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Recurrent aphthous stomatitis in the diagnosis of Behçet's disease.

Recurrent aphthous stomatits (RAS) is also known as recurrent oral ulcers, recurrent aphthous ulcers, or simple or complex aphthosis. RAS is the most common inflammatory ulcerative condition of the oral mucosa in North American patients. RAS has been the subject of active investigation along multiple lines of research including epidemiology, immunology, clinical correlations and therapy. Clinical evaluation of the patient requires correct diagnosis of RAS and classification of the disease based on morphology (MIAU, MJAU, HU) and severity (simple versus complex). In order to properly diagnose and treat a patient with lesions of RAS, the clinician must exclude other causes of acute oral ulcers. Complex aphthosis and complex aphthosis variants associated with systemic disorders should be considered. The aphthous-like oral ulcerations of patients with HIV disease represent a challenging differential diagnosis. The association of lesions of RAS with hematinic deficiencies and gastrointestinal diseases provides an opportunity to identify a "correctable cause" which, with appropriate treatment, can result in a remission or substantial lessening of disease activity. Finally, when all of these factors are considered, the evaluation of the patient for Behçet's disease can be continued on firm grounds that one of the major criteria for the diagnosis of Behçet's disease has been met.

Behcet Syndrome↗

Meningioma: the impact of new techniques for the diagnosis and prognosis.

Our knowledge of meningioma has expanded considerably in the last few years. Immunohistochemistry, cytogenetics and molecular biology have given an important contribution to this improvement. Meningiomas can have almost endless variations in cellular morphology, architectural patterns and metaplastic changes. The majority of them have no prognostic implications. But a few variants should be recognised because of peculiar clinico-pathologic correlations or biological behavior. Histological features useful in distinguishing benign from potentially aggressive meningiomas have been identified. According to the WHO classification meningiomas are classified as benign (Grade 1), atypical (Grade 2) and anaplastic (Grade 3). Since histological appearance fails to predict accurately the clinical behaviour in a significant percentage of meningiomas, the attention has turned from tumor histology to tumor biology. Proliferative indices can be used, together with other histologic features, in assessing the prognosis as well as the postoperative management of the patients. Karyotyping may be of use to identify a subgroup of patients at higher risk for recurrence who may need special follow-up and treatment. The most consistent chromosome aberration in meningiomas seems to be a monosomy 22. As the karyotype becomes progressively abnormal, the tumor becomes more aggressive. Molecular genetic analysis has shown that TP53 gene mutation may be considered as a marker for malignant transformation in meningioma. P53 immunoreactivity is not always associated with the gene mutation but is not detectable in benign meningiomas.

Journal Article↗

[Benign multilocular cystic nephroma versus cystic nephroblastoma. A review and classification of cystic metanephric neoplasms (author's transl)].

A review of reported cases of cystic metanephric tumors is given. It is shown that among these neoplasms two distinct pathologic entities exist: the cystic nephroblastoma and the benign multilocular cystic nephroma. The former, a benign variant of Wilms' tumor, is found in children of younger age. Its possible precursor is the infantile form of nephroblastomatosis. The second neoplasm, a clinically and biologically benign tumor, occurs in older children and in half of the cases it is also encountered in adults. It derives from metanephric hamartomas which have their origin in the huvenile form of nephroblastomatosis.

Age Factors↗

Contributions of Common, Rare, and Somatic Genetic Variants to Incidence of Atrial Fibrillation.

IMPORTANCE: Atrial fibrillation (AF) has a complex genetic architecture involving common, rare, and somatic variants. The association between these components requires further investigation. OBJECTIVE: To examine the individual and combined contributions of polygenic, monogenic, and somatic genetic variants to AF incidence, and develop an integrated genomic model (IGM-AF) for improved risk prediction. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used whole-genome sequence data from participants of the UK Biobank, with follow-up for AF events through hospital records, death registries, and self-report. The UK Biobank recruited participants aged 40 to 69 years in the UK between 2006 and 2010. Study data were analyzed from August 2022 to November 2024. EXPOSURES: IGM-AF comprising an AF polygenic risk score (PRS), a composite rare variant gene set (AFgeneset), and somatic variants associated with clonal hematopoiesis of indeterminate potential (CHIP). Clinical AF risk was estimated using the Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) score. MAIN OUTCOMES AND MEASURES: The primary outcome was hazard ratios (HRs) for 5-year incident AF attributable to PRS, AFgeneset, CHIP, and their interactions. The predictive performance of IGM-AF and its components was quantified using HRs, C statistics, and reclassification indices. RESULTS: A total of 416&#x202f;085 individuals (mean [SD] age, 56.6 [8.0] years; 224&#x202f;642 female [54.0%]) with 30&#x202f;797 AF cases were included. The PRS (HR per 1 SD, 1.65; 95% CI, 1.63-1.67; P&#x2009;<&#x2009;1&#x2009;&#xd7;&#x2009;10-8), AFgeneset (HR, 1.63; 95% CI, 1.52-1.75; P&#x2009;=&#x2009;1.46&#x2009;&#xd7;&#x2009;10-42), and CHIP (HR, 1.26; 95% CI, 1.15-1.38; P&#x2009;=&#x2009;1.41&#x2009;&#xd7;&#x2009;10-6) were associated with incident AF. The 5-year cumulative incidence of AF was at least 2-fold among individuals having all 3 genetic drivers (common, rare, and somatic drivers) compared with those with only 1 driver. Integration of IGM-AF with a clinical risk model (CHARGE-AF) showed higher predictive performance (C statistic, 0.80; 95% CI, 0.80-0.80) compared with IGM-AF and CHARGE-AF alone. The classification of the at-risk population for AF was improved when IGM-AF was added to CHARGE-AF (net reclassification index, 0.08; 95% CI, 0.07-0.09). CONCLUSIONS AND RELEVANCE: Results of this cohort study demonstrated the complementary value of common, rare, and somatic variants in shaping genomic AF risk. Leveraging comprehensive genetic information may enhance screening and preventive interventions for AF.

Humans↗

Normal and anomalous coronary arteries: definitions and classification.

Results of a comprehensive survey of the literature concerning coronary artery anatomy, embryology, and pathophysiology show the lack of an adequate definition of normal coronary arteries. To fill this gap, the present review considers the available data concerning the embryogenesis of the coronary arteries and proposes a new definition of normality that refers to essential anatomic features. The concepts of normal variant versus anomaly are introduced, based on a statistical definition of the normal range (99% of the presentations observed in a normal, unselected population). Coronary anomalies are defined as those patterns found in less than 1% of the cases. The wide spectrum of coronary abnormalities is then organized according to a comprehensive classification scheme. For clinical purposes the conceptual difference between anatomic and pathophysiologic anomalies is stressed. The current paucity of experimental studies concerning normal and abnormal embryogenesis of the coronary arteries is found to be the major limitation to an understanding of this subject.

Coronary Vessel Anomalies↗

Genotypic resistance and HIV-1 subtype in Brazilian children on dual and triple combination therapy.

BACKGROUND: Antiretroviral therapy is provided by the Brazilian Ministry of Health to eligible HIV-infected individuals. Based on clinical and immunological classification, the Brazilian guidelines recommend dual or triple therapy for children. However, the development of drug-resistant strains or poor adherence to therapy could impact the efficacy of this approach. OBJECTIVES: We examined relationships between RNA levels, CD4+ T-cell counts, treatment history, and the prevalence of drug-resistant variants in a cohort of HIV-1-infected children in Rio de Janeiro, Brazil. STUDY DESIGN: Direct sequencing of reverse transcriptase and protease genes from plasma was performed. Virologic and CD4+ T-cell counts responses to therapy were assessed by changes in HIV-1 RNA levels and CD4+ T-cell counts from baseline. RESULTS: Thirty-seven patients were receiving dual therapy and 38 were on triple therapy at enrollment, segregated by antiretroviral history. Both groups had a higher increase in CD4+ T cell counts and a lower viral load in pre-treatment antiretroviral-naïve subjects. Notably, there was a direct correlation between the higher frequencies of drug-resistance mutations and cross-resistance with previous usage of antiretroviral (ARV) therapy in both groups. Non-B subtypes isolates were found in 21.3% of samples. A smaller increase in CD4+ T cell counts was found between non-B subtypes when compared to B-subtypes. CONCLUSIONS: These results suggest that less immunological recovery and a higher number of mutations related to drug resistance were associated with previous usage of ARV and consequent higher time under drug selective pressure in these HIV-infected Brazilian children. These facts suggest the preferential use of triple drug combination as first line regimen in children.

Adolescent↗

From the jumping Frenchmen of Maine to post-traumatic stress disorder: the startle response in neuropsychiatry.

The startle response is a universal and phylogenetically ancient reflex. Pathological exaggerations and modifications of startle underlie the symptomatology of a surprisingly diverse range of neuropsychiatric disorders, a fact that seems to have gone largely unappreciated. We review the available literature on the physiology of the normal human startle response and examine the neuropsychiatric conditions characterized by pathological startle. Startle epilepsy and primary hyperekplexia are considered as neurological disorders involving abnormal startle. Patients with hyperstartle and exotic culture-bound syndromes characterized by excessive startle are considered by the authors to represent extreme variants of the normal startle response. Post-traumatic stress disorder, drug and alcohol withdrawal states and schizophrenia all have abnormal startle as a clinical feature secondary to increased arousal and presumed disturbance of central neurotransmitter systems. The neurophysiological mechanisms by which abnormalities of the startle response may occur are discussed and a system of classification of neuropsychiatric hyperstartles is suggested.

Humans↗

Erythroleukemia: a need for a new definition.

The new WHO classification abolishes the frontier between RAEB-t with 20% of blasts and leukemia with 30% of blasts. We review the definitions of erythroleukemia and discuss the relationship between FAB AML6, RAEB-t and AML6 variant. We ask whether secondary erythroleukemias are the same entity as RAEB-t on survival, karyotype and cytologic characteristics. We suggest that 'AML6 variant' with pure erythroid lineage proliferation would be the real de novo erythroleukemia. Current FAB AML6 entity will probably be classified in either subgroup (1) multilineage dysplasia; (2) therapy-related leukemia; or (3) acute erythroid leukemia subdivided into erythroleukemia (erythroid/myeloid) and pure erythroid leukemia, in the WHO classification - a classification which highlights the importance of clinical and cytogenetic prognostic factors.

Adolescent↗

Human immunodeficiency virus type 1 reverse-transcriptase and protease subtypes: classification, amino acid mutation patterns, and prevalence in a northern California clinic-based population.

Phylogenetic analysis of the reverse transcriptase (RT) and protease of 117 published complete human immunodeficiency virus (HIV) type 1 genome sequences demonstrated that these genes cluster into distinct subtypes. There was a slightly higher proportion of informative sites in the RT (40.4%) than in the protease (34.8%; P= .03). Although most variation between subtypes was due to synonymous nucleotide substitutions, several subtype-specific amino acid patterns were observed. In the protease, the subtype-specific variants included 7 positions associated with drug resistance. Variants at positions 10, 20, 36, and 82 were more common in non-B isolates, whereas variants at positions 63, 77, and 93 were more common in subtype B isolates. In the RT, the subtype-specific mutations did not include positions associated with anti-retroviral drug resistance. RT and protease sequences from 2246 HIV-infected persons in northern California were also examined: 99.4% of the sequences clustered with subtype B, whereas 0.6% clustered with subtype A, C, or D.

Amino Acid Sequence↗

[Colitic variant of the gastrointestinal form of salmonellosis].

Of 3327 hospitalized patients with salmonellosis, a clinical picture of isolated distal colitis was noted in 142 (4.3%). Acute dysentery was diagnosed in them before the results of bacteriological stool examination were ready. In this variant of salmonellosis S. enteritidis and S. haifa were detected twice as more frequently than in the other variants. As compared to dysentery, the colitic variant of salmonellosis was characterized by more marked intoxication syndrome whereas stomach pains were less spasmodic, less frequently localized in the sigmoid colon; important symptoms for differential diagnosis like tenesmus, false rectal tenesmus, pains and spasms of the sigmoid colon were less frequently noted. Therefore this type of salmonellosis should be included in the clinical classification of salmonellosis of adults on the basis of an obvious clinical picture.

Acute Disease↗

In vivo evaluation of the pathogenicity of field isolates of infectious bronchitis virus.

The pathogenicity of 13 field isolates of infectious bronchitis virus (IBV) isolated from Georgia broiler farms from 1989 to 1992 was evaluated using the IBV and Escherichia coli mixed-infection model. Based on the clinical signs, mortality, and lesions, the isolates were classified as high, intermediate, and low in pathogenicity. The in vivo classification was compared with the serotype classification results obtained by reverse transcriptase-polymerase chain reaction-restriction fragment length polymorphism analysis. The high-pathogenicity group was composed of five isolates representing three serotypes: Arkansas, Georgia variant (GAV), and Massachusetts. Isolates in the intermediate- and low-pathogenicity groups were all representatives of the Connecticut serotype, except for one isolate, which belonged to the Massachusetts serotype.

Animals↗

[Evaluation of the proliferation and line of lymphoid cells in various lymphoproliferative diseases using a double immunocytochemical method].

The increased range of the diagnostic criteria and the introduction of the classification scheme "Practical Formulation of Non-Hodgkin's Lymphomas for Clinical Application" made the authors to study proliferative potential of lymphoid cells with identification of the cell line affiliation. The investigation was carried out with the use of the double immunocytochemical test employing anti-nuclear (Ki-67) and line-specific monoclonal antibodies on peripheral blood lymphocytes, those of lymph nodes and bone marrow obtained from 40 patients with lymphoproliferative diseases and on the cells of lymphoblastoid line 501. The disease variant was classified according to the WHO criteria. The highest (> 60%) proliferative activity of lymphoid cells was found in the bone marrow in acute non-T non-B lymphoblast leukemia and in lymph node in T-cell and non-T non-B-cell lymphoblast lymphosarcoma. A broad range in the number of proliferative cells existed among B-cell lymphosarcomas of lymphoblast (12-73%) and prolymphocytic (0-91%) variants. Together with heterogeneous immunological phenotype, this reflects a wide spectrum of various nosological entities recognized by the WHO classification as lymphoblast and prolymphocytic variants of lymphosarcoma, says about the defects of the above classification. Extremely low (< 1%) percent of proliferative cells was observed in B-cell chronic lymphoid leukemia and hairy-cell leukemia. These differences in tumor cell proliferative potential in different lymphoproliferative diseases agree with the views on maturation and differentiation of lymphoid cells. The data obtained by the authors support the necessity of correcting routine histological data by immunological characteristics of pathological lymphoid cells, primarily, by introduction of data on cell proliferative activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗

Interviewer effects on epidemiologic diagnoses of posttraumatic stress disorder.

In an epidemiologic study of 641 interviewed subjects in the Australian Vietnam Veterans Health Study, three diagnoses of Vietnam combat-related posttraumatic stress disorder (PTSD) were obtained: lifetime prevalence using a variant of the Diagnostic Interview Schedule and lifetime and current (1-month) PTSD prevalence using the Standardized Clincical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Third Revision. Prevalence estimates using the Standardized Clinical Interview varied according to interviewer characteristics (female vs. male, clinician vs. nonclinician) but not for the Diagnostic Interview Schedule. The authors use a simple variant of logistic regression to distill estimates of two informative parameters characterizing interviewers' judgments: severity threshold (related to the individual interviewer's criterion of "caseness") and reliability (related to degree of classification error of the individual interviewers). Examination of these estimates shows that female clinicians adopted lower severity thresholds for diagnosis of PTSD than other interviewers and hence had higher prevalence estimates while being relatively reliable in their judgments. Examination also shows that nonclinician interviewers can perform at least as reliably as clinicians. The Diagnostic Interview Schedule measure of PTSD was not moderated by these interviewer aspects. This use of threshold and reliability parameters is offered for routine use in epidemiologic field studies to examine potential interviewer effects.

Australia↗

Antigenic and molecular analyses of different Chlamydia pneumoniae strains.

Chlamydia pneumoniae is an important human respiratory pathogen. Classification of C. pneumoniae isolates into distinguishable serovars or genotypes has not yet been reported. To determine whether antigenic or molecular variants among C. pneumoniae isolates exist, six strains were studied via immunoblot analysis and DNA sequence determination of the entire major outer membrane protein (MOMP) gene omp1. The strains included four prototype strains and two clinical isolates from our laboratory. Immunoblot analysis of sera from patients infected with C. pneumoniae revealed antigenic differences between the C. pneumoniae strains. Strong reactivity of one serum sample with a 65-kDa protein in two C. pneumoniae strains which was not observed with the other strains was the most prominent finding. All sera reacted with the 40-kDa MOMP. Comparison of the omp1 DNA sequences revealed that the omp1 genes of all strains were identical and were 100% identical to the sequence of the omp1 gene of C. pneumoniae AR-39. The results of this study demonstrate that unlike C. trachomatis, the omp1 gene is conserved in C. pneumoniae. Furthermore, it was shown that C. pneumoniae strains are antigenically different. This finding indicates that more than one serovar of C. pneumoniae exist.

Antigenic Variation↗

Scheuermann's kyphoscoliosis associated with Charcot-Marie-Tooth syndrome.

Much confusion and disagreement exists regarding the classification and characteristics of inherited disorders manifesting neurogenic muscular atrophy. Many authors consider Charcot-Marie-Tooth syndrome (CMTS) and Roussy Levy syndrome (RLS) forme fruste or variants of Friedreich's ataxia (FA). Familial kyphoscoliosis has often been described in FA and RLS but not with CMTS. The purpose of this paper is to present detailed clinical and laboratory findings in a family with three cases of Scheuermann's kyphoscoliosis and CMTS in three generations. In all cases Scheuermann's kyphoscoliosis was associated with pes cavus, markedly diminished vibratory and position sensation in the lower extremities, absent deep tendon reflexes and muscular atrophy, predominantly of the distal muscles. Fine rhythmic tremor of outstretched hands and positive Romberg sign were present in one case only. Serum creating phosphokinase was elevated in two cases. Motor nerve conduction studies revealed impaired function in the median, ulnar, tibial and peroneal nerves. Sensory nerve conduction wal also impaired in median and ulnar nerves. There was evidence of left ventricular hypertrophy in one case only. The nosology and relationship between CMTS, RLS and FA are discussed.

Adolescent↗

Congenital dyserythropoietic anemias: epidemiology, clinical significance, and progress in understanding their pathogenesis.

The congenital dyserythropoietic anemias (CDAs) comprise a group of rare hereditary disorders of erythropoiesis, characterized by ineffective erythropoiesis as the predominant mechanism of anemia and by distinct morphological abnormalities of the majority of erythroblasts in the bone marrow. The classification in three types as proposed in 1968 is still valid, but there is genetic heterogeneity within each type, and there are additional variants of unknown genetic basis. CDA II is the most frequent, and the nonfamilial type of CDA III the rarest group. The genes of CDA II and CDA III were mapped to chromosome 20 and 15, respectively, and the gene of CDA I on 15q was recently cloned. Therapeutic decision making requires definition of the type, an estimate of individual severity, and presence of or risk for complications. Therapeutic measures include interferon-alpha for CDA I, splenectomy for CDA II, and iron depletion for all individuals at risk for secondary hemochromatosis.

Anemia, Dyserythropoietic, Congenital↗

A comparison of delusional and nondelusional body dysmorphic disorder in 100 cases.

A controversial issue that was debated for DSM-IV is whether body dysmorphic disorder (BDD)--a preoccupation with an imagined defect in appearance--can be psychotic. BDD is classified separately from its delusional counterpart (delusional disorder, somatic type) in DSM-IV, but does it have a psychotic variant that overlaps with, and may even be the same diagnostic entity as, its delusional disorder variant? One hundred consecutive patients with DSM-III-R-defined BDD or its delusional variant were assessed with a semistructured interview, the Structured Clinical Inverview for DSM-III-R, and a modified version of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The 48 patients with nondelusional BDD were compared with the 52 patients with delusional BDD (i.e., delusional disorder, somatic type). The two groups did not differ significantly in terms of most variables examined, including demographics, phenomenology, course, associated features, comorbidity, and treatment response. Thus, BDD may have a psychotic subtype that significantly overlaps with, and may even be the same disorder as, its delusional disorder variant. However, delusional subjects had higher total scores on the modified Y-BOCS, suggesting that the delusional variant of BDD may be a more severe form of the disorder. Although preliminary, these findings have implications for BDD's treatment and classification, suggesting that inclusion of a delusional (psychotic) subtype of BDD should be considered for future editions of DSM.

Adolescent↗

Genotype-phenotype correlations in disorders of peroxisome biogenesis.

Genetically determined human peroxisomal disorders are subdivided into two major categories: disorders of peroxisome biogenesis (PBD), in which the organelle is not formed normally, and those that involve a single peroxisomal enzyme. Twelve PBD have been identified, and the molecular defects have been defined in 10. All involve defects in the import of proteins into the organelle. Factors required for this import are now referred to as peroxins (PEX) and form the basis of a new and preferred classification system. The PBD are associated with four clinical phenotypes, named before their association with the organelle was recognized: Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and rhizomelic chondrodysplasia punctata (RCDP). The first three are associated with 9 of the 10 PEX defects that have been defined so far, and represent a clinical continuum with variant severity, with ZS the most severe, NALD intermediate, and IRD the least severe. RCDP is associated with PEX7. Genotype-phenotype correlations are complicated by the fact that the clinical manifestations of the ZS-NALD-IRD continuum can be mimicked by disorders that affect single enzymes of peroxisomal fatty acid oxidation, and PEX7 by disorders of plasmalogen synthesis enzymes. Furthermore, clinical manifestations of each of the PEX disorders may vary. Phenotypic expression varies with the nature of the mutation, the milder phenotypes being associated with mutations that do not abolish function completely, or with mosaicism. Definition of the molecular defects is of great value for genetic counseling and may be of aid in establishing prognosis.

Genotype↗