Subsequent Manifestations Research Articles

The Obstructed Hemivagina, Ipsilateral Renal Anomaly, and Uterine Didelphys Triad and the Subsequent Manifestation of Cervical Aplasia

Study ObjectiveTo compare a case series of the obstructed hemivagina, ipsilateral renal anomaly and uterine didelphys triad with the literature, with a focus on a subset of patients with cervical aplasia. Design, Setting, and ParticipantsA retrospective case series was conducted of all patients with the triad managed between 2005-2013 at a tertiary center for adolescent gynecology. ResultsSimilarities in this cohort, compared to the literature, included heterogeneity of presentation, presence of endometriosis, and asymmetry of affected side. Notable differences included 1 patient with a 16p11.2 microdeletion and 2 patients with subsequent unilateral cervical aplasia. All patients underwent magnetic resonance imaging for diagnosis. Vaginal septum division was performed in 8 cases and excision in 1 case. Both cases with cervical aplasia ultimately underwent hemi-hysterectomy, and highlight the implications of this rare variant in regards to its existence, limitations of magnetic resonance imaging in this context, and suggestions for improvement in diagnosis and management. ConclusionThe complexity of these cases, especially the evolving manifestation of cervical aplasia postoperatively, illustrates the need to recognize limitations in imaging and divergence in definitive management.

What’s Hidden in Gravity Falls: Strange Creatures and the Gothic Intertext

What’s Hidden in Gravity Falls: Strange Creatures and the Gothic Intertext

ХАРАКТЕРНІ КЛІНІЧНІ ОЗНАКИ У СВІЙСЬКИХ КОТІВ ЗА ГЕПАТОЛІПІДОЗУ

Більшість захворювань печінки у свійських котівмають спільну клінічну картину, але кожному з нихпритаманні свої особливості прояву. У статті наве-дено клінічні ознаки гепатоліпідозу у свійських котів:іктеричність кон’юнктиви, слизової оболонки рото-вої порожнини, носа та шкіри, наявність блювання,погіршення якості шерсті та свербіж. Встановлено,що ожиріння тварин, з наступним проявом анорексії,є сприятливим фактором розвитку ліпідозу печінки.Наведена вікова та порідна схильність свійських ко-тів до захворювання на гепатоліпідоз.
 Most liver diseases in domestic cats have the same clinical picture, but each of them has its own features of display. The article presents clinical symptoms of hepatolipidosis in domestic cats: icterus of the conjunctiva, the mucous shell of oral cavity, nose and skin, vomiting, deterioration of the wool and itching. Established that obesity of animals, with subsequent manifestation of anorexia is a favorable factor for development of liver lipidosis. Explained age and pedigree susceptibility of domestic cats to liver lipidosis.

Microscopic polyangiitis: a large single-center series.

Microscopic polyangiitis (MPA) is a rare systemic vasculitis, antineutrophil cytoplasmic antibody associated, characterized by necrotizing small vessel involvement with few or no immune complex deposits. Necrotizing glomerulonephritis is common. Pulmonary capillaritis causing alveolar hemorrhage and hemoptysis is well recognized, but most case series are reported in the nephrology literature and emphasize renal considerations. We present a single-center 10-year retrospective review of 40 patients meeting the 2012 Revised Chapel Hill Nomenclature of MPA, with specific p-antineutrophil cytoplasmic antibody and myeloperoxidase positivity, emphasizing initial and subsequent pulmonary manifestations. We searched the electronic database of our large integrated clinic-hospital system and reviewed charts of all patients with related International Classification of Diseases, Ninth Revision codes for vasculitis in the last 10 years. Several variables were reviewed. Onset of illness was usually abrupt and included respiratory symptoms, and the most common presenting complaint was cough. Hemoptysis occurred during the course of illness in 40%. Pulmonary complaints were found in 80% of patients upon presentation, whereas pulmonary infiltrates were noted in 92%. Managing subspecialty and treatment modalities were quite variable. Pulmonary involvement is much more frequent than the currently reported 25% to 50% when features in addition to hemorrhage are recorded. No clear guidelines direct the evaluation and management of MPA patients. Consistent communication between pulmonary, nephrology, and rheumatology services could improve our understanding of the disease process.

HIV-1-Tat excites cardiac parasympathetic neurons of nucleus ambiguus and triggers prolonged bradycardia in conscious rats

The mechanisms of autonomic imbalance and subsequent cardiovascular manifestations in HIV-1-infected patients are poorly understood. We report here that HIV-1 transactivator of transcription (Tat, fragment 1-86) produced a concentration-dependent increase in cytosolic Ca(2+) in cardiac-projecting parasympathetic neurons of nucleus ambiguus retrogradely labeled with rhodamine. Using store-specific pharmacological agents, we identified several mechanisms of the Tat-induced Ca(2+) elevation: 1) lysosomal Ca(2+) mobilization, 2) Ca(2+) release via inositol 1,4,5-trisphosphate-sensitive endoplasmic reticulum pools, and 3) Ca(2+) influx via transient receptor potential vanilloid type 2 (TRPV2) channels. Activation of TRPV2, nonselective cation channels, induced a robust and prolonged neuronal membrane depolarization, thus triggering an additional P/Q-mediated Ca(2+) entry. In vivo microinjection studies indicate a dose-dependent, prolonged bradycardic effect of Tat administration into the nucleus ambiguus of conscious rats, in which neuronal TRPV2 played a major role. Our results support previous studies, indicating that Tat promotes bradycardia and, consequently, may be involved in the QT interval prolongation reported in HIV-infected patients. In the context of an overall HIV-dependent autonomic dysfunction, these Tat-mediated mechanisms may account for the higher prevalence of sudden cardiac death in HIV-1-infected patients compared with general population with similar risk factors. Our results may be particularly relevant in view of the recent findings that significant Tat levels can still be identified in the cerebrospinal fluid of HIV-infected patients with viral load suppression due to efficient antiretroviral therapy.

Evidence for Epigenetic Alterations in Turner Syndrome Opens up Feasibility of New Pharmaceutical Interventions

DNA methylation is an important regulatory component which influences phenotypes by modulating gene expression. Changes in DNA methylation may lead to altered phenotypes and ability of an organism to respond to stress leading to subsequent manifestation of life style diseases, cancer, etc. The human X chromosome represents a classical model for epigenetic processes governing differential regulation of homologous chromosomes. X monosomy (45, XO) leads to Turner's syndrome in human with mild to severe phenotypes. Using a novel cDNA based high throughput approach of assessing genome wide methylation; we have examined the methylation landscape in human fibroblasts in 45, XO and 46, XX individuals. We report here that as expected methylation of X linked genes is different in these two situations. It was observed that methylation of several autosomal genes is also affected in this X monosomy state. Genes involved in bone remodeling, glucose sensitivity and ovarian function appear to be altered in addition to genes involved in epigenetic regulatory processes. This opens up interesting possibility of misregulation of DNA methylation in the X monosomy state resulting in altered gene expression and altered phenotypes. This may be one of the reasons for the variance, differential severity and penetrance in case of Turner's syndrome. We propose that a systematic analysis of the molecular genetic mechanisms governing this epigenetic regulation will open up new therapeutic interventions which will certainly help in reducing severity of the disease and help in better management of X monosomy (Turner's syndrome).

T-Cell Immunity to Infection with Dengue Virus in Humans

Dengue virus (DENV) is the etiologic agent of dengue fever, the most significant mosquito-borne viral disease in humans. Up to 400 million DENV infections occur every year, and severity can range from asymptomatic to an acute self-limiting febrile illness. In a small proportion of patients, the disease can exacerbate and progress to dengue hemorrhagic fever and/or dengue shock syndrome, characterized by severe vascular leakage, thrombocytopenia, and hemorrhagic manifestations. A unique challenge in vaccine development against DENV is the high degree of sequence variation, characteristically associated with RNA viruses. This is of particular relevance in the case of DENV since infection with one DENV serotype (primary infection) presumably affords life-long serotype-specific immunity but only partial and temporary immunity to other serotypes in secondary infection settings. The role of T cells in DENV infection and subsequent disease manifestations is not fully understood. According to the original antigenic sin theory, skewing of T-cell responses induced by primary infection with one serotype causes less effective response upon secondary infection with a different serotype, predisposing to severe disease. Our recent study has suggested an HLA-linked protective role for T cells. Herein, we will discuss the role of T cells in protection and pathogenesis from severe disease as well as the implications for vaccine design.

Association between autoimmune rheumatic diseases and the risk of dementia.

Aim. Autoimmune rheumatic diseases (ARD) are characterized by systemic inflammation and may affect multiple organs and cause vascular events such as ischemic stroke and acute myocardial infarction. However, the association between ARD and increased risk of dementia is uncertain. This is a retrospective cohort study to investigate and compare the risk of dementia between patients clinically diagnosed with ARD and non-ARD patients during a 5-year follow-up period. Methods. Data were obtained from the Longitudinal Health Insurance Database 2000 (LHID2000). We included 1221 patients receiving ambulatory or hospitalization care and 6105 non-ARD patients; patients were matched by sex, age, and the year of index use of health care. Each patient was studied for 5 years to identify the subsequent manifestation of dementia. The data obtained were analyzed by Cox proportional hazard regression. Results. During the 5-year follow-up period, 30 ARD (2.48%) and 141 non-ARD patients (2.31%) developed dementia. During the 5-year follow-up period, there were no significant differences in the risks of any type of dementia (adjusted hazard ratio (HR), 1.18; 95% CI, 0.79–1.76) in the ARD group after adjusting for demographics and comorbidities. Conclusions. Within the 5-year period, patients with and without ARD were found to have similar risks of developing dementia.

Calculating optimal surveillance for detection of von Hippel–Lindau-related manifestations

von Hippel-Lindau (VHL) mutation carriers develop benign and malignant tumors, requiring regular surveillance. The aim of this study was to calculate the optimal organ-specific age to initiate surveillance and optimal intervals to detect initial and subsequent VHL-related manifestations. In this study, we compare these results with the current VHL surveillance guidelines. We collected data from 82 VHL mutation carriers in the Dutch VHL surveillance program. The cumulative proportion of carriers diagnosed with a first VHL-related manifestation was estimated by the Kaplan-Meier method. The Poisson distribution model was used to calculate average time to detection of the first VHL-related manifestation and subsequent manifestations. We used this to calculate the optimal organ-specific age to initiate surveillance and the surveillance interval that results in a detection probability of 5%. The calculated organ-specific ages to initiate surveillance were 0 years (birth) for adrenal glands, 7 years for the retina, 14 years for the cerebellum, 15 years for the spinal cord, 16 years for pancreas, and 18 years for the kidneys. The calculated surveillance intervals were 4 years for the adrenal glands, biennially for the retina and pancreas, and annually for the cerebellum, spinal cord, and kidneys. Compared with current VHL guidelines, the calculated starting age of surveillance was 6 years later for the retina and 5 years earlier for adrenal glands. The surveillance intervals were two times longer for the retina and four times longer for the adrenal glands. To attain a 5% detection probability rate per organ, our mathematical model indicates that several modifications of current VHL surveillance guidelines should be considered.

Psychosis effect on hippocampal reduction in schizophrenia

In schizophrenia, disruption of the neurodevelopmental processes may lead to brain changes and subsequent clinical manifestations of the illness. Reports of the progressive nature of these morphological brain changes raise questions about their causes. The possible toxic effects of repeated stressful psychotic episodes may contribute to the disease progression. To analyze the influence of illness duration and previous psychotic episodes on hippocampal gray matter volume (GMV) in schizophrenia. We performed an analysis of hippocampal GMV correlations with illness duration, number of previous psychotic episodes, and age in 24 schizophrenia patients and 24 matched healthy controls. We found a cluster of GMV voxels in the left hippocampal tail that negatively correlated with the number of previous psychotic episodes, independent from the effect of age. On the other hand we found no effect of illness duration independent of age on the hippocampal GMV. Finally, we found a cluster of significant group-by-age interaction in the left hippocampal head. We found an additive adverse effect of psychotic episodes on hippocampal morphology in schizophrenia. Our findings support toxicity of psychosis concept, together with etiological heterogeneity of brain changes in schizophrenia.

Touching practice and physical education: deconstruction of a contemporary moral panic

This paper explores the insecurities and discursive moral panics elicited by the discussion of intergenerational touch in education, and their subsequent manifestation in ‘classroom panopticism’. In a number of contexts, public hysteria has grown around the interaction between adult and child, and whether this interaction stays within the narrow parameters of a generally consensual ‘acceptability’. Crossing these boundaries carries grave consequences for those deemed to be exploiting their position and this has had significant implications for the self-identity of practitioners. This climate of preventative fear has also served to manipulate regulatory method, realigning conceptions of practitioner independence. Drawing on interviews with Physical Education teachers in English secondary schools, and applying a Foucauldian theoretical framework, with particular reference to his interpretation of panopticism, this paper investigates the conceptual transformation of contemporary education. Whilst school spaces were once representative of stability, in which roles were clearly defined, the hierarchical dynamic has changed. The teacher, who previously presided with relative professional freedom and autonomy, is now subject to myriad pressures associated with ‘appropriate’ behaviour and the avoidance of any ‘problematic’ interactional incident. Foucault's treatment of panopticism is apt here, as teachers must conduct themselves with an acceptance that they are now governed by an unpredictable yet persistent practical scrutiny.

Association Between Traumatic Experiences and Psychosis Among Incarcerated Men

The possible influence of traumatic experiences on subsequent manifestations of psychosis has been the subject of intense scientific debate in the last decade. Whereas some authors have found a clear association between trauma and psychosis, others have pointed out methodological deficiencies in the research or have found only weak associations. Others found no association between trauma and psychosis in exclusive samples of men and recommend the use of studies stratified by sex. This article uses the data from an epidemiological study of a random sample of 500 male inmates in two prisons in Andalusia (Spain) to analyze the association between psychosis and trauma. The inmates were diagnosed using The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) interviews by teams of experienced clinicians. The results show a clear association between traumatic events and some functional psychosis or some psychosis, including induced psychoses. These associations resist the possible effect of confusing variables such as the origin of the inmates, educational level, or having an addictive disorder. We discuss the need to pay special attention to traumatic experiences such as witnessing extreme violence against others or participating in acts of violence, particularly in men. Our results are compatible with different theories that defend the association between trauma and psychosis.

Pericardial Constriction Attributable to Graft-Versus-Host Disease

Graft-versus-host disease (GVHD) occurs as a complication of hematopoietic stem cell transplantation when donor immune cells attack host cells identified as immunologically nonself. This is beneficial in completing the eradication of residual malignant cells (the graft versus tumor effect), but detrimental through attack on other host cells and subsequent manifestations of acute and chronic GVHD. Cardiac manifestations of GVHD are rare and include pericardial effusion, coronary artery disease, and conduction abnormalities.1 There are only 2 previously described cases of GVHD-induced pericardial constriction.2,3 Here, we report a case of hematopoietic stem cell transplantation complicated by constrictive pericarditis associated with chronic GVHD of the pericardium, which showed rapid response to systemic corticosteroids. A 44-year-old information technology consultant and keen long-distance cyclist was referred to the cardiac clinic for investigation of dyspnoea. He was diagnosed 4 years previously with Philadelphia-positive acute lymphoblastic leukemia, and was refractory to induction chemotherapy, later achieving morphological remission with imatinib and Ida-FLAG (idarubicin, fludarabine, cytarabine, and granulocyte colony–stimulating factor). He went on to have hematopoietic stem cell transplantation with a regime involving full intensity myeloablation and total body irradiation, followed by infusion of matched unrelated donor hematopoietic stem cells. He made a good initial recovery, complicated only a pleural effusion managed …

X-linked inhibitor of apoptosis (XIAP) deficiency: The spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis

X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in BIRC4 was initially described in patients with X-linked lymphoproliferative syndrome (XLP) who had no mutations in SH2D1A. In the initial reports, EBV-associated hemophagocytic lymphohistiocytosis (HLH) was the predominant clinical phenotype. Among 25 symptomatic patients diagnosed with XIAP deficiency, we identified 17 patients who initially presented with manifestations other than HLH. These included Crohn-like bowel disease (n=6), severe infectious mononucleosis (n=4), isolated splenomegaly (n=3), uveitis (n=1), periodic fever (n=1), fistulating skin abscesses (n=1) and severe Giardia enteritis (n=1). Subsequent manifestations included celiac-like disease, antibody deficiency, splenomegaly and partial HLH. Screening by flow cytometry identified 14 of 17 patients in our cohort. However, neither genotype nor protein expression nor results from cell death studies were clearly associated with the clinical phenotype. Only mutation analysis can reliably identify affected patients. XIAP deficiency must be considered in a wide range of clinical presentations.

Maritime Strategies of Rising Powers: developments in China and Russia

This paper seeks to uncover the drivers of maritime strategy formulation in Russia and China, two active players on the international stage that have often been identified as both rising and regional powers. The paper takes as its starting point the realist theory of state power and threat perception, which provide the means and motivation for states to accumulate material capabilities in an effort to safeguard their position in the international system. Given the increasing pressures of a changing security environment, China’s and Russia’s maritime strategies show a trend towards greater complexity and capability. The paper also addresses the impact of the revolution in military affairs ( rma ) and its subsequent manifestation as force transformation in Western states, especially the USA. Given that this new, qualitatively focused way of war has gained supremacy, at least where high-intensity inter-state war is concerned, the question remains of whether the Chinese and Russians will choose to emulate the leading powers in the system or, instead, will forge into the unknown and formulate an entirely different and innovative maritime strategy.

Formation mechanisms of nano and microcones by laser radiation on surfaces of Si, Ge, and SiGe crystals

In this work we study the mechanisms of laser radiation interaction with elementary semiconductors such as Si and Ge and their solid solution SiGe. As a result of this investigation, the mechanisms of nanocones and microcones formation on a surface of semiconductor were proposed. We have shown the possibility to control the size and the shape of cones both by the laser. The main reason for the formation of nanocones is the mechanical compressive stresses due to the atoms’ redistribution caused by the gradient of temperature induced by strongly absorbed laser radiation. According to our investigation, the nanocone formation mechanism in semiconductors is characterized by two stages. The first stage is characterized by formation of a p-n junction for elementary semiconductors or of a Ge/Si heterojunction for SiGe solid solution. The generation and redistribution of intrinsic point defects in elementary semiconductors and Ge atoms concentration on the irradiated surface of SiGe solid solution in temperature gradient field take place at this stage due to the thermogradient effect which is caused by strongly absorbed laser radiation. The second stage is characterized by formation of nanocones due to mechanical plastic deformation of the compressed Ge layer on Si. Moreover, a new 1D-graded band gap structure in elementary semiconductors due to quantum confinement effect was formed. For the formation of microcones Ni/Si structure was used. The mechanism of the formation of microcones is characterized by two stages as well. The first stage is the melting of Ni film after irradiation by laser beam and formation of Ni islands due to surface tension force. The second step is the melting of Ni and subsequent manifestations of Marangoni effect with the growth of microcones.

THU0373 Clinical presentation of erdheim-chester disease: Data from a cohort of 10 patients and review of the literature

BackgroundErdheim-Chester disease (ECD) is a rare, inflammatory disease of unknown etiology, characterized by the infiltration of non-Langerhans histiocytes. ECD typically involves long bones, with almost pathognomonic nuclear medicine finding. The...

Characterization of the Huntington intermediate CAG repeat expansion phenotype in PHAROS

We aimed to describe the clinical phenotype conferred by the intermediate-length huntingtin allele CAG repeat expansion in a population-based study. The Prospective Huntington At Risk Observational Study (PHAROS) enrolled adults at risk for Huntington disease (HD). They were assessed approximately every 9 months with the Unified Huntington's Disease Rating Scale (UHDRS) by investigators unaware of participants' gene status. UHDRS scores were compared according to the Huntingtin gene CAG repeat number: expanded >36, intermediate 27-35, and nonexpanded controls <26. Fifty (5.1%) of the 983 participants had an intermediate allele (IA). They were similar to controls on UHDRS motor, cognitive, and functional measures, but significantly worse behaviorally on apathy and suicidal ideation. On 5 of the 9 other behavioral items and on total behavior, the IA group's scores were worse than those of controls and expanded participants, who themselves scored significantly worse than controls on 6 behavioral measures. Retention rates at 4 years were 48% for the IA group compared to 58% and 60% for the expanded and control groups. In a cohort at risk for HD, the IA was associated with significant behavioral abnormalities but normal motor and cognition. This behavioral phenotype may represent a prodromal stage of HD, with the potential for subsequent clinical manifestations, or be part of a distinct phenotype conferred by pathology independent of the CAG expansion length.

Pure epileptic headache and related manifestations: a video‐EEG report and discussion of terminology

We present the first video-EEG recording of episodes of "epileptic headache". The case reported is that of a 9-year-old girl with brief episodes (of a few minutes) of severe frontal headache, which corresponded to the presence of concurrent spikes and slow waves, starting in the right temporal area. A dysplastic lesion of the right temporal lobe was observed by MRI and the patient received surgery, with subsequent disappearance of headaches. This case highlights ictal EEG as the main diagnostic tool for epileptic headache. We discuss the terminology regarding this type of manifestation and believe that cases without subsequent epileptic manifestations, as in the present case, should be more appropriately referred to as "pure ictal epileptic headache" or simply "pure epileptic headache". [Published with video sequences].

Sympathetic Nervous System

Activation of the sympathetic nervous system after myocardial infarction results in the mobilization of hematopoietic stem cells, causing an inflammatory boost that accelerates atherosclerosis. This may have important implications for future therapeutic interventions targeting inflammatory pathways. The social and economic impacts of atherosclerosis and subsequent macrovascular clinical manifestations like myocardial infarction (MI) and stroke are immense. Complications of atherosclerosis and MI, such as heart failure, and also recurrent cardiovascular events present a major challenge. They seem to occur more frequently after MI than expected by presumed linear progression of atherosclerosis. In a recent article in Nature , Dutta et al1 found strong evidence that, like in a vicious cycle, acute MI itself accelerates atherosclerosis by triggering a burst of acute systemic inflammation initiated by progenitor cell mobilization from the bone marrow niche. The authors present 4 major findings: (1) acute MI (but also stroke) activates the sympathetic nervous system (SNS); (2) this causes the release of upstream progenitor cells from bone marrow niches; (3) these cells are hosted by the spleen leading to amplified extramedullary myelopoiesis; and (4) at the end of this multimodal cascade, there is a strong increase in inflammation in atherosclerotic plaques, leading to increased size and instability. The authors also show that experimental MI in apolipoprotein E–/– mice activates inflammatory pathways. In serial measurements after coronary ligation, concentrations of cathepsin in aortic plaques and the expression of the inflammatory cytokines interleukin (IL)-6, myeloperoxidase, and matrix metalloproteinase-9 were increased. Consecutively, this was associated with higher vulnerability of atherosclerotic plaque, as demonstrated by decreased thickness of the fibrous cap, and enlarged necrotic cores. Moreover, after MI, the number of macrophages and monocytes, especially the Ly-6Chigh monocyte subset, were increased in the aorta of apolipoprotein E–/– mice and exhibited higher levels of messenger …