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At least 1,117 records · Page 62Linked to original sources
PubMed2006

Pontomedullary sulcus infarct: a variant of lateral medullary syndrome.

With the advent of magnetic resonance imaging (MRI) technology, it is now possible to identify and determine the precise location of medullary infarcts. The lateral part of the medulla is most commonly affected by infarction. Classifications of lateral medullary infarcts are usually based on anatomical data, using rostrocaudal and dorsoventral axes to establish correlations with clinical symptoms. Different subtypes of lateral medullary syndrome, depending on location, shape and size of the infarct, have been described in the literature. We report a rare case of a patient presenting with an unusual clinical picture in relation to an infarct specifically located in the lateral part of the pontomedullary sulcus.

Cerebral Infarction↗
PubMedDate not supplied

Follicular variant of papillary thyroid carcinoma: diagnostic limitations of fine needle aspiration cytology.

OBJECTIVE: To study the diagnostic sensitivity and specificity of fine needle aspiration cytology (FNAC) offollicular variant of papillary thyroid carcinoma (FVPTC). STUDY DESIGN: The study group consisted of 390 papillary thyroid carcinoma (PTC) cases diagnosed histologically with thyroidectomy specimens. The FNAC and histopathologic classification were compared in terms of the appearance of FVPTC and non-FVPTC statistically with the chi squared test. Also, several features of the cytologic smears of FVPTC were reviewed. RESULTS: Twelve of the 390 PTC cases were classified as FVPTC histologically. Five of the 12 cases were also reported as FVPTC in the diagnosis by FNAC and the other 7 as the usual type of PTC (UTPTC). There was 1 case classified as UVPTC histologically but FVPTC cytologically. If we use histologic diagnosis as the gold standard, the sensitivity and specificity of FNAC diagnosis of FVPTC were 42% and 83%, respectively. CONCLUSION: FNAC may be a good tool for diagnosing PTC, but it is unreliable to differentiate between FVPTC and UTPTC.

Adolescent↗
PubMed2001

Current concepts in tall stature and overgrowth syndromes.

In this overview an update is given on the pathogenesis, classification and differential diagnosis of overgrowth syndromes. In addition, height prognosis and therapeutic modalities available for managing mainly constitutional tall stature are discussed. Constitutional tall stature comprises normal variants in which one or both parents are tall. Primary disorders may have a prenatal onset and may be of chromosomal or genetic origin. Secondary overgrowth syndromes are most often the result of hormonal disturbances. Height prediction plays a key role in the management of tall children. Prediction equation models have been developed based on the growth data of healthy tall children. There is general agreement that a favourable effect on reducing ultimate height is obtained using high doses of sex steroids (girls 100-300 microg ethinyloestradiol; boys testosterone (T) ester depot preparations 250-1000 mg/month), the height reduction being greater when the treatment is started at a lower chronological and/or bone age. An alternative is the induction of puberty with low doses of sex steroids (girls 5-50 microg ethinyloestradiol; boys T esters 25-50 mg/m2/3 wk). In addition orthopaedic procedures have been suggested, but there is limited experience. Although psychosocial factors constitute the main reason for treating tall stature, extensive psychological investigations before or during height limiting therapy are lacking. Moreover, there are no objective data indicating lifelong psychosocial damage resulting from being tall.

Adolescent↗
PubMed2003

Familial severe myoclonic epilepsy of infancy: truncation of Nav1.1 and genetic heterogeneity.

BACKGROUND: Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome has been long suspected of having a genetic origin. Recently, mutations in SCN1A and GABRG2 have been described in SMEI patients. The sporadic nature of the SMEI syndrome and the occurrence of SCN1A and GABRG2 mutations in a mild familial phenotype, termed generalized epilepsy with febrile seizure plus complicates genotype-phenotype correlations. In order to further investigate the role of SCN1A and GABRG2 in the pathogenesis of SMEI we have screened for mutations three families with at least two members affected by Dravet syndrome. METHODS: Clinical criteria followed the international classification of epileptic syndromes. Mutational screening of SCN1A and GABRG2 genes was performed by denaturing high performance liquid chromatography (DHPLC) and direct sequencing of DNA fragments showing a variant chromatogram. RESULTS: Thirty-eight fragments spanning 26 exons of SCN1A and nine exons of GABRG2 were analysed in three probands. Five variant chromatograms were identified; four corresponded to known polymorphisms, one to a novel dinucleotide insertion on exon 26 of SCN1A. The mutation leads to a frameshift and a premature stop codon at amino acid 1 779 of the protein. The mutation was present in the affected sibling and was inherited from the mother who had experienced a single febrile seizure in childhood. CONCLUSIONS: Among three families analysed, a single family was mutant for SCN1A. Our study suggests that the syndrome is genetically heterogeneous. The variable expressivity we observed for the c5240insAA mutation suggests that other factors are needed for the development of the full SMEI phenotype.

Adolescent↗
PubMed1988

Autoantibodies in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which the predominant autoantibodies are antinuclear antibodies (ANA) reactive with DNA and histones, and antibodies reactive with the non-histone extractable nuclear antigens (ENA), Sm and Ro. Racial differences demonstrable in predisposition to SLE are also evident in the prevalence of autoantibodies, the frequency of anti-Sm and anti-Ro being 2-4 times higher in Asians with SLE than in Caucasians with SLE. Autoantibodies have also played a role in the classification of lupus and the recognition of multisystem autoimmune diseases that fail to meet the classical criteria for the identification of patients with SLE but appear to be variants of lupus. Anti-Ro is a diagnostic marker for subacute cutaneous lupus, anti-(U1)RNP a marker for mixed connective tissue disease, antibodies to phospholipids a marker for the syndrome comprising stroke, fetal wastage, thromboembolism and thrombocytopenia and antibodies to histones a marker for lupus induced by the drugs hydralazine and procainamide. There is still no unaminity on whether these antibodies play an integral role in the disease process or whether they are "epiphenomena". The challenge for research in the 1980s is the understanding of the relationship of these antibodies to the pathogenesis of SLE.

Antibodies, Antinuclear↗
PubMed1995

von Willebrand factor: its function and its measurement in the laboratory.

von Willebrand factor (vWF) is a complex protein essential to normal haemostasis. It is vital to platelet adhesion in the high shear stress conditions encountered in the small blood vessels. Deficient overall levels of, or the presence of abnormally functioning variants of, vWF lead to the common bleeding disorder termed von Willebrand's disease. Laboratory investigation is aimed at both quantitative and qualitative investigation with a view to classification of the abnormality for each individual patient into a particular sub-type.

Hemostasis↗
PubMed1997

Systemic mast cell disease (mastocytosis). General aspects and histopathological diagnosis.

Systemic mast cell disease/mastocytosis (SMCD) is best defined as a multitopic proliferation of cytologically and/or functionally abnormal tissue mast cells (TMC). SMCD preferentially involves the bone marrow, skin, spleen, liver, and lymph nodes. The histopathological diagnosis of SMCD may be very difficult to make, and the disease is often not considered in the differential diagnosis of lymphoreticular neoplasia. In suspected cases of SMCD, basic dyes such as Giemsa and toluidine blue are useful to demonstrate the specific metachromatic granules of TMC. The naphthol AS-D chloroacetate esterase reaction has also proved to be very reliable for enzyme-histochemical identification of TMC. Major diagnostic problems may arise in cases of malignant or "aggressive" SMCD exhibiting tissue infiltrates consisting predominantly of highly atypical, non-metachromatic TMC, which are usually also only weakly reactive for chloroacetate esterase. Immunostaining with antibodies against the mast cell-specific proteases tryptase and chymase has proved to be of great value of establishing the correct diagnosis in such cases. Anti-tryptase antibodies have major diagnostic significance due to their extremely high sensitivity and specificity. The classification of SMCD is controversial, but there is increasing support for the differentiation of at least two major subtypes that differ in prognosis: (i) a benign or "indolent" variant in which skin involvement (urticaria pigmentosa-like skin lesions) is usual, but associated malignant hematological disorders are rare; and (ii) a malignant or "aggressive" variant where skin involvement is usually absent but concomitant malignant hematological disorders (myelodysplastic and myeloproliferative syndromes and acute non-lymphocytic leukemias) are very common. Preliminary molecular biological studies of a few cases of malignant SMCD using the recently developed HUMARA assay have yielded evidence that the disease is monoclonal.

Animals↗
PubMed1997

Bellini duct carcinoma of the kidney--a case report.

Bellini duct carcinoma (BDC), originating from the principal cells of the collecting duct of the kidney, accounts for only 1% of renal carcinomas. This lesion is a histogenetically, morphologically and cytogenetically defined entity. We report an eosinophilic variant of BDC. A 71-year old male presented with a tumor in the right kidney. Nephrectomy was performed. BDC (stage pT3a N0 M0 G2, based on UICC classification) was diagnosed. Electron microscopy revealed an abundance of mitochondria. Intranuclear rodlets were seen. Neuroendocrine differentiation was not demonstrated. After a three-year observation period, there are no signs of recurrence or metastases.

Aged↗
PubMed2006

Use of a novel FISH assay on paraffin-embedded tissues as an adjunct to diagnosis of alveolar rhabdomyosarcoma.

A valuable diagnostic adjunct and important prognostic parameter in alveolar rhabdomyosarcoma (ARMS) is the identification of translocations t(2;13)(q35;q14) and t(1;13)(p36;q14), and the associated PAX3-FKHR and PAX7-FKHR fusion transcripts, respectively. Most RMS fusion gene type studies have been based on reverse transcriptase-polymerase chain reaction (RT-PCR) detection of the fusion transcript, a technique limited by RNA quality and failure of devised primer sets to detect unusual variants. As an alternative approach, we developed a fluorescence in situ hybridization (FISH) assay that can: (1) distinguish between the two most common ARMS-associated fusion genes; (2) identify potential unusual variant translocations; (3) assess histologic components in mixed alveolar/embryonal RMS; and (4) be performed on paraffinized tissue. FISH analyses of 75 specimens (40 ARMS, 16 ERMS, 8 mixed ARMS/ERMS, and 11 non-RMS tumors) using selected cosmid clone, bacterial, P1-derived, and yeast artificial chromosome probe sets were successful in all but two cases. Among specimens with informative results for both FISH and RT-PCR or standard karyotyping, PAX/FKHR classification results were concordant in 94.6% (53/56). The three discordant cases included one exhibiting a t(2;13) by FISH that was subsequently confirmed by repeat RT-PCR, a second showing a rearrangement of the PAX3 locus only (consistent with the presence of a PAX3 variant translocation), and a third revealing a t(2;13) by FISH that lacked this translocation cytogenetically. Both alveolar and embryonal components of the mixed ARMS/ERMS subtype were negative for PAX3, PAX7, and FKHR rearrangements, a surprising finding confirmed by RT-PCR and/or conventional karyotyping. These data demonstrate that FISH with newly designed probe sets is a reliable and highly specific method of detecting t(1;13) and t(2;13) in routinely processed tissue and may be useful in differentiating ARMS from other small round cell tumors. The findings also suggest that FISH may be a more sensitive assay than RT-PCR in some settings, capable of revealing variant translocations.

Biological Assay↗
PubMed2005

The -670A > G polymorphism in the promoter region of the FAS gene is associated with necrosis in periportal areas in patients with chronic hepatitis C.

Evidence suggests that apoptosis of liver cells may play a significant role in the pathogenesis of hepatitis C virus (HCV) infection. One of the best characterized apoptotic pathway is that mediated by the death receptor Fas. Fas expression has been found to be up-regulated on hepatocytes in chronic HCV infection, particularly in periportal areas. Recently, two polymorphisms have been identified in the promotor region of the FAS gene, -1377G > A and -670A > G. We have evaluated the involvement of these variants in the susceptibility to HCV infection, the severity of liver damage and progression of fibrosis in chronic hepatitis C. A cohort of 197 patients with chronic hepatitis C and 100 controls were analysed for both polymorphisms by Fluorescence Resonance Energy Transfer using specific probes and the Lightcycler system. In addition, liver biopsies were taken in 167 patients and scored using the Knodell classification system. We have found that the allele frequencies and the distribution of both polymorphisms do not differ significantly in the HCV cohort and in the control population. Thus, none of the polymorphisms seems to be related with susceptibility to HCV infection. However, we have examined the possible association between the two variants and the grade of necroinflammatory activity and the stage of fibrosis and we have detected an under-representation of the -670A > G variant among those patients with higher Knodell's scores (P = 0.049) and necroinflammatory activity (P = 0.036). The -670A allele was associated with higher levels of periportal necrosis (P = 0.012). In conclusion, our findings suggest an association between the -670A > G polymorphism and the grade of necrosis in periportal areas in patients with chronic hepatitis C.

Adolescent↗
PubMed1981

Improved interpretation of a continuous variable in diagnostic testing: probabilistic analysis of scintigraphic rest and exercise left ventricular ejection fractions for coronary disease detection.

The interpretation of a diagnostic modality requires consideration of the entire distribution of potential responses in both the normal and diseases population to extract the maximum available information from the test. Accordingly, we developed a probabilistic format for interpretation of scintigraphic left ventricular ejection fraction (LVEF) in the diagnosis of coronary artery disease (CAD). This format is distinguished (1) by accurate assessment of CAD likelihood based upon age, sex, and symptom classification using a logistical regression model (mean r = 0.9991, mean SEE = 0.008) and (2) by consideration of LVEF as a continuous probabilistic variable which obeys beta frequency distribution. This format allows assessment of the probability of CAD in an individual patient, according to Bayes' theorem of conditional probability of disease, given combinations of LVEF at rest and/or with exercise, and thereby is designed to provide more information than conventional categorical classification of "normal" or "abnormal" test observations.

Adult↗
PubMed1980

Classification of transferrin (Tf) subtypes by isoelectric focusing.

A sample of 450 sera from unrelated individuals from Southern Germany was examined by isoelectric focusing on polyacrylamide gels. Three common subtypes, TfC1, C2-1, and C2, were differentiated. In addition, the rare variants TfB1, B1-2, B2, D1, D1-2, D2, and D3 were observed. The frequencies of the Tf alleles in our sample were found to be: TfC1 = 0.8544, TfC2 = 0.1367, TfB1 = 0.0011, TfB1-2 = 0.0022, TfB2 = 0.0045, and TfD1 = 0.0011. Analysis of 73 parents with 73 children did not show deviations from the expected mode of inheritance. Modification of the method by addition of 0.01 M FeCl3 to the sera prior to examination did, however, reveal further variation and permitted the distinction of six subtypes, C1, C2-1, C2, C3, C3-1, and C3-2.

Adult↗
PubMed2003

[Contemporary variants of occupational diseases].

Contemporary forms of occupational diseases are often characterized by many body systems involved, with response of specific and nonspecific effects. Due to observed transformation in character and course of the main occupational entities, specifying the new clinical classifications, new "List of Occupational Diseases" adapted to ICD-10, by specialists remains topical.

Humans↗
PubMed2003

Clinical utility of grading criteria for submucosal invasion in the prognosis of T1 colorectal carcinomas.

BACKGROUND: The clinical utility of relative and absolute grading criteria for submucosal invasion in T1 colorectal carcinomas has been controversial. METHODS: In 51 T1 colorectal carcinomas, depth of submucosal invasion was graded either according to a modified Haggitt's classification (a relative criterion) or by direct measurement using a micrometer (an absolute criterion), and immunostaining for E-cadherin, alpha-catenin, beta-catenin, matrilysin, and CD44 variant 6 was performed on formalin-fixed, paraffin-embedded sections. The associations between lymph node metastasis or local recurrence (locoregional failure) and tumor budding, and clinicopathologic parameters and immunoreactivity were examined statistically. RESULTS: By univariate analysis, tumor budding, histology, and the co-expression pattern of nuclear beta-catenin and CD44 variant 6 were significantly associated with locoregional failure. The relative and absolute grading of submucosal invasion were not significantly associated with locoregional failure. Multivariate analysis showed that tumor budding alone was significantly associated with locoregional failure, and the association between the co-expression pattern of nuclear beta-catenin and CD44 variant 6, and locoregional failure was marginally significant ( P = 0.0502). Lymphatic invasion and absolute grading of depth and width of submucosal invasion were significantly associated with tumor budding, and the associations between tumor budding, and histologic differentiation and membranous alpha-catenin expression were marginally significant ( P = 0.06; P= 0.08), whereas, a relative grading of submucosal invasion was not significant ( P = 0.58). Analysis of variance showed that histologic differentiation and lymphatic invasion were independently and significantly associated with tumor budding ( P = 0.005; P < 0.001). CONCLUSIONS: These results suggest that the grading of submucosal invasion, either relative or absolute, may not be a useful risk factor for lymph node metastasis or local recurrence in T1 colorectal carcinomas.

Adult↗
PubMed1991

Estimating allele frequencies of hypervariable DNA systems.

Several polymorphisms of human DNA have been shown to be hypervariable due to the recurrence of a variable number of tandem repeats (VNTRs) in the lengths of allelic restriction fragments. The recurrence of allelic variants in this novel class of polymorphisms seems to comply well with a model of continuous random variables. Based on this assumption, we have compiled some simple algorithms for classification of continuous data and estimation of classes of relative frequencies and have implemented these routines for the management of databases storing hypervariable single locus DNA genetic systems. The algorithms are compiled in BASIC language and can be incorporated in task-oriented computer programs. Three procedures are discussed, based in turn on: (a) using predetermined, arbitrary classes; (b) point estimations of frequencies for single fragments using error measurements associated with the kilobase value assignment; (c) estimates of phenotype frequencies according to error measurements. Error measurements are obtained from a statistic of values pertaining to several restriction fragments (genomic controls) repeatedly tested in different experiments. Problems related to these approaches are discussed.

Algorithms↗
PubMed2025

Clinical, Morphologic, and Molecular Findings in Neurotrophic Tyrosine Receptor Kinase 3 (NTRK3) Fusion Spitz Neoplasms.

Neurotrophic tyrosine receptor kinase 3 (NTRK3) fusions are a relatively common driver of Spitz neoplasms. This subset of Spitz neoplasms may have smaller cells without the typical abundant glassy eosinophilic cytoplasm seen in most Spitz neoplasms. This can make it difficult to recognize them as belonging to the Spitz family and potentially result in misdiagnosis as melanoma. In this study, we assessed the clinical, morphologic, and genomic features of 60 NTRK3 fusion Spitz neoplasms (13 previously reported and 47 new cases) and performed a comprehensive review of the literature. We identified 5 characteristic morphologic patterns: (1) conventional Spitz nevus (SN) or Spitz tumor (ST), (2) spindle cell nevus of Reed, (3) spindle cell tumor of Reed, (4) dysplastic SN, and (5) exclusively spindle cell variant of SN/ST. The most common fusion partners were MYO5A and ETV6. DNA copy number changes were infrequent (18% of cases), with an average of 1 copy number variant per case. Among 54 cases tested for a TERT promoter mutation, all were negative. One case had a homozygous deletion of 9p21. The majority of cases were diagnosed as SN or Reed nevi (n = 37), rather than ST or Reed tumor (n = 23), and none were diagnosed as Spitz melanoma. Among the 30 patients with outcome data, none experienced recurrence following excision (mean follow-up time was 15 months). NTRK3 fusions can produce morphologic variants of Spitz neoplasms that may be difficult to recognize as belonging to the Spitz family. Familiarity with these morphologic patterns can facilitate identification of the NTRK3 fusion, optimizing classification and distinction from melanoma.

Humans↗
PubMed2003

Prognostic significance of CD44v5 expression in human thymic epithelial neoplasms.

BACKGROUND: Cell surface glycoproteins of the CD44 family play roles in cell-cell and cell-matrix interactions. Their aberrant expression has been implicated in tumor invasion and metastasis of a variety of neoplasms, but not, to date, of thymic epithelial tumors. METHODS: To investigate the expression of CD44 molecules, immunohistochemical staining using monoclonal antibodies against human CD44 standard form (CD44 s) and two common splicing variant (CD44v) isoforms, CD44v5 and CD44v6, was performed on 64 resected thymomas and 20 normal thymuses. These tumors were categorized histologically according to the World Health Organization (WHO) histologic classification, and the pathologic staging was classified according to the definitions of Masaoka. RESULTS: The positive expression rates in these patients were as follows: CD44 s (normal thymuses, 10%; thymomas, 22%), CD44v5 (normal thymuses, 0%; thymomas, 67%), and CD44v6 (normal thymuses, 0%; thymomas, 26%). CD44 s and CD44v5 immunoreactivity showed a positive correlation with tumor stages (p = 0.034 and 0.027, respectively). The CD44v5 expression of neoplastic cells in tumor capsules has significant correlation with tumor stages (II, 5%; III, 70%; IVA, 100%; p < 0.001). On the basis of univariate survival analysis, the Masaoka staging system, WHO histologic classification, and CD44v5 expression showed a statistically significant positive relation to survival (p < 0.001, 0.002, 0.011, respectively). Using Cox's regression model, increasing CD44v5 expression, the Masaoka staging, and the WHO classification system were found to be significant independent prognostic factors. CONCLUSIONS: CD44v5 expression is independently positively correlated with the aggressiveness of thymic epithelial tumors. The expression of CD44v5 may be a potential trigger of tumor invasion in thymomas.

Adult↗