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Self-organized acoustic feature map in detection of fricative-vowel coarticulation.

The self-organizing map, a neural network algorithm of Kohonen, was used for the detection of coarticulatory variation of fricative [s] preceding vowels [a:], [i:], and [u:]. The results were compared with the psychoacoustic classification of the same samples to find out whether the map had extracted perceptually meaningful features of [s]. The map distinguished samples of [s] in front of [u:] from those in front of [a:] or [i:] throughout the fricative duration. Samples of [s] preceding [a:] and [i:] were distinguished from each other only just before (about 40 ms) the vowel onset. The results agreed with the perceptual classifications. Most judgments (82%) of [s] in front of [u:] were correct, and this variant of [s] was recognized from the first and second halves of segmented fricatives equally well. Samples of [s] in front of [a:] and [i:] were distinguished from each other less accurately. When halves of segmented [s] were perceptually judged, the differentiation between the following [a] and [i] was possible only on the basis of the second half of the fricative. The results demonstrate that the self-organizing map is a useful tool for the extraction of intersubject regularities in speech spectra. The map also provides an easily understandable, on-line, visualization of speech that can be used as feedback in therapy and education.

Acoustic Stimulation↗

Involvement of the central nervous system in non-Hodgkin's lymphoma.

Fifteen of 146 (10%) adult patients with non-Hodgkin's lymphoma showed clinical and pathologic evidence of involvement of the central nervous system (CNS): in 6 patients, the CNS lymphoma was present at the onset of disease, in 3 of them it was the only sign detected. In the remaining 9 cases, CNS involvement appeared during the course of systemic disease. In all cases symptoms related to infiltration of the CNS were associated with advanced disease (stage IV); bone marrow or bone involvement was found in 9 patients (60%). The histologic subtypes were mostly of high-grade malignancy according to the Kiel classification: immunoblastic (3), centroblastic (3), Burkitt type (2), lymphoblastic (1), LP immunocytoma in polymorphic variant (3), unclassifiable (3). The prominent signs and symptoms of CNS lymphoma are listed: the cranial nerve palsies are the most common finding. The principal means of detecting CNS involvement are discussed: cerebrospinal fluid cytology, brain scan and CAT scan were the most useful diagnostic procedures. The reported data allow identification of patients at high risk of CNS lymphoma: this includes histologies of high-grade malignancy, advanced stage of disease, and bone marrow or bone infiltration. Therefore, either intensive systemic chemotherapy or CNS prophylaxis are recommended for patients with high risk of CNS disease.

Adult↗

Classification and characterization of hereditary types 2A, 2B, 2C, 2D, 2E, 2M, 2N, and 2U (unclassifiable) von Willebrand disease.

All variants of type 2 von Willebrand disease (VWD) patients, except 2N, show a defective von Willebrand factor (VWF) protein (on cross immunoelectrophoresis or multimeric analysis), decreased ratios for VWF:RCo/Ag and VWF:CB/Ag and prolonged bleeding time. The bleeding time is normal and FVIII:C levels are clearly lower than VWF:Ag in type 2N VWD. High resolution multimeric analysis of VWF in plasma demonstrates that proteolysis of VWF is increased in type 2A and 2B VWD with increased triplet structure of each visuable band (not present in types 2M and 2U), and that proteolysis of VWF is minimal in type 2C, 2D, and 2E variants that show aberrant multimeric structure of individual oligomers. VWD 2B differs from 2A by normal VWF in platelets, and increased ristocetine-induced platelet aggregation (RIPA). RIPA, which very likely reflects the VWF content of platelets, is normal in mild, decreased in moderate, and absent in severe type 2A VWD. RIPA is decreased or absent in 2M, 2U, 2C, and 2D, variable in 2E, and normal in 2N. VWD 2M is usually mild and characterized by decreased VWF:RCo and RIPA, a normal or near normal VWF multimeric pattern in a low resolution agarose gel. VWD 2A-like or unclassifiable (2U) is distinct from 2A and 2B and typically featured by low VWF:RCo and RIPA with the relative lack of high large VWF multimers. VWD type 2C is recessive and shows a characteristic multimeric pattern with a lack of high molecular weight multimers, the presence of one single-banded multimers instead of triplets caused by homozygosity or double hereozygosity for a mutation in the multimerization part of VWF gene. Autosomal dominant type 2D is rare and characterized by the lack of high molecular weight multimers and the presence of a characteristic intervening subband between individual oligimers due to mutation in the dimerization part of the VWF gene. In VWD type 2E, the large VWF multimers are missing and the pattern of the individual multimers shows only one clearly identifiable band, and there is no intervening band and no marked increase in the smallest oligomer. 2E appears to be less well defined, is usually autosomal dominant, and accounts for about one third of patients with 2A in a large cohort of VWD patients.

Antigens↗

Diagnosing tests: using and misusing diagnostic and screening tests.

Tests can be used either diagnostically (i.e., to confirm or rule out the presence of a condition in people suspected of having it) or as a screening instrument (determining who in a large group of people has the condition and often when those people are unaware of it or unwilling to admit to it). Tests that may be useful and accurate for diagnosis may actually do more harm than good when used as a screening instrument. The reason is that the proportion of false negatives may be high when the prevalence is high, and the proportion of false positives tends to be high when the prevalence of the condition is low (the usual situation with screening tests). My first aim of this article is to discuss the effects of the base rate, or prevalence, of a disorder on the accuracy of test results. My second aim is to review some of the many diagnostic efficiency statistics that can be derived from a 2 x 2 table, including the overall correct classification rate, kappa, phi, the odds ratio, positive and negative predictive power and some variants of them, and likelihood ratios. In the last part of this article, I review the recent Standards for Reporting of Diagnostic Accuracy guidelines (Bossuyt et al., 2003) for reporting the results of diagnostic tests and extend them to cover the types of tests used by psychologists.

Abstracting and Indexing↗

External auditory canal duplication anomalies associated with congenital aural atresia.

Maldevelopment of the first branchial cleft can produce a broad spectrum of anomalies in its derivative structure, the external auditory canal (EAC). Failure of the cleft to develop normally can result in either the absence of a normally patent EAC (atresia, or stenosis) or a duplication anomaly (cyst, sinus, or fistula). Despite their common origins, the coexistence of these anatomical abnormalities is quite unusual. We present four patients with both aural atresia and duplication anomalies of the EAC. Three patients had non-syndromic unilateral aural atresia and presented with periauricular lesions originating from the first branchial cleft. The other patient had a variant of Treacher Collins syndrome and presented with draining infra-auricular fistulae. The classification and management of first branchial cleft anomalies is reviewed in light of these cases. An understanding of the embryogenesis of the external ear is necessary to successfully recognize and treat this spectrum of deformities. A classification system is presented that encompasses the full spectrum of first cleft anomalies.

Adult↗

Multilocular cystic renal cell carcinoma : a report of 45 cases of a kidney tumor of low malignant potential.

The 2004 World Health Organization (WHO) classification of kidney tumors recognizes multilocular cystic renal cell carcinoma (MCRCC) as a rare variant of clear cell renal cell carcinoma with a good prognosis. Available information on its clinical significance is limited. The study cohort included 45 MCRCC cases classified according to 2004 WHO criteria obtained through a multi-institutional international search. Most patients had unilateral MCRCC with no side predominance that was found incidentally; 62% were men, but women had tumors at an earlier age (P = .385). MCRCC occurred slightly more often in men than in women (1.7:1). At diagnosis, 82% of patients had stage T1 and 16%, stage T2; 1 patient had stage T3. The Fuhrman grade was 1 (62%) or 2 (38%), with smaller tumors (<or=4 cm) most likely Fuhrman grade 1 (P = .911). All 45 patients were alive with no evidence of disease at mean follow-up of 66.1 months, confirming an extremely good prognosis after surgery and a 5-year disease-specific survival rate of 100%. To rename this tumor as multilocular cystic renal cell neoplasm of low malignant potential might help urologists approach the patients conservatively.

Adult↗

[The possibilities for improving the surgical procedure in hemorrhaging gastroduodenal ulcer].

The article describes an original variant of treatment of patients with bleeding ulcer of the stomach or duodenum. A classification of surgical interventions is proposed depending on the time of performing the operation. Verification of unstable hemostasis with the help of a computer expert program in patients with arrested bleeding and performing preventive emergency operation led to less postoperative lethality.

Algorithms↗

[Viral encephalitis (etiology, pathogenesis, classification)].

The existing classifications of viral encephalitis are based on mixed, heterogenous principles. The author on the grounds of comparing modern data, related to the etiology, pathogenesis, predilectiveness, gives his suggestions as to a new classification of viral encephalitis. This classification is structured according to the pathogenetical principles, with a consideration of the different variants of the dynamics and polymorphism of separate nozological forms, depending upon the interrelationships of the viral and the immunity factors.

Clinical Trials as Topic↗

Differential characteristics of a small gram-negative anaerobe associated with non-gonococcal urethritis which morphologically resembles Bacteroides ureolyticus.

Strains of a small, Gram-negative anaerobe described as 'NGU-associated' because of its apparent association with non-gonococcal urethritis (NGU), grew synergistically with anaerobic cocci on primary isolation. Subsequently, it was found that the addition of formate-fumarate to the media enhanced their growth. The organisms were asaccharolytic and, unlike most anaerobes, produced oxidase (cytochrome c) and tolerated 5% oxygen when grown in an atmosphere of 2% hydrogen, 7.5% carbon dioxide and 85.5% nitrogen. The strains examined appeared homogeneous culturally, morphologically and biochemically, and had some characteristics in common with Bacteroides ureolyticus (NCTC 10948) and Wolinella succinogenes (ATCC 29543). However, the latter was flagellated and had a DNA G + C content (46-49 mol%) that was different from B. ureolyticus (28 mol%) and the NGU-associated strains (28-30 mol%). These strains and B. ureolyticus shared many properties but electron microscopy of the NGU-associated strains revealed polar pili which were not seen on the strain of B. ureolyticus examined. Other tests which differentiated B. ureolyticus from the NGU-associated strains, being positive only for the latter, were lysine and ornithine decarboxylation, beta-haemolysis and growth in 5% oxygen: those that were negative for the NGU-associated strains were pitting of agar on primary culture and the production of acetate and lactate as metabolic end-products. Despite these differences, the NGU-associated strains may be biotypes or variants of B. ureolyticus, a species which we now consider needs further study and classification.

Bacteroides↗

von Willebrand disease: a database of point mutations, insertions, and deletions. For the Consortium on von Willebrand Factor Mutations and Polymorphisms, and the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.

The current system for the diagnosis and classification of von Willebrand disease (vWD) is quite complex, with more than 20 distinct variants described. Over the past few years considerable progress has been made toward an understanding of vWD at the molecular level. A small cluster of mutations within the vWF A1 homologous repeat appears responsible for over 90% of type IIB vWD. A similar cluster of mutations in the vWF A2 homologous repeat accounts for the majority of type IIA vWD. By RFLP analysis, several type II vWD mutations have been shown to be recurrent on distinct haplotype backgrounds, suggesting independent genetic origins (see accompanying manuscript for a complete list of known polymorphisms). Several mutations at the N-terminus of the mature vWF subunit have been identified in association with abnormal factor VIII binding. Homozygotes for this abnormal vWF present with a hemophilia-like phenotype that is autosomal recessive in inheritance. In a small subset of patients with type III vWD large gene deletions have been identified on one or both vWF alleles. Carriers heterozygous for a deleted locus and one normal vWF gene are generally asymptomatic. Nonsense mutations and other defects resulting in loss of vWF mRNA expression from one allele have also been associated with a recessive type III vWD phenotype. No distinct molecular defect responsible for classic type I vWD has yet been defined.

DNA Mutational Analysis↗

[Angiographic research on the blood supply of the colon with a view to oesophagoplasty (author's transl)].

The author presents an angiographic study of 34 cadavers concerning the colonic vessels, and draws up an original classification of colonic vessels which arise from the inferior mesenteric artery. He found 16 variants of the left colonic artery which he groups into 5 main types, the classical type being only encountered in 22.6 p. cent of cases. In 32 p. cent, the ascending and descending branches of the left colonic artery had a separate origin from the inferior mesenteric artery. The variants of the sigmoid arteries and of the left colonic veins were also identified. In one case, the inferior mesenteric vein was absent, being supplanted by the marginal vein. As for colo-oesophagoplasty, the isoperistaltic transverse colon was found to be better than the ileo-colon in 64 p. cent of cases and equivalent in 20 p. cent. In 16 p. cent the ileo-colon was preferable. The site of the arterial sections in colo-oesophagoplasty according to the colonic vascular type is discussed.

Adolescent↗

Approach to lymphoproliferative infiltrates of the skin. The difficult lesions.

Primary cutaneous lymphomas (CLs) are the second most common group of extranodal non-Hodgkin's lymphomas. Cutaneous T-cell lymphomas (CTCLs) account for 60% to 65% of all primary CLs, whereas 20% to 25% of CLs are of B-cell origin. Besides the most common and well-known forms of CL, such as mycosis fungoides and follicular B-cell lymphomas, there are some rare and unusual variants of CL that represent about 10% of lymphoproliferative skin infiltrates. Discussed in detail are T- and B-cell pseudolymphomas as simulators of CL, the group of parapsoriasis and early mycosis fungoides, circumscribed CTCL, such as pagetoid reticulosis and syringolymphoid hyperplasia, granulomatous variants of CTCL, the group of primary CD30+ CTCL and the controversies in the classification and some rare, but distinct cutaneous B-cell lymphomas. The final diagnosis in CL is based on a constellation of clinical, histopathologic, and molecular-biologic criteria.

Humans↗

Mannose-binding lectin in susceptibility and progression of HIV-1 infection in children.

BACKGROUND: Mannose-binding lectin (MBL; encoded by MBL-2) is a circulating pattern-recognition molecule that recognizes microbial carbohydrate motifs, leading to complement activation and cell lysis. Mutations in the MBL-2 promoter and of the MBL-2 gene exon 1 result in reduced protein levels and increased susceptibility to infection. We have investigated the effect of MBL-2 polymorphisms on susceptibility and progression of HIV-1 infection in children. PATIENTS AND METHODS: One-hundred and twenty-eight children, aged 2-16 years were recruited. MBL-2 genotypes were determined by PCR and heteroduplex analyses. Serum MBL levels were measured by ELISA. Comparison of genotypes (A=wild type, O=variant alleles) and protein levels between groups was performed using chi-squared, Mann-Whitney U or Kruskal-Wallis tests. RESULTS: Children were classified according to the Centers for Disease Control and Prevention clinical classification: A, B or C (mildly symptomatic [n=39], moderately symptomatic [n=58] or severely symptomatic AIDS [n=31]) or immune category 1 (n=77), 2 (n=46) or 3 (n=5). Analysis of MBL-2 genotypes with respect to clinical classification yielded minimal differences. However, patients in immunological categories 2 and 3 (<25% CD4+ T cells) were more likely to have MBL-2 variant alleles (P=0.01). We further explored MBL status with respect to disease progression. Only 1/10 long-term non-progressors (LTNPs) had an MBL-2 mutation (A/D) with a corresponding protein level of 611 ng/ml. CONCLUSIONS: MBL deficiency was more frequent in patients with severe disease as assessed by CD4+ T-cell status. MBL-2 variants may be less frequent in children classified as LTNPs. MBL analysis could be useful in identifying children with slow disease progression and, consequently, may not require immediate antiretroviral treatement.

Adolescent↗

Molecular and clinical classification of human prion disease.

While rare in humans, the prion diseases have become an area of intense clinical and scientific interest. The recognition that variant Creutzfeldt-Jakob disease is caused by the same prion strain as bovine spongiform encephalopathy in cattle has dramatically highlighted the need for a precise understanding of the molecular biology of human prion diseases. Detailed clinical, pathological and molecular data from a large number of human prion disease cases have shown that distinct abnormal isoforms of prion protein are associated with prion protein gene polymorphism and neuropathological phenotypes. A molecular classification of human prion diseases seems achievable through characterisation of structural differences of the infectious agent itself.

Adult↗

Cloning, in vitro expression, and novel phylogenetic classification of a channel catfish estrogen receptor.

We obtained two channel catfish estrogen receptor (ccER) cDNA from liver of female fish using RT-PCR. The two fragments were identical in sequence except that the smaller one had an out-of-frame deletion in the E domain, suggesting the existence of ccER splice variants. The larger fragment was used to screen a cDNA library from liver of a prepubescent female. A cDNA was obtained that encoded a 581-amino-acid ER with a deduced molecular weight of 63.8 kDa. Extracts of COS-7 cells transfected with ccER cDNA bound estrogen with high affinity (Kd = 4.7 nM) and specificity. Maximum parsimony and Neighbor Joining analyses were used to generate a phylogenetic classification of ccER on the basis of 18 full-length ER sequences. The tree suggested the existence of two major ER branches. One branch contained two clearly divergent clades which included all piscine ER (except Japanese eel ER) and all tetrapod ERalpha, respectively. The second major branch contained the eel ER and the mammalian ERbeta. The high degree of divergence between the eel ER and mammalian ERbeta suggested that they also represent distinct piscine and tetrapod ER. These data suggest that ERalpha and ERbeta are present throughout vertebrates and that these two major ER types evolved by duplication of an ancestral ER gene. Sequence alignments with other members of the nuclear hormone receptor superfamily indicated the presence of 8 amino acids in the E domain that align exclusively among ER. Four of these amino acids have not received prior research attention and their function is unknown. The novel finding of putative ER splice variants in a nonmammalian vertebrate and the novel phylogenetic classification of ER offer new perspectives in understanding the diversification and function of ER.

Amino Acid Sequence↗

Unusual histological variants of cutaneous malignant melanoma with some clinical and possible prognostic correlations.

Malignant melanoma is known for the wide range of histological patterns it can assume mimicking other malignant tumors. We present a review of most of the unusual histological variants of cutaneous melanoma and describe their immunohistochemical features, associate clinical findings, and possible behavior related to the histological subtype. In addition, we propose their classification into four groups corresponding to the (1) architectural patterns; (2) cytologic features; (3) stromal changes; and (4) the possible association of these findings (i.e. architectural + cytologic features). Although most of these unusual variants have the same prognosis as conventional melanomas, with Breslow thickness and ulceration, being the most important predictor of survival in clinical stage I, some of them have a peculiar biologic behavior that the clinicians and the dermatopathologists should know in order to give melanoma patients all educational information available.

Humans↗

Systemic anaplastic large-cell lymphoma: results from the non-Hodgkin's lymphoma classification project.

Anaplastic large-cell lymphoma (ALCL) is a heterogeneous process that may have a T-cell, B-cell, or indeterminant (null) phenotype and which may or may not express the anaplastic lymphoma kinase (ALK) oncoprotein. Because the clinical significance of these variants of ALCL is unclear, we evaluated the cases of ALCL-T/null and ALCL-B identified in the Non-Hodgkin's Lymphoma Classification Project. We evaluated 1,378 cases of non-Hodgkin's lymphoma (NHL), and a consensus diagnosis of ALCL-T/null was made in 33 patients (2.4%) with a diagnostic accuracy of 85%. Compared to 96 patients with other forms of peripheral T-cell lymphoma (PTCL), those with ALCL-T/null were significantly younger, less likely to have advanced-stage disease or bone marrow involvement, more likely to have a low International Prognostic Index score, and had a significantly better survival. Among those with ALCL-T/null, there were no significant differences in the clinical features or survival on the basis of ALK expression. A consensus diagnosis of ALCL-B was made in 15 patients (1.1%), and the diagnostic accuracy was 67%. However, compared to 366 patients with other forms of diffuse large B-cell lymphoma (DLBCL), those with ALCL-B were no different with regard to clinical features or survival. We conclude that patients with ALCL-T/null have favorable prognostic features and excellent survival and should be separated from those with other forms of PTCL for prognostic and therapeutic purposes. In contrast, patients with ALCL-B appear to be similar to those with other forms of DLBCL.

Adult↗