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PubMedDate not supplied

Sacroiliac joints: anatomical variants on CT.

The purpose of this work was to examine the type and prevalence of anatomical variants of the sacroiliac joints (SJs) in patients without SJ disease on CT examinations. The study comprised 534 consecutive patients undergoing pelvic CT with various indications not related to diseases that could involve the SJ. Images printed on bone window settings were evaluated with reference to any deviation from the usual appearance of the SJ. Physical data and history of low back pain were recorded in each patient. Six types of anatomical variants were observed: accessory joints in 102 patients (19.1%), "iliosacral complex" in 31 (5.8%), bipartite iliac bony plate in 22 (4.1%), crescent-like iliac bony plate in 20 (3.7%), semicircular defects at the sacral or iliac side in 16 (3%), and ossification centers in 3 patients (0.6%). Accessory joints were more common in obese than in normal-weight individuals (p < 0.05) and in older than younger (<60 years) patients (p < 0.001) and presented degenerative alterations especially in patients with episodes of low back pain. Three of these variants (iliosacral complex, bipartite iliac bony plate, and crescent-like iliac bony plate) had higher incidence in women than in men (p < 0.05) and were not associated with degenerative changes. Knowledge of the normal variations in the SJ appearance broadens the understanding of SJ anatomy, facilitating image interpretation.

Adolescent↗
PubMed1999

Linkage disequilibrium of interleukin-1 genetic polymorphisms with early-onset periodontitis.

BACKGROUND: Genetic polymorphisms at interleukin (IL)-1alpha and IL-1beta were recently suggested to be associated with severity of adult periodontitis. We evaluated whether these polymorphisms might also be associated with early-onset periodontitis (EOP) in 28 African American families and 7 Caucasian American families with 2 or more affected members. METHODS: Genomic DNA from peripheral blood was amplified, followed by restriction endonuclease digestion and acrylamide gel electrophoresis to distinguish alleles of different fragment sizes. Genetic epidemiological methods suitable for family data were used that are robust to false-positive findings due to mismatching of cases and controls or mixed subpopulations of different ethnic or geographic origin. The 2 major EOP subtypes, localized juvenile periodontitis (LJP), and generalized early-onset periodontitis (G-EOP, encompassing rapidly progressive periodontitis and generalized juvenile periodontitis), were analyzed both separately and together. RESULTS: We obtained highly significant evidence of linkage disequilibrium for both African American and Caucasian G-EOP subjects. A similar trend was noted for LJP. The IL- alleles associated with high risk of EOP had been suggested previously to be correlated with low risk for severe adult periodontitis. Disequilibrium with G-EOP was equally strong for smoking and non-smoking subjects. IL-1alpha and IL-1beta polymorphisms were in strong disequilibrium with each other in Caucasians, but not in African Americans. Haplotype analyses evaluating both polymorphisms simultaneously indicated that the IL-1beta variant is likely to be most important for EOP risk. Sibpair linkage analyses, by contrast, provided only marginal support for a gene of very major effect on EOP risk attributable to these IL-1 polymorphisms. CONCLUSIONS: Recent theoretical analyses indicate that our findings are most consistent with an interpretation of EOP as a complex, oligogenic disorder, with IL-1 genetic variation contributing an important but not exclusive influence on disease risk.

Adolescent↗
PubMed2001

Probability binning and testing agreement between multivariate immunofluorescence histograms: extending the chi-squared test.

BACKGROUND: A key problem in immunohistochemistry is assessing when two sample histograms are significantly different. One test that is commonly used for this purpose in the univariate case is the chi-squared test. Comparing multivariate distributions is qualitatively harder, as the "curse of dimensionality" means that the number of bins can grow exponentially. For the chi-squared test to be useful, data-dependent binning methods must be employed. An example of how this can be done is provided by the "probability binning" method of Roederer et al. (1,2,3). METHODS: We derive the theoretical distribution of the probability binning statistic, giving it a more rigorous foundation. We show that the null distribution is a scaled chi-square, and show how it can be related to the standard chi-squared statistic. RESULTS: A small simulation shows how the theoretical results can be used to (a) modify the probability binning statistic to make it more sensitive and (b) suggest variant statistics which, while still exploiting the data-dependent strengths of the probability binning procedure, may be easier to work with. CONCLUSIONS: The probability binning procedure effectively uses adaptive binning to locate structure in high-dimensional data. The derivation of a theoretical basis provides a more detailed interpretation of its behavior and renders the probability binning method more flexible.

Chi-Square Distribution↗
PubMed2002

HHV-6 A- or B-specific P41 antigens do not reveal virus variant-specific IgG or IgM responses in human serum.

The etiology of multiple sclerosis (MS) remains unknown, but there are indications of a role of human herpesvirus 6 (HHV-6), especially variant A, in the pathogenesis. Higher serum antibody reactivity against an HHV-6 early protein, p41, has been found in MS cases than in controls. The antigen, however, was purified from infected cells with a monoclonal antibody also reactive with a protein (p38) likely to be of cellular origin. To avoid serological crossreactivity with the cellular protein, recombinant p41 proteins from HHV-6A strain GS and HHV-6B strain Z29 were expressed as glutathione-S-transferase fusion proteins (p41-GST), and used as antigens in an enzyme-linked immunosorbent assay (ELISA). p41 variant specific monoclonal antibodies reacted strongly with the respective recombinant proteins. Serum IgM and IgG reactivities with the recombinant p41 antigens were analysed in patients with manifest MS, patients with optic neuritis, patients with other neurological diseases, and in one group of healthy controls. All sera were HHV-6 IgG seropositive by immunofluorescence. The serum IgM or IgG reactivities against the recombinant p41 antigens did not differ significantly between the groups, and the reactivities against the variant A and B antigens were identical. In many samples, the reactivity was very low. The results indicate that p41 is not an optimal target for HHV-6 serology studies, and that the data obtained with the p41 antigen prepared from infected cells (possibly including also p38) should be interpreted with caution.

Antibodies, Monoclonal↗
PubMed1994

Clinical and biochemical characteristics of peroxisomal disorders: an update.

Peroxisomal disorders represent a recently recognized group of inherited diseases in man, now comprising 14 different disorders. If discussion is restricted to those peroxisomal disorders in which there is neurological involvement (thereby excluding hyperoxaluria and acatalasaemia), results over the least few years have shown that analysis of very-long-chain fatty acids (VLCFAs) is a highly reliable initial test to establish whether or not one is dealing with a peroxisomal disorder. Rhizomelic chondrodysplasia punctata, its recently identified variant form and glutaryl-CoA oxidase deficiency will show no abnormalities and must be identified by other means. Recently we have found a few clinically proven cases of adrenoleukodystrophy showing normal VLCFA in plasma but clearly abnormal values in fibroblasts. This suggests that great care is warranted in interpreting plasma VLCFA analyses. Furthermore, plasma bile acids, phytanic acid, pristanic acid and pipecolic acid should be analysed in any patient with clinical symptoms suggestive for a peroxisomal disorder but normal plasma VLCFAs.

Adrenoleukodystrophy↗
PubMed2004

A thermodynamic basis of DNA sequence selectivity by the ETS domain of murine PU.1.

The ETS domain of the transcription factor PU.1 tolerates a large number of DNA cognate variants that differ exclusively in the sequences flanking a critical central consensus, 5'-GGAA-3'. We investigated the thermodynamics of site selection by the DNA-binding domain by following the PU.1 ETS/DNA equilibrium with a large set of cognate variants under various temperature and salt conditions by filter binding. Our results indicate that the stability of the ETS/DNA complex is quantitatively tied to variations in the change in heat capacity. Thermodynamic effects induced by changing Na(+) concentrations from 150 mM to 250 mM are complex and not readily interpreted by polyelectrolyte theory. We also extended our understanding of data from our previous investigation on energetic base-neighbour coupling, by dissecting the thermodynamic contributions underlying the observed free-energy coupling. In conjunction with available structural and biochemical data, we propose that site selectivity by the PU.1 ETS domain arises from differential protein/DNA contacts in the flanking sequences that modulate the orientation of the ETS recognition helix and trigger a coupled reduction in the flexibility observed in the unbound ETS domain.

Animals↗
PubMed2004

Qualitative aspects of verbal fluency in HIV-associated dementia: a deficit in rule-guided lexical-semantic search processes?

HIV-associated dementia (HAD) is widely considered a "subcortical" dementia that involves a disruption of frontal-basal ganglia circuits. Deficits in verbal fluency are common in HAD; however, the cognitive underpinnings of these deficits are not well understood. To elucidate the cognitive mechanisms underlying the diminished verbal fluency output in HAD, we examined several qualitative aspects of letter fluency in 21 individuals with HAD, 51 nondemented persons with HIV infection (HIV+), and 30 healthy controls (HC) who were comparable for age, education, sex, ethnicity, and estimated premorbid verbal intelligence. The verbal fluency protocols were scored to obtain the total number of correct words, average phonemic cluster size, total number of switches between phonemic clusters, and the proportion of error responses (i.e., intrusions, perseverations, and variants). Consistent with prior research, HAD participants produced significantly fewer total correct words relative to the HC and nondemented HIV+ groups. The HAD group also demonstrated fewer switches and a higher proportion of response errors (especially intrusion errors), but no differences were observed in average cluster size. Findings are interpreted as reflecting a disruption of rule-guided lexical-semantic search strategies in HAD, perhaps mediated by prefrontal-striatal circuit dysfunction, rather than depleted lexical-semantic memory stores.

AIDS Dementia Complex↗
PubMed2026

The importance of integrating genetic testing into reproductive medicine: a retrospective observational study investigating the monogenic causes of human infertility in couples considering ICSI.

The genetic landscape of human infertility is complex with diverse etiologies. Identifying the underlying etiology is crucial for guiding reproductive decisions and improving management for infertile couples. Here, we aim to report on the molecular spectrum of monogenic genetic causes of reproductive failure. Over a 3-year period, we recruited all infertile couples considering assisted reproductive technologies (ART) for whom the underlying genetic cause had been identified, in either partner, using exome sequencing (ES). Clinical data of all participants along with their hormonal profiles, sonographic findings and spermograms were recorded. The study included 50 couples with primary infertility. Clinically, male factor infertility was documented in 26 patients, female factor infertility in 10, while reproductive failure was unexplained in the remaining 14 couples. All participating couples had potentially disease-causing variants in infertility genes. ES identified variants related to male infertility in 26 men, while variants in female infertility-related genes were detected in the remaining couples (n&#x2009;=&#x2009;24). According to ACMG classification criteria, 78% (39/50) of couples harbored pathogenic/likely pathogenic (P/LP) variants, whereas 22% (11/50) carried variants of uncertain significance (VUS). In view of the identified genetic etiologies, the cohort was stratified into two groups based on the predicted reproductive outcome: (1) couples with significantly impaired reproductive potential, and (2) couples who can have biological children using appropriate medical interventions. However, classifications involving VUS were interpreted cautiously and considered exploratory. This study provides further evidence for the molecular heterogeneity of human infertility and highlights the usefulness of genetic testing for infertile couples pursuing ARTs.

Humans↗
PubMed1997

Immunohistochemical vs molecular biology methods. Complementary techniques for effective screening of p53 alterations in head and neck cancer.

The purpose of this study was to correlate p53 gene alterations and their expression in 85 head and neck squamous cell carcinomas. Genomic p53 was amplified with the polymerase chain reaction (PCR) from formalin-fixed, paraffin-embedded tissues. Exons 5 through 8 were screened for mutations by means of non-isotopic single-strand conformation polymorphism (SSCP) analysis. p53 expression was detected by means of immunohistochemistry (IHC) with the p53 monoclonal antibody DO-7. Twenty-three lesions (27%) showed both SSCP variants and DO-7 immunostaining, whereas 37 (44%) demonstrated both SSCP normal patterns and negative staining. Twenty-five lesions (29%) were discordant, including 12 IHC-positive (14%) and 13 SSCP-positive (15%) lesions. However, discordant IHC-negative, SSCP-positive lesions could have been easily interpreted after sequencing of the abnormal samples. Had these been screened with IHC only, all nonsense or frameshift p53 mutations would have been missed. IHC-positive, SSCP-negative lesions were interpreted in light of current models of p53 immunodetection. Had these been screened with SSCP or sequencing only, a sizeable number of tumors expressing p53 protein abnormalities would have been undetected. Therefore, simultaneous use of both methods increases the number of p53 abnormalities detected, and is warranted.

Antibodies, Monoclonal↗
PubMed1995

Radiology practices in emergency departments associated with pediatric residency training programs.

To examine the current radiology practices in academic emergency departments (EDs) serving children, a postal survey was done of 116 directors of EDs that serve as routine teaching sites for pediatric residents. One hundred three ED directors (89%) completed the survey, representing 75 pediatric-only EDs and 28 combined pediatric/adult EDs. Thirty-four of these EDs offer a pediatric emergency medicine fellowship. Hospitals were self-categorized as children's hospitals in 41 and non-children's hospitals in 62. Radiologists immediately read every study in 8% of the 103 EDs. Overall, 66% of the EDs have a radiology resident in-house overnight, which is significantly more likely in non-children's hospitals than in children's (79 vs 46%, P < 0.001). Overnight, ED radiographs of children may at times be solely interpreted by emergency attending physicians in 57% or emergency house staff in 44%. In EDs that allow their house staff to interpret solo overnight, emergency attending physicians are readily available to help with these interpretations less than half the time. A radiologist's second opinion overnight is readily or usually available in 63% of EDs. When any emergency physician interprets a radiograph solo overnight, the interpretation is almost always or often available later to the radiologist during the official interpretation only 40% of the time. Overnight, pediatric cervical spine studies are cleared, at times, solely by emergency attending physicians in 46% and by emergency house staff in 4%. Only 18% of programs have a daily or weekly ED radiograph review with radiologists. An ED atlas of common radiographic variants or a pediatric radiology textbook is available in 69% of EDs.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMedDate not supplied

Radiographic and CT appearances of the major fissures.

The major fissure is an important anatomic landmark in the interpretation of chest radiographs and computed tomographic (CT) scans. At radiography, the major fissures normally appear as hairlines of soft-tissue density; at conventional CT, they typically appear as lucent, hypovascular bands; and at high-resolution CT, they most often appear as sharp lines. The superolateral major fissure usually manifests as a curving edge at the upper lateral lung field with lateral opacity and medial lucency. The vertical fissure line appears as a fine, linear shadow, commencing in or near the costophrenic angle and coursing upward. The superomedial major fissure manifests as a short, obliquely oriented straight line. Progressive widening of the major fissure inferiorly manifests as a triangular area of increased opacity and represents intrafissural fat. Various inflammatory, granulomatous, neoplastic, and abnormal hemodynamic conditions involving the major fissure can affect its imaging appearance. Oblique orientation of the major fissure may complicate radiographic interpretation. The fissure may be incomplete or absent, complicating identification of various diseases. An incomplete major fissure may lead to disease spread, collateral air drift, or the "incomplete fissure sign," a sign that may, however, also be present in cases of complete fissure. Knowledge of the anatomy and normal variants of the major fissures is essential for recognizing their variable imaging appearances as well as related abnormalities.

Humans↗
PubMed2001

Myxoid leiomyosarcoma of the left atrium: a rare malignancy of the heart and its comparison with atrial myxoma.

Primary tumours of the heart are rare. The majority of these tumours are benign, with myxomas located in the left atrium being the most common form. Almost all malignant tumours are sarcomas and occur preferentially in the right side of the heart. An exception to this rule is leiomyosarcoma, a rare form of primary cardiac sarcoma that occurs predominantly in the left atrium, as does cardiac myxoma. The case of a 53-year-old woman who presented with symptoms of mitral valve stenosis and pulmonary hypertension is reported. Cardiac catheterization, angiography and echocardiography revealed a left atrial mass that was interpreted as atrial myxoma. At the time of operation, the myxoid appearance of the tumour mass further supported this assumption. The tumour, including a wide rim of atrial septum, was removed with cautery. Histopathological examination unexpectedly showed that the tumour was not an atrial myxoma but rather a myxoid variant of a primary leiomyosarcoma. Immunohistochemistry and electron microscopy confirmed the diagnosis. Local radiotherapy was considered but deemed contraindicated in view of the longstanding pulmonary hypertension. Two months after excision, a repeat echocardiogram indicated recurrence of tumour in the left atrium, and the patient died a few days later. The preferential left atrial location and the frequently myxoid appearance of primary leiomyosarcomas of the heart make it particularly difficult to differentiate them preoperatively from atrial myxomas. The authors recommend resection of all atrial myxoid tumours with a wide (at least 1 cm) margin, combined with intraoperative frozen section diagnosis, because complete surgical resection appears to correlate with prolonged survival in the few reported cases of atrial leiomyosarcomas. In cases of incomplete initial resection or local recurrence in the absence of metastatic disease, heart transplantation may be a valid option in appropriately selected patients.

Cardiac Catheterization↗
PubMedDate not supplied

[Morphological study of brainstem auditory evoked potentials. The effect of the position of the reference electrode].

INTRODUCTION: In view of the discrepancy between the siting of electrodes and the effects on BAEP, we made a morphological study of 30 healthy volunteers, 15 men and 15 women. DEVELOPMENT: In each person we obtained the BAEP with the active electrode on the ear lobe ipsilateral to the stimulated ear and the reference ear successively at four different sites: vertex (Cz), high frontal (Fz), earlobe contralateral to the stimulated ear and the spinous process of the seventh cervical vertebra (CV7). The I, III and V waves were present in all cases and tests, followed in frequency by II, IV and VII. In Cz and Fz the first five deflections were almost always seen, and these are the most useful for neurodiagnosis. The waves of greatest amplitude were 1 in both sexes in the ear lobe and CV7 for Fz and Cz in men and V for women. Regarding the complex morphological variants, the greatest incidence in the III IV V complex was observed in Fz in both sexes. In CV7 there was a greater range of variants, as found by other workers, but with greater morphological separation of waves IV and V. They were infrequent in waves I II and VI VII and least common in Fz and Cz. CONCLUSION: We consider that the BAEP obtained with reference to Cz and Fz are ideal for interpretation, since there is greater constancy, global amplitude and morphological clarity of the first five deflections and less morphological complexity of the other waves.

Adolescent↗
PubMed1992

Idiosyncratic drug reactions: interaction of development and genetics.

There is a major need for biologic markers closely linked to the mechanisms of susceptibility and toxicity of xenobiotics that can aid in elucidation of populations at risk. Such markers, genetic or developmental, need to be interpreted in light of the mechanism of toxicity of the specific compound. It is likely that maximum progress in this area will be made by integration of biologic markers of susceptibility (closely linked to the basic toxicologic mechanisms of the compound in question) with human epidemiologic studies. "New" pharmacogenetic variants in drug metabolism are being discovered at an ever-increasing rate. Molecular biology approaches to variant genes, as well as in vivo and cellular probes of toxicologically important metabolic pathways, are likely to serve as significant tools in predicting who is at risk for an ADR, and in confirming clinical impressions of ADR causality. Linked with epidemiologic studies of ADR incidence, it will be increasingly possible to discover the relative roles of development and genetics in ADRs.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1997

Location of the BCR-ABL fusion gene on the 9q34 band in two cases of Ph-positive chronic myeloid leukemia.

Two new variant Philadelphia (Ph) chromosomes with an aberrant location of the BCR-ABL fusion gene on 9q34 of the derivative 9 are reported. One presented cytogenetically as a standard t(9;22)(q34;q11), whereas the other was classified as an ins(9;22)(q34;q11.1q11.2) using the combined interpretation of cytogenic, FISH, and molecular data. The mechanisms of the two rearrangements are presented. It is suggested that the insertion has occurred in a single event in the patient with ins(9;22). In the patient with t(9;22), both a translocation and an insertion, occurring either sequentially or simultaneously, can account for the location of the BCR-ABL fusion gene on the derivative 9. A possible poor prognostic impact of this aberrant location of the BCR-ABL is also suggested by the clinical data reported in such patients.

Aged↗
PubMed1989

[Unstable angina, Prinzmetal's variant and transient Q waves. Report of a case].

A case is reported of the variant form of Prinzmetal angina, occurring two months after effort angina, in which the electrocardiogram revealed a Q wave in V2 in addition to ST segment elevation in precordial leads all of which disappeared in a few minutes. Several hours later, the ECG changes were suggestive of antero-septal infarction. However, four days later an R wave was present in lead V2, and 12 days after the acute episode, the tracing became entirely normal. Cinecoronary angiography revealed severe obstruction of the anterior descending artery, and a moderate obstruction of the left circumflex artery. The possibilities of spasm and/or coronary thrombosis, of spontaneous recanalization and of reperfusion due to thrombolysis are discussed, in addition to interpreting the abnormal Q waves as presumably due to severe myocardial ischemia resulting from acute coronary insufficiency. The present case exemplifies the concept that the syndromes of acute coronary heart disease cannot always be precisely differentiated, since they often overlap and are difficult to identify.

Angina Pectoris, Variant↗
PubMedDate not supplied

Substance P-immunoreactive nerves in endobronchial biopsies in cough-variant asthma and classic asthma.

BACKGROUND: Unlike classic asthma, cough-variant asthma does not show any evidence of airway obstruction. The main symptom is a dry cough with little known pathophysiology. Hypersensitivity of the cough receptors in cough-variant asthma and an increase in the sensory nerve density of the airway epithelium in persistent dry cough patients have been reported. Therefore, it is possible that there is a higher sensory nerve density in cough-variant asthma patients than in classic asthma patients. OBJECTIVES: This study was undertaken to compare the substance P (SP)-immunoreactive nerve density in mucosal biopsies of cough-variant asthma patients, classic asthma patients, and in control subjects. METHODS: Bronchoscopic biopsies were performed in 6 cough-variant asthma patients, 14 classic asthma patients, and 5 normal controls. The tissues obtained were stained immunohistochemically. The SP-immunoreactive nerve density was measured in the bronchial epithelium using a light microscope at 400 x magnification. RESULTS: SP- immunoreactive nerve density for the cough-variant asthma group was significantly higher than that of the classic asthma group (p = 0.001), and of the normal control group (p = 0.006). CONCLUSIONS: It is possible that a sensory nerve abnormality within the airway may be related to hypersensitivity of the cough receptor, and that this may be one of the pathophysiologies of cough-variant asthma.

Adult↗
PubMed2005

Time-variant parametric estimation of transient quadratic phase couplings during electroencephalographic burst activity.

OBJECTIVES: Electroencephalographic burst activity characteristic of burst-suppression pattern (BSP) in sedated patients and of burst-interburst pattern (BIP) in the quiet sleep of healthy neonates have similar linear and non-linear signal properties. Strong interrelations between a slow frequency component and rhythmic, spindle-like activities with higher frequencies have been identified in previous studies. Time-varying characteristics of BSP and BIP prevent a definite patternrelated analysis. A continuous estimation of the bispectrum is essential to analyze these patterns. Parametric bispectral approaches provide this opportunity. METHODS: The adaptation of an AR model leads to a parametric bispectrum by using the transfer function of the estimated AR filter. Time-variant parametric bispectral approaches require an estimation of AR parameters which consider higher order moments to preserve phase information. Accordingly, a time-variant parametric estimation of the bispectrum was introduced. Data driven simulations were performed to provide optimal parameters. BSP (12 patients) and BIP (6 neonates) were analyzed using this novel approach. RESULTS: Significant differences in the time course of burst pattern during BSP and burst-like pattern before the onset of BSP could be shown. A rhythmic quadratic phase coupling (period 10 sec) was identified during BIP in all neonates. CONCLUSION: Quadratic phase couplings during BSP increases in the time course depending on depth of sedation. The visually detected burst activity in BIP is only the temporarily observable EEG correlate of a hidden neural process. Time-variant bispectral approaches offer the possibility of a better characterization of underlying neural processes leading to improved diagnostic tools used in clinical routine.

Algorithms↗