

Ortiz, Alberto; Abiose, Ademola; Bichet, Daniel G; Cabrera, Gustavo; Charrow, Joel; Germain, Dominique P; Hopkin, Robert J; Jovanovic, Ana; Linhart, Aleš; Maruti, Sonia S; Mauer, Michael; Oliveira, João P; Patel, Manesh R; Politei, Juan; Waldek, Stephen; Wanner, Christoph; Yoo, Han-Wook; Warnock, David G

2016-01-01

Background Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a ‘lag time’ to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β. Methods The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase β (average dose 1 mg/kg every 2 weeks) for up to 5 years. Results The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40–58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged ≥40 years when agalsidase β was initiated. Conclusions Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase β 1 mg/kg every 2 weeks. Trial registration number NCT00196742. PMID:26993266

Parents who hit and scream: interactive effects of verbal and severe physical aggression on clinic-referred adolescents' adjustment.

PubMed

LeRoy, Michelle; Mahoney, Annette; Boxer, Paul; Gullan, Rebecca Lakin; Fang, Qijuan

2014-05-01

The goals of this study were first, to delineate the co-occurrence of parental severe physical aggression and verbal aggression toward clinic-referred adolescents, and second, to examine the interactive effects of parental severe physical aggression and verbal aggression on adolescent externalizing and internalizing behavior problems. This research involved 239 referrals of 11- to 18-year-old youth and their dual-parent families to a non-profit, private community mental health center in a semi-rural Midwest community. Multiple informants (i.e., adolescents and mothers) were used to assess parental aggression and adolescent behavior problems. More than half of clinic-referred adolescents (51%) experienced severe physical aggression and/or high verbal aggression from one or both parents. A pattern of interactive effects of mother-to-adolescent severe physical aggression and verbal aggression on adolescent behavior problems emerged, indicating that when severe physical aggression was present, mother-to-adolescent verbal aggression was positively associated with greater adolescent behavior problems whereas when severe physical aggression was not present, the links between verbal aggression and behavior problems was no longer significant. No interactive effects were found for father-to-adolescent severe physical aggression and verbal aggression on adolescent adjustment; however, higher father-to-adolescent verbal aggression was consistently linked to behavior problems above and beyond the influence of severe physical aggression. The results of this study should promote the practice of routinely assessing clinic-referred adolescents and their parents about their experiences of verbal aggression in addition to severe physical aggression and other forms of abuse. Copyright © 2013 Elsevier Ltd. All rights reserved.

Affective lability mediates the association between childhood trauma and suicide attempts, mixed episodes and co-morbid anxiety disorders in bipolar disorders.

PubMed

Aas, M; Henry, C; Bellivier, F; Lajnef, M; Gard, S; Kahn, J-P; Lagerberg, T V; Aminoff, S R; Bjella, T; Leboyer, M; Andreassen, O A; Melle, I; Etain, B

2017-04-01

Many studies have shown associations between a history of childhood trauma and more severe or complex clinical features of bipolar disorders (BD), including suicide attempts and earlier illness onset. However, the psychopathological mechanisms underlying these associations are still unknown. Here, we investigated whether affective lability mediates the relationship between childhood trauma and the severe clinical features of BD. A total of 342 participants with BD were recruited from France and Norway. Diagnosis and clinical characteristics were assessed using the Diagnostic Interview for Genetic Studies (DIGS) or the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Affective lability was measured using the short form of the Affective Lability Scale (ALS-SF). A history of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Mediation analyses were performed using the SPSS process macro. Using the mediation model and covariation for the lifetime number of major mood episodes, affective lability was found to statistically mediate the relationship between childhood trauma experiences and several clinical variables, including suicide attempts, mixed episodes and anxiety disorders. No significant mediation effects were found for rapid cycling or age at onset. Our data suggest that affective lability may represent a psychological dimension that mediates the association between childhood traumatic experiences and the risk of a more severe or complex clinical expression of BD.

[Smallpox, bioterrorism agent].

PubMed

Bossi, Philippe; Bricaire, François

2002-11-30

A CONSIDERABLE RISK: Among the infectious agents that might be used as terrorist weapons, the smallpox virus represents a sufficiently high risk, which is difficult to manage and must be seriously taken into account. Two viral strains of the smallpox virus, which belong to the Poxviridae and orthopoxvirus-type families, are known. They are associated with various clinical presentations of smallpox, i.e., variola major and variola minor or "alastrim". Five clinical forms of varying prognosis are described. Common smallpox, haemorrhagic smallpox (the most severe form of the disease), mild smallpox (predominantly observed in vaccinated patients), flat-type smallpox (defined by coalescent and slowly progressive lesions) and so-called "sine eruptione" smallpox. This form is not as severe as variola major and the mortality rate is lesser. Smallpox must be systematically evoked on clinical elements and confirmed by electronic microscopy of a sample of liquid from a vesicle or pustule or a scab. The strains can be characterised by PCR (Polymerase Chain Reaction). It is symptomatic. Early vaccination, within 4 days following exposure to the virus, permits the reduction in mortality by 50%. The only efficient prevention is vaccination prior to any exposure to the virus. In the case of a bioterrorist attack, the United States and most of the EC countries propose to vaccinate only the health professionnals most exposed to the virus and those having contacted identified cases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hart, Y.M.; Andermann, E.; Mitchison, H.M.

The neuronal ceroid lipofuscinoses (NCL) are a group of related lysosomal storage diseases classified according to the age of onset, clinical syndrome, and pathology. The clinical syndromes include myoclonus, visual failure, progressive dementia, ataxia and generalized tonic clonic seizures in varying combinations depending on the age of onset and pathology. The mode of inheritance is autosomal recessive in most cases, except for several families with the adult form (Kufs` disease) which have autosomal dominant inheritance. Linkage for the infantile (Halatia-Santavuori) form (CLN1), characterized ultrastructurally by lysosomal granular osmiophilic deposits (GROD), has been demonstrated with markers on chromosome lp, while themore » gene for the typical juvenile (Spielmeyer-Vogt) form (CLN3), characterized by fingerprint-profile inclusions, has been linked to chromosome 16p. The gene locations of the late infantile (Jansky-Bielschowsky) and adult (Kufs` disease) forms are unknown, although it has recently been shown that the late infantile form does not link to chromosome 16p. We describe three siblings, including a pair of monozygotic twins, with juvenile onset NCL with GROD in whom linkage to the CLN3 region of chromsome 16p has been excluded. This would suggest that there is genetic heterogeneity not only among the different clinical syndromes, but also among identical clinical syndromes with different ultrastructural characteristics. Preliminary studies of linkage to chromosome 1p employing the microsatellite marker HY-TM1 have been uninformative. Further studies with other chromosome 1 markers are underway.« less

Molecular and clinical characterization of the myopathic form of mitochondrial DNA depletion syndrome caused by mutations in the thymidine kinase (TK2) gene.

PubMed

Chanprasert, Sirisak; Wang, Jing; Weng, Shao-Wen; Enns, Gregory M; Boué, Daniel R; Wong, Brenda L; Mendell, Jerry R; Perry, Deborah A; Sahenk, Zarife; Craigen, William J; Alcala, Francisco J Climent; Pascual, Juan M; Melancon, Serge; Zhang, Victor Wei; Scaglia, Fernando; Wong, Lee-Jun C

2013-01-01

Mitochondrial DNA (mtDNA) depletion syndromes (MDSs) are a clinically and molecularly heterogeneous group of mitochondrial cytopathies characterized by severe mtDNA copy number reduction in affected tissues. Clinically, MDSs are mainly categorized as myopathic, encephalomyopathic, hepatocerebral, or multi-systemic forms. To date, the myopathic form of MDS is mainly caused by mutations in the TK2 gene, which encodes thymidine kinase 2, the first and rate limiting step enzyme in the phosphorylation of pyrimidine nucleosides. We analyzed 9 unrelated families with 11 affected subjects exhibiting the myopathic form of MDS, by sequencing the TK2 gene. Twelve mutations including 4 novel mutations were detected in 9 families. Skeletal muscle specimens were available from 7 out of 11 subjects. Respiratory chain enzymatic activities in skeletal muscle were measured in 6 subjects, and enzymatic activities were reduced in 3 subjects. Quantitative analysis of mtDNA content in skeletal muscle was performed in 5 subjects, and marked mtDNA content reduction was observed in each. In addition, we outline the molecular and clinical characteristics of this syndrome in a total of 52 patients including those previously reported, and a total of 36 TK2 mutations are summarized. Clinically, hypotonia and proximal muscle weakness are the major phenotypes present in all subjects. In summary, our study expands the molecular and clinical spectrum associated with TK2 deficiency. © 2013.

Evaluation of in-house ELISA using Trypanosoma cruzi lysate and recombinant antigens for diagnosis of Chagas disease and discrimination of its clinical forms.

PubMed

Longhi, Silvia A; Brandariz, Silvia B; Lafon, Sonia O; Niborski, Leticia L; Luquetti, Alejandro O; Schijman, Alejandro G; Levin, Mariano J; Gómez, Karina A

2012-08-01

The aim of this work was to investigate the potential usefulness of Trypanosoma cruzi lysate, recombinant protein JL7, and peptides P013, R13, JL18, JL19, and P0β as serological markers for human Chagas disease. We analyzed 228 sera from Brazilian Chagas disease patients classified into four clinical groups and 108 from non-chagasic patients. We defined the diagnostic sensitivity, specificity, and Kappa index measured by enzyme-linked immunosorbent assay (ELISA). As previously described, the highest values of diagnostic parameters were achieved for T. cruzi lysate and JL7; peptide P013 showed high specificity but low sensitivity. The other peptides resulted in lower sensitivity and specificity in our ELISA than T. cruzi lysate and JL7 protein. Antibodies against JL7 protein were mainly detected in sera from patients with severe chagasic cardiomyopathy, compared with those from the indeterminate form, whereas peptides failed to discriminate between the clinical forms of the disease.

Severe Cutaneous Drug Reactions: Do Overlapping Forms Exist?

PubMed

Horcajada-Reales, C; Pulido-Pérez, A; Suárez-Fernández, R

2016-01-01

Acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms are all severe hypersensitivity reactions to medications. While each of these reactions is a well-established entity with specific diagnostic criteria, clinicians see cases that fulfill criteria for more than one form, prompting discussion on the possibility of combined forms. Such overlapping clinical pictures meeting the criteria for 2 conditions have thus become a topic of debate in dermatology in recent years. We describe 2 patients with cutaneous drug reactions having the characteristics of both acute generalized exanthematous pustulosis and Stevens-Johnson syndrome -toxic epidermal necrolysis. We also review previously published cases and current thinking on such overlapping conditions. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Antisocial personality disorder is on a continuum with psychopathy.

PubMed

Coid, Jeremy; Ullrich, Simone

2010-01-01

Antisocial personality disorder (ASPD) and psychopathy are different diagnostic constructs. It is unclear whether they are separate clinical syndromes or whether psychopathy is a severe form of ASPD. A representative sample of 496 prisoners in England and Wales was interviewed in the second phase of a survey carried out in 1997 using the Schedules for Clinical Assessment in Neuropsychiatry, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis II personality disorders, and the Psychopathy Checklist-Revised. Among those 18 years and older (n = 470), 211 (44.9%) received a diagnosis of ASPD, of whom 67 (31.8%) were classified as psychopaths, indicated by Psychopathy Checklist-Revised scores of 25 and above. Symptoms of ASPD and psychopathy both demonstrated low diagnostic contrast when comparing subgroups of ASPD above and below the cutoff for psychopathy. There were no differences in demography, Axis I comorbidity, and treatment-seeking behavior. Psychopathic individuals with ASPD demonstrated comorbid schizoid and narcissistic personality disorder, more severe conduct disorder and adult antisocial symptoms, and more violent convictions. Psychopathy and ASPD are not separate diagnostic entities, but psychopathic ASPD is a more severe form than ASPD alone with greater risk of violence. Dimensional scores of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition personality disorders (other than ASPD) may be helpful in identifying this specific subgroup. Copyright 2010 Elsevier Inc. All rights reserved.

Vesical Artery Embolization in Haemorrhagic Cystitis in Children

DOE Office of Scientific and Technical Information (OSTI.GOV)

García-Gámez, Andrés, E-mail: agargamez@gmail.com; Bermúdez Bencerrey, Patricia, E-mail: PBERMUDE@clinic.ub.es; Brio-Sanagustin, Sonia, E-mail: sbrio@santpau.cat

Haemorrhagic cystitis is an uncommon and, in its severe form, potentially life-threatening complication of haematopoietic stem cell transplantation or cancer therapy in children. The severe form involves macroscopic haematuria with blood clots, urinary obstruction and/or renal impairment. There are many therapeutic options to treat acute haemorrhage, but only recombinant factor VII has a high level of clinical evidence in children. Supraselective vesical artery embolization (SVAE) is an increasingly used therapeutic procedure for controlling haemorrhage in adults, but is less commonly used in children. This might be due to several factors, such as the invasive nature of the procedure, lack ofmore » appropriate medical experience and possible long-term side effects. We present three cases of children successfully treated by means of effective SVAE.« less

Attenuated variants of Lesch-Nyhan disease

PubMed Central

Ceballos-Picot, Irene; Torres, Rosa J.; Visser, Jasper E.; Schretlen, David J.; Verdu, Alfonso; Laróvere, Laura E.; Chen, Chung-Jen; Cossu, Antonello; Wu, Chien-Hui; Sampat, Radhika; Chang, Shun-Jen; de Kremer, Raquel Dodelson; Nyhan, William; Harris, James C.; Reich, Stephen G.; Puig, Juan G.

2010-01-01

Lesch–Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine–guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the classic disease, variant forms of the disease occur wherein some clinical features are absent or unusually mild. The current studies provide the results of a prospective and multi-centre international study focusing on neurological manifestations of the largest cohort of Lesch–Nyhan disease variants evaluated to date, with 46 patients from 3 to 65 years of age coming from 34 families. All had evidence for overproduction of uric acid. Motor abnormalities were evident in 42 (91%), ranging from subtle clumsiness to severely disabling generalized dystonia. Cognitive function was affected in 31 (67%) but it was never severe. Though none exhibited self-injurious behaviours, many exhibited behaviours that were maladaptive. Only three patients had no evidence of neurological dysfunction. Our results were compared with a comprehensive review of 78 prior reports describing a total of 127 Lesch–Nyhan disease variants. Together these results define the spectrum of clinical features associated with hypoxanthine–guanine phosphoribosyltransferase deficiency. At one end of the spectrum are patients with classic Lesch–Nyhan disease and the full clinical phenotype. At the other end of the spectrum are patients with overproduction of uric acid but no apparent neurological or behavioural deficits. Inbetween are patients with varying degrees of motor, cognitive, or behavioural abnormalities. Recognition of this spectrum is valuable for understanding the pathogenesis and diagnosis of all forms of hypoxanthine–guanine phosphoribosyltransferase deficiency. PMID:20176575

Subjective binge eating with compensatory behaviors: a variant presentation of bulimia nervosa.

PubMed

Watson, Hunna J; Fursland, Anthea; Bulik, Cynthia M; Nathan, Paula

2013-03-01

To determine whether a variant bulimic-type presentation, whereby one meets criteria for bulimia nervosa (BN) except that binge eating episodes are not objectively large (i.e., "subjective bulimia nervosa," SBN), has comparable clinical severity to established eating disorders, particularly BN. Treatment-seeking adults with BN (N = 112), SBN (N = 28), anorexia nervosa restricting type (AN-R) (N = 45), and AN-binge/purge type (AN-B/P) (N = 24) were compared. Overall, SBN could not be meaningfully distinguished from BN. SBN and BN had equivalent eating pathology, depression and anxiety symptoms, low quality of life, impulsivity, Axis I comorbidity, and lifetime psychiatric history, and comparable clinical severity to AN-R and AN-B/P. Individuals with SBN, differing from BN only by the smaller size of their binge eating episodes, had a form of eating disorder comparable in clinical severity to threshold AN and BN and warranting clinical attention. Health professionals and the community require greater awareness of this variant to optimize detection, treatment-seeking, and outcomes. Copyright © 2012 Wiley Periodicals, Inc.

[Congenital myotonic dystrophy in a Neonatal Intensive Care Unit: case series].

PubMed

Domingues, Sara; Alves Pereira, Clara; Machado, Angela; Pereira, Sandra; Machado, Leonilde; Fraga, Carla; Oliveira, Abílio; Vale, Isabel; Quelhas, Ilídio

2014-02-01

Steinert myotonic dystrophy is a multisystemic disease, autosomal dominant, with a wide spectrum of severity and clinical manifestations. The most severe form is one that manifests in the neonatal period, called congenital myotonic dystrophy. This condition is distinguished by overall hypotonia at birth and respiratory function compromise. Complications are frequent, mainly psychomotor development delay, growth failure, food difficulties and constipation. It is associated with a poor prognosis, with an overall mortality of up to 50% of severely affected children. We present five patients with congenital myotonic dystrophy in order to describe clinical manifestations, diagnosis, treatment and prognosis. Existing data in the literature on psychomotor development, complications and prognosis of survivors with congenital myotonic dystrophy are scarce. In our case studies, we have found significant chronic psychomotor limitations.

Hyperemesis gravidarum: a holistic overview and approach to clinical assessment and management.

PubMed

Castillo, Melody J; Phillippi, Julia C

2015-01-01

Hyperemesis gravidarum (HG) is a rare and severe form of nausea and vomiting of pregnancy associated with significant costs and psychosocial impacts. The etiology of HG remains largely unknown, although maternal genetics and placental factors are suspected. Prompt recognition and treatment of HG are essential to minimize associated maternal and fetal morbidity. Diagnosis is made on the basis of typical presentation, with exclusion of other causes of severe nausea and vomiting of pregnancy. Validated clinical tools are available to assess severity of symptoms and guide plans of care. Evidence to guide management of HG is limited, but many nonpharmacologic and pharmacologic interventions are available with published guidelines to inform implementation. Care of the woman with HG requires compassion and acknowledgement of individual needs and responses to interventions.

The clinical features of osteogenesis imperfecta in Vietnam.

PubMed

Binh, Ho Duy; Maasalu, Katre; Dung, Vu Chi; Ngoc, Can T Bich; Hung, Ton That; Nam, Tran V; Nhan, Le N Thanh; Prans, Ele; Reimann, Ene; Zhytnik, Lidiia; Kõks, Sulev; Märtson, Aare

2017-01-01

Osteogenesis imperfecta (OI) has not been studied in a Vietnamese population before. The aim of this study was to systematically collect epidemiological information, investigate clinical features and create a clinical database of OI patients in Vietnam for future research and treatment strategy development. Participants underwent clinical and physical examinations; also medical records were reviewed. Genealogical information was collected and family members' phenotypical manifestations recorded. Cases were classified according to the Sillence classification. In total, 146 OI patients from 120 families were studied: 46 with OI Type I, 46 with Type III and 54 with Type IV. Almost patients had skeletal deformations. One hundred and forty-two had a history of fractures, 117 blue sclera, 89 dentinogenesis imperfecta and 26 hearing loss. The total number of fractures was 1,932. Thirty-four patients had intra-uterine fractures and nine had perinatal fractures. Surgery was performed 163 times in 58 patients; 100 osteosyntheses and 63 osteotomies. Bisphosphonate treatment was used in 37 patients. The number of affected individuals and predominance of severe forms of OI indicate that the disease is under diagnosed in Vietnam, especially in cases without a family history or with mild form of OI. Deformities appeared in all patients with different severity and localisation, affecting mostly the lower limbs. OI medical and surgical treatment rates are low and in most cases surgery was performed due to fractures. Compared to previous studies, our results indicate a lower OI prevalence and greater severity of symptoms in the Vietnamese population when compared with other areas. Further investigation, improved diagnosis and treatment are needed to increase the patients' quality of life.

[Results of the use of pumpan preparation in the treatment of severe forms of angina pectoris].

PubMed

Parshina, S S; Golovacheva, T V; Afanas'eva, T N; Panchenko, O V; Baldina, A A; Starostina, N V; Lial'chenko, I F; Egorova, L P

2000-01-01

To assess validity of adjuvant use of pumpan, a homeopathic compound, in patients with unstable angina pectoris and angina of effort (functional class III-IV) receiving conventional treatment. A direct open controlled trial for 15 months performed initially in hospital, then outpatiently, covered 49 patients with severe angina. Examination of the patients included evaluation of clinical condition and the disease course, lipid metabolism, hemostasis, blood plasma electrolytes, aminotransferases, echo-CG, bicycle exercise, rheoencephalography, ultrasonic dopplerography of head and neck vessels. Pumpan produced a positive effect total nonspecific systemic resistance improved, number of hospitalizations reduced, intracardiac hemodynamics improved in some cases with severe angina. Homeopathic compound pumpan can be recommended in the treatment of severe angina to reinforce antianginal effect, improve the disease clinical course, to obtain a hypocoagulative and hypocholesterolemic effect, to normalize intracardiac hemodynamics, to raise myocardial performance and intracoronary reserve as well as nonspecific resistance of the body.

Premenstrual syndrome and premenstrual dysphoric disorder: definitions and diagnosis.

PubMed

Freeman, Ellen W

2003-08-01

Because of the prevalence, chronicity and distress caused by premenstrual symptoms (PMS), diagnosis and effective treatments are important information for clinicians. The DSM-IV requires at least five specified symptoms for premenstrual dysphoric disorder (PMDD), a severe dysphoric form of PMS, while the ICD-10 requires only one distressing symptom for a diagnosis of PMS. Many women who seek treatment fall between these two diagnostic approaches, and standard diagnostic criteria for clinically significant PMS are needed. A diagnosis of PMS consists of determining the timing of the symptoms in relation to menses, meaningful change between post- and premenstrual symptom severity and a clinically significant severity of the symptoms. A differential diagnosis to distinguish PMS from other medical and psychiatric conditions is important for appropriate treatment. No hormone or laboratory test indicates a PMS diagnosis. The current diagnostic standard requires confirmation of subjective symptom reports by prospective daily diaries. Diagnostic criteria for PMS must recognize the broad range of symptoms, the temporal pattern of the symptoms and the critical issue of symptom severity, which differentiates clinically significant PMS from normal menstrual cycle changes.

Tumor heterogeneity in small cell lung cancer defined and investigated in pre-clinical mouse models

PubMed Central

Shue, Yan Ting; Lim, Jing Shan

2018-01-01

Small cell lung carcinoma (SCLC) is a fast-growing, highly metastatic form of lung cancer. A major difference between SCLC and other forms of lung cancer is that SCLC tumors often respond well to chemotherapy initially; unfortunately, resistant tumors rapidly recur. In addition, despite a large number of clinical trials with a variety of therapeutic agents, little progress has been achieved in the past three decades in improving the survival of SCLC patients. These clinical observations indicate that SCLC tumors have a high degree of plasticity and rapid adaptability to changes in growth conditions. Here we consider recent evidence pointing to several levels of heterogeneity in SCLC that may explain the ability of these tumors to adjust to different microenvironment and therapeutics. In particular, we review new data pointing to the existence of several subpopulations of tumor cells that interact with each other to promote tumor growth. We also discuss how SCLC tumors that look similar at the histopathological level may actually represent distinct subtypes of tumors and how these differences impact the response to specific therapeutic agents. A better understanding of genetic and cellular heterogeneity will guide the development of personalized approaches to help SCLC patients. PMID:29535910

[Bartonella henselae, an ubiquitous agent of proteiform zoonotic disease].

PubMed

Edouard, S; Raoult, D

2010-06-01

Bartonella henselae is the causative agent of cat scratch disease, a human infection usually characterized by persistent regional lymphadenopathy. It is transmitted to humans by cat scratches or bites. Cats are the major reservoir for this bacterium thus B. henselae has a worldwide distribution. The bacterial pathogenicity may bay emphasized by the immune status of the infected host. Angiomatosis or hepatic peliosis are the most frequent clinical manifestations in immunocompromised patients. B. henselae is also responsible for endocarditis in patients with valvular diseases, and may induce various clinical presentations such as: bacteriemia, retinitis, musculoskeletal disorders, hepatic or splenic diseases, encephalitis, or myocarditis. Several diagnostic tools are available; they may be combined and adapted to every clinical setting. B. henselae is a fastidious bacterium; its diagnosis is mainly made by PCR and blood tests. No treatment is required for the benign form of cat scratch disease. For more severe clinical presentations, the treatment must be adapted to every clinical presentation.

Early onset marfan syndrome: Atypical clinical presentation of two cases

PubMed Central

Ozyurt, A; Baykan, A; Argun, M; Pamukcu, O; Halis, H; Korkut, S; Yuksel, Z; Gunes, T; Narin, N

2015-01-01

Early onset Marfan Syndrome (eoMFS) is a rare, severe form of Marfan Syndrome (MFS). The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system. PMID:26929908

Embedding measurement within existing computerized data systems: scaling clinical laboratory and medical records heart failure data to predict ICU admission.

PubMed

Fisher, William P; Burton, Elizabeth C

2010-01-01

This study employs existing data sources to develop a new measure of intensive care unit (ICU) admission risk for heart failure patients. Outcome measures were constructed from laboratory, accounting, and medical record data for 973 adult inpatients with primary or secondary heart failure. Several scoring interpretations of the laboratory indicators were evaluated relative to their measurement and predictive properties. Cases were restricted to tests within first lab draw that included at least 15 indicators. After optimizing the original clinical observations, a satisfactory heart failure severity scale was calibrated on a 0-1000 continuum. Patients with unadjusted CHF severity measures of 550 or less were 2.7 times more likely to be admitted to the ICU than those with higher measures. Patients with low HF severity measures (550 or less) adjusted for demographic and diagnostic risk factors are about six times more likely to be admitted to the ICU than those with higher adjusted measures. A nomogram facilitates routine clinical application. Existing computerized data systems could be programmed to automatically structure clinical laboratory reports using the results of studies like this one to reduce data volume with no loss of information, make laboratory results more meaningful to clinical end users, improve the quality of care, reduce errors and unneeded tests, prevent unnecessary ICU admissions, lower costs, and improve patient satisfaction. Existing data typically examined piecemeal form a coherent scale measuring heart failure severity sensitive to increased likelihood of ICU admission. Marked improvements in ROC curves were found for the aggregate measures relative to individual clinical indicators.

Could intervention by clinics such as Primeros Pasos affect the prevalence of childhood malnutrition in the developing world?

PubMed

Seccombe, Adam; Hughes, Elizabeth

2009-12-01

Guatemala is a country severely affected by malnutrition, particularly in its child population. The present study aimed to assess the impact of recognised aetiological factors on the prevalence of malnutrition and to establish the efficacy of a Guatemalan malnutrition clinic by examining the changes in the prevalence of malnutrition in the ten surrounding communities served by the clinic. Records of children (n 7681) aged 5-16 years seen by the clinic between 2004 and 2006 were examined. Anthropometric data for each child were taken from these records and used as an indicator for their nutritional status to estimate the change in rates of malnutrition during this period. An overall reduction was seen in all forms of malnutrition over the 3-year period, although over 50 % of the study population remained malnourished in 2006. A consistent reduction was also seen in rates of moderate and severe malnutrition, but not in rates of mild malnutrition. The results demonstrate that clinics such as Primeros Pasos can have a beneficial effect on schoolchildren, particularly those who are severely malnourished. A need has been highlighted for more research in this area, particularly how clinics such as Primeros Pasos can be best used in the fight against malnutrition.

Therapeutic risk management of the suicidal patient: augmenting clinical suicide risk assessment with structured instruments.

PubMed

Homaifar, Beeta; Matarazzo, Bridget; Wortzel, Hal S

2013-09-01

This column is the second in a series presenting a model for therapeutic risk management of the suicidal patient. As discussed in the first part of the series, the model involves several elements including augmenting clinical risk assessment with structured instruments, stratifying risk in terms of both severity and temporality, and developing and documenting a safety plan. This column explores in more detail how to augment clinical risk assessment with structured instruments. Unstructured clinical interviews have the potential to miss important aspects of suicide risk assessment. By augmenting the free-form clinical interview with structured instruments that demonstrate reliability and validity, a more nuanced and multifaceted approach to suicide risk assessment is achieved. Incorporating structured instruments into practice also serves a medicolegal function, since these instruments may become a living part of the medical record, establishing baseline levels of suicidal thoughts and behaviors and facilitating future clinical determinations regarding safety needs. We describe several instruments used in a multidisciplinary suicide consultation service, each of which has demonstrated relevance to suicide risk assessment and screening, ease of administration, and strong psychometric properties. In addition, we emphasize the importance of viewing suicide risk assessment as an ongoing process rather than as a singular event. Finally, we discuss special considerations in the evolving practice of risk assessment.

Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry.

PubMed

Ortiz, Alberto; Abiose, Ademola; Bichet, Daniel G; Cabrera, Gustavo; Charrow, Joel; Germain, Dominique P; Hopkin, Robert J; Jovanovic, Ana; Linhart, Aleš; Maruti, Sonia S; Mauer, Michael; Oliveira, João P; Patel, Manesh R; Politei, Juan; Waldek, Stephen; Wanner, Christoph; Yoo, Han-Wook; Warnock, David G

2016-07-01

Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β. The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase β (average dose 1 mg/kg every 2 weeks) for up to 5 years. The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40-58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged ≥40 years when agalsidase β was initiated. Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase β 1 mg/kg every 2 weeks. NCT00196742. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Validity and reliability of the Turkish version of the DSM-5 Dissociative Symptoms Severity Scale-Child Form.

PubMed

Yalın Sapmaz, Şermin; Ergin, Dilek; Şen Celasin, Nesrin; Özek Erkuran, Handan; Karaarslan, Duygu; Öztekin, Siğnem; Uzel Tanrıverdi, Bengisu; Köroğlu, Ertuğrul; Aydemir, Ömer

2017-01-01

The goal of this study was to assess the validity and reliability of the Turkish version of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) Dissociative Symptoms Severity Scale-Child Form. The scale was prepared by translating and then back-translating the DSM-5 Dissociative Symptoms Severity Scale. The study groups included one group of 30 patients diagnosed with posttraumatic stress disorder who were treated in a child and adolescent psychiatry unit and another group of 83 healthy volunteers from middle and high schools in the community. For assessment, the Adolescent Dissociative Experiences Scale (ADES) was used in addition to the DSM-5 Dissociative Symptoms Severity Scale. Regarding the reliability of the DSM-5 Dissociative Symptoms Severity Scale, Cronbach's alpha was .824 and item-total score correlation coefficients were between .464 and .648. The test-retest correlation coefficient was calculated to be r = .784. In terms of construct validity, one factor accounted for 45.2% of the variance. Furthermore, in terms of concurrent validity, the scale showed a high correlation with the ADES. In conclusion, the Turkish version of the DSM-5 Dissociative Symptoms Severity Scale-Child Form is a valid and reliable tool for both clinical practice and research.

Measuring economic outcomes of alcohol treatment using the Economic Form 90.

PubMed

Bray, Jeremy W; Zarkin, Gary A; Miller, William R; Mitra, Debanjali; Kivlahan, Daniel R; Martin, Daniel J; Couper, David J; Cisler, Ron A

2007-03-01

This article assesses the ability of the economic outcome measures in the Economic Form 90 to detect differences across levels of alcohol dependence as measured by the Alcohol Dependence Scale. We used baseline data from the Combining Medications and Behavioral Interventions (COMBINE) Study, a large, multisite clinical trial, to assess the extent to which the economic items on the Economic Form 90 instrument can detect differences across levels of alcohol dependence. After adjusting for differences in demographic characteristics, the Economic Form 90 can detect significant differences across a range of dependence severity levels for the economic outcomes of inpatient medical care, emergency-department medical care, behavioral health care, being on parole or probation, and missed workdays, conditional on being employed. We did not detect significant differences across dependence severity for employment status, outpatient medical care, other criminal justice involvement, or motor vehicle accidents. The Economic Form 90 can identify differences in many economic outcomes associated with differing levels of alcohol dependence. This suggests that the Economic Form 90 may be useful in assessing changes in economic outcomes that result from changes in alcohol dependence.

Gas gangrene and related infection: classification, clinical features and aetiology, management and mortality. A report of 88 cases.

PubMed

Darke, S G; King, A M; Slack, W K

1977-02-01

The clinical features of gas gangrene and related infection seen in 88 patients over a 10-year period are described. It is suggested that clostridial infection could be simply classified as either 'gas-forming' or 'non-gas-forming'. The gas-forming group represents the more severe form of infection. Non-clostridial gas gangrene may present in a variety of forms. The anaerobic streptococcus was the organism most frequently responsible, but these cases were indistinguishable from clostridial infection on clinical grounds. The treatment of gas gangrene in this series of patients is reported. Emphasis is laid on the importance of adequate prophylaxis with penicillin in patients at risk. The value of antibiotics in established infection remains equivocal. The evidence supporting the value of hyperbaric oxygen therapy is assessed and an attempt made to quantify the response to this treatment. Benefit was apparent in only a proportion of patients. A favourable response indicated clostridial infection and guaranteed immediate survival. Extensive debridement or amputation is unnecessary in this group. No response following hyperbaric oxygen therapy indicated widespread mixed clostridial and non-clostridial infection, or infection due to organisms other than clostridia. Urgent and extensive debridement and amputation remain the predominant measures in this group.

21-Hydroxylase deficiency: an exemplary model of the contribution of molecular biology in the understanding and management of the disease.

PubMed

Forest, M G; Tardy, V; Nicolino, M; David, M; Morel, Y

2005-06-01

Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders caused by mutations in genes encoding the enzymes involved in one of the various steps of adrenal steroid synthesis. Steroid 21-hydroxylase deficiency (21-OHD) is responsible for over 95% of the 5 forms of CAH, and results due to enzymatic defect owing to mutation in the CYP21 gene. The disease has two major clinical presentations. The "classical" form is severe, and divided into a salt wasting (SW) and simple virilizing (SV) subgroups. In both, affected female fetuses undergo virilization of the external genitalia prenatally and present at birth with sexual ambiguity. In addition, in both sexes infants with SW CAH are at risk of life-threatening adrenal crisis without treatment. This is why it is so important to make a diagnosis and to counsel the families. The diagnosis is easy by measuring the plasma levels of 17-hydroxyprogesterone (17-OHP) in antenatal (amniotic fluid), or perinatal samples (peripheral blood). Confirmation by molecular genetic analysis is advised. The second form of 21-OHD is called "non classical" because the presentation is much less severe and the onset of clinical expression occurs long after birth, often in the peripubertal period, as non-specific symptoms of hyperandrogeny. The unambiguous diagnosis of the latter requires a simple short ACTH test, with the measurement of 17-OHP at 60 min. In both forms, the mutations on the gene CYP21 responsible for the disease are now well known and can be identified by molecular biology techniques. There is a good correlation between phenotypes and genotypes, due to variable amount of the 21-hydroxylase-enzyme activity left (null to 50-60%). SW, SV and NC forms are associated with distinct mutations or combination of mutations. Nowadays, by combining hormonal and molecular tests, it is possible to predict the clinical form of the disease in a given family in the context of a prenatal diagnosis, which can lead to a prenatal treatment. Therefore, 21-OHD genotyping also appears essential for a new approach of genetic counseling, prediction of clinical form after postnatal screening and to define the post-ACTH 17-OHP values indicating the cut-off lines between NC, heterozygote and normal subjects.

The Role of Biofilms in Drinking Water Exposure to Potentially Pathogenic Legionella spp.

EPA Science Inventory

Legionellosis is a bacterial infection caused by species of the genera Legionella and is the most common waterborne disease reported in the United States. This type of infection has two clinically distinct forms: Legionnaire's disease, a severe type of infection, which include...

A Future for Adult Educators in Patient Education

ERIC Educational Resources Information Center

Fleming, Jean E.

2014-01-01

Adult education in healthcare comes in several forms: degree and certificate programs aimed at preparing better academic and clinical educators; and community education programs aimed at wellness, rehabilitation, or learning to live with chronic diseases. Patient-centered healthcare, however, is part of something new: coordinated and transitional…

HYPOTHYROIDISM - A SPECIAL COMORBIDITY FACTOR IN PATIENTS WITH OSTEOARTHROSIS: CLINICAL, PATHOPHYSIOLOGICAL AND PROGNOSTIC ASPECTS.

PubMed

Voloshyna, L; Doholich, О; Sithinska, I

2017-11-01

Objective - to study the features of the functional and morphological condition of the thyroid gland (TG) in patients with osteoarthrosis (OA), the incidence and forms of hypothyroidism and their effects on clinical manifestations, metabolic disorders and the results of the treatment of OA and comorbid processes. A complex examination involved 312 patients with OA aged 37-76 years. Methods used: anthropometric, clinical, ultrasonographic, biochemical, radioimmunological (levels of TSH, free thyroxine, antibodies to thyroid peroxidase). It has been established that with increasing age in patients OA phenomena are progressing, there is an increase in comorbid diseases, especially of the cardiovascular system with atherosclerotic genesis, they become more severe. Against this background, clinical hypothyroidism was found in 4.44% and subclinical one in 13.78%. Stratification of the clinical form of hypothyroidism contributed to the deterioration of the course and outcome of the treatment of OA and comorbid diseases. Both forms of hypothyroidism intensified the degrees of metabolic disorders in the blood, reduced the glomerular filtration rate, especially the clinical form. Manifestations of hypothyroidism were observed in patients with OA with its significant systemic manifestations, high comorbidity rate, in individuals aged over 50, especially 60 years, mainly in women (83,72%). In patients with OA aged over 50 years with a high comorbidity rate, it is advisable to conduct an ultrasound examination of the thyroid gland, to measure the levels of TSH, free thyroxine in order to diagnose hypothyroidism early and to treat it timely as one of the ways to improve the overall outcomes of the treatment of such patients.

Clinical features of avian vacuolar myelinopathy in American coots

USGS Publications Warehouse

Larsen, R.S.; Nutter, F.B.; Augspurger, T.; Rocke, T.E.; Tomlinson, L.; Thomas, N.J.; Stoskopf, M.K.

2002-01-01

Objectivea??To characterize clinical features of avian vacuolar myelinopathy (AVM) in American coots. Designa??Case-control study. Animalsa??26 AVM-affected American coots and 12 unaffected coots. Proceduresa??Complete physical, neurologic, hematologic, and plasma biochemical evaluations were performed. Affected coots received supportive care. All coots died or were euthanatized, and AVM status was confirmed via histopathologic findings. Resultsa??3 severely affected coots were euthanatized immediately after examination. Seventeen affected coots were found dead within 7 days of admission, but 5 affected coots survived > 21 days and had signs of clinical recovery. Abnormal physical examination findings appeared to be related to general debilitation. Ataxia (88%), decreased withdrawal reflexes (88%), proprioceptive deficits (81%), decreased vent responses (69%), beak or tongue weakness (42%), and head tremors (31%), as well as absent pupillary light responses (46%), anisocoria (15%), apparent blindness (4%), nystagmus (4%), and strabismus (4%) were detected. Few gross abnormalities were detected at necropsy, but histologically, all AVM-affected coots had severe vacuolation of white matter of the brain. None of the control coots had vacuolation. Conclusions and Clinical Relevancea??Although there was considerable variability in form and severity of clinical neurologic abnormalities, clinical signs common in AVM-affected birds were identified. Clinical recovery of some AVM-affected coots can occur when supportive care is administered. Until the etiology is identified, caution should be exercised when rehabilitating and releasing coots thought to be affected by AVM.

[Current management of thalassemia intermedia].

PubMed

Thuret, I

2014-11-01

Thalassemia intermedia is a clinical entity where anemia is mild or moderate, requiring no or occasional transfusion. Non-transfusion-dependent thalassemia encompasses 3 main clinical forms: beta-thalassemia intermedia, hemoglobin E/beta-thalassemia and alpha-thalassemia intermedia (HbH disease). Clinical severity of thalassemia intermedia increases with age, with more severe anemia and more frequent complications such as extramedullary hematopoiesis and iron overload mainly related to increased intestinal absorption. Numerous adverse events including pulmonary hypertension and hypercoagulability have been associated with splenectomy, often performed in thalassemia intermedia patients. The potential preventive benefit of transfusion and chelation therapies on the occurrence of numerous complications supports the strategy of an earlier therapeutic intervention. Increasing knowledge about pathophysiological mechanisms involved in thalassemia erythropoiesis and related iron overload is currently translating in novel therapeutic approaches. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Infectious optic neuropathies: a clinical update

PubMed Central

Kahloun, Rim; Abroug, Nesrine; Ksiaa, Imen; Mahmoud, Anis; Zeghidi, Hatem; Zaouali, Sonia; Khairallah, Moncef

2015-01-01

Different forms of optic neuropathy causing visual impairment of varying severity have been reported in association with a wide variety of infectious agents. Proper clinical diagnosis of any of these infectious conditions is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular findings. Diagnosis is confirmed by serologic testing and polymerase chain reaction in selected cases. Treatment of infectious optic neuropathies involves the use of specific anti-infectious drugs and corticosteroids to suppress the associated inflammatory reaction. The visual prognosis is generally good, but persistent severe vision loss with optic atrophy can occur. This review presents optic neuropathies caused by specific viral, bacterial, parasitic, and fungal diseases. PMID:28539795

A Founder Effect of c.257 + 2T > C Mutation in NCF2 Gene Underlies Severe Chronic Granulomatous Disease in Eleven Patients.

PubMed

Ben-Farhat, Khaoula; Ben-Mustapha, Imen; Ben-Ali, Meriem; Rouault, Karen; Hamami, Saber; Mekki, Najla; Ben-Chehida, Amel; Larguèche, Beya; Fitouri, Zohra; Abdelmoula, Selim; Khemiri, Monia; Guediche, Mohamed-Neji; Boukthir, Samir; Barsaoui, Sihem; Chemli, Jalel; Barbouche, Mohamed-Ridha

2016-08-01

Chronic granulomatous disease (CGD) is the prototypic functional neutrophil disorder caused by genetic defects in one of the five genes encoding the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase subunits of phagocytes. Mutations causing the most prevalent form of CGD in western populations are located in the X-linked-CYBB gene. The four remaining autosomal recessive (AR) forms collectively account for one-third of CGD cases. We investigated the clinical and molecular features of eleven patients with CGD from 6 consanguineous families, originating from contiguous regions in the west of Tunisia. The patients' clinical phenotype is characterized by a high incidence of mycobacterial infections. Five out of the eleven patients died despite treatment arguing in favor of a severe clinical form of CGD. These findings correlated with the absence of functional p67phox protein as well as the absence of residual reactive oxygen intermediates (ROI) production. Genetic analysis showed the presence, in all patients, of a unique mutation (c.257 + 2T > C) in NCF2 gene predicted to affect RNA splicing. Segregating analysis using nine polymorphic markers overlapping the NCF2 gene revealed a common haplotype spanning 4.1 Mb. The founder event responsible for this mutation was estimated to have arisen approximately 175 years ago. These findings will facilitate the implementation of preventive approaches through genetic counseling in affected consanguineous families.

Clinical characteristics of generalized anxiety disorder: older vs. young adults.

PubMed

Altunoz, Umut; Kokurcan, Ahmet; Kirici, Sevinc; Bastug, Gulbahar; Ozel-Kizil, Erguvan Tugba

2018-02-01

Generalized anxiety disorder (GAD) is one of the most common anxiety disorders in older people. Although GAD in older adults seems to differ in many aspects like clinical presentation, severity and treatment response, there is a paucity of comparative research. The aim of the study is to compare the clinical presentation of GAD between older and young adults. One hundred and two non-demented older patients (age ≥65) and 64 young patients (age <45) who were diagnosed with GAD according to the DSM-IV-TR criteria were included to the study. Socio-demographic Data Form, the Structured Clinical Interview for DSM Disorders-1 (SCID-1), the Questionnaire for the Suggested Behavioral Criteria of GAD for DSM-5, the Hamilton Depression Scale (HAM-D), the Generalized Anxiety Disorder Severity Scale (GADSS) and the Sheehan Disability Scale (SDS) were applied to both groups. Older GAD patients had more disturbances of sleep, less reassurance seeking behaviors, higher rates of depression and higher depression severity when compared to the young patients. Although older people seemed to have a lower severity of GAD, they had higher disability due to worries. Older patients worried more about their own health and family well-being, whereas young patients worried more about future and other's health.

ZAP-70 staining in chronic lymphocytic leukemia.

PubMed

Villamor, Neus

2005-05-01

Chronic lymphocytic leukemia (CLL) is the most common chronic leukemia in Western countries. The disease has an extremely variable clinical course, and several prognostic features have been identified to assess individual risk. The configuration of the immunoglobulin variable heavy-chain gene (IgV(H)) is a strong predictor of the outcome. CLL patients with unmutated IgV(H) status have an aggressive clinical course and a short survival. Unfortunately, analysis of IgV(H) gene configuration is not available in most clinical laboratories. A small number of genes are differentially expressed between unmutated IgV(H) and mutated IgV(H) clinical forms of CLL. One of these genes is ZAP-70, which is detected in leukemic cells from patients with the unmutated IgV(H) form of CLL. Flow cytometry presents advantages over other methods to detect ZAP-70, and its quantification by flow cytometry has proved its predictive value. This unit focuses on protocols to quantify ZAP-70 by flow cytometry in CLL.

Serological diagnosis of Toxoplasma gondii infection: Recommendations from the French National Reference Center for Toxoplasmosis.

PubMed

Villard, O; Cimon, B; L'Ollivier, C; Fricker-Hidalgo, H; Godineau, N; Houze, S; Paris, L; Pelloux, H; Villena, I; Candolfi, E

2016-01-01

Toxoplasmosis manifests no clinical signs in 80% of cases in immunocompetent patient, causing immunization characterized by the persistence of cysts, particularly in brain, muscles, and retina. Assessing the serological status, based on testing for serum toxoplasma IgG and IgM antibodies, is essential in cases that are increasingly at risk for the more severe disease forms, such as congenital or ocular toxoplasmosis. This disease also exposes immunosuppressed patients to reactivation, which can lead to more widespread forms and increased mortality. By interpreting the serological results, we can estimate the risk of contamination or reactivation and define appropriate prophylactic and preventive measures, such as hygienic and dietetic, therapeutic, biological, and clinical follow-up, according to the clinical context. We hereby propose practical approaches based on serological data, resulting from a consensus of a group of experts from the French National Reference Center Network for Toxoplasmosis, according to both routine and specific clinical situations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

T-lymphocyte Subsets as a Prognostic Factor in a Clinical Course of Chickenpox

PubMed Central

Baljic, Rusmir; Konjo, Hadzan; Hrustemovic, Dzenana; Gazibera, Belma; Katica, Amela; Hukic, Mirsada

2017-01-01

Objective: To investigate possible prognostic values of CD4+, CD8+ T-lymphocytes, CD4/CD8 ratio to clinical course of chickenpox in immunocompetent hosts. Materials and methods: We performed a prospective study which included 69 immunocompetent patients with chickenpox who were addmited to Clinic for infectious disease, Clinical Center University of Sarajevo, in a 18 month period. All patients were divided into two groups depending on clinical presentation on admission. Patients with mild clinical form were dedicated to „outpatient” group, and patients with moderate, severe or life-threatening clinical forms were dedicated to „hospitalized” group. Also 30 healthy volunteers are included in study as a control group. We analyzed values of CD4+, CD8+ percentage, CD4/CD8 ratio with comparison to clinical course of chickenpox. All specimens were taken in acute phase of illness. Results: Values of CD4+ percentage were significantly declined in a group of hospitalized patients, compared to group of outpatients and control group. Values of CD8+ percentage were higher in a group of hospitalized patients, while CD4/CD8 values were lower in comparison to a group of outpatients and control group. Conclusion: We found significant correlation between these parameters and clinical course of chickenpox. PMID:28484347

Clinical forms of actinic keratosis and levels of dysplasia of the epidermis.

PubMed

Oshyvalova, Olena O; Kaliuzhna, Lydia D; Kropelnytskyi, Vladislav O

Introduction: Actinic keratosis (AK) is precancerous skin lesion that occurs in the sun-exposedskin areas characterized by local intraepidermal dysplasia of different severity (KIN I, KIN II and KIN III). The aim of this research was to study distribution patterns and morphological features of AK histological types. Materials and Methods: The study included skin biopsy material from 68 patients with different clinical forms of AK. The diagnosis of AK was histologically confirmed in 100% of cases. Results: There were 63.21% of men and 36.8% of women among all patients with AK. The average age of patients was 73.3 ± 8.3.The most common clinico-histological forms of actinic keratosis were typical (41.2%), hypertrophic (16.2%), atrophic (14.7%) and pigmentary (11.7%), bowenoid (8.8%), acantholytic (7.4%). Among the rate of epidermal dysplasia there diagnosed cases of KIN І (50%), KIN ІІ (36.8%) and KIN III (13.2%). Conclusions: It was found a direct correlation between KIN I and typical and pigment forms of AK, KIN II and hypertrophic and bowenoid forms of AK.

Acute optic neuropathy associated with a novel MFN2 mutation.

PubMed

Leonardi, Luca; Marcotulli, Christian; Storti, Eugenia; Tessa, Alessandra; Serrao, Mariano; Parisi, Vincenzo; Santorelli, F M; Pierelli, Francesco; Casali, Carlo

2015-07-01

Mutations in the mitofusin 2 (MFN2) gene cause CMT2A the most common form of autosomal dominant axonal Charcot-Marie-Tooth (CMT). In addition, mutations in MFN2 have been shown to be responsible for Hereditary Motor Sensory Neuropathy type VI (HSMN VI), a rare early-onset axonal CMT associated with optic neuropathy. Most reports of HMSN VI presented with a sub-acute form of optic neuropathy. Herein, we report a CMT2A patient, who developed very rapidly progressing severe optic neuropathy. A 40-year-old Caucasian man was evaluated for gait disturbance and lower limbs weakness, slowly progressed over the last 2 years. Due to clinical data and family history, a diagnosis of CMT2 was made. The novel heterozygous c.775C > T (p.Arg259Cys) mutation in MFN2 was detected in the patient and his clinical affected mother. Interestingly, the patient developed a severe sudden bilateral visual deterioration few years early, with clinical and instrumental picture suggestive of acute bilateral optic neuropathy. Our report expands the spectrum of MFN2-related manifestation because it indicates that visual symptoms of HMSN VI may enter in the differential with acquired or hereditary acute optic neuropathies, and that severe optic neuropathy is not invariably an early manifestation of the disease but may occur as disease progressed. This report could have an impact on clinicians who evaluate patients with otherwise unexplainable bilateral acute-onset optic neuropathy, especially if associated with a motor and sensory axonal neuropathy.

WES homozygosity mapping in a recessive form of Charcot-Marie-Tooth neuropathy reveals intronic GDAP1 variant leading to a premature stop codon.

PubMed

Masingue, Marion; Perrot, Jimmy; Carlier, Robert-Yves; Piguet-Lacroix, Guenaelle; Latour, Philippe; Stojkovic, Tanya

2018-05-01

Charcot-Marie-Tooth disease (CMT) refers to a group of clinically and genetically heterogeneous inherited neuropathies. Ganglioside-induced differentiation-associated protein 1 GDAP1-related CMT has been reported in an autosomal dominant or recessive form in patients presenting either axonal or demyelinating neuropathy. We report two Sri Lankan sisters born to consanguineous parents and presenting with a severe axonal sensorimotor neuropathy. The early onset of the disease, the distal and proximal weakness and atrophy leading to major disability, along with areflexia, and, most notably, vocal cord and diaphragm paralysis were highly evocative of a GDAP1-related CMT. However, sequencing of the coding regions of the gene was normal. Whole-exome sequencing (WES) was performed and revealed that the largest region of homozygosity was around GDAP1 with several variants, mostly in non-coding regions. In view of the high clinical suspicion of GDAP1 gene involvement, we examined the variants in this gene and this, along with functional studies, allowed us to identify an alternative splicing site revealing a cryptic in-frame stop codon in intron 4 responsible for a severe loss of wild-type GDAP1. This work is the first to describe a deleterious mutation in GDAP1 gene outside of coding sequences or intronic junctions and emphasizes the importance of interpreting molecular analysis, and in particular WES results, in light of the clinical and electrophysiological phenotype.

Neurocognitive dysfunction in strategic and non-strategic gamblers.

PubMed

Grant, Jon E; Odlaug, Brian L; Chamberlain, Samuel R; Schreiber, Liana R N

2012-08-07

It has been theorized that there may be subtypes of pathological gambling, particularly in relation to the main type of gambling activities undertaken. Whether or not putative pathological gambling subtypes differ in terms of their clinical and cognitive profiles has received little attention. Subjects meeting DSM-IV criteria for pathological gambling were grouped into two categories of preferred forms of gambling - strategic (e.g., cards, dice, sports betting, stock market) and non-strategic (e.g., slots, video poker, pull tabs). Groups were compared on clinical characteristics (gambling severity, and time and money spent gambling), psychiatric comorbidity, and neurocognitive tests assessing motor impulsivity and cognitive flexibility. Seventy-seven subjects were included in this sample (45.5% females; mean age: 42.7±14.9) which consisted of the following groups: strategic (n=22; 28.6%) and non-strategic (n=55; 71.4%). Non-strategic gamblers were significantly more likely to be older, female, and divorced. Money spent gambling did not differ significantly between groups although one measure of gambling severity reflected more severe problems for strategic gamblers. Strategic and non-strategic gamblers did not differ in terms of cognitive function; both groups showed impairments in cognitive flexibility and inhibitory control relative to matched healthy volunteers. These preliminary results suggest that preferred form of gambling may be associated with specific clinical characteristics but are not dissociable in terms of cognitive inflexibility and motor impulsivity. Copyright © 2012 Elsevier Inc. All rights reserved.

Oral treatment of paracoccidioidomycosis and histoplasmosis with itraconazole in humans.

PubMed

Negroni, R; Palmieri, O; Koren, F; Tiraboschi, I N; Galimberti, R L

1987-01-01

Twenty-five patients with paracoccidioidomycosis and 17 patients with histoplasmosis were treated with itraconazole. All patients were adults. Those with paracoccidioidomycosis exhibited the chronic disseminated form of the disease; 21 of these patients had lesions in two or more locations, and four had lesions only on the larynx or mouth. Itraconazole was administered at a daily dosage of 50 mg for six months in the majority of these cases. All infections were clinically cured or showed striking improvement. Patients with histoplasmosis had the chronic pulmonary or chronic disseminated form of the disease. A daily dose of 100 mg was administered until clinical cure was established; the dose was then changed to 50 mg until the completion of six months of treatment. Twelve infections were clinically cured; four were strikingly alleviated. The remaining patient, who discontinued treatment with itraconazole after two months, had a severe relapse and died of respiratory failure.

Development of a diagnostic diagram for rapid field assessment of acidosis severity in diarrheic calves.

PubMed

Bellino, Claudio; Arnaudo, Fabrizio; Biolatti, Cristina; Borrelli, Antonio; Gianella, Paola; Maurella, Cristiana; Zabaldano, Giuseppe; Cagnasso, Aurelio; D'Angelo, Antonio

2012-02-01

To develop a diagnostic diagram for rapid field assessment of acidosis severity in diarrheic calves. Prospective cross-sectional study. 148 Piedmontese calves (38 calves in preliminary experiments; 83 diarrheic calves and 27 healthy control calves in the primary experiment). Physical examination was performed and a standard data collection form was completed for each calf. Blood samples were obtained and submitted for evaluation of acid-base balance, performance of a CBC, and measurement of electrolyte and total protein concentrations. Severe metabolic acidosis (extracellular base excess more negative than -10 mmol/L) was associated with abnormal mental status, delayed or absent suckle reflex, abnormal posture or gait, enophthalmos, and cold oral mucosal membranes. Clinical signs associated with severe metabolic acidosis were arranged into a grid to create a diagnostic diagram. Sensitivity and specificity of the diagnostic diagram for the prediction of severe metabolic acidosis were 88% and 79%, respectively. Use of the diagnostic diagram may aid differentiation between severe and nonsevere acidosis patterns as determined on the basis of clinical signs.

On the question of self-disclosure by the analyst: error or advance in technique?

PubMed

Jacobs, T

1999-04-01

The question of self-disclosure by the analyst and its uses in treatment is an issue widely debated today. In this paper, the author reviews this controversial technique from historical and contemporary points of view, delineates several forms of self-disclosure, and, by means of several clinical examples, discusses the effects on the patient and the analytic process of utilizing one or another kind of self-disclosure in these particular situations.

PubMed Central

MAGGI, LORENZO; SALERNO, FRANCO; BRAGATO, CINZIA; SAREDI, SIMONA; BLASEVICH, FLAVIA; MACCAGNANO, ELIO; PASANISI, BARBARA; DANESINO, CESARE; MORA, MARINA; MORANDI, LUCIA

2013-01-01

The adult-onset form of Pompe disease had a wide clinical spectrum, ranging from asymptomatic patients with increased CK to muscle cramps and pain syndrome or rigid-spine syndrome. In addition clinical severity and disease progression are greatly variable. We report on a family with 3 siblings characterized by an unusual adult-onset Pompe disease including dysphagia and weakness of tongue, axial and limb-girdle muscles, in association with atypical globular inclusions in muscle fibres. Our study confirms the great clinical and histological variability of adult-onset Pompe disease and further supports the need of careful evaluation of bulbar function in patients affected by this pathology. PMID:24399864

Validity and reliability of the Turkish version of the DSM-5 Generalized Anxiety Disorder Severity Scale for children aged 11–17 years

PubMed

Yalın Sapmaz, Şermin; Özek Erkuran, Handan; Ergin, Dilek; Öztürk, Masum; Şen Celasin, Nesrin; Karaarslan, Duygu; Aydemir, Ömer

2018-02-23

Background/aim: This study aimed to assess the validity and reliability of the Turkish version of the DSM-5 Generalized Anxiety Disorder Severity Scale - Child Form. Materials and methods: The study sample consisted of 32 patients treated in a child psychiatry unit and diagnosed with generalized anxiety disorder and 98 healthy volunteers who were attending middle or high school during the study period. For the assessment, the Screen for Child Anxiety and Related Emotional Disorders (SCARED) was also used along with the DSM-5 Generalized Anxiety Disorder Severity Scale - Child Form. Results: Regarding reliability analyses, the Cronbach alpha internal consistency coefficient was calculated as 0.932. The test-retest correlation coefficient was calculated as r = 0.707. As for construct validity, one factor that could explain 62.6% of the variance was obtained and this was consistent with the original construct of the scale. As for concurrent validity, the scale showed a high correlation with SCARED. Conclusion: It was concluded that Turkish version of the DSM-5 Generalized Anxiety Disorder Severity Scale - Child Form could be utilized as a valid and reliable tool both in clinical practice and for research purposes.

The phenomenology of parkinsonian tremor.

PubMed

Deuschl, Günther; Papengut, Frank; Hellriegel, Helge

2012-01-01

The definition of Parkinsonian tremor covers all different forms occurring in Parkinson's disease. The most common form is rest tremor, labelled as typical Parkinsonian tremor. Other variants cover also postural and action tremors. Data support the notion that suppression of rest tremor may be more specific for PD tremors. Several differential diagnoses like rest tremor in ET, dystonic tremor, psychogenic tremor and Holmes' tremor may be misinterpreted as PD-tremor. Tests and clinical clues to separate them are presented. Copyright © 2011 Elsevier Ltd. All rights reserved.

Thiamine Deficiency in Tropical Pediatrics: New Insights into a Neglected but Vital Metabolic Challenge

PubMed Central

Hiffler, Laurent; Rakotoambinina, Benjamin; Lafferty, Nadia; Martinez Garcia, Daniel

2016-01-01

In humans, thiamine is a micronutrient prone to depletion that may result in severe clinical abnormalities. This narrative review summarizes current knowledge on thiamine deficiency (TD) and bridges the gap between pathophysiology and clinical presentation by integrating thiamine metabolism at subcellular level with its function to vital organs. The broad clinical spectrum of TD is outlined, with emphasis on conditions encountered in tropical pediatric practice. In particular, TD is associated with type B lactic acidosis and classic forms of beriberi in children, but it is often unrecognized. Other severe acute conditions are associated with hypermetabolism, inducing a functional TD. The crucial role of thiamine in infant cognitive development is also highlighted in this review, along with analysis of the potential impact of TD in refeeding syndrome during severe acute malnutrition (SAM). This review aims to increase clinical awareness of TD in tropical settings where access to diagnostic tests is poor, and advocates for an early therapeutic thiamine challenge in resource-limited settings. Moreover, it provides evidence for thiamine as treatment in critical conditions requiring metabolic resuscitation, and gives rationale to the consideration of increased thiamine supplementation in therapeutic foods for malnourished children. PMID:27379239

What does risperidone add to parent training and stimulant for severe aggression in child attention-deficit/hyperactivity disorder?

PubMed

Aman, Michael G; Bukstein, Oscar G; Gadow, Kenneth D; Arnold, L Eugene; Molina, Brooke S G; McNamara, Nora K; Rundberg-Rivera, E Victoria; Li, Xiaobai; Kipp, Heidi; Schneider, Jayne; Butter, Eric M; Baker, Jennifer; Sprafkin, Joyce; Rice, Robert R; Bangalore, Srihari S; Farmer, Cristan A; Austin, Adrienne B; Buchan-Page, Kristin A; Brown, Nicole V; Hurt, Elizabeth A; Grondhuis, Sabrina N; Findling, Robert L

2014-01-01

Although combination pharmacotherapy is common in child and adolescent psychiatry, there has been little research evaluating it. The value of adding risperidone to concurrent psychostimulant and parent training (PT) in behavior management for children with severe aggression was tested. One hundred sixty-eight children 6 to 12 years old (mean age 8.89 ± 2.01 years) with severe physical aggression were randomized to a 9-week trial of PT, stimulant (STIM), and placebo (Basic treatment; n = 84) or PT, STIM, and risperidone (Augmented treatment; n = 84). All had diagnoses of attention-deficit/hyperactivity disorder and oppositional-defiant disorder (n = 124) or conduct disorder (n = 44). Children received psychostimulant (usually Osmotic Release Oral System methylphenidate) for 3 weeks, titrated for optimal effect, while parents received PT. If there was room for improvement at the end of week 3, placebo or risperidone was added. Assessments included parent ratings on the Nisonger Child Behavior Rating Form (Disruptive-Total subscale was the primary outcome) and Antisocial Behavior Scale; blinded clinicians rated change on the Clinical Global Impressions scale. Compared with Basic treatment (PT + STIM [44.8 ± 14.6 mg/day] + placebo [1.88 mg/day ± 0.72]), Augmented treatment (PT + STIM [46.1 ± 16.8 mg/day] + risperidone [1.65 mg/day ± 0.75]) showed statistically significant improvement on the Nisonger Child Behavior Rating Form Disruptive-Total subscale (treatment-by-time interaction, p = .0016), the Nisonger Child Behavior Rating Form Social Competence subscale (p = .0049), and Antisocial Behavior Scale Reactive Aggression subscale (p = .01). Clinical Global Impressions scores were substantially improved for the 2 groups but did not discriminate between treatments (Clinical Global Impressions-Improvement score ≤2, 70% for Basic treatment versus 79% for Augmented treatment). Prolactin elevations and gastrointestinal upset occurred more with Augmented treatment; other adverse events differed modestly from Basic treatment; weight gain in the Augmented treatment group was minor. Risperidone provided moderate but variable improvement in aggressive and other seriously disruptive child behaviors when added to PT and optimized stimulant treatment. Clinical trial registration information-Treatment of Severe Childhood Aggression (The TOSCA Study), URL: http://clinicaltrials.gov, unique identifier: NCT00796302. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. All rights reserved.

Distributed user interfaces for clinical ubiquitous computing applications.

PubMed

Bång, Magnus; Larsson, Anders; Berglund, Erik; Eriksson, Henrik

2005-08-01

Ubiquitous computing with multiple interaction devices requires new interface models that support user-specific modifications to applications and facilitate the fast development of active workspaces. We have developed NOSTOS, a computer-augmented work environment for clinical personnel to explore new user interface paradigms for ubiquitous computing. NOSTOS uses several devices such as digital pens, an active desk, and walk-up displays that allow the system to track documents and activities in the workplace. We present the distributed user interface (DUI) model that allows standalone applications to distribute their user interface components to several devices dynamically at run-time. This mechanism permit clinicians to develop their own user interfaces and forms to clinical information systems to match their specific needs. We discuss the underlying technical concepts of DUIs and show how service discovery, component distribution, events and layout management are dealt with in the NOSTOS system. Our results suggest that DUIs--and similar network-based user interfaces--will be a prerequisite of future mobile user interfaces and essential to develop clinical multi-device environments.

Replacement of missing teeth with fiber-reinforced composite FPDs: clinical protocol.

PubMed

Bouillaguet, Serge; Schütt, Andrea; Marin, Isabelle; Etechami, Leila; Di Salvo, Giancarlo; Krejci, Ivo

2003-04-01

The concept of minimally invasive preparation protocols has resulted in reduced loss of critical tooth structures and maintenance of optimal strength, form, and aesthetics. While various treatment options have been described for single-tooth replacement, fiber-reinforced composite (FRC) fixed partial dentures (FPDs) provide a viable treatment alternative with proven mechanical properties, aesthetics, and function. This article presents several clinical scenarios in which minimally invasive adhesive FRC FPDs are provided to deliver enhanced predictability, strength, and durability.

The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fransen, E.; Vits, L.; Van Camp, G.

1996-07-12

Mutations in the gene encoding the neuronal cell adhesion molecule L1 are responsible for several syndromes with clinical overlap, including X-linked hydrocephalus (XLH, HSAS), MASA (mental retardation, aphasia, shuffling gait, adducted thumbs) syndrome, complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb (MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum (ACC). We review 34 L1 mutations in patients with these phenotypes. 22 refs., 3 figs., 4 tabs.

Autopsy diagnosis of fat embolism syndrome.

PubMed

Miller, Peter; Prahlow, Joseph A

2011-09-01

The fat embolism syndrome (FES) is considered a clinical diagnosis. It typically occurs within several days following major traumatic injury, usually involving fractures of the pelvis and/or lower extremities. Fat embolism syndrome is characterized by the onset of respiratory, neurological, cutaneous, and hematologic manifestations and is thought to be related to intravascular embolization of fat, presumably arising from within the fractured bone marrow space. In its most severe form, FES can be lethal. The presence of fat emboli within the microvasculature of the lungs, brain, and sometimes other organs verifies the clinical impression of FES. Despite its relatively well-known clinical characterization, debate exists within the clinical literature regarding the most appropriate diagnostic criteria for FES. Given this fact, along with the fact that FES is a clinical diagnosis, it is not surprising that forensic pathologists may be somewhat reluctant to make a postmortem diagnosis of FES, especially in cases where insufficient clinical information is available. A case of fatal FES is presented in which rapid clinical deterioration occurred, followed by death, such that a clinical diagnosis of FES was never rendered. We propose that, given the correct circumstances, clinical scenario, and autopsy findings, it is appropriate and acceptable to make a postmortem diagnosis of FES. A multitiered approach to the postmortem diagnosis of FES is presented.

Frontal fibrosing alopecia: a multicenter review of 355 patients.

PubMed

Vañó-Galván, Sergio; Molina-Ruiz, Ana M; Serrano-Falcón, Cristina; Arias-Santiago, Salvador; Rodrigues-Barata, Ana R; Garnacho-Saucedo, Gloria; Martorell-Calatayud, Antonio; Fernández-Crehuet, Pablo; Grimalt, Ramón; Aranegui, Beatriz; Grillo, Emiliano; Diaz-Ley, Blanca; Salido, Rafael; Pérez-Gala, Sivia; Serrano, Salvio; Moreno, Jose Carlos; Jaén, Pedro; Camacho, Francisco M

2014-04-01

To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. We sought to describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. In all, 355 patients (343 women [49 premenopausal] and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). The retrospective design is a limitation. Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

[Treatment of early-onset generalized dystonia by chronic bilateral stimulation of the internal globus pallidus. Apropos of a case].

PubMed

Coubes, P; Echenne, B; Roubertie, A; Vayssière, N; Tuffery, S; Humbertclaude, V; Cambonie, G; Claustres, M; Frerebeau, P

1999-05-01

Dystonia musculorum deformans is an inherited severe disease, with a wide clinical polymorphism. The most severe clinical forms with early onset carry a high risk of life-threatening complications. In the absence of any efficient medical treatment, bilateral pallidotomy has previously been reported to be of value in the management of this disease. We report the first clinical case of a severe early-onset generalized dystonia dramatically improved by a bilateral stimulation of the internal globus pallidus. In November 1996, we proposed this neurosurgical procedure for a 8-year-old girl, who had suffered since the age of 3 from severe generalized dystonia, and who progressively became totally dependent and bedridden. She had been under sedation and permanent controlled respiratory assistance for the last two months. The etiology of the disease remained unknown (the DYT1 mutation was absent). Under general anesthesia, we bilaterally implanted a four-contacts electrode in the internal globus pallidus, using the Leksell's stereotactic frame and a 1.5 tesla MRI control. A dramatic improvement was noted 6 weeks later and led us to connect the two electrodes to neurostimulators inserted under the abdominal skin.

Pediatric Hypothyroidism: Diagnosis and Treatment.

PubMed

Wassner, Ari J

2017-08-01

Thyroid hormone has important physiologic functions in nearly every organ system. The critical role of thyroid hormone in growth and in physical and neurologic development lends particular importance to the prompt diagnosis and appropriate treatment of hypothyroidism in infants and children. Congenital hypothyroidism is common and has potentially devastating neurologic consequences. While the approach to diagnosis and treatment of severe congenital hypothyroidism is well established, data continue to emerge about the genetic causes, clinical significance, and prognosis of the milder forms of congenital hypothyroidism that are increasingly being diagnosed by newborn screening. Similarly, the diagnosis and treatment of severe acquired hypothyroidism is straightforward and clearly of clinical benefit, but uncertainty remains about the optimal management of mild subclinical hypothyroidism. This review summarizes current knowledge of the causes, clinical manifestations, diagnosis, treatment, and prognosis of hypothyroidism in infants and children, with a focus on recent developments and areas of uncertainty in this field.

Heat stress disorders and headache: a case of new daily persistent headache secondary to heat stroke.

PubMed

Di Lorenzo, C; Ambrosini, A; Coppola, G; Pierelli, F

2009-01-01

Headache is considered as a common symptom of heat stress disorders (HSD), but no forms of secondary headache from heat exposure are reported in the International Classification of Headache Disorders-2 Edition (ICHD-II). Heat-stroke (HS) is the HSD most severe condition, it may be divided into two forms: classic (due to a long period environmental heat exposure) and exertional (a severe condition caused by strenuous physical exercises in heat environmental conditions). Here we report the case of a patient who developed a headache clinical picture fulfilling the diagnostic criteria for new daily persistent headache (NDPH), after an exertional HS, and discuss about possible pathophysiological mechanisms and classification aspects of headache induced by heat conditions.

Heat stress disorders and headache: a case of new daily persistent headache secondary to heat stroke

PubMed Central

Di Lorenzo, C; Ambrosini, A; Coppola, G; Pierelli, F

2009-01-01

Headache is considered as a common symptom of heat stress disorders (HSD), but no forms of secondary headache from heat exposure are reported in the International Classification of Headache Disorders-2 Edition (ICHD-II). Heat-stroke (HS) is the HSD most severe condition, it may be divided into two forms: classic (due to a long period environmental heat exposure) and exertional (a severe condition caused by strenuous physical exercises in heat environmental conditions). Here we report the case of a patient who developed a headache clinical picture fulfilling the diagnostic criteria for new daily persistent headache (NDPH), after an exertional HS, and discuss about possible pathophysiological mechanisms and classification aspects of headache induced by heat conditions. PMID:21686677

Osteopetroses, emphasizing potential approaches to treatment.

PubMed

Teti, Anna; Econs, Michael J

2017-09-01

Osteopetroses are a heterogeneous group of rare genetic bone diseases sharing the common hallmarks of reduced osteoclast activity, increased bone mass and high bone fragility. Osteoclasts are bone resorbing cells that contribute to bone growth and renewal through the erosion of the mineralized matrix. Alongside the bone forming activity by osteoblasts, osteoclasts allow the skeleton to grow harmonically and maintain a healthy balance between bone resorption and formation. Osteoclast impairment in osteopetroses prevents bone renewal and deteriorates bone quality, causing atraumatic fractures. Osteopetroses vary in severity and are caused by mutations in a variety of genes involved in bone resorption or in osteoclastogenesis. Frequent signs and symptoms include osteosclerosis, deformity, dwarfism and narrowing of the bony canals, including the nerve foramina, leading to hematological and neural failures. The disease is autosomal, with only one extremely rare form associated so far to the X-chromosome, and can have either recessive or dominant inheritance. Recessive ostepetroses are generally lethal in infancy or childhood, with a few milder forms clinically denominated intermediate osteopetroses. Dominant osteopetrosis is so far associated only with mutations in the CLCN7 gene and, although described as a benign form, it can be severely debilitating, although not at the same level as recessive forms, and can rarely result in reduced life expectancy. Severe osteopetroses due to osteoclast autonomous defects can be treated by Hematopoietic Stem Cell Transplant (HSCT), but those due to deficiency of the pro-osteoclastogenic cytokine, RANKL, are not suitable for this procedure. Likewise, it is unclear as to whether HSCT, which has high intrinsic risks, results in clinical improvement in autosomal dominant osteopetrosis. Therefore, there is an unmet medical need to identify new therapies and studies are currently in progress to test gene and cell therapies, small interfering RNA approach and novel pharmacologic treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

Development and validation of panoptic Meso scale discovery assay to quantify total systemic interleukin-6

PubMed Central

Chaturvedi, Shalini; Siegel, Derick; Wagner, Carrie L; Park, Jaehong; van de Velde, Helgi; Vermeulen, Jessica; Fung, Man-Cheong; Reddy, Manjula; Hall, Brett; Sasser, Kate

2015-01-01

Aim Interleukin-6 (IL-6), a multifunctional cytokine, exists in several forms ranging from a low molecular weight (MW 20–30 kDa) non-complexed form to high MW (200–450 kDa), complexes. Accurate baseline IL-6 assessment is pivotal to understand clinical responses to IL-6-targeted treatments. Existing assays measure only the low MW, non-complexed IL-6 form. The present work aimed to develop a validated assay to measure accurately total IL-6 (complexed and non-complexed) in serum or plasma as matrix in a high throughput and easily standardized format for clinical testing. Methods Commercial capture and detection antibodies were screened against humanized IL-6 and evaluated in an enzyme-linked immunosorbent assay format. The best antibody combinations were screened to identify an antibody pair that gave minimum background and maximum recovery of IL-6 in the presence of 100% serum matrix. A plate-based total IL-6 assay was developed and transferred to the Meso Scale Discovery (MSD) platform for large scale clinical testing. Results The top-performing antibody pair from 36 capture and four detection candidates was validated on the MSD platform. The lower limit of quantification in human serum samples (n = 6) was 9.77 pg l–1, recovery ranged from 93.13–113.27%, the overall pooled coefficients of variation were 20.12% (inter-assay) and 8.67% (intra-assay). High MW forms of IL-6, in size fractionated serum samples from myelodysplastic syndrome and rheumatoid arthritis patients, were detected by the assay but not by a commercial kit. Conclusion This novel panoptic (sees all forms) IL-6 MSD assay that measures both high and low MW forms may have clinical utility. PMID:25847183

Practice databases and their uses in clinical research.

PubMed

Tierney, W M; McDonald, C J

1991-04-01

A few large clinical information databases have been established within larger medical information systems. Although they are smaller than claims databases, these clinical databases offer several advantages: accurate and timely data, rich clinical detail, and continuous parameters (for example, vital signs and laboratory results). However, the nature of the data vary considerably, which affects the kinds of secondary analyses that can be performed. These databases have been used to investigate clinical epidemiology, risk assessment, post-marketing surveillance of drugs, practice variation, resource use, quality assurance, and decision analysis. In addition, practice databases can be used to identify subjects for prospective studies. Further methodologic developments are necessary to deal with the prevalent problems of missing data and various forms of bias if such databases are to grow and contribute valuable clinical information.

Characterization of chronic fatigue in patients with sarcoidosis in clinical remission.

PubMed

Korenromp, Ingrid H E; Heijnen, Cobi J; Vogels, Oscar J M; van den Bosch, Jules M M; Grutters, Jan C

2011-08-01

Patients with sarcoidosis frequently complain of fatigue, even when sarcoidosis has come into clinical remission. The primary aim of this study was to assess the severity of fatigue in patients with sarcoidosis in clinical remission and to characterize it according to the international criteria for chronic fatigue syndrome (CFS). Furthermore, we evaluated whether fatigue is associated with depression and anxiety, health status, and patient-reported sleep quality, and we recorded physical activity levels and muscle strength as objective assessments of fatigue. Data on 75 patients with sarcoidosis in clinical remission were obtained by questionnaires (Checklist Individual Strength [CIS], Symptom Checklist-90, Beck Depression Inventory for primary care, Medical Outcomes Study 36-Item Short-Form Health Survey), standardized interview (CFS criteria), sleep diary, accelerometer, and muscle strength tests. Fatigue severity mean score in patients with sarcoidosis in clinical remission was high (CIS fatigue severity 30.5 ± 15.5), and criteria for CFS were met in 47% of fatigued participants. Median time since diagnosis was 9 years. Fatigue was associated with depression (P = .01), anxiety (P = .013), and reduced health status (P < .001). Scores on sleep quality were normal. Physical activity levels were reduced in fatigued participants. Muscle strength, particularly handgrip (P = .006) and quadriceps strength (P < .001), was significantly associated with fatigue. Fatigue in patients with sarcoidosis in clinical remission is a frequent symptom and can be characterized as a severe and long-lasting problem, symptomatically similar to CFS. Psychologic distress and reduced health status are associated with fatigue. Interestingly, we observed significantly reduced physical activity and muscle weakness in fatigued patients.

Evaluating machine learning algorithms estimating tremor severity ratings on the Bain-Findley scale

NASA Astrophysics Data System (ADS)

Yohanandan, Shivanthan A. C.; Jones, Mary; Peppard, Richard; Tan, Joy L.; McDermott, Hugh J.; Perera, Thushara

2016-12-01

Tremor is a debilitating symptom of some movement disorders. Effective treatment, such as deep brain stimulation (DBS), is contingent upon frequent clinical assessments using instruments such as the Bain-Findley tremor rating scale (BTRS). Many patients, however, do not have access to frequent clinical assessments. Wearable devices have been developed to provide patients with access to frequent objective assessments outside the clinic via telemedicine. Nevertheless, the information they report is not in the form of BTRS ratings. One way to transform this information into BTRS ratings is through linear regression models (LRMs). Another, potentially more accurate method is through machine learning classifiers (MLCs). This study aims to compare MLCs and LRMs, and identify the most accurate model that can transform objective tremor information into tremor severity ratings on the BTRS. Nine participants with upper limb tremor had their DBS stimulation amplitude varied while they performed clinical upper-extremity exercises. Tremor features were acquired using the tremor biomechanics analysis laboratory (TREMBAL). Movement disorder specialists rated tremor severity on the BTRS from video recordings. Seven MLCs and 6 LRMs transformed TREMBAL features into tremor severity ratings on the BTRS using the specialists’ ratings as training data. The weighted Cohen’s kappa ({κ\\text{w}} ) defined the models’ rating accuracy. This study shows that the Random Forest MLC was the most accurate model ({κ\\text{w}}   =  0.81) at transforming tremor information into BTRS ratings, thereby improving the clinical interpretation of tremor information obtained from wearable devices.

Physician Beware: Severe Cyanide Toxicity from Amygdalin Tablets Ingestion

PubMed Central

Dang, Tam; Nguyen, Cham

2017-01-01

Despite the risk of cyanide toxicity and lack of efficacy, amygdalin is still used as alternative cancer treatment. Due to the highly lethal nature of cyanide toxicity, many patients die before getting medical care. Herein, we describe the case of a 73-year-old female with metastatic pancreatic cancer who developed cyanide toxicity from taking amygdalin. Detailed history and physical examination prompted rapid clinical recognition and treatment with hydroxocobalamin, leading to resolution of her cyanide toxicity. Rapid clinical diagnosis and treatment of cyanide toxicity can rapidly improve patients' clinical outcome and survival. Inquiries for any forms of ingestion should be attempted in patients with clinical signs and symptoms suggestive of poisoning. PMID:28912981

Chronic fatigue syndrome and idiopathic intracranial hypertension: Different manifestations of the same disorder of intracranial pressure?

PubMed

Higgins, J Nicholas P; Pickard, John D; Lever, Andrew M L

2017-08-01

Though not discussed in the medical literature or considered in clinical practice, there are similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) which ought to encourage exploration of a link between them. The cardinal symptoms of each - fatigue and headache - are common in the other and their multiple other symptoms are frequently seen in both. The single discriminating factor is raised intracranial pressure, evidenced in IIH usually by the sign of papilloedema, regarded as responsible for the visual symptoms which can lead to blindness. Some patients with IIH, however, do not have papilloedema and these patients may be clinically indistinguishable from patients with chronic fatigue syndrome. Yet IIH is rare, IIH without papilloedema (IIHWOP) seems rarer still, while chronic fatigue syndrome is common. So are the clinical parallels spurious or is there a way to reconcile these conflicting observations? We suggest that it is a quirk of clinical measurement that has created this discrepancy. Specifically, that the criteria put in place to define IIH have led to a failure to appreciate the existence, clinical significance or numerical importance of patients with lower level disturbances of intracranial pressure. We argue that this has led to a grossly implausible distortion of the epidemiology of IIH such that the milder form of the illness (IIHWOP) is seen as less common than the more severe and that this would be resolved by recognising a connection with chronic fatigue syndrome. We hypothesise, therefore, that IIH, IIHWOP, lesser forms of IIH and an undetermined proportion of chronic fatigue cases are all manifestations of the same disorder of intracranial pressure across a spectrum of disease severity, in which this subset of chronic fatigue syndrome would represent the most common and least severe and IIH the least common and most extreme. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

A new framework for the documentation and interpretation of oral food challenges in population-based and clinical research.

PubMed

Grabenhenrich, L B; Reich, A; Bellach, J; Trendelenburg, V; Sprikkelman, A B; Roberts, G; Grimshaw, K E C; Sigurdardottir, S; Kowalski, M L; Papadopoulos, N G; Quirce, S; Dubakiene, R; Niggemann, B; Fernández-Rivas, M; Ballmer-Weber, B; van Ree, R; Schnadt, S; Mills, E N C; Keil, T; Beyer, K

2017-03-01

The conduct of oral food challenges as the preferred diagnostic standard for food allergy (FA) was harmonized over the last years. However, documentation and interpretation of challenge results, particularly in research settings, are not sufficiently standardized to allow valid comparisons between studies. Our aim was to develop a diagnostic toolbox to capture and report clinical observations in double-blind placebo-controlled food challenges (DBPCFC). A group of experienced allergists, paediatricians, dieticians, epidemiologists and data managers developed generic case report forms and standard operating procedures for DBPCFCs and piloted them in three clinical centres. The follow-up of the EuroPrevall/iFAAM birth cohort and other iFAAM work packages applied these methods. A set of newly developed questionnaire or interview items capture the history of FA. Together with sensitization status, this forms the basis for the decision to perform a DBPCFC, following a standardized decision algorithm. A generic form including details about severity and timing captures signs and symptoms observed during or after the procedures. In contrast to the commonly used dichotomous outcome FA vs no FA, the allergy status is interpreted in multiple categories to reflect the complexity of clinical decision-making. The proposed toolbox sets a standard for improved documentation and harmonized interpretation of DBPCFCs. By a detailed documentation and common terminology for communicating outcomes, these tools hope to reduce the influence of subjective judgment of supervising physicians. All forms are publicly available for further evolution and free use in clinical and research settings. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

Hypoplasia-associated Severe Early Childhood Caries – A Proposed Definition

PubMed Central

Caufield, P.W.; Li, Y.; Bromage, T.G.

2012-01-01

We propose a new classification of severe early childhood caries (S-ECC): hypoplasia-associated severe early childhood caries (HAS-ECC). This form of caries affects mostly young children living at or below poverty, characterized by structurally damaged primary teeth that are particularly vulnerable to dental caries. These predisposing developmental dental defects are mainly permutations of enamel hypoplasia (EHP). Anthropologists and dental researchers consider EHP an indicator for infant and maternal stresses including malnutrition, a variety of illnesses, and adverse birthing conditions. Differentiation of HAS-ECC from other forms of early childhood caries is warranted because of its distinct etiology, clinical presentation, and eventual management. Defining HAS-ECC has important clinical implications: Therapies that control or prevent other types of caries are likely to be less effective with HAS-ECC because the structural integrity of the teeth is compromised prior to their emergence into the oral cavity. By the time these children present to the dentist, the treatment options often become limited to surgical management under general anesthesia. To prevent HAS-ECC, dentists must partner with other health providers to develop interventions that begin with pregnant mothers, with the aim of eliminating or ameliorating the covariates accompanying poverty, including better pre- and post-natal care and nutrition. PMID:22529242

Deja vu in neurology.

PubMed

Wild, Edward

2005-01-01

The significance of deja vu is widely recognised in the context of temporal lobe epilepsy, and enquiry about deja vu is frequently made in the clinical assessment of patients with possible epilepsy. Deja vu has also been associated with several psychiatric disorders. The historical context of current understanding of deja vu is discussed. The literature reveals deja vu to be a common phenomenon consistent with normality. Several authors have suggested the existence of a "pathological" form of deja vu that differs, qualitatively or quantitatively, from "non-pathological" deja vu. The features of deja vu suggesting neurological or psychiatric pathology are discussed. Several neuroanatomical and psychological models of the deja vu experience are highlighted, implicating the perceptual, mnemonic and affective regions of the lateral temporal cortex, hippocampus and amygdala in the genesis of deja vu. A possible genetic basis for a neurochemical model of deja vu is discussed. Clinical approaches to the patient presenting with possible deja vu are proposed.

The effectiveness of psychoanalytic-interactional psychotherapy in borderline personality disorder.

PubMed

Leichsenring, Falk; Masuhr, Oliver; Jaeger, Ulrich; Dally, Andreas; Streeck, Ulrich

2010-01-01

Different methods are available for the psychotherapeutic treatment of patients with severe personality disorders. In Germany, a special form of dynamically oriented therapy called psychoanalytic-interactional psychotherapy or method (PiM) has been clinically applied for many years. PiM was derived from psychoanalytic therapy and has been specifically adapted for the treatment of severely disordered patients, for example, patients with borderline personality disorders, prepsychotic disorders, addictions, and perversions. In a naturalistic study, the effectiveness of PiM was tested in a sample of patients with borderline personality disorders (N = 132). The patients were treated in the Clinic Tiefenbrunn near Göettingen. Standardized, reliable, and valid diagnostic instruments were used to study the treatment effects. According to the results, PiM achieved significant improvements in target symptoms, general symptoms, interpersonal problems, and contentedness with life. The results are discussed with regard to the treatment of severely disordered patients.

FDI World Dental Federation - clinical criteria for the evaluation of direct and indirect restorations. Update and clinical examples.

PubMed

Hickel, Reinhard; Peschke, Arnd; Tyas, Martin; Mjör, Ivar; Bayne, Stephen; Peters, Mathilde; Hiller, Karl-Anton; Randall, Ross; Vanherle, Guido; Heintze, Siegward D

2010-08-01

In 2007, new clinical criteria were approved by the FDI World Dental Federation and simultaneously published in three dental journals. The criteria were categorized into three groups: esthetic parameters (four criteria), functional parameters (six criteria), and biological parameters (six criteria). Each criterion can be expressed with five scores, three for acceptable and two for non-acceptable (one for reparable and one for replacement). The criteria have been used in several clinical studies since 2007, and the resulting experience in their application has led to a requirement to modify some of the criteria and scores. The two major alterations involve staining and approximal contacts. As staining of the margins and the surface have different causes, both phenomena do not appear simultaneously. Thus, staining has been differentiated into marginal staining and surface staining. The approximal contact now appears under the name "approximal anatomic form" as the approximal contour is a specific, often non-esthetic issue that cannot be integrated into the criterion "esthetic anatomical form". In 2008, a web-based training and calibration tool called e-calib (www.e-calib.info) was made available. Clinical investigators and other research workers can train and calibrate themselves interactively by assessing clinical cases of posterior restorations, which are presented as high quality pictures. Currently, about 300 clinical cases are included in the database which is regularly updated. Training for 8 of the 16 clinical criteria is available in the program: "Surface luster"; "Staining (surface, margins)"; "Color match and translucency"; "Esthetic anatomical form"; "Fracture of material and retention"; "Marginal adaptation"; "Recurrence of caries, erosion, abfraction"; and "Tooth integrity (enamel cracks, tooth fractures)". Typical clinical cases are presented for each of these eight criteria and their corresponding five scores.

Virtual Reality: An Experiential Tool for Clinical Psychology

ERIC Educational Resources Information Center

Riva, Giuseppe

2009-01-01

Several Virtual Reality (VR) applications for the understanding, assessment and treatment of mental health problems have been developed in the last 15 years. Typically, in VR the patient learns to manipulate problematic situations related to his/her problem. In fact, VR can be described as an advanced form of human-computer interface that is able…

Non-Clinical Interventions for Families with Temperamentally Difficult Children.

ERIC Educational Resources Information Center

Mettetal, Gwendolyn

This study sought to determine if general parent education, in the form of books and workshops, was an effective intervention in cases of moderate parental distress due to difficult child temperament. The parents of six "difficult" children answered questionnaires and were interviewed over several years concerning their child's temperament and its…

Schizophrenia Delays and Alters Maturation of the Brain in Adolescence

ERIC Educational Resources Information Center

Douaud, Gwenaelle; Mackay, Clare; Andersson, Jesper; James, Susan; Quested, Digby; Ray, Manaan Kar; Connell, Julie; Roberts, Neil; Crow, Timothy J.; Matthews, Paul M.; Smith, Stephen; James, Anthony

2009-01-01

Early-onset schizophrenia appears to be clinically more severe than the adult-onset form of the disease. In a previous study, we showed that anatomically related grey and white matter abnormalities found in adolescents patients were larger and more widespread than what had been reported in the literature on adult schizophrenia. Particularly, we…

Multimodal Homesickness Prevention in Boys Spending 2 Weeks at a Residential Summer Camp

ERIC Educational Resources Information Center

Thurber, Christopher A.

2005-01-01

Homesickness is the distress or impairment caused by an actual or anticipated separation from home. It is characterized by preoccupying thoughts of home and attachment objects. In its severe form, homesickness is subjectively distressing and has clinically significant cognitive, emotional, and behavioral sequelae. This study provided 75 boys who…

Social Communication Deficits in Conduct Disorder: A Clinical and Community Survey

ERIC Educational Resources Information Center

Gilmour, J.; Hill, B.; Place, M.; Skuse, D. H.

2004-01-01

Background: Increasing numbers of children are referred to Child and Adolescent Mental Health Services because of disruptive behaviour. Recent reviews on the origins of conduct problems indicate that the most severe and persistent forms are found predominantly among males with a range of neurodevelopmental vulnerabilities, which are likely to have…

Establishing the Brief Assessment of Cognition - Short form.

PubMed

Lam, Max; Wang, Mingyuan; Huang, Wanping; Eng, Goi Khia; Rapisarda, Attilio; Kraus, Michael; Kang, Sim; Keefe, R S E; Lee, Jimmy

2017-10-01

The study aims to identify and validate a parsimonious subset of tests in the commonly used Brief Assessment of Cognition in Schizophrenia (BACS) that allows the evaluation of global cognitive ability. Several permutations of subtests from the BACS were examined to identify the best subset of tests to compose the short form measure. The Brief Assessment of Cognition-Short Form (BAC-SF) was evaluated for convergent validity in healthy and psychiatric samples (N = 3718). Verbal Memory, Digit Sequencing, and Symbol Coding subtests were found to best summarize the variance of composite scores in both Asian and US Norming samples (r = 0.91) indicating that BAC-SF is an appropriate approximation of cognitive deficits. Test re-test reliability of the BAC-SF was adequate (Intraclass Correlation Coefficient (ICC) = 0.73) and showed sufficient separation between healthy controls and schizophrenia (Average Predictive Accuracy = 79.9%; replication = 76.5%). Findings indicate that the BAC-SF an could be used as a cognitive screener for large-scale clinical and epidemiological studies. The short form does not replace the need for comprehensive neuropsychological batteries purposed for detailed neuropsychological and clinical investigation of cognitive function. Further replication of the construct might be necessary in other clinical populations. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates

PubMed Central

Dwibedi, Chinmay Kumar; Sjöström, Karin; Edquist, Petra; Wai, Sun Nyunt; Uhlin, Bernt Eric

2016-01-01

Acinetobacter baumannii has emerged as an important opportunistic pathogen equipped with a growing number of antibiotic resistance genes. Our study investigated the molecular epidemiology and antibiotic resistance features of 28 consecutive carbapenem-resistant clinical isolates of A. baumannii collected throughout Sweden in 2012 and 2013. The isolates mainly belonged to clonal complexes (CCs) with an extensive international distribution, such as CC2 (n = 16) and CC25 (n = 7). Resistance to carbapenems was related to blaOXA-23 (20 isolates), blaOXA-24/40-like (6 isolates), blaOXA-467 (1 isolate), and ISAba1-blaOXA-69 (1 isolate). Ceftazidime resistance was associated with blaPER-7 in the CC25 isolates. Two classical point mutations were responsible for resistance to quinolones in all the isolates. Isolates with high levels of resistance to aminoglycosides carried the 16S rRNA methylase armA gene. The isolates also carried a variety of genes encoding aminoglycoside-modifying enzymes. Several novel structures involved in aminoglycoside resistance were identified, including Tn6279, ΔTn6279, Ab-ST3-aadB, and different assemblies of Tn6020 and TnaphA6. Importantly, a number of circular forms related to the IS26 or ISAba125 composite transposons were detected. The frequent occurrence of these circular forms in the populations of several isolates indicates a potential role of these circular forms in the dissemination of antibiotic resistance genes. PMID:26824943

The epidemiology of asthma and its comorbidities in Poland--Health problems of patients with severe asthma as evidenced in the Province of Lodz.

PubMed

Panek, Michał; Mokros, Łukasz; Pietras, Tadeusz; Kuna, Piotr

2016-03-01

Population studies supply interesting data regarding the epidemiology, comorbidity and risk factors of asthma, which have direct clinical implications for patients. The aim of the work was to evaluate the degree of severity of asthma in the studied group, the levels of anti-asthma treatment, the prevalence of asthma comorbidities and their influence on the clinical course of the illness. The study encompassed 451 participants: 52.11% were asthma patients (study group) and 47.89% were healthy subjects (controls). Respiratory function tests, ACT™ test and skin prick tests were performed. Asthma severity was mild in 14.89%, moderate in 49.36% and severe in 35.74%. Oral GCS were used by 29%, inhalers 44%, LABA 68%, SABA 67%, LAMA 6%, SAMA 14% and MX 16%. Rhinitis and allergy were significantly more common in patients. GERD and neurological diseases were risk factors for asthma, and GERD significantly intensified the risk of severe asthma. GERD, atherosclerosis, hypertension, ischaemic heart disease and other cardiac diseases, lipid disorders, COPD, and the presence of any neoplastic disease significantly worsened the degree of asthma control. Severe asthma was a significant clinical issue in over 35% of cases. The most commonly-used group of drugs were LABAs, while inhaled GCS and LAMA were uncommon, especially among severe cases. A significant problem was the high percentage of systemic GCS used by severe cases. The most important risk factor for asthma, including its severe form, is GERD. Numerous comorbid conditions significantly worsen the degree of asthma control. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular surveillance of traditional and emerging pathogens associated with canine infectious respiratory disease.

PubMed

Decaro, Nicola; Mari, Viviana; Larocca, Vittorio; Losurdo, Michele; Lanave, Gianvito; Lucente, Maria Stella; Corrente, Marialaura; Catella, Cristiana; Bo, Stefano; Elia, Gabriella; Torre, Giorgio; Grandolfo, Erika; Martella, Vito; Buonavoglia, Canio

2016-08-30

A molecular survey for traditional and emerging pathogens associated with canine infectious respiratory disease (CIRD) was conducted in Italy between 2011 and 2013 on a total of 138 dogs, including 78 early acute clinically ill CIRD animals, 22 non-clinical but exposed to clinically ill CIRD dogs and 38 CIRD convalescent dogs. The results showed that canine parainfluenza virus (CPIV) was the most commonly detected CIRD pathogen, followed by canine respiratory coronavirus (CRCoV), Bordetella bronchiseptica, Mycoplasma cynos, Mycoplasma canis and canine pneumovirus (CnPnV). Some classical CIRD agents, such as canine adenoviruses, canine distemper virus and canid herpesvirus 1, were not detected at all, as were not other emerging respiratory viruses (canine influenza virus, canine hepacivirus) and bacteria (Streptococcus equi subsp. zooepidemicus). Most severe forms of respiratory disease were observed in the presence of CPIV, CRCoV and M. cynos alone or in combination with other pathogens, whereas single CnPnV or M. canis infections were detected in dogs with no or very mild respiratory signs. Interestingly, only the association of M. cynos (alone or in combination with either CRCoV or M. canis) with severe clinical forms was statistically significant. The study, while confirming CPIV as the main responsible for CIRD occurrence, highlights the increasing role of recently discovered viruses, such as CRCoV and CnPnV, for which effective vaccines are not available in the market. Copyright © 2016 Elsevier B.V. All rights reserved.

New insights into genotype-phenotype correlations for the doublecortin-related lissencephaly spectrum.

PubMed

Bahi-Buisson, Nadia; Souville, Isabelle; Fourniol, Franck J; Toussaint, Aurelie; Moores, Carolyn A; Houdusse, Anne; Lemaitre, Jean Yves; Poirier, Karine; Khalaf-Nazzal, Reham; Hully, Marie; Leger, Pierre Louis; Elie, Caroline; Boddaert, Nathalie; Beldjord, Cherif; Chelly, Jamel; Francis, Fiona

2013-01-01

X-linked isolated lissencephaly sequence and subcortical band heterotopia are allelic human disorders associated with mutations of doublecortin (DCX), giving both familial and sporadic forms. DCX encodes a microtubule-associated protein involved in neuronal migration during brain development. Structural data show that mutations can fall either in surface residues, likely to impair partner interactions, or in buried residues, likely to impair protein stability. Despite the progress in understanding the molecular basis of these disorders, the prognosis value of the location and impact of individual DCX mutations has largely remained unclear. To clarify this point, we investigated a cohort of 180 patients who were referred with the agyria-pachygyria subcortical band heterotopia spectrum. DCX mutations were identified in 136 individuals. Analysis of the parents' DNA revealed the de novo occurrence of DCX mutations in 76 cases [62 of 70 females screened (88.5%) and 14 of 60 males screened (23%)], whereas in the remaining cases, mutations were inherited from asymptomatic (n = 14) or symptomatic mothers (n = 11). This represents 100% of families screened. Female patients with DCX mutation demonstrated three degrees of clinical-radiological severity: a severe form with a thick band (n = 54), a milder form (n = 24) with either an anterior thin or an intermediate thickness band and asymptomatic carrier females (n = 14) with normal magnetic resonance imaging results. A higher proportion of nonsense and frameshift mutations were identified in patients with de novo mutations. An analysis of predicted effects of missense mutations showed that those destabilizing the structure of the protein were often associated with more severe phenotypes. We identified several severe- and mild-effect mutations affecting surface residues and observed that the substituted amino acid is also critical in determining severity. Recurrent mutations representing 34.5% of all DCX mutations often lead to similar phenotypes, for example, either severe in sporadic subcortical band heterotopia owing to Arg186 mutations or milder in familial cases owing to Arg196 mutations. Taken as a whole, these observations demonstrate that DCX-related disorders are clinically heterogeneous, with severe sporadic and milder familial subcortical band heterotopia, each associated with specific DCX mutations. There is a clear influence of the individual mutated residue and the substituted amino acid in determining phenotype severity.

Recommendations for incorporating biologicals into management of moderate to severe plaque psoriasis: individualized patient approaches.

PubMed

Langley, Richard G; Ho, Vincent; Lynde, Charles; Papp, Kim A; Poulin, Yves; Shear, Neil; Toole, Jack; Zip, Catherine

2006-01-01

Psoriasis is a T-cell mediated skin disease that affects approximately 2% of the population worldwide. Despite the prevalence of the disease and long-standing efforts to develop strategies to treat it, there is a need for safe and effective therapies to treat psoriasis, particularly the more severe forms. Biological agents such as alefacept, efalizumab, etanercept, and infliximab have been recognized as a class of treatment distinct from other forms of therapy in the treatment algorithm of psoriasis. Recent national and international consensus meetings have developed statements that position biological agents as an important addition to the treatment armamentarium for moderate to severe psoriasis, along with phototherapy and traditional systemic agents. There has been consensus that treatment should be individualized to each patient's needs and circumstances. Biological agents offer the hope of safe, effective, long-term management of moderate to severe psoriasis. As new agents receive approval from Health Canada, the available range of therapeutic options for treating this chronic disease will broaden. A Canadian Psoriasis Expert Panel recently convened in February 2005 to analyze, based on a series of clinical case scenarios, the indications, contraindications, and considerations for and against each of the four biological agents, derived from product labelling, where available, and from the efficacy and safety data from phase 3 and earlier clinical trials, as well as post-marketing reports. The Panel has formulated a set of recommendations for incorporating these biological agents into the current treatment paradigm of moderate to severe plaque psoriasis and has identified the preferred biological agents for each patient based on individual needs and circumstances.

Severe periodontitis in Marfan's syndrome: a case report.

PubMed

Straub, Antje M; Grahame, Rodney; Scully, Crispian; Tonetti, Maurizio S

2002-07-01

Connective tissue disorders, such as some forms of Ehlers-Danlos syndrome, have been associated with severe periodontitis. This report describes a case of Marfan's syndrome, an inherited disorder of connective tissue caused by mutations in the fibrillin-1 gene, in which the patient presented with severe periodontitis. At examination, an average full-mouth clinical attachment level loss of 5.6+/-2.1 mm, furcation involvement, and severe alveolar bone loss were observed in a 41-year-old Caucasian male. Tooth hypermobility was also present. This case appears to be the first documentation of severe periodontitis in a patient with Marfan's syndrome. It supports the hypothesis that a variety of connective tissue disorders may confer increased susceptibility to periodontal tissue breakdown.

Feline sporotrichosis: histopathological profile of cutaneous lesions and their correlation with clinical presentation.

PubMed

Miranda, Luisa H M; Conceição-Silva, Fátima; Quintella, Leonardo P; Kuraiem, Bianca P; Pereira, Sandro A; Schubach, Tânia M P

2013-07-01

Cutaneous lesions of feline sporotrichosis show high fungal load and are associated with severe disease and elevated zoonotic potential. The present study describes the histopathology and fungal load of the lesions in different clinical presentations of feline sporotrichosis. Cats with sporotrichosis were separated into groups L1, L2 and L3 (lesions in one, two and three or more locations, respectively) and subjected to skin biopsies for histopathology. Eighty-six cats were included in the study. Lesions were suppurative granulomatous in 84 cases and poorly formed granulomas were predominant. The well-formed granulomas were associated with group L1. The high fungal load was predominant in group L3 and in poorly formed granuloma cases and did not occur in well-formed granulomas cases. The good general condition was associated with low fungal load. These findings suggest that the fungal load control in animals with more localized lesions and well-organized response is linked with the improvement in the outcome of infected cats. Copyright © 2013 Elsevier Ltd. All rights reserved.

High-frequency intimate partner violence during pregnancy, postnatal depression and suicidal tendencies in Harare, Zimbabwe.

PubMed

Shamu, Simukai; Zarowsky, Christina; Roelens, Kristien; Temmerman, Marleen; Abrahams, Naeemah

2016-01-01

Intimate partner violence (IPV) is a common form of violence experienced by pregnant women and is believed to have adverse mental health effects postnatally. This study investigated the association of postnatal depression (PND) and suicidal ideation with emotional, physical and sexual IPV experienced by women during pregnancy. Data were collected from 842 women interviewed postnatally in six postnatal clinics in Harare, Zimbabwe. We used the World Health Organization versions of IPV and Centre for Epidemiological Studies - Depression Scale measures to assess IPV and PND respectively. We derived a violence severity variable and combined forms of IPV variables from IPV questions. Logistic regression was used to analyse data whilst controlling for past mental health and IPV experiences. One in five women [21.4% (95% CI 18.6-24.2)] met the diagnostic criteria for PND symptomatology whilst 21.6% (95% CI 18.8-24.4) reported postpartum suicide thoughts and 4% (95% CI 2.7-5.4) reported suicide attempts. Two thirds (65.4%) reported any form of IPV. Although individual forms of severe IPV were associated with PND, stronger associations were found between PND and severe emotional IPV or severe combined forms of IPV. Suicidal ideation was associated with emotional IPV. Other forms of IPV, except when combined with emotional IPV, were not individually associated with suicidal ideation. Emotional IPV during pregnancy negatively affects women's mental health in the postnatal period. Clinicians and researchers should include it in their conceptualisation of violence and health. Further research must look at possible indirect relationships between sexual and physical IPV on mental health. Copyright © 2016 Elsevier Inc. All rights reserved.

[Negative symptoms of schizophrenia: historical aspects].

PubMed

Pringuey, D; Paquin, N; Cherikh, F; Giordana, B; Belzeaux, R; Cermolacce, M; Adida, M; Azorin, J-M

2015-12-01

The history of negative symptoms of schizophrenia rises early days of medicine in clinical and pathophysiological differences between positive and negative and their complex joint. Forming a set of typical core of symptoms, and some feature of a syndrome belonging to a specific pathophysiological mechanism, negative symptoms of schizophrenia emerge from old descriptions of clinical pictures, related to the overall look of madness, the heart of alienation, a central sign of early dementia, gradually more precisely describing the strange nature of the autistic withdrawal and schizophrenic apragmatism. At therapeutic era, negative symptoms have taken over the positive symptoms to establish an operational criteria whose importance lies in the progressive severity of this clinical type and in their contribution to therapeutic resistance. Despite the efforts of modern typological classifications, this work rehabilitates the old concept of "unitary psychosis" by defining a common symptomatic core to multiple clinical forms of psychosis, combining deficit of emotional expression and avolition, meaning a native psychopathology and a pathophysiology possibly in a common final way, and calling the arrival of new treatment strategies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The severe perinatal form of autosomal recessive polycystic kidney disease maps to chromosome 6p21.1-p12: Implications for genetic counseling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guay-Woodford, L.M.; Hopkins, S.D.; Waldo, F.B.

Autosomal recessive polycystic kidney disease (ARPKD) is a one of the most common hereditary renal cystic diseases in children. Its clinical spectrum is widely variable with most cases presenting in infancy. Most affected neonates die within the first few hours of life. At present, prenatal diagnosis relies on fetal sonography, which is often imprecise in detecting even the severe form of the disease. Recently, in a cohort of families with mostly milder ARPKD phenotypes, an ARPKD locus was mapped to a 13-cM region of chromosome 6p21-cen. To determine whether severe perinatal ARPKD also maps to chromosome 6p, we have analyzedmore » the segregation of seven microsatellite markers from the ARPKD interval in 22 families with the severe phenotype. In the majority of the affected infants, ARPKD was documented by hisopathology. Our data confirm linkage and refine the ARPKD region to a 3.8-cM interval, delimited by the markers D6S465/D6S427/D6S436/D6S272 and D6S466. Taken together, these results suggest that, despite the wide variability in clinical phenotypes, there is a single ARPKD gene. These linkage data and the absence of genetic heterogeneity in all families tested to date have important implications for DNA-based prenatal diagnoses as well as for the isolation of the ARPKD gene. 22 refs., 4 figs., 1 tab.« less

Evaluation and Referral for Developmental Dysplasia of the Hip in Infants.

PubMed

Shaw, Brian A; Segal, Lee S

2016-12-01

Developmental dysplasia of the hip (DDH) encompasses a wide spectrum of clinical severity, from mild developmental abnormalities to frank dislocation. Clinical hip instability occurs in 1% to 2% of full-term infants, and up to 15% have hip instability or hip immaturity detectable by imaging studies. Hip dysplasia is the most common cause of hip arthritis in women younger than 40 years and accounts for 5% to 10% of all total hip replacements in the United States. Newborn and periodic screening have been practiced for decades, because DDH is clinically silent during the first year of life, can be treated more effectively if detected early, and can have severe consequences if left untreated. However, screening programs and techniques are not uniform, and there is little evidence-based literature to support current practice, leading to controversy. Recent literature shows that many mild forms of DDH resolve without treatment, and there is a lack of agreement on ultrasonographic diagnostic criteria for DDH as a disease versus developmental variations. The American Academy of Pediatrics has not published any policy statements on DDH since its 2000 clinical practice guideline and accompanying technical report. Developments since then include a controversial US Preventive Services Task Force "inconclusive" determination regarding usefulness of DDH screening, several prospective studies supporting observation over treatment of minor ultrasonographic hip variations, and a recent evidence-based clinical practice guideline from the American Academy of Orthopaedic Surgeons on the detection and management of DDH in infants 0 to 6 months of age. The purpose of this clinical report was to provide literature-based updated direction for the clinician in screening and referral for DDH, with the primary goal of preventing and/or detecting a dislocated hip by 6 to 12 months of age in an otherwise healthy child, understanding that no screening program has eliminated late development or presentation of a dislocated hip and that the diagnosis and treatment of milder forms of hip dysplasia remain controversial. Copyright © 2016 by the American Academy of Pediatrics.

Variation of SNOMED CT coding of clinical research concepts among coding experts.

PubMed

Andrews, James E; Richesson, Rachel L; Krischer, Jeffrey

2007-01-01

To compare consistency of coding among professional SNOMED CT coders representing three commercial providers of coding services when coding clinical research concepts with SNOMED CT. A sample of clinical research questions from case report forms (CRFs) generated by the NIH-funded Rare Disease Clinical Research Network (RDCRN) were sent to three coding companies with instructions to code the core concepts using SNOMED CT. The sample consisted of 319 question/answer pairs from 15 separate studies. The companies were asked to select SNOMED CT concepts (in any form, including post-coordinated) that capture the core concept(s) reflected in the question. Also, they were asked to state their level of certainty, as well as how precise they felt their coding was. Basic frequencies were calculated to determine raw level agreement among the companies and other descriptive information. Krippendorff's alpha was used to determine a statistical measure of agreement among the coding companies for several measures (semantic, certainty, and precision). No significant level of agreement among the experts was found. There is little semantic agreement in coding of clinical research data items across coders from 3 professional coding services, even using a very liberal definition of agreement.

Advances in Basic and Clinical Immunology 2009

PubMed Central

Chinen, Javier; Shearer, William T.

2010-01-01

In 2009, reports on basic and clinical immunology had an increased focus on human disease mechanisms and management. The molecular pathogenesis of familial angioedema associated with estrogen was further explored to find possible factors affecting severity, including polymorphisms in enzymes and receptors related to bradykinin pathways. A placebo-controlled clinical trial of C1INH concentrate in hereditary angioedema patients demonstrated the safety of its use and the efficacy to reduce duration of angioedema attacks. The interaction of innate immunity and adaptive responses was further examined in several reports establishing the significant role of toll-like receptor stimulation for the development of optimal specific antibody responses. The 2009 update of the classification of primary immunodeficiencies introduced over 15 new genetic defects related to the immune response, including DOCK8 mutations responsible for the autosomal recessive form of the hyper IgE syndrome. Other reports expanded the clinical spectrum of disease and improved the characterization of conditions such as warts, hypogammaglobulinemia and myelokathexis (WHIM) syndrome, or the occurrence of mucormycosis and Serratia infections in chronic granulomatous disease. The frequent presentation of gastrointestinal disorders in humoral immunodeficiencies was recognized and recommendations for management were reviewed. Clinical research focused in severe combined immunodeficiency included the development and implementation of a state-wide newborn screening program for this condition, a desired goal considering the significant reduction of mortality rate when diagnosis is made early before opportunistic infections occur. PMID:20226292

Bronchiolitis caused by respiratory syncytial virus in an area of portugal: epidemiology, clinical features, and risk factors.

PubMed

Flores, P; Rebelo-de-Andrade, H; Gonçalves, P; Guiomar, R; Carvalho, C; Sousa, E N; Noronha, F T; Palminha, J M

2004-01-01

The aim of the present study was to analyse the clinical and epidemiological characteristics of bronchiolitis caused by respiratory syncytial virus (RSV) in 225 children observed in a paediatric hospital in Lisbon, Portugal, and to determine the clinical, epidemiological, or laboratory parameters that correlate with greater severity of the disease. This prospective study included hospitalised and ambulatory children younger than 36 months of age with a diagnosis of bronchiolitis and was conducted during two consecutive RSV epidemiological seasons (November-March 2000/01 and 2001/02). The median age of the patients was 5 months, and the male-to-female ratio was 1.6:1. RSV was isolated in 60.9% of patients, predominantly in the hospitalised group. The subtype A:B ratio was 7.4:1 and was similar in both seasons. RSV-positive patients were younger, had more severe clinical forms of bronchiolitis, and fewer changes in leucocyte total and differential counts. Among infected patients, higher clinical severity scores occurred in association with first wheezing episodes, overcrowded households, attendance at day-care centres, or prematurity (<36 weeks). This first prospective study of RSV epidemiology in Portugal provides a foundation for appropriate surveillance programmes of RSV infection in this country. A multicentre study is desirable in order to delineate optimal prophylactic and therapeutic guidelines for RSV infection in Portugal.

Clinical, laboratorial and immunological aspects of severe malaria in children from Guinea-Bissau.

PubMed

Domingos, Janine; Casimiro, Anaxore; Portugal-Calisto, Daniela; Varandas, Luís; Nogueira, Fátima; Silva, Marcelo Sousa

2018-04-21

Malaria is a parasitic disease of which Plasmodium falciparum causes the most severe form of the disease. The immune response against Plasmodium spp. is complex and remains unclear. The present report aimed to better understand the humoral immune response in severe malaria and analyse new immunodominant antigen candidates as possible serological marker in severe malaria in children. This study included children aged 0-16 years from Guinea-Bissau with clinical signs of severe malaria. Serological and immunochemical characterisation of different anti-P. falciparum antibodies were made by ELISA and immunoblotting using a crude protein extract of P. falciparum. Sera from 12 children with severe malaria were analysed. Nine samples were positive for total anti-P. falciparum antibodies, seven for IgM and eight for total IgG anti-P. falciparum. There was a predominance of IgG1 response, suggesting a cytophilic action in severe malaria and a major role of IgG1 over other immunoglobulins. The antigenic profile of P. falciparum showed a consistent immunoblotting pattern of approximately 180 kDa, 100 kDa and around 50-40 kDa. The serological reactivity found in protein bands makes them as immunodominant antigens and promising candidates for serological markers in the context of severe malaria. Copyright © 2018 Elsevier B.V. All rights reserved.

Episodic and Binge Gambling: An Exploration and Preliminary Quantitative Study.

PubMed

Cowlishaw, S; Nespoli, E; Jebadurai, J K; Smith, N; Bowden-Jones, H

2018-03-01

The DSM-5 includes provisions for episodic forms of gambling disorder, with such changes aligned with earlier accounts of potential binge gambling behaviours. However, there is little research that indicates the utility of these classifications of episodic or binge gambling, and this study considered their characteristics in a clinical sample. It involved administration of a new binge gambling screening tool, along with routine measures, to n = 214 patients entering a specialist treatment clinic for gambling problems. Results indicated that episodic gambling was common in this clinical context, with 28 and 32% of patients reporting gambling episodes that were (a) regular and alternating, and (b) irregular and intermittent, respectively. These patterns were distinguished by factors including associations with covariates that indicated differences from continuous gamblers. For example, the irregular episodic gamblers, but not the regular pattern, demonstrated lower levels of problem gambling severity and comorbidity. Rates of potential binge gambling, which was defined in terms of additional criteria, were around 4% and numbers were insufficient for comparable analyses. The findings support inclusion of episodic forms of gambling disorder in the DSM-5, but highlight the need for improved recognition and research on heterogeneous forms of episodic gambling.

[Clinical view of toxoplasmosis in children--personal observations].

PubMed

Czarnecka-Rudnik, D; Stanek-Bazylko, F

1997-05-01

In this work we presented our own experience with recognized and treated toxoplasmosis among children. Treated cases were observed over several years afterwards. We analyzed the frequency and character of clinical changes, evaluated the validity of serological screening and the effectiveness of treatment. The largest age group treated were children 13 months to 5 years old. 13 children had the congenital and 12 the acquired form. The most cases occurred in the nodal, ocular and ocular-cranial forms. Thus, the most common symptoms were enlarged lymphatic nodes, strabismus, febrile seizures, intracranial calcifications. In the acquired forms of the illness a distinct correlation between treatment and the decrease antibody levels, the clinical pictures showed stagnation. The fall in antibody levels occurred earlier with intermediate immunofluorescence than with ELISA method. Among 20 children associated 30-day treatment was implemented (Daraprim, Rovamycine, Biseptol), among 4 with Fansidar and Rovamycine for 2-3 weeks. Few complications occurred at the end of or after treatment and did not require treatment/intervention. Usually it was leukopenia and thrombocytopenia. Long time observation allows to state that both therapeutic models prevent renewal of illness and can be recommended for further use.

Tinea capitis favosa misdiagnosed as tinea amiantacea

PubMed Central

Anane, Sonia; Chtourou, Olfa

2012-01-01

Introduction Favus of the scalp or tinea capitis favosa is a chronic dermatophyte infection of the scalp. In almost cases, favus is caused by Trichophyton schoenleinii, anthropophilic dermatophyte. It is characterized by the presence of scutula and severe alopecia. Besides the classic clinical type of tinea capitis favosa, there are many variant of clinical form which may persist undiagnosed for many years. In this work, we report an atypical form of favus to Trichophyton schoenleinii which was misdiagnosed as tinea amiantacea. Case-report An 11-year old girl came to the outpatient department of dermatology (day 0) with history of tinea amiantacea treated unsuccessfully with keratolytic shampoo (day – 730). She presented a diffuse scaling of the scalp with thick scaly patches and without scutula or alopecia. A diagnosis of tinea favosa by T. schoenleinii was made by mycological examination. She was treated with griseofulvin and ketoconazole in the form of foaming gel for twelve weeks. Despite treatment, clinical evolution was marked by appearance of permanent alopecia patches. The follow-up mycological examination was negative. Conclusion Because of ultimate evolution of favus into alopecia, we emphasize the importance of mycological examination in case of diffuse scaling. PMID:24432210

Disseminated sporotrichosis

PubMed Central

Romero-Cabello, Raúl; Bonifaz, Alexandro; Romero-Feregrino, Raúl; Sánchez, Carlos Javier; Linares, Yancy; Zavala, Jorge Tay; Romero, Leticia Calderón; Romero-Feregrino, Rodrigo; Vega, José T Sánchez

2011-01-01

Sporotrichosis is a subacute or chronic infection caused by Sporothrix schenckii. It is a primary cutaneous infection and it has different clinical forms: disseminated by lymphatic vessels (75%), localised cutaneous form (20%), disseminated cutaneous and extracuteus rarely. The systemic disseminated sporotrichosis is considered a severe opportunistic infection. The best diagnostic test is the culture. The authors report a case of a 36-year-old man, originally from Puebla, Mexico, with a diagnosis of disseminated sporotrichosis. Differential diagnosis with other pathologies includes leishmaniasis, chromoblastomycosis, tuberculosis verrucose and lymphangitis. The development of unusual presentations in immunocompromised patients has been reported. PMID:22700076

Solar elastosis in its papular form: uncommon, mistakable.

PubMed

Heng, Jun Khee; Aw, Derrick Chen Wee; Tan, Kong Bing

2014-01-01

Solar elastosis is a degenerative condition of elastic tissue in the dermis due to prolonged sun exposure. There are a variety of clinical manifestations of solar elastosis. In its most common form, solar elastosis manifests as yellow, thickened, coarsely wrinkled skin. We report two uncommon cases of severe solar elastosis with a papular morphology. Its presentation can closely mimic a host of cutaneous disorders and thus, although it is helpful to be cognizant of this entity, it is still crucial to biopsy these lesions to avoid missing a more sinister condition.

Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency.

PubMed

Olsen, Rikke K J; Andresen, Brage S; Christensen, Ernst; Bross, Peter; Skovby, Flemming; Gregersen, Niels

2003-07-01

Mutations in electron transfer flavoprotein (ETF) and its dehydrogenase (ETFDH) are the molecular basis of multiple acyl-CoA dehydrogenation deficiency (MADD), an autosomal recessively inherited and clinically heterogeneous disease that has been divided into three clinical forms: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). To examine whether these different clinical forms could be explained by different ETF/ETFDH mutations that result in different levels of residual ETF/ETFDH enzyme activity, we have investigated the molecular genetic basis for disease development in nine patients representing the phenotypic spectrum of MADD. We report the genomic structures of the ETFA, ETFB, and ETFDH genes and the identification and characterization of seven novel and three previously reported disease-causing mutations. Our molecular genetic investigations of these nine patients are consistent with three clinical forms of MADD showing a clear relationship between the nature of the mutations and the severity of disease. Interestingly, our data suggest that homozygosity for two null mutations causes fetal development of congenital anomalies resulting in a type I disease phenotype. Even minute amounts of residual ETF/ETFDH activity seem to be sufficient to prevent embryonic development of congenital anomalies giving rise to type II disease. Overexpression studies of an ETFB-D128N missense mutation identified in a patient with type III disease showed that the residual activity of the mutant enzyme could be rescued up to 59% of that of wild-type activity when ETFB-D128N-transformed E. coli cells were grown at low temperature. This indicates that the effect of the ETF/ETFDH genotype in patients with milder forms of MADD, in whom residual enzyme activity allows modulation of the enzymatic phenotype, may be influenced by environmental factors like cellular temperature. Copyright 2003 Wiley-Liss, Inc.

Mere exposure effect can be elicited in transient global amnesia.

PubMed

Marin-Garcia, Eugenia; Ruiz-Vargas, Jose M; Kapur, Narinder

2013-01-01

Transient global amnesia (TGA) is one of the most severe forms of anterograde amnesia seen in clinical practice, yet patients may show evidence of spared learning during the amnesic episode. The scope of spared learning in such a severe form of amnesia remains uncertain, and it is also unclear whether findings from single-case studies hold up in group studies of TGA patients. In this group study, we found evidence that extended the domain of spared learning in TGA to include the mere exposure effect, whereby enhanced preference is primed by prior exposure to stimuli. We demonstrate this effect during an acute episode in a group of TGA patients, where they showed enhanced preference for previously exposed faces, despite markedly impaired performance on standard anterograde memory tests.

Optimal Cut-Off Points on the Health Anxiety Inventory, Illness Attitude Scales and Whiteley Index to Identify Severe Health Anxiety

PubMed Central

Hedman, Erik; Lekander, Mats; Ljótsson, Brjánn; Lindefors, Nils; Rück, Christian; Andersson, Gerhard; Andersson, Erik

2015-01-01

Background Health anxiety can be viewed as a dimensional phenomenon where severe health anxiety in form of DSM-IV hypochondriasis represents a cut-off where the health anxiety becomes clinically significant. Three of the most reliable and used self-report measures of health anxiety are the Health Anxiety Inventory (HAI), the Illness Attitude Scales (IAS) and the Whiteley Index (WI). Identifying the optimal cut-offs for classification of presence of a diagnosis of severe health anxiety on these measures has several advantages in clinical and research settings. The aim of this study was therefore to investigate the HAI, IAS and WI as proximal diagnostic instruments for severe health anxiety defined as DSM-IV hypochondriasis. Methods We investigated sensitivity, specificity and predictive value on the HAI, IAS and WI using a total of 347 adult participants of whom 158 had a diagnosis of severe health anxiety, 97 had obsessive-compulsive disorder and 92 were healthy non-clinical controls. Diagnostic assessments were conducted using the Anxiety Disorder Interview Schedule. Results Optimal cut-offs for identifying a diagnosis of severe health anxiety was 67 on the HAI, 47 on the IAS, and 5 on the WI. Sensitivity and specificity were high, ranging from 92.6 to 99.4%. Positive and negative predictive values ranged from 91.6 to 99.4% using unadjusted prevalence rates. Conclusions The HAI, IAS and WI have very good properties as diagnostic indicators of severe health anxiety and can be used as cost-efficient proximal estimates of the diagnosis. PMID:25849477

Single Nucleotide Polymorphisms Predict Symptom Severity of Autism Spectrum Disorder

ERIC Educational Resources Information Center

Jiao, Yun; Chen, Rong; Ke, Xiaoyan; Cheng, Lu; Chu, Kangkang; Lu, Zuhong; Herskovits, Edward H.

2012-01-01

Autism is widely believed to be a heterogeneous disorder; diagnosis is currently based solely on clinical criteria, although genetic, as well as environmental, influences are thought to be prominent factors in the etiology of most forms of autism. Our goal is to determine whether a predictive model based on single-nucleotide polymorphisms (SNPs)…

Update on Research and Application of Problem-Based Learning in Medical Science Education

ERIC Educational Resources Information Center

Fan, Chuifeng; Jiang, Biying; Shi, Xiuying; Wang, Enhua; Li, Qingchang

2018-01-01

Problem-based learning (PBL) is a unique form of pedagogy dedicated to developing students' self-learning and clinical practice skills. After several decades of development, although applications vary, PBL has been recognized all over the world and implemented by many medical schools. This review summarizes and updates the application and study of…

Interpersonal and Affective Features of Psychopathy in Children and Adolescents: Advancing a Developmental Perspective--Introduction to Special Section

ERIC Educational Resources Information Center

Pardini, Dustin A.; Loeber, Rolf

2007-01-01

The interpersonal (e.g., manipulative, deceitful) and affective (e.g., callous, unemotional) features associated with adult psychopathy have been identified in children and adolescents. Although early research suggests that these features have clinical utility in identifying a particularly severe and recalcitrant form of antisocial behavior with…

Autosomal dominant polycystic kidney disease in a family with mosaicism and hypomorphic allele.

PubMed

Reiterová, Jana; Štekrová, Jitka; Merta, Miroslav; Kotlas, Jaroslav; Elišáková, Veronika; Lněnička, Petr; Korabečná, Marie; Kohoutová, Milada; Tesař, Vladimír

2013-03-15

Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations. The large intra-familial variability of ADPKD highlights a role for genetic background. Here we report a case of ADPKD family initially appearing unlinked to the PKD1 or PKD2 loci and the influence of mosaicism and hypomorphic allele on the variability of the clinical course of the disease. A grandmother with the PKD1 gene mutation in mosaicism (p.Val1105ArgfsX4) and with mild clinical course of ADPKD (end stage renal failure at the age of 77) seemed to have ADPKD because of PKD2 gene mutation. On the other hand, her grandson had a severe clinical course (end stage renal disease at the age of 45) in spite of the early treatment of mild hypertension. There was found by mutational analysis of PKD genes that the severe clinical course was caused by PKD1 gene frameshifting mutation inherited from his father and mildly affected grandmother in combination with inherited hypomorphic PKD1 allele with described missense mutation (p.Thr2250Met) from his clinically healthy mother. The sister with two cysts and with PKD1 hypomorphic allele became the kidney donor to her severely affected brother. We present the first case of ADPKD with the influence of mosaicism and hypomorphic allele of the PKD1 gene on clinical course of ADPKD in one family. Moreover, this report illustrates the role of molecular genetic testing in assessing young related kidney donors for patients with ADPKD.

Performance improvement: the organization's quest.

PubMed

McKinley, C O; Parmer, D E; Saint-Amand, R A; Harbin, C B; Roulston, J C; Ellis, R A; Buchanan, J R; Leonard, R B

1999-01-01

In today's health care marketplace, quality has become an expectation. Stakeholders are demanding quality clinical outcomes, and accrediting bodies are requiring clinical performance data. The Roosevelt Institute's quest was to define and quantify quality outcomes, develop an organizational culture of performance improvement, and ensure customer satisfaction. Several of the organization's leaders volunteered to work as a team to develop a specific performance improvement approach tailored to the organization. To date, over 200 employees have received an orientation to the model and its philosophy and nine problem action and process improvement teams have been formed.

Use of text messaging to audit early clinical outcome following vasectomy in primary care.

PubMed

Cooper, Graham; Walker, Jean; Harris, Douglas; Stewart, Rorie; Nicol, Douglas; Ogg, Mike

2011-04-01

Fifty patients undergoing vasectomy at community-based day surgery clinics in Grampian were invited to participate in follow-up by text message. Forty-six (92%) of the patients responded, 14 reporting problems, generally of a minor nature, but severe enough to result in unscheduled time off work (n = 4) and oral antibiotic therapy (n = 5). Text messaging appears to be a useful form of communication for audit in this setting. The study findings have influenced the information provided by the authors at preoperative counselling.

Ocular Changes and Approaches of Ophthalmopathy in Basedow – Graves- Parry- Flajani Disease

PubMed Central

SARACI, George; TRETA, Anamaria

2011-01-01

ABSTRACT Basedow-Graves disease is an autoimmune condition with multiple local and systemic aspects. Among these, oculopathy has a major impact on patient's life from both functional and esthetic point of view. Basedow-Graves oculopathy requires an appropriate positive and differential diagnosis using clinical and imagistic approaches. Treatment is always required in moderate or severe forms and it begins with simple general points and continues with medical and surgical therapies. Current article stresses upon the most characteristic clinical signs of thyroidian ophthalmopathy and the required current therapeutic approaches. PMID:22205899

Patterns of clinical nail appearances in patients with cutaneous psoriasis

PubMed Central

MARINA, ELENA MIHAELA; BOTAR-JID, CAROLINA; BOLBOACA, SORANA DANIELA; ROMAN, IULIA IOANA; SENILA, CORINA SIMONA; MIHU, CARMEN MIHAELA; TATARU, DUMITRU ALEXANDRU

2017-01-01

Background and aim Nail manifestations are often an overlooked aspect in psoriatic disease, cutaneous and joint involvement being far more often reported and investigated. The reported prevalence of nail changes varies in literature, specific fingernail clinical features having different degrees of occurrence. The aim of this study was to describe specific clinical patterns of fingernail alterations in adult patients with plaque-type psoriasis in a university hospital in the North-West of Romania. Methods Clinical data of 35 patients with fingernail psoriasis were collected and analyzed. Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI) scores were used to quantify disease extension in each patient. Results PASI score proved linearly correlated with NAPSI score (p<0.05). The age of onset of fingernail psoriasis was positively correlated with age of onset cutaneous psoriasis (p<0.0001). Furthermore, the duration of cutaneous involvement and NAPSI proved significantly related (p<0.05). The third fingernail in the right hand and first fingernail in the left hand were in most of the cases severely affected. The most common observed nail pattern was pitting, followed by salmon patches and subungual hyperkeratosis. Conclusion Important nail changes appear even in moderate forms of cutaneous psoriasis. Particular localization of specific fingernail psoriasis pattern enables the possibility of detecting early stage disease. PMID:28246493

[Chronic active hepatitis: clinical, biochemical, and histopathologic correlation].

PubMed

Subauste, M C

1989-01-01

A retrospective study over 26 female patients with chronic active hepatitis was made. The mean age was 39 years old, the mean length of illness of 8 months; 5 patients had positive markers for hepatitis B. Patients were selected with the grade of histological activity: 8 patients had a mild form from disease (2A) and 16 with a severe one (2B). The predominant group was 2B. Severe inflammatory infiltration was the hallmark and multiobulillar necrosis, bridging, eosinophils and hiperplasia of kuppfer cells were found only in this group. Clinical features range from hepatic manifestations to systemic ones. Chronic active hepatitis may present with cholestasis, but the latter is not always related with the grade of activity. Group 2B had elevated aminotransferases and a low concentration for protrobine.

[Imported dengue: an emerging arbovirosis in Spain].

PubMed

Ramos Geldres, T T; García López-Hortelano, M; Baquero-Artigao, F; Montero Vega, D; López Quintana, B; Mellado Peña, M J

2015-01-01

Dengue is caused by one of 4 serotypes of dengue virus. Only imported cases have been reported in Spain. The main clinical findings are fever and exanthema, although there may be severe forms, particularly in secondary infections. Five children with a primary, non severe dengue infection are presented. The diagnosis was based on clinical suspicion and epidemiological history, and confirmed by immunochromatography and ELISA tests. The outcome was favourable in all cases. It is important to consider this diagnosis in international travellers that present with fever within the 14 days of returning from an endemic area, in order to get an early diagnosis, adequate treatment and a good prognosis. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Lomitapide for the treatment of hypertriglyceridemia.

PubMed

Brahm, Amanda J; Hegele, Robert A

2016-12-01

Severe genetic forms of hypertriglyceridemia carry a risk of life-threatening pancreatitis and lack available effective treatments. Lomitapide is a microsomal triglyceride transfer protein inhibitor currently approved for treatment of homozygous familial hypercholesterolemia that may be useful in the management of severe hypertriglyceridemia. Areas covered: Published trials of lomitapide that reported plasma triglyceride response were reviewed, as was a case report of a patient with hypertriglyceridemia who was treated for 13 years with lomitapide. ClinicalTrials.gov was also reviewed for any unpublished results and ongoing trials. Expert opinion: Lomitapide demonstrates effective triglyceride lowering and may be a useful treatment for patients with genetic hypertriglyceridemia and recurrent acute pancreatitis who are refractory to traditional treatment. However, long term hepatic safety may be a concern and direct clinical trial-level data are lacking for this indication.

An autistic dimension: a proposed subtype of obsessive-compulsive disorder.

PubMed

Bejerot, Susanne

2007-03-01

This article focuses on the possibility that autism spectrum disorder (ASD: Asperger syndrome, autism and atypical autism) in its milder forms may be clinically important among a substantial proportion of patients with obsessive-compulsive disorder (OCD), and discusses OCD subtypes based on this proposition. The hypothesis derives from extensive clinical experience of OCD and ASD, and literature searches on MEDLINE. Neuropsychological deficits are more common in OCD than in panic disorder and depression. Moreover, obsessive-compulsive and schizotypal personality disorders are over-represented in OCD. These may constitute mis-perceived clinical manifestations of ASD. Furthermore, repetitive behaviours and hoarding are common in Asperger syndrome. It is suggested that the comorbidity results in a more severe and treatment resistant form of OCD. OCD with comorbid ASD should be recognized as a valid OCD subtype, analogous to OCD with comorbid tics. An odd personality, with paranoid, schizotypal, avoidant or obsessive-compulsive traits, may indicate these autistic dimensions in OCD patients.

A physiotherapy perspective of musculoskeletal imaging in sport.

PubMed

Callaghan, M J

2012-08-01

This paper presents a physiotherapy perspective on the role that imaging is now playing in the diagnosis and management of musculoskeletal and sporting injuries. Although the Royal College of Radiologists and the UK Chartered Society of Physiotherapy were founded in the latter part of the nineteenth century, it is 100 years later that developments in the UK NHS have led to increased roles for non-medical healthcare professionals and allied health professionals, such as physiotherapists, in an extended clinical role. Physiotherapists, perhaps because of their knowledge of clinical and applied anatomy, have keenly taken up the opportunities offered to request and interpret imaging in its various forms; the most commonly available are plain radiography, musculoskeletal ultrasound and MRI. This has meant taking formal courses under the auspices of universities with mentorship and tutoring within the clinical setting, which are part of a continuing professional development. The ability to request several forms of imaging has enhanced physiotherapy practice and has increased the appreciation of the responsibilities which accompany this new role.

Bacterial Biofilms in Chronic Rhinosinusitis and Their Implications for Clinical Management.

PubMed

Karunasagar, Abhilasha; Garag, Santosh S; Appannavar, Suma B; Kulkarni, Raghavendra D; Naik, Ashok S

2018-03-01

To study the microbiological profile in patients with chronic rhino-sinusitis. To correlate disease severity with the presence of biofilms and host risk factors. To assess outcome of Sinus Surgery 2 weeks post operatively in terms of presence of bacteria and their ability to form biofilm. Prospective study. 50 cases of chronic rhino-sinusitis requiring Functional Endoscopic Sinus Surgery admitted in SDM Hospital, Dharwad, Karnataka were studied using intra-operative mucosal samples for microbiological analysis. The organisms isolated were tested for biofilm forming ability using three in vitro tests. Severity of disease was assessed using SNOT 22 scoring system. Of 50 cases studied, 66% showed presence of chronic rhino-sinusitis with polyposis and had higher SNOT scores compared to those without polyps. Bacterial isolates were obtained from only 17 samples. Staphylococcus species was isolated from 16 samples and Klebsiella pneumoniae from one. 11 Staph spp. isolates showed biofilm forming ability in vitro. Postoperative events in 3 cases yielded biofilm-forming Staphylococcus. Staphylococcus was the most dominant organism isolated and 11 isolates were biofilm formers. Thus the detection of biofilm forming organisms can be considered as a negative prognostic indicator and should forewarn the surgeon about the risk of recurrence.

Increased resistance of contact lens related bacterial biofilms to antimicrobial activity of soft contact lens care solutions

PubMed Central

Szczotka-Flynn, Loretta B.; Imamura, Yoshifumi; Chandra, Jyotsna; Yu, Changping; Mukherjee, Pranab K.; Pearlman, Eric; Ghannoum, Mahmoud A.

2014-01-01

PURPOSE To determine if clinical and reference strains of Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus aureus form biofilms on silicone hydrogel contact lenses, and ascertain antimicrobial activities of contact lens care solutions. METHODS Clinical and American Type Culture Collection (ATCC) reference strains of Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus aureus were incubated with lotrafilcon A lenses under conditions that facilitate biofilm formation. Biofilms were quantified by quantitative culturing (colony forming units, CFUs), and gross morphology and architecture were evaluated using scanning electron microscopy (SEM) and confocal microscopy. Susceptibilities of the planktonic and biofilm growth phases of the bacteria to five common multipurpose contact lens care solutions and one hydrogen peroxide care solution were assessed. RESULTS P. aeruginosa, S. marcescens, and S. aureus reference and clinical strains formed biofilms on lotrafilcon A silicone hydrogel contact lenses, as dense networks of cells arranged in multiple layers with visible extracellular matrix. The biofilms were resistant to commonly used biguanide preserved multipurpose care solutions. P. aeruginosa and S. aureus biofilms were susceptible to a hydrogen peroxide and a polyquaternium preserved care solution, whereas S. marcescens biofilm was resistant to a polyquaternium preserved care solution but susceptible to hydrogen peroxide disinfection. In contrast, the planktonic forms were always susceptible. CONCLUSIONS P. aeruginosa, S. marcescens, and S. aureus form biofilms on lotrafilcon A contact lenses, which in contrast to planktonic cells, are resistant to the antimicrobial activity of several soft contact lens care products. PMID:19654521

Severe Propanil [N-(3,4-dichlorophenyl) propanamide] Pesticide Self-Poisoning

PubMed Central

Eddleston, Michael; Rajapakshe, Manjula; Roberts, Darren; Reginald, K; Sheriff, M H Rezvi; Dissanayake, Wasantha; Buckley, Nick

2007-01-01

Background propanil pesticide poisoning can produce methaemoglobinaemia, tissue hypoxia, and depression of CNS and respiratory system. It has been recorded only rarely worldwide and most current poison texts consider propanil to be of low toxicity. However, propanil self-poisoning is a significant clinical problem in parts of Sri Lanka and a not uncommon cause of death. Aim of study to report the clinical features and management of severe propanil poisoning. Patients and Methods we report a retrospective case series of patients who were treated in the intensive care unit (ICU) of and/or died in Anuradhapura General Hospital between 1998 and early 2002. Results sixteen patients were identified. Common manifestations of toxicity included confusion, reduced conscious level, cyanosis, and respiratory depression. Marked haemolysis was noted in several patients. Nine deaths occurred due to respiratory depression and cardiorespiratory arrest. Management was difficult given the lack of IV methylene blue, inability to measure methaemoglobin levels, and paucity of ICU beds. Conclusions this series indicates that propanil poisoning can be a severe form of self-poisoning, particularly in resource-poor settings. We have now initiated the establishment of a prospective series of propanil poisoned patients to further describe its clinical features, responsiveness to therapy, and case fatality rate. PMID:12507053

Clinical translation of handheld optical coherence tomography: practical considerations and recent advancements

NASA Astrophysics Data System (ADS)

Monroy, Guillermo L.; Won, Jungeun; Spillman, Darold R.; Dsouza, Roshan; Boppart, Stephen A.

2017-12-01

Since the inception of optical coherence tomography (OCT), advancements in imaging system design and handheld probes have allowed for numerous advancements in disease diagnostics and characterization of the structural and optical properties of tissue. OCT system developers continue to reduce form factor and cost, while improving imaging performance (speed, resolution, etc.) and flexibility for applicability in a broad range of fields, and nearly every clinical specialty. An extensive array of components to construct customized systems has also become available, with a range of commercial entities that produce high-quality products, from single components to full systems, for clinical and research use. Many advancements in the development of these miniaturized and portable systems can be linked back to a specific challenge in academic research, or a clinical need in medicine or surgery. Handheld OCT systems are discussed and explored for various applications. Handheld systems are discussed in terms of their relative level of portability and form factor, with mention of the supporting technologies and surrounding ecosystem that bolstered their development. Additional insight from our efforts to implement systems in several clinical environments is provided. The trend toward well-designed, efficient, and compact handheld systems paves the way for more widespread adoption of OCT into point-of-care or point-of-procedure applications in both clinical and commercial settings.

Clinical relevance of diagnosing COPD by fixed ratio or lower limit of normal: a systematic review.

PubMed

van Dijk, Wouter D; Gupta, Nisha; Tan, Wan C; Bourbeau, Jean

2014-02-01

Different spirometric criteria in diagnosing COPD have been advocated by different groups, debilitating adequate diagnosis and treatment of COPD. We reviewed the clinical relevance of fixed ratio and lower limit of normal (LLN) in diagnosing COPD and explored if modifying factors may affect their clinical relevance. Two reviewers independently searched PubMed and Embase for papers that compared both criteria on any clinically relevant outcome, published before June 1st, 2012, without any language restriction. Two reviewers independently extracted the study characteristics, including study design, population characteristics and diagnostic criteria used, and summarized the results of clinical relevance. Study quality was assessed by scoring forms for bias and level of evidence. Of 394 studies retrieved, 11 studies were included, with a median of 1,258 participants. Although both criteria appeared related with various clinically relevant outcomes, we were unable to prefer one criterion over the other, with various performances of the criteria for different outcomes. Should the criteria disagree on diagnosis, an alternative diagnosis should be suspected, in particular in those (elderly) with less severe airflow limitation for whom the LLN appears a better criterion. The fixed ratio appears to perform better in subjects with more severe airflow limitation. In diagnosing COPD, severity of airflow limitation appears an important factor for choosing whether the fixed ratio or LLN. Disagreement between the criteria is suggestive for an alternative diagnosis. Future studies on clinical relevance should further reveal the criterion of choice, in order to improve adequate diagnosis and consequent treatments.

A screening tool to enhance clinical trial participation at a community center involved in a radiation oncology disparities program.

PubMed

Proctor, Julian W; Martz, Elaine; Schenken, Larry L; Rainville, Rebecca; Marlowe, Ursula

2011-05-01

To investigate the effectiveness of a screening tool to enhance clinical trial participation at a community radiation oncology center involved in a National Cancer Institute-funded disparities program but lacking on-site clinical trials personnel. The screening form was pasted to the front of the charts and filled out for all new patients over the 9-month period of the study, during which time five external beam radiation therapy (EBRT) trials and a patient perception study were open for accrual. Patient consent was obtained by assorted personnel at several different sites. Patients potentially eligible for a trial were identified and approached by one of the clinic staff. Patients who were under- or uninsured, age > 80 years, members of an racial/ethnic minority, or recipients of medical assistance were identified as at risk for health care disparities and were offered patient navigator services. Of 196 patients consulted during the study, 144 were treated with EBRT. Of the 24 patients eligible for EBRT trials, 23 were approached (one had an incomplete screening form), and 15 accepted. Of 77 patients eligible for a patient perception trial, 72 were approached (five had incomplete forms), and 45 accepted. The eligibility and acceptance rates for EBRT trials were similar for disparities and nondisparities patients. Screening was completed for 96 patients (67%). When completed, the screening tool ensured clinical trial accrual. The major factor limiting overall accrual was a shortage of available trials.

A Screening Tool to Enhance Clinical Trial Participation at a Community Center Involved in a Radiation Oncology Disparities Program

PubMed Central

Proctor, Julian W.; Martz, Elaine; Schenken, Larry L.; Rainville, Rebecca; Marlowe, Ursula

2011-01-01

Purpose: To investigate the effectiveness of a screening tool to enhance clinical trial participation at a community radiation oncology center involved in a National Cancer Institute–funded disparities program but lacking on-site clinical trials personnel. Patients and Methods: The screening form was pasted to the front of the charts and filled out for all new patients over the 9-month period of the study, during which time five external beam radiation therapy (EBRT) trials and a patient perception study were open for accrual. Patient consent was obtained by assorted personnel at several different sites. Patients potentially eligible for a trial were identified and approached by one of the clinic staff. Patients who were under- or uninsured, age > 80 years, members of an racial/ethnic minority, or recipients of medical assistance were identified as at risk for health care disparities and were offered patient navigator services. Results: Of 196 patients consulted during the study, 144 were treated with EBRT. Of the 24 patients eligible for EBRT trials, 23 were approached (one had an incomplete screening form), and 15 accepted. Of 77 patients eligible for a patient perception trial, 72 were approached (five had incomplete forms), and 45 accepted. The eligibility and acceptance rates for EBRT trials were similar for disparities and nondisparities patients. Screening was completed for 96 patients (67%). Conclusion: When completed, the screening tool ensured clinical trial accrual. The major factor limiting overall accrual was a shortage of available trials. PMID:21886496

Comparison of health-related quality of life among men with different co-existing severe mental disorders in treatment for substance use.

PubMed

Adan, Ana; Marquez-Arrico, Julia E; Gilchrist, Gail

2017-10-23

Patient-perceived health-related quality of life has become an important outcome in health care as an indicator of treatment effectiveness and recovery for patients with substance use disorder. As no study has assessed health-related quality of life among male patients with substance use disorder and co-existing severe mental illness, we compared health-related quality of life among patients with substance use disorder and the following severe mental illness diagnosis in Barcelona, Spain: schizophrenia, bipolar disorder, major depressive disorder, and examined the associations with clinically related variables. Additionally, we compared results for health-related quality of life in patients with substance use disorder and severe mental illness, with Spanish population norms. We assessed 107 substance use disorder male patients using the 36-Item Short Form Health Survey comparing results across three groups with: comorbid schizophrenia (n = 37), comorbid bipolar disorder (n = 34), and comorbid major depressive disorder (n = 36). Multiple analyses of variance were performed to explore health-related quality of life by the type of co-existing SMI and linear regression analyses examined clinical correlates for the 36-Item Short Form Health Survey dimensions for each group. There were differences in Physical Functioning, Vitality and the Physical Composite Scale among groups. Poorer Physical Functioning was observed for patients with comorbid schizophrenia (80.13±3.27) and major depressive disorder (81.97±3.11) compared with comorbid bipolar disorder patients (94.26±1.93). Patients with substance use disorder and schizophrenia presented lower scores in Vitality (41.6±2.80) than those with co-existing bipolar disorder (55.68±3.66) and major depressive disorder (53.63±2.92). Finally, results in the Physical Composite Scale showed lower scores for patients with comorbid schizophrenia (51.06±1.41) and major depressive disorder (51.99±1.87) than for those with bipolar disorder (60.40±2.17). Moreover, all groups had poorer health-related quality of life, especially Social Functioning, Role-Emotional and Mental Health, compared with population norms. Different clinical variables (e.g. medical disease comorbidity, severity of addiction, psychiatric symptomatology, suicide attempts, drug relapses) were related to different health-related quality of life dimensions depending on the co-existing severe mental illness. Among male patients with substance use disorder, co-existing severe mental illness may influence some health-related quality of life dimensions and clinically related variables. Such differences may require tailored therapeutic interventions.

[Treatment of systemic lupus erythematosus: myths, certainties and doubts].

PubMed

Ruiz-Irastorza, Guillermo; Danza, Alvaro; Khamashta, Munther

2013-12-21

Systemic lupus erythematosus (SLE) is a complex disease with different clinical forms of presentation, including a wide range of severity and organic involvement. Such circumstance, along with the fact of the uncommon nature of the disease and the absence of clinically representative response criteria, make it difficult to design controlled clinical trials in SLE patients. As a result, observational studies have a special relevance, being a source of valuable information of SLE prognosis and outcome as well as of the efficacy and adverse effects of the different therapies. Herein we update some of the main treatments used in SLE. Steroids may have more risks than benefits if used at high doses. New mechanisms of action have been described, supporting the use of lower doses, possibly with the same efficacy and less adverse effects. Intravenous pulses of cyclophosphamide still have a role in the treatment of proliferative lupus nephritis and other serious SLE manifestations. Mycophenolate mofetil has shown its efficacy both as induction and maintenance therapy of selected cases of lupus nephritis. Biological therapies have emerged as new promising options. Although clinical trials have not confirmed a clear superiority of rituximab in SLE, observational studies have shown good response rates in severe SLE manifestations or refractory forms. Belimumab has recently been added to the therapeutic armamentarium of SLE; although its place in clinical practice is not well-defined, it may be recommended in active patients with no response or good tolerance to standard therapies. Hydroxichloroquine improves survival, decreases the risk of thrombosis and flares and is safe in pregnancy, and should be considered the baseline therapy in most SLE patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Biomarkers and Surrogate Endpoints in Uveitis: The Impact of Quantitative Imaging.

PubMed

Denniston, Alastair K; Keane, Pearse A; Srivastava, Sunil K

2017-05-01

Uveitis is a major cause of sight loss across the world. The reliable assessment of intraocular inflammation in uveitis ('disease activity') is essential in order to score disease severity and response to treatment. In this review, we describe how 'quantitative imaging', the approach of using automated analysis and measurement algorithms across both standard and emerging imaging modalities, can develop objective instrument-based measures of disease activity. This is a narrative review based on searches of the current world literature using terms related to quantitative imaging techniques in uveitis, supplemented by clinical trial registry data, and expert knowledge of surrogate endpoints and outcome measures in ophthalmology. Current measures of disease activity are largely based on subjective clinical estimation, and are relatively insensitive, with poor discrimination and reliability. The development of quantitative imaging in uveitis is most established in the use of optical coherence tomographic (OCT) measurement of central macular thickness (CMT) to measure severity of macular edema (ME). The transformative effect of CMT in clinical assessment of patients with ME provides a paradigm for the development and impact of other forms of quantitative imaging. Quantitative imaging approaches are now being developed and validated for other key inflammatory parameters such as anterior chamber cells, vitreous haze, retinovascular leakage, and chorioretinal infiltrates. As new forms of quantitative imaging in uveitis are proposed, the uveitis community will need to evaluate these tools against the current subjective clinical estimates and reach a new consensus for how disease activity in uveitis should be measured. The development, validation, and adoption of sensitive and discriminatory measures of disease activity is an unmet need that has the potential to transform both drug development and routine clinical care for the patient with uveitis.

[Monitoring intracranial pressure in severe traumatic brain injury].

PubMed

García-Lira, José Ramón; Zapata-Vázquez, Rita Esther; Alonzo-Vázquez, Felipe; Rodríguez-Ruz, Suemy Gabriela; Medina-Moreno, Manuel Rene; Torres-Escalante, Jose Luis

Severe traumatic brain injury (TBI) is a serious condition. Intracranial pressure (ICP) monitoring can be used to direct treatment, which is of limited access in developing countries. To describe the clinical experience of pediatric patients with severe TBI. A clinical experience in patients with severe TBI was conducted. Age was 1-17 years, exclusion criteria were chronic illness and psicomotor retardation. Informed consent was obtained in each case. Two groups were formed based on the criterion of neurosurgeons: with and without intracraneal pressure (ICP) monitoring. PIC monitoring was performed through a 3PN Spiegelberg catheter and a Spiegelberg HDM 26 monitor. Patients were treated according international pediatric guides. The characteristics of both groups are described at 6 months of follow-up. Forty-two patients (CM=14 and SM=28). Those in the CM Group had lower Glasgow coma scale score and Marshall classification with poorer prognosis. Among them survival rate was lower, although the outcome was from moderate to good. No complications were reported with the use of the ICP catheter. Patients with ICP monitoring had greater severity at admission and an increased mortality; however, the outcome for the survivors was from moderate to good. It is necessary to conduct randomized clinical trials to define the impact of ICP monitoring on survival and quality of life in severe TBI patients. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF).

PubMed

Gelhorn, Heather L; Roberts, Laurie J; Khandelwal, Nikhil; Revicki, Dennis A; DeRogatis, Leonard R; Dobs, Adrian; Hepp, Zsolt; Miller, Michael G

2017-08-01

The Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF) is a patient-reported outcome measurement designed to evaluate the symptoms of hypogonadism. The HIS-Q-SF is an abbreviated version including17 items from the original 28-item HIS-Q. To conduct item analyses and reduction, evaluate the psychometric properties of the HIS-Q-SF, and provide guidance on score interpretation. A 12-week observational longitudinal study of hypogonadal men was conducted as part of the original HIS-Q psychometric evaluation. Participants completed the original HIS-Q every 2 weeks. Blood samples were collected to evaluate testosterone levels. Participants completed the Aging Male's Symptoms Scale, the International Index of Erectile Function, the Short Form-12, and the PROMIS Sexual Activity, Satisfaction with Sex Life, Sleep Disturbance, and Applied Cognition Scales (baseline and weeks 6 and 12). Clinicians completed the Clinical Global Impression of Severity and Change scales and a clinical form. Item performance was evaluated using descriptive statistics and Rasch analyses. Reliability (internal consistency and test-retest), validity (concurrent and know groups), and responsiveness were assessed. One hundred seventy-seven men participated (mean age = 54.1 years, range = 23-83). Similar to the full HIS-Q, the final abbreviated HIS-Q-SF instrument includes five domains (sexual, energy, sleep, cognition, and mood) with two sexual subdomains (libido and sexual function). For key domains, test-retest reliability was very good, and construct validity was good for all domains. Known-groups validity was demonstrated for all domain scores, subdomain scores, and total score based on the Clinical Global Impression-Severity. All domains and subdomains were responsive to change based on patient-rated anchor questions. The HIS-Q-SF could be a useful tool in clinical practice, epidemiologic studies, and other academic research settings. Careful consideration was given to the selection of the final HIS-Q-SF items based on quantitative data and clinical expert feedback. Overall, the reduced set of items demonstrated strong psychometric properties. Testosterone levels for the participating men were not as low as anticipated, which could have limited the ability to examine the relations between the HIS-Q-SF and testosterone levels. Further, the analyses used data collected through administration of the full HIS-Q, and future studies should administer the standalone HIS-Q-SF to replicate the psychometric analyses reported in the present study. Similar to the original HIS-Q, the HIS-Q-SF has evidence supporting reliability, validity, and responsiveness. The short form includes a smaller set of items that might be more suitable for use in clinical practice or academic research settings. Gelhorn HL, Roberts LJ, Khandelwal N, et al. Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF). J Sex Med 2017;14:1046-1058. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Correlation between the season, temperature and atmospheric pressure with incidence and pathogenesis of acute appendicitis.

PubMed

Karanikolić, Aleksandar; Karanikolić, Vesna; Djordjević, Lidija; Pešić, Ivan

2016-01-01

There is very little literature data on the correlation between the seasons, temperature and atmospheric pressure, and pathogenesis of acute appendicitis (AA). The aim of this research is to investigate the association between the seasons, changes in atmospheric temperature and pressure, and patients’ age and severity of the clinical form of AA in the city of Niš This study included 395 patients diagnosed with AA, who, during the two-year period, from July 1st 2011 to June 30th 2013, were hospitalized and operated on at the Department of General Surgery, Clinical Center in Niš, Serbia. The increased average daily values of barometric pressure by 1 millibar on the day when the event took place was associated (p < 0.05) with the decrease of total risk of the occurrence of appendicitis by 2.2% (0.2–4.1%). In all observed patients, each increase of the mean daily temperature by 1°C three days before the event took place (Lag 3) was associated (p < 0.05) with the increase of total risk of the occurrence of appendicitis by 1.3% (0.1–2.5%). According to the results of this research, we can conclude that patients’ sex, age and severity of the clinical form of AA are not in connection with the seasons, while there are certain connections between appendicitis occurrence and atmospheric temperature and pressure.

Why do women not return family history forms when referred to breast cancer genetics services? A mixed-method study.

PubMed

Hanning, Kirstie A; Steel, Michael; Goudie, David; McLeish, Lorna; Dunlop, Jackie; Myring, Jessica; Sullivan, Frank; Berg, Jonathan; Humphris, Gerry; Ozakinci, Gozde

2015-10-01

Personal and family data forms, completed by women referred to breast cancer genetics clinics, are valuable tools for verification and extension of family history, crucial steps in accurate risk evaluation. A significant minority of women do not complete and return these forms, despite reminders, even when completion is a pre-requisite for a clinic appointment. To facilitate access of women at increased familial risk of breast cancer to screening and counselling services by investigating reasons for non-return of the forms. Based on a single regional 'breast cancer family' service in the UK, Analysis of quantitative data comparing women who did not return forms (n = 55) with those who had done so (n = 59), together with qualitative evaluation of potential barriers to form-completion through semi-structured telephone interviews with a random subset of 'non-returners' (n = 23). Non-returners have higher proportions of the very young (below the age at which surveillance could be offered) and of women from lower social deprivation categories. Interviews revealed that the majority of non-returners are anxious, rather than unconcerned about their breast cancer risk and circumstances and attitudes contributed to non-compliance. Twenty-one participants confirmed that they would welcome an appointment at a 'breast cancer family' clinic, but nine did not attend for the appointment. They were significantly younger than those who attend, but were not at lower familial risk. Many women who fail to complete and return a family history form would benefit from risk assessment and genetic counselling. Several steps are suggested that might help them access the relevant services. © 2014 John Wiley & Sons Ltd.

[Mechanisms of immune deposit formation in glomerulonephritis].

PubMed

Bussolati, B; Camussi, G

1996-03-01

Recent experimental studies allowed the identification of several mechanisms of immune deposit formation, which are able to reproduce the morphological and clinical pattern of human glomerulonephritis. Moreover, it was shown that most of the lesions considered, in the past, as due to circulating immune complexes (IC), are instead caused by the "in situ" formation of IC. As a result of these studies, the following schematic classification was proposed: 1) immune deposits formed by glomerular localization of IC primarily formed in the circulation; 2) immune deposits formed "in situ" by reaction of circulating antibodies with fixed structural antigens; 3) immune deposits formed "in situ" by antibodies reactive with movable structural antigens; 4) immune deposits formed "in situ" by antibodies reactive with sequestered antigens leaking out of tissues; 5) IC formed "in situ" by antibodies reactive with exogenous or non-glomerular endogenous antigens planted in the glomeruli; 6) ANCA-associated glomerular disease.

OCT investigation of dental lesions

NASA Astrophysics Data System (ADS)

Osiac, Eugen; Popescu, Sanda Mihaela; Scrieciu, Monica; Mercuţ, Rǎzvan; Mercuţ, Veronica; Vǎtu, Mihaela

2018-03-01

There are several important non carious lesions affecting the tooth structure, lesions which may be classified into four clinical forms of dental wear: abfraction, erosion, attrition and abrasion, and different types of root resorption. Search for new, non-invasive and fast methods able to detect and describe such injuries is of utmost importance. Optical coherence tomography (OCT) proved itself as an appropriate investigation method for several medical fields including ophthalmology, dermatology, cardiology etc. Our study reveals OCT preliminary investigations as a promising tool for detecting and evaluating of the mentioned lesions.

[Dengue shock syndrome].

PubMed

Docquir, J; Tuerlinckx, D; Bodart, E

2009-11-01

Célia, 21 month-old child, presented to our pediatric clinic a few months ago with a fever of unknown origin after a stay in St-Domingue with her parents. Complementary investigations led to a diagnosis of Dengue Fever. The condition, not very frequent and thus not well known in our countries, represents a major world health problem especially because of the global failure of prophylactic measures. If the disease is self-limited in most cases, severe form can occur, with significant mortality and morbidity. Delay in diagnosis and treatment of these severe cases is often fatal.

Periodontal Regeneration Of 1-, 2-, and 3-Walled Intrabony Defects Using Accell Connexus (registered trademark) Versus Demineralized Freeze-Dried Bone Allograft: A Randomized Parallel Arm Clinical Control Trial

DTIC Science & Technology

2015-06-01

localized or generalized), duration ( chronic or aggressive) and severity (mild, moderate or severe) of periodontal disease which will assist in rendering...intrabony defects can be seen in chronic forms of periodontal disease. 9 Figure 4a shows a normal bony pattern in which the bone level follows the... PERIODONTAL REGENERATION OF 1-, 2-, AND 3-WALLED INTRABONY DEFECTS USING ACCELL CONNEXUS® VERSUS DEMINERALIZED FREEZE- DRIED BONE ALLOGRAFT: A

Management of minor soft tissue trauma in adolescent athletes.

PubMed

Dyment, P G

1986-11-01

Rest, ice therapy, compression, and elevation (RICE) are important components of the initial management of acute soft-tissue injuries such as contusions, strains, and sprains. Cryotherapy should be used, in the form of an ice pack, as soon as possible after the injury, and then several times a day for 20 minutes for several days. The use of ice has a theoretical, clinical, and experimental basis. Mild pain due to an injury should be treated with acetaminophen rather than aspirin because of the latter's effect on blood coagulation.

Modelling of Cerebral Tuberculosis: Hope for Continuous Research in Solving the Enigma of the Bottom Billion’s Disease

PubMed Central

Hernández Pando, Rogelio

2011-01-01

Cerebral tuberculosis is a severe type of extrapulmonary disease that is highly predominant in children. It is thought that meningeal tuberculosis, the most common form of cerebral tuberculosis, begins with respiratory infection followed by early haematogenous dissemination to extrapulmonary sites involving the brain. Host genetic susceptibility factors and specific mycobacteria substrains could be involved in the development of this serious form of tuberculosis. In this editorial the different animal models of cerebral tuberculosis are commented, highlighting a recently described murine model in which BALB/c mice were infected by the intratracheal route with clinical isolates, which exhibited rapid dissemination and brain infection. These strains were isolated from the cerebrospinal fluid of patients with meningeal tuberculosis; they showed specific genotype and induced a peculiar immune response in the infected brain. This model could be a useful tool to study host and bacilli factors involved in the pathogenesis of the most severe form of tuberculosis. PMID:22135568

Exclusion of chromosome 1q21-q31 from linkage to three pedigrees affected by the pigment-dispersion syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paglinauan, C.; Haines, J.L.; Del Bono, E.A.

1995-05-01

The pigment-dispersion syndrome is a form of open-angle glaucoma that usually affects individuals in the first 3 decades of life. In addition to the typical optic-nerve degeneration seen in all types of glaucoma, the pigment-dispersion syndrome is characterized by distinctive clinical features including the deposition of pigment granules from the iris epithelium on a variety of ocular structures including the trabecular meshwork. Frequently this disorder affects young myopic individuals. In the early stages of the disease, affected individuals may have clinical evidence of dispersed pigment without an associated elevation of intraocular pressure and optic-nerve degeneration. However, as the disease processmore » progresses, many affected individuals ({approximately}50%) will develop elevated intraocular pressure and degeneration of the optic nerve, causing a permanent loss of sight. The pigment-dispersion syndrome shares several clinical features with the form of autosomal dominant juvenile open-angle glaucoma that recently has been mapped to the 1q21-q31 region of chromosome 1. Our results indicate that the pigment-dispersion syndrome, a form of glaucoma that may also affect the juvenile population, is genetically unrelated to the autosomal dominant form of juvenile glaucoma caused by a defect in a gene located in the 1q21-q31 region of chromosome 1. 15 refs., 2 figs., 1 tab.« less

Molecular characterization of circulating Foot and mouth disease virus (FMDV) serotype O topotype EA-3 and serotype A (African topotype) genotype IV in Egypt, 2016.

PubMed

Soltan, Mohamed A; Negmaldin, Ali H; El-Diasty, Mohamed M; Mansour, Shimaa M G; Elbadry, Maha A; Wilkes, Rebecca P

2017-09-01

In January-April 2016, cattle and buffalo farm owners and veterinarians reported clinical signs suggestive of foot and mouth disease virus (FMDV) outbreaks among non-vaccinated cattle and buffalo herds in Egypt. The clinical disease observed was either mild (small oral lesions and speedy recovery) or severe (extensive oral lesions and/or mortalities), and the form of the disease (either mild or severe) segregated by farm. This study aimed to confirm the presence of FMDV and to characterize the circulating strains associated with the outbreaks. Vesicular epithelia were collected from 41 animals representing 15 affected cattle and buffalo farms in five governorates (Behira, Cairo, Daqahlia, Giza and Ismailia), and tested by real time (rt) RT-PCR. Consequently, 92% (38/41) of examined samples were positive. Furthermore, the VP1 coding region of 60% (23/38) of positive specimens were amplified by RT-PCR and sequenced. The phylogenetic analysis identified two distinct strains characterized as serotype O topotype EA-3 and serotype A (African topotype) of genotype IV in the severe and mild disease forms, respectively. The newly identified strains clustered in distinct clades in the phylogenetic trees, indicating the likelihood of new incursions into Egypt. Those strains were most closely related to previously described Sudanese strains. Copyright © 2017 Elsevier B.V. All rights reserved.

"Idiopathic" mental retardation and new chromosomal abnormalities

PubMed Central

2010-01-01

Mental retardation is a heterogeneous condition, affecting 1-3% of general population. In the last few years, several emerging clinical entities have been described, due to the advent of newest genetic techniques, such as array Comparative Genomic Hybridization. The detection of cryptic microdeletion/microduplication abnormalities has allowed genotype-phenotype correlations, delineating recognizable syndromic conditions that are herein reviewed. With the aim to provide to Paediatricians a combined clinical and genetic approach to the child with cognitive impairment, a practical diagnostic algorithm is also illustrated. The use of microarray platforms has further reduced the percentage of "idiopathic" forms of mental retardation, previously accounted for about half of total cases. We discussed the putative pathways at the basis of remaining "pure idiopathic" forms of mental retardation, highlighting possible environmental and epigenetic mechanisms as causes of altered cognition. PMID:20152051

The variable presentations of glycogen storage disease type IV: a review of clinical, enzymatic and molecular studies.

PubMed

Moses, Shimon W; Parvari, Ruti

2002-03-01

Glycogen storage disease type IV (GSD-IV), also known as Andersen disease or amylopectinosis (MIM 23250), is a rare autosomal recessive disorder caused by a deficiency of glycogen branching enzyme (GBE) leading to the accumulation of amylopectin-like structures in affected tissues. The disease is extremely heterogeneous in terms of tissue involvement, age of onset and clinical manifestations. The human GBE cDNA is approximately 3-kb in length and encodes a 702-amino acid protein. The GBE amino acid sequence shows a high degree of conservation throughout species. The human GBE gene is located on chromosome 3p14 and consists of 16 exons spanning at least 118 kb of chromosomal DNA. Clinically the classic Andersen disease is a rapidly progressive disorder leading to terminal liver failure unless liver transplantation is performed. Several mutations have been reported in the GBE gene in patients with classic phenotype. Mutations in the GBE gene have also been identified in patients with the milder non-progressive hepatic form of the disease. Several other variants of GSD-IV have been reported: a variant with multi-system involvement including skeletal and cardiac muscle, nerve and liver; a juvenile polysaccharidosis with multi-system involvement but normal GBE activity; and the fatal neonatal neuromuscular form associated with a splice site mutation in the GBE gene. Other presentations include cardiomyopathy, arthrogryposis and even hydrops fetalis. Polyglucosan body disease, characterized by widespread upper and lower motor neuron lesions, can present with or without GBE deficiency indicating that different biochemical defects could result in an identical phenotype. It is evident that this disease exists in multiple forms with enzymatic and molecular heterogeneity unparalleled in the other types of glycogen storage diseases.

Severe forms of fibromyalgia with acute exacerbation of pain: costs, comorbidities, and length of stay in inpatient care.

PubMed

Romeyke, Tobias; Noehammer, Elisabeth; Scheuer, Hans Christoph; Stummer, Harald

2017-01-01

As a disease of the musculoskeletal system, fibromyalgia is becoming increasingly important, because of the direct and indirect costs to health systems. The purpose of this study of health economics was to obtain information about staff costs differentiated by service provider, and staff and material costs of the nonmedical infrastructure in inpatient care. This study looked at 263 patients who received interdisciplinary inpatient treatment for severe forms of fibromyalgia with acute exacerbation of pain between 2011 and 2014. Standardized cost accounting and an analysis of additional diagnoses were performed. The average cost per patient was €3,725.84, with staff and material costs of the nonmedical infrastructure and staff costs of doctors and nurses accounting for the highest proportions of the costs. Each fibromyalgia patient had an average of 6.1 additional diagnoses. Severe forms of fibromyalgia are accompanied by many concomitant diseases and associated with both high clinical staff costs and high medical and nonmedical infrastructure costs. Indication-based cost calculations provide important information for health policy and hospital managers if they include all elements that incur costs in both a differentiated and standardized way.

Psychometric properties of the Geriatric Anxiety Inventory (GAI) and its short-form (GAI-SF) in a clinical and non-clinical sample of older adults.

PubMed

Johnco, Carly; Knight, Ashleigh; Tadic, Dusanka; Wuthrich, Viviana M

2015-07-01

The Geriatric Anxiety Inventory is a 20-item geriatric-specific measure of anxiety severity. While studies suggest good internal consistency and convergent validity, divergent validity from measures of depression are weak. Clinical cutoffs have been developed that vary across studies due to the small clinical samples used. A six-item short form (GAI-SF) has been developed, and while this scale is promising, the research assessing the psychometrics of this scale is limited. This study examined the psychometric properties of GAI and GAI-SF in a large sample of 197 clinical geriatric participants with a comorbid anxiety and unipolar mood disorder, and a non-clinical control sample (N = 59). The internal consistency and convergent validity with other measures of anxiety was adequate for GAI and GAI-SF. Divergent validity from depressive symptoms was good in the clinical sample but weak in the total and non-clinical samples. Divergent validity from cognitive functioning was good in all samples. The one-factor structure was replicated for both measures. Receiver Operating Characteristic analyses indicated that the GAI is more accurate at identifying clinical status than the GAI-SF, although the sensitivity and specificity for the recommended cutoffs was adequate for both measures. Both GAI and GAI-SF show good psychometric properties for identifying geriatric anxiety. The GAI-SF may be a useful alternative screening measure for identifying anxiety in older adults.

Acute pancreatitis following scoliosis surgery: description and clinical course in 14 adolescents.

PubMed

El Bouyousfi, Maalik; Leveque, Christine; Miladi, Lotfi; Irtan, Sabine; Hamza, Jamil; Oualha, Mehdi

2016-10-01

Acute pancreatitis is a possible complication after scoliosis surgery. Although some risk factors have been documented in the literature, clinical description of pancreatitis diagnosis and ensuing course still remain very poor. The aim of this study was to describe characteristics of acute pancreatitis after scoliosis surgery. A descriptive, retrospective and single-center study of fourteen adolescents with postoperative acute pancreatitis after spine fusion surgery in scoliosis management between April 2003 and August 2012 was performed. Acute pancreatitis occurred within 9.5 days (4-51) after surgery. Abdominal pain was atypical and was expressed in only half of the children. Ileus, nausea and vomiting were the most frequent signs. None of the acute pancreatitis cases was severe. Acute pancreatitis is an early complication of scoliosis surgery. Clinical signs are atypical and non-severe and can induce misleading forms. Presence of delayed digestive problems should alert the clinician to the risk of pancreatitis in the aftermath of scoliosis surgery.

Severe Cutaneous Adverse Reactions: The Pharmacogenomics from Research to Clinical Implementation

PubMed Central

Su, Shih-Chi; Hung, Shuen-Iu; Fan, Wen-Lang; Dao, Ro-Lan; Chung, Wen-Hung

2016-01-01

Severe cutaneous adverse reactions (SCARs), previously thought to be idiosyncratic or unpredictable, are a deadly form of adverse drug reactions with skin manifestations. Current pharmacogenomic studies of SCARs have made important strides, as the prevention of SCARs, to some extent, appears attainable with the identification of genetic variants for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). Despite the improvement of incidence, a treatment guideline for this devastating condition is still unavailable, highlighting the inadequacy of contemporary accepted therapeutic interventions. As such, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we discuss recent cutting-edge findings concerning the discovery of biomarkers for SCARs and their clinical utilities in the better prediction and early diagnosis of this disease. The knowledge compiled herein provides clues for future investigations on deciphering additional genetic markers for SCARs and the design of clinical trials for the prospective identification of subjects at genetic risk for this condition, ultimately personalizing the medicine. PMID:27854302

Two-Photon and Second Harmonic Microscopy in Clinical and Translational Cancer Research

PubMed Central

PERRY, SETH W.; BURKE, RYAN M.; BROWN, EDWARD B.

2012-01-01

Application of two-photon microscopy (TPM) to translational and clinical cancer research has burgeoned over the last several years, as several avenues of pre-clinical research have come to fruition. In this review, we focus on two forms of TPM—two-photon excitation fluorescence microscopy, and second harmonic generation microscopy—as they have been used for investigating cancer pathology in ex vivo and in vivo human tissue. We begin with discussion of two-photon theory and instrumentation particularly as applicable to cancer research, followed by an overview of some of the relevant cancer research literature in areas that include two-photon imaging of human tissue biopsies, human skin in vivo, and the rapidly developing technology of two-photon microendoscopy. We believe these and other evolving two-photon methodologies will continue to help translate cancer research from the bench to the bedside, and ultimately bring minimally invasive methods for cancer diagnosis and treatment to therapeutic reality. PMID:22258888

A prospective double-blind, randomized clinical trial of levocarnitine to treat autism spectrum disorders

PubMed Central

Geier, David A.; Kern, Janet K.; Davis, Georgia; King, Paul G.; Adams, James B.; Young, John L.; Geier, Mark R.

2011-01-01

Summary Background L-carnitine was proposed as a potential treatment for patients diagnosed with an autism spectrum disorder to improve mitochondrial dysfunction, but no prior randomized controlled trials have been conducted. Material/Methods Thirty subjects diagnosed with an ASD were randomly assigned to receive a standardized regimen (50 mg L-carnitine/kg bodyweight/day) of liquid L-carnitine (n=19) or placebo (n=11) for 3-months. Measures included changes in professionally completed Childhood Autism Rating Scale (CARS), hand muscle testing, and modified clinical global impression (CGI) forms; parent completed Autism Treatment Evaluation Checklist (ATEC), treatment adherence measurement (TAM), frequency and intensity of side effect rating (FISER)/global rating of side effect burden (GRSEB)/patient report of incidence of side effects (PRISE) forms; and lab testing. Results Significant improvements were observed in CARS (−2.03, 95% CI=−3.7 to −0.31), CGI (−0.69, 95% CI=−1.1 to −0.06), and ATEC scores. Significant correlations between changes in serum free-carnitine levels and positive clinical changes were observed for hand muscle strength (R2=0.23, P=0.046), cognitive scores (R2=0.27, P=0.019), and CARS scores (R2=0.20, P=0.047). Study subjects were protocol-compliant (average adherence was >85%) and generally well-tolerated the L-carnitine therapy given. Conclusions L-carnitine therapy (50 mg/kilogram-bodyweight/day) administered for 3-months significantly improved several clinical measurements of ASD severity, but subsequent studies are recommended. PMID:21629200

Association of time under immunosuppression and different immunosuppressive medication on periodontal parameters and selected bacteria of patients after solid organ transplantation.

PubMed

Schmalz, G; Berisha, L; Wendorff, H; Widmer, F; Marcinkowski, A; Teschler, H; Sommerwerck, U; Haak, R; Kollmar, O; Ziebolz, D

2018-05-01

Aim of this study was to investigate the association of the time under immunosuppression and different immunosuppressive medication on periodontal parameters and selected periodontal pathogenic bacteria of immunosuppressed patients after solid organ transplantation (SOT). 169 Patients after SOT (lung, liver or kidney) were included and divided into subgroups according their time under (0-1, 1-3, 3-6, 6-10 and >10 years) and form of immunosuppression (Tacrolimus, Cyclosporine, Mycophenolate, Glucocorticoids, Sirolimus and monotherapy vs. combination). Periodontal probing depth (PPD) and clinical attachment loss (CAL) were assessed. Periodontal disease severity was classified as healthy/mild, moderate or severe periodontitis. Subgingival biofilm samples were investigated for eleven selected potentially periodontal pathogenic bacteria using polymerasechainreaction. The mean PPD and CAL as well as prevalence of Treponema denticola and Capnocytophaga species was shown to be different but heterogeneous depending on time under immunosuppression (p<0.05). Furthermore, only the medication with Cyclosporine was found to show worse periodontal condition compared to patients without Cyclosporine (p<0.05). Prevalence of Porphyromonas gingivalis, Tannerella forsythia and Fusobacterium nucleatum was reduced and prevalence of Parvimonas micra and Capnocytophaga species was increased in patients under immunosuppression with Glucocorticoids, Mycophenolate as well as combination therapy. Time under and form of immunosuppression might have an impact on the clinical periodontal and microbiological parameters of patients after SOT. Patients under Cyclosporine medication should receive increased attention. Differences in subgingival biofilm, but not in clinical parameters were found for Glucocorticoids, Mycophenolate and combination therapy, making the clinical relevance of this finding unclear.

Social functioning in youth with anxiety disorders: association with anxiety severity and outcomes from cognitive-behavioral therapy.

PubMed

Settipani, Cara A; Kendall, Philip C

2013-02-01

Social functioning was assessed using the Child Behavior Checklist and Teacher Report Form for children with anxiety disorders who participated in a randomized clinical trial (N = 161, aged 7-14). Significant relationships were found between severity of children's principal anxiety disorder and most measures of social functioning, such that poorer social functioning was associated with more severe anxiety. Among youth who received cognitive-behavioral therapy (n = 111), significant associations were found between parent-reported social competence and both absence of principal anxiety disorder and lower anxiety severity at posttreatment and 1-year follow-up, controlling for the severity of the child's principal anxiety disorder at pretreatment. Findings support a relationship between anxiety severity and social difficulties, and suggest the importance of social competence for a favorable treatment response.

Methodology of Clinical Trials Aimed at Assessing Interventions for Cutaneous Leishmaniasis

PubMed Central

Olliaro, Piero; Vaillant, Michel; Arana, Byron; Grogl, Max; Modabber, Farrokh; Magill, Alan; Lapujade, Olivier; Buffet, Pierre; Alvar, Jorge

2013-01-01

The current evidence-base for recommendations on the treatment of cutaneous leishmaniasis (CL) is generally weak. Systematic reviews have pointed to a general lack of standardization of methods for the conduct and analysis of clinical trials of CL, compounded with poor overall quality of several trials. For CL, there is a specific need for methodologies which can be applied generally, while allowing the flexibility needed to cover the diverse forms of the disease. This paper intends to provide clinical investigators with guidance for the design, conduct, analysis and report of clinical trials of treatments for CL, including the definition of measurable, reproducible and clinically-meaningful outcomes. Having unified criteria will help strengthen evidence, optimize investments, and enhance the capacity for high-quality trials. The limited resources available for CL have to be concentrated in clinical studies of excellence that meet international quality standards. PMID:23556016

Primary Ovarian Insufficiency: X chromosome defects and autoimmunity.

PubMed

Persani, Luca; Rossetti, Raffaella; Cacciatore, Chiara; Bonomi, Marco

2009-08-01

Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche or premature depletion of ovarian follicles before the age of 40 years. However, in several instances the distinction between definitive or intermittent POF may be difficult on clinical bases, therefore the more appropriate term Primary Ovarian Insufficiency (POI) has been recently proposed and will be used in this review. POI is a heterogeneous disorder affecting approximately 1% of women <40 years. The most severe forms present with absent pubertal development and primary amenorrhea, whereas forms with post-pubertal onset are characterized by disappearance of menstrual cycles (secondary amenorrhea) associated with a defective folliculogenesis. POI is generally characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). Heterogeneity of POI is reflected by the variety of possible causes, including autoimmunity, toxics, drugs, as well as genetic defects. Several data indicate that POI has a strong genetic component. In this manuscript we discuss the X chromosome abnormalities that are associated with POI.

Annual Progress Report (SEATO Medical Research Laboratory)

DTIC Science & Technology

1975-03-01

Vibrio porahemolyticus Infection in Thailand . 105 Cholera Study at Samutsongkram . . . . .. 110 Detection of Specific Bacterial Antigen by...clinical picture of the mild form of the disease needs to be described. Dehydration was not as severe as that seen in infection with Vibrio cholera ...co-trimoxazole, neomycin, erythromycin and streptomycin. Only 6 , and 62 % of the vibrios tested were sensitive to ampicillin and colistin

Adapting the Forms of Yesterday to the Functions of Today and the Needs of Tomorrow: A Genealogical Case Study of Clinical Teaching Units in Canada

ERIC Educational Resources Information Center

Schrewe, Brett; Pratt, Daniel D.; McKellin, William H.

2016-01-01

Emergent discourses of social responsibility and accountability have in part fuelled the expansion of distributed medical education (DME). In addition to its potential for redressing physician maldistribution, DME has conferred multiple unexpected educational benefits. In several countries, its recent rise has occurred around the boundaries of…

Construct Validity of Fluency and Implications for the Factorial Structure of Memory

ERIC Educational Resources Information Center

Jewsbury, Paul A.; Bowden, Stephen C.

2017-01-01

Fluency is an important construct in clinical assessment and in cognitive taxonomies. In the Cattell-Horn-Carroll (CHC) model, Fluency is represented by several narrow factors that form a subset of the long-term memory encoding and retrieval (Glr) broad factor. The CHC broad classification of Fluency was evaluated in five data sets, and the CHC…

Dupuytren disease: on our way to a cure?

PubMed

Degreef, Ilse; De Smet, Luc

2013-06-01

Despite its high prevalence, the clinical presentation and severity of Dupuytren disease is extremely variable. The disease features a broad spectrum of symptoms, from simple nodules without the slightest clinical impact towards an extremely disabling form requiring multiple surgical procedures, sometimes even partial hand amputations. Recurrence after surgery is considered a failure for both patient and surgeon, but its definition is vague. The term 'recontracture' was coined by a patient and reflects the disappointment of recurrent disease. Wether or not a treatment option will insure a definite result, may depend more on the severity of the disease, which is patient specific, than on the treatment method itself. If a patient presents with Dupuytren disease, one should not merely evaluate his hands. Different clinical and personal history features may uncover a severe fibrosis diathesis and both correct information to the patient and an individualized treatment plan are needed. In the near future, a simple genetic test may help to identify patients at risk. Similar to the evolving knowledge and treatment modalities seen in rheumatoid arthritis, treatment of Dupuytren disease is likely to advance in the direction of disease control with pharmacotherapy and single shot minimal invasive enzymatic fasciotomy with collagenase to correct established contractures.

A comparison of high viscosity bone cement and low viscosity bone cement vertebroplasty for severe osteoporotic vertebral compression fractures.

PubMed

Zhang, Liang; Wang, Jingcheng; Feng, Xinmin; Tao, Yuping; Yang, Jiandong; Wang, Yongxiang; Zhang, Shengfei; Cai, Jun; Huang, Jijun

2015-02-01

To compare the clinical outcome and complications of high viscosity and low viscosity poly-methyl methacrylate bone cement PVP for severe OVCFs. From December 2010 to December 2012, 32 patients with severe OVCFs were randomly assigned to either group H using high viscosity cement (n=14) or group L using low viscosity cement (n=18). The clinical outcomes were assessed by the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Short Form-36 General Health Survey (SF-36), kyphosis Cobb's angle, vertebral height, and complications. Significant improvement in the VAS, ODI, SF-36 scores, kyphosis Cobb's angle, and vertebral height were noted in both the groups, and there were no significant differences between the two groups. Cement leakage was seen less in group H. Postoperative assessment using computed tomography identified cement leakage in 5 of 17 (29.4%) vertebrae in group H and in 15 of 22 (68.2%) vertebrae in group L (P=0.025). The PVP using high viscosity bone cement can provide the same clinical outcome and fewer complications compared with PVP using low viscosity bone cement. Copyright © 2014. Published by Elsevier B.V.

Long-term natural history and complications of collagenous colitis.

PubMed

Freeman, Hugh J

2012-09-01

Microscopic forms of colitis have been described, including collagenous colitis, a possibly heterogeneous disorder. Collagenous colitis most often appears to have an entirely benign clinical course that usually responds to limited treatment. Sometimes significant extracolonic disorders, especially arthritis, spondylitis, thyroiditis and skin disorders, such as pyoderma gangrenosum, dominate the clinical course and influence the treatment strategy. However, rare fatalities have been reported and several complications, some severe, have been attributed directly to the colitis. Toxic colitis and toxic megacolon may develop. Concomitant gastric and small intestinal inflammatory disorders have been described including celiac disease and more extensive collagenous inflammatory disease. Colonic ulceration has been associated with the use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn disease, may evolve directly from collagenous colitis. Submucosal 'dissection', colonic fractures, or mucosal tears and perforation, possibly from air insufflation during colonoscopy, have been reported. Similar changes may result from increased intraluminal pressures that may occur during radiological imaging of the colon. Neoplastic disorders of the colon may also occur during the course of collagenous colitis, including colon carcinoma and neuroendocrine tumours (ie, carcinoids). Finally, lymphoproliferative disease has been reported.

Misconceptions regarding the pathogenicity of silicas and silicates.

PubMed

Feigin, D S

1989-01-01

Several inhaled substances, from occupational or other environmental exposure, produce significant pulmonary disease and abnormalities demonstrated by pulmonary imaging. Areas of controversy and misconception relate principally to the extent and nature of both the clinical disease and the imaging abnormalities specific to each substance. The size and shape of the inhaled particles is an important determinant of the nature and severity of the disease produced, with fibrous shapes usually being the most pathogenetic. Fibrogenicity is another important pathogenetic characteristic of talc and kaolin, as well as asbestos. Talc produces four distinct forms of pulmonary disease, depending not only on the other substances with which it is inhaled, but also whether it is inhaled or injected intravenously. When inhaled alone, talc does not appear to produce significant pulmonary fibrosis or malignancy. Kaolin, mica, fuller's earth, zeolite, and fiberglass all vary in disease production according to their shape and fibrogenicity. Silica, diatomaceous earth, and other forms of silica are all highly fibrogenic and thus produce clinically obvious disease with sufficient inhalation. The largest particles usually produce nodular patterns in the upper pulmonary fields, as is typical of silicosis. The fibrous particles are more likely to manifest themselves as interstitial patterns in the lower pulmonary fields.

Mental health of Chinese primary care patients with lower urinary tract symptoms.

PubMed

Choi, Edmond P H; Lam, Cindy L K; Chin, Weng Yee

2016-01-01

The aim of this study was to evaluate the mental health of Chinese primary care patients with lower urinary tract symptoms (LUTS). This was a cross-sectional observational study. Five hundred and nineteen subjects with LUTS completed a structured questionnaire containing the Depression, Anxiety, and Stress Scale-Short Form, the International Prostate Symptom Score, the adapted International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and questions about socio-demographics. Overall, 17.7% of subjects reported depressive symptoms, 24.3% anxiety symptoms and 9.6% stress symptoms. In males, demographic factors associated with poorer mental health included being not married; clinical factors included higher LUTS severity, weak stream, straining and mixed urinary incontinence. In females, demographic factors associated with poorer mental health included being younger, not married and lower household income; clinical factors included higher LUTS severity, incomplete bladder emptying, urgency and weak stream. Chinese primary care patients with LUTS appear to be an at-risk group for poorer mental health with increased prevalence of anxiety and depressive symptoms and may require routine screening to identify those who may require more tailored interventions to address both their urinary symptoms and psychological distress.

An official multi-society statement: the role of clinical research results in the practice of critical care medicine.

PubMed

Tonelli, Mark R; Curtis, J Randall; Guntupalli, Kalpalatha K; Rubenfeld, Gordon D; Arroliga, Alejandro C; Brochard, Laurent; Douglas, Ivor S; Gutterman, David D; Hall, Jesse R; Kavanagh, Brian P; Mancebo, Jordi; Misak, Cheryl J; Simpson, Steven Q; Slutsky, Arthur S; Suffredini, Anthony F; Thompson, B Taylor; Ware, Lorraine B; Wheeler, Arthur P; Levy, Mitchell M

2012-05-15

While the results of clinical research are clearly valuable in the care of critically ill patients, the limitations of such information and the role of other forms of medical knowledge for clinical decision making have not been carefully examined. The leadership of three large professional societies representing critical care practitioners convened a diverse group representing a wide variety of views regarding the role of clinical research results in clinical practice to develop a document to serve as a basis for agreement and a framework for ongoing discussion. Consensus was reached on several issues. While the results of rigorous clinical research are important in arriving at the best course of action for an individual critically ill patient, other forms of medical knowledge, including clinical experience and pathophysiologic reasoning, remain essential. No single source of knowledge is sufficient to guide clinical decisions, nor does one kind of knowledge always take precedence over others. Clinicians will find clinical research compelling for a variety of reasons that go beyond study design. While clinical practice guidelines and protocols based upon clinical research may improve care and decrease variability in practice, clinicians must be able to understand and articulate the rationale as to why a particular protocol or guideline is used or why an alternative approach is taken. Making this clinical reasoning explicit is necessary to understand practice variability. Understanding the strengths and weaknesses of different kinds of medical knowledge for clinical decision making and factors beyond study design that make clinical research compelling to clinicians can provide a framework for understanding the role of clinical research in practice.

Cognitive Behaviour therapy for Older Adults with Insomnia and Depression: A Randomized Controlled Trial in Community Mental Health Services.

PubMed

Sadler, Paul; McLaren, Suzanne; Klein, Britt; Harvey, Jack; Jenkins, Megan

2018-05-24

To investigate whether cognitive behaviour therapy was effective for older adults with comorbid insomnia and depression in a community mental health setting, and explore whether an advanced form of cognitive behaviour therapy for insomnia produced better outcomes compared to a standard form of cognitive behaviour therapy for insomnia. An 8 week randomized controlled clinical trial was conducted within community mental health services, Victoria, Australia. Seventy-two older adults (56% female, M age 75 years ± 7) with diagnosed comorbid insomnia and depression participated. Three conditions were tested using a group therapy format: cognitive behaviour therapy for insomnia (CBT-I, standard), cognitive behaviour therapy for insomnia plus positive mood strategies (CBT-I+, advanced), psychoeducation control group (PCG, control). The primary outcomes were insomnia severity (Insomnia Severity Index) and depression severity (Geriatric Depression Scale). Primary and secondary measures were collected at pre (week 0), post (week 8), and follow-up (week 20). CBT-I and CBT-I+ both generated significantly greater reductions in insomnia and depression severity compared to PCG from pre to post (p < .001), which were maintained at follow-up. Although the differences between outcomes of the two treatment conditions were not statistically significant, the study was not sufficiently powered to detect either superiority of one treatment or equivalence of the two treatment conditions. CBT-I and CBT-I+ were both effective at reducing insomnia and depression severity for older adults. Mental health services that deliver treatment for comorbid insomnia with cognitive behaviour therapy may improve recovery outcomes for older adults with depression. Australian and New Zealand Clinical Trials Registry (ANZCTR) URL: https://www.anzctr.org.au Trial ID: ACTRN12615000067572 Date Registered: 12th December 2014.

Fortune telling addiction: Unfortunately a serious topic about a case report.

PubMed

Grall-Bronnec, Marie; Bulteau, Samuel; Victorri-Vigneau, Caroline; Bouju, Gaëlle; Sauvaget, Anne

2015-03-01

Constant social change brings about new forms of behavior, such as smartphone use, social networking,indoor tanning, cosmetic surgery, etc., that could become excessive or even lead to new forms of addictive disorders. We report the case of a woman who starts consulting for “clairvoyance addiction”. We then discuss the addictive nature of her disorder, based on several classifications of addiction. The patient fulfilled the criteria for addiction and her clinical features were typical of that of addicted people. Other differential diagnoses were discussed. As for any addictive behavior, the interaction of several risk factors should be considered.They are related to the individual himself, but also to the object of addiction and to the socio-environmental context. In this case, all the conditions were met for fortune telling use to become addictive.

Radiation-induced cystitis following intracavitary irradiation for superficial bladder cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maatman, T.J.; Novick, A.C.; Montague, D.K.

Intracavitary irradiation is effective in the treatment of noninvasive papillary transitional cell carcinoma and carcinoma in situ of the bladder. Mortality has not been associated with this form of therapy. The morbidity associated with intracavitary irradiation consists of mild to severe radiation cystitis and we report 2 such cases. One patient is from a series of 65 patients with noninvasive bladder tumors treated with intracavitary irradiation at this clinic since 1965. The second patient had noninvasive bladder tumors and was treated with intracavitary irradiation elsewhere. In both patients severe radiation cystitis subsequently developed, requiring simple cystectomy and urinary diversion. Themore » potential for this serious side effect must be considered when choosing a form of therapy for patients with noninvasive papillary transitional cell carcinoma and carcinoma in situ of the bladder.« less

Co-infection with coxsackievirus A5 and norovirus GII.4 could have been the trigger of the first episode of severe acute encephalopathy in a six-year-old child with the intermittent form of maple syrup urine disease (MSUD).

PubMed

Boros, Ákos; Pankovics, Péter; Kőmíves, Sándor; Liptai, Zoltán; Dobner, Sarolta; Ujhelyi, Enikő; Várallyay, György; Zsidegh, Petra; Bolba, Nóra; Reuter, Gábor

2017-06-01

In this case study, a co-infection with coxsackievirus A5 (family Picornaviridae) and norovirus GII.4 (family Caliciviridae) was detected by RT-PCR in a faecal sample from a six-year-old girl with symptoms of severe acute encephalopathy subsequently diagnosed as the intermittent form of maple syrup urine disease (MSUD). The two co-infecting viruses, which had been detected previously, appeared to have triggered the underlying metabolic disorder. Here, we describe the genotyping of the viruses, as well as the chronological course, laboratory test results, and clinical presentation of this case, which included recurrent vomiting without diarrhoea, metabolic acidosis, unconsciousness, seizure and circulatory collapse, but with a positive final outcome.

Fortune telling addiction: Unfortunately a serious topic. About a case report

PubMed Central

BULTEAU, SAMUEL; VICTORRI-VIGNEAU, CAROLINE; BOUJU, GAËLLE; SAUVAGET, ANNE

2015-01-01

Background Constant social change brings about new forms of behavior, such as smartphone use, social networking, indoor tanning, cosmetic surgery, etc., that could become excessive or even lead to new forms of addictive disorders. Methods We report the case of a woman who starts consulting for “clairvoyance addiction”. We then discuss the addictive nature of her disorder, based on several classifications of addiction. Results The patient fulfilled the criteria for addiction and her clinical features were typical of that of addicted people. Other differential diagnoses were discussed. Conclusion As for any addictive behavior, the interaction of several risk factors should be considered. They are related to the individual himself, but also to the object of addiction and to the socio-environmental context. In this case, all the conditions were met for fortune telling use to become addictive. PMID:25786497

qPCR detection of Mycobacterium leprae in biopsies and slit skin smear of different leprosy clinical forms.

PubMed

Azevedo, Michelle de Campos Soriani; Ramuno, Natália Mortari; Fachin, Luciana Raquel Vincenzi; Tassa, Mônica; Rosa, Patrícia Sammarco; Belone, Andrea de Faria Fernandes; Diório, Suzana Madeira; Soares, Cleverson Teixeira; Garlet, Gustavo Pompermaier; Trombone, Ana Paula Favaro

Leprosy, whose etiological agent is Mycobacterium leprae, is a chronic infectious disease that mainly affects the skin and peripheral nervous system. The diagnosis of leprosy is based on clinical evaluation, whereas histopathological analysis and bacilloscopy are complementary diagnostic tools. Quantitative PCR (qPCR), a current useful tool for diagnosis of infectious diseases, has been used to detect several pathogens including Mycobacterium leprae. The validation of this technique in a robust set of samples comprising the different clinical forms of leprosy is still necessary. Thus, in this study samples from 126 skin biopsies (collected from patients on all clinical forms and reactional states of leprosy) and 25 slit skin smear of leprosy patients were comparatively analyzed by qPCR (performed with primers for the RLEP region of M. leprae DNA) and routine bacilloscopy performed in histological sections or in slit skin smear. Considering clinical diagnostic as the gold standard, 84.9% of the leprosy patients were qPCR positive in skin biopsies, resulting in 84.92% sensitivity, with 84.92 and 61.22% positive (PPV) and negative (NPV) predictive values, respectively. Concerning bacilloscopy of histological sections (BI/H), the sensitivity was 80.15% and the PPV and NPV were 80.15 and 44.44%, respectively. The concordance between qPCR and BI/H was 87.30%. Regarding the slit skin smear, 84% of the samples tested positive in the qPCR. Additionally, qPCR showed 100% specificity, since all samples from different mycobacteria, from healthy individuals, and from other granulomatous diseases presented negative results. In conclusion, the qPCR technique for detection of M. leprae using RLEP primers proved to be specific and sensitive, and qPCR can be used as a complementary test to diagnose leprosy irrespective of the clinical form of disease. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

[Late-onset depression and a new psychometric scale for its clinical evaluation].

PubMed

Ivanets, N N; Kinkul'kina, M A; Avdeeva, T I

2012-01-01

The most of existed psychometric scales for depression have some shortcomings hampering their use in old patients. The authors worked out the original scale for clinical evaluation of symptoms of late-onset depression. The list of symptoms was made up basing on literature data. The most significant symptoms that characterized the structure and severity of depression in old patients were singled out. According to results of factor analyses they were combined in the groups forming the corresponding items of the scale. In addition, some symptoms with particular clinical significance for late-onset depression (suicidal thoughts, senesto-hypochondriac symptoms, insight) were singled out. The scale comprises 13 items with scores from -6 to +6. It can be implemented for symptom screening, clinical diagnosis and rating, including dynamics of depression in elderly patients.

Interaction of malaria with a common form of severe thalassemia in an Asian population

PubMed Central

O'Donnell, A.; Premawardhena, A.; Arambepola, M.; Samaranayake, R.; Allen, S. J.; Peto, T. E. A.; Fisher, C. A.; Cook, J.; Corran, P. H.; Olivieri, Nancy F.; Weatherall, D. J.

2009-01-01

In many Asian populations, the commonest form of severe thalassemia results from the coinheritance of HbE and β thalassemia. The management of this disease is particularly difficult because of its extreme clinical diversity; although some genetic and adaptive factors have been identified as phenotypic modifiers, the reasons remain unclear. Because the role of the environment in the course of severe thalassemia has been neglected completely and because malaria due to both Plasmodium falciparum and Plasmodium vivax has been prevalent in Sri Lanka, we carried out a pilot study of patients with HbE β thalassemia that showed high frequencies of antibodies to both parasite species and that 28.6% of the children had DNA-based evidence of current infection with P. vivax. Malarial antibodies then were assessed in patients with HbE β thalassemia compared with those in age-matched controls. There was a significant increase in the frequency of antibodies in the thalassemic patients, particularly against P. vivax and in young children. There was also a higher frequency in those who had been splenectomized compared with those with intact spleens, although in the latter it was still higher than that in the controls. The thalassemic patients showed significant correlations between malaria antibody status and phenotype. Patients with HbE β thalassemia may be more prone to malaria, particularly P. vivax, which is reflected in their clinical severity. Because P. vivax malaria is widespread in Asia, further studies of its interaction with HbE β thalassemia and related diseases are required urgently as a part of ongoing thalassemia control programs. PMID:19841268

Clinical reasoning and its application to nursing: concepts and research studies.

PubMed

Banning, Maggi

2008-05-01

Clinical reasoning may be defined as "the process of applying knowledge and expertise to a clinical situation to develop a solution" [Carr, S., 2004. A framework for understanding clinical reasoning in community nursing. J. Clin. Nursing 13 (7), 850-857]. Several forms of reasoning exist each has its own merits and uses. Reasoning involves the processes of cognition or thinking and metacognition. In nursing, clinical reasoning skills are an expected component of expert and competent practise. Nurse research studies have identified concepts, processes and thinking strategies that might underpin the clinical reasoning used by pre-registration nurses and experienced nurses. Much of the available research on reasoning is based on the use of the think aloud approach. Although this is a useful method, it is dependent on ability to describe and verbalise the reasoning process. More nursing research is needed to explore the clinical reasoning process. Investment in teaching and learning methods is needed to enhance clinical reasoning skills in nurses.

[Hypophosphatasia: Clinical manifestations, diagnostic recommendations and therapeutic options].

PubMed

Martos-Moreno, Gabriel A; Calzada, Joan; Couce, María L; Argente, Jesús

2018-06-01

Hypophosphatasia is a very rare bone metabolism disorder caused by a deficiency in alkaline phosphatase activity, due to mutations in the ALPL gene. Its clinical hallmark is the impairment of skeletal and teeth mineralisation, although extra-skeletal manifestations are frequent. Its phenotypic spectrum is widely variable from a subtype with exclusive odontological impairment (odontohypophosphatasia) to five subtypes with systemic involvement, classified according to the age at the onset of the first symptoms (four of them in the paediatric age range: perinatal lethal, perinatal benign, infant and childhood hypophosphatasia). Those subtypes of hypophosphatasia with an earliest onset usually involve a worse prognosis, due to the risk of developing potentially lethal complications, such as seizures or severe respiratory insufficiency, secondary to rib cage malformations. Due to the extremely low prevalence of the severe forms of hypophosphatasia, its clinical variability and overlapping phenotypic features with several more prevalent conditions, the diagnosis of hypophosphatasia in the clinical setting is challenging. However, its potential lethality and impact on the patient's quality of life, along with the recent availability of an enzyme replacement therapy, increases the relevance of the early and accurate identification of patients affected with hypophosphatasia. On the basis of published evidence and clinical experience, this article suggests an algorithm with practical recommendations for the differential diagnosis of childhood hypophosphatasia, as well as an updated review of current therapeutic options. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes.

PubMed

Kerr, J R; Burke, B; Petty, R; Gough, J; Fear, D; Mattey, D L; Axford, J S; Dalgleish, A G; Nutt, D J

2008-06-01

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. The authors have recently reported a study of gene expression that identified differential expression of 88 human genes in patients with CFS/ME. Clustering of quantitative PCR (qPCR) data from patients with CFS/ME revealed seven distinct subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes and severity. In this study, for each CFS/ME subtype, those genes whose expression differed significantly from that of normal blood donors were identified, and then gene interactions, disease associations and molecular and cellular functions of those gene sets were determined. Genomic analysis was then related to clinical data for each CFS/ME subtype. Genomic analysis revealed some common (neurological, haematological, cancer) and some distinct (metabolic, endocrine, cardiovascular, immunological, inflammatory) disease associations among the subtypes. Subtypes 1, 2 and 7 were the most severe, and subtype 3 was the mildest. Clinical features of each subtype were as follows: subtype 1 (cognitive, musculoskeletal, sleep, anxiety/depression); subtype 2 (musculoskeletal, pain, anxiety/depression); subtype 3 (mild); subtype 4 (cognitive); subtype 5 (musculoskeletal, gastrointestinal); subtype 6 (postexertional); subtype 7 (pain, infectious, musculoskeletal, sleep, neurological, gastrointestinal, neurocognitive, anxiety/depression). It was particularly interesting that in the seven genomically derived subtypes there were distinct clinical syndromes, and that those which were most severe were also those with anxiety/depression, as would be expected in a disease with a biological basis.

Antiradiation Vaccine: Technology Development- Radiation Tolerance,Prophylaxis, Prevention And Treatment Of Clinical Presentation After Heavy Ion Irradiation.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

Introduction: Research in the field of biological effects of heavy charged particles is necessary for both heavy-ion therapy (hadrontherapy) and protection from the exposure to galactic cosmic radiation in long-term manned space missions.[Durante M. 2004] In future crew of long-term manned missions could operate in exremely high hadronic radiation areas of space and will not survive without effective radiation protection. An Antiradiation Vaccine (AV) must be an important part of a countermeasures regimen for efficient radiation protection purposes of austronauts-cosmonauts-taukonauts: immune-prophylaxis and immune-therapy of acute radiation toxic syndromes developed after heavy ion irradiation. New technology developed (AV) for the purposes of radiological protection and improvement of radiation tolerance and it is quite important to create protective immune active status which prevent toxic reactions inside a human body irradiated by high energy hadrons.[Maliev V. et al. 2006, Popov D. et al.2008]. High energy hadrons produce a variety of secondary particles which play an important role in the energy deposition process, and characterise their radiation qualities [Sato T. et al. 2003] Antiradiation Vaccine with specific immune-prophylaxis by an anti-radiation vaccine should be an important part of medical management for long term space missions. Methods and experiments: 1. Antiradiation vaccine preparation standard, mixture of toxoid form of Radiation Toxins [SRD-group] which include Cerebrovascular RT Neurotoxin, Cardiovascular RT Neurotoxin, Gastrointestinal RT Neurotoxin, Hematopoietic RT Hematotoxin. Radiation Toxins of Radiation Determinant Group isolated from the central lymph of gamma-irradiated animals with Cerebrovascular, Cardiovascular, Gastro-intestinal, Hematopoietic forms of ARS. Devices for radiation are "Panorama", "Puma". 2. Heavy ion exposure was accomplished at Department of Research Institute of Nuclear Physics, Dubna, Russia. The heavy ions irradiation was generated in heavy ion (Fe56) accelerator - UTI. Heavy Ion linear transfer energy - 2000- 2600 KeV -mkm, 600 MeV -92U. Absorbed Dose - 3820 Rad. Experimental Design: Rabbits from all groups were irradiated by heavy ion accelerator. Group A: control-10 rabbits; Group B: placebo-5 rabbits; Group C: Radioprotectant Cystamine (50 mg-kg)-5 rabbits, 15 minutes before irradiation - 5 rabbits; Group D: Radioprotectant Gammafos (Amifostine 400mg -kg ) - 5 rabbits; Group E: Antiradiation Vaccine: subcutaneus administration or IM - 2 ml of active substance, 14 days before irradiation Results: Group A 100% mortality within two hours after heavy ion irradiation with clinical symptoms of Acute Cerebro- and Cardio-Vascular Radiation syndromes. Group B 100% mortality within 15 hours following irradiation. Group C 100% mortality within 14-15 hours after irradiation. Group D 100% mortality within 15-16 hours after irradiation. In groups A- D registered the development of acute radiation cerebrovascular and cardiovascular syndromes and also extensive burns. of skin produced rapid death. Group E -100% mortality in 280-290 hours (12 days) following heavy ion irradiation with animals exhibiting a combination or individual forms of Acute Cerebrovascular, Cardiovascular, and Gastrointestinal forms and focal skin burns. Discussion Antiradiation vaccine and immune-prophylaxis is an effective method of neutralization of Radiation Toxins. Vaccination before irradiation extended survival time after irradiation with heavy ions from two hours up to 300 hours. Clinical signs, clinical features, symptoms were somewhat attenuated. Degree of clinical forms of Acute Radiation Syndromes were diminished in their clinical manifestation and severity. Groups A-D demonstrated extremely severe level of Cerebrovascular and Cardiovascular forms of Acute Radiation Syndromes and lethality 100% was registered in short time after irradiation. Radiation induced burns in this groups (with Cutaneous sub-syndrome of ARS - Degree 4, that diffuse deep into soft tissues with extensive and total dysfunction and muscle involvement developed. Animals from group E - Radioprotectant Antiradiation Vaccine demonstrated later development of moderate-severe form forms of Cerebrovascular and Cardiovascular forms of ARS and survival time of irradiated animals was prolonged. Cutaneous sub-syndrome developed in Degree 3 or Degree 2-3. Our results have demonstrated potential radioprotection efficacy of immune-prophylaxis with Antiradiation Vaccine against high doses heavy ion irradiation.

African genetic ancestry is associated with a protective effect on Dengue severity in colombian populations.

PubMed

Chacón-Duque, Juan Camilo; Adhikari, Kaustubh; Avendaño, Efren; Campo, Omer; Ramirez, Ruth; Rojas, Winston; Ruiz-Linares, Andrés; Restrepo, Berta Nelly; Bedoya, Gabriel

2014-10-01

The wide variation in severity displayed during Dengue Virus (DENV) infection may be influenced by host susceptibility. In several epidemiological approaches, differences in disease outcomes have been found between some ethnic groups, suggesting that human genetic background has an important role in disease severity. In the Caribbean, It has been reported that populations of African descent present considerable less frequency of severe forms compared with Mestizo and White self-reported groups. Admixed populations offer advantages for genetic epidemiology studies due to variation and distribution of alleles, such as those involved in disease susceptibility, as well to provide explanations of individual variability in clinical outcomes. The current study analysed three Colombian populations, which like most of Latin American populations, are made up of the product of complex admixture processes between European, Native American and African ancestors; having as a main goal to assess the effect of genetic ancestry, estimated with 30 Ancestry Informative Markers (AIMs), on DENV infection severity. We found that African ancestry has a protective effect against severe outcomes under several systems of clinical classification: Severe Dengue (OR: 0.963 for every 1% increase in African ancestry, 95% confidence interval (0.934-0.993), p-value: 0.016), Dengue Haemorrhagic Fever (OR: 0.969, 95% CI (0.947-0.991), p-value: 0.006), and occurrence of haemorrhages (OR: 0.971, 95% CI (0.952-0.989), p-value: 0.002). Conversely, decrease from 100% to 0% African ancestry significantly increases the chance of severe outcomes: OR is 44-fold for Severe Dengue, 24-fold for Dengue Haemorrhagic Fever, and 20-fold for occurrence of haemorrhages. Furthermore, several warning signs also showed statistically significant association given more evidences in specific stages of DENV infection. These results provide consistent evidence in order to infer statistical models providing a framework for future genetic epidemiology and clinical studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Prevalence and severity of non-alcoholic fatty liver disease are underestimated in clinical practice: impact of a dedicated screening approach at a large university teaching hospital.

PubMed

Marjot, T; Sbardella, E; Moolla, A; Hazlehurst, J M; Tan, G D; Ainsworth, M; Cobbold, J F L; Tomlinson, J W

2018-01-01

To define the attitudes and current clinical practice of diabetes specialists with regard to non-alcoholic fatty liver disease and, based on the results, implement an evidenced-based pathway for non-alcoholic fatty liver disease assessment. An online survey was disseminated to diabetes specialists. Based on findings from this survey, we sought a local solution by launching an awareness campaign and implementing a screening algorithm across all diabetes clinics at a secondary/tertiary referral centre. A total of 133 diabetes specialists responded to the survey. Fewer than 5% of responders correctly assessed the prevalence and severity of advanced fibrotic non-alcoholic fatty liver disease in people with diabetes as 50-75%. Whilst most clinicians performed liver function tests, only 5.7% responded stating that they would use, or had used, a non-invasive algorithm to stage the severity of non-alcoholic fatty liver disease. Implementing a local non-alcoholic fatty liver disease awareness campaign and screening strategy using pre-printed blood request forms, we ensured that 100% (n=395) of all people with Type 1 and Type 2 diabetes mellitus attending secondary/tertiary care diabetes clinics over a 6-month period were appropriately screened for advanced fibrotic non-alcoholic fatty liver disease using the Fib-4 index; 17.9% required further investigation or assessment. The prevalence and severity of non-alcoholic fatty liver disease are underestimated among diabetes specialists. The Fib-4 index can easily be incorporated into clinical practice in secondary/tertiary care to identify those individuals at risk of advanced fibrosis who require further assessment and who may benefit from a dedicated multidisciplinary approach to their management. © 2017 Diabetes UK.

A clinical evaluation committee assessment of recombinant human tissue factor pathway inhibitor (tifacogin) in patients with severe community-acquired pneumonia

PubMed Central

Laterre, Pierre-François; Opal, Steven M; Abraham, Edward; LaRosa, Steven P; Creasey, Abla A; Xie, Fang; Poole, Lona; Wunderink, Richard G

2009-01-01

Introduction The purpose of this analysis was to determine the potential efficacy of recombinant human tissue factor pathway inhibitor (tifacogin) in a subpopulation of patients with community-acquired pneumonia (CAP) from a phase III study of severe sepsis. Methods A retrospective review of patients with suspected pneumonia was conducted by an independent clinical evaluation committee (CEC) blinded to treatment assignment. The CEC reanalyzed data from patients enrolled in an international multicenter clinical trial of sepsis who had a diagnosis of pneumonia as the probable source of sepsis. The primary efficacy measure was all-cause 28-day mortality. Results Of 847 patients identified on case report forms with a clinical diagnosis of pneumonia, 780 (92%) were confirmed by the CEC to have pneumonia. Of confirmed pneumonia cases, 496 (63.6%) met the definition for CAP. In the CEC CAP population, the mortality rates of the tifacogin and placebo groups were 70/251 (27.9%) and 80/245 (32.7%), respectively. The strongest signals were seen in patients with CAP not receiving concomitant heparin, having microbiologically confirmed infection, or having the combination of documented infection and no heparin. The reduction in mortality in this narrowly defined subgroup when treated with tifacogin compared with placebo was statistically significant (17/58 [29.3%] with tifacogin and 28/54 [51.9%] with placebo; unadjusted P value of less than 0.02). Conclusions Tifacogin administration did not significantly reduce mortality in any severe CAP patient. Exploratory analyses showed an improved survival in patients who did not receive concomitant heparin with microbiologically confirmed infections. These data support the rationale of an ongoing phase III study exploring the potential benefit of tifacogin in severe CAP. Trial Registration ClinicalTrials.gov identifier NCT00084071. PMID:19284881

Restoring Neurological Physiology: The Innovative Role of High-Energy MR-Guided Focused Ultrasound (HIMRgFUS). Preliminary Data from a New Method of Lesioning Surgery.

PubMed

Giugno, Antonella; Maugeri, Rosario; Graziano, Francesca; Gagliardo, Cesare; Franzini, Angelo; Catalano, Carlo; Midiri, Massimo; Iacopino, Domenico Gerardo

2017-01-01

Tremor is a disabling condition, common to several neurodegenerative diseases. Lesioning procedures and deep brain stimulation, respectively, of the ventralis intermedius nucleus for intentional tremor, and of the subthalamic nucleus for parkinsonian resting tremor, have been introduced in clinical practice for patients refractory to medical treatment. The combination of high-energy focused ultrasound (HIFUS) with sophisticated magnetic resonance (MR) instrumentation, together with accurate knowledge of the stereotactic brain coordinates, represents a revolution in neuromodulation. At the Neurosurgical Clinic and the Radiology Department of the University of Palermo,, two patients affected by severe and refractory forms of intentional tremor were treated by MRI-guided FUS (MRgFUS) with a unique 1.5 T MR scanner prototype that uses FUS. This apparatus is the only one of its type in the world." This is the first Italian experience, and the second in Europe, of treatment with MRI-gFUS for intentional tremor. But this is the very first experience in which a 1.5 T MRI apparatus was used. In both patients, the treatment completely abolished the tremor on the treated side, with results being excellent and stable after 7 and 5 months, respectively; no side effects were encountered. MRgFUS, recently introduced in clinical practice, and widely used at several clinical centers, has been shown to be a valid therapeutic alternative in the treatment of tremor in several neurodegenerative diseases. It is virtually safe, noninvasive, and very efficacious. We report this technique in which a 1.5 T MR scanner was used. Further investigations with long-term follow up and larger clinical series are needed.

Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer's Disease

PubMed Central

Solfrizzi, Vincenzo; Imbimbo, Bruno P.; Lozupone, Madia; Santamato, Andrea; Zecca, Chiara; Barulli, Maria Rosaria; Bellomo, Antonello; Pilotto, Alberto; Daniele, Antonio; Greco, Antonio

2016-01-01

The failure of several Phase II/III clinical trials in Alzheimer's disease (AD) with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized form (MT+). MT chloride (methylene blue) was investigated in a 24-week Phase II clinical trial in 321 patients with mild to moderate AD that failed to show significant positive effects in mild AD patients, although long-term observations (50 weeks) and biomarker studies suggested possible benefit. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected AD patients and cerebral blood flow in mildly affected patients. Further clinical evidence will come from the large ongoing Phase III trials for the treatment of AD and the behavioral variant of frontotemporal dementia on a new form of this TAI, more bioavailable and less toxic at higher doses, called TRx0237. More recently, inhibitors of tau acetylation are being actively pursued based on impressive results in animal studies obtained by salsalate, a clinically used derivative of salicylic acid. PMID:27429978

Clinical and genetic features of dyskeratosis congenita, cryptic dyskeratosis congenita, and Hoyeraal-Hreidarsson syndrome in Japan.

PubMed

Yamaguchi, Hiroki; Sakaguchi, Hirotoshi; Yoshida, Kenichi; Yabe, Miharu; Yabe, Hiromasa; Okuno, Yusuke; Muramatsu, Hideki; Takahashi, Yoshiyuki; Yui, Shunsuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Inokuchi, Koiti; Ito, Etsuro; Ogawa, Seishi; Kojima, Seiji

2015-11-01

Dyskeratosis congenita (DKC) is an inherited bone marrow failure (BMF) syndrome typified by reticulated skin pigmentation, nail dystrophy, and mucosal leukoplakia. Hoyeraal-Hreidarsson syndrome (HHS) is considered to be a severe form of DKC. Unconventional forms of DKC, which develop slowly in adulthood but without the physical anomalies characteristic of DKC (cryptic DKC), have been reported. Clinical and genetic features of DKC have been investigated in Caucasian, Black, and Hispanic populations, but not in Asian populations. The present study aimed to determine the clinical and genetic features of DKC, HHS, and cryptic DKC among Japanese patients. We analyzed 16 patients diagnosed with DKC, three patients with HHS, and 15 patients with cryptic DKC. We found that platelet count was significantly more depressed than neutrophil count or hemoglobin value in DKC patients, and identified DKC patients with large deletions in the telomerase reverse transcriptase and cryptic DKC patients with RTEL1 mutations on both alleles. This led to some patients previously considered to have unclassifiable BMF being diagnosed with cDKC through identification of new gene mutations. It thus seems important from a clinical viewpoint to re-examine the clinical characteristics, frequency of genetic mutations, and treatment efficacy in DKC, HHS, and cDKC.

Human toxocariasis: diagnosis, worldwide seroprevalences and clinical expression of the systemic and ocular forms.

PubMed

Rubinsky-Elefant, G; Hirata, C E; Yamamoto, J H; Ferreira, M U

2010-01-01

Although human toxocariasis ranks among the most common zoonotic infections worldwide, it remains relatively unknown to the public. The causal agents are the nematode parasites Toxocara canis and T. cati, whose definitive hosts are dogs and cats, respectively. When embryonated eggs are accidentally ingested by humans, larvae hatch in the small intestine, penetrate the intestinal wall and migrate, via the bloodstream, to the liver, lungs, muscles, eye and central nervous system. Although most human infections are asymptomatic, two well-defined clinical syndromes are classically recognised: visceral larva migrans (a systemic disease caused by larval migration through major organs) and ocular larva migrans (a disease limited to the eyes and optic nerves). Two less-severe syndromes have recently been described, one mainly in children (covert toxocariasis) and the other mainly in adults (common toxocariasis). Here, the current laboratory diagnosis, epidemiology and main clinical features of both the systemic and ocular forms of human toxocariasis are reviewed. New developments in serological diagnosis are described, the available seroprevalence data are analysed, and the results of relevant clinical studies that have been published over the last decade are explored, to provide an updated overview of this neglected but highly prevalent human infection.

Diagnostic accuracy of peripheral venous lactate and the 2009 WHO warning signs for identifying severe dengue in Thai adults: a prospective observational study.

PubMed

Thanachartwet, Vipa; Wattanathum, Anan; Oer-areemitr, Nittha; Jittmittraphap, Akanitt; Sahassananda, Duangjai; Monpassorn, Chalida; Surabotsophon, Manoon; Desakorn, Varunee

2016-02-01

Dengue is the most common mosquito-borne viral disease in humans. However, the sensitivities of warning signs (WSs) for identifying severe dengue in adults are low, and the utility of lactate levels for identifying severe dengue in adults has not been verified. Therefore, we aimed to evaluate the diagnostic accuracy of using peripheral venous lactate levels (PVL), as well as WSs established by the World Health Organization, for identifying severe dengue. We prospectively evaluated individuals hospitalized for dengue who were admitted to the Hospital for Tropical Diseases in Thailand between May 2013 and January 2015. Blood samples to evaluate PVL levels were collected at admission and every 24 h until the patient exhibited a body temperature of <37.8 °C for at least 24 h. Data were recorded on a pre-defined case report form, including baseline characteristics, clinical parameters, and laboratory findings. Among 125 patients with confirmed dengue, 105 (84.0%) patients had non-severe dengue, and 20 (16.0%) patients had severe dengue. The presence of clinical fluid accumulation as a WS provided high sensitivity (75.0%, 95% confidence interval [CI]: 50.9-91.3%) and specificity (90.5%, 95% CI: 83.2-95.3%). The PVL level at admission was used to evaluate its diagnostic value, and receiver operating characteristic curve analysis revealed an area under the curve of 0.84 for identifying severe dengue. At the optimal cutoff value (PVL: 2.5 mmol/L), the sensitivity and specificity were 65.0% (95% CI: 40.8-84.6%) and 96.2% (95% CI: 90.5-99.0%), respectively. A combined biomarker comprising clinical fluid accumulation and/or PVL of ≥2.5 mmol/L provided the maximum diagnostic accuracy for identifying severe dengue, with a sensitivity of 90.0% (95% CI: 68.3-98.8%) and a specificity of 87.6% (95% CI: 79.8-93.2%). Clinical fluid accumulation and/or PVL may be used as a diagnostic biomarker of severe dengue among adults. This biomarker may facilitate early recognition and timely treatment of patients with severe dengue, which may reduce dengue-related mortality and hospital burden.

Acupuncture combined with Chinese herbs for the treatment in hemivertebral French bulldogs with emergent paraparesis.

PubMed

Liu, Ching Ming; Holyoak, G Reed; Lin, Chung Tien

2016-10-01

This study follows the treatment of six French bulldogs with paraparesis caused by congenital hemivertebra which were structurally mild but clinically severe. A standardized acupuncture ( zhēn jiǔ) treatment using Hua-Tuo-Jiaji (HTJJ) as local points and other distant points combined with Chinese herbs improved the clinical signs. Few, if any, published papers mention Traditional Chinese Veterinary Medicine (TCVM) for treatment of hemivertebral paraparesis in French bulldogs. Based on the rapid treatment outcome, we encourage practitioners to integrate this form of conservative management into emergency treatment.

Update on the evaluation and treatment of osteogenesis imperfecta.

PubMed

Harrington, Jennifer; Sochett, Etienne; Howard, Andrew

2014-12-01

Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that presents with a wide clinical phenotype spectrum: from perinatal lethality and severe deformities to very mild forms without fractures. Most cases of OI are due to autosomal dominant mutations of the type I collagen genes. A multidisciplinary approach with rehabilitation, orthopedic surgery, and consideration of medical therapy with bisphosphonates underpins current management. Greater understanding of the pathogenesis of OI may lead to novel, therapeutic approaches to help improve clinical symptoms of children with OI in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

[Other viral food poisoning (hepatitis A and E)].

PubMed

Yano, Kunio

2012-08-01

Hepatitis A and E viruses are spread via the fecal-oral route. In the endemic area, restaurant and school outbreaks due to contaminated water or food have been reported. The clinical signs and symptoms in patients with typical hepatitis A and E are similar to those seen with other forms of acute viral hepatitis. Hepatitis A tends to be more severe when acquired at older ages. Hepatitis E appears to be relatively severe compared with hepatitis A. Although both hepatitis are self-limited illness, severe hepatits are rarely observed. Hepatitis A and E can be prevented by improved sanitary conditions, handwashing, heating foods appropriately. Avoidance of water and foods from endemic areas is also effective.

Processing Speed Predicts Behavioral Treatment Outcomes in Children with Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Type.

PubMed

Adalio, Christopher J; Owens, Elizabeth B; McBurnett, Keith; Hinshaw, Stephen P; Pfiffner, Linda J

2018-05-01

Neuropsychological functioning underlies behavioral symptoms of attention-deficit/hyperactivity disorder (ADHD). Children with all forms of ADHD are vulnerable to working memory deficits and children presenting with the inattentive form of ADHD (ADHD-I) appear particularly vulnerable to processing speed deficits. As ADHD-I is the most common form of ADHD presented by children in community settings, it is important to consider how treatment interventions for children with ADHD-I may be affected by deficits in processing speed and working memory. We utilize data collected from 199 children with ADHD-I, aged 7 to 11 years, who participated in a randomized clinical trial of a psychosocial-behavioral intervention. Our aims are first to determine whether processing speed or working memory predict treatment outcomes in ADHD-I symptom severity, and second whether they moderate treatment effects on ADHD-I symptom severity. Results of linear regression analyses reveal that baseline processing speed significantly predicts posttreatment ADHD-I symptom severity when controlling for baseline ADHD-I symptom severity, such that better processing speed is associated with greater symptom improvement. However, predictive effects of working memory and moderation effects of both working memory and processing speed are not supported in the present study. We discuss study limitations and implications of the relation between processing speed and treatment benefits from psychosocial treatments for children with ADHD-I.

Growth hormone and insulin-like growth factor 1 affect the severity of Graves' disease.

PubMed

Di Cerbo, Alfredo; Pezzuto, Federica; Di Cerbo, Alessandro

2017-01-01

Graves' disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves' disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves' disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves' disease improve after the surgical remission of acromegaly. We also discuss by which signaling pathways GH and IGF1 may play an integrating role in regulating the function of the immune system in Graves' disease and synergize the stimulatory activity of Graves' IgGs. Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly.The coexistence of acromegaly and Graves' disease is a very unusual event, the prevalence being <1%.Previous in vitro studies have showed that IGF1 synergizes the TSH-induced thyroid cell growth-activating pathways independent of TSH/cAMP/PKA cascade.We report the first case of a severe form of Graves' disease associated with acromegaly and show that surgical remission of acromegaly leads to a better control of symptoms of Graves' disease.

Growth hormone and insulin-like growth factor 1 affect the severity of Graves’ disease

PubMed Central

Pezzuto, Federica; Di Cerbo, Alessandro

2017-01-01

Graves’ disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves’ disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves’ disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves’ disease improve after the surgical remission of acromegaly. We also discuss by which signaling pathways GH and IGF1 may play an integrating role in regulating the function of the immune system in Graves’ disease and synergize the stimulatory activity of Graves’ IgGs. Learning points: Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly. The coexistence of acromegaly and Graves’ disease is a very unusual event, the prevalence being <1%. Previous in vitro studies have showed that IGF1 synergizes the TSH-induced thyroid cell growth-activating pathways independent of TSH/cAMP/PKA cascade. We report the first case of a severe form of Graves’ disease associated with acromegaly and show that surgical remission of acromegaly leads to a better control of symptoms of Graves’ disease. PMID:28620496

Androgen deficiency: association with increased anxiety and depression symptom severity in anorexia nervosa.

PubMed

Miller, Karen K; Wexler, Tamara L; Zha, Alicia M; Lawson, Elizabeth A; Meenaghan, Erinne M; Misra, Madhusmita; Binstock, Anna B; Herzog, David B; Klibanski, Anne

2007-06-01

Anorexia nervosa is associated with a high prevalence of psychiatric comorbidities, including anxiety and depression, and with endocrine dysfunction, including relative androgen deficiency compared with healthy young women. Because androgens are known to affect mood and behavior, we hypothesized that low endogenous androgen production in anorexia nervosa would predict anxiety and depression severity. Serum androgen levels and severity of depression (Hamilton Rating Scale for Depression) and anxiety (Hamilton Rating Scale for Anxiety) were measured in 43 community-dwelling women with DSM-IV-defined anorexia nervosa from May 2004 to July 2006. Strong inverse associations were observed between both total and free testosterone and anxiety and depression severity, independent of weight. Free testosterone was also inversely associated with 4 eating-disordered thinking and behavior subscales of the Eating Disorder Inventory 2 (EDI-2). Mean free testosterone blood levels were lower in women with clinically significant anxiety and in women with clinically significant depression, compared with those without. In stepwise regression models, free testosterone was an important predictor of anxiety and depression severity. EDI-2 ineffectiveness, perfectionism, interpersonal distress, and social insecurity scores were also inversely associated with androgen levels, independent of weight. Our data suggest that low androgen levels may contribute to anxiety, depression, and eating-disordered thinking and behavior in women with anorexia nervosa and form the basis for future studies to investigate the effectiveness of androgen replacement therapy. ClinicalTrials.gov identifier NCT00089843.

Meropenem: an updated review of its use in the management of intra-abdominal infections.

PubMed

Lowe, M N; Lamb, H M

2000-09-01

Meropenem is a carbapenem antibacterial agent with a broad spectrum of activity which encompasses gram-negative, gram-positive and anaerobic bacteria. Like other carbapenems, meropenem is stable against chromosomal and extended-spectrum beta-lactamases. In patients with moderate to severe intra-abdominal infections, empirical monotherapy with meropenem achieved clinical response rates ranging from 91 to 100% in 7 randomised comparative trials. Efficacy rates were similar to those of imipenem/cilastatin (94 to 97%), clindamycin plus tobramycin (93%) and, overall, to cefotaxime plus metronidazole (75 to 100%), although there were differences between trials versus this combination regimen. According to limited data, meropenem also achieved clinical response rates of over 80% in patients with severe intra-abdominal infections. Meropenem is well tolerated, the most common adverse events being diarrhoea, rash, nausea/vomiting and inflammation at the injection site which are reported in <2.5% of patients each. Meropenem also has an improved CNS tolerability profile compared with imipenem/cilastatin. Extensive comparative clinical data demonstrate that meropenem can be used effectively as empirical monotherapy in moderate to severe intra-abdominal infections. It also shows potential in the most severe forms of infection, although experience in this infection type remains limited. Compared with standard combination regimens, meropenem offers the benefits of ease of administration without the need for monitoring. It also offers improved CNS tolerability compared with imipenem/cilastatin with the option of a higher maximum dosage, which may be a particular advantage in patients with severe intra-abdominal infections.

Guillain-Barré Syndrome, variants & forms fruste: Reclassification with new criteria.

PubMed

Hiew, Fu Liong; Ramlan, Rahmansah; Viswanathan, Shanthi; Puvanarajah, Santhi

2017-07-01

This study aimed to evaluate the clinical and electrophysiological characteristics of various distinctive classical and localised Guillain-Barré syndrome (GBS) subtypes. Clinical characteristics and electrophysiological data of sixty-one consecutive patients admitted between 2012 and 2015 were systematically analysed and reclassified according to the new GBS clinical classification. Neurophysiology was evaluated with Hadden et al.'s vs recently proposed Rajabally et al.'s criteria. Functional severity and clinical outcome of various GBS subtypes were ascertained. All patients initially identified as GBS or related disorders can be sub-classified into having classical GBS (41, 67%), classic Miller-Fisher Syndrome (MFS) (6, 10%), Pharyngeal-cervical-brachial (PCB) (3, 5%), paraparetic GBS (4, 7%), bifacial weakness with paresthesia (3, 5%), acute ophthalmoparesis (AO) (1, 2%) and overlap syndrome (3, 5%): one (2%) with GBS/Bickerstaff brainstem encephalitis overlap and 2 (3%) with GBS/MFS overlap. Greater proportion of axonal classical GBS (67% vs 55%, p=0.372) seen with Rajabally et al.'s criteria and a predominantly axonal form of paraparetic variant (75%) independent of electrodiagnostic criteria were more representative of Asian GBS cohort. Classical GBS patients had lowest admission and discharge Medical Research Council Sum Score (MRCSS), greater functional disability and longest length of in-patient stay. Twenty (20/21, 95%) patients who needed mechanical ventilation had classical GBS. Patients required repeated dose of intravenous immunoglobulin (5/6, 3%) or plasma exchange (4/4, 100%) more frequently had axonal form of classical GBS. Phenotype recognition based on new GBS clinical classification, supported by electrodiagnostic study permits more precise clinical subtypes determination and outcome prognostication. Copyright © 2017 Elsevier B.V. All rights reserved.

[Treatment of a serious autistic disorder in a child with Naltrexone in an oral suspension form].

PubMed

Desjardins, S; Doyen, C; Contejean, Y; Kaye, K; Paubel, P

2009-04-01

CLINICAL BACKGROUND: Autism is a developmental disorder that is usually diagnosed in early childhood. According to ICD-10 criteria, autism can be characterized by delays in language skills, by impaired social interaction, verbal or non-verbal communication and by repetitive, stereotyped or severely restricted activities and interests. The causes of autism are not yet elucidated, but both genetics and environment seem to play a role in 10 to 25% of autism cases. Several biochemical abnormalities, such as impairment of serotoninergic, catecholinergic, dopaminergic, and opioid systems have been reported. Autism therapies are designed to treat symptoms, and medication can be associated with psychoeducational and environmental interventions. Generally, the medications that are currently used are not intended for autism, and must be used with caution and selected according to the type and intensity of symptoms. The most common medication consists of psychotropic therapies by administration of dopaminergic and/or serotoninergic receptor antagonists (haloperidol, risperidone, clomipramine). Several drugs, such as anxiolytics (buspirone), mood stabilisers (lithium, sodium valproate), vitamins (vitamins B6, B12) or opioid antagonists (naltrexone) can be prescribed, in second intention, in cases of severe behavioural disorders. The prescription of opioid antagonists is based on the possible implication of an opioid system disorder observed in some cases. Nevertheless, several clinical studies reveal its variable effectiveness. Naltrexone is a competitive antagonist of opioid receptors OPRM1, OPRD1 and OPRK1. In France, this drug is prescribed for treating opioid and alcohol dependence. Moreover, several studies describe naltrexone as a possible treatment of autistic children in cases of developmental disorder and hyperactivity. In the Child and Adolescent Psychopathology Department of Sainte-Anne's Hospital, autistic children benefit from a multidisciplinary treatment program that sometimes includes the administration of psychotropic medication. One of these children presented with a severe autistic disorder according to the Childhood Autism Rating Scale (CARS). Considering ICD-10 criteria, he benefited from a multidisciplinary program, associating cognitive psychotherapy, psychomotor rehabilitation, speech therapy and educational intervention. However, persistent sleep disorder and motor instability led to successive prescriptions of several different psychotropic drugs. Initial treatment by thioridazine (10mg per day) followed by propericiazine (2.5mg per day) improved sleep, but was not efficient in reducing self-mutilating behaviour. A new treatment by risperidone (from 0.5mg to 1.5mg per day) was therefore chosen; however it lost its efficacy after five months. Finally, an anxiolytic (cyamemazine) and a thymoregulator (sodium valproate) were successively tried without yielding any clinical improvement. Owing to the persistence of communication difficulties, major instability, self-mutilating behaviour and heteroaggressiveness, treatment with naltrexone was subsequently chosen with parental consent. In France, naltrexone hydrochloride is only available in tablet form (Nalorex 50mg and Revia 50mg), which is not adapted to children at the efficient dose. Consequently, an oral suspension form marketed in Spain (Antaxone 50mg) was imported, having obtained the Afssaps' (the French drug administration) authorisation for its temporary use. The Connors and Nisonger scales were used as outcome measures of behavioural symptom change. The Conners scale is used to assess attention deficit and hyperactivity, whereas the Nisonger scale analyses social skills and behaviour disorders in children and adolescents with mental retardation. The onset of treatment, at a dose of 1mg/kg/day, led to a transitory increase in negative behaviour. However, a dose of 0.75mg/kg per day subsequently led to significant improvements, as shown by outcome measurements. Self-mutilating behaviour disappeared completely. Certain side effects were observed, namely transitory sedation at the beginning of treatment and moderate constipation. This clinical case confirms that treatment of a serious autistic disorder in children using Naltrexone in oral suspension form is a potentially interesting therapeutic alternative for treating behavioural symptoms resistant to classical drug therapy.

[Hypertensive crisis and anticholinergic toxidrome secondary to accidental consumption of datura stramonium in two children].

PubMed

Batouche, D D; Benatta, N-F; Tabeliouna, K; Boudjahfa, S; Touhami, Y; Hakkoum, S

2018-05-11

To identify a hypertensive clinical form of atropine or anticholinergic toxidrome secondary to accidental consumption of Datura seeds. We report two cases of Datura intoxication in two children who presented marked anticholinergic syndrome whose diagnosis was made by the anamnesis and the clinic. Patient 1: A 5-year-old boy, returns home agitated with balance disorders. He was admitted to pediatric resuscitation unit. His Glasgow score was 11/15. The child made inconsistent remarks. The neurological examination revealed mydriasis. Hemodynamically, the blood pressure was 145/91mmHg, the heart rate was 145 bpm. The rest of the examination noted a temperature of 37.5°, a bladder globe. Standard biological tests were normal. ECG found sinus tachycardia. Urine analysis revealed a positive alkaloid reaction with the presence of atropine. The evolution was favorable after 48hours. Patient 2: 45-month-old boy admitted to a state of severe agitation of toxic origin. The clinical examination showed a central and peripheral anticholinergic symptomatology with severe hallucinations, severe hypertension, and a heart rate at 190 bpm. The rest of the examination found erythema in the thorax and upper limbs, bilateral mydriasis. The toxicological report confirmed the presence of alkaloids. The evolution was favorable. Hypertension crisis and other anticholinergic clinical signs of Datura stramonium intoxication achieve favorable outcomes in children. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Cognitive and family correlates of current suicidal ideation in children with bipolar disorder.

PubMed

Weinstein, Sally M; Van Meter, Anna; Katz, Andrea C; Peters, Amy T; West, Amy E

2015-03-01

Suicidality among youth with bipolar disorder is an extreme, but largely unaddressed, public health problem. The current study examined the psychosocial characteristics differentiating youth with varying severities of suicidal ideation that may dictate targets for suicide prevention interventions. Participants included 72 youth aged 7-13 (M=9.19, SD=1.61) with DSM-IV-TR bipolar I, II, or NOS and a parent/caregiver. Current suicidal ideation and correlates were assessed at intake, including: demographics and clinical factors (diagnosis, symptom severity, psychiatric comorbidity); child factors (cognitive risk and quality of life); and family factors (parenting stress, family cohesion, and family rigidity). Current ideation was prevalent in this young sample: 41% endorsed any ideation, and 31% endorsed active forms. Depression symptoms, quality of life, hopelessness, self-esteem, and family rigidity differentiated youth with increasing ideation severity. Separate logistic regressions examined all significant child- and family-level factors, controlling for demographic and clinical variables. Greater family rigidity and lower self-esteem remained significant predictors of current planful ideation. Diagnosis, index episode, comorbidity, and mania severity did not differentiate non-ideators from those with current ideation. Limitations include the small sample to examine low base-rate severe ideation, cross-sectional analyses and generalizability of findings beyond the outpatient clinical sample. Findings underscore the importance of assessing and addressing suicidality in preadolescent youth with bipolar disorder, before youth progress to more severe suicidal behaviors. Results also highlight child self-esteem and family rigidity as key treatment targets to reduce suicide risk in pediatric bipolar disorder. Copyright © 2014 Elsevier B.V. All rights reserved.

Cognitive and Family Correlates of Current Suicidal Ideation in Children with Bipolar Disorder

PubMed Central

Weinstein, Sally M.; Van Meter, Anna; Katz, Andrea C.; Peters, Amy T.; West, Amy E.

2014-01-01

Background Suicidality among youth with bipolar disorder is an extreme, but largely unaddressed, public health problem. The current study examined the psychosocial characteristics differentiating youth with varying severities of suicidal ideation that may dictate targets for suicide prevention interventions. Methods Participants included 72 youth aged 7–13 (M = 9.19, SD = 1.61) with DSM-IV-TR bipolar I, II, or NOS and a parent/caregiver. Current suicidal ideation and correlates were assessed at intake, including: demographics and clinical factors (diagnosis, symptom severity, psychiatric comorbidity); child factors (cognitive risk and quality of life); and family factors (parenting stress, family cohesion, and family rigidity). Results Current ideation was prevalent in this young sample: 41% endorsed any ideation, and 31% endorsed active forms. Depression symptoms, quality of life, hopelessness, self-esteem, and family rigidity differentiated youth with increasing ideation severity. Separate logistic regressions examined all significant child- and family-level factors, controlling for demographic and clinical variables. Greater family rigidity and lower self-esteem remained significant predictors of current planful ideation. Diagnosis, index episode, comorbidity, and mania severity did not differentiate non-ideators from those with current ideation. Limitations Limitations include the small sample to examine low base-rate severe ideation, cross-sectional analyses and generalizability of findings beyond the outpatient clinical sample. Conclusions Findings underscore the importance of assessing and addressing suicidality in preadolescent youth with bipolar disorder, before youth progress to more severe suicidal behaviors. Results also highlight child self-esteem and family rigidity as key treatment targets to reduce suicide risk in pediatric bipolar disorder. PMID:25462390

[Cutaneous lupus erythematosus and skin manifestations in systemic lupus erythematosus].

PubMed

Sticherling, M

2013-06-01

Skin manifestations are frequently observed in lupus erythematosus (LE) and are manifold. Nonspecific and specific symptoms can be differentiated with the latter belonging to the dermatologically well-characterized clinical entities of acute cutaneous, subacute cutaneous, chronic cutaneous as well as intermittent cutaneous LE. These forms are differentially related to systemic LE. Patient history and clinical examinations, laboratory and immunoserological findings as well as organ imaging results determine the time point as well as the intensity of therapy. Apart from cessation of smoking and alcohol consumption as well as stringent UV protection, topical therapy with corticosteroids or calcineurin inhibitors may suffice with limited forms of the disease. In many cases, however, systemic treatment with antimalarial drugs as a basic treatment is mandatory. Several immunosuppressive agents can alternatively be used in conjunction with systemic corticosteroids. Early and effective therapy is important to prevent irreversible scarring of the skin and to avoid internal organ damage.

Treatment of systemic mast cell disorders.

PubMed

Worobec, A S

2000-06-01

The heterogeneous nature of disease manifestations in mastocytosis requires the individualization of therapy to each patient's clinical presentation and prognosis. The mainstay of treatment for most categories of mastocytosis are H1 and H2 antihistamines with the addition of corticosteroids for more severe symptoms. This article presents a summary of treatment strategies for indolent and aggressive forms of mastocytosis along with a discussion of future therapeutic directions.

Cell therapies for Chagas disease.

PubMed

Carvalho, Adriana Bastos; Goldenberg, Regina Coeli Dos Santos; Campos de Carvalho, Antonio Carlos

2017-11-01

In this review of cell therapies in Chagas disease, we cover aspects related to the disease, its treatment and world demographics, before proceeding to describe the preclinical and clinical trials performed using cell therapies in the search for an alternative therapy for the most severe and lethal form of this disease, chronic chagasic cardiomyopathy. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Current and emerging treatments for the management of osteogenesis imperfecta

PubMed Central

Monti, Elena; Mottes, Monica; Fraschini, Paolo; Brunelli, PierCarlo; Forlino, Antonella; Venturi, Giacomo; Doro, Francesco; Perlini, Silvia; Cavarzere, Paolo; Antoniazzi, Franco

2010-01-01

Osteogenesis imperfecta (OI) is the most common bone genetic disorder and it is characterized by bone brittleness and various degrees of growth disorder. Clinical severity varies widely; nowadays eight types are distinguished and two new forms have been recently described although not yet classified. The approach to such a variable and heterogeneous disease should be global and therefore multidisciplinary. For simplicity, the objectives of treatment can be reduced to three typical situations: the lethal perinatal form (type II), in which the problem is survival at birth; the severe and moderate forms (types III–IX), in which the objective is ‘autonomy’; and the mild form (type I), in which the aim is to reach ‘normal life’. Three types of treatment are available: non-surgical management (physical therapy, rehabilitation, bracing and splinting), surgical management (intramedullary rod positioning, spinal and basilar impression surgery) and medical-pharmacological management (drugs to increase the strength of bone and decrease the number of fractures as bisphosphonates or growth hormone, depending on the type of OI). Suggestions and guidelines for a therapeutic approach are indicated and updated with the most recent findings in OI diagnosis and treatment. PMID:20856683

Advanced glycation end products in clinical nephrology.

PubMed

Kalousová, M; Zima, T; Tesar, V; Stípek, S; Sulková, S

2004-01-01

As a result of oxidative and carbonyl stress, advanced glycation end products (AGEs) are involved in the pathogenesis of severe and frequent diseases and their fatal vascular/cardiovascular complications, i.e. diabetes mellitus and its complications (nephropathy, angiopathy, neuropathy and retinopathy, renal failure and uremic and dialysis-associated complications), atherosclerosis and dialysis-related amyloidosis, neurodegenerative diseases, and rheumatoid arthritis. They are formed via non-enzymatic glycation which is specifically enhanced through the presence of oxidative and carbonyl stress, and their ability to form glycoxidation products in peptide and protein structures finally modulating or inducing biological reactivity. Food can be another source of AGEs; however, high serum AGEs in hemodialysis patients might reflect nutritional status better. Several methods of renal replacement therapy have been studied in connection with the AGE removal, but unfortunately the possibilities are still unsatisfactory even if high flux dialysis, hemofiltration, or hemodiafiltration give better results than conventional low flux dialysis. AGEs are currently being studied in the patients on peritoneal dialysis as their precursors can be formed in the dialysis fluid. AGEs can cause damage to the peritoneum and so a loss of ultrafiltration capacity. Many compounds give promising results in AGE inhibition (inhibition of formation of AGEs, inhibition of their action or degradation of AGEs), are tested for these properties, and eventually undergo clinical studies (e.g. aminoguanidine, OPB-9195, pyridoxamine, antioxidants, N-phenacylthiazolium bromide, antihypertensive drugs, angiotensin-converting enzyme inhibitors and angiotensin II receptor-1 antagonists). Copyright 2004 S. Karger AG, Basel

Treatment of Anxiety and Depression in the Preschool Period

PubMed Central

Luby, Joan L.

2013-01-01

Objective Empirical studies have now established that clinical anxiety and depressive disorders may arise in preschool children as early as age 3.0. As empirical studies validating and characterizing these disorders in preschoolers are relatively recent, less work has been done on the development and testing of age-appropriate treatments. Method A comprehensive literature search revealed several small randomized controlled trials (RCTs) of psychotherapeutic treatments for preschool anxiety and depression. The literature also contains case series of behavioral and psychopharmacologic interventions for specific anxiety disorders. However, to date, no large-scale RCTs of treatment for any anxiety or depressive disorder specifically targeting preschool populations have been published. Results Several age-adapted forms of cognitive behavioral therapy have been developed and preliminarily tested in small RCTs, and appear promising for a variety of forms of preschool anxiety disorders. Notably, these adaptations centrally involve primary caregivers and utilize age-adjusted methodology such as cartoon-based materials and co-constructed drawing or narratives. Modified forms of Parent Child Interaction Therapy (PCIT) have been tested and appear promising for both anxiety and depression. While preventive interventions that target parenting have shown significant promise in anxiety, these methods have not been explored in area of early childhood depression. Studies of the impact of parental treatment on infants suggest that direct treatment of the youngest children may be necessary to affect long-term change. Conclusions Recommendations are made for clinical treatment of these disorders where psychotherapy is the first line of intervention. PMID:23582866

[Gluten--mechanisms of intolerance, symptoms and treatment possibilities of IgE-related allergy for gluten in the light of actual clinical and immunological studies].

PubMed

Obtułowicz, Krystyna; Waga, Jacek; Dyga, Wojciech

2015-01-01

Gluten is the product of a chemical bond of wheat prolamin proteins (glia- dins and glutenins) in an aqueous me- dium. IgE mediated gluten allergy can be induced either by gluten as an in- gredient in foods or wheat prolamines present in the air. The aim of the study was clinical analysis of 13 patients, who demonstrated elevated levels of gluten specific IgE and identification of the most allergenic protein fractions from several samples of wheat using serum of examined subjects. Clinical analysis showed the occupational allergy to gluten in the form of rhinitis, asthma and airborne dermatistis in 9 subjects, whose symptoms disappeared during isolation from occupational exposure despite the use of a normal diet. In case of 4 patients with severe forms of chronic urticaria and atopic dermatitis, who are also allergic to grass pollen at the same time, the introduction of a gluten-free diet resulted in improvement of health conditions. The study of wheat protein fractions revealed a significant polymorphism dependent on the wheat sample. In the protein fractions, low and high molecular glutenin fractions, and alpha, beta, gamma, and omega-gliadins were separated. It has been shown that the strongest immunogenic effect causes omega-5 gliadin fraction. The removal of this fraction resulted in reduction of skin reactivity evaluated by skin prick test in the studied patients.

Standardization and utilization of biobank resources in clinical protein science with examples of emerging applications.

PubMed

Marko-Varga, György; Végvári, Ákos; Welinder, Charlotte; Lindberg, Henrik; Rezeli, Melinda; Edula, Goutham; Svensson, Katrin J; Belting, Mattias; Laurell, Thomas; Fehniger, Thomas E

2012-11-02

Biobanks are a major resource to access and measure biological constituents that can be used to monitor the status of health and disease, both in unique individual samples and within populations. Most "omic" activities rely on access to these collections of stored samples to provide the basis for establishing the ranges and frequencies of expression. Furthermore, information about the relative abundance and form of protein constituents found in stored samples provides an important historical index for comparative studies of inherited, epidemic, and developing disease. Standardizations of sample quality, form, and analysis are an important unmet need and requirement for gaining the full benefit from collected samples. Coupled to this standard is the provision of annotation describing clinical status and metadata of measurements of clinical phenotype that characterizes the sample. Today we have not yet achieved consensus on how to collect, manage, and build biobank archives in order to reach goals where these efforts are translated into value for the patient. Several initiatives (OBBR, ISBER, BBMRI) that disseminate best practice examples for biobanking are expected to play an important role in ensuring the need to preserve the sample integrity of biosamples stored for periods that reach one or several decades. These developments will be of great value and importance to programs such as the Chromosome Human Protein Project (C-HPP) that will associate protein expression in healthy and disease states with genetic foci along of each of the human chromosomes.

Point Prevalence, Clinical Characteristics, and Treatment Variation for Infants with Severe Bronchopulmonary Dysplasia

PubMed Central

Guaman, Milenka Cuevas; Gien, Jason; Baker, Christopher D.; Zhang, Huayan; Austin, Eric D.; Collaco, Joseph M.

2015-01-01

Objectives Despite improvements in survival of preterm infants, bronchopulmonary dysplasia (BPD) remains a persistent morbidity. The incidence, clinical course, and current management of severe BPD (sBPD) remain to be defined. To address these knowledge gaps, a multicenter collaborative was formed to improve outcomes in this population. Study Design We performed a “snapshot” in eight neonatal intensive care units (NICUs) on December 17, 2013. A standardized clinical data form for each inpatient born at < 32 weeks was completed and collated centrally for analysis. sBPD was defined as receiving ≥ 30% supplemental oxygen and/or receiving positive pressure ventilation at 36 weeks postmenstrual age (PMA). Results Of a total census of 710 inpatients, 351 infants were born at < 32 weeks and 128 of those (36.5%) met criteria for sBPD. The point prevalence of sBPD varied between centers (11–58%; p < 0.001). Among infants with sBPD there was a variation among centers in the use of mechanical ventilation at 28 days of life (p < 0.001) and at 36 weeks PMA (p = 0.001). We observed differences in the use of diuretics (p = 0.018), inhaled corticosteroids (p < 0.001), and inhaled β-agonists (p < 0.001). Conclusion The high point prevalence of sBPD and variable management among NICUs emphasizes the lack of evidence in guiding optimal care to improve long-term outcomes of this high-risk, understudied population. PMID:25738785

Non-extraction treatment of severe crowding with pendulum appliance.

PubMed

Gandikota, Chandrasekhar; Venkata, Yudhister Palla; Challa, Padmalatha; Juvvadi, Shubhaker Rao

2013-07-01

An extraction case was planned for non-extraction treatment using pendulum appliance and the effect of appliance was evaluated in a 14-year-old girl with a severe maxillary and mandibular crowding followed by non-extraction fixed appliance preadjusted edgewise appliance mechanotherapy. Total treatment time was for 22 months. The obtuse nasolabial angle was maintained intact. Correction of crowding, co-ordinated arch forms was achieved with molar distalization. The impetus on soft-tissue paradigm is stressed in this case report and pendulum appliance can indeed boost our clinical acumen and swing our priorities toward non-extraction treatment.

Common and rare forms of diabetes mellitus: towards a continuum of diabetes subtypes.

PubMed

Flannick, Jason; Johansson, Stefan; Njølstad, Pål R

2016-07-01

Insights into the genetic basis of type 2 diabetes mellitus (T2DM) have been difficult to discern, despite substantial research. More is known about rare forms of diabetes mellitus, several of which share clinical and genetic features with the common form of T2DM. In this Review, we discuss the extent to which the study of rare and low-frequency mutations in large populations has begun to bridge the gap between rare and common forms of diabetes mellitus. We hypothesize that the perceived division between these diseases might be due, in part, to the historical ascertainment bias of genetic studies, rather than a clear distinction between disease pathophysiologies. We also discuss possible implications of a new model for the genetic basis of diabetes mellitus subtypes, where the boundary between subtypes becomes blurred.

Genetic mapping of a locus for multiple ephiphyseal dysplasia (EDM2) to a region of chromosome 1 containing a type IX collagen gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briggs, M.D.; Choi, HiChang; Warman, M.L.

1994-10-01

Multiple epiphyseal dysplasia (MED) is a dominantly inherited chondrodysplasia characterized by mild short stature and early-onset osteoarthrosis. Some forms of MED clinically resemble another chondrodysplasia phenotype, the mild form of pseudoachondroplasia (PSACH). On the basis of their clinical similarities as well as similar ultra-structural and biochemical features in cartilage from some patients, it has been proposed that MED and PSACH belong to a single bone-dysplasia family. Recently, both mild and severe PSACH as well as a form of MED have been linked to the same interval on chromosome 19, suggesting that they may be allelic disorders. Linkage studies with themore » chromosome 19 markers were carried out in a large family with MED and excluded the previously identified interval. Using this family, we have identified a MED locus on the short arm of chromosome 1, in a region containing the gene (COL9A2) that encodes the {alpha}2 chain of type IX collagen, a structural component of the cartilage extracellular matrix. 39 refs., 3 figs., 3 tabs.« less

THE PANC 3 SCORE PREDICTING SEVERITY OF ACUTE PANCREATITIS.

PubMed

Beduschi, Murilo Gamba; Mello, André Luiz Parizi; VON-Mühlen, Bruno; Franzon, Orli

2016-03-01

About 20% of cases of acute pancreatitis progress to a severe form, leading to high mortality rates. Several studies suggested methods to identify patients that will progress more severely. However, most studies present problems when used on daily practice. To assess the efficacy of the PANC 3 score to predict acute pancreatitis severity and its relation to clinical outcome. Acute pancreatitis patients were assessed as to sex, age, body mass index (BMI), etiology of pancreatitis, intensive care need, length of stay, length of stay in intensive care unit and mortality. The PANC 3 score was determined within the first 24 hours after diagnosis and compared to acute pancreatitis grade of the Revised Atlanta classification. Out of 64 patients diagnosed with acute pancreatitis, 58 met the inclusion criteria. The PANC 3 score was positive in five cases (8.6%), pancreatitis progressed to a severe form in 10 cases (17.2%) and five patients (8.6%) died. Patients with a positive score and severe pancreatitis required intensive care more often, and stayed for a longer period in intensive care units. The PANC 3 score showed sensitivity of 50%, specificity of 100%, accuracy of 91.4%, positive predictive value of 100% and negative predictive value of 90.6% in prediction of severe acute pancreatitis. The PANC 3 score is useful to assess acute pancreatitis because it is easy and quick to use, has high specificity, high accuracy and high predictive value in prediction of severe acute pancreatitis.

THE PANC 3 SCORE PREDICTING SEVERITY OF ACUTE PANCREATITIS

PubMed Central

BEDUSCHI, Murilo Gamba; MELLO, André Luiz Parizi; VON-MÜHLEN, Bruno; FRANZON, Orli

2016-01-01

Background : About 20% of cases of acute pancreatitis progress to a severe form, leading to high mortality rates. Several studies suggested methods to identify patients that will progress more severely. However, most studies present problems when used on daily practice. Objective : To assess the efficacy of the PANC 3 score to predict acute pancreatitis severity and its relation to clinical outcome. Methods : Acute pancreatitis patients were assessed as to sex, age, body mass index (BMI), etiology of pancreatitis, intensive care need, length of stay, length of stay in intensive care unit and mortality. The PANC 3 score was determined within the first 24 hours after diagnosis and compared to acute pancreatitis grade of the Revised Atlanta classification. Results : Out of 64 patients diagnosed with acute pancreatitis, 58 met the inclusion criteria. The PANC 3 score was positive in five cases (8.6%), pancreatitis progressed to a severe form in 10 cases (17.2%) and five patients (8.6%) died. Patients with a positive score and severe pancreatitis required intensive care more often, and stayed for a longer period in intensive care units. The PANC 3 score showed sensitivity of 50%, specificity of 100%, accuracy of 91.4%, positive predictive value of 100% and negative predictive value of 90.6% in prediction of severe acute pancreatitis. Conclusion : The PANC 3 score is useful to assess acute pancreatitis because it is easy and quick to use, has high specificity, high accuracy and high predictive value in prediction of severe acute pancreatitis. PMID:27120730

Sub-Optimal Treatment of Bacterial Biofilms

PubMed Central

Song, Tianyan; Duperthuy, Marylise; Wai, Sun Nyunt

2016-01-01

Bacterial biofilm is an emerging clinical problem recognized in the treatment of infectious diseases within the last two decades. The appearance of microbial biofilm in clinical settings is steadily increasing due to several reasons including the increased use of quality of life-improving artificial devices. In contrast to infections caused by planktonic bacteria that respond relatively well to standard antibiotic therapy, biofilm-forming bacteria tend to cause chronic infections whereby infections persist despite seemingly adequate antibiotic therapy. This review briefly describes the responses of biofilm matrix components and biofilm-associated bacteria towards sub-lethal concentrations of antimicrobial agents, which may include the generation of genetic and phenotypic variabilities. Clinical implications of bacterial biofilms in relation to antibiotic treatments are also discussed. PMID:27338489

Reexpression of Prior Stroke Symptoms in Adults: When is a Mimic a Mimic?

PubMed

Siegler, James E; George, Alexander J; Martin-Schild, Sheryl

2017-09-01

A "stroke mimic" refers to any clinical condition that causes neurological symptoms clinically indistinguishable from a cerebral lesion that affects a vascular distribution, but is not caused by ischemia. One subtype of stroke mimic, termed stroke reexpression, is a form of mimicry in which previously recovered or improved stroke symptoms recur in the setting of a neurological disturbance (seizure, hypoperfusion state) or a systemic disturbance (toxic, metabolic, infectious). Many reports of stroke reexpression exist in the literature and are well known to clinicians, but there has been no consensus regarding terminology that has been published to date. The purpose of this review is to summarize several examples of stroke reexpression and propose simple, useful criteria for this clinical condition.

[Cough and hypoxemia as clinical manifestation of pulmonary alveolar proteinosis. Clinical case report].

PubMed

Nieto, Mary; Dicembrino, Manuela; Ferraz, Rubén; Romagnoli, Fernando; Giugno, Hilda; Ernst, Glenda; Siminovich, Monica; Botto, Hugo

2016-06-01

Alveolar proteinosis is a rare chronic lung disease, especially in children, characterized by abnormal accumulation of lipoproteins and derived surfactant in the intra-alveolar space that generates a severe reduction of gas exchange. Idiopathic presentation form constitutes over 90% of cases, a phenomenon associated with production of autoimmune antibodies directed at the receptor for granulocyte-macrophage colony-stimulating factor. A case of a girl of 5 years of age treated because of atypical pneumonia with unfavorable evolution due to persistent hypoxemia is presented. The diagnosis is obtained through pathologic examination of lung biopsy by thoracotomy, as treatment is carried out by 17bronchopulmonary bronchoscopy lavages and the patient evidences marked clinical improvement. Sociedad Argentina de Pediatría.

[Clinical and epidemiological aspects of neurocysticercosis in Brazil: a critical approach].

PubMed

Agapejev, Svetlana

2003-09-01

With the objective to show the characteristics of neurocysticercosis (NCC) in Brazil, was performed a critical analysis of national literature which showed a frequency of 1.5% in autopsies and 3.0% in clinical studies, corresponding to 0.3% of all admissions in general hospitals. In seroepidemiological studies the positivity of specific reactions was 2.3%. Brazilian patient with NCC presents a general clinical-epidemilogical profile (31-50 years old man, rural origin, complex partial epileptic crisis, increased protein levels or normal CSF, CT showing calcifications, constituting the inactive form of NCC), and a profile of severity (21-40 years old woman, urban origin, vascular headache and intracranial hypertension, typical CSF syndrome of NCC or alteration of two or more CSF parameters, CT showing vesicles and/or calcifications, constituting the active form of NCC). Although two localities from the state of S o Paulo have 72:100000 and 96:100000/habitants as prevalence coefficients, regional and national prevalences are very underestimated. Some aspects related to underestimation of NCC prevalence in Brazil are discussed.

Nutritional agents with anti-inflammatory properties in chemoprevention of colorectal neoplasia.

PubMed

Hull, Mark A

2013-01-01

The strong link between inflammation and colorectal carcinogenesis provides the rationale for using anti-inflammatory agents for chemoprevention of colorectal cancer (CRC). Several naturally occurring substances with anti-inflammatory properties, used in a purified 'nutraceutical' form, including omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and polyphenols such as curcumin and resveratrol, have been demonstrated to have anti-CRC activity in preclinical models. As expected, these agents have an excellent safety and tolerability profile in Phase II clinical trials. Phase III randomized clinical trials of these naturally occurring substances are now beginning to be reported. The omega-3 polyunsaturated fatty acid EPA, in the free fatty acid (FFA) form, has been demonstrated to reduce adenomatous polyp number and size in patients with familial adenomatous polyposis (FAP), a finding which has prompted evaluation of this formulation of EPA for prevention of 'sporadic' colorectal neoplasia. Anti-inflammatory 'nutraceuticals' require further clinical evaluation in polyp prevention trials as they exhibit many of the characteristics of the ideal cancer chemoprevention agent, including safety, tolerability and patient acceptability.

Unstable argininosuccinate lyase in variant forms of the urea cycle disorder argininosuccinic aciduria.

PubMed

Hu, Liyan; Pandey, Amit V; Balmer, Cécile; Eggimann, Sandra; Rüfenacht, Véronique; Nuoffer, Jean-Marc; Häberle, Johannes

2015-09-01

Loss of function of the urea cycle enzyme argininosuccinate lyase (ASL) is caused by mutations in the ASL gene leading to ASL deficiency (ASLD). ASLD has a broad clinical spectrum ranging from life-threatening severe neonatal to asymptomatic forms. Different levels of residual ASL activity probably contribute to the phenotypic variability but reliable expression systems allowing clinically useful conclusions are not yet available. In order to define the molecular characteristics underlying the phenotypic variability, we investigated all ASL mutations that were hitherto identified in patients with late onset or mild clinical and biochemical courses by ASL expression in human embryonic kidney 293 T cells. We found residual activities >3% of ASL wild type (WT) in nine of 11 ASL mutations. Six ASL mutations (p.Arg95Cys, p.Ile100Thr, p.Val178Met, p.Glu189Gly, p.Val335Leu, and p.Arg379Cys) with residual activities ≥16% of ASL WT showed no significant or less than twofold reduced Km values, but displayed thermal instability. Computational structural analysis supported the biochemical findings by revealing multiple effects including protein instability, disruption of ionic interactions and hydrogen bonds between residues in the monomeric form of the protein, and disruption of contacts between adjacent monomeric units in the ASL tetramer. These findings suggest that the clinical and biochemical course in variant forms of ASLD is associated with relevant residual levels of ASL activity as well as instability of mutant ASL proteins. Since about 30% of known ASLD genotypes are affected by mutations studied here, ASLD should be considered as a candidate for chaperone treatment to improve mutant protein stability.

Major Depressive Disorder with Sub-threshold Bipolarity in the National Comorbidity Survey Replication

PubMed Central

Angst, Jules; Cui, Lihong; Swendsen, J. Joel; Rothen, S.; Cravchik, Anibal; Kessler, Ronald; Merikangas, Kathleen

2011-01-01

Objectives There is growing clinical and epidemiologic evidence indicating that major mood disorders form a spectrum from Major Depressive Disorder (MDD) to pure mania. The present investigation examined the prevalence and clinical correlates of MDD with sub-threshold bipolarity vs. pure MDD in the National Comorbidity Survey Replication (NCS-R). Methods The NCS-R is a nationally representative face-to-face household survey of the U.S. population conducted between February, 2001 and April, 2003. Lifetime history of mood disorders, symptoms and clinical indicators of severity were collected using version 3.0 of the WHO Composite International Diagnostic Interview, a fully structured lay-administered diagnostic interview. Results Nearly 40% of study participants with a history of major depressive disorder had a history of sub-threshold hypomania. This subgroup had a younger age of disorder onset, more episodes of depression, and higher rates of comorbidity than those without a history of hypomania, and lower levels of clinical severity than those with bipolar II disorder. Conclusions The findings demonstrate heterogeneity of major depressive disorder and support the validity of inclusion of sub-threshold mania in the diagnostic classification. The broadening of criteria for bipolar disorder would have important implications for research and clinical practice. PMID:20713498

Acute posttraumatic stress symptoms and depression after exposure to the 2005 Saskatchewan Centennial Air Show disaster: prevalence and predictors.

PubMed

Taylor, Steven; Asmundson, Gordon J G; Carleton, R Nicholas; Brundin, Peter

2007-01-01

The purpose of this study was to determine the prevalence of acute distress-that is, clinically significant posttraumatic stress symptoms (PTSS) and depression-and to identify predictors of each in a sample of people who witnessed a fatal aircraft collision at the 2005 Saskatchewan Centennial Air Show. Air Show attendees (N = 157) were recruited by advertisements in the local media and completed an Internet-administered battery of questionnaires. Based on previously established cut-offs, 22 percent respondents had clinically significant PTSS and 24 percent had clinically significant depressive symptoms. Clinically significant symptoms were associated with posttrauma impairment in social and occupational functioning. Acute distress was associated with several variables, including aspects of Air Show trauma exposure, severity of prior trauma exposure, low posttrauma social support (ie, negative responses by others), indices of poor coping (eg, intolerance of uncertainty, rumination about the trauma), and elevated scores on anxiety sensitivity, the personality trait of absorption, and dissociative tendencies. Results suggest that clinically significant acute distress is common in the aftermath of witnessed trauma. The statistical predictors (correlates) of acute distress were generally consistent with the results of studies of other forms of trauma. People with elevated scores on theoretical vulnerability factors (eg, elevated anxiety sensitivity) were particularly likely to develop acute distress.

Pathogenesis of canine distemper virus in experimentally infected raccoon dogs, foxes, and minks.

PubMed

Zhao, Jianjun; Shi, Ning; Sun, Yangang; Martella, Vito; Nikolin, Veljko; Zhu, Chunsheng; Zhang, Hailing; Hu, Bo; Bai, Xue; Yan, Xijun

2015-10-01

Canine distemper virus (CDV) infects a broad range of carnivores and causes a highly contagious disease with severe immunosuppression. The disease severity markedly varies in different species. To investigate the pathogenesis of CDV in raccoon dog (Nyctereutes procyonoides), fox (Vulpes vulpes) and mink (Neovison vison) species, three groups of CDV sero-negative animals were infected with CDV strain LN(10)1. This CDV strain belongs to the Asia-1 genotype, which is epidemiologically predominant in carnivores in China. CDV infection provoked marked differences in virulence in the three species that were studied. Raccoon dogs developed fever, severe conjunctivitis, and pathological lesions, with 100% (5/5) mortality and with high viral RNA loads in organs within 15 days post infection (dpi). In infected foxes, the onset of the disease was delayed, with 40% (2/5) mortality by 21 dpi. Infected minks developed only mild clinical signs and pathological lesions, and mortality was not observed. Raccoon dogs and foxes showed more severe immune suppression (lymphopenia, decreased lymphocyte proliferation, viremia and low-level virus neutralizing antibodies) than minks. We also observed a distinct pattern of cytokine mRNA transcripts at different times after infection. Decreased IFN-γ and IL-4 mRNA responses were evident in the animals with fatal disease, while up-regulation of these cytokines was observed in the animals surviving the infection. Increased TNF-α response was detected in animals with mild or severe clinical signs. Based on the results, we could distinguish three different patterns of disease after experimental CDV infection, e.g. a mild form in minks, a moderate form in foxes and a severe disease in raccoon dogs. The observed differences in susceptibility to CDV could be related to distinct host cytokine profiles. Comparative evaluation of CDV pathogenesis in various animal species is pivotal to generate models suitable for the evaluation of CDV-host interactions and of vaccine response. Copyright © 2015 Elsevier B.V. All rights reserved.

Feedback in clinical education, part I: Characteristics of feedback provided by approved clinical instructors.

PubMed

Nottingham, Sara; Henning, Jolene

2014-01-01

Providing students with feedback is an important component of athletic training clinical education; however, little information is known about the feedback that Approved Clinical Instructors (ACIs; now known as preceptors) currently provide to athletic training students (ATSs). To characterize the feedback provided by ACIs to ATSs during clinical education experiences. Qualitative study. One National Collegiate Athletic Association Division I athletic training facility and 1 outpatient rehabilitation clinic that were clinical sites for 1 entry-level master's degree program accredited by the Commission on Accreditation of Athletic Training Education. A total of 4 ACIs with various experience levels and 4 second-year ATSs. Extensive field observations were audio recorded, transcribed, and integrated with field notes for analysis. The constant comparative approach of open, axial, and selective coding was used to inductively analyze data and develop codes and categories. Member checking, triangulation, and peer debriefing were used to promote trustworthiness of the study. The ACIs gave 88 feedback statements in 45 hours and 10 minutes of observation. Characteristics of feedback categories included purpose, timing, specificity, content, form, and privacy. Feedback that ACIs provided included several components that made each feedback exchange unique. The ACIs in our study provided feedback that is supported by the literature, suggesting that ACIs are using current recommendations for providing feedback. Feedback needs to be investigated across multiple athletic training education programs to gain more understanding of certain areas of feedback, including frequency, privacy, and form.

Impulsivity and Gambling Type Among Treatment-Seeking Disordered Gamblers: An Explorative Study.

PubMed

Lutri, Vittorio; Soldini, Emiliano; Ronzitti, Silvia; Smith, Neil; Clerici, Massimo; Blaszczynski, Alex; Bowden-Jones, Henrietta

2018-03-03

Several studies have found that certain traits of impulsivity are associated with gambling disorder, and influence its severity. Furthermore, it has been suggested that some forms of gambling, particularly electronic gambling machines, are particularly widespread among pathological gamblers. In the present, exploratory study, we aim to clarify the role played by impulsivity in influencing the choice of specific gambling activities, by examining the relation between individual dimensions of impulsivity, and the choice of specific gambling activities in a clinical population. 100 consecutively admitted pathological gamblers at the National Problem Gambling Clinic in London (UK) in 2014 were administered the UPPS-P and BIS-11 impulsivity questionnaires, the Problem Gambling Severity Index, and underwent a structured interview concerning their gambling activities in the month and year prior to assessment. The correlation between individual gambling activities and impulsivity dimensions was analyzed both at a bivariate level, and using logistic regression. We found a significant correlation between Negative Urgency, Motor impulsivity and low-stakes machine gambling on multivariate analysis. Negative urgency (i.e. the tendency to act impulsively in response to negative affect), and Motor impulsivity (a tendency to rash action and restlessness) might be mediating factors in the choice of electronic gambling machines, particularly among patients whose gambling is escape-oriented. Structural and situational characteristics of gambling machines, particularly the widespread availability of low-stakes-rather than high-stakes-gaming machines, might concur to the choice of this form of gambling among individuals who present higher negative urgency and restlessness.

Adherence predictors in an Internet-based Intervention program for depression.

PubMed

Castro, Adoración; López-Del-Hoyo, Yolanda; Peake, Christian; Mayoral, Fermín; Botella, Cristina; García-Campayo, Javier; Baños, Rosa María; Nogueira-Arjona, Raquel; Roca, Miquel; Gili, Margalida

2018-05-01

Internet-delivered psychotherapy has been demonstrated to be effective in the treatment of depression. Nevertheless, the study of the adherence in this type of the treatment reported divergent results. The main objective of this study is to analyze predictors of adherence in a primary care Internet-based intervention for depression in Spain. A multi-center, three arm, parallel, randomized controlled trial was conducted with 194 depressive patients, who were allocated in self-guided or supported-guided intervention. Sociodemographic and clinical characteristics were gathered using a case report form. The Mini international neuropsychiatric interview diagnoses major depression. Beck Depression Inventory was used to assess depression severity. The visual analogic scale assesses the respondent's self-rated health and Short Form Health Survey was used to measure the health-related quality of life. Age results a predictor variable for both intervention groups (with and without therapist support). Perceived health is a negative predictor of adherence for the self-guided intervention when change in depression severity was included in the model. Change in depression severity results a predictor of adherence in the support-guided intervention. Our findings demonstrate that in our sample, there are differences in sociodemographic and clinical variables between active and dropout participants and we provide adherence predictors in each intervention condition of this Internet-based program for depression (self-guided and support-guided). It is important to point that further research in this area is essential to improve tailored interventions and to know specific patients groups can benefit from these interventions.

Perceived mental health related stigma, gender, and depressive symptom severity in a psychiatric facility in South India.

PubMed

Kulesza, Magdalena; Raguram, R; Rao, Deepa

2014-06-01

Few studies exist on the topic of gender associated with depression and mental health-related stigma coming out of non-Western countries such as India. We aimed to add to the literature by assessing these relationships among adults seeking psychiatric services in India. Participants were 60 individuals seeking care at a psychiatric clinic in Bangalore, India. The majority of participants were female with a mean age of 36 years (SD=9.75). Contrary to our prediction, there were no significant differences between men (M=28.96; SD=9.85) and women (M=33.03; SD=12.08) on depression severity, t(58)=1.42, p=.16. Yet, women (M=10.09, SD=8.23) reported significantly more perceived stigma than men (M=5.79, SD=5.86), t(58)=2.30, p=.02. While men and women seeking psychiatric services at the psychiatric clinic in India report similar levels of depression severity, women reported more perceived mental illness stigma. Having experienced regular forms of discrimination associated with female status in India, it may be the case that women are more attuned to other forms of stigma, such as mental health stigma investigated in the present study. Given the detrimental impact of stigma on treatment adherence and engagement in care, additional research is needed support this work, including research on interventions to reduce stigma and improve engagement in care. Copyright © 2014 Elsevier B.V. All rights reserved.

[Hidradenitis Suppurativa: Combined Treatment with Dermal Template, Skin Graft and Negative Pressure Wound Therapy, a Case Study].

PubMed

Ribeiro, Luís Mata; Guerra, Ana Silva

2018-01-31

Hidrosadenitis supurativa is a chronic inflammatory disease with great physical and psychological impact. Although conservative treatments may be effective in mild forms of the disease, extensive surgical resection and reconstruction are necessary in more severe forms of the disease. The purpose of this paper is to describe our two-stage reconstructive procedure regarding this kind of disease. We present a clinical case of a patient with severe, bilateral axillary hidrosadenitis. In the first surgical step we excised the lesions and applied the artificial dermis secured with negative pressure wound therapy. In the second step we used a split thickness skin graft to close the wound and again applied negative pressure wound therapy. The graft take was very good, without complications. The cosmetic outcome is acceptable and shoulder mobility was not compromised. No recurrence was detected (nine months follow up).

Point mutations which should not be overlooked in Hb H disease.

PubMed

Farashi, Samaneh; Bayat, Nooshin; Vakili, Shadi; Faramarzi Garous, Negin; Ashki, Mehri; Imanian, Hashem; Najmabadi, Hossein; Azarkeivan, Azita

2016-01-01

Hb H disease is an alpha-thalassemia (α-thal) syndrome characterized by chronic hemolytic anemia that occurs when three of total four α-globin genes lost their function due to completely deletions or different kind of mutations. We here described 66 patients who have been diagnosed for Hb H disease during the last five years in our center. The genotypes involving point mutations present more severe phenotype than deletional forms that make them of primary important to health management. Hb H subjects carry different α-globin genotypes including deletional and non-deletional mutations showing heterogenous clinical manifestations. The Hb H patients presenting a wide range of phenotype carried different deletional, non-deletional mutations or compound heterozygosity of them. We emphasize the importance of some point mutations responsible for more severe form of Hb H disease in Iranian population and the necessity for consideration of prenatal diagnosis (PND) in high-risk couples.

[No X-chromosome linked juvenile foveal retinoschisis].

PubMed

Pérez Alvarez, M J; Clement Fernández, F

2002-08-01

To describe the clinical characteristics of two cases of juvenile foveal retinoschisis in women with an atypical hereditary pattern, no X-chromosome linked. An autosomal recessive inheritance is proposed. Two generations of a family (5 members) in which only two sisters were evaluated. The complete examination of these two cases includes retinography, fluorescein angiography, automated perimetry, color vision testing, electroretinogram, electrooculogram and visually evoked potentials. Comparing our cases with the classic form of X-linked juvenile retinoschisis, they are less severely affected. The best visual acuity and the less disturbed or even normal electroretinogram confirm this fact. We emphasise the existence of isolated plaques of retinal pigment epithelium atrophy with perivascular pigment clumps without foveal schisis in one patient, which could represent an evolved form of this entity. The hereditary foveal juvenile retinoschisis in women suggests an autosomal inheritance (autosomal recessive in our cases) and presents less severe involvement (Arch Soc Esp Oftalmol 2002; 77: 443-448).

Retrospective natural history of thymidine kinase 2 deficiency.

PubMed

Garone, Caterina; Taylor, Robert W; Nascimento, Andrés; Poulton, Joanna; Fratter, Carl; Domínguez-González, Cristina; Evans, Julie C; Loos, Mariana; Isohanni, Pirjo; Suomalainen, Anu; Ram, Dipak; Hughes, M Imelda; McFarland, Robert; Barca, Emanuele; Lopez Gomez, Carlos; Jayawant, Sandeep; Thomas, Neil D; Manzur, Adnan Y; Kleinsteuber, Karin; Martin, Miguel A; Kerr, Timothy; Gorman, Grainne S; Sommerville, Ewen W; Chinnery, Patrick F; Hofer, Monika; Karch, Christoph; Ralph, Jeffrey; Cámara, Yolanda; Madruga-Garrido, Marcos; Domínguez-Carral, Jana; Ortez, Carlos; Emperador, Sonia; Montoya, Julio; Chakrapani, Anupam; Kriger, Joshua F; Schoenaker, Robert; Levin, Bruce; Thompson, John L P; Long, Yuelin; Rahman, Shamima; Donati, Maria Alice; DiMauro, Salvatore; Hirano, Michio

2018-03-30

Thymine kinase 2 (TK2) is a mitochondrial matrix protein encoded in nuclear DNA and phosphorylates the pyrimidine nucleosides: thymidine and deoxycytidine. Autosomal recessive TK2 mutations cause a spectrum of disease from infantile onset to adult onset manifesting primarily as myopathy. To perform a retrospective natural history study of a large cohort of patients with TK2 deficiency. The study was conducted by 42 investigators across 31 academic medical centres. We identified 92 patients with genetically confirmed diagnoses of TK2 deficiency: 67 from literature review and 25 unreported cases. Based on clinical and molecular genetics findings, we recognised three phenotypes with divergent survival: (1) infantile-onset myopathy (42.4%) with severe mitochondrial DNA (mtDNA) depletion, frequent neurological involvement and rapid progression to early mortality (median post-onset survival (POS) 1.00, CI 0.58 to 2.33 years); (2) childhood-onset myopathy (40.2%) with mtDNA depletion, moderate-to-severe progression of generalised weakness and median POS at least 13 years; and (3) late-onset myopathy (17.4%) with mild limb weakness at onset and slow progression to respiratory insufficiency with median POS of 23 years. Ophthalmoparesis and facial weakness are frequent in adults. Muscle biopsies show multiple mtDNA deletions often with mtDNA depletion. In TK2 deficiency, age at onset, rate of weakness progression and POS are important variables that define three clinical subtypes. Nervous system involvement often complicates the clinical course of the infantile-onset form while extraocular muscle and facial involvement are characteristic of the late-onset form. Our observations provide essential information for planning future clinical trials in this disorder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mozart Ear Deformity: a Rare Diagnosis in the Ear Reconstruction Clinic.

PubMed

Telich-Tarriba, Jose E; Victor-Baldin, Andre; Apellaniz-Campo, Armando

2017-07-01

Mozart ear is a rare auricular deformity; clinically the auricle is characterized by the bulging appearance of the anterosuperior portion of the auricle due to fusion of the crura of the antihelix, an inversion in the normal form of the cavum conchae resulting in its convexity and a slit-like narrowing of the orifice of the external auditory meatus.A retrospective review of clinical and photographic records of patients attended at the ear reconstruction clinic of our hospital between June of 2010 and May 2016 was performed; out of 576 consecutive patients only 3 fulfilled the inclusion criteria, with a prevalence of 0.5%. The authors present these patients.Surgical interventions mainly focus on the correction of the convex concha; however, the procedure should be tailored to the severity of the deformity and the wishes of the patient.

Higher Impulsivity As a Distinctive Trait of Severe Cocaine Addiction among Individuals Treated for Cocaine or Alcohol Use Disorders.

PubMed

García-Marchena, Nuria; Ladrón de Guevara-Miranda, David; Pedraz, María; Araos, Pedro Fernando; Rubio, Gabriel; Ruiz, Juan Jesús; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Santín, Luis J; Rodríguez de Fonseca, Fernando

2018-01-01

Despite alcohol being the most often used addictive substance among addicted patients, use of other substances such as cocaine has increased over recent years, and the combination of both drugs aggravates health impairment and complicates clinical assessment. The aim of this study is to identify and characterize heterogeneous subgroups of cocaine- and alcohol-addicted patients with common characteristics based on substance use disorders, psychiatric comorbidity and impulsivity. A total of 214 subjects with cocaine and/or alcohol use disorders were recruited from outpatient treatment programs and clinically assessed. A latent class analysis was used to establish phenotypic categories according to diagnosis of cocaine and alcohol use disorders, mental disorders, and impulsivity scores. Relevant variables were examined in the latent classes (LCs) using correlation and analyses of variance and covariance. Four LCs of addicted patients were identified: Class 1 (45.3%) formed by alcohol-dependent patients exhibiting lifetime mood disorder diagnosis and mild impulsivity; Class 2 (14%) formed mainly by lifetime cocaine use disorder patients with low probability of comorbid mental disorders and mild impulsivity; Class 3 (10.7%) formed by cocaine use disorder patients with elevated probability to course with lifetime anxiety, early and personality disorders, and greater impulsivity scores; and Class 4 (29.9%) formed mainly by patients with alcohol and cocaine use disorders, with elevated probability in early and personality disorders and elevated impulsivity. Furthermore, there were significant differences among classes in terms of Diagnostic and Statistical Manual of Mental Disorders-4th Edition-Text Revision criteria for abuse and dependence: Class 3 showed more criteria for cocaine use disorders than other classes, while Class 1 and Class 4 showed more criteria for alcohol use disorders. Cocaine- and alcohol-addicted patients who were grouped according to diagnosis of substance use disorders, psychiatric comorbidity, and impulsivity show different clinical and sociodemographic variables. Whereas mood and anxiety disorders are more prevalent in alcohol-addicted patients, personality disorders are associated with cocaine use disorders and diagnosis of comorbid substance use disorders. Notably, increased impulsivity is a distinctive characteristic of patients with severe cocaine use disorder and comorbid personality disorders. Psychiatric disorders and impulsivity should be considered for improving the stratification of addicted patients with shared clinical and sociodemographic characteristics to select more appropriate treatments.

CDC Grand Rounds: Improving the Lives of Persons with Sickle Cell Disease.

PubMed

Hulihan, Mary; Hassell, Kathryn L; Raphael, Jean L; Smith-Whitley, Kim; Thorpe, Phoebe

2017-11-24

Approximately 100,000 Americans have sickle cell disease (SCD), a group of recessively inherited red blood cell disorders characterized by abnormal hemoglobin, called hemoglobin S or sickle hemoglobin, in the red blood cells. Persons with hemoglobin SS or hemoglobin Sß 0 thalassemia, also known as sickle cell anemia (SCA), have the most severe form of SCD. Hemoglobin SC disease and hemoglobin Sß + thalassemia are other common forms of SCD. Red blood cells that contain sickle hemoglobin are inflexible and can stick to vessel walls, causing a blockage that slows or stops blood flow. When this happens, oxygen cannot reach nearby tissues, leading to attacks of sudden, severe pain, called pain crises, which are the clinical hallmark of SCD. The red cell sickling and poor oxygen delivery can also cause damage to the brain, spleen, eyes, lungs, liver, and multiple other organs and organ systems. These chronic complications can lead to increased morbidity, early mortality, or both. Tremendous strides in treating and preventing the complications of SCD have extended life expectancy. Now, nearly 95% of persons born with SCD in the United States reach age 18 years (1); however, adults with the most severe forms of SCD have a life span that is 20-30 years shorter than that of persons without SCD (2).

Association of Van Wyk Grumbach and Debre Semelaigne Syndromes with Severe Hypothyroidism.

PubMed

Oden Akman, Alkim; Tayfun, Meltem; Demirel, Fatma; Ucakturk, Seyit Ahmed; Gungor, Ali

2015-12-01

Van Wyk Grumbach syndrome (VWGS) and Kocher-Debre Semelaigne syndrome (KDSS) are rare forms of pseudo-precocious puberty and myopathy in patients with longstanding untreated hypothyroidism. We present the case of an adolescent girl who developed pseudo-precocious puberty and myopathy caused by long-term untreated hypothyroidism. A 17-year-old female patient was referred to our outpatient clinic due to menstrual irregularities. She had muscle pain and multiple cystic ovaries in addition to clinical signs of severe congenital hypothyroidism. High levels of creatinine and creatinine kinase and accompanying muscle hypertrophy were present. After the initiation of L-thyroxine therapy, the symptoms were alleviated in a short time. Congenital and acquired hypothyroidism should be considered in the differential diagnosis of pseudo-precocious puberty and myopathy that presents with muscle pain, muscle hypertrophy, and elevated creatinine kinase levels. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

A Case of Myxedema Coma Presenting as a Brain Stem Infarct in a 74-Year-Old Korean Woman

PubMed Central

Ahn, Ji Yun; Kwon, Hyuk-Sool; Ahn, Hee Chol

2010-01-01

Myxedema coma is the extreme form of untreated hypothyroidism. In reality, few patients present comatose with severe myxedema. We describe a patient with myxedema coma which was initially misdiagnosed as a brain stem infarct. She presented to the hospital with alteration of the mental status, generalized edema, hypothermia, hypoventilation, and hypotension. Initially her brain stem reflexes were absent. After respiratory and circulatory support, her neurologic status was not improved soon. The diagnosis of myxedema coma was often missed or delayed due to various clinical findings and concomitant medical condition and precipitating factors. It is more difficult to diagnose when a patient has no medical history of hypothyroidism. A high index of clinical suspicion can make a timely diagnosis and initiate appropriate treatment. We report this case to alert clinicians considering diagnosis of myxedema coma in patients with severe decompensated metabolic state including mental change. PMID:20808690

A case of myxedema coma presenting as a brain stem infarct in a 74-year-old Korean woman.

PubMed

Ahn, Ji Yun; Kwon, Hyuk-Sool; Ahn, Hee Chol; Sohn, You Dong

2010-09-01

Myxedema coma is the extreme form of untreated hypothyroidism. In reality, few patients present comatose with severe myxedema. We describe a patient with myxedema coma which was initially misdiagnosed as a brain stem infarct. She presented to the hospital with alteration of the mental status, generalized edema, hypothermia, hypoventilation, and hypotension. Initially her brain stem reflexes were absent. After respiratory and circulatory support, her neurologic status was not improved soon. The diagnosis of myxedema coma was often missed or delayed due to various clinical findings and concomitant medical condition and precipitating factors. It is more difficult to diagnose when a patient has no medical history of hypothyroidism. A high index of clinical suspicion can make a timely diagnosis and initiate appropriate treatment. We report this case to alert clinicians considering diagnosis of myxedema coma in patients with severe decompensated metabolic state including mental change.

[Strychnine poisoning: uncommon, but does still happen].

PubMed

van Berlo-van de Laar, Inge R F; Arbouw, Maurits E L; Bles, Carmen M A

2015-01-01

Acute strychnine poisoning is an uncommon form of intoxication, characterized by severe tonic clonic seizures and tetanus-like contractions while the patient is fully conscious. It can result in respiratory failure, leading to death. A 47-year-old man was admitted to the casualty department 2 hours after self-poisoning with strychnine. The clinical picture consisted of persistent seizures, which were treated with midazolam and propofol. The patient went into respiratory failure and asystole, so intubation and cardiac massage were initiated. Other complications were severe metabolic acidosis, hyperthermia and rhabdomyolysis with renal failure. The treatment consisted of cooling, hyperhydration and intravenous administration of sodium bicarbonate. He was discharged to a mental care institution with no persistent symptoms 11 days later. Early aggressive treatment of a strychnine intoxication can be life-saving. Knowledge of the clinical picture and the right treatment is important. Treatment is primarily focussed on stopping the convulsions and securing the airway.

Variability in dentofacial phenotypes in four families with WNT10A mutations

PubMed Central

Vink, Christian P; Ockeloen, Charlotte W; ten Kate, Sietske; Koolen, David A; Ploos van Amstel, Johannes Kristian; Kuijpers-Jagtman, Anne-Marie; van Heumen, Celeste C; Kleefstra, Tjitske; Carels, Carine E L

2014-01-01

This article describes the inter- and intra-familial phenotypic variability in four families with WNT10A mutations. Clinical characteristics of the patients range from mild to severe isolated tooth agenesis, over mild symptoms of ectodermal dysplasia, to more severe syndromic forms like odonto-onycho-dermal dysplasia (OODD) and Schöpf–Schulz–Passarge syndrome (SSPS). Recurrent WNT10A mutations were identified in all affected family members and the associated symptoms are presented with emphasis on the dentofacial phenotypes obtained with inter alia three-dimensional facial stereophotogrammetry. A comprehensive overview of the literature regarding WNT10A mutations, associated conditions and developmental defects is presented. We conclude that OODD and SSPS should be considered as variable expressions of the same WNT10A genotype. In all affected individuals, a dished-in facial appearance was observed which might be helpful in the clinical setting as a clue to the underlying genetic etiology. PMID:24398796

The quest for fragile X biomarkers.

PubMed

Westmark, Cara J

2014-12-01

Fragile X is the most common form of inherited intellectual disability and the leading known genetic cause of autism. There is currently no cure or approved medication for fragile X although various drugs target specific disease symptoms and a large number of therapeutics are in various stages of clinical development. Multiple recent clinical trials have failed on their primary endpoints indicating that there is a compelling need for validated biomarkers and outcome measures in fragile X. There are currently no validated blood-based biomarkers to assess disease severity or to monitor drug efficacy in fragile X syndrome. Herein, we review candidate blood protein biomarkers including extracellular-regulated kinase, phosphoinositide 3-kinase, matrix metalloproteinase 9, amyloid-beta and amyloid-beta protein precursor. Bench-to-bedside plans for fragile X syndrome are severely limited by the lack of validated outcome measures. The reviewed candidate biomarkers are at early stages of validation and deserve further investigation.

Clinical characteristics of self-mutilating behavior in Turkish male subjects with antisocial personality disorder: relationship to psychopathy.

PubMed

Alpay Ates, M; Algul, Ayhan; Semiz, Umit B; Gecici, Omer; Basoglu, Cengiz; Ebrinc, Servet; Cetin, Mesut

2011-05-01

The aims of this study were to determine the characteristics of self-mutilation (SM) and examine the relationship between SM and psychopathy in male subjects with antisocial personality disorder (APD). APD diagnosis was established by the Structured Clinical Interview for DSM-III-R Axis II Disorders. Subjects (N = 116) were assessed using the Psychopathy Checklist-Revised and a semi-structured self-mutilation questionnaire form. In males with APD, the percentages of psychopathy and SM were 48.3% (N =56) and 96.6% (N = 112), respectively. There were positive correlations between severity of psychopathy and severity, number, and frequency of SM. Considerably high rates of SM and psychopathy were found in Turkish males with APD. The features of SM were associated with comorbidity of psychopathy. These results showed the importance of exploring the self-injurious behavior and psychopathy when diagnosed with APD.

Cystic fibrosis: a clinical view.

PubMed

Castellani, Carlo; Assael, Baroukh M

2017-01-01

Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude. Classical treatment includes pancreatic enzyme replacement, respiratory physiotherapy, mucolitics, and aggressive antibiotic therapy. A significant proportion of patients with severe symptoms still requires lung or, less frequently, liver transplantation. The great number of mutations and their diverse effects on the CFTR protein account only partially for CF clinical variability, and modifier genes have a role in modulating the clinical expression of the disease. Despite the increasing understanding of CFTR functioning, several aspects of CF need still to be clarified, e.g., the worse outcome in females, the risk of malignancies, the pathophysiology, and best treatment of comorbidities, such as CF-related diabetes or CF-related bone disorder. Research is focusing on new drugs restoring CFTR function, some already available and with good clinical impact, others showing promising preliminary results that need to be confirmed in phase III clinical trials.

Sensitivity of alternative measures of functioning and wellbeing for adults with sickle cell disease: comparison of PROMIS® to ASCQ-Me℠.

PubMed

Keller, San; Yang, Manshu; Treadwell, Marsha J; Hassell, Kathryn L

2017-06-02

Sickle Cell Disease (SCD) causes profound suffering and decrements in daily functioning. Demand is growing for valid and reliable measures to systematically document these effects, particularly in adults. The Adult Sickle Cell Quality of Life Measurement System, ASCQ-Me℠, was developed for this purpose. ASCQ-Me℠ is one of four measurement systems housed within the Person-Centered Assessment Resource (PCAR), funded by the National Institutes of Health, to support clinical research. To help users select the best of these measures for adults with SCD, we evaluated and compared two PCAR systems: one designed to be "universally applicable" (the Patient-Reported Outcome Measurement Information System, PROMIS®) and one designed specifically for SCD (ASCQ-Me℠). Respondents to PROMIS and ASCQ-Me questions were 490 adults with SCD from seven geographically-disbursed clinics within the US. Data were collected for six ASCQ-Me measures (Emotional Impact, Sleep Impact, Social Impact, Stiffness Impact, Pain Impact, SCD Pain Episode Frequency and Severity) and ten PROMIS measures (Pain Impact, Pain Behavior, Physical Functioning, Anxiety, Depression, Fatigue, Satisfaction with Discretionary Social Activities, Satisfaction with Social Roles, Sleep Disturbance, and Sleep-Related Impairment). Statistical analyses, including analysis of variance and multiple linear regression, were conducted to determine the sensitivity of measures to SCD severity. SCD severity was assessed via a checklist of associated treatments and conditions. For those with the most severe SCD, PROMIS scores showed worse health compared to the general population for nine of ten health domains: the magnitude of the difference ranged 0.5 to 1.1 standard deviation units. The PROMIS domains most severely affected were Physical Functioning and Pain (Impact and Behavior). Significant differences by tertile of the SCD-MHC were shown for most PROMIS short forms and all ASCQ-Me short and fixed forms. In most models, ASCQ-Me measures explained statistically significant unique variance in SCD-MHC scores complementary to that explained by corresponding PROMIS measures. Study results supported the validity of both PROMIS and ASCQ-Me measures for use in adults with SCD. Compared to comparable PROMIS scores, most ASCQ-Me scores were better predictors of SCD disease severity, as measured by a medical history checklist. The clinical implications of these results require further investigation.

[Erectile dysfunction and diabetes in Conakry (Guinea): frequency and clinical characteristics from 187 diabetic patients].

PubMed

Baldé, N M; Diallo, A B; Baldé, M C; Kaké, A; Diallo, M M; Diallo, M B; Maugendre, D

2006-09-01

Sexual dysfunction is frequent in the diabetic population. In Africa, medical care for erectile dysfunction is underprovided, profoundly altering the quality of life of the patients. We report the prevalence of erectile dysfunction in 187 diabetic patients followed in the department of Endocrinology of the Conakry teaching hospital. Prevalence was estimated from the French version of the International Index of Erectile Function (IIEF). Erectile dysfunction concerned 90 patients (48%) of whom a severe form was observed in 54%, a moderate form in 35% and a mild form in 12%. The patients who presented erectile dysfunction were significantly older, displayed longer duration of diabetes with more complications (sensorial neuropathy and macroangiopathy) and often took drugs for associated cardiovascular diseases. In 28% of the cases, erectile dysfunction was associated with a decline in libido and in 26% with ejaculation disorders. In conclusion, erectile dysfunction is frequent and severe among diabetic patients in Guinea. The medical staff plays an essential role to initiate early diagnosis, promote psychological support and provide medication, if possible.

Placental abruption: etiopathogenic aspects, diagnostic and therapeutic implications.

PubMed

Brăila, Anca Daniela; Gluhovschi, Adrian; Neacşu, Adrian; Lungulescu, Cristian Virgil; Brăila, Mihai; Vîrcan, Elena Luminiţa; Cotoi, Bogdan Virgil; Gogănău, Alexandru Marian

2018-01-01

The severe form of retroplacental hematoma is a serious accident in the second stage of pregnancy and at birth with frightening for the mother and fetus that often lead to death. The pathological mechanism presumes conditions for a "special ground" capital for the "efficiency" of the acute intradecidual vascular accident with the rupture of the uterus-placental arterioles. The complete clinical picture of this severe form of retroplacental hematoma - the placental abruption, observed and mentioned by the classics (vascular drama of Couvelaire) consists of five syndromes, 18 signs and symptoms, four paradoxes, phenomena not fully met in the other forms of retroplacental hematoma (minor and intermediate). The rate of incidence of retroplacental hematoma is in between 0.13-1.38% and depends on the environment, on the socio-economic and medical conditions, on the "obstetric education" and associated pathology. Our study aims at re-evaluating the clinico-paraclinical phenomenon imposed by the dramatism of the phenomenon of in utero placental apoplexy, the impact on neonatal mortality and on the functional prognosis from the point of view of surgical climax.

Veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic stem cell transplantation: Middle East/North Africa regional consensus on prevention, diagnosis and management.

PubMed

Al Jefri, A H; Abujazar, H; Al-Ahmari, A; Al Rawas, A; Al Zahrani, Z; Alhejazi, A; Bekadja, M A; Ibrahim, A; Lahoucine, M; Ousia, S; Bazarbachi, A

2017-04-01

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) of the liver is a serious, early complication of haematopoietic stem cell transplantation (HSCT), severe and very severe forms of which are associated with a high mortality rate. A wide variety of patient, disease and treatment-related risk factors for VOD/SOS have been identified. Several bodies have published recommendations for the diagnosis, prevention and management of VOD/SOS following HSCT. A group of regional experts have developed a consensus statement on the diagnosis, prevention and management of VOD/SOS in the Middle East and North Africa region to help in the management of HSCT patients in the region. Risk factors of particular relevance in the region include iron overload in thalassaemia patients, some hereditary metabolic disorders due to consanguinity and infection with hepatitis virus B or C. Recommendations include diagnosis of VOD/SOS based on established clinical criteria, prophylaxis with defibrotide and/or ursodeoxycholic acid in patients at increased risk of VOD/SOS, and treatment with defibrotide for patients with severe/very severe VOD/SOS (and, if clinically indicated, in those with moderate or rapidly progressing VOD/SOS, as per the new European Society for Blood and Marrow Transplantation classification).

Management of Neurologic Manifestations in Patients with Liver Disease.

PubMed

Ferro, José M; Viana, Pedro; Santos, Patrícia

2016-08-01

Liver disease, both in its acute and chronic forms, can be associated with a wide spectrum of neurologic manifestations, both central and peripheral, ranging in severity from subclinical changes to neurocritical conditions. Neurologists are frequently consulted to participate in their management. In this review, we present an overview of management strategies for patients with hepatic disease whose clinical course is complicated by neurologic manifestations. Type A hepatic encephalopathy (HE), which occurs in acute liver failure, is a neurologic emergency, and multiple measures should be taken to prevent and treat cerebral edema. In Type C HE, which occurs in chronic liver disease, management should be aimed at correcting precipitant factors and hyperammonemia. There is an increasing spectrum of drug treatments available to minimize ammonia toxicity. Acquired hepatocerebral degeneration is a rare complication of the chronic form of HE, with typical clinical and brain MRI findings, whose most effective treatment is liver transplantation. Epilepsy is frequent and of multifactorial cause in patients with hepatic disease, and careful considerations should be made regarding choice of the appropriate anti-epileptic drugs. Several mechanisms increase the risk of stroke in hepatic disease, but many of the drugs used to treat and prevent stroke are contraindicated in severe hepatic failure. Hepatitis C infection increases the risk of ischemic stroke. Hemorrhagic stroke is more frequent in patients with liver disease of alcoholic etiology. Viral hepatitis is associated with a wide range of immune-mediated complications, mostly in the peripheral nervous system, which respond to different types of immunomodulatory treatment. Several drugs used to treat hepatic disease, such as the classical and the new direct-acting antivirals, may have neurologic complications which in some cases preclude its continued use.

Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis.

PubMed

Panés, Julián; Aceituno, Montserrat; Gil, Fèlix; Miquel, Rosa; Piqué, Josep M; Salas, Azucena; McLean, Peter

2007-10-01

Modulation of adhesion molecule expression or function is regarded as a promising therapy for inflammatory conditions. This study evaluates the effects of an inhibitor of adhesion molecule expression (GI270384X) in two experimental models of colitis. Colitis of different severity was induced in C57BL/6J mice by administering 1, 2, or 3% dextran sulfate sodium (DSS). GI270384X (3, 10, or 25 mg.kg(-1).day(-1)) was administered as pretreatment or started 3 days after colitis induction. In IL-10-deficient mice, the highest dose was given for 2 wk. The clinical course of colitis, pathological changes, serum inflammatory biomarkers, expression of adhesion molecules, and leukocyte-endothelial cell interactions in colonic venules were measured in mice treated with vehicle or with active drug. In the most severe forms of colitis (2% and 3% DSS and IL-10-deficient mice), the magnitude of colonic inflammation was not modified by treatment with GI270384X. In a less severe form of colitis (1% DSS), GI270384X treatment dose dependently ameliorated the clinical signs of colitis, colonic pathological changes, and serum levels of biomarkers (IL-6 and serum amyloid A). Administration of 25 mg.kg(-1).day(-1) GI270384X abrogated upregulation of ICAM-1 in the inflamed colon but had no effect on VCAM-1 or E-selectin expression. This was associated with a significant reduction in number of rolling and firmly adherent leukocytes in colonic venules. These results indicate that GI270384X is effective in the treatment of experimental colitis of moderate severity. Reduced adhesion molecule expression and leukocyte recruitment to the inflamed intestine contribute to this beneficial effect.

[Case Report - Metamizole-Induced Agranulocytosis].

PubMed

Gonnert, Falk A; Meißner, Winfried

2018-05-01

Metamizole is primarily used for severe perioperative pain, acute injury and colic, and cancer pain. For other acute/chronic forms of pain and high fever, it should only be used if unresponsive to other agents. Metamizole should not be used for middle and low pain. Oral application should be preferred. A contraindication for metamizole is leukopenia. Clinical signs for agranulocytosis are fever, tonsillitis and aphthous stomatitis. Georg Thieme Verlag KG Stuttgart · New York.

French national consensus clinical guidelines for the management of ulcerative colitis.

PubMed

Peyrin-Biroulet, Laurent; Bouhnik, Yoram; Roblin, Xavier; Bonnaud, Guillaume; Hagège, Hervé; Hébuterne, Xavier

2016-07-01

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of multifactorial etiology that primarily affects the colonic mucosa. The disease progresses over time, and clinical management guidelines should reflect its dynamic nature. There is limited evidence supporting UC management in specific clinical situations, thus precluding an evidence-based approach. To use a formal consensus method - the nominal group technique (NGT) - to develop a clinical practice expert opinion to outline simple algorithms and practices, optimize UC management, and assist clinicians in making treatment decisions. The consensus was developed by an expert panel of 37 gastroenterologists from various professional organizations with experience in UC management using the qualitative and iterative NGT, incorporating deliberations based on the European Crohn's and Colitis Organisation recommendations, recent reviews of scientific literature, and pertinent discussion topics developed by a steering committee. Examples of clinical cases for which there are limited evidence-based data from clinical trials were used. Two working groups proposed and voted on treatment algorithms that were then discussed and voted for by the nominal group as a whole, in order to reach a consensus. A clinical practice guideline covering management of the following clinical situations was developed: (i) moderate and severe UC; (ii) acute severe UC; (iii) pouchitis; (iv) refractory proctitis, in the form of treatment algorithms. Given the limited available evidence-based data, a formal consensus methodology was used to develop simple treatment guidelines for UC management in different clinical situations that is now accessible via an online application. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Current perspectives on dengue episode in Malaysia.

PubMed

Pang, Ee Leen; Loh, Hwei-San

2016-04-01

Prevalence of dengue transmission has been alarmed by an estimate of 390 million infections per annum. Urban encroachment, ecological disruption and poor sanitation are all contributory factors of increased epidemiology. Complication however arises from the fact that dengue virus inherently exists as four different serotypes. Secondary infection is often manifested in the more severe form, such that antibody-dependent enhancement (ADE) could aggravate ailment by allowing pre-existing antibodies to form complexes with infecting viruses as means of intrusion. Consequently, increased viraemic titter and suppression of antiviral response are observed. Deep concerns are thus expressed in regards to escalating trend of hospitalisation and mortality rates. In Malaysia, situation is exacerbated by improper clinical management and pending vector control operations. As a preparedness strategy against the potential deadly dengue pandemic, the call for development of a durable and cost-effective dengue vaccine against all infecting serotypes is intensified. Even though several vaccine candidates are currently being evaluated in clinical trials, uncertainties in regards to serotypes interference, incomplete protection and dose adequacy have been raised. Instead of sole reliance on outsourcing, production of local vaccine should be considered in coherent to government's efforts to combat against dengue. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome.

PubMed

Roma, Maria; Marden, Colleen L; De Wandele, Inge; Francomano, Clair A; Rowe, Peter C

2018-03-05

To review the association between orthostatic intolerance syndromes and both joint hypermobility and Ehlers-Danlos syndrome, and to propose reasons for identifying hereditary connective tissue disorders in those with orthostatic intolerance in the context of both clinical care and research. We searched the published peer-reviewed medical literature for papers reporting an association between joint hypermobility or Ehlers-Danlos syndrome and orthostatic intolerance. We identified 10 relevant papers. Although methodological variability between studies introduces some limitations, the published literature consistently identifies a significantly higher prevalence of orthostatic intolerance symptoms in patients with joint hypermobility or Ehlers-Danlos syndrome than in healthy controls, and a significantly higher prevalence of cardiovascular and autonomic abnormalities both at rest and during orthostatic challenge. Postural tachycardia syndrome is the most commonly recognized circulatory disorder. The severity of orthostatic symptoms in those with EDS correlates with impairments in quality of life. There is a strong association between several forms of cardiovascular dysfunction, most notably postural tachycardia syndrome, and joint hypermobility or Ehlers-Danlos syndrome. We propose that recognition of joint hypermobility and Ehlers-Danlos syndrome among those with orthostatic intolerance syndromes has the potential to improve clinical care and the validity of research findings. Copyright © 2018 Elsevier B.V. All rights reserved.

A novel locus for Usher syndrome type I, USH1G, maps to chromosome 17q24-25.

PubMed

Mustapha, Mirna; Chouery, Eliane; Torchard-Pagnez, Delphine; Nouaille, Sylvie; Khrais, Awni; Sayegh, Fouad N; Mégarbané, André; Loiselet, Jacques; Lathrop, Mark; Petit, Christine; Weil, Dominique

2002-04-01

Usher syndrome (USH) is an autosomal recessive disorder associated with sensorineural hearing impairment and progressive visual loss attributable to retinitis pigmentosa. This syndrome is both clinically and genetically heterogeneous. Three clinical types have been described of which type I (USH1) is the most severe. Six USH1 loci have been identified. We report a Palestinian consanguineous family from Jordan with three affected children. In view of the combination of profound hearing loss, vestibular dysfunction, and retinitis pigmentosa in the patients, we classified the disease as USH1. Linkage analysis excluded the involvement of any of the known USH1 loci. A genome-wide screening allowed us to map this novel locus, USH1G, in a 23-cM interval on chromosome 17q24-25. The USH1G interval overlaps the intervals for two dominant forms of isolated hearing loss, namely DFNA20 and DFNA26. Since several examples have been reported of syndromic and isolated forms of deafness being allelic, USH1G, DFNA20, and DFNA26 might result from alterations of the same gene. Finally, a mouse mutant, jackson shaker ( js), with deafness and circling behavior has been mapped to the murine homologous region on chromosome 11.

Majewski osteodysplastic primordial dwarfism type II: clinical findings and dental management of a child patient

PubMed Central

Terlemez, Arslan; Altunsoy, Mustafa; Celebi, Hakki

2015-01-01

Majewski osteodysplastic primordial dwarfism type II (MOPD II) is an unusual autosomal recessive inherited form of primordial dwarfism, which is characterized by a small head diameter at birth, but which also progresses to severe microcephaly, progressive bony dysplasia, and characteristic facies and personality. This report presents a case of a five-year-old girl with MOPD II syndrome. The patient was referred to our clinic with the complaint of severe tooth pain at the left mandibular primary molar teeth. Clinical examination revealed that most of the primary teeth had been decayed and all primary teeth were hypoplastic. Patient’s history revealed delayed development in the primary dentition and radiographic examination showed rootless primary molar teeth and short-rooted incisors. The treatment was not possible due to the lack of root of the left mandibular primary molars; so the teeth were extracted. Thorough and timely dental evaluation is crucial for the prevention of dental problems and the maintenance of oral health in patients with MOPD II syndrome is of utmost importance. PMID:28955524

Majewski osteodysplastic primordial dwarfism type II: clinical findings and dental management of a child patient.

PubMed

Terlemez, Arslan; Altunsoy, Mustafa; Celebi, Hakki

2015-01-01

Majewski osteodysplastic primordial dwarfism type II (MOPD II) is an unusual autosomal recessive inherited form of primordial dwarfism, which is characterized by a small head diameter at birth, but which also progresses to severe microcephaly, progressive bony dysplasia, and characteristic facies and personality. This report presents a case of a five-year-old girl with MOPD II syndrome. The patient was referred to our clinic with the complaint of severe tooth pain at the left mandibular primary molar teeth. Clinical examination revealed that most of the primary teeth had been decayed and all primary teeth were hypoplastic. Patient's history revealed delayed development in the primary dentition and radiographic examination showed rootless primary molar teeth and short-rooted incisors. The treatment was not possible due to the lack of root of the left mandibular primary molars; so the teeth were extracted. Thorough and timely dental evaluation is crucial for the prevention of dental problems and the maintenance of oral health in patients with MOPD II syndrome is of utmost importance.

Levels of Social Sharing and Clinical Implications for Severe Social Withdrawal in Patients with Personality Disorders.

PubMed

Colle, Livia; Pellecchia, Giovanni; Moroni, Fabio; Carcione, Antonino; Nicolò, Giuseppe; Semerari, Antonio; Procacci, Michele

2017-01-01

Social sharing capacities have attracted attention from a number of fields of social cognition and have been variously defined and analyzed in numerous studies. Social sharing consists in the subjective awareness that aspects of the self's experience are held in common with other individuals. The definition of social sharing must take a variety of elements into consideration: the motivational element, the contents of the social sharing experience, the emotional responses it evokes, the behavioral outcomes, and finally, the circumstances and the skills which enable social sharing. The primary objective of this study is to explore some of the diverse forms of human social sharing and to classify them according to levels of complexity. We identify four different types of social sharing, categorized according to the nature of the content being shared and the complexity of the mindreading skills required. The second objective of this study is to consider possible applications of this graded model of social sharing experience in clinical settings. Specifically, this model may support the development of graded, focused clinical interventions for patients with personality disorders characterized by severe social withdrawal.

Don't just do something, stand there! The value and art of deliberate clinical inertia.

PubMed

Keijzers, Gerben; Cullen, Louise; Egerton-Warburton, Diana; Fatovich, Daniel M

2018-04-01

It can be difficult to avoid unnecessary investigations and treatments, which are a form of low-value care. Yet every intervention in medicine has potential harms, which may outweigh the potential benefits. Deliberate clinical inertia is the art of doing nothing as a positive response. This paper provides suggestions on how to incorporate deliberate clinical inertia into our daily clinical practice, and gives an overview of current initiatives such as 'Choosing Wisely' and the 'Right Care Alliance'. The decision to 'do nothing' can be complex due to competing factors, and barriers to implementation are highlighted. Several strategies to promote deliberate clinical inertia are outlined, with an emphasis on shared decision-making. Preventing medical harm must become one of the pillars of modern health care and the art of not intervening, that is, deliberate clinical inertia, can be a novel patient-centred quality indicator to promote harm reduction. © 2018 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Transforming the practice of medicine using genomics

PubMed Central

Ginsburg, Geoffrey S.; Ginsburg, Geoffrey S.; J. McCarthy, Jeanette

2009-01-01

Recent studies have demonstrated the use of genomic data, particularly gene expression signatures, as clinical prognostic factors in complex diseases. Such studies herald the future for genomic medicine and the opportunity for personalized prognosis in a variety of clinical contexts that utilize genomescale molecular information. Several key areas represent logical and critical next steps in the use of complex genomic profiling data towards the goal of personalized medicine. First, analyses should be geared toward the development of molecular profiles that predict future events – such as major clinical events or the response, resistance, or adverse reaction to therapy. Secondly, these must move into actual clinical practice by forming the basis for the next generation of clinical trials that will employ these methodologies to stratify patients. Lastly, there remain formidable challenges is in the translation of genomic technologies into clinical medicine that will need to be addressed: professional and public education, health outcomes research, reimbursement, regulatory oversight and privacy protection. PMID:22461094

The changing face of Usher syndrome: clinical implications.

PubMed

Cohen, Mazal; Bitner-Glindzicz, Maria; Luxon, Linda

2007-02-01

Usher syndrome is both genetically and phenotypically heterogeneous. Traditionally, the condition has been classified into three clinical types, differentiated by the severity and progression of the hearing impairment and by the presence or absence of vestibular symptoms. Recent advances in molecular genetics have enabled researchers to study the phenotypic expression in confirmed molecular groups of Usher. In response to the expansion of clinical and genetic information on Usher, we report an up to date review of the different clinical forms of Usher in known molecular groups and use the emerging evidence to appraise the diagnostic utility of the traditional classification of Usher. Our findings undermine the traditional view that the clinical types of Usher have distinct genetic causes. The pleiotropic effects of some of the major causes of Usher lead to considerable overlap between the different clinical types, with very little evidence for phenotypic-genotypic correlations. The novel synthesis emerging from this review suggests more productive approaches to the diagnosis of Usher in hearing-impaired children which would provide more accurate prognostic information to families.

Clinics in diagnostic imaging (160). Levocardia with abdominal situs inversus

PubMed Central

Abdullah, Nor Lenny; Quek, Swee Chye; Seto, Kar Yin; Teo, Lynette Li San

2015-01-01

Levocardia (left-sided cardiac apex) with abdominal situs inversus is extremely rare. This is also known as isolated levocardia and is almost always associated with severe forms of congenital heart defects with poor prognosis. We report isolated levocardia in a 13-year-old symptomatic male patient. The purpose of this paper is to outline the imaging features of isolated levocardia and to highlight the role of cardiovascular magnetic resonance imaging (CMR) in the diagnosis and management of such cases. Other forms of cardiac malposition, including dextrocardia, mesocardia and criss-cross heart, with chest radiograph and CMR correlation, are also discussed. PMID:25917470

The spectrum of clinical presentation, diagnosis, and management of mitochondrial forms of diabetes.

PubMed

Karaa, Amel; Goldstein, Amy

2015-02-01

Primary mitochondrial diseases refer to a group of heterogeneous and complex genetic disorders affecting 1:5000 people. The true prevalence is anticipated to be even higher because of the complexity of achieving a diagnosis in many patients who present with multisystemic complaints ranging from infancy to adulthood. Diabetes is a prominent feature of several of these disorders which might be overlooked by the endocrinologist. We here review mitochondrial disorders and describe the phenotypic and pathogenetic differences between mitochondrial diabetes mellitus (mDM) and other more common forms of diabetes mellitus. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Effects of residents' care needs classification (and misclassification) in nursing homes: the example of SOSIA classification].

PubMed

Nebuloni, G; Di Giulio, P; Gregori, D; Sandonà, P; Berchialla, P; Foltran, F; Renga, G

2011-01-01

Since 2003, the Lombardy region has introduced a case-mix reimbursement system for nursing homes based on the SOSIA form which classifies residents into eight classes of frailty. In the present study the agreement between SOSIA classification and other well documented instruments, including Barthel Index, Mini Mental State Examination and Clinical Dementia Rating Scale is evaluated in 100 nursing home residents. Only 50% of residents with severe dementia have been recognized as seriously impaired when assessed with SOSIA form; since misclassification errors underestimate residents' care needs, they determine an insufficient reimbursement limiting nursing home possibility to offer care appropriate for the case-mix.

Reversible infantile mitochondrial diseases.

PubMed

Boczonadi, Veronika; Bansagi, Boglarka; Horvath, Rita

2015-05-01

Mitochondrial diseases are usually severe and progressive conditions; however, there are rare forms that show remarkable spontaneous recoveries. Two homoplasmic mitochondrial tRNA mutations (m.14674T>C/G in mt-tRNA(Glu)) have been reported to cause severe infantile mitochondrial myopathy in the first months of life. If these patients survive the first year of life by extensive life-sustaining measures they usually recover and develop normally. Another mitochondrial disease due to deficiency of the 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) causes severe liver failure in infancy, but similar to the reversible mitochondrial myopathy, within the first year of life these infants may also recover completely. Partial recovery has been noted in some other rare forms of mitochondrial disease due to deficiency of mitochondrial tRNA synthetases and mitochondrial tRNA modifying enzymes. Here we summarize the clinical presentation of these unique reversible mitochondrial diseases and discuss potential molecular mechanisms behind the reversibility. Understanding these mechanisms may provide the key to treatments of potential broader relevance in mitochondrial disease, where for the majority of the patients no effective treatment is currently available.

Characteristics of erythrocyte-derived microvesicles and its relation with atherosclerosis.

PubMed

Li, Kai-Yin; Zheng, Lei; Wang, Qian; Hu, Yan-Wei

2016-12-01

Microvesicles are formed under many circumstances, especially in atheromatous plaques. Erythrocyte-derived microvesicles (ErMVs) have been proved to promote atherosclerosis by promoting hypercoagulation, mediating inflammation and inducing cell adhesion. Several clinical studies have reported potential roles of ErMVs in cardiovascular disease diagnosis, but the current understanding of ErMVs remains insufficient. In this paper, we will review current research on the formation and degradation of ErMVs and the possible effects of ErMVs in atherosclerosis, discuss potential clinical applications in cardiovascular disease, and hope to raise awareness of the relation with atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Advances in the development of new tuberculosis drugs and treatment regimens.

PubMed

Zumla, Alimuddin; Nahid, Payam; Cole, Stewart T

2013-05-01

Despite the introduction 40 years ago of the inexpensive and effective four-drug (isoniazid, rifampicin, pyrazinamide and ethambutol) treatment regimen, tuberculosis (TB) continues to cause considerable morbidity and mortality worldwide. For the first time since the 1960s, new and novel drugs and regimens for all forms of TB are emerging. Such regimens are likely to utilize both repurposed drugs and new chemical entities, and several of these regimens are now progressing through clinical trials. This article covers current concepts and recent advances in TB drug discovery and development, including an update of ongoing TB treatment trials, newer clinical trial designs, TB biomarkers and adjunct host-directed therapies.

Tuberculous meningoencephalitis.

PubMed

Muçaj, Sefedin; Dreshaj, Shemsedin; Kabashi, Serbeze; Hundozi, Hajrije; Gashi, Sanije; Zhjeqi, Valbona; Shala, Nexhmedin; Kryeziu, Manushaqe

2010-01-01

Tuberculous meningitis is an infection of the the membranes covering the brain and spinal cord (meninges). Tuberculous meningitis is a major global health problem and is the most severe form of extrapulmonary tuberculosis, with high rate mortality. Last years in Kosovo incidence of TB was decreased in less than 1000 cases per year and 10-20 cases per year of TB meningoencephalitis. Still Kosovo has limited numbers of TB. TBM is diagnosed on the basis of clinical features, cerebrospinal fluid (CSF) studies, and radiological findings. Clinical picture, neurological status, anamnestic data, suspect (but not specific) lab tests, and imaging new methods, together can give very valuable help to clinicians for early adequate and successful treatment.

Antiradiation vaccine: Technology and development of prophylaxis, prevention and treatment of biological consequences from Heavy Ion irradiation.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Vecheslav

Introduction: An anti-radiation vaccine could be an important part of a countermeasures reg-imen for effective radioprotection, immunoprophylaxis and immunotherapy of the acute radi-ation syndromes (ARS) after gamma-irradiation, neutron irradiation or heavy ion irradiation. Reliable protection of non-neoplastic regions of patients with different forms of cancer which undergo to heavy ion therapy ( e.g. Hadron-therapy) can significantly extend the efficiency of the therapeutic course. The protection of cosmonauts astronauts from the heavy ion ra-diation component of space radiation with specific immunoprophylaxis by the anti-radiation vaccine may be an important part of medical management for long term space missions. Meth-ods and experiments: 1. The Antiradiation Vaccine preparation -standard (mixture of toxoid form of Radiation Toxins -SRD-group) which include Cerebrovascular RT Neurotoxin, Car-diovascular RT Neurotoxin, Gastrointestinal RT Neurotoxin, Hematopoietic RT Hematotoxin. Radiation Toxins Specific Radiation Determinant Group were isolated from a central lymph of gamma-irradiated animals with Cerebrovascular, Cardiovascular, Gastrointestiinal, Hematopoi-etic forms of ARS. Devices for γ-radiation are "Panorama", "Puma". 2. Heavy ion exposure was accomplished at Department of Scientific Research Institute of Nuclear Physics, Dubna, Russia. The heavy ions irradiation was generated in heavy ion (Fe56) accelerator -UTI. Heavy Ion linear transfer energy -2000-2600 KeV mkm, 600 MeV U. Absorbed Dose -3820 Rad. 3. Experimental Design: Rabbits from all groups were irradiated by heavy ion accelerator. Group A -control -10 rabbits; Group B -placebo -5 rabbits; Group C -radioprotectant Cystamine (50 mg kg)-5 rabbits, 15 minutes before irradiation -5 rabbits; Group D -radioprotectant Gammafos (Amifostine -400mg kg ), -5 rabbits; Group E -Antiradiation Vaccine: subcuta-neus administration or IM -2 ml of active substance, 14 days before irradiation -5 rabbits. 4. Results: Group A -100% mortality within two hours after heavy ion irradiation with clinical symptoms of the acute cerebrovascular and cardiovascular syndromes. Group B -100% mortal-ity within 15 hours following irradiation. Group C -100% mortality within 14-15 hours after irradiation. Group D -100% mortality within 15-16 hours after irradiation. In groups A-D, development of the acute radiation cerebrovascular and cardiovascular syndromes as well as ex-tensive burns of skin caused rapid death. Group E -100% mortality in 280-290 hours (12 days) following heavy ion irradiation while animals were exhibiting a combination or individual forms of the acute cerebrovascular, cardiovascular, and gastrointestinal forms and focal skin burns. Discussion: The Antiradiation Vaccine (ARV) and specific immune-prophylaxis are an effective method of neutralization of Radiation Toxins. Vaccination with the ARV significantly extended the survival time after irradiation with heavy ions from two hours up to 300 hours. Clinical signs, clinical features, symptoms were somewhat attenuated. Degree of clinical forms of the Acute Radiation Syndromes were diminished in their severity. Groups A-D demonstrated an extremely severe degree (Degree 4) of Cerebrovascular and Cardiovascular forms of the Acute Radiation Syndromes and lethality 100% was registered in a short time after irradiation. Radi-ation induced burns in this groups (with Cutaneous sub-syndrome of ARS -Degree 4) that were deep with extensive and total dysfunction and possible muscle involvement developed. Animals from group E -Radioprotectant -anti-radiation vaccine had demonstrated later development of the severe Degree 3 or even Degree 2-3 forms of Cerebrovascular and Cardiovascular forms of the ARS and a survival time of irradiated animals was significantly prolonged. Cutaneous sub-syndrome developed in Degree 3 or Degree 2-3. Our results have demonstrated the potential radioprotection efficacy of specific immune-prophylaxis with the Antiradiation vaccine against heavy ion irradiation.

Cognitive performance is of clinical importance, but is unrelated to pain severity in women with chronic fatigue syndrome.

PubMed

Ickmans, Kelly; Meeus, Mira; Kos, Daphne; Clarys, Peter; Meersdom, Geert; Lambrecht, Luc; Pattyn, Nathalie; Nijs, Jo

2013-10-01

In various chronic pain populations, decreased cognitive performance is known to be related to pain severity. Yet, this relationship has not been investigated in patients with chronic fatigue syndrome (CFS). This study investigated the relationship between cognitive performance and (1) pain severity, (2) level of fatigue, and (3) self-reported symptoms and health status in women with CFS. Examining the latter relationships is important for clinical practice, since people with CFS are often suspected to exaggerate their symptoms. A sample of 29 female CFS patients and 17 healthy controls aged 18 to 45 years filled out three questionnaires (Medical Outcomes Study 36-Item Short-Form Health Survey, Checklist Individual Strength (CIS), and CFS Symptom List) and performed three performance-based cognitive tests (psychomotor vigilance task, Stroop task, and operation span task), respectively. In both groups, pain severity was not associated with cognitive performance. In CFS patients, the level of fatigue measured with the CFS Symptom List, but not with the CIS, was significantly correlated with sustained attention. Self-reported mental health was negatively correlated with all investigated cognitive domains in the CFS group. These results provide evidence for the clinical importance of objectively measured cognitive problems in female CFS patients. Furthermore, a state-like measure (CFS Symptom List) appears to be superior over a trait-like measure (CIS) in representing cognitive fatigue in people with CFS. Finally, the lack of a significant relationship between cognitive performance and self-reported pain severity suggests that pain in CFS might be unique.

The interrelationship between disease severity, dynamic stability, and falls in cerebellar ataxia.

PubMed

Schniepp, Roman; Schlick, Cornelia; Pradhan, Cauchy; Dieterich, Marianne; Brandt, Thomas; Jahn, Klaus; Wuehr, Max

2016-07-01

Cerebellar ataxia (CA) results in discoordination of body movements (ataxia), a gait disorder, and falls. All three aspects appear to be obviously interrelated; however, experimental evidence is sparse. This study systematically correlated the clinical rating of the severity of ataxia with dynamic stability measures and the fall frequency in patients with CA. Clinical severity of CA in patients with sporadic (n = 34) and hereditary (n = 24) forms was assessed with the Scale for the Assessment and Rating of Ataxia (SARA). Gait performance was examined during slow, preferred, and maximally fast walking speeds. Spatiotemporal variability parameters in the fore-aft and medio-lateral directions were analyzed. The fall frequency was assessed using a standardized interview about fall events within the last 6 months. Fore-aft gait variability showed significant speed-dependent characteristics with highest magnitudes during slow and fast walking. The SARA score correlated positively with fore-aft gait variability, most prominently during fast walking. The fall frequency was significantly associated to fore-aft gait variability during slow walking. Severity of ataxia, dynamic stability, and the occurrence of falls were interrelated in a speed-dependent manner: (a) Severity of ataxia symptoms was closely related to instability during fast walking. (b) Fall frequency was associated with instability during slow walking. These findings suggest the presence of a speed-dependent, twofold cerebellar locomotor control. Assessment of gait performance during non-preferred, slow and fast walking speeds provides novel insights into the pathophysiology of cerebellar locomotor control and may become a useful approach in the clinical evaluation of patients with CA.

Treatment of premenstrual dysphoric disorder with luteal phase dosing of sertraline.

PubMed

Halbreich, Uriel; Kahn, Linda S

2003-11-01

Sertraline (Zoloft, Pfizer Inc.) is a selective serotonin re-uptake inhibitor (SSRI) which has been approved by the US FDA for the treatment of premenstrual dysphoric disorder (PMDD). PMDD is a severe form of premenstrual syndrome (PMS) which affects at least 5 - 8% of women of reproductive age. It is characterised by cyclic appearance at the late luteal phase of the menstrual cycle, and disappearance following the beginning of menses, with no symptoms during at least 1 week of the cycle - usually during the mid-follicular phase. Due to the cyclic luteal occurrence of PMDD, luteal phase dosing of SSRIs has been suggested and proven effective for sertraline as well as several other SSRIs. The clinical response of sertraline is reported to be within several days following initiation of treatment. Despite repeated cyclic discontinuation, no significant discontinuation adverse effects have been reported. In addition to its proven clinical efficacy, luteal-phase dosing may offer the advantages of minimising adverse effects of SSRIs while reducing the personal and economic burden of taking a prescription medication continuously for long periods and thus increasing compliance.

Long-term maintenance of weight loss in patients with severe mental illness through a behavioural treatment programme in the UK.

PubMed

Pendlebury, J; Bushe, C J; Wildgust, H J; Holt, R I G

2007-04-01

Obesity is common among people with severe mental illness (SMI). We report our experience from the first 4 years of The Cromwell House weight management clinic. Ninety-three patients with SMI aged 43.7 +/- 1.2 years referred themselves to this clinic. The patients were seen in weekly group sessions that involved weight measurement, discussion and education. Mean baseline weight was 89.5 +/- 1.8 kg [body mass index (BMI) 32.3 +/- 0.5 kg/m(2)]. Twenty-three per cent dropped out within the first 8 weeks. There was progressive statistically significant reduction in mean weight and BMI throughout the duration of monitoring with no suggestion of a plateau. The mean final weight loss was 6.2 +/- 0.6 kg. Weight loss was correlated only with the number of sessions attended (r = 0.53, P < 0.0001). Long-term weight management of obese and overweight patients with severe forms of mental illness was possible through the provision of simple lifestyle advice within the group setting.

PubMed Central

Broccolini, A.; Gidaro, T.; Morosetti, R.; Sancricca, C.; Mirabella, M.

2011-01-01

The hereditary inclusion-body myopathies encompass several syndromes with autosomal recessive or dominant inheritance. Despite a different clinical presentation they all have a progressive course leading to severe disability and share similar pathologic findings at the muscle biopsy. Quadriceps-sparing autosomal recessive hereditary inclusion-body myopathy (h-IBM) is the commonest form and is tied to mutations of the UDP-Nacetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. Despite the identification of the causative gene defect, it has not been clarified how mutations of the GNE gene impair muscle homeostasis. Although several lines of evidence argue in favor of an abnormal sialylation of muscle glycoproteins playing a key role in h-IBM pathogenesis, others studies have demonstrated new functions of the GNE gene, outside the sialic acid biosynthetic pathway, that may also be relevant. This review illustrates the clinical and pathologic characteristics of h- IBM and the main clues available to date concerning the possible pathogenic mechanisms of this disorder. Understanding the molecular mechanism underlying h-IBM pathology is a fundamental requisite to plan a future attempt to therapy. PMID:22106710

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

PubMed

Clarke, Geraldine M; Rockett, Kirk; Kivinen, Katja; Hubbart, Christina; Jeffreys, Anna E; Rowlands, Kate; Jallow, Muminatou; Conway, David J; Bojang, Kalifa A; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D; Bougouma, Edith C; Sirima, Sodiomon B; Modiano, David; Amenga-Etego, Lucas N; Ghansah, Anita; Koram, Kwadwo A; Wilson, Michael D; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi K; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N; Manjurano, Alphaxard; Sepúlveda, Nuno; Clark, Taane G; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy Me; Michon, Pascal; Mueller, Ivo; Molloy, Síle F; Campino, Susana; Kerasidou, Angeliki; Cornelius, Victoria J; Hart, Lee; Shah, Shivang S; Band, Gavin; Spencer, Chris Ca; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P

2017-01-09

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.

Rett syndrome: revised diagnostic criteria and nomenclature.

PubMed

Neul, Jeffrey L; Kaufmann, Walter E; Glaze, Daniel G; Christodoulou, John; Clarke, Angus J; Bahi-Buisson, Nadia; Leonard, Helen; Bailey, Mark E S; Schanen, N Carolyn; Zappella, Michele; Renieri, Alessandra; Huppke, Peter; Percy, Alan K

2010-12-01

Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was to revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials. RettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT. The clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed. These revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research.

Health literacy and usability of clinical trial search engines.

PubMed

Utami, Dina; Bickmore, Timothy W; Barry, Barbara; Paasche-Orlow, Michael K

2014-01-01

Several web-based search engines have been developed to assist individuals to find clinical trials for which they may be interested in volunteering. However, these search engines may be difficult for individuals with low health and computer literacy to navigate. The authors present findings from a usability evaluation of clinical trial search tools with 41 participants across the health and computer literacy spectrum. The study consisted of 3 parts: (a) a usability study of an existing web-based clinical trial search tool; (b) a usability study of a keyword-based clinical trial search tool; and (c) an exploratory study investigating users' information needs when deciding among 2 or more candidate clinical trials. From the first 2 studies, the authors found that users with low health literacy have difficulty forming queries using keywords and have significantly more difficulty using a standard web-based clinical trial search tool compared with users with adequate health literacy. From the third study, the authors identified the search factors most important to individuals searching for clinical trials and how these varied by health literacy level.

Outbreak of Chikungunya in the French Caribbean Islands of Martinique and Guadeloupe: Findings from a Hospital-Based Surveillance System (2013-2015).

PubMed

Dorléans, Frédérique; Hoen, Bruno; Najioullah, Fatiha; Herrmann-Storck, Cécile; Schepers, Kinda Maria; Abel, Sylvie; Lamaury, Isabelle; Fagour, Laurence; Césaire, Raymond; Guyomard, Stéphanie; Troudard, Ruth; Adélaïde, Yvette; Romagne, Marie-José; Davidas, Magguy; Rochais, Séverine; Boa, Sylvie; de Saint-Alary, Frédérique; Preira, Annabel; Saint-Martin, Patrick; Vaidie, Amandine; Melin, Mathilde; Daudens-Vaysse, Elise; Rosine, Jacques; Blateau, Alain; Carvalho, Luisiane; Septfons, Alexandra; Paty, Marie-Claire; Leduc, Ghislain; Cassadou, Sylvie; Ledrans, Martine; Cabié, André

2018-04-23

Chikungunya virus (CHIKV) emerged in the Caribbean island of Saint-Martin in December 2013. We implemented a hospital-based surveillance system to detect and describe CHIKV cases including severe forms of the infection and deaths in the islands of Martinique and Guadeloupe. A case was defined as a patient with a CHIKV laboratory confirmation cared for in a public hospital for chikungunya for at least 24 hours, and a severe CHIKV case was defined as a CHIKV case presenting one or more organ failures. Sociodemographic, clinical, and laboratory data were collected and cases classified into severe or nonsevere based on medical records. From December 2013 to January 2015, a total of 1,836 hospitalized cases were identified. Rate of hospital admissions for CHIKV infection was 60 per 10,000 suspected clinical CHIKV cases and severity accounted for 12 per 10,000. A total of 74 deaths related to CHIKV infection occurred. Infants and elderly people were more frequently hospitalized compared with others and severity was more frequently reported in elderly subjects and subjects with underlying health condition. Fifteen neonatal infections consecutive to mother-to-child transmission were diagnosed, seven of which were severe. The most vulnerable groups of the population, such as the elderly, infants, individuals with comorbidities, and pregnant women, should remain the main targets of public health priorities.

The mediating effect of 'bothersome' urinary incontinence on help-seeking intentions among community-dwelling women.

PubMed

Xu, Dongjuan; Wang, Xiaojuan; Li, Jingjing; Wang, Kefang

2015-02-01

To explore the mediating effect of bother of urinary incontinence between urinary incontinence severity and help-seeking intentions and detect whether the International Consultation on Incontinence Questionnaire-UI Short Form could be a valid measure to delineate bothersome urinary incontinence. Urinary incontinence is a common condition among women, which has a profound adverse effect on quality of life. However, many of them experiencing significant clinical symptoms do not seek medical help. A cross-sectional survey design. Women with urinary incontinence (N = 620) from three randomized selected community health service centres from May-October 2011 participated in the study. Data were collected using a pencil-and-paper questionnaire. Multivariate regression models were used to test the role of bother as a mediator in the relation between urinary incontinence severity and help-seeking intentions. Receiver operating characteristic analysis was used to find the best cut-off International Consultation on Incontinence Questionnaire-UI Short Form score (range: 0-21) to delineate the bother of urinary incontinence. Bothersome urinary incontinence mediated the relationship between urinary incontinence severity and help-seeking intentions. Age and duration of urine leakage had a negative association on help-seeking intentions, while educational level and previous help-seeking behaviours had a positive association. Bother was a mediator in the relation between urinary incontinence severity and help-seeking intentions. The International Consultation on Incontinence Questionnaire-UI Short Form was a discriminative measure to delineate the bothersome urinary incontinence. © 2014 John Wiley & Sons Ltd.

Hypericum perforatum: pharmacokinetic, mechanism of action, tolerability, and clinical drug-drug interactions.

PubMed

Russo, Emilio; Scicchitano, Francesca; Whalley, Benjamin J; Mazzitello, Carmela; Ciriaco, Miriam; Esposito, Stefania; Patanè, Marinella; Upton, Roy; Pugliese, Michela; Chimirri, Serafina; Mammì, Maria; Palleria, Caterina; De Sarro, Giovambattista

2014-05-01

Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP. Copyright © 2013 John Wiley & Sons, Ltd.

[Hepatic alterations in patients with dengue].

PubMed

Larreal, Yraima; Valero, Nereida; Estévez, Jesús; Reyes, Ivette; Maldonado, Mery; Espina, Luz Marina; Arias, Julia; Meleán, Eddy; Añez, German; Atencio, Ricardo

2005-06-01

Clinical features of Dengue are very variable due to multiple alterations induced by the virus in the organism. Increased levels of transaminases similar to those produced by the Hepatitis virus have been reported in patients with Dengue from hiperendemic zones in Asia. The objectives of this study were to determine alterations in the liver tests in patients with Dengue and to relate them to the disease, clinically and serologically. Clinical history, hemathological tests serum transaminases (ALT y AST) and bilirubin assays were performed in 62 patients with clinical and serological diagnosis of Dengue. According to clinical features 38.7% of the patients with classical (CD) and hemorrhagic (DHF) forms of Dengue reffered abdominal pain and 2 patients with DHF had ictericia and hepatomegaly. Laboratory test findings showed leucopenia in 72.5% in both forms of Dengue and of patients with DHF severe thrombocytopenia (< 50.000 platelets x mm3), long PT and PPT in 70.9%, 23.0% and 42.3%, respectively. Transaminase values five fold higher than the normal values (p < 0.005) were observed in 36.8% and 74.4% of patients with CD and DHF respectively; AST was predominant in both groups. Our results suggest liver damage during the course of Dengue. A differential diagnosis has to be done between the hepatic involvement of Dengue cases and others viral diseases with hepatic disfunctions.

Research funders' roles and perceived responsibilities in relation to the implementation of clinical research results: a multiple case study of Swedish research funders.

PubMed

Brantnell, Anders; Baraldi, Enrico; van Achterberg, Theo; Winblad, Ulrika

2015-07-17

Implementation of clinical research results is challenging, yet the responsibility for implementation is seldom addressed. The process from research to the use of clinical research results in health care can be facilitated by research funders. In this paper, we report the roles of ten Swedish research funders in relation to implementation and their views on responsibilities in implementation. Ten cases were studied and compared using semi-structured interviews. In addition, websites and key documents were reviewed. Eight facilitative roles for research funders in relation to the implementation of clinical research results were identified. Three of them were common for several funders: "Advocacy work," "Monitoring implementation outcomes," and "Dissemination of knowledge." Moreover, the research funders identified six different actors responsible for implementation, five of which belonged to the healthcare setting. Collective and organizational responsibilities were the most common forms of responsibilities among the identified actors responsible for implementation. The roles commonly identified by the Swedish funders, "Advocacy work," "Monitoring implementation outcomes," and "Dissemination of knowledge," seem feasible facilitative roles in relation to the implementation of clinical research results. However, many actors identified as responsible for implementation together with the fact that collective and organizational responsibilities were the most common forms of responsibilities entail a risk of implementation becoming no one's responsibility.

Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001–12: a retrospective observational study

PubMed Central

Lazzerini, Marzia; Seward, Nadine; Lufesi, Norman; Banda, Rosina; Sinyeka, Sophie; Masache, Gibson; Nambiar, Bejoy; Makwenda, Charles; Costello, Anthony; McCollum, Eric D; Colbourn, Tim

2017-01-01

Summary Background Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012. Methods Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi’s Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children’s clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2–11 months of age, and 12–59 months of age using separate multivariable mixed effects logistic regression models. Findings Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92.7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6.6% (95% CI 6.4–6.7). The case fatality rate significantly decreased between 2001 (15.2% [13.4–17.1]) and 2012 (4.5% [4.1–4.9]; ptrend<0.0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors significantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2–11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11.8%), severe undernutrition (15.4%), severe acute malnutrition (34.8%), and symptom duration of more than 21 days (9.0%). Interpretation Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specific subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of sufficient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of effective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi. PMID:26718810

Factor structure and reliability of the childhood trauma questionnaire and prevalence estimates of trauma for male and female street youth.

PubMed

Forde, David R; Baron, Stephen W; Scher, Christine D; Stein, Murray B

2012-01-01

This study examines the psychometric properties of the Childhood Trauma Questionnaire short form (CTQ-SF) with street youth who have run away or been expelled from their homes (N = 397). Internal reliability coefficients for the five clinical scales ranged from .65 to .95. Confirmatory Factor Analysis (CFA) was used to test the five-factor structure of the scales yielding acceptable fit for the total sample. Additional multigroup analyses were performed to consider items by gender. Results provided only evidence of weak factorial invariance. Constrained models showed invariance in configuration, factor loadings, and factor covariances but failed for equality of intercepts. Mean trauma scores for street youth tended to fall in the moderate to severe range on all abuse/neglect clinical scales. Females reported higher levels of abuse and neglect. Prevalence of child maltreatment of individual forms was very high with 98% of street youth reporting one or more forms; 27.4% of males and 48.9% of females reported all five forms. Results of this study support the viability of the CTQ-SF for screening maltreatment in a highly vulnerable street population. Caution is recommended when comparing prevalence estimates for male and female street youth given the failure of the strong factorial multigroup model.

Texas Christian University (TCU) Short Forms for Assessing Client Needs and Functioning in Addiction Treatment

PubMed Central

SIMPSON, D. DWAYNE; JOE, GEORGE W.; KNIGHT, KEVIN; ROWAN-SZAL, GRACE A.; GRAY, JULIE S.

2012-01-01

The TCU Short Forms contain a revised and expanded set of assessments for planning and managing addiction treatment services. They are formatted as brief (1-page) forms to measure client needs and functioning, including drug use severity and history (TCUDS II), criminal thinking and cognitive orientation (CTSForm), motivation and readiness for treatment (MOTForm), psychological functioning (PSYForm), social relations and functioning (SOCForm), and therapeutic participation and engagement (ENGForm). These instruments facilitate optically-scanned data entry, computerized scoring, and rapid graphical feedback for clinical decisions. The present study (based on 5,022 inmates from eight residential prison treatment programs) examines evidence on scale reliabilities and measurement structures of these tools. Results confirmed their integrity and usefulness as indicators of individual and group-level therapeutic dynamics. PMID:22505795

Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

PubMed Central

Ita, Kevin

2015-01-01

Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use. PMID:26131647

Restless legs syndrome: differential diagnosis and management with rotigotine

PubMed Central

Merlino, Giovanni; Serafini, Anna; Robiony, Francesca; Valente, Mariarosaria; Gigli, Gian Luigi

2009-01-01

RLS is a common sleep disorder with distinctive clinical features. The prevalence of RLS in Caucasians and North Americans ranges from 5% to 10%. However, only some of these subjects (almost the 3% of the general population) report being affected by a frequent and severe form of the sleep disorder. RLS is diagnosed clinically by means of four internationally recognized criteria that summarize the main characteristics of the sleep disorder. Besides the essential criteria, supportive and associated features of RLS have been established by experts in order to help physicians treat patients with doubtful symptoms. Several clinical conditions may mimic this sleep disorder. In order to increase the sensibility and specificity of RLS diagnosis, doctors should perform a meticulous patient history and then an accurate physical and neurological examination. Dopamine agonists are recognized as the preferred first-line treatment for RLS. Rotigotine is a non-ergoline dopamine agonist with selectivity for D1, D2 and D3 receptors. The drug is administered via transdermal patches which release rotigotine for 24 hours. Four clinical trials demonstrated that this compound is able to improve RLS symptomatology with few and moderate adverse events. Head to head trials are required to compare the efficacy and tolerability of rotigotine with other dopamine agonists administered via oral intake. Rotigotine has been approved by the FDA and EMEA for Parkinson’s disease. For the treatment of moderate to severe idiopathic RLS, rotigotine has been recommended for approval by the EMEA and is under review by the FDA. PMID:19557102

Clinical presentation of mania compared with depression: data from a geriatric clinic in India.

PubMed

Prakash, Om; Kumar, Channaveerachari Naveen; Shivakumar, P T; Bharath, Srikala; Varghese, Mathew

2009-08-01

This retrospective chart review evaluated a comparison of the clinical profiles of older outpatients having mania and those with unipolar depression. The charts of elderly outpatients with mania and unipolar depression in tertiary care settings were reviewed and relevant information incorporated regarding clinical presentation, past and family history of affective disorder, treatment history and previous psychiatric and neurological history. Charts for 30 patients with mania (23 men and 7 women with mean (+/-SD) age of 68.5(+/- 5.75 years) and 92 with depression (47 men and 45 women with mean (+/-SD) age of 68.18 (+/-6.0 years) were evaluated. Fifteen patients (50%) with manic episodes had psychotic symptoms in the form of delusions and hallucinations while only 33 (35.8%) depressed patients had psychotic symptoms. One-third of manic patients received mood stabilizers at index visit. More than half (n = 16; 53.3%) of the patients in the mania group were prescribed antipsychotic medications. On cognitive functions, patients with manic episodes scored poorly compared with those with depression. These findings suggest that mania in the elderly is a severe form of affective disorder with respect to psychotic and cognitive symptoms. Conclusions from this study are limited due to its retrospective design. Further studies in this area are warranted.

An uncommon clinical form of foot-and-mouth disease in beef cattle presented with cornual skin lesions.

PubMed

Mohebbi, M R; Barani, S M; Mahravani, H

2017-01-01

Foot-and-mouth disease (FMD) is a major infectious disease in livestock. The common clinical signs in cattle include epidermal vesicles that are majorly distributed around oronasal cavity, feet and teats. The aim of this report is to document an uncommon clinical form of the disease which comprises the occurrence of classic vesicular lesion in a rarely observed location of the horn vegetative tissue. During Iran's outbreak of FMD in 2013, field investigation, clinical examination and sampling from the affected herds in Qom province were performed. Specimens of mouth epithelium and horn vegetative tissue were collected for virology and histopathologic study. All the samples collected from horns were positive for foot-and-mouth disease virus (FMDV) in both enzyme linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) tests, and the strain of the virus was identified as A05. Surprisingly, all the animals with horn lesion came from beef herds, were less than 12 months old and had more severe signs of the systemic disease. Since the same strain of virus did not cause similar lesions in surrounding dairy cows, it was concluded that occurrence of horn lesions may be more associated with host factors rather than virus strain.

Nutritional screening of patients at a memory clinic--association between patients' and their relatives' self-reports.

PubMed

Lyngroth, Anne Liv; Hernes, Susanne Miriam Sørensen; Madsen, Bengt-Ove; Söderhamn, Ulrika; Grov, Ellen Karine

2016-03-01

To compare individual reports by patients and relatives (proxy) of the Nutritional Form For the Elderly and relate the Nutritional Form For the Elderly scores to Mini Mental Status Examination scores, weight loss, Body Mass Index, five-point Clock Drawing Test and background variables. Undernutrition or risk of undernutrition is a significant problem among people with dementia. A poor nutritional state increases the risk of infections, delayed convalescence after acute illness and reduced quality of life. A cross-sectional study. Application of the Nutritional Form For the Elderly in addition to clinical nutrition parameters and cognitive tests in a memory clinic among 213 persons referred for assessment due to possible cognitive impairment or dementia. Patients' and proxy Nutritional Form For the Elderly scores yielded comparative results. Nutritional Form For the Elderly scores ≥6 (medium to high risk of undernutrition) were found in 32% of the patients vs. 43% of proxy. Mean Mini Mental Status Examination score was 23·2 (SD 4·5) and 50% failed the Clock Drawing Test. Involuntary weight loss was reported by 42% of the patients, and in 26% of the patients, Body Mass Index values were below 22 kg/m(2) , indicating undernutrition. By regression analysis, Clock Drawing Test (p = 0·019) and Mini Mental Status Examination (p = 0·04) might predict the risk of reduced nutritional status. The study demonstrates that a significant proportion of patients at our memory clinic were at nutritional risk. Corresponding results exist between patients' and proxy Nutritional Form For the Elderly scores; however, the patients assessed themselves more well-nourished as compared to proxy assessment. The discrepancies seem to increase with more severe cognitive impairment. Females and single-dwelling individuals were at higher risk of undernutrition compared to males and cohabitants. Self-reporting and proxy-rating seem both applicable for nutritional screening among moderate cognitive impaired. Cognitive decline seems to affect the accuracy when patients rate themselves. A reduced Mini Mental Status Examination and/or failed Clock Drawing Test might predict the risk of undernutrition. © 2016 John Wiley & Sons Ltd.

The clinical case for proton beam therapy

PubMed Central

2012-01-01

Abstract Over the past 20 years, several proton beam treatment programs have been implemented throughout the United States. Increasingly, the number of new programs under development is growing. Proton beam therapy has the potential for improving tumor control and survival through dose escalation. It also has potential for reducing harm to normal organs through dose reduction. However, proton beam therapy is more costly than conventional x-ray therapy. This increased cost may be offset by improved function, improved quality of life, and reduced costs related to treating the late effects of therapy. Clinical research opportunities are abundant to determine which patients will gain the most benefit from proton beam therapy. We review the clinical case for proton beam therapy. Summary sentence Proton beam therapy is a technically advanced and promising form of radiation therapy. PMID:23083010

Systemic and localized scleroderma in children: current and future treatment options.

PubMed

Rosenkranz, Margalit E; Agle, Lucila M A; Efthimiou, Petros; Lehman, Thomas J A

2006-01-01

Scleroderma is a group of rare and complex diseases with varied clinical manifestations. The most obvious manifestation of the diseases is skin hardening and sclerosis. Scleroderma can be divided into two main subgroups: systemic and localized. The systemic form, also known as systemic sclerosis, involves diffuse skin involvement and potentially severe visceral involvement. Localized scleroderma on the other hand is more common in children and usually confined to a specific region of the body with no internal organ involvement. The juvenile forms of systemic sclerosis and localized scleroderma are important conditions in children because of the clinical severity and substantial mortality of systemic scleroderma and the major growth defects associated with childhood-onset localized disease even if the active disease itself is self-limited. The pathogenic pathways of the various forms of scleroderma are only partially defined, but the main defect in scleroderma is abnormal collagen deposition leading to eventual fibrosis in the skin as well as multiple organ systems such as the heart and lungs in juvenile systemic sclerosis. Therapeutics are divided into three main subgroups for systemic sclerosis: antifibrotics, anti-inflammatories, and vasodilators. For localized disease, anti-inflammatories, vitamin D analogs, and UV irradiation have been investigated. However, the infrequency of scleroderma in the pediatric population plus the fact that this disease is very often self-limiting makes randomized controlled trials very difficult. It is for this reason that most data on treatment modalities for this disease have been extrapolated from studies in adult patients. There is no one therapy for systemic sclerosis or localized scleroderma that has proven to be very effective or significantly disease modifying. However, current therapeutic strategies must be initiated early in the disease course for maximum beneficial clinical effects. New interventions such as autologous stem cell transplant and cytokine-directed therapies are under investigation as potential treatments for this complex disease.

Optimal management of Alzheimer’s disease patients: Clinical guidelines and family advice

PubMed Central

Haberstroh, Julia; Hampel, Harald; Pantel, Johannes

2010-01-01

Family members provide most of the patient care and administer most of the treatments to patients with Alzheimer’s disease (AD). Family caregivers have an important impact on clinical outcomes, such as quality of life (QoL). As a consequence of this service, family caregivers suffer high rates of psychological and physical illness as well as social and financial burdens. Hence, it is important to involve family caregivers in multimodal treatment settings and provide interventions that are both suitable and specifically tailored to their needs. In recent years, several clinical guidelines have been presented worldwide for evidence-based treatment of AD and other forms of dementia. Most of these guidelines have considered family advice as integral to the optimal clinical management of AD. This article reviews current and internationally relevant guidelines with emphasis on recommendations concerning family advice. PMID:20520788

Radiation therapy and PD-1/PD-L1 blockade: the clinical development of an evolving anticancer combination.

PubMed

Gong, Jun; Le, Thang Q; Massarelli, Erminia; Hendifar, Andrew E; Tuli, Richard

2018-06-04

Several inhibitors of programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved as a form of immunotherapy for multiple cancers. Ionizing radiation therapy (RT) has been shown to enhance the priming and effector phases of the antitumor T-cell response rendering it an attractive therapy to combine with PD-1/PD-L1 inhibitors. Preclinical data support the rational combination of the 2 modalities and has paved way for the clinical development of the combination across a spectrum of cancers. In this review, we highlight the preclinical and clinical development of combined RT and PD-1/PD-L1 blockade to date. In addition to a comprehensive evaluation of available safety and efficacy data, we discuss important points of consideration in clinical trial design for this promising combination.

Integration of Ancillary Data for Improved Clinical Use: A Prototype within the VA's DHCP

PubMed Central

Andrews, Robert D.

1989-01-01

The Department of Veterans Affairs' (VA) Decentralized Hospital Computer Program (DHCP) is composed of several clinical modules that provide for the clinical information needs of their respective ancillary services. Using information from multiple ancillary packages is sometimes cumbersome. A prototype is being developed aimed at integrating ancillary data by storing clinical data oriented to the patient so that there is easy interaction of data from multiple services. A set of program utilities provide for user-defined functions of reporting, queries, entry, and decision support. Information can be used to monitor quality of care by providing feedback in the form of reports, reminders, and bulletins. Initial testing has indicated the prototype's design and implementation are feasible (in terms of space requirements, speed, and ease of use) in both outpatient and inpatient environments. The design and development of this prototype are described.

THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves' orbitopathy.

PubMed

Campi, Irene; Vannucchi, Guia; Salvi, Mario

2016-09-01

Management of Graves' orbitopathy (GO) must be based on the correct assessment of activity and severity of the disease. Activity is usually assessed with the Clinical Activity Score, whereas severity is classified according to a European Group On Graves' Orbitopathy (EUGOGO) consensus statement as mild, moderate-to-severe, and sight-threatening. Myopathic and chronic congestive forms are uncommon clinical presentations of GO. Restoration and maintenance of stable euthyroidism are recommended in the presence of GO.In moderate-to-severe disease, steroids have been widely employed and have shown to possess an anti-inflammatory activity, but about 20-30% of patients are not responsive and present recurrence. Some novel immunosuppressors have already been employed in clinical studies and have shown interesting results, although the lack of randomized and controlled trials suggests caution for their use in clinical practice. Potential targets for therapy in GO are the thyroid-stimulating hormone and the insulin-like growth factor 1 receptor on the fibroblasts, inflammatory cytokines, B and T cells, and the PIK3/mTORC1 signaling cascades for adipogenesis. A recent open study has shown that tocilizumab, an anti-sIL-6R antibody, inactivates GO. Consistent reports on the efficacy of rituximab have recently been challenged by randomized controlled trials.As the main goal of treatment is the well-being of the patient, the therapeutic strategy should be addressed to better suit the patient needs, more than improving one or more biological parameters. The increasing availability of new therapies will expand the therapeutic options for GO patients and allow the clinician to really personalize the treatment to better suit the patients' personal needs. © 2016 European Society of Endocrinology.

Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies.

PubMed

Calcagni, Giulio; Adorisio, Rachele; Martinelli, Simone; Grutter, Giorgia; Baban, Anwar; Versacci, Paolo; Digilio, Maria Cristina; Drago, Fabrizio; Gelb, Bruce D; Tartaglia, Marco; Marino, Bruno

2018-04-01

RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. New short-term therapy with a mammalian target of rapamycin inhibitor has recently been used to prevent heart failure in these patients with a severe form of hypertrophic cardiomyopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

Subependymal mass lesions and peripheral polyneuropathy in adult-onset glutaric aciduria type I.

PubMed

Herskovitz, Moshe; Goldsher, Dorith; Sela, Ben-Ami; Mandel, Hanna

2013-08-27

Glutaric aciduria type I (GA-I) is an autosomal recessive disease caused by a deficiency of the mitochondrial enzyme glutaryl CoA dehydrogenase (GCDH). This metabolic block causes increased urinary concentrations of glutaric and 3-hydroxyglutaric acids. The accumulation and excretion of glutarylcarnitine esters leads to secondary carnitine deficiency. GA-I has an incidence of 1:30,000. The clinical hallmark of GA-I is an acute encephalopathic crisis, with bilateral striatal necrosis presented by severe dystonic dyskinetic disorder. Most patients have their first symptoms during infancy, but some have a less severe form of the disease and some may even remain asymptomatic.

From neurogenic pulmonary edema to fat embolism syndrome: a brief review of experimental and clinical investigations of acute lung injury and acute respiratory distress syndrome.

PubMed

Chen, Hsing I

2009-11-30

Acute respiratory distress syndrome (ARDS) is the most devastating form of acute lung injury (ALI) or pulmonary edema (PE). We presented the experimental studies and clinical investigations of two serious forms of ALI. Drastic and severe PE could be induced by intracranial hypertension or cerebral compression (CC). The CC-induced PE was attributed to overactivation of the medullary sympathetic mechanism. Sympathetic vasoconstriction of the systemic and pulmonary resistance and capacitance vessels caused shift of blood volume from the splanchnic vascular beds to the lung. The hemodynamic changes led to systemic and pulmonary hypertension. Consequently, left ventricular failure as evidenced by dramatic decline in aortic flow with a slow decrease in pulmonary flow resulted in pressure and volume loading in the pulmonary circulation. These changes finally produced severe alveolar flooding and sudden death. Vasodilators such as sodium nitroprusside or nitroglycerin were capable of reducing the CC-induced pulmonary pathology and hemodynamic alterations. Fat embolism syndrome (FES) is a serious clinical problem in patients suffering from long bone fractures. ARDS may develop and cause mortality. Our laboratory reported a total of 14 subjects associated with FES and died of ARDS. We also developed a simple technique to produce FES. Corn oil was mixed with distilled water to form fatty micelles. Intravenous administration of or introduction of fatty micelles in anesthetized rats or isolated perfused lungs caused severe alveolar damage. Our clinical observation and animal experimentation revealed that infusion of fatty acids caused physical phase, resulting in microvascular obstruction accompanied by pulmonary hypertension and increased capillary permeability. Thereafter, the lipases in the lung hydrolyzed the neutral fat and released free fatty acids and biochemical mediators which were toxic to the lung. Our data have suggested that nitric oxide (NO), inducible NO synthase (iNOS), phospholipase A2, free radical and inflammatory cytokines (tumor necrosis factor alpha, interleukin-1beta and interleukin-6) are involved in the biochemical phase of FES with ARDS. The alveolar macrophages are the major source of iNOS. Later study also found that neutrophil elastase and myeloperoxidase were elevated following fat embolism. N-acetylcysteine (an antioxidant), and NOS inhibitors such as Nomega nitro-L-arginine methyl ester (L-NAME), S-methylisothiourea (SMT) or L-N6 (1-iminoethyl)-lysine (L-Nil) were able to abrogate the FES or the fat embolism-induced changes.

Nemaline myopathy and heart failure: role of ivabradine; a case report.

PubMed

Sarullo, Filippo M; Vitale, Giuseppe; Di Franco, Antonino; Sarullo, Silvia; Salerno, Ylenia; Vassallo, Laura; Baviera, Emanuela Petrona; Marazia, Stefania; Mandalà, Giorgio; Lanza, Gaetano A

2015-01-19

Nemaline myopathy (NM) is a rare congenital myopathy characterized by muscle weakness, hypotonia and the presence in muscle fibers of inclusions known as nemaline bodies and a wide spectrum of clinical phenotypes, ranging from severe forms with neonatal onset to asymptomatic forms. The adult-onset form is heterogeneous in terms of clinical presentation and disease progression. Cardiac involvement occurs in the minority of cases and little is known about medical management in this subgroup of NM patients. We report a rare case of heart failure (HF) in a patient with adult-onset NM in whom ivabradine proved to be able to dramatically improve the clinical picture. We report a case of a 37-year-old man with adult-onset NM, presenting with weakness and hypotonia of the proximal limb muscles and shoulder girdle, severely limiting daily activities. He developed progressive HF over a period of 6 months while attending a rehabilitation program, with reduced left ventricular ejection fraction (LVEF = 20%), manifested by dyspnea and signs of systemic congestion. The patient was started HF therapy with enalapril, carvedilol, spironolactone and loop diuretics. Target HF doses of these drugs (including carvedilol) were not reached because of symptomatic hypotension causing a high resting heart rate (HR) ≥70 beats per minute (bpm). Further deterioration of the clinical picture occurred with several life-threatening arrhythmic episodes requiring external defibrillation. An implantable cardioverter defibrillator (ICD) was then implanted. Persistent high resting HR was successfully treated with ivabradine with HR lowering from 90 bpm to 55 bpm at 1 month follow up, LVEF rising to 50% at 3 month follow up and to 54% at 2,5 year follow up. To date no more hospitalizations for heart failure occurred. A single hospitalization due to aspiration pneumonia required insertion of a tracheostomy tube to protect airways from further aspiration. At present, the patient is attending a regular rehabilitation program with net improvement in neuromotor control and less limitations in daily activities. HF is a rare feature of NM, but it can negatively influence prognosis. Conventional HF therapy and/or heart transplant are the only reasonable strategy in these patients. Ivabradine is a useful, effective and safe drug for therapy in NM patients with HF and should be considered when resting HR remains high despite beta-blockers' full titration or beta-blockers' underdosing due to intolerance or side effects.

PCR-RFLP of ribosomal internal transcribed spacers highlights inter and intra-species variation among Leishmania strains native to La Paz, Bolivia.

PubMed

Buitrago, Rosio; Cupolillo, Elisa; Bastrenta, Brigitte; Le Pont, Francois; Martinez, Eddy; Barnabé, Christian; Brenière, Simone Frédérique

2011-04-01

Human leishmaniasis is highly endemic in Bolivia and shows a growing incidence. This report reveals the genetic variability of 35 isolates mainly belonging to Leishmania braziliensis and Leishmania amazonensis species. Among them, 31 were from human patients with different clinical presentations, 3 strains from Lutzomya nuneztovari anglesi (the proven vector of L. amazonensis) and 1 strain of a mammal (Conepatus chinga). The isolates were analyzed by isoenzyme electrophoresis (MLEE) and PCR-RFLP of ITS rRNA genes, a genetic marker highly polymorphic and better adapted to sub-structuring of populations. MLEE and RFLP-ITS were in agreement to discriminate the species, 12 belong to L. (V.) braziliensis, 21 to L. (L.) amazonensis, 1 to Leishmania (V.) lainsoni and 1 to Leishmania (L.) chagasi. Among L. (V.) braziliensis the RFLP-ITS only highlights variability. Ten isolates from either cutaneous or mucocutaneous clinical forms, were grouped together (bootstrap value of 99.8%) apart from two others, one from a mammal (C. chinga), the other from a patient with a cutaneous form. Among L. (L.) amazonensis both markers detect variability but no significant sub-division was identified including isolates from different clinical forms. Moreover, the high frequency of several isolates from cutaneous forms occurred during an outbreak, with putative hybrid character (multiloci heterozygous patterns depicted by MLEE) could be linked to better fitness of these parasites. However, in the absence of observation of hypothetical parents, their hybrid status remains a question. Copyright © 2010. Published by Elsevier B.V.

TYPES OF ALBINISM IN THE BLACK SOUTHERN AFRICA POPULATION.

PubMed

Kromberg, J G R; Bothwell, J; Kidson, S H; Manga, P; Kerr, R; Jenkins, T

2012-01-01

Oculocutaneous albinism (OCA) is the most common inherited disorder in Southern African blacks and several types have been described. Molecular techniques, where available, can be used to confirm a clinical diagnosis and the type of OCA, if necessary, and for prenatal diagnosis. To investigate and classify the different types of albinism commonly found and to determine the clinical implications for each type. A descriptive survey. Gauteng province, South Africa, and Lesotho. Three groups of subjects with OCA (96 from a genetics clinic, 62 from a dermatology clinic, and 31 from community surveys) from the black African population participated. Subjects underwent clinical and/or dermatological examinations and were then classified according to type of OCA. Four forms of OCA were identified: most (82%) subjects had OCA2 (a tyrosinase- positive type) with three sub-types: those without large freckles (ephelides) on exposed areas (named OCA 2a in this study), those with such freckles (named OCA 2b), and those with brown albinism (BOCA); the remainder had red/rufous albinism, ROCA (OCA 3). The four forms could be distinguished from each other clinically without using molecular genetic testing. The most common types of albinism found in the black population of Southern Africa are OCA2 and OCA3. Given the high prevalence of the disorder, together with the high risk of skin cancer, and the recent persecution of affected individuals in certain East African countries, these findings and their clinical implications have significance in terms of both education and awareness for health professionals and lay people caring for those with albinism.

Feedback in Clinical Education, Part I: Characteristics of Feedback Provided by Approved Clinical Instructors

PubMed Central

Nottingham, Sara; Henning, Jolene

2014-01-01

Context Providing students with feedback is an important component of athletic training clinical education; however, little information is known about the feedback that Approved Clinical Instructors (ACIs; now known as preceptors) currently provide to athletic training students (ATSs). Objective To characterize the feedback provided by ACIs to ATSs during clinical education experiences. Design Qualitative study. Setting One National Collegiate Athletic Association Division I athletic training facility and 1 outpatient rehabilitation clinic that were clinical sites for 1 entry-level master's degree program accredited by the Commission on Accreditation of Athletic Training Education. Patients or Other Participants A total of 4 ACIs with various experience levels and 4 second-year ATSs. Data Collection and Analysis Extensive field observations were audio recorded, transcribed, and integrated with field notes for analysis. The constant comparative approach of open, axial, and selective coding was used to inductively analyze data and develop codes and categories. Member checking, triangulation, and peer debriefing were used to promote trustworthiness of the study. Results The ACIs gave 88 feedback statements in 45 hours and 10 minutes of observation. Characteristics of feedback categories included purpose, timing, specificity, content, form, and privacy. Conclusions Feedback that ACIs provided included several components that made each feedback exchange unique. The ACIs in our study provided feedback that is supported by the literature, suggesting that ACIs are using current recommendations for providing feedback. Feedback needs to be investigated across multiple athletic training education programs to gain more understanding of certain areas of feedback, including frequency, privacy, and form. PMID:24143902

Surgical Treatment of Anal Stenosis with Diamond Flap Anoplasty Performed in a Calibrated Fashion.

PubMed

Gülen, Merter; Leventoğlu, Sezai; Ege, Bahadir; Menteş, B Bülent

2016-03-01

Regarding anoplasty for anal stenosis, it is not clear to what extent the final anal caliber should be targeted. The aim of this study was to investigate the results of diamond-flap anoplasty performed in a calibrated manner for the treatment of severe anal stenosis due to a previous hemorrhoidectomy. Prospectively prepared standard forms were evaluated retrospectively. Anoplasty with unilateral or bilateral diamond flaps was performed for moderate or severe anal stenosis, targeting a final anal caliber of 25 to 26 mm. The demographic characteristics, causes of anal stenosis, number of previous surgeries, anal stenosis staging (Milsom and Mazier), anal calibers (millimeter), the Cleveland Clinic Incontinence Score, and the modified obstructed defecation syndrome Longo score were recorded on pre-prepared standard forms, as well as postoperative complications and the time of return to work. From January 2011 to July 2013, 18 patients (12 males, 67%) with a median age of 39 years (range, 27-70) were treated. All of the patients had a history of previous hemorrhoidectomy. The number of previous corrective interventions was 2.1 ± 1.8 (range, 0-4), and 2 patients had a history of failed anoplasty. Five patients (28%) had moderate anal stenosis and 13 (72%) had severe anal stenosis. Preoperative, intraoperative, and 12-month postoperative anal calibration values were 9 ± 3 mm (range, 5-15), 25 ± 0.75 mm (range, 24-26), and 25 ± 1 mm (range, 23-27) (p < 0.0001, for immediate postoperative and 12-month postoperative anal calibers compared with the intraoperative). Preoperative and 12-month postoperative Cleveland Clinic Incontinence Scores were 0.83 ± 1.15 (range, 0-4) and 0.39 ± 0.70 (range, 0-2) (p = 1.0). The clinical success rate was 88.9%. No severe postoperative complications were observed. This study was limited because it was a single-armed, retrospective analysis of prospectively designed data. Diamond-flap anoplasty performed in a standardized and calibrated manner is a highly successful method for the treatment of anal stenosis caused by previous hemorrhoidectomy.

Role of Altered mGluR Activity in Cognitive Impairments in TSC: Implications for a Novel Method of Treatment

DTIC Science & Technology

2013-04-01

epilepsy, autism , anxiety and mood disorders. Fragile X syndrome (FXS), another form of inherited mental retardation and autism , shares many of the...therapeutic intervention for several of the deficits observed in TSC. 15. SUBJECT TERMS autism , Tuberous Sclerosis Complex, Fragile X Syndrome...clinical features being mental retardation, epilepsy, autism , anxiety and mood disorders (Prather & de Vries, 2004). Fragile X syndrome (FXS

Epidemiology and Outcomes of Non-compressible Torso Hemorrhage

DTIC Science & Technology

2013-01-01

a r t i c l e i n f o Article history : Received 4 January 2013 Received in revised form 15 April 2013 Accepted 30 May 2013 Available online 21 June...military definition of NCTH, which incorporates anatomic and physiological criteria, to a civilian population treated at trauma centers in the US. Methods...injury (Glasgow Coma Scale, injury type, Injury Severity Score, anatomic region), and clinical (major surgical procedure, need for transfusion, and

[Thyroid Storm and Myxedema Coma].

PubMed

Milkau, Malte; Sayk, Friedhelm

2018-03-01

Thyroid storm and myxedema coma are the most severe clinical forms of thyroid dysfunction. While both hyper- and hypothyroidsm are common diseases, thyroid storm and myxedema coma are rare. Due to their unspecific signs and symptoms they are often difficult to diagnose. Both disorders are medical emergencies, which still show a significant mortality. The following article summarizes diagnostic tools and treatment options for these disorders. © Georg Thieme Verlag KG Stuttgart · New York.

Olfactory Hallucinations without Clinical Motor Activity: A Comparison of Unirhinal with Birhinal Phantosmia

PubMed Central

Henkin, Robert I.; Potolicchio, Samuel J.; Levy, Lucien M.

2013-01-01

Olfactory hallucinations without subsequent myoclonic activity have not been well characterized or understood. Herein we describe, in a retrospective study, two major forms of olfactory hallucinations labeled phantosmias: one, unirhinal, the other, birhinal. To describe these disorders we performed several procedures to elucidate similarities and differences between these processes. From 1272, patients evaluated for taste and smell dysfunction at The Taste and Smell Clinic, Washington, DC with clinical history, neurological and otolaryngological examinations, evaluations of taste and smell function, EEG and neuroradiological studies 40 exhibited cyclic unirhinal phantosmia (CUP) usually without hyposmia whereas 88 exhibited non-cyclic birhinal phantosmia with associated symptomology (BPAS) with hyposmia. Patients with CUP developed phantosmia spontaneously or after laughing, coughing or shouting initially with spontaneous inhibition and subsequently with Valsalva maneuvers, sleep or nasal water inhalation; they had frequent EEG changes usually ipsilateral sharp waves. Patients with BPAS developed phantosmia secondary to several clinical events usually after hyposmia onset with few EEG changes; their phantosmia could not be initiated or inhibited by any physiological maneuver. CUP is uncommonly encountered and represents a newly defined clinical syndrome. BPAS is commonly encountered, has been observed previously but has not been clearly defined. Mechanisms responsible for phantosmia in each group were related to decreased gamma-aminobutyric acid (GABA) activity in specific brain regions. Treatment which activated brain GABA inhibited phantosmia in both groups. PMID:24961619

Correlation between presence of Leishmania RNA virus 1 and clinical characteristics of nasal mucosal leishmaniosis.

PubMed

Ito, Marcos Massayuki; Catanhêde, Lilian Motta; Katsuragawa, Tony Hiroshi; Silva Junior, Cipriano Ferreira da; Camargo, Luis Marcelo Aranha; Mattos, Ricardo de Godoi; Vilallobos-Salcedo, Juan Miguel

2015-01-01

Mucosal leishmaniosis (ML) is a severe clinical form of leishmaniosis. Complex factors related to the parasite and the host are attributed to the development of mucosal lesions. Leishmania RNA virus 1 (LRV1) can disrupt immune response, and may be the main determinant of severity of the disease; it should be investigated. To study the existence of clinical differences between patients with ML with endosymbiosis by LRV1 and. those without it. A cross-sectional cohort study with clinical evaluation, polymerase chain reaction (PCR) detection of Leishmania, species classification, and search of LRV1 was performed. Only patients with confirmed diagnosis of ML by positive PCR and with nasal mucosa injuries were included in this analysis. Out of 37 patients, 30 (81.1%) were diagnosed with Leishmania braziliensis, five (13.5%) with Leishmania guyanensis, and two (5.4%) with mixed infection of L. braziliensis and L. guyanensis. LVR1 virus was present in 26 (70.3%) of the cases. Correlation between clinical phenotype and presence of LRV1 was not observed, although the frequency of the virus is two-fold higher in mucosal lesions than that found in the literature on skin lesions in the same geographical area. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Evaluation of autoCPAP devices in home treatment of sleep apnea/hypopnea syndrome.

PubMed

Meurice, J C; Cornette, A; Philip-Joet, F; Pepin, J L; Escourrou, P; Ingrand, P; Veale, D

2007-11-01

Quality of life (QOL) and sleepiness for patients with sleep apnea/hypopnea syndrome (SAHS) might improve with continuous positive airway pressure devices working in auto-adjust mode (autoCPAP) by allowing pressure modulations following patient needs. Clinical comparisons between devices driven by different algorithms are needed. We compared the clinical effectiveness of fixed pressure CPAP and four different autoCPAP devices by assessing compliance and QOL (36-item short-form health survey [SF-36]). SAHS patients were randomly allocated to five groups. Polysomnography (PSG) was performed to titrate the effective pressure in the constant CPAP group and evaluate residual apnea/hypopnea index (AHI) under autoCPAP. Follow-up consisted of clinical visits at three and six months by homecare technicians who assessed compliance, symptom scores and SF-36 scores. A laboratory-based PSG using the same CPAP/autoCPAP device as at home was performed at six months. Eighty-three patients (mean age 56+/-10 yrs) with mean body mass index (BMI) 30.8+/-5.3 kg/m(2) and severe SAHS (mean AHI: 52.3+/-17.8/h) were included. There were no differences in clinical symptoms or QOL scores, and similar clinical and PSG improvements were seen in all groups. CPAP use was >5 h per night, without any significant difference between groups. AutoCPAP is equally as effective as fixed CPAP for long-term home treatment in severe SAHS patients.

A 12-month study of the hikikomori syndrome of social withdrawal: Clinical characterization and different subtypes proposal.

PubMed

Malagón-Amor, Ángeles; Martín-López, Luis Miguel; Córcoles, David; González, Anna; Bellsolà, Magda; Teo, Alan R; Pérez, Víctor; Bulbena, Antoni; Bergé, Daniel

2018-03-23

Social withdrawal is a new mental health problem increasingly common, present in different cultures, whose psychopathology and treatment is not yet established. This study aims to determine the socio-demographic and clinical features and possible clinical subtypes that predict the 12-month outcomes of cases with hikikomori syndrome, a severe form of social withdrawal. Socio-demographic and clinical data at baseline were analysed as well as data obtained for 12 months after at-home treatment in 190 cases. The inclusion criteria were: spending all time at home, avoiding social situations and relationships, significant deterioration due to social isolation, with a minimum duration of 6 months. Six major diagnostic groups were identified: affective, anxiety, psychotic, drug use, personality and other Axis I disorders. The anxiety-affective subgroup demonstrated lower clinical severity, but worse evolution. Less than half of the cases were available for medical follow-up at 12-months. Subjects undergoing intensive treatment had a higher medical follow-up rate and better social networks at 12-months. Therefore, our findings provide data to reach consensus on the specific characteristics of social isolation hikikomori syndrome. The analysis demonstrated the fragility and tendency to relapse and have disengagement, particularly relevant in the anxiety-affective subgroup, suggesting that intensive treatments are more effective. Copyright © 2018 Elsevier B.V. All rights reserved.

A clinical information systems strategy for a large integrated delivery network.

PubMed Central

Kuperman, G. J.; Spurr, C.; Flammini, S.; Bates, D.; Glaser, J.

2000-01-01

Integrated delivery networks (IDNs) are an emerging class of health care institutions. IDNs are formed from the affiliation of individual health care institutions and are intended to be more efficient in the current fiscal health care environment. To realize efficiencies and support their strategic visions, IDNs rely critically on excellent information technology (IT). Because of its importance to the mission of the IDN, strategic decisions about IT are made by the top leadership of the IDN. At Partners HealthCare System, a large IDN in Boston, MA, a clinical information systems strategy has been created to support the Partners clinical vision. In this paper, we discuss the Partners' structure, clinical vision, and current IT initiatives in place to address the clinical vision. The initiatives are: a clinical data repository, inpatient process support, electronic medical records, a portal strategy, referral applications, knowledge resources, support for product lines, patient computing, confidentiality, and clinical decision support. We address several of the issues encountered in trying to bring excellent information technology to a large IDN. PMID:11079921

The relationship of PTSD to key somatic complaints and cultural syndromes among Cambodian refugees attending a psychiatric clinic: the Cambodian Somatic Symptom and Syndrome Inventory (CSSI).

PubMed

Hinton, Devon E; Kredlow, M Alexandra; Pich, Vuth; Bui, Eric; Hofmann, Stefan G

2013-06-01

This article describes a culturally sensitive questionnaire for the assessment of the effects of trauma in the Cambodian refugee population, the Cambodian Somatic Symptom and Syndrome Inventory (CSSI), and gives the results of a survey with the instrument. The survey examined the relationship of the CSSI, the two CSSI subscales, and the CSSI items to posttraumatic stress disorder (PTSD) severity and self-perceived functioning. A total of 226 traumatized Cambodian refugees were assessed at a psychiatric clinic in Lowell, MA, USA. There was a high correlation of the CSSI, the CSSI somatic and syndrome scales, and all the CSSI items to the PTSD Checklist (PCL), a measure of PTSD severity. All the CSSI items varied greatly across three levels of PTSD severity, and patients with higher levels of PTSD had very high scores on certain CSSI-assessed somatic items such as dizziness, orthostatic dizziness (upon standing), and headache, and on certain CSSI-assessed cultural syndromes such as khyâl attacks, "fear of fainting and dying upon standing up," and "thinking a lot." The CSSI was more highly correlated than the PCL to self-perceived disability assessed by the Short Form-12 Health Survey (SF-12). The study demonstrates that the somatic symptoms and cultural syndromes described by the CSSI form a central part of the Cambodian refugee trauma ontology. The survey indicates that locally salient somatic symptoms and cultural syndromes need be profiled to adequately assess the effects of trauma.

Development and Preliminary Psychometric Evaluation of a Brief Self-Report Questionnaire for the Assessment of the DSM-5 level of Personality Functioning Scale: The LPFS Brief Form (LPFS-BF).

PubMed

Hutsebaut, Joost; Feenstra, Dine J; Kamphuis, Jan H

2016-04-01

The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013) alternative model for personality disorders (PDs) introduced a new paradigm for the assessment of PDs that includes levels of personality functioning indexing the severity of personality pathology irrespective of diagnosis. In this study, we describe the development and preliminary psychometric evaluation of a newly developed brief self-report questionnaire to assess levels of personality functioning, the Level of Personality Functioning Scale-Brief Form (LPFS-BF; Bender, Morey, & Skodol, 2011). Patients (N = 240) referred to a specialized setting for the assessment and treatment of PDs completed the LPFS-BF, the Brief Symptom Inventory (BSI; Derogatis, 1975), the Severity Indices of Personality Problems (SIPP-118; Verheul et al., 2008), and were administered the Structured Clinical Interview for DSM-IV Axis I Personality Disorders (SCID-I; APA, 1994; First, Spitzer, Gibbon, & Williams, 1997) and the SCID Axis II Personality Disorders (SCID-II; First, Spitzer, Gibbon, Williams, & Benjamin, 1996). When constrained to a 2-factor oblique solution, the LPFS-BF yielded a structure that corresponded well to an interpretation of Self- and Interpersonal Functioning scales. The instrument demonstrated fair to satisfactory internal consistency and promising construct validity. The LPFS-BF constitutes a short, user-friendly instrument that provides a quick impression of the severity of personality pathology, specifically oriented to the DSM-5 model. Clearly, more research is needed to test its validity and clinical utility. (c) 2016 APA, all rights reserved).

Response to Drs. Shastry and Trese: Phenotype-genotype correlations in X-linked retinitis pigmentosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaplan, J.; Munnich, A.

1996-11-11

Shastry and Trese recently reported on a large kindred with X-linked retinitis pigmentosa (XLRP) characterized by a loss of central vision and preserved peripheral function. In their report, the disease had an early onset with severe myopia and a loss of central vision, while night blindness occurred later. Genetic analysis suggested that the disease was linked to the RP2 locus, and the authors raised the question of whether other cases linked to RP2 could display a similar loss of central vision. Three years ago, we reported on 4 large XLRP pedigrees with a very early onset with severe myopia andmore » early loss of visual acuity, while in 5 other families the disease started later with night blindness. We showed that the first clinical form was linked to RP2, while the second was linked to RP3. Thus, the major difference between the two forms concerns the initial symptom, information which can be obtained from the parents and patients after careful questioning. By contrast, in adult life, no difference in either severity of disease or aspect of the fundus was observed in our series, regardless of the clinical subtype of XLRP. Some months later, Jacobson et al. reported on a pedigree with an RP2 genotype, and their data support the notion that in XLRP of RP2 type 1, cone dysfunction takes place first, and as the disease advances both rods and cones are affected. We were very happy, therefore, to read that the study of Shastry and Trese fully confirmed our previous findings. 3 refs.« less

Clinical and sociodemographic correlates of severe insomnia in psychotropic drug-free, Asian outpatients with major depressive disorder.

PubMed

Srisurapanont, Manit; Likhitsathian, Surinporn; Chua, Hong Choon; Udomratn, Pichet; Chang, Sungman; Maneeton, Narong; Maneeton, Benchaluk; Chen, Chia-Hui; Shih-Yen Chan, Edwin; Bautista, Dianne; Bin Sulaiman, Ahmad Hatim

2015-11-01

Little has been known regarding the correlates of severe insomnia in major depressive disorder (MDD). This post-hoc analysis aimed to examine the sociodemographic and clinical correlates of severe insomnia in psychotropic drug-free, Asian adult outpatients with MDD. Participants were psychotropic drug-free patients with MDD, aged 18-65 years. By using the Symptom Checklist-90 Items, Revised (SCL-90-R), a score of 4 (severe distress) on any one of three insomnia items was defined as severe insomnia. Other measures included the Montgomery-Asberg Depression Rating Scale (MADRS), the Fatigue Severity Scale (FSS), the nine psychopathology subscales of SCL-90-R, the Physical and Mental Component Summaries of Short Form Health Survey (SF-36 PCS and SF-36 MCS), and the Sheehan Disability Scale (SDS). Of 528 participants, their mean age being 39.5 (SD=13.26) years, 64.2% were females, and 239 (45.3%) had severe insomnia. The logistic regression model revealed that low educational qualifications (less than secondary school completion), high SCL-90-R Depression scores, high SCL-90-R Anxiety scores, and low SF-36 PCS scores were independently correlated with severe insomnia (p's<.05). Insomnia was determined only by the patient's distress. Middle insomnia was not assessed. Psychotropic drug-free patients with MDD are not commonly seen in psychiatric practice. Severe insomnia is common in patients with MDD. It is closely related with low educational qualification, subjective depression and anxiety severity, and poor physical health. These findings may implicate the treatment of comorbid MDD and severe insomnia, for example, sleep hygiene education, pharmacological treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

Reaching clinically relevant outcome measures for new pharmacotherapy and immunotherapy of atopic eczema.

PubMed

Chalmers, Joanne; Deckert, Stefanie; Schmitt, Jochen

2015-06-01

This article describes the core outcome set (COS) for atopic eczema trials. COS describe a minimum set of outcomes to be assessed in a defined situation. COS are required to overcome the current situation of different trials using different endpoints with unclear/insufficient measurement properties resulting in incomparable trials. The global multi-stakeholder Harmonising Outcomes Measures for Eczema initiative developed the Harmonising Outcomes Measures for Eczema roadmap as a generic framework for COS development. Following the establishment of a panel representing all stakeholders, a core set of outcome domains need to be selected based on systematic reviews and consensus methods. Outcome measurement instruments to assess these core domains need to be valid, reliable, and feasible. There is broad global consensus that clinical signs, quality of life, symptoms, and long-term control of flares form the COS for atopic eczema trials. The Eczema Area and Severity Index is recommended to assess clinical signs in atopic eczema trials. Systematic reviews to identify adequate outcome measurement instruments for the other core outcome domains are underway. Clinical signs should be assessed in all atopic eczema trials by at least the Eczema Area and Severity Index. Quality of life, symptoms, and flares should also be assessed in all atopic eczema trials by a valid, reliable, and feasible instrument.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis.

PubMed

Papachristou, Georgios I; Machicado, Jorge D; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C; Singh, Vikesh K; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O; Triantafyllou, Konstantinos; Barbu, Sorin T; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch; Nawaz, Haq; Park, Walter G; de-Madaria, Enrique; Lee, Peter J; Wu, Bechien U; Greer, Phil J; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

Engineered cell and tissue models of pulmonary fibrosis.

PubMed

Sundarakrishnan, Aswin; Chen, Ying; Black, Lauren D; Aldridge, Bree B; Kaplan, David L

2018-04-01

Pulmonary fibrosis includes several lung disorders characterized by scar formation and Idiopathic Pulmonary Fibrosis (IPF) is a particularly severe form of pulmonary fibrosis of unknown etiology with a mean life expectancy of 3years' post-diagnosis. Treatments for IPF are limited to two FDA approved drugs, pirfenidone and nintedanib. Most lead candidate drugs that are identified in pre-clinical animal studies fail in human clinical trials. Thus, there is a need for advanced humanized in vitro models of the lung to improve candidate treatments prior to moving to human clinical trials. The development of 3D tissue models has created systems capable of emulating human lung structure, function, and cell and matrix interactions. The specific models accomplish these features and preliminary studies conducted using some of these systems have shown potential for in vitro anti-fibrotic drug testing. Further characterization and improvements will enable these tissue models to extend their utility for in vitro drug testing, to help identify signaling pathways and mechanisms for new drug targets, and potentially reduce animal models as standard pre-clinical models of study. In the current review, we contrast different in vitro models based on increasing dimensionality (2D, 2.5D and 3D), with added focus on contemporary 3D pulmonary models of fibrosis. Copyright © 2017. Published by Elsevier B.V.

THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET

PubMed Central

Schmidt-Erfurth, Ursula; van Lookeren Campagne, Menno; Henry, Erin C.; Brittain, Christopher

2017-01-01

Purpose: Geographic atrophy (GA) is an advanced, vision-threatening form of age-related macular degeneration (AMD) affecting approximately five million individuals worldwide. To date, there are no approved therapeutics for GA treatment; however, several are in clinical trials. This review focuses on the pathophysiology of GA, particularly the role of complement cascade dysregulation and emerging therapies targeting the complement cascade. Methods: Primary literature search on PubMed for GA, complement cascade in age-related macular degeneration. ClinicalTrials.gov was searched for natural history studies in GA and clinical trials of drugs targeting the complement cascade for GA. Results: Cumulative damage to the retina by aging, environmental stress, and other factors triggers inflammation via multiple pathways, including the complement cascade. When regulatory components in these pathways are compromised, as with several GA-linked genetic risk factors in the complement cascade, chronic inflammation can ultimately lead to the retinal cell death characteristic of GA. Complement inhibition has been identified as a key candidate for therapeutic intervention, and drugs targeting the complement pathway are currently in clinical trials. Conclusion: The complement cascade is a strategic target for GA therapy. Further research, including on natural history and genetics, is crucial to expand the understanding of GA pathophysiology and identify effective therapeutic targets. PMID:27902638

[Congenital nephrogenic diabetes insipidus: about a case report].

PubMed

Esselmani, Hicham; Yassine, Asmaa; Bouabdellah, Mounya; Benchekroun, Laila; Handor, Najat; Elalami, Sanae; Chabraoui, Layachi

2013-01-01

Congenital nephrogenic diabetes insipidus is a rare, hereditary in nature, characterized by an inability of the kidney to concentrate urine, secondary to the manifold resistance to the action of vasopressin. X-linked forms of transmission (90%) are expressed in boys, from the neonatal period in general, by polyuria and polydipsia. Symptomatology in transmissive girls is variable but can sometimes be quite marked. These forms are secondary to mutations in the gene encoding the vasopressin V2 receptor, located at position Xq28, responsible for a loss of function of this receptor. Some of these mutations may cause a partial phenotype, less severe. Forms of autosomal, recessive or dominant are more rare (10%). Treatment is symptomatic, sometimes difficult in infants. It aims to avoid episodes of dehydration. It is based on a conventional diet hypo-osmotic and administration of hydrochlorothiazide and indomethacin. We report here the case of a child with congenital nephrogenic diabetes insipidus hospitalized at Children's Hospital of Rabat and throughout this case we review the pathophysiology and clinical and biological characteristics of the disease and including importance of contribution of clinical biochemistry laboratory in the diagnosis and monitoring of this disease.

[Implications in primary health care of medical genetics and genomic in type 2 diabetes mellitus].

PubMed

Ramirez-Garcia, Sergio Alberto; Cabrera-Pivaral, Carlos E; Huacuja-Ruiz, Luis; Flores-Alvarado, Luis Javier; Pérez-García, Guillermo; González-Rico, José Luis; López-Velázquez, Alma; Topete-González, Luz Rosalba; Rosales-Góme, Roberto Carlos; Candelario-Mejía, Gerardo; Villa-Ruano, Nemesio

2013-01-01

Type 2 diabetes mellitus is a complex disease and a global health problem. Therefore, the first level of health care should handle the approaches of medical genetics and genomics to reduce its incidence. The aim is to present perspectives analyzed by our group in two areas of genetics and its clinical application. Emphasis is placed on the coexistence of several genetic forms clinically detectable in patients with diabetes, missing heritability associated with low penetrance, and epigenomics mechanism. It is discussed the effect of genetic variation associated with resistance to insulin, beta-cell dysfunction, shaft incretin, and other points of interest, such as thrifty genotype hypothesis, conformational disease, genetically unknown foods, phenocopies as clinically silent hypercortisolism, molecular phytopharmacology in the clinical management. Finally, the result was displayed in the Mexican population from genetic studies and new findings of clinical importance, such as involvement of melatonin and effect of variations in the number of copies in a genomic region.

Myotonic Dystrophy Type 1 Management and Therapeutics.

PubMed

Smith, Cheryl A; Gutmann, Laurie

2016-12-01

Myotonic dystrophy (DM1) is the most common form of adult muscular dystrophy. It is a multisystem disorder with a complex pathophysiology. Although inheritance is autosomal dominant, disease variability is attributed to anticipation, a maternal expansion bias, variable penetrance, somatic mosaicism, and a multitude of aberrant pre-mRNA splicing events. Patient presentations range from asymptomatic or mild late onset adult to severe congenital forms. Multiple organ systems may be affected. Patients may experience early cataracts, myotonia, muscle weakness/atrophy, fatigue, excessive daytime sleepiness, central/obstructive apnea, respiratory failure, cardiac arrhythmia, insulin resistance, dysphagia, GI dysmotility, cognitive impairment, Cluster C personality traits, and/or mood disorders. At present, there is no curative or disease-modifying treatment, although clinical treatment trials have become more promising. Management focuses on genetic counseling, preserving function and independence, preventing cardiopulmonary complications, and symptomatic treatment (e.g., pain, myotonia, hypersomnolence, etc.). Currently, there is an increasing international consensus on monitoring and treatment options for these patients which necessitates a multidisciplinary team to provide comprehensive, coordinated clinical care.

Dropped-head in recessive oculopharyngeal muscular dystrophy.

PubMed

Garibaldi, Matteo; Pennisi, Elena Maria; Bruttini, Mirella; Bizzarri, Veronica; Bucci, Elisabetta; Morino, Stefania; Talerico, Caterina; Stoppacciaro, Antonella; Renieri, Alessandra; Antonini, Giovanni

2015-11-01

A 69-year-old woman presented a dropped head, caused by severe neck extensor weakness that had started two years before. She had also developed a mild degree of dysphagia, rhinolalia, eyelid ptosis and proximal limb weakness during the last months. EMG revealed myopathic changes. Muscle MRI detected fatty infiltration in the posterior neck muscles and tongue. Muscle biopsy revealed fiber size variations, sporadic rimmed vacuoles, small scattered angulated fibers and a patchy myofibrillar network. Genetic analysis revealed homozygous (GCN)11 expansions in the PABPN1 gene that were consistent with recessive oculopharyngeal muscular dystrophy (OPMD). There are a few reports of the recessive form, which has a later disease onset with milder symptoms and higher clinical variability than the typical dominantly inherited form. This patient, who is the first Italian and the eighth worldwide reported case of recessive OPMD, is also the first case of OPMD with dropped-head syndrome, which thus expands the clinical phenotype of recessive OPMD. Copyright © 2015 Elsevier B.V. All rights reserved.

Chronic ankle pain and fibrosis successfully treated with a new noninvasive augmented soft tissue mobilization technique (ASTM): a case report.

PubMed

Melham, T J; Sevier, T L; Malnofski, M J; Wilson, J K; Helfst, R H

1998-06-01

This clinical case report demonstrates the clinical effectiveness of a new form of soft tissue mobilization in the treatment of excessive connective tissue fibrosis (scar tissue) around an athlete's injured ankle. The scar tissue was causing the athlete to have pain with activity, pain on palpation of the ankle, decreased range of motion, and loss of function. Surgery and several months of conventional physical therapy failed to alleviate the athlete's symptoms. As a final resort, augmented soft tissue mobilization (ASTM) was administered. ASTM is an alternative nonsurgical treatment modality that is being researched at Performance Dynamics (Muncip, IN). ASTM is a process that uses ergonomically designed instruments that assist therapists in the rapid localization and effective treatment of areas exhibiting excessive soft tissue fibrosis. This is followed by a stretching and strengthening program. Upon the completion of 6 wk of ASTM therapy, the athlete had no pain and had regained full range of motion and function. This case report is an example of how a noninvasive augmented form of soft tissue mobilization (ASTM) demonstrated impressive clinical results in treating a condition caused by connective tissue fibrosis.

Diagnosis and Treatment of Transthyretin Cardiac Amyloidosis. Progress and Hope.

PubMed

González-López, Esther; López-Sainz, Ángela; Garcia-Pavia, Pablo

2017-11-01

Cardiac amyloidosis is an infiltrative disorder caused by extracellular protein deposition. Transthyretin is a proamyloidotic protein that produces one of the most frequent forms of cardiac amyloidosis, either through mutations or a wild-type form (previously known as senile amyloidosis). Until very recently, diagnosis of transthyretin amyloidosis (ATTR) was very uncommon and histological confirmation was mandatory, making diagnosis of ATTR a real challenge in daily clinical practice. Moreover, the specific therapeutic options to alter the clinical course of the disease were very limited. However, advances in cardiac imaging and diagnostic strategies have improved recognition of ATTR. In addition, several compounds able to modify the natural history of the disease are in the final phases of research, with promising results. Given that effective therapies are on the horizon, cardiologists should be well-versed in this disease and be familiar with its diagnosis and treatment. This review describes the broad clinical spectrum of ATTR in detail, as well as recent advances in the diagnosis and treatment of this condition. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Recent advances in bulbar syndromes: genetic causes and disease mechanisms.

PubMed

Manole, Andreea; Fratta, Pietro; Houlden, Henry

2014-10-01

With advances in next-generation gene sequencing, progress in deep phenotyping and a greater understanding of the pathogenesis of motor neuron disease, our knowledge of the progressive bulbar syndromes has significantly increased in recent years. This group of heterogeneous conditions, in which the primary disorder is focused around degeneration of the lower cranial nerves, can occur in children or adults and form a spectrum of severity, based around the common feature of bulbar dysfunction. Early genetic diagnosis may allow treatment in some bulbar syndromes. Brown-Vialetto-Van Laere and Fazio-Londe syndromes are the most recent childhood forms of progressive bulbar palsy to be genetically defined. The clinical phenotype of this group of childhood disorders was first reported over 120 years ago. Recently, it was demonstrated that in a third of these patients Brown-Vialetto-Van Laere is caused by mutations in the SLC52A2 and SLC52A3 genes, both of which encode riboflavin transporters. Importantly, supplementation of riboflavin can lead to significant clinical improvement if started early in the disease process. Here, we outline the clinical features, management and an update on the disease mechanisms and genetic causes of the progressive bulbar syndromes.

HIV RELATED ADMISSIONS IN A PSYCHIATRIC HOSPITAL A FIVE YEAR PROFILE

PubMed Central

Chandra, P.S.; Krishna, V.A.S.; Ravi, V.; Desai, A.; Puttaram, S.

1999-01-01

Recent reports have indicated an increasing prevalence of HIV infection in the mentally ill. Reports have also emphasised the etiological role of HIV infection in psychiatric illness. The aim of this study was to assess the clinical and risk profile of psychiatric inpatients found seropositive for HIV infection. All psychiatric inpatients from a psychiatric hospital who tested positive for HI V infection over a five year period were assessed. The assessments included a detailed clinical history, psychiatric assessment and risk behaviour evaluation. Of the 2283 psychiatric patients tested, 51 were found to be seropositive. 43 patients were included in the study. 30 (69.7%) had a diagnosis of alcohol dependence, of which, 11 patients had comorbid psychiatnc diagnosis in the form of affective disorders (23%) and psychosis (14%). Personality disorders were seen in 9 patients. In 19% the clinical manifestation was considered to be etiologically related to HIV infection. The predominant risk behaviour was in the form of multiple partner heterosexual contacts. In several patients the risk behaviour had occurred during an episode of mental illness or under the influence of alcohol. The study demonstrates the importance of detecting and describing HIV infection and its manifestation among psychiatric patients. PMID:21430804

Factor structure and clinical correlates of the 61-item Wender Utah Rating Scale (WURS).

PubMed

Calamia, Matthew; Hill, Benjamin D; Musso, Mandi W; Pella, Russell D; Gouvier, Wm Drew

2018-02-09

The objective of this study was to assess the factor structure and clinical correlates of a 61-item version of the Wender Utah Rating Scale (WURS), a self-report retrospective measure of childhood problems, experiences, and behavior used in ADHD assessment. Given the currently mostly widely used form of the WURS was derived via a criterion-keyed approach, the study aimed to use latent variable modeling of the 61-item WURS to potentially identify more and more homogeneous set of items reflecting current conceptualizations of ADHD symptoms. Exploratory structural equation modeling was used to generate factor scores which were then correlated with neuropsychological measures of intelligence and executive attention as well as a broad measure of personality and emotional functioning. Support for a modified five-factor model was found: ADHD, disruptive mood and behavior, negative affectivity, social confidence, and academic problems. The ADHD factor differed somewhat from the traditional 25-item WURS short form largely through weaker associations with several measures of personality and psychopathology. This study identified a factor more aligned with DSM-5 conceptualization of ADHD as well as measures of other types of childhood characteristics and symptoms which may prove useful for both research and clinical practice.

An homozygous mutation in KCNK3 is associated with an aggressive form of hereditary pulmonary arterial hypertension.

PubMed

Navas Tejedor, P; Tenorio Castaño, J; Palomino Doza, J; Arias Lajara, P; Gordo Trujillo, G; López Meseguer, M; Román Broto, A; Lapunzina Abadía, P; Escribano Subía, P

2017-03-01

Pulmonary arterial hypertension (PAH) is a rare devastating disease characterized by a high genetic heterogeneity with several related genes recently described, including BMPR2,TBX4 and KCNK3. The association between KCNK3 and PAH has been recently identified, but the prognosis and phenotype associated with these mutations have been poorly described. We studied a series of 136 idiopathic and hereditary PAH Spanish patients for BMPR2, TBX4 and KCNK3 mutations. We report the results of KCNK3 in which we were able to describe two new mutations (p.Gly106Arg and p.Leu214Arg) in three patients. The first one was found in a patient belonging to a consanguineous Romani family, who carried a homozygous mutation in KCNK3 and developed a severe and early form of the disease. To the best of our knowledge, this is the first time that a homozygous mutation in KCNK3 is reported in a PAH patient. The second one was found in a patient who presented at the young adult age a severe form of the disease. The present report supports the contribution of KCNK3 mutations to the genetic etiology of PAH and strongly suggests that mutations in KCNK3 follow incomplete dominance with worsening of the clinical features in homozygous patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Severe nutritional rickets in young children: Resurgence of an old disease].

PubMed

Estrade, S; Majorel, C; Tahhan, N; Dulac, Y; Baunin, C; Gennero, I; Chaix, Y; Salles, J-P; Edouard, T

2017-08-01

Nutritional rickets remains a significant public health issue for children worldwide. Although it has almost disappeared in industrialized countries following routine vitamin D supplementation, recent evidence suggests an increasing incidence, especially in young children. In addition to the classical clinical consequences on bone and the growth plate, rickets may also be associated with life-threatening neurological and cardiac complications in the most severe forms. Consequently, early screening and treatment are required. Here, we report the case of a 2-year-old child who presented with severe nutritional rickets associated with seizure and cardiomyopathy. Family screening revealed rickets in all the siblings. This case report emphasizes the importance of being aware of this disease, notably in population with sociocultural risk factors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A novel mutation in the EDAR gene causes severe autosomal recessive hypohidrotic ectodermal dysplasia.

PubMed

Henningsen, Emil; Svendsen, Mathias Tiedemann; Lildballe, Dorte Launholt; Jensen, Peter Kjestrup Axel

2014-08-01

We report on a 2-year-old girl presenting with a severe form of hypohidrotic ectodermal dysplasia (HED). The patient presented with hypotrichosis, anodontia, hypohidrosis, frontal bossing, prominent lips and ears, dry, pale skin, and dermatitis. The patient had chronic rhinitis with malodorous nasal discharge. The girl was the second born child of first-cousin immigrants from Northern Iraq. A novel homozygous mutation (c.84delC) in the EDAR gene was identified. This mutation most likely causes a frameshift in the protein product (p.S29fs*74). This results in abolition of all ectodysplasin-mediated NF-kB signalling. This complete loss-of-function mutation likely accounts for the severe clinical abnormalities in ectodermal structures in the described patient. © 2014 Wiley Periodicals, Inc.

Haemolytic disease of the fetus and newborn.

PubMed

de Haas, M; Thurik, F F; Koelewijn, J M; van der Schoot, C E

2015-08-01

Haemolytic Disease of the Fetus and Newborn (HDFN) is caused by maternal alloimmunization against red blood cell antigens. In severe cases, HDFN may lead to fetal anaemia with a risk for fetal death and to severe forms of neonatal hyperbilirubinaemia with a risk for kernicterus. Most severe cases are caused by anti-D, despite the introduction of antental and postnatal anti-D immunoglobulin prophylaxis. In general, red blood cell antibody screening programmes are aimed to detect maternal alloimmunization early in pregnancy to facilitate the identification of high-risk cases to timely start antenatal and postnatal treatment. In this review, an overview of the clinical relevance of red cell alloantibodies in relation to occurrence of HDFN and recent views on prevention, screening and treatment options of HDFN are provided. © 2015 International Society of Blood Transfusion.

Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition.

PubMed

Di Giovanni, Valeria; Bourdon, Celine; Wang, Dominic X; Seshadri, Swapna; Senga, Edward; Versloot, Christian J; Voskuijl, Wieger; Semba, Richard D; Trehan, Indi; Moaddel, Ruin; Ordiz, M Isabel; Zhang, Ling; Parkinson, John; Manary, Mark J; Bandsma, Robert Hj

2016-12-01

Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. We studied children aged 9-59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953. © 2016 American Society for Nutrition.

Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition123

PubMed Central

Di Giovanni, Valeria; Wang, Dominic X; Seshadri, Swapna; Senga, Edward; Versloot, Christian J; Semba, Richard D; Moaddel, Ruin; Ordiz, M Isabel; Zhang, Ling; Parkinson, John; Manary, Mark J; Bandsma, Robert HJ

2016-01-01

Background: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. Objectives: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. Methods: We studied children aged 9–59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. Results: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. Conclusions: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953. PMID:27807038

Premenstrual syndrome, premenstrual dysphoric disorder, and beyond: a clinical primer for practitioners.

PubMed

Johnson, Susan R

2004-10-01

The management of adverse premenstrual symptoms has presented a difficult challenge for clinicians. However, based on numerous well-designed research studies over the last decade, we now have diagnostic criteria for the severe form of the syndrome, premenstrual dysphoric disorder, and a variety of evidence-based therapeutic strategies. This review presents a comprehensive, practical description of what the clinician needs to know to diagnose and treat adverse premenstrual symptoms at all levels of severity. Diagnostic criteria are described in detail, including a discussion of the distinction between premenstrual dysphoric disorder and premenstrual syndrome (PMS). The rationale for including prospective symptom calendars as a routine part of the diagnostic evaluation of severe symptoms is presented. The differential diagnosis of cyclic symptoms, including depression and anxiety disorders, menstrual migraine, and mastalgia, and an approach for the management of each of these problems are presented. A treatment approach is recommended that matches the treatment to the degree of problems the woman is experiencing. Serotonin reuptake inhibitors are the treatment of choice for severe symptoms, and most women with PMS/premenstrual dysphoric disorder will respond to intermittent, luteal phase-only therapy. Ovulation suppression should be reserved for women who do not respond to other forms of therapy. The role of oophorectomy is limited, and guidelines for its use are presented.

Natural history of the classical form of primary growth hormone (GH) resistance (Laron syndrome).

PubMed

Laron, Z

1999-04-01

A description of the clinical, biochemical and endocrinological features of the classical form of the syndrome of primary growth hormone (GH) resistance (Laron syndrome) is presented including the progressive changes during follow-up from infancy into adulthood. The main diagnostic features are: severe growth retardation, acromicria, small gonads and genitalia, and obesity. Serum GH levels are elevated and insulin-like growth factor-I (IGF-I) values are low and do not rise upon stimulation by exogenous hGH. The pathogenesis of this syndrome is due to various molecular defects from exon deletion to nonsense, frameshift, splice and missense mutations in the GH receptor (GH-R) gene or in its post-receptor pathways.

[CLINICAL AND LABORATORY FEATURES OF ACUTE PANCREATITIS BILIARY ETIOLOGY COURSE IN PATIENTS WITH DIABETES MELLITUS].

PubMed

Godlevskiy, A I; Savolyuk, S I; Tomashevskiy, Ya V

2015-07-01

The dynamics of cytopathic hypoxia markers in patients with acute pancreatitis (AP) biliary etiology (BE), depending on the presence of concomitant diabetes mellitus (DM), which is an independent factor of premorbid severity increase and increase in the degree of operational and anesthetic risk. Markers of cytopathic hypoxia use as methods for early diagnosis of acute liver failure (ALF) and monitoring the effectiveness of its correction promising. In terms of cytopathic hypoxia may be at the stage of laboratory diagnostics to distinguish between destructive and non-destructive forms APBE, and for markers of endothelial dysfunction--destructive forms on the area and depth of destruction of the pancreas.

Spectrophotometric estimation of ambroxol and cetirizine hydrochloride from tablet dosage form.

PubMed

Gowekar, N M; Pande, V V; Kasture, A V; Tekade, A R; Chandorkar, J G

2007-07-01

Fixed dose combination tablets containing ambroxol HCl and cetirizine HCl are clinically used as mucolytic and antiallergic. Several spectrophotometric and HPLC methods have been reported for simultaneous estimation of these drugs with other drugs. The drugs individually and in mixture obeys Beer's law over conc. range 1.2-4.4 microg/mL for cetirizine HCL and for ambroxol HCL 15-52 microg/mL at all five sampling wavelengths (correlation coeff. well above 0.995). The mean recoveries from tablet by standard addition method were 100.18% (+/-2.4) and 100.66 % (+/-2.31). The present work reports simple, accurate and precise spectrophotometric methods for their simultaneous estimation from tablet dosage form.

Health perceptions and clinical characteristics of relapsing-remitting multiple sclerosis patients: baseline data from an international clinical trial.

PubMed

Robinson, D; Zhao, N; Gathany, T; Kim, L-L; Cella, D; Revicki, D

2009-05-01

Baseline clinical and health-related quality of life (HRQoL) data from a phase 2, multi-site, international, randomized, controlled trial were analyzed to: (1) characterize the health status of patients with relapsing-remitting multiple sclerosis (RRMS), (2) explore cross-sectional relationships between HRQoL and clinical measures, and (3) evaluate differences in HRQoL scores for subsequent validation as minimally important differences (MID). www.clinicaltrials.gov, NCT00207727. Baseline clinical and HRQoL data were selected and analyzed. HRQoL questionnaires included the Short Form-36 (SF-36), Fatigue Severity Scale (FSS), a Patient Assessment of multiple sclerosis (MS) Impact (PAMSI), and MS-specific symptom scales for Bladder and Bowel Control, Cognition, and Sexual Satisfaction. Standard summary statistics described the population while Pearson and Spearman correlations evaluated the baseline association between HRQoL and clinical measures. Cross-sectional estimates of MID in HRQoL scores were derived using several clinical anchors, the PAMSI, and two tests: Tukey multiple comparisons and adjacent mean difference. Patients (n = 249) had a mean age of 39.0 (Standard deviation, SD = 10.5), 70% were female, 63% resided in Europe, and 96% were Caucasian. Baseline median Expanded Disability Severity Scale (EDSS) was 2.5 (range = 0.0-6.5); median disease duration was 1.9 years (range = 0.1-33.6). The worst baseline mean (normalized) SF-36 scores were for General Health (39.9), Role Physical (40.4), Physical Functioning (41.0), and Vitality (42.7). The worst MS symptom mean scores were for Cognition (6.3) and FSS (4.4). Fatigue scores indicated substantial burden and were consistent with SF-36 Vitality results. Baseline HRQoL scores (SF-36, FSS, MS symptom scales) correlated most with EDSS, Multiple Sclerosis Functional Composite (MSFC), age and disease duration. Lesion count and pre-baseline relapse rate had no meaningful association with HRQoL or other clinical measures. The MID for several HRQoL measures are proposed for confirmation in longitudinal patient datasets. Clinical and HRQoL assessments documented health impairments in physical functioning, fatigue, and cognition among these RRMS patients with relatively short disease duration. HRQoL data varied with clinical measures and contributed new information regarding disease burden. The association between clinical and HRQoL measures was limited to cross-sectional analysis and requires confirmation in longitudinal datasets. These findings reflect an ambulatory, early-stage RRMS population that was mostly European in location or descent. The PAMSI also requires further validation as a measure of patient health status.

A neurologist's reflections on boxing. V. Conclude remarks.

PubMed

Unterharnscheidt, F

1995-01-01

Clinical and morphological publications have shown convincingly, that participation in boxing leads to a severe permanent brain damage. The extent of the brain damage is correlated to the number of bouts fought, which correspondents in a certain way how many blows against his head a boxer received and to his weight class. The intensity of a boxing blow of a heavyweight is much more severe than those achieved by boxers of lighter weight classes. The permanent brain damage in a boxer, the amateur and the professional boxer, manifests itself in several clinical syndromes in which the pyramidal, the extrapyramidal and the cerebellar systems are involved. A traumatic Parkinsonism, in its complete or abortive form, develops as the result of the numerous boxing blows a boxer sustains in his boxing career. Especially lateral parts of the substantia nigra are affected and reveal at macroscopical and microscopical examination a severe loss of pigmented neurons. Melanin pigment is visible free in the tissue and/or is phagozytosed in macrophages and glial cells. The traumatic Parkinson syndrome, often only in an abortive form, is combined in a boxer with additional clinical and morphological findings due to traumatic lesions in other areas of the brain. It is not as pure as in a patient with a Parkinson syndrome sui generis. The permanent brain damage in a boxer is diffuse, involving all areas of the brain. Especially involved are the large neurons of different layers of the cerebral cortex, the neurons of the Ammons horn formation, the Purkinje cells of the cerebellum. In place of destroyed and lost neurons, proliferation of glial elements, especially astroglial cells, has occurred. The defects are first replaced by protoplasmatic astroglial elements, and later by fibrillary astroglia. The destroyed neurons are replaced by glial scar tissue, which cannot perform the functions of the lost neurons. It is a process which is called partial necrosis of brain tissue. There is no reparation or restitution of the destroyed neural tissue of the brain. What is destroyed remains so, a restitution ad integrum does not occur. As the result of the diffuse loss of neurons in the brain a cerebral atrophy exists. The septum pellucidum, which consists of two thin lamellae, and is small or very small in a normal brain, forms a Cavum septi pellucidi, which is considerably enlarged. The walls of this structure, especially in its dorsal parts are considerably thinned; they show fenestrations and are, in dorsal parts no longer detectable, so that a direct connection between the two lateral ventricles exists. The clinically and morphologically existing permanent brain damage is the result of the boxing activity. Diagnostically, processes of another origin, such as alcoholism, luetic processes, other forms of dementia, etc. can undoubtedly be excluded. A permanent brain damage develops in professional and amateur boxers. The objection, which are voiced by members of the different Amateur Boxing Association, that such permanent brain damage in amateur boxers today no longer exists, after stricter protective measurements were introduced, is not tenable. Individuals who represent today the opinion, that a permanent brain damage or punch drunkenness in boxers does not occur, are not familiar with the pertinent medical literature. The argument, the injury quotient in boxing is lower than in all other athletic activities is not sound, since the statistics show only the inconsequential injuries of boxers, as lesions of the skin of the face, injuries of the hand, fractures, etc. but not the much more important and severe permanent brain damage, which is not taken into consideration in these so-called statistics. Besides of the permanent brain damage of former boxers as the result of the repeated and numerous blows against their head, severe permanent damage of the eyes and the hearing organ exists.

Pathways, Contributors, and Correlates of Functional Limitation across Specialties: Workshop Summary.

PubMed

Kritchevsky, Stephen B; Forman, Daniel E; Callahan, Kathryn; Ely, E Wesley; High, Kevin P; McFarland, Frances; Pérez-Stable, Eliseo J; Schmader, Kenneth; Studenski, Stephanie; Williams, John; Zieman, Susan; Guralnik, Jack M

2018-04-25

Traditional clinical care models focus on the measurement and normalization of individual organ systems and de-emphasize aspects of health related to the integration of physiologic systems. Measures of physical, cognitive and sensory, and psychosocial or emotional function predict important health outcomes like death and disability independently from the severity of a specific disease, cumulative co-morbidity, or disease severity measures. A growing number of clinical scientists in several subspecialties are exploring the utility of functional assessment to predict complication risk, indicate stress resistance, inform disease screening approaches and risk factor interpretation, and evaluate care. Because a substantial number of older adults in the community have some form of functional limitation, integrating functional assessment into clinical medicine could have a large impact. Although interest in functional implications for health and disease management is growing, the science underlying functional capacity, functional limitation, physical frailty, and functional metrics is often siloed among different clinicians and researchers, with fragmented concepts and methods. On August 25-26, 2016, participants at a trans-disciplinary workshop, supported by the National Institute on Aging and the John A. Hartford Foundation, explored what is known about the pathways, contributors, and correlates of physical, cognitive and sensory functional measures across conditions and disease states; considered social determinants and health disparities; identified knowledge gaps, and suggested priorities for future research. This paper summarizes those discussions.

Evaluation of oral tilmicosin efficacy against severe cryptosporidiosis in neonatal kids under field conditions.

PubMed

Paraud, C; Pors, I; Chartier, C

2010-05-28

Many compounds have been screened for their potential anti-cryptosporidial activity in ruminants but none of them has been totally efficient in controlling the disease. Macrolide antibiotics have demonstrated some activity against Cryptosporidium spp. in humans. Tilmicosin is a macrolide antibiotic, available in France in an oral form (Pulmotil AC, Lilly France). The preventive efficacy of tilmicosin was evaluated in a goat farm experiencing severe clinical cryptosporidiosis in kids. Twenty-two kids were separated from their dams just after birth and placed in a separated pen. They were divided into 3 groups: an untreated group (10 kids), group 1 (6 kids) receiving tilmicosin at 25mg/kg BW/day and group 2 (6 kids) receiving tilmicosin at 50mg/kg BW/day. Tilmicosin was individually given by oral route from day 2 of age for 10 days. Three times a week, individual faecal samples were performed to assess the oocyst output. Clinical data, i.e. diarrhea and mortality, were recorded. In control kids, the highest prevalence and intensity of excretion were observed between day 6 and day 16 of age and mortality reached 90%. Excretion dynamic and clinical consequences were similar in both treated kid groups. Finally, tilmicosin did not demonstrate any activity against severe kid cryptosporidiosis in field conditions. (c) 2010 Elsevier B.V. All rights reserved.

Antibiotic-Associated Apoptotic Enterocolitis in the Absence of a Defined Pathogen: The Role of Intestinal Microbiota Depletion*

PubMed Central

Wurm, Philipp; Spindelboeck, Walter; Krause, Robert; Plank, Johannes; Fuchs, Gottfried; Bashir, Mina; Petritsch, Wolfgang; Halwachs, Bettina; Langner, Cord; Högenauer, Christoph

2017-01-01

Objective: Antibiotic therapy is a major risk factor for the development of diarrhea and colitis with varying severity. Often the origin of antibiotic-associated gastrointestinal deterioration remains elusive and no specific infectious agents could be discerned. Patients: We represent three cases of intractable high-volume diarrhea associated with combined antibiotic and steroid therapy in critically ill patients not fitting into established disease entities. Cases presented with severe apoptotic enterocolitis resembling acute intestinal graft-versus-host-disease. Microbiologic workup precluded known enteropathogens, but microbiota analysis revealed a severely depleted gut microbiota with concomitant opportunistic pathogen overgrowth. Interventions: Fecal microbiota transplantation, performed in one patient, was associated with correction of dysbiosis, rapid clinical improvement, and healing of enterocolitis. Conclusions: Our series represents a severe form of antibiotic-associated colitis in critically ill patients signified by microbiota depletion, and reestablishment of a physiologic gastrointestinal microbiota might be beneficial for this condition. PMID:28333760

[Combined forecasting system of peritonitis outcome].

PubMed

Lebedev, N V; Klimov, A E; Agrba, S B; Gaidukevich, E K

To create a reliable system for assessing of severity and prediction of the outcome of peritonitis. Critical analysis of the systems for peritonitis severity assessment is presented. The study included outcomes of 347 patients who admitted at the Department of Faculty Surgery of Peoples' Friendship University of Russia in 2015-2016. The cause of peritonitis were destructive forms of acute appendicitis, cholecystitis, perforated gastroduodenal ulcer, various perforation of small and large intestines (including tumor). Combined forecasting system for peritonitis severity assessment is created. The system includes clinical, laboratory data, assessment of systemic inflammatory response (SIRS) and severity of organ failure (qSOFA). The authors focused on easily identifiable parameters which are available in virtually any surgical hospital. Threshold value (lethal outcome probability over 50%) is 8 scores in this system. Sensitivity, specificity and accuracy were 93.3, 99.7 and 98.9%, respectively according to ROC-curve that exceeds those parameters of MPI and APACHE II.

Investigating Mechanisms of Chronic Kidney Disease in Mouse Models

PubMed Central

Eddy, Allison A.; Okamura, Daryl M.; Yamaguchi, Ikuyo; López-Guisa, Jesús M.

2011-01-01

Animal models of chronic kidney disease (CKD) are important experimental tools that are used to investigate novel mechanistic pathways and to validate potential new therapeutic interventions prior to pre-clinical testing in humans. Over the past several years, mouse CKD models have been extensively used for these purposes. Despite significant limitations, the model of unilateral ureteral obstruction (UUO) has essentially become the high throughput in vivo model, as it recapitulates the fundamental pathogenetic mechanisms that typify all forms of CKD in a relatively short time span. In addition, several alternative mouse models are available that can be used to validate new mechanistic paradigms and/or novel therapies. Several models are reviewed – both genetic and experimentally induced – that provide investigators with an opportunity to include renal functional study end-points together with quantitative measures of fibrosis severity, something that is not possible with the UUO model. PMID:21695449

Laparoscopic cholecystectomy in a patient with Steinert myotonic dystrophy. Case report.

PubMed

Agrusa, A; Mularo, S; Alessi, R; Di Paola, P; Mularo, A; Amato, G; Romano, G

2011-01-01

Myotonic dystrophy (MD) is a serious multi-systemic autosomal dominant disease. The estimated incidence is 1 in every 8000 births, with an estimated prevalence of between 2.1 and 14.3 cases per 100,000 inhabitants. Signs and symptoms vary from a severe form of congenital myopathy, present from birth and often fatal, to a classic form and a delayed form, which generally presents after the age of 50 and in which the only sign is a cataract and life expectancy is completely normal. We describe the clinical case of a 40-year-old woman with Steinert myotonic dystrophy who underwent laparoscopic cholecystectomy (under general anesthesia) for symptomatic gallbladder stones. The conduct of anesthesia in such patients must be carefully considered, as hypothermia, shivering, electrical and mechanical stimulation, and the drugs used can all trigger myotonia.

Integration of a Zero-footprint Cloud-based Picture Archiving and Communication System with Customizable Forms for Radiology Research and Education.

PubMed

Hostetter, Jason; Khanna, Nishanth; Mandell, Jacob C

2018-06-01

The purpose of this study was to integrate web-based forms with a zero-footprint cloud-based Picture Archiving and Communication Systems (PACS) to create a tool of potential benefit to radiology research and education. Web-based forms were created with a front-end and back-end architecture utilizing common programming languages including Vue.js, Node.js and MongoDB, and integrated into an existing zero-footprint cloud-based PACS. The web-based forms application can be accessed in any modern internet browser on desktop or mobile devices and allows the creation of customizable forms consisting of a variety of questions types. Each form can be linked to an individual DICOM examination or a collection of DICOM examinations. Several uses are demonstrated through a series of case studies, including implementation of a research platform for multi-reader multi-case (MRMC) studies and other imaging research, and creation of an online Objective Structure Clinical Examination (OSCE) and an educational case file. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Strongyloides stercoralis hyperinfection associated with impaired intestinal motility disorder

PubMed Central

Figueira, Cláudia Frangioia; Cos, Lynda Dorene; Ussami, Edson Yassushi; Otoch, José Pinhata; Felipe-Silva, Aloisio

2015-01-01

Infection by Strongyloides stercoralis is a highly prevalent helminthiasis, which is mostly distributed in the tropical and subtropical regions of the world. Although a substantial number of cases are asymptomatic or paucisymtomatic, severe and life-threatening forms of this infection still occur and not infrequently is lately diagnosed. Gram-negative bacteria septicemia, which frequently accompanies the severe helminthiasis, contributes to the high mortality rate. Severe infection is invariably triggered by any imbalance in the host's immunity, favoring the auto-infective cycle, which increases the intraluminal parasite burden enormously. Clinical presentation of severe cases is varied, and diagnosis requires a high suspicion index. Acute abdomen has been reported in association with S. stercoralis infection, but intestinal necrosis is rarely found during the surgical approach. The authors report the case of a man who sought the emergency unit with recent onset abdominal pain. Clinical and imaging features were consistent with obstructive acute abdomen. Scattered adhesions and a necrotic ileal segment with a tiny perforation represented the surgical findings. The patient outcome was unfavorable and respiratory distress required an open lung biopsy. Both surgical specimens showed S. stercoralis infection. Unfortunately the patient underwent multiple organ failure and septicemia, and subsequently died. The authors call attention to the finding of intestinal necrosis and impaired intestinal motility disorder as possibilities for the diagnosis and risk factor, respectively, for a severe infection of S. stercoralis. PMID:26484331

SFE/SFHTA/AFCE consensus on primary aldosteronism, part 5: Genetic diagnosis of primary aldosteronism.

PubMed

Zennaro, Maria-Christina; Jeunemaitre, Xavier

2016-07-01

While the majority of cases of primary aldosteronism (PA) are sporadic, four forms of autosomal-dominant inheritance have been described: familial hyperaldosteronism (FH) types I to IV. FH-I, also called glucocorticoid-remediable aldosteronism, is characterized by early and severe hypertension, usually before the age of 20 years. It is due to the formation of a chimeric gene between the adjacent CYP11B2 and CYP11B1 genes (coding for aldosterone synthase and 11β-hydroxylase, respectively). FH-I is often associated with family history of stroke before 40years of age. FH-II is clinically and biochemically indistinguishable from sporadic forms of PA and is only diagnosed on the basis of two or more affected family members. No causal genes have been identified so far and no genetic test is available. FH-III is characterized by severe and early-onset hypertension in children and young adults, resistant to treatment and associated with severe hypokalemia. Mild forms, resembling FH-II, have been described. FH-III is due to gain-of-function mutations in the KCNJ5 gene. Recently, a new autosomal-dominant form of familial PA, FH-IV, associated with mutations in the CACNA1H gene, was described in patients with hypertension and PA before the age of 10years. In rare cases, PA may be associated with complex neurologic disorder involving epileptic seizures and cerebral palsy (Primary Aldosteronism, Seizures, and Neurologic Abnormalities [PASNA]) due to de novo germline CACNA1D mutations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Perinatal depression and affective bonds: experience in close relationship during pregnancy].

PubMed

Aceti, Franca; Giacchetti, Nicoletta; Meuti, Valentina; Carluccio, Giuseppe Mattia; Zaccagni, Michela; Marini, Isabella; Di Lorenzo, Flavia; Grillo, Alessandra; Mancini, Guido; Serio, Valentina; Rocchi, Giordana; Giancola, Orazio; Biondi, Massimo

2015-01-01

This study aims to investigate the influence of the "romantic attachment" style, stressful life events, social factors on the risk of developing a depression during pregnancy and on the severity of depressive symptoms. The study started with a screening on a sample of 453 women, during their third trimester of pregnancy, to which has been administered a survey data form, the Edinburgh Postnatal Depression Scale (EPDS) and the Experience in Close Relationship (ECR). Based on the results at EPDS, a clinical group of pre-natal depression (D=89) was selected and compared with a control group (C=89), in regards to psychopathological and social variables, exposure to stressful life events and attachment patterns. Analysis of correlation were performed to evaluate the influence of these factors on depressive symptoms severity. In D group, 52.8% of subjects reported previous psychiatric disorders and 49.4% a familiarity; 29.2% of these women complains of conflicts with their family of origin and 32.6% with partner. The ECR showed a prevalence of "fearful-avoidant" attachment style in clinical group (29.2% vs 1.1%, p=0.000); besides, ECR dimensions ("Avoidance", "Anxiety"), correlate with the severity of depressive symptoms. Positive family history for psychiatric disorders and an insecure romantic attachment might influence the development and the severity of perinatal depression.

Distinct intestinal adaptation for vitamin B12 and bile acid absorption revealed in a new mouse model of massive ileocecal resection.

PubMed

Matsumoto, Yuka; Mochizuki, Wakana; Akiyama, Shintaro; Matsumoto, Taichi; Nozaki, Kengo; Watanabe, Mamoru; Nakamura, Tetsuya

2017-09-15

Ileocecal resection (ICR), one of several types of intestinal resection that results in short bowel syndrome (SBS), causes severe clinical disease in humans. We here describe a mouse model of massive ICR in which 75% of the distal small intestine is removed. We demonstrate that mice underwent 75% ICR show severe clinical signs and high mortality, which may recapitulate severe forms of human SBS, despite an adaptive response throughout the remnant intestine. By using this model, we also investigated whether the epithelium of the remnant intestine shows enhanced expression of factors involved in region-specific functions of the ileum. Cubn mRNA and its protein product, which play an essential role in vitamin B12 absorption in the ileum, are not compensatory up-regulated in any part of the remnant intestine, demonstrating a clear contrast with post-operative up-regulation of genes involved in bile acid absorption. Our study suggests that functional adaptation by phenotypical changes in the intestinal epithelium is not a general feature for nutrient absorption systems that are confined to the ileum. We also propose that the mouse model developed in this study will become a unique system to facilitate studies on SBS with ICR in humans. © 2017. Published by The Company of Biologists Ltd.

Update on signal inhibitors in chronic lymphocytic leukemia.

PubMed

Boddu, Prajwal; Jain, Nitin

2018-04-01

The last decade has seen major progress in our understanding of the pathobiology of chronic lymphocytic leukemia (CLL) and the identification of potential new therapeutic targets. As a result, researchers have developed novel targeted therapies, several of which are already approved and many of which are in advanced stages of clinical development. These new agents are much less toxic than chemoimmunotherapy and may be preferred for their superior efficacy in patients with certain high-risk features, such as del(17p). The place of these therapies in CLL management is becoming better defined, and they are gradually replacing traditional forms of chemoimmunotherapy. This review provides an update on the clinical data regarding various signal transduction inhibitors in CLL.

Immediate and long-term efficacy and safety of photodynamic therapy with Photolon (Fotolon): a seven-year clinical experience

NASA Astrophysics Data System (ADS)

Istomin, Yuri P.; Kaplan, Michael A.; Shliakhtsin, Siarhei V.; Lapzevich, Tatsiana P.; Cerkovsky, Dmitriy A.; Marchanka, Ludmila N.; Fedulov, Alexander S.; Trukhachova, Tatsiana V.

2009-06-01

The purpose of the present study was to summarize data on the long-term efficacy of photodynamic therapy (PDT) with Photolon in patients with malignant tumors of various types and localizations. The data obtained show that PDT with Photolon is a highly effective therapeutic modality for the treatment of skin tumors, cervical intraepithelial neoplasias, lung cancers, disseminated forms of melanoma, primary and metastatic brain tumors, several ophthalmologic diseases. This paper provides a review of most illustrative studies of the application of PDT with Photolon for the treatment of different oncological and non-oncological diseases performed in leading clinical centers of the Republic of Belarus and Russia.

Summary of third Nordic symposium on digital pathology.

PubMed

Lundström, Claes; Waltersson, Marie; Persson, Anders; Treanor, Darren

2016-01-01

Cross-disciplinary and cross-sectorial collaboration is a key success factor for turning the promise of digital pathology into actual clinical benefits. The Nordic symposium on digital pathology (NDP) was created to promote knowledge exchange in this area, among stakeholders in health care, industry, and academia. This article is a summary of the third NDP symposium in Linkφping, Sweden. The Nordic experiences, including several hospitals using whole-slide imaging for substantial parts of their primary reviews, formed a fertile base for discussions among the 190 NDP attendees originating from 15 different countries. This summary also contains results from a survey on adoption and validation aspects of clinical digital pathology use.

Summary of third Nordic symposium on digital pathology

PubMed Central

Lundström, Claes; Waltersson, Marie; Persson, Anders; Treanor, Darren

2016-01-01

Cross-disciplinary and cross-sectorial collaboration is a key success factor for turning the promise of digital pathology into actual clinical benefits. The Nordic symposium on digital pathology (NDP) was created to promote knowledge exchange in this area, among stakeholders in health care, industry, and academia. This article is a summary of the third NDP symposium in Linkφping, Sweden. The Nordic experiences, including several hospitals using whole-slide imaging for substantial parts of their primary reviews, formed a fertile base for discussions among the 190 NDP attendees originating from 15 different countries. This summary also contains results from a survey on adoption and validation aspects of clinical digital pathology use. PMID:27141318

Some business and tax aspects of clinical practice plans.

PubMed

Mancino, D

1978-10-01

Medical schools throughout the country have developed diverse organizational forms through which their faculty members provide clinical services. In this article the author reviews several of the reasons frequently offered to support involvement of a medical school in a faculty practice plan and suggests many business and tax considerations which should be taken into account by a medical school in developing a plan to meet its objectives. He also reviews many of the considerations involved in establishing and operating specific types of group practice plans. The author concludes that, with conscientious planning and implementation, faculty members can receive professional satisfaction, medical schools can obtain many benefits, and the public will benefit from improved health care.

Pulmonary aspergillosis in patients with AIDS. Clinical and radiographic correlations.

PubMed

Miller, W T; Sais, G J; Frank, I; Gefter, W B; Aronchick, J M; Miller, W T

1994-01-01

To evaluate the clinical and radiographic features of pulmonary aspergillosis as they present in AIDS patients; in particular, to determine similarities and differences between Aspergillus infection in patients with AIDS vs those without AIDS. Six new cases of confirmed or probable pulmonary aspergillosis were discovered during a search of hospital records. These are reviewed with 30 previously reported cases with special attention to radiographic appearance of disease and how radiographic appearance influences clinical outcome. Symptoms of pulmonary aspergillosis in AIDS were nonspecific, most often including fever, cough, and dyspnea, and less commonly, chest pain or hemoptysis. Major risk factors for the development of pulmonary aspergillosis in patients with AIDS were steroid administration and neutropenia. Neutropenia was often a complication of therapies for AIDS, in particular, ganciclovir and zidovudine. Radiographic appearance of disease could be divided into three general categories. One third of the patients (13/36) presented with cavitary upper lobe disease resembling noninvasive or chronic necrotizing aspergillosis. Fatal hemoptysis occurred in 42 percent of patients with this form of disease. Twenty-two percent (8/36) of the cases presented as a nondescript focal alveolar opacity similar to invasive aspergillosis. In several patients, the focal infiltrate remained stable for several months, a feature that is unusual for aspergillosis in non-AIDS patients. The air crescent sign was present in none of the 36 reported cases. Patients with only focal disease had the best prognosis of patients with pulmonary aspergillosis. Bilateral alveolar or interstitial disease similar to invasive aspergillosis was present in 23 percent (9/36) of the patients. Bilateral disease appears to be a marker for disseminated infection and was associated with a high mortality due to aspergillosis. Two new forms of bronchial aspergillosis (5/36 cases) have been described previously. These patients presented with either obstructing fungal casts or bronchial pseudomembranes demonstrated bronchoscopically. In some patients with the bronchial forms of aspergillosis, transient alveolar opacities were seen on chest radiographs. These opacities may represent regions of atelectasis due to airway obstruction. One patient who had bilateral pneumothoraces without parenchymal opacities did not correspond to any of the three previously mentioned categories. Mortality due to aspergillosis was greater than 50 percent among AIDS patients. Death was subsequent to fatal hemoptysis or widespread pulmonary or systemic infection. Unlike other risk groups that tend to contract only one form of pulmonary aspergillosis, AIDS patients can develop the whole spectrum of aspergillosis-related pulmonary disorders, including chronic cavitary, invasive, and bronchial forms of aspergillosis. Clinical symptoms are nonspecific and major risk factors include neutropenia, which is often a side effect of various therapies for AIDS, and steroid administration. Patients with the chronic cavitary form of disease have an unusually high mortality due to fatal hemoptysis. Patients with bilateral pulmonary infiltrates and aspergillosis have a high mortality due to disseminated infection.

Hashimoto thyroiditis: clinical and diagnostic criteria.

PubMed

Caturegli, P; De Remigis, A; Rose, N R

2014-01-01

Hashimoto thyroiditis (HT), now considered the most common autoimmune disease, was described over a century ago as a pronounced lymphoid goiter affecting predominantly women. In addition to this classic form, several other clinico-pathologic entities are now included under the term HT: fibrous variant, IgG4-related variant, juvenile form, Hashitoxicosis, and painless thyroiditis (sporadic or post-partum). All forms are characterized pathologically by the infiltration of hematopoietic mononuclear cells, mainly lymphocytes, in the interstitium among the thyroid follicles, although specific features can be recognized in each variant. Thyroid cells undergo atrophy or transform into a bolder type of follicular cell rich in mitochondria called Hürthle cell. Most HT forms ultimately evolve into hypothyroidism, although at presentation patients can be euthyroid or even hyperthyroid. The diagnosis of HT relies on the demonstration of circulating antibodies to thyroid antigens (mainly thyroperoxidase and thyroglobulin) and reduced echogenicity on thyroid sonogram in a patient with proper clinical features. The treatment remains symptomatic and based on the administration of synthetic thyroid hormones to correct the hypothyroidism as needed. Surgery is performed when the goiter is large enough to cause significant compression of the surrounding cervical structures, or when some areas of the thyroid gland mimic the features of a nodule whose cytology cannot be ascertained as benign. HT remains a complex and ever expanding disease of unknown pathogenesis that awaits prevention or novel forms of treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Rectal suppositories of 8-methoxsalen produce fewer gastrointestinal side effects than the oral formulation.

PubMed

Bolognia, J L; Freije, L; Amici, L; Dellostritto, J; Gasparro, F P

1996-09-01

Gastrointestinal side effects are associated with the oral ingestion of 8-methoxsalen (8-MOP), including the liquid and crystalline formulations. The objective of this study was to determine whether the gastrointestinal symptoms associated with 8-MOP could be decreased by altering the route of administration. In an open pilot study, 8-MOP rectal suppositories were given to six patients with psoriasis vulgaris who had significant nausea or abdominal pain with the oral liquid form of the drug. On a scale of 0 to 5, this group of patients reported a mean score of 4.4 for nausea, 0.3 for vomiting, 2.1 for abdominal pain, and 1.3 for headaches with oral 8-MOP. With the suppository form, the mean scores were 0 for nausea, 0 for vomiting, 0 for abdominal pain, and 0 for headaches. These latter values represent scores for the entire treatment period. Clinical severity scores of psoriasis improved from a mean of 6.5 (maximum possible score = 9) at the start of the trial to a mean of 1 at its conclusion. Plasma 8-MOP levels of more than 100 ng/ml were observed in all patients who received the suppositories; in only one patient were the 8-MOP plasma levels significantly higher with the oral form than with the rectal form. Rectal suppositories of 8-MOP were associated with significantly fewer gastrointestinal side effects than the oral form of the drug; this was accomplished without compromising clinical efficacy.

Evaluation of patient-rated stiffness associated with fibromyalgia: a post-hoc analysis of 4 pooled, randomized clinical trials of duloxetine.

PubMed

Bennett, Robert; Russell, I Jon; Choy, Ernest; Spaeth, Michael; Mease, Philip; Kajdasz, Daniel; Walker, Daniel; Wang, Fujun; Chappell, Amy

2012-04-01

Patients with fibromyalgia (FM) rate stiffness as one of the most troublesome symptoms of the disorder. However, there are few published studies that have focused on better understanding the nature of stiffness in FM. The primary objectives of these analyses were to characterize the distribution of stiffness severity in patients at baseline, evaluate changes in stiffness after 12 weeks of treatment with duloxetine, and determine which outcomes were correlated with stiffness. These were post-hoc analyses of 3-month data from 4 randomized, double-blind, placebo-controlled studies that assessed efficacy of duloxetine in adults with FM. Severity of stiffness was assessed by using the Fibromyalgia Impact Questionnaire (FIQ) on a scale from 0 (no stiffness) to 10 (most severe stiffness). The association between changes in stiffness and other measures was evaluated by using Pearson's correlation coefficient. The FIQ total score and items, the Brief Pain Inventory (BPI-modified short form), the Clinical Global Impression-Severity scale, the Multidimensional Fatigue Inventory, the 17-item Hamilton Depression Rating Scale, the Sheehan Disability Scale, the 36-item Short-Form Health Survey, and the EuroQoL Questionnaire-5 Dimensions were evaluated in the correlation analyses. Stepwise linear regression was used to identify the variables that were most highly predictive of the changes in FIQ stiffness. The analysis included 1332 patients (mean age, 50.2 years; 94.7% female; and 87.8% white). The mean (SD) baseline FIQ stiffness score was 7.7 (2.0), and this score correlated with baseline BPI pain score and FIQ function. Duloxetine significantly improved the FIQ stiffness score compared with placebo (P < 0.001) and provided a moderate effect size (0.23 for the 60-mg dose and 0.38 for the 120-mg dose). Changes in stiffness were best correlated (range, 0.52-0.75; all, P < 0.001) with changes in BPI/FIQ pain and interference scores, FIQ nonrefreshing sleep, FIQ anxiety, 36-item Short-Form Health Survey bodily pain, and Sheehan Disability Scale total score. Variables related to severity of pain, pain interfering with daily activities, and physical functioning were predictors of change in stiffness. Stiffness scores were high in this population with FM and best correlated at baseline with BPI pain score and FIQ function. Not unexpectedly, improvement in stiffness with duloxetine correlated with many of the other markers of FM severity, presumably a result of amelioration in FM comorbidities. Copyright © 2012. Published by EM Inc USA.

Investigating Non-Invasive Hemodynamic Monitoring Devices Using Severe Dengue as a Surrogate for Trauma-Induced Shock

DTIC Science & Technology

2014-12-01

dengue hemorrhagic fever. In future work we will continue to evaluate the use of pulse wave forms to predict shock and will assess other...Index Three laboratory Phase I clinical trials have been completed to support a 510(k) application for FDA approval of the first prototype Pulse ... Oximeter with the CRI algorithm and capability for real-time continuous collection of photoplethymographic (PPG) analog signals. An FDA-cleared

Benign Breast Disease: Toward Molecular Prediction of Breast Cancer Risk

DTIC Science & Technology

2004-06-01

stored in groups according to immunostain (i.e., all of the number 3 slides together, the number 4 slides, and so on) to match the stain in bar coded...standoff between the DOD and Wayne State on consent form language around institutional coverage for any "research- related risks". Dr. Beitens from the...Sponsoring this Study Clinic will not be jeopardized. This work has been, and continues to be, sponsored by several groups including the Confidentiality

[Spot diagnosis of infectious exanthema].

PubMed

Ishiwada, Naruhiko

2007-03-01

There are lots of infectious diseases accompanied with exanthema. When the physicians see the patients with exanthema, they should carefully examine the form of exanthema and accessory symptoms. The physicians also should inquire of the patients about past history, history of vaccination and situation of current infectious disease epidemic in surrounding area. These clinical approaches lead to specific diagnosis. On this manuscript, I show the photos of several major infectious exanthema caused by viral, bacterial, bacterial toxin and so on.

Virulence of Curvularia in a murine model.

PubMed

Paredes, Katihuska; Capilla, Javier; Sutton, Deanna A; Mayayo, Emilio; Fothergill, Annette W; Guarro, Josep

2013-09-01

We have evaluated the virulence of two clinically relevant species of Curvularia; Curvularia spicifera and C. hawaiiensis, using an experimental model of disseminated infection in immunocompromised mice. Several inocula were tested over a range 1 × 10(3) -1 × 10(6) colony-forming units/animal. Both species had a similar behaviour, producing a high mortality. Tissue burden and histopathology studies demonstrated that lung was the organ most affected. © 2013 Blackwell Verlag GmbH.

Current Standards of Care and Long Term Outcomes for Thalassemia and Sickle Cell Disease.

PubMed

Chonat, Satheesh; Quinn, Charles T

2017-01-01

Thalassemia and sickle cell disease (SCD) are disorders of hemoglobin that affect millions of people worldwide. The carrier states for these diseases arose as common, balanced polymorphisms during human history because they afforded protection against severe forms of malaria. These complex, multisystem diseases are reviewed here with a focus on current standards of clinical management and recent research findings. The importance of a comprehensive, multidisciplinary and lifelong system of care is also emphasized.

Physical Trauma and Infection as Precipitating Factors in Patients with Fibromyalgia.

PubMed

Jiao, Juan; Vincent, Ann; Cha, Stephen S; Luedtke, Connie A; Kim, Chul H; Oh, Terry H

2015-12-01

The objective of this study was to evaluate both precipitating factors in patients with fibromyalgia and any differences in clinical presentation, symptom severity, and quality-of-life between those with and without precipitating physical trauma or infection. In a retrospective cross-sectional study, the authors compared patient characteristics and fibromyalgia symptom severity and quality-of-life with the Fibromyalgia Impact Questionnaire and the Short Form-36 Health Survey in patients seen in a fibromyalgia treatment program. Of 939 patients, 27% reported precipitating factors (trauma, n = 203; infection, n = 53), with the rest having idiopathic fibromyalgia (n = 683). Patients with precipitating trauma were more likely to have worse Fibromyalgia Impact Questionnaire physical function than patients with idiopathic onset (P = 0.03). Compared with patients with idiopathic onset and precipitating trauma, patients with precipitating infection were more likely to have worse Short Form-36 Health Survey physical component summary (P = 0.01 and P = 0.003) but better role emotional (P = 0.04 and P = 0.005), mental health index (P = 0.02 and P = 0.007), and mental component summary (P = 0.03 and P = 0.004), respectively. One-fourth of this study's patients with fibromyalgia had precipitating physical trauma or infection. Patients with precipitating infection had different sociodemographic characteristics, clinical presentation, and quality-of-life from the idiopathic and trauma groups. Further studies are needed to look into the relationships between precipitating events and fibromyalgia.

Current diagnosis and treatment of Castleman's disease.

PubMed

González García, A; Moreno Cobo, M Á; Patier de la Peña, J L

2016-04-01

Castleman's disease is not just a single disease but rather an uncommon, heterogeneous group of nonclonal lymphoproliferative disorders, which have a broad spectrum of clinical expression. Three histological types have been reported, along with several clinical forms according to clinical presentation, histological substrate and associated diseases. Interleukin-6, its receptor polymorphisms, the human immunodeficiency virus and the human herpes virus 8 are involved in the etiopathogenesis of Castleman's disease. The study of this disease has shed light on a syndrome whose incidence is unknown. Despite recent significant advances in our understanding of this disease and the increasing therapeutic experience with rituximab, tocilizumab and siltuximab, there are still difficult questions concerning its aetiology, prognosis and optimal treatment. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Atypical femur fractures: a review of the evidence and its implication to clinical practice

PubMed Central

Girgis, Christian M.

2011-01-01

Whilst bisphosphonates are an established modality in the treatment of osteoporosis, there have been increasing concerns regarding the risk of an unusual form of femur fracture amongst patients receiving bisphosphonates for prolonged periods. These fractures, referred to as ‘atypical’, have been characterized by a number of clinical and radiographic features that distinguish them from ‘typical’ osteoporotic fractures. The evidence base is currently split between a large number of case series demonstrating an association between the occurrence of atypical fractures and bisphosphonate use and several population-based studies that do not confirm such an association. Hence, a degree of uncertainty surrounds this important issue. In this review, we examine the emerging evidence on atypical femur fractures, assess hypotheses on their biomechanical evolution and discuss the wider clinical implications of this phenomenon. PMID:22870488

Muscle ischaemia associated with NXP2 autoantibodies: a severe subtype of juvenile dermatomyositis.

PubMed

Aouizerate, Jessie; De Antonio, Marie; Bader-Meunier, Brigitte; Barnerias, Christine; Bodemer, Christine; Isapof, Arnaud; Quartier, Pierre; Melki, Isabelle; Charuel, Jean-Luc; Bassez, Guillaume; Desguerre, Isabelle; Gherardi, Romain K; Authier, François-Jérôme; Gitiaux, Cyril

2018-05-01

Myositis-specific autoantibodies (MSAs) are increasingly used to delineate distinct subgroups of JDM. The aim of our study was to explore without a priori hypotheses whether MSAs are associated with distinct clinical-pathological changes and severity in a monocentric JDM cohort. Clinical, biological and histological findings from 23 JDM patients were assessed. Twenty-six histopathological parameters were subjected to multivariate analysis. Autoantibodies included anti-NXP2 (9/23), anti-TIF1γ (4/23), anti-MDA5 (2/23), no MSAs (8/23). Multivariate analysis yielded two histopathological clusters. Cluster 1 (n = 11) showed a more severe and ischaemic pattern than cluster 2 (n = 12) assessed by: total score severity ⩾ 20 (100.0% vs 25.0%); visual analogic score ⩾6 (100.0% vs 25.0%); the vascular domain score >1 (100.0% vs 41.7%); microinfarcts (100% vs 58.3%); ischaemic myofibrillary loss (focal punched-out vacuoles) (90.9 vs 25%); and obvious capillary loss (81.8% vs 16.7). Compared with cluster 2, patients in cluster 1 had strikingly more often anti-NXP2 antibodies (7/11 vs 2/12), more pronounced muscle weakness, more gastrointestinal involvement and required more aggressive treatment. Furthermore, patients with anti-NXP2 antibodies, mostly assigned in the first cluster, also displayed more severe muscular disease, requiring more aggressive treatment and having a lower remission rate during the follow-up period. Marked muscle ischaemic involvement and the presence of anti-NXP2 autoantibodies are associated with more severe forms of JDM.

[Clinical and psychopathological factors associated with impulse control disorders in Parkinson's disease].

PubMed

Sáez-Francàs, N; Martí Andrés, G; Ramírez, N; de Fàbregues, O; Álvarez-Sabín, J; Casas, M; Hernández-Vara, J

2016-05-01

Impulse control disorders (ICD) constitute a complication that may arise during the course of Parkinson's disease (PD). Several factors have been linked to the development of these disorders, and their associated severe functional impairment requires specific and multidisciplinary management. The objective of this study was to evaluate the frequency of ICDs and the clinical and psychopathological factors associated with the appearance of these disorders. Cross-sectional, descriptive, and analytical study of a sample of 115 PD patients evaluated to determine the presence of an ICD. Clinical scales were administered to assess disease severity, personality traits, and presence of psychiatric symptoms at the time of evaluation. Of the 115 patients with PD, 27 (23.48%) displayed some form of ICD; hypersexuality, exhibited by 14 (12.2%), and binge eating, present in 12 (10.1%), were the most common types. Clinical factors associated with ICD were treatment with dopamine agonists (OR: 13.39), earlier age at disease onset (OR: 0.92), and higher score on the UPDRS-I subscale; psychopathological factors with a significant association were trait anxiety (OR: 1.05) and impulsivity (OR: 1.13). ICDs are frequent in PD, and treatment with dopamine agonists is the most important risk factor for these disorders. High impulsivity and anxiety levels at time of evaluation, and younger age at disease onset, were also linked to increased risk. However, presence of these personality traits prior to evaluation did not increase risk of ICD. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Identification of chronic rhinosinusitis phenotypes using cluster analysis.

PubMed

Soler, Zachary M; Hyer, J Madison; Ramakrishnan, Viswanathan; Smith, Timothy L; Mace, Jess; Rudmik, Luke; Schlosser, Rodney J

2015-05-01

Current clinical classifications of chronic rhinosinusitis (CRS) have been largely defined based upon preconceived notions of factors thought to be important, such as polyp or eosinophil status. Unfortunately, these classification systems have little correlation with symptom severity or treatment outcomes. Unsupervised clustering can be used to identify phenotypic subgroups of CRS patients, describe clinical differences in these clusters and define simple algorithms for classification. A multi-institutional, prospective study of 382 patients with CRS who had failed initial medical therapy completed the Sino-Nasal Outcome Test (SNOT-22), Rhinosinusitis Disability Index (RSDI), Medical Outcomes Study Short Form-12 (SF-12), Pittsburgh Sleep Quality Index (PSQI), and Patient Health Questionnaire (PHQ-2). Objective measures of CRS severity included Brief Smell Identification Test (B-SIT), CT, and endoscopy scoring. All variables were reduced and unsupervised hierarchical clustering was performed. After clusters were defined, variations in medication usage were analyzed. Discriminant analysis was performed to develop a simplified, clinically useful algorithm for clustering. Clustering was largely determined by age, severity of patient reported outcome measures, depression, and fibromyalgia. CT and endoscopy varied somewhat among clusters. Traditional clinical measures, including polyp/atopic status, prior surgery, B-SIT and asthma, did not vary among clusters. A simplified algorithm based upon productivity loss, SNOT-22 score, and age predicted clustering with 89% accuracy. Medication usage among clusters did vary significantly. A simplified algorithm based upon hierarchical clustering is able to classify CRS patients and predict medication usage. Further studies are warranted to determine if such clustering predicts treatment outcomes. © 2015 ARS-AAOA, LLC.

Lifetime eating disorder comorbidity associated with delayed depressive recovery in bipolar disorder.

PubMed

Balzafiore, Danielle R; Rasgon, Natalie L; Yuen, Laura D; Shah, Saloni; Kim, Hyun; Goffin, Kathryn C; Miller, Shefali; Wang, Po W; Ketter, Terence A

2017-12-01

Although eating disorders (EDs) are common in bipolar disorder (BD), little is known regarding their longitudinal consequences. We assessed prevalence, clinical correlates, and longitudinal depressive severity in BD patients with vs. without EDs. Outpatients referred to Stanford University BD Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) affective disorders evaluation, and while receiving naturalistic treatment for up to 2 years, were monitored with the STEP-BD clinical monitoring form. Patients with vs. without lifetime EDs were compared with respect to prevalence, demographic and unfavorable illness characteristics/current mood symptoms and psychotropic use, and longitudinal depressive severity. Among 503 BD outpatients, 76 (15.1%) had lifetime EDs, which were associated with female gender, and higher rates of lifetime comorbid anxiety, alcohol/substance use, and personality disorders, childhood BD onset, episode accumulation (≥10 prior mood episodes), prior suicide attempt, current syndromal/subsyndromal depression, sadness, anxiety, and antidepressant use, and earlier BD onset age, and greater current overall BD severity. Among currently depressed patients, 29 with compared to 124 without lifetime EDs had significantly delayed depressive recovery. In contrast, among currently recovered (euthymic ≥8 weeks) patients, 10 with compared to 95 without lifetime EDs had only non-significantly hastened depressive recurrence. Primarily Caucasian, insured, suburban, American specialty clinic-referred sample limits generalizability. Small number of recovered patients with EDs limited statistical power to detect relationships between EDs and depressive recurrence. Further studies are warranted to explore the degree to which EDs impact longitudinal depressive illness burden in BD.

Very early onset of autoimmune thyroiditis in a toddler with severe hypothyroidism presentation: a case report.

PubMed

Marzuillo, Pierluigi; Grandone, Anna; Perrotta, Silverio; Ruggiero, Laura; Capristo, Carlo; Luongo, Caterina; Miraglia Del Giudice, Emanuele; Perrone, Laura

2016-06-18

In infants under 3 years of age acquired primary hypothyroidism caused by autoimmune thyroiditis is very rare. Hypothyroidism can manifest with different signs and symptoms and has a wide range of presentations from subclinical hypothyroidism to overt form. We describe a child with acquired autoimmune thyroiditis during a very early period of life and with a severe hypothyroidism presentation. A 22-month-old white male patient with normal neonatal screening presented with a six-month history of asthenia and cutaneous pallor. At general clinical and biochemical exams he showed weight gain, statural growth deceleration, poor movements, sleepy expression, instability while walking, myxoedema, bradycardia, open anterior fontanelle, changes in the face habitus, macrocytic anaemia, ascites, and high CPK, creatinine and cholesterol levels. Acquired autoimmune thyroiditis was the final diagnosis. The thyroxine replacement therapy normalized all the clinical and biochemical abnormalities but at the age of 30 months his mental age showed a delay of 6 months. Our case could give useful learning points: i) although the screening for congenital hypothyroidism is routinely performed, a severe hypothyroidism (for example due to autoimmune thyroiditis) can anyway occur early in life and the clinicians should consider this possibility; ii) hypothyroidism can have a misleading and multi-face clinical presentation; iii) anemia, rhabdomyolysis and high creatinine levels should always include the hypothyroidism in the differential diagnosis; iv) thyroxine replacement therapy is able to revert all the clinical manifestations related to the hypothyroidism; v) evaluating the patient's previous pictures could play an important role in resolving a diagnostic conundrum.

Subgroup Analysis in Burnout: Relations Between Fatigue, Anxiety, and Depression

PubMed Central

van Dam, Arno

2016-01-01

Several authors have suggested that burned out patients do not form a homogeneous group and that subgroups should be considered. The identification of these subgroups may contribute to a better understanding of the burnout construct and lead to more specific therapeutic interventions. Subgroup analysis may also help clarify whether burnout is a distinct entity and whether subgroups of burnout overlap with other disorders such as depression and chronic fatigue syndrome. In a group of 113 clinically diagnosed burned out patients, levels of fatigue, depression, and anxiety were assessed. In order to identify possible subgroups, we performed a two-step cluster analysis. The analysis revealed two clusters that differed from one another in terms of symptom severity on the three aforementioned measures. Depression appeared to be the strongest predictor of group membership. These results are considered in the light of the scientific debate on whether burnout can be distinguished from depression and whether burnout subtyping is useful. Finally, implications for clinical practice and future research are discussed. PMID:26869983

How Obesity Affects Tendons?

PubMed

Abate, Michele; Salini, Vincenzo; Andia, Isabel

Several epidemiological and clinical observations have definitely demonstrated that obesity has harmful effects on tendons. The pathogenesis of tendon damage is multi-factorial. In addition to overload, attributable to the increased body weight, which significantly affects load-bearing tendons, systemic factors play a relevant role. Several bioactive peptides (chemerin, leptin, adiponectin and others) are released by adipocytes, and influence tendon structure by means of negative activities on mesenchymal cells. The ensuing systemic state of chronic, sub-clinic, low-grade inflammation can damage tendon structure. Metabolic disorders (diabetes, impaired glucose tolerance, and dislipidemia), frequently associated with visceral adiposity, are concurrent pathogenetic factors. Indeed, high glucose levels increase the formation of Advanced Glycation End-products, which in turn form stable covalent cross-links within collagen fibers, modifying their structure and functionality.Sport activities, so useful for preventing important cardiovascular complications, may be detrimental for tendons if they are submitted to intense acute or chronic overload. Therefore, two caution rules are mandatory: first, to engage in personalized soft training program, and secondly to follow regular check-up for tendon pathology.

Drugs currently under investigation for the treatment of invasive candidiasis.

PubMed

McCarthy, Matthew W; Walsh, Thomas J

2017-07-01

The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.

Granulomatosis with polyangiitis mimicking infective endocarditis in an adolescent male.

PubMed

Varnier, Giulia Camilla; Sebire, Neil; Christov, Georgi; Eleftheriou, Despina; Brogan, Paul A

2016-09-01

Granulomatosis with polyangiitis (GPA) is a rare but serious small vessel vasculitis with heterogeneous clinical presentation ranging from mainly localised disease with a chronic course, to a florid, acute small vessel vasculitic form characterised by severe pulmonary haemorrhage and/or rapidly progressive vasculitis or other severe systemic vasculitic manifestations. Cardiac involvement is, however, uncommon in the paediatric population. We report a case of a 16-year-old male who presented with peripheral gangrene and vegetation with unusual location on the supporting apparatus of the tricuspid valve, initially considered to have infective endocarditis but ultimately diagnosed with GPA. We provide an overview of the limited literature relating to cardiac involvement in GPA, and the diagnostic challenge relating to infective endocarditis in this context, especially focusing on the interpretation of the antineutrophil cytoplasmic antibody (ANCA) and the characteristic clinical features to identify in order to promptly recognise GPA, since timely diagnosis and treatment are essential for this potentially life-threatening condition.

Novel methotrexate soft nanocarrier/fractional erbium YAG laser combination for clinical treatment of plaque psoriasis.

PubMed

Ramez, Shahenda A; Soliman, Mona M; Fadel, Maha; Nour El-Deen, Faisal; Nasr, Maha; Youness, Eman R; Aboel-Fadl, Dalea M

2018-02-15

Psoriasis is a commonly encountered chronic dermatological disease, presenting with inflammatory symptoms in patients. Systemic treatment of psoriasis is associated with several adverse effects, therefore the development of a customized topical treatment modality for psoriasis would be an interesting alternative to systemic delivery. The therapeutic modality explored in this article was the comparative treatment of psoriatic patients using nanoparticulated methotrexate in the form of jojoba oil-based microemulsion with or without fractional erbium YAG laser. Assessment parameters included follow-up photography for up to 8 weeks of treatment, estimation of the psoriasis severity [TES (thickness, erythema, scales)] score, and histopathological skin evaluation. The prepared methotrexate microemulsion was clinically beneficial and safe in treatment of psoriasis vulgaris. The concomitant use of the fractional laser provided improvement in the psoriatic plaques within shorter time duration (3 weeks compared to 8 weeks of treatment), presenting an alternative topical treatment modality for psoriasis vulgaris.

Physiopathological, Epidemiological, Clinical and Therapeutic Aspects of Exercise-Associated Hyponatremia

PubMed Central

Urso, Caterina; Brucculeri, Salvatore; Caimi, Gregorio

2014-01-01

Exercise-associated hyponatremia (EAH) is dilutional hyponatremia, a variant of inappropriate antidiuretic hormone secretion (SIADH), characterized by a plasma concentration of sodium lower than 135 mEq/L. The prevalence of EAH is common in endurance (<6 hours) and ultra-endurance events (>6 hours in duration), in which both athletes and medical providers need to be aware of risk factors, symptom presentation, and management. The development of EAH is a combination of excessive water intake, inadequate suppression of the secretion of the antidiuretic hormone (ADH) (due to non osmotic stimuli), long race duration, and very high or very low ambient temperatures. Additional risk factors include female gender, slower race times, and use of nonsteroidal anti-inflammatory drugs. Signs and symptoms of EAH include nausea, vomiting, confusion, headache and seizures; it may result in severe clinical conditions associated with pulmonary and cerebral edema, respiratory failure and death. A rapid diagnosis and appropriate treatment with a hypertonic saline solution is essential in the severe form to ensure a positive outcome. PMID:26237602

The muscular dystrophies associated with central nervous system lesions: a brief review from a standpoint of the localization and function of causative genes.

PubMed

Yamamoto, Tomoko; Hiroi, Atsuko; Osawa, Makiko; Shibata, Noriyuki

2014-01-01

The muscular dystrophies have been traditionally classified based mainly on clinical manifestation and mode of inheritance. Owing to the discoveries of causative genes, new terminologies derived from each gene, such as dystrophinopathy, α-dystroglycanopathy, sarcoglycanopathy and fukutinopathy, have also become common. Mutations of each gene may cause several clinical phenotypes. Some muscular dystrophies accompany central nervous system (CNS) lesions, especially in the congenital muscular dystrophies. Cobblestone lissencephaly (type II lissencephaly) is a well-known CNS malformation observed in severe forms of α-dystroglycanopathy. Moreover, CNS involvement has been reported in other muscular dystrophies, such as Duchenne muscular dystrophy. In this review, genes related to the muscular dystrophies associated with CNS lesions are briefly described along with the molecular characteristics of each gene and the pathomechanism of the CNS lesions. Understanding of both the clinicopathological characteristics of these CNS lesions and their molecular mechanisms is important for the diagnosis, care of patients, and development of new therapeutic strategies.

Self injurious behavior in autism: clinical aspects and treatment with risperidone.

PubMed

Canitano, R

2006-03-01

Self injurious behavior (SIB) is frequent in autistic spectrum disorders. The aim of this study was to investigate the phenomenology of SIB in a group of children with autistic disorder, and to test whether treatment with risperidone might reduce it. A group of eleven children diagnosed with autistic disorder according to the DSM-IV criteria (mean age 8.7+/-2.2 ys) and with severe SIB were recruited for an open study of six months of treatment with risperidone. The Yale-Paris Self-Injurious Behavior Scale was used to delineate the clinical characteristics and as an outcome measure. Head-hitting and hand biting were the most frequent forms of self aggression observed. Nine children presented a mild improvement in SIB and 2 did not show any variation. A decrease in Yale-Paris Self Injurious Behavior Scale score (from M 15.1+/-1.4 to 13.3+/-1.4) was noted mainly due to the reduction of frequency. Side effects of risperidone were not severe.

Bayesian inference on risk differences: an application to multivariate meta-analysis of adverse events in clinical trials.

PubMed

Chen, Yong; Luo, Sheng; Chu, Haitao; Wei, Peng

2013-05-01

Multivariate meta-analysis is useful in combining evidence from independent studies which involve several comparisons among groups based on a single outcome. For binary outcomes, the commonly used statistical models for multivariate meta-analysis are multivariate generalized linear mixed effects models which assume risks, after some transformation, follow a multivariate normal distribution with possible correlations. In this article, we consider an alternative model for multivariate meta-analysis where the risks are modeled by the multivariate beta distribution proposed by Sarmanov (1966). This model have several attractive features compared to the conventional multivariate generalized linear mixed effects models, including simplicity of likelihood function, no need to specify a link function, and has a closed-form expression of distribution functions for study-specific risk differences. We investigate the finite sample performance of this model by simulation studies and illustrate its use with an application to multivariate meta-analysis of adverse events of tricyclic antidepressants treatment in clinical trials.

Leigh Syndrome and the Mitochondrial m.13513G>A Mutation: Expanding the Clinical Spectrum.

PubMed

Monlleo-Neila, Laura; Toro, Mireia Del; Bornstein, Belen; Garcia-Arumi, Elena; Sarrias, Axel; Roig-Quilis, Manuel; Munell, Francina

2013-11-01

The mitochondrial DNA m.13513G>A mutation in the ND5 subunit gene is a frequent cause of Leigh syndrome. Patients harboring this mutation typically present with ptosis and cardiac conduction abnormalities, particularly Wolff-Parkinson-White syndrome, and have a late clinical onset, which contrasts with the typical infantile form. The authors describe a patient presenting with intrauterine growth retardation and visual impairment at 3 months of age, followed by infantile spasms, severe gastrointestinal dysmotility, and neurological regression. The patient had hyperlactacidemia and bilateral basal ganglia and brainstem lesions on MRI. Although he did not present cardiac conduction abnormalities, his mother had been diagnosed with Wolff-Parkinson-White syndrome. The m.13513G>A mutation was found in the patient's muscle and in several tissues of his mother. The present results expand the phenotype of Leigh syndrome associated with the m.13513G>A mutation, which should be suspected in patients with early-onset mitochondrial encephalopathy with infantile spasms or prominent gastrointestinal smooth muscle involvement.

Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides.

PubMed

Nishikimi, Toshio; Kuwahara, Koichiro; Nakao, Kazuwa

2011-03-01

The mammalian natriuretic peptide family consists of atrial (ANP), brain [B-type; BNP] and C-type natriuretic peptide (CNP) and three receptors, natriuretic receptors-A (NPR-A), -B (NPR-B) and -C (NPR-C). Both ANP and BNP are abundantly expressed in the heart and are secreted mainly from the atria and ventricles, respectively. By contrast, CNP is mainly expressed in the central nervous system, bone and vasculature. Plasma concentrations of both ANP and BNP are elevated in patients with cardiovascular disease, though the magnitude of the increase in BNP is usually greater than the increase in ANP. This makes BNP is a clinically useful diagnostic marker for several pathophysiological conditions, including heart failure, ventricular remodeling and pulmonary hypertension, among others. Recent studies have shown that in addition to BNP-32, proBNP-108 also circulates in human plasma and that levels of both forms are increased in heart failure. Furthermore, proBNP-108 is O-glycosylated and circulates at higher levels in patients with severe heart failure. In this review we discuss recent progress in our understanding of the biochemistry, molecular biology and clinical relevance of the natriuretic peptide system. Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Molecular Diagnosis of Thalassemias and Hemoglobinopathies: An ACLPS Critical Review.

PubMed

Sabath, Daniel E

2017-07-01

To describe the use of molecular diagnostic techniques for patients with hemoglobin disorders. A clinical scenario is presented in which molecular diagnosis is important for genetic counseling. Globin disorders, techniques for their diagnosis, and the role of molecular genetic testing in managing patients with these disorders are described in detail. Hemoglobin disorders, including thalassemias and hemoglobinopathies, are among the commonest genetic diseases, and the clinical laboratory is essential for the diagnosis of patients with these abnormalities. Most disorders can be diagnosed with protein-based techniques such as electrophoresis and chromatography. Since severe syndromes can result due to inheritance of combinations of globin genetic disorders, genetic counseling is important to prevent adverse outcomes. Protein-based methods cannot always detect potentially serious thalassemia disorders; in particular, α-thalassemia may be masked in the presence of β-thalassemia. Deletional forms of β-thalassemia are also sometimes difficult to diagnose definitively with standard methods. Molecular genetic testing serves an important role in identifying individuals carrying thalassemia traits that can cause adverse outcomes in offspring. Furthermore, prenatal genetic testing can identify fetuses with severe globin phenotypes. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis☆

PubMed Central

Pangrazio, Alessandra; Puddu, Alessandro; Oppo, Manuela; Valentini, Maria; Zammataro, Luca; Vellodi, Ashok; Gener, Blanca; Llano-Rivas, Isabel; Raza, Jamal; Atta, Irum; Vezzoni, Paolo; Superti-Furga, Andrea; Villa, Anna; Sobacchi, Cristina

2014-01-01

Autosomal Recessive Osteopetrosis is a genetic disorder characterized by increased bone density due to lack of resorption by the osteoclasts. Genetic studies have widely unraveled the molecular basis of the most severe forms, while cases of intermediate severity are more difficult to characterize, probably because of a large heterogeneity. Here, we describe the use of exome sequencing in the molecular diagnosis of 2 siblings initially thought to be affected by “intermediate osteopetrosis”, which identified a homozygous mutation in the CTSK gene. Prompted by this finding, we tested by Sanger sequencing 25 additional patients addressed to us for recessive osteopetrosis and found CTSK mutations in 4 of them. In retrospect, their clinical and radiographic features were found to be compatible with, but not typical for, Pycnodysostosis. We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative. In conclusion, we underline the difficulties of differential diagnosis in some patients whose clinical appearance does not fit the classical malignant or benign picture and recommend that CTSK gene be included in the molecular diagnosis of high bone density conditions. PMID:24269275

Self-neglect: adaptation of a clinical tool to the practice of the medical examiner.

PubMed

Sauvageau, Anny; Hunter, Brian C

2012-09-01

Self-neglect is the inability or unwillingness to provide for oneself the goods and services needed to live safely and independently. It is the most common allegation reported to Adult Protective Services agencies throughout the United States. Unfortunately, it seems that most medical examiners and their teams are not trained appropriately on self-neglect and forget to ask pertinent questions and document relevant observations. The most important aspect of self-neglect for the medical examiner is to recognize the diagnosis to avoid confusion with other forms of elder abuse, particularly neglect from a third party. In this context, a self-neglect scale could be a useful tool to assist the death investigation team. In the clinical field, a self-neglect severity scale was developed by the Consortium for Research in Elder Self-Neglect of Texas. It is here proposed that a self-neglect severity scale for medical examiners should be developed, to assist the investigative team in assessing these common cases. This scale is developed by modifying the clinical scale to adapt it to the particular needs of death investigation. This scale can help the medical examiner and his team in approaching these deaths in a systematic and comprehensive way.

Levels of Social Sharing and Clinical Implications for Severe Social Withdrawal in Patients with Personality Disorders

PubMed Central

Colle, Livia; Pellecchia, Giovanni; Moroni, Fabio; Carcione, Antonino; Nicolò, Giuseppe; Semerari, Antonio; Procacci, Michele

2017-01-01

Social sharing capacities have attracted attention from a number of fields of social cognition and have been variously defined and analyzed in numerous studies. Social sharing consists in the subjective awareness that aspects of the self’s experience are held in common with other individuals. The definition of social sharing must take a variety of elements into consideration: the motivational element, the contents of the social sharing experience, the emotional responses it evokes, the behavioral outcomes, and finally, the circumstances and the skills which enable social sharing. The primary objective of this study is to explore some of the diverse forms of human social sharing and to classify them according to levels of complexity. We identify four different types of social sharing, categorized according to the nature of the content being shared and the complexity of the mindreading skills required. The second objective of this study is to consider possible applications of this graded model of social sharing experience in clinical settings. Specifically, this model may support the development of graded, focused clinical interventions for patients with personality disorders characterized by severe social withdrawal. PMID:29255430

Pulmonary Embolization of Fat and Bone Marrow in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

Fong, Derek L.; Murnane, Robert D.; Hotchkiss, Charlotte E.; Green, Damian J.; Hukkanen, Renee R.

2011-01-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma. PMID:21819686

Pulmonary embolization of fat and bone marrow in cynomolgus Macaques (Macaca fascicularis).

PubMed

Fong, Derek L; Murnane, Robert D; Hotchkiss, Charlotte E; Green, Damian J; Hukkanen, Renee R

2011-02-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma.

Autoregulation in the Neuro ICU.

PubMed

Wang, Anson; Ortega-Gutierrez, Santiago; Petersen, Nils H

2018-05-17

The purpose of this review is to briefly describe the concept of cerebral autoregulation, to detail several bedside techniques for measuring and assessing autoregulation, and to outline the impact of impaired autoregulation on clinical and functional outcomes in acute brain injury. Furthermore, we will review several autoregulation studies in select forms of acute brain injuries, discuss the potential for its use in patient management in the ICU, and suggest further avenues for research. Cerebral autoregulation plays a critical role in regulating cerebral blood flow, and impaired autoregulation has been associated with worse functional and clinical outcomes in various acute brain injuries. There exists a multitude of methods to assess the autoregulatory state in patients using both invasive and non-invasive modalities. Continuous monitoring of patients in the ICU has yielded autoregulatory-derived optimal perfusion pressures that may prevent secondary injury and improve outcomes. Measuring autoregulation continuously at the bedside is now a feasible option for clinicians working in the ICU, although there exists a great need to standardize autoregulatory measurement. While the clinical benefits await prospective and randomized trials, autoregulation-derived parameters show enormous potential for creating an optimal physiological environment for the injured brain.

Investigation of a Possible Link Between Vaccination and the 2010 Sheep Pox Epizootic in Morocco.

PubMed

Haegeman, A; Zro, K; Sammin, D; Vandenbussche, F; Ennaji, M M; De Clercq, K

2016-12-01

Sheep pox is endemic in most parts of Northern Africa and has the potential to cause severe economic problems. Live attenuated vaccines are used in Morocco, and in many other countries, to control the disease. Sheep pox virus (SPPV) re-appeared in 2010 causing a nodular clinical form previously not observed in Morocco. The severe clinical signs observed during the course of this outbreak and initial reports citing similarity in nucleotide sequence between the Moroccan vaccine strain and field isolates warranted a more in depth analysis of this epizootic. In this study, sequence analysis showed that isolates obtained from four provinces of eastern Morocco were identical, demonstrating that a single SPPV strain was responsible for the 2010 epizootic. In addition, the genome fragments sequenced and phylogenetic analyses undertaken as part of this study showed significant differences between field isolates and the Moroccan vaccine strain. New PCR methods were developed to differentiate between wild-type isolates and vaccine strains of SPPV. Using these methods, no trace of wild-type SPPV was found in the vaccine and no evidence was found to suggest that the vaccine strain was causing clinical disease. © 2015 Blackwell Verlag GmbH.

Rett Syndrome: Revised Diagnostic Criteria and Nomenclature

PubMed Central

Neul, Jeffrey L.; Kaufmann, Walter E.; Glaze, Daniel G.; Christodoulou, John; Clarke, Angus J.; Bahi-Buisson, Nadia; Leonard, Helen; Bailey, Mark E. S.; Schanen, N. Carolyn; Zappella, Michele; Renieri, Alessandra; Huppke, Peter; Percy, Alan K.

2010-01-01

Objective Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials. Method RettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT. Results The clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed. Interpretation These revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research. PMID:21154482

Nursing students' clinical competencies: a survey on clinical education objectives.

PubMed

Arrigoni, C; Grugnetti, A M; Caruso, R; Gallotti, M L; Borrelli, P; Puci, M

2017-01-01

Developing clearly defined competencies and identifying strategies for their measurement remain unfortunately a critical aspect of nursing training. In the current international context, which continues to be characterised by deep economic crisis, universities have a fundamental role to play in redefining the educational goals to respond to the expectations of certain geographical areas of interest, as underscored in the Bologna Process (Joint Declaration of the European Ministers of Education Convened in Bologna 19 June 1999). The aim of this observational study was to examine the clinical learning context of nursing students using a tool developed by a team of teachers for the analysis of clinical learning. Redefinition of the clinical learning objectives with reference to the competencies set out in the questionnaire validated by Venturini et al. (2012) and the subsequent use of the tool created by the team of teachers for students in the first, second and third-year courses of the 2013/14 academic year, covering all the internships called for in those years. All nursing students enrolled in the first, second and third year of the nursing undergraduate degree program at the University of Pavia (no. 471) participated in this survey. A total of 1,758 clinical internships were carried out: 461 for the first year, 471 for the second year and 826 for the third year. Setting objectives, beginning with the educational offerings in the several clinical contexts, represents a strong point for this process. The results highlight a level of heterogeneity and complexity intrinsic to the University of Pavia educational system, characterized by clinical settings with different clinical levels (Research hospital and other traditional hospitals) that offering different levels of training. The use of the self-evaluation form for clinical learning made it possible to perform real-time observations of the training activities of the entire student body. An educational model structured in this way allows the student to develop their capacity for critical thinking. For educational activities, such a self-evaluation form represents an ideal instrument for identifying areas in need of improvement. This explorative study, carried out by means of a self-evaluation form, is the first-step toward the development of an educational programme that is more uniform and easily traceable within the academic system.

Clinical and MRI characterization of MS patients with a pure and severe cognitive onset.

PubMed

Assouad, Rana; Louapre, Celine; Tourbah, Ayman; Papeix, Caroline; Galanaud, Damien; Lubetzki, Catherine; Stankoff, Bruno

2014-11-01

Cognitive and behavioural symptoms are common in multiple sclerosis (MS), but they are rarely the inaugural and predominant manifestation of the disease. Our objective is to characterize the clinical and radiological features of cognitive-multiple sclerosis (cog-MS), defined as MS subjects who entered into the disease with cognitive symptoms, which subsequently remain the predominant manifestation. We describe the disease course, and clinical and radiological features of 18 subjects with a cognitive form of MS. Memory loss and behavioural changes were the primary symptoms at disease onset. They remained prominent and led to severe cognitive impairment during disease course. The main associated manifestations were depression, pathological laughing and/or crying, urinary incontinence and gait disturbance suggestive of high-level gait disorder. Motor, sensory or cerebellar abnormalities were uncommon. During disease course, superimposed neurological relapses occurred in 61% of cases. Brain MRI revealed multiple periventricular lesions that were extensive and confluent in half of cases, and a severe atrophy measured as an increase in the third ventricular width compared to age-matched healthy controls. Gadolinium-enhancing lesions were common (72%). The mean diagnosis delay from disease onset was 2 years. A principal component analysis on the neuropsychological results revealed that verbal memory assessment is complementary to global cognitive functioning evaluation in these patients with severe cognitive deficit. Verbal memory deficit was associated with high EDSS. cog-MS patients might represent a challenging diagnosis, which needs to be individualized for an early management. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical, genetic, and structural basis of apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase type 2 deficiency.

PubMed

Yau, Mabel; Haider, Shozeb; Khattab, Ahmed; Ling, Chen; Mathew, Mehr; Zaidi, Samir; Bloch, Madison; Patel, Monica; Ewert, Sinead; Abdullah, Wafa; Toygar, Aysenur; Mudryi, Vitalii; Al Badi, Maryam; Alzubdi, Mouch; Wilson, Robert C; Al Azkawi, Hanan Said; Ozdemir, Hatice Nur; Abu-Amer, Wahid; Hertecant, Jozef; Razzaghy-Azar, Maryam; Funder, John W; Al Senani, Aisha; Sun, Li; Kim, Se-Min; Yuen, Tony; Zaidi, Mone; New, Maria I

2017-12-26

Mutations in 11β-hydroxysteroid dehydrogenase type 2 gene ( HSD11B2 ) cause an extraordinarily rare autosomal recessive disorder, apparent mineralocorticoid excess (AME). AME is a form of low renin hypertension that is potentially fatal if untreated. Mutations in the HSD11B2 gene result either in severe AME or a milder phenotype (type 2 AME). To date, ∼40 causative mutations have been identified. As part of the International Consortium for Rare Steroid Disorders, we have diagnosed and followed the largest single worldwide cohort of 36 AME patients. Here, we present the genotype and clinical phenotype of these patients, prominently from consanguineous marriages in the Middle East, who display profound hypertension and hypokalemic alkalosis. To correlate mutations with phenotypic severity, we constructed a computational model of the HSD11B2 protein. Having used a similar strategy for the in silico evaluation of 150 mutations of CYP21A2 , the disease-causing gene in congenital adrenal hyperplasia, we now provide a full structural explanation for the clinical severity of AME resulting from each known HSD11B2 missense mutation. We find that mutations that allow the formation of an inactive dimer, alter substrate/coenzyme binding, or impair structural stability of HSD11B2 yield severe AME. In contrast, mutations that cause an indirect disruption of substrate binding or mildly alter intramolecular interactions result in type 2 AME. A simple in silico evaluation of novel missense mutations could help predict the often-diverse phenotypes of an extremely rare monogenic disorder.

Pediatric social anxiety disorder: predictors of response to pharmacological treatment.

PubMed

Masi, Gabriele; Pfanner, Chiara; Mucci, Maria; Berloffa, Stefano; Magazù, Angela; Parolin, Giulia; Perugi, Giulio

2012-12-01

Pediatric social anxiety disorder (SAD) is associated with an increased risk of comorbid mental disorders, with implications for prognosis and treatment strategy. The aim of this study is to explore predictors of treatment response, and the role of comorbidity in affecting refractoriness. One hundred and forty consecutive youths (81 males, 57.9%), ages 7-18 years (mean age 13.7 ± 2.5 years, mean age at onset of SAD 10.6 ± 2.7 years) met American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for SAD as primary diagnosis, according to a structured clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version [K-SADS-PL]). All received a pharmacological treatment with serotonin reuptake inhibitors (SSRIs) targeted to SAD, associated with additional medications for comorbidities (mood stabilizers in 27.1%, antipsychotics in 12.8%) and 57.9% received an additional psychotherapy. Eighty-nine patients (63.6%) responded to treatments after 3 months, namely 72.8% with psychotherapy plus medication and 50.8% with medication only. Nonresponders had more severe symptoms at baseline in terms of both clinical severity and functional impairment, and had more comorbid disruptive behavior disorders. The backward logistic regression indicated that clinical severity and functional impairment at baseline, comorbid disruptive behavior disorders, and bipolar disorders were predictors of nonresponse. Our data suggest that SSRIs can be effective in pediatric SAD, but that the more severe forms of the disorder and those with heavier comorbidity are associated with poorer prognosis.

tuberculous otitis media in a renal transplant recipient.

PubMed

Ergün, Ihsan; Keven, Kenan; Sengül, Sule; Kutlay, Sim; Sertcelik, Ayse; Ertürk, Sehsuvar; Erbay, Bülent

2004-06-01

Tuberculous otitis media is a rare cause of chronic suppurative infection of the middle ear and a very uncommon form of extrapulmonary tuberculosis. Although there have been several case reports in the nonimmunosuppressive population of tuberculous otitis media, it has never been reported in an immunosuppressed allograft recipient. We present a case of diagnosed tuberculous otitis media after recurrent chronic otitis media treated several times with empiric antibiotic treatment. After the patient developed postauricular fistula and underwent surgical removal of granulation tissue, the diagnosis was made on the basis of histopathology and growth in culture of Ziehl-Neelsen. Clinical response promptly followed institution of antituberculous treatment including isoniazid, rifampicin, ethambutol, and pyrazinamide.

Periocular necrotizing fasciitis causing blindness.

PubMed

Shield, David R; Servat, Javier; Paul, Sean; Turbin, Roger E; Moreau, Annie; de la Garza, Adam; El Rassi, Edward; Silbert, Jonathan; Lesser, Robert; Levin, Flora

2013-09-01

Periocular necrotizing fasciitis is a rare but potentially devastating disease, accompanied by high rates of morbidity and mortality. We report 5 cases of periocular necrotizing fasciitis resulting in severe vision loss, 3 of which required exenteration to contain the disease and only 1 of which recovered vision. Three cases were caused by group A streptococcus; 1, by methicillin-resistant Staphylococcus aureus; and 1, by Streptococcus anginosus constellatus. Providers should maintain a high clinical suspicion for necrotizing fasciitis and distinguish it from more common forms of cellulitis. As seen in these 5 cases, periocular necrotizing fasciitis may cause severe visual loss more often than previously recognized. To our knowledge, this is also the first report of Streptococcus anginosus constellatus causing necrotizing fasciitis.

Commentary: Childhood conduct problems are a public health crisis and require resources: a commentary on Rivenbark et al. ().

PubMed

Burt, S Alexandra; Hyde, Luke W; Frick, Paul J; Jaffee, Sara R; Shaw, Daniel S; Tremblay, Richard

2018-06-01

Conduct problems (CP) are actions that violate societal norms and/or the personal/property rights of others, and include behaviors such as vandalism, theft, bullying, and assault. Roughly 8%-10% of children engage in the more severe childhood-onset form of CP, while another 25% initiate clinically-significant levels of CP during adolescence. As deftly observed in Rivenbark et al. (), however, the high prevalence of CP belies its severity: Youth with CP are at increased risk for a number of deleterious individual outcomes, including academic delay/dropout, low professional achievement, psychopathology, addiction, and family instability. © 2018 Association for Child and Adolescent Mental Health.

Guidelines for the management and treatment of periodic fever syndromes: Cryopyrin-associated periodic syndromes (cryopyrinopathies - CAPS).

PubMed

Terreri, Maria Teresa R A; Bernardo, Wanderley Marques; Len, Claudio Arnaldo; da Silva, Clovis Artur Almeida; de Magalhães, Cristina Medeiros Ribeiro; Sacchetti, Silvana B; Ferriani, Virgínia Paes Leme; Piotto, Daniela Gerent Petry; Cavalcanti, André de Souza; de Moraes, Ana Júlia Pantoja; Sztajnbok, Flavio Roberto; de Oliveira, Sheila Knupp Feitosa; Campos, Lucia Maria Arruda; Bandeira, Marcia; Santos, Flávia Patricia Sena Teixeira; Magalhães, Claudia Saad

2016-01-01

To establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes. The Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. 1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations. 1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1β inhibitors prevents progression of bone lesions. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Torticollis associated with positional plagiocephaly: a growing epidemic.

PubMed

de Chalain, Tristan M B; Park, Serena

2005-05-01

The primary study aim was to identify characteristics of torticollis associated with plagiocephaly without synostosis (PWS) and to differentiate this from other forms of torticollis. The three commonest causes of infantile torticollis are idiopathic muscular causes such as sternocleidomastoid fibrosis, structural anomalies in the cervical vertebrae, and neurologic or ocular causes, such as certain types of strabismus. Recently, several units have reported increasing numbers of babies presenting with head tilt and reduced range of cervical motion, a form of torticollis apparently associated with PWS and unrelated to the etiologies enumerated above. A secondary aim was to identify local trends in referral patterns over the preceding 3 years. This was a retrospective review of 159 children attending a secondary referral center for management of positional plagiocephaly or torticollis. The data was collected in a university-affiliated child development clinic, and the records of one of three similar, community-based outpatient clinics, staffed by physical therapists and working in conjunction with our tertiary craniofacial surgery center were analyzed by medical staff. There was a persistent escalation in referrals for both PWS and associated torticollis (ie, not attributable to 1 of the 3 causes mentioned) over the study period. Anatomic and clinical features of PWS-associated torticollis were characterised and contrasted with the classic forms of torticollis. Current treatment strategies are outlined and discussed. Torticollis can predispose to PWS, but in a large proportion of our cases of PWS, torticollis appears to develop secondary to plagiocephaly, and the number of presentations is escalating.

Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001-12: a retrospective observational study.

PubMed

Lazzerini, Marzia; Seward, Nadine; Lufesi, Norman; Banda, Rosina; Sinyeka, Sophie; Masache, Gibson; Nambiar, Bejoy; Makwenda, Charles; Costello, Anthony; McCollum, Eric D; Colbourn, Tim

2016-01-01

Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012. Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi's Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children's clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2-11 months of age, and 12-59 months of age using separate multivariable mixed effects logistic regression models. Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92·7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6·6% (95% CI 6·4-6·7). The case fatality rate significantly decreased between 2001 (15·2% [13·4-17·1]) and 2012 (4·5% [4·1-4·9]; ptrend<0·0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors significantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2-11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11·8%), severe undernutrition (15·4%), severe acute malnutrition (34·8%), and symptom duration of more than 21 days (9·0%). Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specific subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of sufficient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of effective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi. Bill & Melinda Gates Foundation. Copyright © 2016 Lazzerini et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Patients receiving anti-TNF therapies experience clinically important improvements in RA-related fatigue: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

PubMed

Druce, Katie L; Jones, Gareth T; Macfarlane, Gary J; Basu, Neil

2015-06-01

Pro-inflammatory cytokines such as TNF-α are important in the pathogenesis of fatigue in conditions such as RA. This study aimed to determine whether fatigue improved in a cohort of RA patients with clinically relevant fatigue commencing anti-TNF-α therapy and, if so, to identify predictors of improvement. Participants recruited to a long-term observational cohort study (the British Society for Rheumatology Biologics Register for RA) provided information on fatigue using the 36-item Short Form Health Survey (SF-36) vitality subscale. The prevalence of severe baseline fatigue (SF-36 vitality ≤12.5) was calculated and improvements, considered as (i) absolute values and (ii) improvement from severe to non-severe fatigue (SF-36 vitality >12.5), were examined 6 months subsequently. A comprehensive set of putative predictors of fatigue improvement were evaluated using multivariable logistic regression. In 6835 participants the prevalence of severe baseline fatigue was 38.8%. Of those with severe fatigue, 70% reported clinically relevant improvement and 66% moved to the non-severe fatigue category (i.e. improvers). The mean change for improvers was three times the minimum clinically important difference for improvement (33.0 U). Independent baseline predictors of improvement were female sex [odds ratio (OR) 1.3 (95% CI 1.1, 1.7)], not being unemployed due to ill health [OR 1.5 (95% CI 1.2, 1.7)], low disability [OR 1.2 (95% CI 1.001, 1.5)], seropositivity [OR 1.2 (95% CI 0.98, 1.4)], not using steroids [OR 1.2 (95% CI 1.03, 1.5)], no history of hypertension [OR 1.4 (95% CI 1.1, 1.6)] or depression [OR 1.3 (95% CI 1.1, 1.5)] and good mental health [SF-36 mental health subscale >35; OR 1.4 (95% CI 1.2, 1.7)]. Fatigued RA patients reported substantial improvement in their fatigue after commencing anti-TNF-α therapy. Further, a number of clinical and psychosocial baseline factors identified those most likely to improve, supporting future stratified approaches to RA fatigue management. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A comparison of the clinical characteristics of women with recurrent major depression with and without suicidal symptomatology.

PubMed

Bi, B; Xiao, X; Zhang, H; Gao, J; Tao, M; Niu, H; Wang, Y; Wang, Q; Chen, C; Sun, N; Li, K; Fu, J; Gan, Z; Sang, W; Zhang, G; Yang, L; Tian, T; Li, Q; Yang, Q; Sun, L; Li, Ying; Rong, H; Guan, C; Zhao, X; Ye, D; Zhang, Y; Ma, Z; Li, H; He, K; Chen, J; Cai, Y; Zhou, C; Luo, Y; Wang, S; Gao, S; Liu, J; Guo, L; Guan, J; Kang, Z; Di, D; Li, Yajuan; Shi, S; Li, Yihan; Chen, Y; Flint, J; Kendler, K; Liu, Y

2012-12-01

The relationship between recurrent major depression (MD) in women and suicidality is complex. We investigated the extent to which patients who suffered with various forms of suicidal symptomatology can be distinguished from those subjects without such symptoms. We examined the clinical features of the worst episode in 1970 Han Chinese women with recurrent DSM-IV MD between the ages of 30 and 60 years from across China. Student's t tests, and logistic and multiple logistic regression models were used to determine the association between suicidality and other clinical features of MD. Suicidal symptomatology is significantly associated with a more severe form of MD, as indexed by both the number of episodes and number of MD symptoms. Patients reporting suicidal thoughts, plans or attempts experienced a significantly greater number of stressful life events. The depressive symptom most strongly associated with lifetime suicide attempt was feelings of worthlessness (odds ratio 4.25, 95% confidence interval 2.9-6.3). Excessive guilt, diminished concentration and impaired decision-making were also significantly associated with a suicide attempt. This study contributes to the existing literature on risk factors for suicidal symptomatology in depressed women. Identifying specific depressive symptoms and co-morbid psychiatric disorders may help improve the clinical assessment of suicide risk in depressed patients. These findings could be helpful in identifying those who need more intense treatment strategies in order to prevent suicide.

The use of renal replacement therapy in acute decompensated heart failure.

PubMed

Udani, Suneel M; Murray, Patrick T

2009-01-01

The worsening of renal function in the context of decompensated heart failure is an increasingly common clinical scenario, dubbed the cardiorenal syndrome. Its development is not completely understood; however, it results from the hemodynamic and neurohumoral alterations that occur in the setting of left ventricular pressure and volume overload with poor cardiac output. Diuretics have been the mainstay of treatment; however, they are often unsuccessful in reversing the vicious cycle of volume overload, worsening cardiac function, and azotemia. Renal replacement therapy (RRT) in the form of isolated or continuous ultrafiltration (UF) with or without a component of solute clearance (hemofiltration or hemodialysis) has been increasingly utilized as a therapeutic tool in this setting. Initial clinical trial data on the use of UF have demonstrated promising cardiac outcomes with regard to fluid removal and symptom relief without worsening renal function. The addition of a component of solute clearance may provide additional benefits in these patients with varying degrees of renal impairment. The exact clinical setting in which the various forms of RRT should be applied as initial or early therapy for acute decompensated heart failure (ADHF) remains unknown. More research examining the use of RRT in ADHF is necessary; however, it appears that the patients with the most severe clinical presentations have the best chance of benefiting from the early application of RRT.

The clinical assessment of aggressive periodontitis patients

PubMed Central

Cho, Chan-Myung; You, Hyung-Keun

2011-01-01

Purpose Few epidemiologic studies have investigated aggressive periodontitis in Koreans, but such studies of disease prevalence and other clinical characteristics would be invaluable in providing proper treatment. The aim of this study was to assess the prevalence of aggressive periodontitis and to measure the extent of associated periodontal breakdown. Methods The study population consisted of 1,692 patients who visited the Department of Periodontology, Wonkwang Daejeon Dental Hospital from January to December, 2010. Clinical parameters (probing depth, gingival recession, periodontal attachment loss) were measured by a single examiner, and radiographic examination was performed at the baseline. Results Twenty-eight (1.65%) patients showed clinical features of aggressive periodontitis, of which 27 patients exhibited the generalized form, and 1 exhibited the localized form. There was no significant difference between the percentage of male and female patients. The probing pocket depth of the maxillary first molar was deeper than that of the other teeth and gingival recession was also the most serious at the maxillary first molar. The periodontal attachment loss was the highest at the maxillary first molar. The average number of missing teeth was 1.29 per subject. Loss of the second molar was prominent. Conclusions Within the limitations of this study, the periodontal breakdown evaluated by attachment loss was found to be most severe at the first molars of aggressive periodontitis patients. However, further large scale multicenter studies are necessary to access more precise data, including prevalence. PMID:21811690

Neurocognitive similarities between severe chronic schizophrenia and behavioural variant frontotemporal dementia.

PubMed

Chan, Hui-Minn; Stolwyk, Rene; Neath, Joanna; Kelso, Wendy; Walterfang, Mark; Mocellin, Ramon; Pantelis, Christos; Velakoulis, Dennis

2015-02-28

This study focuses on a group of patients with chronic schizophrenia who have a more severe form of the disorder, as indicated by socio-functional decline, treatment resistance, and recurrent hospitalisation. Previous research has suggested that the pattern and severity of cognitive deficits in people with severe chronic schizophrenia is similar to that observed in behavioural variant frontotemporal dementia (bvFTD). In the current study, we compared neurocognitive performance in 16 cognitive domains in 7 inpatients with severe chronic schizophrenia, 13 community-dwelling outpatients with chronic schizophrenia, 12 patients with bvFTD, and 18 healthy controls. Our findings revealed more similar cognitive profiles between the schizophrenia inpatient and bvFTD groups compared to the schizophrenia outpatient group, who outperformed the former groups. The current results provide preliminary evidence for a distinct schizophrenia subgroup, distinguishable from other chronic schizophrenia patients by poorer clinical and functional status, who have levels of cognitive impairment comparable to those seen in bvFTD patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A novel KRT5 mutation associated with generalized severe epidermolysis bullosa simplex in a 2-year-old Chinese boy

PubMed Central

Zhang, Jia; Yan, Ming; Liang, Jianying; Li, Ming; Yao, Zhirong

2016-01-01

Mutations in keratin 5 (KRT5) or KRT14 genes are responsible for the most severe form of epidermolysis bullosa simplex (EBS), which is EBS generalized severe (EBS-gen sev). To date, only four pathogenic mutations (p.Arg165Ser and p.Lys199Asn in KRT5; p.Arg125Cys and p.Arg125His in KRT14) have been reported to be responsible for EBS-gen sev in the Chinese population. In the present study, a 2-year-old Chinese boy was clinically suspected to suffer from EBS, and thus Sanger sequencing was performed in the extracted genomic DNA samples from the patient, his parents and 100 healthy controls. A novel de novo heterozygous missense mutation c.503A>G (p.Glu168Gly) located at the N-terminal end segment of the 1A domain in KRT5 was identified by molecular analysis. In silico analysis tools were used to predict the pathogenicity of the novel missense mutation. A diagnosis of EBS-gen sev was thus confirmed according to the clinical presentations and molecular results. PMID:27882080

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia

PubMed Central

Clarke, Geraldine M; Rockett, Kirk; Kivinen, Katja; Hubbart, Christina; Jeffreys, Anna E; Rowlands, Kate; Jallow, Muminatou; Conway, David J; Bojang, Kalifa A; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D; Bougouma, Edith C; Sirima, Sodiomon B; Modiano, David; Amenga-Etego, Lucas N; Ghansah, Anita; Koram, Kwadwo A; Wilson, Michael D; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi K; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N; Manjurano, Alphaxard; Sepúlveda, Nuno; Clark, Taane G; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy ME; Michon, Pascal; Mueller, Ivo; Molloy, Síle F; Campino, Susana; Kerasidou, Angeliki; Cornelius, Victoria J; Hart, Lee; Shah, Shivang S; Band, Gavin; Spencer, Chris CA; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P

2017-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effect has proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual’s level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations. DOI: http://dx.doi.org/10.7554/eLife.15085.001 PMID:28067620

Paraneoplastic Pemphigus: A Paraneoplastic Autoimmune Multiorgan Syndrome or Autoimmune Multiorganopathy?

PubMed Central

Mahajan, Vikram K.; Sharma, Vikas; Chauhan, Pushpinder S.; Mehta, Karaninder S.; Sharma, Anju Lath; Abhinav, C.; Khatri, Gayatri; Prabha, Neel; Sharma, Saurabh; Negi, Muninder

2012-01-01

Paraneoplastic pemphigus (PNP), a clinically and immunopathologically distinct mucocutaneous blistering dermatosis, is a severe form of autoimmune multiorgan syndrome generally associated with poor therapeutic outcome and high mortality. This IgG-mediated disease is initiated by an obvious or occult lymphoproliferative disorder in most cases. Clinically severe mucositis, and polymorphic blistering skin eruptions, and histologically acantholysis, keratinocyte necrosis and interface dermatitis are its hallmark features. A 58-year-old female presented with recurrent, severe, recalcitrant stomatitis and widespread erosions/blistering lesions of one-year duration. Treatment with repeated courses of systemic corticosteroids at a peripheral center would provide temporary relief. She also had fever, productive cough, odynophagia and poor oral intake, herpes zoster ophthalmicus, pain in the abdomen, and watery diarrhea. An array of investigations revealed chronic lymphocytic leukemia (CLL), mediastinal and para-aortic lymphadenopathy, bronchiolitis obliterans, and vertebral osteoporosis/fractures. With the diagnosis of CLL-associated PNP she was managed with dexamethasone-cyclophosphamide pulse (DCP) therapy for 3 cycles initially, followed by COP regimen (cyclophosphamide, vincristine, and prednisolone) for 5 cycles. Remission is being maintained with chlorambucil and prednisolone pulse therapy once in 3 weeks with complete resolution of skin lesions and adequate control of CLL. PMID:23316398

Hereditary inclusion-body myopathy with sparing of the quadriceps: the many tiles of an incomplete puzzle.

PubMed

Broccolini, A; Gidaro, T; Morosetti, R; Sancricca, C; Mirabella, M

2011-10-01

The hereditary inclusion-body myopathies encompass several syndromes with autosomal recessive or dominant inheritance. Despite a different clinical presentation they all have a progressive course leading to severe disability and share similar pathologic findings at the muscle biopsy. Quadriceps-sparing autosomal recessive hereditary inclusion-body myopathy (h-IBM) is the commonest form and is tied to mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. Despite the identification of the causative gene defect, it has not been clarified how mutations of the GNE gene impair muscle homeostasis. Although several lines of evidence argue in favor of an abnormal sialylation of muscle glycoproteins playing a key role in h-IBM pathogenesis, others studies have demonstrated new functions of the GNE gene, outside the sialic acid biosynthetic pathway, that may also be relevant. This review illustrates the clinical and pathologic characteristics of h-IBM and the main clues available to date concerning the possible pathogenic mechanisms of this disorder. Understanding the molecular mechanism underlying h-IBM pathology is a fundamental requisite to plan a future attempt to therapy.

An update on the genetics of usher syndrome.

PubMed

Millán, José M; Aller, Elena; Jaijo, Teresa; Blanco-Kelly, Fiona; Gimenez-Pardo, Ascensión; Ayuso, Carmen

2011-01-01

Usher syndrome (USH) is an autosomal recessive disease characterized by hearing loss, retinitis pigmentosa (RP), and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous and is the most common cause underlying deafness and blindness of genetic origin. Clinically, USH is divided into three types. Usher type I (USH1) is the most severe form and is characterized by severe to profound congenital deafness, vestibular areflexia, and prepubertal onset of progressive RP. Type II (USH2) displays moderate to severe hearing loss, absence of vestibular dysfunction, and later onset of retinal degeneration. Type III (USH3) shows progressive postlingual hearing loss, variable onset of RP, and variable vestibular response. To date, five USH1 genes have been identified: MYO7A (USH1B), CDH23 (USH1D), PCDH15 (USH1F), USH1C(USH1C), and USH1G(USH1G). Three genes are involved in USH2, namely, USH2A (USH2A), GPR98 (USH2C), and DFNB31 (USH2D). USH3 is rare except in certain populations, and the gene responsible for this type is USH3A.

An Update on the Genetics of Usher Syndrome

PubMed Central

Millán, José M.; Aller, Elena; Jaijo, Teresa; Blanco-Kelly, Fiona; Gimenez-Pardo, Ascensión; Ayuso, Carmen

2011-01-01

Usher syndrome (USH) is an autosomal recessive disease characterized by hearing loss, retinitis pigmentosa (RP), and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous and is the most common cause underlying deafness and blindness of genetic origin. Clinically, USH is divided into three types. Usher type I (USH1) is the most severe form and is characterized by severe to profound congenital deafness, vestibular areflexia, and prepubertal onset of progressive RP. Type II (USH2) displays moderate to severe hearing loss, absence of vestibular dysfunction, and later onset of retinal degeneration. Type III (USH3) shows progressive postlingual hearing loss, variable onset of RP, and variable vestibular response. To date, five USH1 genes have been identified: MYO7A (USH1B), CDH23 (USH1D), PCDH15 (USH1F), USH1C(USH1C), and USH1G(USH1G). Three genes are involved in USH2, namely, USH2A (USH2A), GPR98 (USH2C), and DFNB31 (USH2D). USH3 is rare except in certain populations, and the gene responsible for this type is USH3A. PMID:21234346

PubMed Central

MEOLA, GIOVANNI

2013-01-01

Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan involvement. To date two distinct forms caused by similar mutations have been identified. Myotonic dystrophy type 1 (DM1, Steinert's disease) was described more than 100 years ago and is caused by a (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) was identified only 18 years ago and is caused by a (CCTG)n expansion in ZNF9/CNBP. When transcribed into CUG/CCUG-containing RNA, mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins, resulting in spliceopathy of downstream effector genes. Despite clinical and genetic similarities, DM1 and DM2 are distinct disorders requiring different diagnostic and management strategies. DM1 may present in four different forms: congenital, early childhood, adult onset and late-onset oligosymptomatic DM1. Congenital DM1 is the most severe form of DM characterized by extreme muscle weakness and mental retardation. In DM2 the clinical phenotype is extremely variable and there are no distinct clinical subgroups. Congenital and childhood-onset forms are not present in DM2 and, in contrast to DM1, myotonia may be absent even on EMG. Due to the lack of awareness of the disease among clinicians, DM2 remains largely underdiagnosed. The delay in receiving the correct diagnosis after onset of first symptoms is very long in DM: on average more than 5 years for DM1 and more than 14 years for DM2 patients. The long delay in the diagnosis of DM causes unnecessary problems for the patients to manage their lives and anguish with uncertainty of prognosis and treatment. PMID:24803843

Quality of life of patients who undergo breast reconstruction after mastectomy: effects of personality characteristics.

PubMed

Bellino, Silvio; Fenocchio, Marina; Zizza, Monica; Rocca, Giuseppe; Bogetti, Paolo; Bogetto, Filippo

2011-01-01

Reconstruction after mastectomy has become an integral part of breast cancer treatment. The effects of psychological factors on quality of life after reconstruction have been poorly investigated. The authors examined clinical and personality characteristics related to quality of life in patients receiving reconstructive surgery. All patients received immediate reconstruction and were evaluated in the week before tissue expander implantation (T0) with a semistructured interview for demographic and clinical characteristics, the Temperament and Character Inventory, the Inventory of Interpersonal Problems, the Short Form Health Survey, the Severity Item of the Clinical Global Impression, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. Assessment with the Short Form was repeated 3 months after expander placement (T1). Statistics were calculated with univariate regression and analysis of variance. Significant variables were included in a multiple regression analysis to identify factors related to the change T1-T0 of the mean of the Short Form-transformed scores. Results were significant when p was less than or equal to 0.05. Fifty-seven women were enrolled. Results of multiple regression analysis showed that the Temperament and Character Inventory personality dimension harm avoidance and the Inventory of Interpersonal Problems domain vindictive/self-centered were significantly and independently related to the change in Short Form mean score. Personality dimensions and patterns of interpersonal functioning produce significant effects on patients' quality of life during breast reconstruction. Patients with high harm avoidance are apprehensive and doubtful. Restoration of body image could help them to reduce social anxiety and insecurity. Vindictive/self-centered patients are resentful and aggressive. Breast reconstruction could symbolize the conclusion of a reparative process and fulfill the desire of revenge on cancer.

AACR precision medicine series: Highlights of the integrating clinical genomics and cancer therapy meeting.

PubMed

Maggi, Elaine; Montagna, Cristina

2015-12-01

The American Association for Cancer Research (AACR) Precision Medicine Series "Integrating Clinical Genomics and Cancer Therapy" took place June 13-16, 2015 in Salt Lake City, Utah. The conference was co-chaired by Charles L. Sawyers form Memorial Sloan Kettering Cancer Center in New York, Elaine R. Mardis form Washington University School of Medicine in St. Louis, and Arul M. Chinnaiyan from University of Michigan in Ann Arbor. About 500 clinicians, basic science investigators, bioinformaticians, and postdoctoral fellows joined together to discuss the current state of Clinical Genomics and the advances and challenges of integrating Next Generation Sequencing (NGS) technologies into clinical practice. The plenary sessions and panel discussions covered current platforms and sequencing approaches adopted for NGS assays of cancer genome at several national and international institutions, different approaches used to map and classify targetable sequence variants, and how information acquired with the sequencing of the cancer genome is used to guide treatment options. While challenges still exist from a technological perspective, it emerged that there exists considerable need for the development of tools to aid the identification of the therapy most suitable based on the mutational profile of the somatic cancer genome. The process to match patients to ongoing clinical trials is still complex. In addition, the need for centralized data repositories, preferably linked to well annotated clinical records, that aid sharing of sequencing information is central to begin understanding the contribution of variants of unknown significance to tumor etiology and response to therapy. Here we summarize the highlights of this stimulating four-day conference with a major emphasis on the open problems that the clinical genomics community is currently facing and the tools most needed for advancing this field. Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Autoimmune Subepidermal Bullous Diseases of the Skin and Mucosae: Clinical Features, Diagnosis, and Management.

PubMed

Amber, Kyle T; Murrell, Dedee F; Schmidt, Enno; Joly, Pascal; Borradori, Luca

2018-02-01

Autoimmune subepidermal blistering diseases of the skin and mucosae constitute a large group of sometimes devastating diseases, encompassing bullous pemphigoid, gestational pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, and anti-p200 pemphigoid. Their clinical presentation is polymorphic. These autoimmune blistering diseases are associated with autoantibodies that target distinct components of the basement membrane zone of stratified epithelia. These autoantigens represent structural proteins important for maintenance of dermo-epidermal integrity. Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease of the skin and mucosae. Although the disease typically presents with a generalized blistering eruption associated with itch, atypical variants with either localized bullous lesions or "non-bullous" presentations are observed in approximately 20% of patients. A peculiar form of BP typically associated with pregnancy is pemphigoid gestationis. In anti-p200 pemphigoid, patients present with tense blisters on erythematosus or normal skin resembling BP, with a predilection for acral surfaces. These patients have antibodies targeting the 200-kDa basement membrane protein. Epidermolysis bullosa is a rare autoimmune blistering disease associated with autoantibodies against type VII collagen that can have several phenotypes including a classical form mimicking dystrophic epidermolysis bullosa, an inflammatory presentation mimicking BP, or mucous membrane pemphigoid-like lesions. Mucous membrane pemphigoid (MMP) is the term agreed upon by international consensus for an autoimmune blistering disorder, which affects one or more mucous membrane and may involve the skin. The condition involves a number of different autoantigens in the basement membrane zone. It may result in severe complications from scarring, such as blindness and strictures. Diagnosis of these diseases relies on direct immunofluorescence microscopy studies and immunoserological assays. Management of affected patients is often challenging. We will here review the clinical and immunopathological features as well as the pathophysiology of this group of organ-specific autoimmune diseases. Finally, we will discuss the diagnostic approach and the principles of management in clinical practice.

Complete stable remission and autoantibody specificity in myasthenia gravis.

PubMed

Baggi, Fulvio; Andreetta, Francesca; Maggi, Lorenzo; Confalonieri, Paolo; Morandi, Lucia; Salerno, Franco; Bernasconi, Pia; Montomoli, Cristina; Barberis, Massimo; Mantegazza, Renato; Antozzi, Carlo

2013-01-08

Patients with myasthenia gravis (MG) are subgrouped as acetylcholine receptor (AChR)-positive, muscle-specific kinase (MuSK)-positive, and AChR/MuSK-negative MG (or double negative [DN]) on the basis of autoantibody assay. We investigated the relationships between autoantibody specificity, main clinical features, and outcome of the disease, in particular the occurrence of complete stable remission (CSR), by means of a retrospective study on a cohort of 677 Italian patients with MG. A total of 517 (76%) patients with AChR-positive MG, 55 (8%) patients with MuSK-positive MG, and 105 (16%) patients with DN MG were included in the study. Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate associations between baseline characteristics, antibody specificity, and CSR. Clinical stage at onset and at maximal worsening was more severe for MuSK-positive patients: bulbar impairment at maximal worsening was found in 83.6% of MuSK-positive patients compared with 58.6% of AChR-positive patients and 43.8% of DN patients (p < 0.001). Baseline characteristics of AChR-positive and DN patients were similar. CSR was observed in 3.6% of MuSK-positive patients compared with 22.2% of AChR-positive and 21.9% of DN patients. In the whole MG cohort, onset before age 40 (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.27-3.02, p = 0.002) and ocular and generalized clinical stages at maximal worsening were associated with CSR (ocular, HR = 8.05, 95% CI 1.88-34.53, p = 0.005; generalized, HR = 3.71, 95% CI 1.16-11.90, p = 0.023; bulbar, HR = 3.16, 95% CI 1.00-10.05, p = 0.051). MuSK antibodies identify a clinically distinguishable, more severe form of MG since the disease onset, with a lower occurrence of CSR. These features should be considered by the clinician in the management of this particular form of MG.