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A new classification for cervical vertebral injuries: influence of CT.

OBJECTIVE: Computed tomography (CT) has been demonstrated to be superior to radiography in identifying cervical vertebral injuries. However, many of these injuries may not be clinically significant, and require only minimal symptomatic and supportive treatment. It is therefore imperative that radiologists and spine surgeons have criteria for distinguishing between those injuries requiring surgical stabilization and those that do not. The authors propose a new classification of cervical vertebral injuries into two categories: major and minor. DESIGN AND PATIENTS: A data base, acquired on 1052 separate cervical injuries in 879 patients seen between 1983 and 1998, was reviewed. Four categories of injury based on mechanism [hyperflexion (four variants), hyperextension (two variants), rotary (two variants), and axial compression (five variants)] were identified. "Major" injuries are defined as having either radiographic or CT evidence of instability with or without associated localized or central neurologic findings, or have the potential to produce the latter. "Minor" injuries have no radiographic and/or CT evidence of instability, are not associated with neurologic findings, and have no potential to cause the latter. RESULTS AND CONCLUSIONS: Cervical injury should be classified as "major" if the following radiographic and/or CT criteria are present: displacement of more than 2 mm in any plane, wide vertebral body in any plane, wide interspinous/interlaminar space, wide facet joints, disrupted posterior vertebral body line, wide disc space, vertebral burst, locked or perched facets (unilateral or bilateral), "hanged man" fracture of C2, dens fracture, and type III occipital condyle fracture. All other types of fractures may be considered "minor".

Cervical Vertebrae↗

Intergroup Rhabdomyosarcoma Study: update for pathologists.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood, and 75% of such cases in the United States are reviewed at the Pathology Center for the Intergroup Rhabdomyosarcoma Study Group (IRSG). The first four generations of IRSG therapeutic trials (IRS I-IV) and supportive pathologic studies have generated a new International Classification of Rhabdomyosarcoma (ICR) that offers new morphologic concepts to the practicing pathologist. The objective of this report is to clearly define emerging histopathologic categories of RMS as defined by the ICR, and to emphasize correlative immunohistochemical or molecular studies. Emerging ICR variants of RMS place the patient in widely divergent prognostic categories (superior, botryoid or spindle cell variants; poor, solid alveolar or diffusely anaplastic variants). The cardinal histopathologic features of the ICR combined with results of studies of fusion genes seen with t(1;13) and t(2;13) will help delineate therapeutic subgroups of RMS for the fifth generation (IRS V) of IRSG studies. Consequently, it is imperative for the practicing pathologist to be familiar with the practical workup and diagnosis of RMS in childhood.

Biomarkers, Tumor↗

Ultrastructural features of solid/trabecular areas in differentiated thyroid carcinoma.

The presence of areas exhibiting a solid/trabecular pattern of growth within an otherwise differentiated thyroid carcinoma represents a source of controversy as regards its proper classification and biologic and prognostic significance. The aim of the current study was to investigate the ultrastructural features of solid/trabecular areas in differentiated thyroid carcinoma and to compare those features with the submicroscopic profile of differentiated, poorly differentiated (insular), and undifferentiated (anaplastic) variants of thyroid cancer. The study series included differentiated carcinoma with solid/trabecular areas (3 cases), conventional papillary carcinoma (4 cases), follicular variant of papillary carcinoma (4 cases), poorly differentiated (insular) carcinoma (3 cases), and undifferentiated (anaplastic) carcinoma (3 cases). It was found that the solid/trabecular areas in differentiated carcinoma and poorly differentiated (insular) carcinoma share similar ultrastructural features and overall retain, even if attenuated, many of the submicroscopic attributes of differentiated carcinomas. In particular, nests of neoplastic cells were observed showing a highly developed cytosecretory apparatus and the presence of numerous abortive/rudimentary follicles, and intercellular and intracellular (intracytoplasmic) lumina/canaliculi of variable morphology. The study supports the hypothesis that the solid/trabecular areas do not merely represent an architectural pattern but rather should be regarded as the expression of a process of reduced differentiation similar to that of poorly differentiated (insular) carcinoma.

Adenocarcinoma↗

Genetic diversity and evolution of hepatitis C virus--15 years on.

In the 15 years since the discovery of hepatitis C virus (HCV), much has been learned about its role as a major causative agent of human liver disease and its ability to persist in the face of host-cell defences and the immune system. This review describes what is known about the diversity of HCV, the current classification of HCV genotypes within the family Flaviviridae and how this genetic diversity contributes to its pathogenesis. On one hand, diversification of HCV has been constrained by its intimate adaptation to its host. Despite the >30 % nucleotide sequence divergence between genotypes, HCV variants nevertheless remain remarkably similar in their transmission dynamics, persistence and disease development. Nowhere is this more evident than in the evolutionary conservation of numerous evasion methods to counteract the cell's innate antiviral defence pathways; this series of highly complex virus-host interactions may represent key components in establishing its 'ecological niche' in the human liver. On the other hand, the mutability and large population size of HCV enables it to respond very rapidly to new selection pressures, manifested by immune-driven changes in T- and B-cell epitopes that are encountered on transmission between individuals with different antigen-recognition repertoires. If human immunodeficiency virus type 1 is a precedent, future therapies that target virus protease or polymerase enzymes may also select very rapidly for antiviral-resistant mutants. These contrasting aspects of conservatism and adaptability provide a fascinating paradigm in which to explore the complex selection pressures that underlie the evolution of HCV and other persistent viruses.

Biological Evolution↗

Anatomic variation of the thoracic duct and visualization of mediastinal lymph nodes: a lymphographic study.

Of 243 thoracic ducts (TD) demonstrated during pedal lymphography, 65 (26.8%) had anatomic variations. In 58 of 65 cases with TD variants, mediastinal lymph nodes were visualized. This suggests that the radiographic appearance of mediastinal nodes is associated with TD anatomic variations. Two or more channels in the cervical portion of the thoracic duct were seen in 195 of the 243 cases. A classification of these anatomic variations is proposed.

Humans↗

Protective function of transcription factor TR3 orphan receptor in atherogenesis: decreased lesion formation in carotid artery ligation model in TR3 transgenic mice.

BACKGROUND: Smooth muscle cells (SMCs) play a key role in intimal thickening in atherosclerosis and restenosis. The precise signaling pathways by which the proliferation of SMCs is regulated are largely unknown. The TR3 orphan receptor, the mitogen-induced nuclear orphan receptor (MINOR), and the nuclear receptor of T cells (NOT) are a subfamily of transcription factors belonging to the nuclear receptor superfamily and are induced in activated SMCs. In this study, we investigated the role of these transcription factors in SMC proliferation in atherogenesis. METHODS AND RESULTS: Multiple human vascular specimens at distinct stages of atherosclerosis (lesion types II to V by American Heart Association classification) derived from 14 different individuals were studied for expression of these transcription factors. We observed expression of TR3, MINOR, and NOT in neointimal SMCs, whereas no expression was detected in medial SMCs. Adenovirus-mediated expression of a dominant-negative variant of TR3, which suppresses the transcriptional activity of each subfamily member, increases DNA synthesis and decreases p27(Kip1) protein expression in cultured SMCs. We generated transgenic mice that express this dominant-negative variant or full-length TR3 under control of a vascular SMC-specific promoter. Carotid artery ligation of transgenic mice that express the dominant-negative variant of TR3 in arterial SMCs, compared with lesions formed in wild-type mice, results in a 3-fold increase in neointimal formation, whereas neointimal formation is inhibited 5-fold in transgenic mice expressing full-length TR3. CONCLUSIONS: Our results reveal that TR3 and possibly other members of this transcription factor subfamily inhibit vascular lesion formation. These transcription factors could serve as novel targets in the treatment of vascular disease.

Adenoviridae↗

Bilateral acinous cell tumors of the parotid gland.

Acinous cell tumors are uncommon neoplasms which arise either from the secretory cells of the salivary gland acini or from pluripotential duct cells and occur almost exclusively in the parotid gland. Nine previous instances of the bilateral occurrence of this tumor in the parotid gland have been reported. We present a tenth case and illustrate several aspects of the clinical behavior of this unique tumor. The histological pattern of this type of tumor was considered universally to be benign until 1953 when attention was called to a malignant variant. It is difficult to find reference to a benign form after that time. It is, in fact, impossible to forecast the clinical behavior of an individual specimen based upon its histopathology. In order to recognize this unpredictability, the World Health Organization Classification of Epithelial Tumors of Salivary Gland Origin proposed a category, "Acinic Cell Tumors," separate from clearly benign or malignant neoplasms. Later, attention was called to the grammatical designation, "acinous cell tumor." Because acinous cell tumors are uncommon, numerically significant series are gathered from several institutions or over several decades during which treatment methods vary widely. This makes it difficult to accept the validity of conclusions based upon the reported data. There is, however, a clearly documented tendency of the tumor to recur after long symptomless intervals so that extended follow-up is necessary before "cure" is established. Treatment of acinous cell tumors is surgical. The value of radiation therapy in the management of recurrent tumors is not firmly established.

Carcinoma↗

[Slow-progressive schizophrenia (actual problems of clinical appearance and systematics)].

Slow-progressive schizophrenia is a slow-progredient endogenous process characterized by a prevalence of either negative disorders which do not reach final stages as in a case of psychotic types, or positive symptom complexes showing affinity to psychopathological appearances of "borderline" level (obsessions, somatoform, dissociate, nonpsychotic affective disorders, over-value formations). The clinical systematics of slow-progressive schizophrenia is built on a model implying a prevalence of either negative or positive disorders. Respectively, in the terms of "negative" schizophrenia, there are disease variants featured by a predominance of basic manifestations of an endogenous process: slow-progredient simple, asthenic, and senestopathic schizophrenia. Positive schizophrenia following the pattern of pseudoneurosis is represented by the following variants: neurotic-like, hysteric, depersonalization, visceral neurotic, hypohondriac as well as reactive schizophrenia.

Diagnosis, Differential↗

[Survival of patients with malignant tumors of the ovaries in relation to the stage according to the TNM classification].

To study the survival of patients in different spread of malignant tumors, the data on 419 patients with serous cystadenocarcinomas of the ovaries were analysed. Late results of treatment in these patients classified by 4 stages did not differ from the routinely observed issues. In staging of the tumor process in these patients according to the TNM system four variants in the degree of the process extension corresponded to each stage, which gave a precise idea as to the extent of the process not only judging by the primary focus condition, but also by metastases spread, thus enabling one to have a complete and proper knowledge of the true extension of the disease.

Cystadenocarcinoma↗

[Laser surgery of cicatricial laryngeal stenosis].

The authors consider possibility of using surgical lasers for treatment of cicatricial laryngostenosis (CL); present classification of stenoses depending on the causes and location; emphasize advantages of high-energy laser vs conventional methods (reduced blood loss, no need in previous tracheotomy or laryngofissure, minimal reactive changes, rapid epithelization); describe the procedure of laser radiation and its variants depending on tumor location in the larynx.

Adolescent↗

Superficial oral fungal infections.

Fungal infections in humans are provoked and exacerbated by defects in the cellular immune system. Hence, the emergence of novel clinical variants of oral candidoses and rare mycoses with the pandemic spread of human immunodeficiency virus infection is not surprising. The new clinical entities of oral candidoses that have been described in the past few years have had a significant impact on the classification of these diseases. Classification of oral candidoses is an issue addressed in some detail here. Angular cheilitis is a disease commonly associated with Candida infection. In the West, it is frequently seen in the elderly, but a report from Asia indicates that the disease may be prevalent in the young age groups due to factors such as anemia, despite the similarity of the infective agents. A novel cofactor implicated in infectious states has been the host blood group secretor status, and data from three studies suggest that the latter may play an intriguing role in the pathogenesis of oral candidosis. Finally, a new mouse model has been described as a substitute for the rat model in investigating the host-parasite interactions in oral candidosis, and its pros and cons are reviewed.

Acquired Immunodeficiency Syndrome↗

[Combinations of different types and variants of ectopia of the ureteral ostia].

Ectopias of the ostia ureteris are generally accepted to be divided into intra- and extravesical ones. It is expedient to divide this abnormality into lower (that of the ureteral ostium below and more medial than the normal site) and upper (that of above and more lateral than the normal site) ectopias of the ostia ureteris. The lower ectopia may be intra- and extravesical. The upper ectopia may be also intra- and extravesical. In ureteral ostial ectopia, the passage of urine from the kidney into the urinary bladder is impaired due to either mechanical ureteral obstruction or vesicoureteral reflux. The lower intravesical ectopia of the ostium ureteris is frequently associated with ureterocele. The study was undertaken to examine 242 patients with ectopia of the ostia ureteris, including those with extravesical (5.3%), intravesical (93.8%) and associated (0.9%) ectopias. Lower ectopia of the ostia ureteris was observed in 28.5%, upper, in 64.5%, and associated ones in 7%. The authors outline 14 different combinations of various types and variants of ureteral ostial ectopias which were observed in 25 patients. The diagnosis of such complicated abnormalities may be made only on the basis of knowledge of all the variants of lower and upper ectopias of the ostia ureteris. All these abnormalities require surgical correction.

Adolescent↗

Near tetraploid prostate carcinoma. Methodologic and prognostic aspects.

BACKGROUND: The clinical value of DNA ploidy analysis in prostate carcinoma has been an issue for investigation for more than 2 decades. In general, diploid or pseudodiploid tumors are associated with a favorable prognosis and aneuploid tumors with an unfavorable prognosis, irrespective of type of treatment. Tumors with DNA values in the tetraploid region (around 4c) present a diagnostic problem. Such DNA distributions may clearly represent aneuploid tumors with an unfavorable prognosis. However, a 4c distribution may conversely represent a tetraploid tumor (possibly a polyploid variant of the diploid tumor) with a favorable prognosis. Previous data from our laboratory indicate the existence of such a tetraploid subgroup. The goal of the current study was to investigate the diagnostic problem of 4c tumors in greater detail. METHODS: Ploidy classification of cytologic smears by image cytometry was performed in a retrospective study of 334 patients with hormonally treated prostate carcinoma. Follow-up time was 30 years or until death. RESULTS: Three ploidy types were defined: near-diploid (D type), near-tetraploid (T type), and highly aneuploid (A type). Tumors with a modal value within the tetraploid region were found in 27% (92 cases) of the total material. Of these, 9% were defined as T type and 18% as A type. Overall, 37% of the tumors were classified as D type, 9% as T type, and 54% as A type. Of the A type tumors, one-third had modal DNA values in the tetraploid (4c) region. Multivariate analysis showed a statistically significant difference between A type tumors and D and T type, but not between D type and T type. Both D and T type tumors progressed slowly and killed the patients 5 to 30 years after diagnosis, whereas A type tumors progressed rapidly and killed the patients within 6 years of diagnosis. CONCLUSIONS: By image cytometry, prostate carcinoma can be divided into three ploidy types: D, T, and A type. Biologically, however, the tumors fall into only two groups: low grade malignant, pseudodiploid tumors of D or T type, and high grade malignant, highly aneuploid tumors of A type.

Carcinoma↗

Heterogeneity among specific phobia types in DSM-IV.

Recently, it has been suggested that situational specific phobias (e.g., phobias of driving, flying, enclosed places) are more closely related to agoraphobia than are other specific phobia types. The present study investigated this hypothesis by examining heterogeneity among the four main DSM-IV specific phobia types, particularly with respect to variables believed to be associated with agoraphobia. Using interviews and behavioral testing, 60 patients with specific phobias of animals, heights, blood/injections, or driving were compared with respect to etiology, age of onset, physiological response, predictability of panic attacks, and focus of apprehension. Fifteen patients suffering from panic disorder with agoraphobia served as a comparison group for some measures. Relative to the other specific phobias, driving phobias were most strongly associated with a later age of onset, similar to that of individuals with agoraphobia. Height phobias were also associated with a late age of onset as well as a more internal focus of apprehension, relative to other groups. Finally, individuals in the blood/injection phobia group reported a more internal focus of apprehension than those in other groups and were the only group to report a history of fainting in the phobic situation. Overall, the results did not support the hypothesis that situational phobias are a variant of agoraphobia. In fact, on several of the variables for which groups did differ, individuals with height phobias (a phobia from the natural environment type) showed a pattern most similar to individuals with agoraphobia. The implications of these results for the classification of specific phobias are discussed.

Adult↗

Anal cloacogenic carcinoma: classification and clinical behavior.

A retrospective study of 35 patients with anal cloacogenic carcinomas showed that the histological characteristics of the tumors were correlated with their biological behavior. The basaloid squamous type of cloacogenic carcinoma was more common in women (3.6:1) and had a more favorable course in both men and women, with a mean survival of 5.0 years. Glandular variants of these tumors, with an adenocystic or mucoepidermoid pattern, occurred predominantly in men and had a more aggressive course, manifested by early metastases to inguinal and mesenteric lymph nodes, liver, and lung, with mean survival limited to 2.5 years. Nine of the 11 patients who survived longer than five years had the basaloid squamous histological pattern and were treated by abdominoperineal resection or pelvic exenteration; five of these patients also received postoperative therapy with radiation. The overall actual five-year survival for patients with anal cloacogenic carcinoma was 41% in this study. The histological pattern of anal cloacogenic carcinoma provides useful prognostic information to the clinician.

Adenocarcinoma↗

[Solid tumors in the child. New advances and the importance of histological sub-classifications. II. Tumors of the peripheral nervous system, soft tissue, liver and pancreas].

According to immunohistochemical, ultrastructural features of neural cells, and identical 11; 22 chromosome translocation, at least some extra osseous Ewing's sarcoma, as well as the malignant small cell tumor of the thoracopulmonary region (Askin's tumor) are actually classified as peripheral neuroepitheliomas. Embryonal rhabdomyosarcoma, including the botryoid variant, is now, when treated with appropriate chemotherapy, a tumor of relatively favorable histology. Its prognosis is still primarily related to clinical stage and location of tumor. The alveolar subtype of rhabdomyosarcoma (including its solid variant) has a less favorable prognosis. Hepatoblastoma (epithelial or mixt variants) have the same long term survival, also mainly related to stage. Pancreatoblastoma is a tumor with well differentiated cytopathology and prolonged course, compared with other pancreatic tumors.

Carcinoma, Hepatocellular↗

Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.

von Willebrand disease (VWD) is a bleeding disorder caused by inherited defects in the concentration, structure, or function of von Willebrand factor (VWF). VWD is classified into three primary categories. Type 1 includes partial quantitative deficiency, type 2 includes qualitative defects, and type 3 includes virtually complete deficiency of VWF. VWD type 2 is divided into four secondary categories. Type 2A includes variants with decreased platelet adhesion caused by selective deficiency of high-molecular-weight VWF multimers. Type 2B includes variants with increased affinity for platelet glycoprotein Ib. Type 2M includes variants with markedly defective platelet adhesion despite a relatively normal size distribution of VWF multimers. Type 2N includes variants with markedly decreased affinity for factor VIII. These six categories of VWD correlate with important clinical features and therapeutic requirements. Some VWF gene mutations, alone or in combination, have complex effects and give rise to mixed VWD phenotypes. Certain VWD types, especially type 1 and type 2A, encompass several pathophysiologic mechanisms that sometimes can be distinguished by appropriate laboratory studies. The clinical significance of this heterogeneity is under investigation, which may support further subdivision of VWD type 1 or type 2A in the future.

ADAM Proteins↗

Basic principles of the ILAE syndrome classification.

The basic principles of the ILAE syndrome classification can be summarised as: clear definitions; reference to the seizure classification; expert consensus based on literature research; providing a taxonomy rather than a diagnostic manual; use of the dichotomies generalised versus localisation-related and idiopathic versus symptomatic; openness for the incorporation of new findings; and promotion of nosological thought. In fact, the publication of the classification stimulated research, especially in the fields of genetics, reflex epileptic mechanisms and advanced imaging, which will probably lead to a major revision of the nosology of epilepsies. Both localisation-related and "generalised" idiopathic epilepsies are about to be understood as related variants of system disorders of the brain, with an ictogenesis making pathological use of existing functional anatomic networks.

Epilepsy↗