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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↗

Sarcomatous dedifferentiated renal cell carcinoma mimicking a severe purulent kidney infection.

Sarcomatous renal cell carcinomas (SRCCs) originate from a dedifferentiation of renal cell carcinoma (RCC). They are characterized by an aggressive course and very poor prognosis. Less known is their ability to imitate inflammatory diseases of the kidney. The aim of the study was to outline the less usual symptoms of SRCCs in a retrospective analysis of 180 patients operated for RCC in 1997-2001. In 11 (6.1%) patients (8 men and 3 women, age 40-76 years, mean age 60 years) SRCC was present. The pTNM classification, results of histological examination, the stage of RCC dedifferentiation and survival after the operation are presented. In almost every patient SRCC was diagnosed at a late stage with combined histological variants of RCC. Survival of the patients after the operation ranged from 1 to 19 (average 8.8) months. In 2 patients an atypical clinical picture imitated abscess of the kidney and calculous pyonephrosis. The authors warn that in spite of the clinical signs of inflammatory disease of the kidneys, a tumorous origin should be excluded. In doubtful cases a quick peroperative biopsy and histology should be performed. Sometimes only a definitive histological examination can reveal the tumorous origin of the disease.

Abscess↗

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↗

A classification of problems regarding gut endocrinomas (carcinoids and relevant neoplasms).

In the field of gut endocrinomas (carcinoids and relevant neoplasms), several classifications have been internationally accepted and utilized at varying frequency. The basis of the concepts regarding gut endocrinomas from which these classifications have been proposed were drawn from the different aspects. These included embryology, histologic growth patterns, histochemistry including silver impregnations, electron microscopic morphology of endocrine secretory granules, endocrine cell types and histologic morphology along with functional characteristics, supplemented by immunohistochemical features. Due to continuous progress being made in this particular field of research and the many new discoveries made by pioneering investigators, the concepts of gut endocrinomas have been modified and revised during such long history of the research activities. This study aims to re-evaluate these classifications in relation to the concepts of gut endocrinomas, and to select and supply rearranged classifications that may be easily utilized for practical purposes. This study also proposes a comprehensive overview of histogenesis in the gut endocrinoma group. This consists of typical carcinoids and their atypical variants taken in relation to the carcinomatous group including ordinary carcinomas and their variants with endocrine elements. Special emphasis is given to the point that there is a gradual transition, one without a definite boundary between these tumors.

Carcinoid Tumor↗

[Exercise-induced thallium-201 myocardial perfusion defects in angina pectoris without significant coronary artery stenosis].

We performed exercise thallium-201 myocardial scintigraphy in 32 patients with angina pectoris to study the incidence of perfusion defects, who had no significant organic stenosis on coronary angiography. None of them had myocardial infarction or cardiomyopathy. Thallium-201 myocardial scintigraphy and 12-lead ECG recording were performed during supine bicycle ergometer exercise. Perfusion defects in thallium-201 scintigrams in SPECT images were assessed during visual analysis by two observers. In the coronary angiograms obtained during intravenous infusion of nitroglycerin, the luminal diameter of 75% stenosis or less in the AHA classification was regarded as an insignificant organic stenosis. Myocardial perfusion defects in the thallium-201 scintigrams were detected in eight (25%) of the 32 patients. Six of these eight patients had variant angina documented during spontaneous attacks with ST elevations in standard 12-lead ECGs. Perfusion defects were demonstrated at the inferior or inferoposterior regions in six patients, one of whom had concomitant anteroseptal defect. The defects were not always accompanied by chest pain. All but one patient demonstrating inferior or inferoposterior defects showed ST depression in leads II, III and aVF on their ECGs, corresponding to inferior wall ischemia. The exception was a case with right bundle branch block. Thus, 25% of the patients with angina pectoris, who had no evidence of significant organic stenosis on their coronary angiograms, exhibited exercise-induced perfusion defects in their thallium-201 scintigrams. Coronary spasms might have caused myocardial ischemia in these patients.

Adult↗

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↗

[Clinical immunological classification of tuberculous uveitis].

Clinical and immunological studies carried out in 251 patients with tuberculous uveitis (TU) revealed three types of inflammatory reactions in the uveal tract in this patient population: productive, exudative, and productive-exudative (mixed), differing by the type of immune disorders. The findings helped develop a clinical immunological classification of TU, taking account of the clinical form of uveitis, type of inflammatory reaction of the uveal tract, disease pattern, involvement of one or both eyes, complications, and the immunopathological variants of TU course.

Adolescent↗

Use of the espZ gene encoded in the locus of enterocyte effacement for molecular typing of shiga toxin-producing Escherichia coli.

Infections with Shiga toxin-producing Escherichia coli (STEC) result in frequent cases of sporadic and outbreak-associated enteric bacterial disease in humans. Classification of STEC is by stx genotype (encoding the Shiga toxins), O and H antigen serotype, and seropathotype (subgroupings based upon the clinical relevance and virulence-related genotypes of individual serotypes). The espZ gene is encoded in the locus of enterocyte effacement (LEE) pathogenicity island responsible for the attaching and effacing (A/E) lesions caused by various E. coli pathogens (but not limited to STEC), and this individual gene ( approximately 300 bp) has previously been identified as hypervariable among these A/E pathogens. Sequence analysis of the espZ locus encoded by additional STEC serotypes and strains (including O26:H11, O121:H19, O111:NM, O145:NM, O165:H25, O121:NM, O157:NM, O157:H7, and O5:NM) indicated that distinct sequence variants exist which correlate to subgroups among these serotypes. Allelic discrimination at the espZ locus was achieved using Light Upon eXtension real-time PCR and by liquid microsphere suspension arrays. The allele subtype of espZ did not correlate with STEC seropathotype classification; however, a correlation with the allele type of the LEE-encoded intimin (eae) gene was supported, and these sequence variations were conserved among individual serotypes. The study focused on the characterization of three clinically significant seropathotypes of LEE-positive STEC, and we have used the observed genetic variation at a pathogen-specific locus for detection and subtyping of STEC.

Bacterial Typing Techniques↗

Genotype determination of hepatitis C virus from northern India: identification of a new subtype.

Hepatitis C virus (HCV) shows substantial nucleotide sequence diversity distributed throughout the viral genome, with many variants showing only 68-79% overall sequence homology. This has led to problems in diagnosis of HCV using commercial immunoassays. Based on clustering of homologous sequences, various genotypes and subtypes of HCV have been described from different geographical regions. In the present study, 11 isolates from India were genotyped using sequence comparison for part of the non-structural (NS5) and structural (core) regions. Parts of the genome covering 451 bp (nt 9-459) of the core gene and a 249 bp fragment (nt 7959-8207) of the NS5 gene were reverse transcribed and amplified using nested polymerase chain reaction (RT-PCR). The amplified fragments were cloned and sequenced. The classification into genotypes was done on the basis of phylogenetic analysis. Four isolates showed sequence homology to type 1b. Two of the isolates were classified as type 3a. One isolate was classified as type 3b and the remaining four isolates were found to be variants of type 3 but did not belong to any designated subtype. On the basis of phylogenetic analysis two of the unclassified isolates were put into a new subtype of 3 named as 3g. In one of these variants, parts of a 5'-noncoding (5' NCR; 204 bp), envelope-E1 (435 bp), and NS3 (502 bp) regions were also amplified, cloned, and sequenced. This study demonstrates the type 3 variants including a new subtype (3g) to be the major cause of HCV infection in India.

Amino Acid Sequence↗

New strategies for the treatment of acute myelogenous leukemia: differentiation induction--present use and future possibilities.

A differentiation block and an accumulation of immature myeloid cells characterize acute myelogenous leukemia (AML). However, native AML cells usually show some morphological signs of differentiation that allow a classification into different subsets, and further differentiation may be induced by exposure to various soluble mediators, for example, all-trans retinoic acid (ATRA) and several cytokines. Combination therapy with ATRA and chemotherapy should now be regarded as the standard treatment of the acute promyelocytic leukemia (APL) variant of AML. Although several agents can also induce leukemic cell differentiation for other AML subgroups, in vitro studies as well as clinical data have demonstrated that these agents often have heterogeneous effects on the leukemic progenitors. This makes the clinical impact of differentiation induction therapy for individual patients difficult to predict. However, differentiation induction should be regarded as a promising therapeutic approach, especially as a part of immunotherapy or in combination with intensive chemotherapy to increase the susceptibility of AML blasts to drug-induced apoptosis. Although the morphology-based French-American-British classification was used to identify APL as an AML subset that required a special treatment, it seems unlikely that this classification alone can be used to identify new subsets of AML patients with special therapeutic requirements. Future studies on differentiation induction in AML should therefore focus on A) the identification of therapeutic agents with more predictable effects; B) the use of clinical and laboratory parameters to define new subsets of AML patients in which differentiation induction has a predictable and beneficial effect, and C) the characterization of how AML blast sensitivity to drug-induced apoptosis is altered by differentiation induction.

Apoptosis↗

Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders.

Recurrent aphthous stomatitis (RAS), commonly known as canker sores, has been reported 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. One of its variants is the most painful condition of the oral mucosa. Recurrent aphthous stomatitis 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). The natural history of individual lesions of RAS is important, because it is the bench mark against which treatment benefits are measured. The lesions of RAS are not caused by a single factor but occur in an environment that is permissive for development of lesions. These factors include trauma, smoking, stress, hormonal state, family history, food hypersensitivity and infectious or immunologic factors. The clinician should consider these elements of a multifactorial process leading to the development of lesions of RAS. To properly diagnose and treat a patient with lesions of RAS, the clinician must identify or exclude associated systemic disorders or "correctable causes." Behçet's disease and complex aphthosis variants, such as ulcus vulvae acutum, mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome, fever, aphthosis, pharyngitis, and adenitis (FAPA) syndrome, and cyclic neutropenia, should be considered. The aphthous-like oral ulcerations of patients with human immunodeficiency virus (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.

AIDS-Related Opportunistic Infections↗

Nosocomial hepatitis C virus infection in a renal transplantation center.

Nosocomial hepatitis C virus (HCV) infections were recorded in the renal transplantation unit of the university hospital. There were cases of acute HCV infection with aggressive clinical courses diagnosed from a positive HCV RNA test in the early post-transplantation period and which remained anti-HCV negative. Their anti-HCV seronegativity was attributed to them having acquired HCV under intense immunosuppressive therapy and suggested that the aggressive clinical course could be due to the deficient immune response resulting in an inability to limit viral replication. There were also donors diagnosed as having acute HCV infection in the early post-operative period. Genotyping and sequence analysis for HCV were performed on the isolates of eight of these patients who were consecutively transplanted and of three donors whose recipients were infected with HCV prior to transplantation, and who acquired acute HCV infection after transplantation. Of the eight recipients in the first group three were genotype 1a, three were genotype 1b, one was genotype 3a, and the last one was genotype 4 according to Simmond's classification. Of the three donor-recipient couples both the HCV isolates from one couple were genotyped as 1b and the phylogenetic analysis indicated that the patients were infected with a common variant of HCV, but the genotypes of HCV isolates from the other couples were different. Recipients were genotype 1b and the donors were genotype 1a in these couples. Genotype results of the first group and donor-recipient couples, and sequence analysis of genotype 1b and 1a isolates, showed that the source of infection was not a unique strain and there were multiple breaks in universal precautions while managing these patients.

Cross Infection↗

A meta-analytic review of the CYP2A6 genotype and smoking behavior.

Individuals who carry variant alleles of the CYP2A6 gene are poor metabolizers of nicotine and are believed to be more sensitive to nicotine's aversive effects than those with normal alleles. This sensitivity is hypothesized to exert a protective effect against smoking initiation and lead to lower cigarette consumption among smokers with variant alleles. Although early studies found an association between variant CYP2A6 alleles and smoking behavior, more recent studies have not. A meta-analysis was conducted to help resolve these conflicting results. A literature search produced 11 studies providing information on CYP2A6 genotyping in smokers or nonsmoking control subjects. Participants were classified as smokers (ever-smokers or current smokers) or nonsmokers (former or never-smokers), and as carrying normal CYP2A6 genes or one or more variant alleles. Information regarding cigarette consumption also was included. Effect sizes were calculated from each study and then aggregated into an overall effect size. This analysis failed to find any empirical evidence of a relationship between variant CYP2A6 alleles and smoking status (n=4091) or cigarette consumption (n=1537). Although these results suggest the CYP2A6 gene is not associated with smoking behavior, the use of broad smoking status classifications (e.g., ever- vs. never-smoking), which fail to account for the complex nature of gene expression (e.g., gene-gene interactions), may have obscured the relatively modest genetic influences that might have been present. What role, if any, the CYP2A6 gene plays in smoking behavior will be understood only if future research addresses these methodological concerns.

Aryl Hydrocarbon Hydroxylases↗

von Willebrand disease.

Considerable progress has been made in characterizing the specific molecular defects responsible for the heterogeneous disorder known as von Willebrand disease (VWD). A large number of molecular defects have been identified and precise characterization may now be possible in the majority of type 2A, type 2B, type 2N, and potentially also type 3 VWD cases. However, the most common variant, type 1 VWD, still remains a major challenge. Continued progress in this area will improve our understanding of the pathogenesis of VWD and lead to more rapid and precise diagnosis and classification for this common disorder. The problems of incomplete VWD penetrance and poor diagnostic sensitivity and accuracy for the currently available clinical laboratory tests provide strong incentives for the development of DNA-based diagnostics. In addition, prenatal diagnosis is now possible either at the level of single point mutations (for some subtypes) or by RFLP analysis (assuming linkage to the von Willebrand factor [VWF] gene) and will probably be applied with increasing frequency for VWD type 3 (17, 133, 175). Understanding the molecular basis of VWD also has important implications for VWF structure and function and is helping to define critical binding domains within the VWF molecule. Insights gained from these studies may eventually lead to improved therapeutic approaches not only for VWD, but also for a variety of other genetic and acquired hemorrhagic and thrombotic disorders.

DNA Probes↗

Exact scaling properties of a hierarchical network model.

We report on the exact results for the degree K, the diameter D, the clustering coefficient C, and the betweenness centrality B of a hierarchical network model with a replication factor M. Such quantities are calculated exactly with the help of recursion relations. Using the results, we show that (i). the degree distribution follows a power law P(K) approximately K-gamma with gamma=1+ln M/ln(M-1), (ii). the diameter grows logarithmically as D approximately ln N with the number of nodes N, (iii). the clustering coefficient of each node is inversely proportional to its degree, C proportional, variant 1/K, and the average clustering coefficient is nonzero in the infinite N limit, and (iv). the betweenness centrality distribution follows a power law P(B) approximately B-2. We discuss a classification scheme of scale-free networks into the universality class with the clustering property and the betweenness centrality distribution.

Journal Article↗

Congenital central nervous system anomalies.

Magnetic resonance imaging, because of its multiplanar capabilities and exquisite contrast differentiation, has risen above all other forms of in vivo imaging for the classification and determination of congenital central nervous system (CNS) anomalies. We briefly discuss pertinent aspects of CNS embryology and, using a recently proposed classification of central nervous system anomalies, present examples of a spectrum of abnormalities that one may encounter in practice. These anomalies include: the Chiari malformations, encephaloceles, holoprosencephaly, septooptic dysplasia, Dandy-Walker variant, hydranencephaly, phakomatoses, schizencephaly, agyria or pachygyria, and dysgenesis of the corpus callosum.

Central Nervous System↗

Characterization of the chicken transitin gene reveals a strong relationship to the nestin intermediate filament class.

Our laboratory previously reported that transitin is a radial glial intermediate filament protein sharing the basic structural features common to all intermediate filament (IF) proteins. It contains an alpha-helical core domain flanked by a short nonhelical head and a long COOH-terminal tail. The core sequence of transitin shows the greatest similarity to Xenopus tanabin and to rat and human nestin. We also reported that transitin has multiple splice variants derived from the deletion or inclusion of a leucine-zipper heptad repeat domain in the COOH-terminal tail. In the present study, we provide new evidence to support the classification of nestin and transitin in the same group of IF proteins based on the number and position of its introns. In addition, we suggest that the different isoforms of transitin are produced by a splicing mechanism that recognizes consensus 5' and 3' splice sites contained within the coding sequence of the leucine-zipper heptad repeat domain.

Animals↗

[Possibilities of the immunodiagnosis of erythroleukemia].

The authors describe 6 cases of acute leukemia in which erythroid antigens identified by monoclonal antibodies HAE-3 and HAE-9 (against glycophorin A and antigen of nuclear erythroid cells) were expressed on blasts. The morphocytochemical methods were employed to establish different varieties of leukemia according to the FAB-classification: 2-L1, 2-L2, 1-M2, and 1-M. In 4 cases, the existence of the markers of the early stages of differentiation was shown immunologically. Two patients demonstrated the mixed, variant of leukemia (erythroid-T-cellular and erythroid-myeloid). In 5 out of the 6 cases, the patients turned out refractory to chemotherapy. The lethal outcomes were recorded in the first acute period or in the stage of a relapse (one patient) after a very short 2-month remission.

Antibodies, Monoclonal↗