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PubMed2002

Development of clinical practice guidelines for dentists: methods for topic selection.

OBJECTIVES: The aim of this study was to compare four methods for assessing the preferences of the dental profession for topics to be considered for the development of clinical practice guidelines. METHODS: The methods were: (1) a survey among dentists, (2) an analysis of topics discussed in dental peer groups, and (3) screening of dental journals. A fourth method was obtained from method number 3. The frequencies of the reported topics were calculated for each of the methods. For the fourth method, the number of publications per topic were plotted against the year of publication, and the slope of the linear regression line was used as an indicator. Within each of the four methods, the topics were ranked according to the frequency in which they were reported, and to the slope value. The reliability of the methods was tested by the "item-rest sum correlation", which is the correlation of the rank positions of one method with the sum of the rank positions obtained by the remaining three methods. RESULTS: In using all methods, a total of 1027 topics were obtained. Reclassification resulted in 34 topics. Moderate item-rest sum correlations ranging from 0.34 to 0.48 were found for all methods, indicating that the rank order of every method moderately predicts the sum of the rank orders obtained by all other methods. The topic 'prevention of cross-infection' had the highest overall rank position. CONCLUSION: It is concluded that the four applied methods appeared to provide a consistent ranking of potential topics. In view of the fact that the questionnaire method is generally applicable, this method should be preferred for assessing dentists' preferences for topics to be considered for the development of clinical practice guidelines.

Data Collection↗
PubMed2000

Computer recognition of skin structures using discriminant and cluster analysis.

BACKGROUND/AIMS: Automated image analysis of complex tissues is usually limited by the difficulty of recognizing special structures by computer. The aim of this study was to test the applicability of discriminant and cluster analysis to the interpretation of skin images. METHODS: Digital images from microscopic, dermatoscopic and clinical views of skin specimens were electronically dissected into elements of equal size and shape, and a set of grey level, colour and texture features was assessed for each element. Elements were classified interactively and submitted to discriminant analysis. Furthermore, hierarchical cluster analysis was used to enable the system to classify the tissue elements automatically, based on the available digital information. The classification results were relocated to the original image in order to evaluate the performance of the procedure. RESULTS: The system performs well in reproducibly detecting different skin structures in digital images. Discriminant analysis of interactively classified elements yielded a correct reclassification in 98 to 100% of tissue elements. Among the cluster analysis procedures, the conservative Ward method after removal of all highly correlated features produced the best results. The method turned out to be applicable irrespective of the image source used. CONCLUSIONS: Discriminant and cluster analysis may be helpful techniques for a user-independent, subjectively unbiased measurement system of skin structures.

Journal Article↗
PubMed2002

Evaluation of facial skin type by sebum secretion: discrepancies between subjective descriptions and sebum secretion.

BACKGROUND/AIMS: Facial skin is usually classified as dry, normal, and oily in the cosmetics field. However, there is no standard objective method for classifying facial skin. METHODS: We measured sebum excretion with Sebumeter at four sites on the face. Based on the amount of sebum secretion, we reclassified skin type according to the guidelines provided by the manufacturer. The mean of sebum excretion (mean facial sebum excretion; MFSE) was also calculated. RESULTS: People secrete varying amounts of sebum at different skin sites. Reclassification of skin type based on sebum secretion revealed that most participants underestimated the amount of facial sebum excretion. When sebum secretion amounts were compared, a statistically significant difference was apparent between the oily and dry skin types. However, there were no statistical differences between oily and normal, and normal and dry skin. CONCLUSION: We showed that subjective skin type does not match the amount of sebum secreted. Thus, this simple and subjective classification is of very limited use and it should be re-evaluated by using an objective and standardized measuring tool.

Adult↗
PubMed1992

Generalized social phobia versus avoidant personality disorder: a commentary on three studies.

The findings of Herbert, Hope, and Bellack (1992), Holt, Heimberg, and Hope (1992), and Turner, Beidel, and Townsley (1992) are largely consistent. Avoidant personality disorder and generalized social phobia appear to be overlapping constructs that have only minor differences with respect to severity of dysfunction. This commentary addresses the implications of the findings with respect to the validity of the categorical distinction in the Diagnostic and Statistical Manual of Mental Disorders (rev. 3rd ed.; American Psychiatric Association, 1987) between avoidant personality and generalized social phobia, revisions of their respective diagnostic criteria, and their reclassification as either an anxiety or a personality disorder. Methodological and substantive suggestions for future research are also discussed.

Adult↗
PubMed1992

Evaluation of cerebral vasomotor reactivity by various vasodilating stimuli: comparison of CO2 to acetazolamide.

To evaluate the role of different vasomotor stimuli for the measurement of cerebrovascular vasomotor reactivity (VMR), 47 patients (i.e., 93 hemispheres) with various degrees of internal carotid artery (ICA) occlusive disease were studied. Patients were divided into clinical [asymptomatic, transient ischemic attack (TIA) or completed stroke] as well as angiological subgroups. Low-grade or high-grade unilateral ICA lesions were compared to bilateral ICA occlusive disease. Relative flow velocity changes within the middle cerebral artery were measured by means of transcranial Doppler during hyper- and hypocapnia (VMRTOT), during hypercapnia alone (VMRCO2), and after injection of 1 g acetazolamide (VMRACE). VMR was expressed as the percentage change in flow velocity after stimulus application as compared with flow velocity at rest. There was a close and statistically highly significant correlation of CO2-induced with acetazolamide-induced VMR (r = 0.69 in VMRTOT versus VMRACE and 0.79 in VMRCO2 versus VMRACE; P less than 0.0001; linear regression), indicating a strong similarity of the vasodilatative effects of CO2 and acetazolamide on cerebral arteries. Both stimulation techniques highly significantly differentiated between asymptomatic patients and those with TIA or completed stroke. Angiological subgroups were separated best by the acetazolamide test. Reclassification of patients into angiological subgroups by linear discriminant analysis was equally good with all three methods. We conclude that both acetazolamide- and CO2-induced stimulation of the cerebral vasomotors are valid techniques to measure reduction in perfusion reserve due to extracranial cerebrovascular occlusive disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed2005

Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach.

Accurate morphologic distinction between small cell carcinoma and poorly differentiated squamous cell carcinoma has critical therapeutic significance, but can be limited by crush artifact, tumor necrosis, limited tumor representation, and overlapping morphologic features. We evaluated a panel of antibodies for their efficacy in distinguishing between these neoplasms. Formalin-fixed paraffin-embedded tissue sections of small cell carcinomas and poorly differentiated squamous cell carcinomas underwent immunohistochemical staining with antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A). Of 28 small cell carcinomas, 26 (93%) small cell carcinomas showed diffuse moderate or strong staining for thyroid transcription factor-1 with no staining for high molecular weight keratin and p63. In contrast, 27/28 (96%) poorly differentiated squamous cell carcinomas manifested opposite immunoreactivities, with diffuse moderate or strong staining for high molecular weight keratin and p63, and no or minimal staining for thyroid transcription factor-1. In two additional cases originally interpreted as small cell carcinoma, high molecular weight keratin highlighted small numbers of neoplastic large cells, leading to reclassification as combined small cell and non-small cell carcinomas. p16(INK4A) expression varied widely in poorly differentiated squamous cell carcinomas, but was consistently moderate or strong and diffuse in small cell carcinomas, and proved helpful in the two thyroid transcription factor-1-negative small cell carcinomas. This study demonstrates that a panel consisting of antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A) is highly effective for distinguishing between small cell carcinoma and poorly differentiated squamous cell carcinoma. This panel also facilitates diagnosis of combined small cell and non-small cell carcinomas.

Carcinoma, Small Cell↗
PubMed2004

Surgical intervention in patients with metastatic renal cancer: current status of metastasectomy and cytoreductive nephrectomy.

It is estimated that in 2004 there will be 35,700 new cases of, and 12,480 deaths from, kidney cancer in the US. Since 1950 there has been a 126% increase in the incidence of renal cancer and a 36.5% increase in annual associated mortality. In the past two decades, our understanding of tumors arising from the renal cortex has dramatically expanded owing to advances in cytogenetics and histopathological reclassification. It is now known that renal cell carcinoma (RCC) is a family of neoplasms that possess unique molecular and cytogenetic defects, with 90% of metastases emanating from conventional clear cell carcinoma subtype. In addition to advancing our understanding of RCC, improved abdominal imaging technology has caused a migration of tumor stage and alteration of surgical strategies, with tumors commonly being diagnosed at an earlier stage. Despite these advances, the prognosis for patients with metastatic RCC is poor. Studies that examine combinations of surgery and systemic therapy aim to improve survival in this high-risk group.

Carcinoma, Renal Cell↗
PubMed2026

Targeted reflex RNA sequencing for enhanced variant classification on exome and genome sequencing improves patient outcomes.

RNA sequencing (RNA-seq) has been utilized to provide functional evidence regarding the impact of splicing variants. This study explores the utility of targeted reflex RNA-seq to inform classification of predicted splicing variants identified through clinical exome sequencing (ES) and genome sequencing (GS). A retrospective analysis was conducted on consecutive ES/GS cases completed at a single center in which targeted reflex RNA-seq was performed following identification of eligible variants. There were 131 cases (4.1%) that had at least one RNA-seq eligible variant reported, with eight of these cases having two unique eligible variants. Of the 139 eligible variants, 125 were classified as variants of uncertain significance (VUS). Sixty-four cases had targeted reflex RNA-seq completed with 27 cases having at least one variant reclassified (42.2%). After reclassification, 23 cases had positive results, and two cases had a likely diagnosis of an autosomal recessive condition. Clinical outcomes data regarding positive RNA-seq cases showed that 71% (10/14) had clinical management changes and 43% (6/14) had treatment changes. Incorporation of targeted reflex RNA-seq analysis into the diagnostic pipeline of rare diseases enhances variant classification and resolves uncertainty regarding predicted splice variants, leading to an estimated 1.6% increase in diagnostic yield of clinical ES/GS.

Journal Article↗
PubMed1999

Beijerinckia sp strain B1: a strain by any other name.

Beijerinckia sp strain B1 grows with biphenyl as its sole source of carbon and energy. A mutant, strain B8/36, oxidized biphenyl to cis-(2S,3R)-dihydroxy-l-phenylcyclohexa-4,6-diene (cis-biphenyl dihydrodiol). Strain B8/36 oxidized anthracene, phenanthrene, benz[a]anthracene and benzo[a]pyrene to cis-dihydrodiols. Other substrates oxidized to cis-dihydrodiols were dibenzofuran, dibenzothiophene and dibenzo-p-dioxin. Biphenyl dioxygenase activity was observed in cells of Beijerinckia B1 and B8/36 after growth in the presence of biphenyl, m-, p-xylene and salicylate. Recent studies have led to the reclassification of Beijerinckia B1 as Sphingomonas yanoikuyae strain B1. Subsequent biotransformation studies showed that S. yanoikuyae B8/36 oxidized chrysene to a bis-cis-diol with hydroxyl substituents at the 3,4- and 9,10-positions. Dihydronaphthalene was oxidized to cis-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene, naphthalene, cis-1,2-dihydroxy-1,2-dihydronaphthalene and 2-hydroxy-1,2-dihydronaphthalene. Anisole and phenetole were oxidized to phenol. Thus the S. yanoikuyae biphenyl dioxygenase catalyzes cis-dihydroxylation, benzylic monohydroxylation, desaturation and dealkylation reactions. To date, the genes encoding biphenyl dioxygenase have not been cloned. However, the nucleotide sequence of a S. yanoikuyaeB1 DNA fragment contains five different alpha subunits as determined by conserved amino acids coordinating iron in a Rieske [2Fe-2S] center and mononuclear iron at the catalytic site. The specific role of the different putative oxygenases in biotransformation reactions catalyzed by S. yanoikuyae is not known and presents an exciting challenge for future studies.

Journal Article↗
PubMed1998

Refractory anemia with severe dysplasia: clinical significance of morphological features in refractory anemia.

Refractory anemia (RA) in myelodysplastic syndromes (MDS) are very heterogeneous diseases regarding their morphology, clinical features and survival. We proposed the new designations 'RA with severe dysplasia (RASD)' and 'RA with minimal dysplasia (RAminiD)'. In our criteria, RASD is considered present if a bone marrow (BM) examination shows Pseudo-Pelger-Huet anomalies of mature neutrophils > or =3% and/or micromegakaryocytes (mMgk) of megakaryocytes > or =10% in RA patients. RAminiD is defined as RA cases other than RASD. After the reclassification of 58 primary RA patients, the group was composed of 45 RAminiD and 13 RASD patients. The blast percentage in the BM and the frequency of cytogenetic abnormalities observed in the RASD patients were intermediate between those in the RAminiD and RAEB patients. The analysis of survival curves revealed differences among the three groups; the RASD patients had lower survival probabilities than those of the RAminiD group, and significantly higher probabilities than those of the RAEB group. (RAminiD vs RASD, P=0.06; RASD vs RAEB, P=0.004.) Our data indicate that in RA patients, RASD is a distinct subset of RA with an unfavorable clinical outcome.

Adult↗
PubMed2005

Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling.

Tumors of low malignant potential (LMP) represent 20% of epithelial ovarian cancers (EOCs) and are associated with a better prognosis than the invasive tumors (TOV). Defining the relationship between LMPs and TOVs remains an important goal towards understanding the molecular pathways that contribute to prognosis, as well as providing molecular markers, for these EOCs. To this end, DNA microarray analyses were performed either in a primary culture or a tumor tissue model system and selected candidate genes showing a distinctive expression profile between LMPs and TOVs were identified using a class prediction approach based on three statistical methods of analysis. Both model systems appear relevant as candidate genes identified by either model allowed the proper reclassification of samples as either LMPs or TOVs. Selected candidate genes (CAS, CCNE1, LGALS8, ITGbeta3, ATP1B1, FLIP, KRT7 and KRT19) were validated by real-time quantitative PCR analysis and show differential expression between LMPs and TOVs. Immunohistochemistry analyses showed that the two tumor classes were distinguishable by their expression of CAS, TNFR1A, FLIP, CKS1 and CCNE1. These results define signature patterns for gene expression of LMPs and TOVs and identify gene candidates that warrant further study to deepen our understanding of the biology of EOC.

Diagnosis, Differential↗
PubMed1976

Dipeptidyl peptidase IV, a kidney brush-border serine peptidase.

Dipeptidyl peptidase IV, an enzyme that releases dipeptides from substrates with N-terminal sequences of the forms X-Pro-Y or X-Ala-Y, was purified 300-fold from pig kidney cortex. The kidney is the main source of the enzyme, where it is one of the major microvillus-membrane proteins. Several other tissues contained demonstrable activity against the usual assay substrate glycylproline 2-naphthylamide. In the small intestine this activity was greatly enriched in the microvillus fraction. In all tissues examined, the activity was extremely sensitive to inhibition by di-isopropyl phosphorofluoridate (Dip-F), but relatively resistant to inhibition by phenylmethylsulphonyl fluoride. It is a serine proteinase which may be covalently labelled with [32P]Dip-F, and is the only enzyme of this class in the microvillus membrane. The apparent subunit mol.wt. estimated by sodium dodecyl-sulphate/polyacrylamide-gel electrophoresis and by titration with [32P]Dip-F was 130 000. Gel-filtration and sedimentation-equilibrium methods gave values in the region of 280 000, which is consistent with a dimeric structure, a conclusion supported by electron micrographs of the purified enzyme. Among other well-characterized serine proteinases, this enzyme is unique in its membrane location and its large subunit size. Investigation of the mode of attack of the peptidase on oligopeptides revealed that it could hydrolyse certain N-blocked peptides, e.g. Z-Gly-Pro-Leu-Gly-Pro. In this respect it is acting as an endopeptidase and as such may merit reclassification and renaming as microvillus-membrane serine peptidase.

Animals↗
PubMed2006

Blood genomic profiling: novel diagnostic and therapeutic strategies for stroke?

Findings from gene expression profiling studies are leading to new diagnostic and therapeutic strategies that can be applied in medical practice, especially in the field of oncology. Promising results of gene expression profiling of the peripheral blood in patients with ischaemic stroke have been obtained in recent pilot studies, demonstrating a partially reproducible gene signature of acute cerebral ischaemia. However, questions remain. Given that blood is at least in part a surrogate tissue for ischaemic stroke, the specificity of these signatures needs to be evaluated. Furthermore, it needs to be determined whether standardization of this methodology is required and whether clinical signatures can be identified that are improvements over the tools currently used in clinical practice. Clinically useful signatures would include those of haemorrhagic as well as ischaemic stroke, reclassification of stroke type and prognosis, and vascular disease risk. If these conditions are met, then it should be possible to develop cost-effective and rapid assays.

Blood↗
PubMed1996

Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study.

During a 9-year-period, 50 cases of primary non-Hodgkin's lymphoma (NHL) of the thyroid gland were reported to a population-based lymphoma registry covering western Denmark giving an incidence of 2.06 x 10(-6) cases per year. The male:female ratio was 1:4, and the mean age was 72.8 years for women and 62.8 years for men. On histomorphological reclassification 83% of the cases showed a high grade and 17% a low grade morphology, 98% had a B-phenotype and 2% a T-phenotype. In at least 33 of the cases, primary NHL of the thyroid gland was preceded by Hashimoto's thyroiditis and at least 25 of the patients had a high grade NHL which was transformed from Hashimoto's thyroiditis through a low grade B-cell lymphoma of MALT type. The most frequent presenting symptoms were goitre (100%), hoarseness (57%), stridor/dyspnoea (55%) and dysphagia (45%); thirty-six percent of the patients were hypothyroid at the time of diagnosis. Seventy-six percent of the patients had localized disease (stages 1-2) and 24% had disseminated lymphoma (stages 3-4). Five year survival was 34.5% and 5 year cause-specific survival 46.2%. The following factors were associated with a poor prognosis: stage 3-4 disease, elevated S-urate, presence of hoarseness and age > 66 years. Morphological subtype did not correlate significantly with survival.

Adult↗
PubMed2000

Diagnostic gold standard for soft tissue tumours: morphology or molecular genetics?

The recognition of recurrent genetic alterations in specific tumour types has provided the basis for the reclassification of certain soft tissue neoplasms, and molecular analysis of patient material has the potential to provide both diagnostic and prognostic information. In this review, we evaluate the role of molecular genetic testing as the prospective 'gold standard' for sarcoma diagnosis. Molecular genetic testing, as with every new method, promises to improve accuracy and to be more sensitive and less subjective, claims that have been made previously by histochemistry, electron microscopy and immunohistochemistry. Technical limitations in molecular assays, as well as more general specificity issues, decrease the clinical usefulness of molecular pathological testing significantly and suggest that, at present, molecular evaluation is best considered an ancillary technique that neither supersedes other ancillary techniques nor eclipses traditional pathological examination.

Adult↗
PubMed2000

Delineation of genetic zones in the European Norway spruce natural range: preliminary evidence.

We applied geostatistics to previously reported chloroplast simple sequence repeats (cpSSR) haplotype frequency data from 95 European Norway spruce populations to provide preliminary evidence about the following issues: (i) delineation of genetically homogeneous regions ('genetic zones'); (ii) prediction of their haplotype frequencies and definition of related criteria to be applied for provenance identification and certification of seedlots; (iii) identification of putative allochthonous stands; and (iv) construction of a continental-scale 'availability map' of the intraspecific biodiversity for Norway spruce. Direct evidence of large-scale geographical structure over the European natural range was obtained, detecting both geographical clines and stationary patterns. The increase of the mean genetic divergence by geographical distance (up to approximately 1800 km apart) provided a strong hint that geographical distance is a major factor of differentiation in Norway spruce. Haplotype frequency surfaces were obtained by applying ordinary kriging to sampling frequency data. Cluster analysis carried out on haplotype frequency surfaces revealed a fair discrimination among 16 genetic zones, with an accuracy of 0.916. Dendrogram analysis carried out on the predicted mean haplotype frequency confirmed a fairly good separability of the genetic zones detected. Reclassification of populations by discriminant analysis confirmed the robustness of the genetic subdivision obtained. Combining the information from discriminant analysis and cross-validation of sampling points, three populations likely to be of nonlocal origin were identified. The application of geostatistical analysis to genetic marker data is discussed in relation to breeding activities and to the formulation of appropriate conservation strategies.

Cluster Analysis↗
PubMed1999

A comparison of ambulatory and conventional urodynamic studies in men with borderline outlet obstruction.

OBJECTIVE: To compare detrusor function and outlet behaviour on ambulatory urodynamic monitoring (AUM) with conventional cystometrography in symptomatic men with borderline evidence of bladder outlet obstruction (BOO), as determined by conventional cystometrography, and to assess the usefulness of AUM in reclassifying this population of patients into obstructed and unobstructed groups. PATIENTS AND METHODS: Sixty-nine consecutive men (mean age 59.6 years) with lower urinary tract symptoms (mean International Prostate Symptom Score 19.1) and borderline BOO on a medium-fill conventional urodynamic study (CUS) were examined prospectively with AUM. Detrusor contractility, obstruction grade, maximal voiding detrusor pressure (pdet(max)), detrusor pressure at peak flow (pdet Qmax) and peak flow rate (Qmax) determined by both methods were compared. The incidence of detrusor instability (DI) detected by both modalities was also evaluated. RESULTS: There was considerable disagreement between the investigations during the voiding phase. Detrusor contractility was higher on AUM than on CUS (P= 0.003) and obstruction grade was significantly lower on AUM (P=0.018). There was no difference in pdet(max) nor pdet Qmax. The mean (95% confidence interval) Qmax was higher on AUM, at 12.9 (1.3) mL/s, than on CUS, at 8.9 (0.8) mL/s. On the Abrams-Griffiths nomogram the most significant changes were six men (10%) from equivocal to obstructed, seven (11%) from equivocal to unobstructed and two (3%) from obstructed to unobstructed on CUS and on AUM, respectively. Thus, in 24% of patients there was a potentially clinically significant change resulting from the information generated by AUM. DI was identified on CUS in 26 (41%) men and on AUM in 25 (40%); 35 men (56%) had evidence of DI on either AUM or CUS. CONCLUSION: The significant disagreement between the findings on CUS and AUM suggests that the conditions under which pressure-flow investigations are carried out significantly affect findings in borderline cases. The reclassification of patients by AUM into obstructed and unobstructed groups occurs in 24% and may be clinically relevant. AUM appears to be complementary to CUS in the assessment of men who are borderline for obstruction on conventional testing, but the clinical implications of this have yet to be determined.

Constriction, Pathologic↗
PubMed1991

MMPI personality profiles in patients with primary headache syndromes.

The role of psychological factors in the course of primary headache syndromes is still controversial. Using the Minnesota Multiphasic Personality Inventory (MMPI) we investigated the personality profiles of 434 headache patients (160 migraineurs, 95 with tension type headache, 30 with cluster headache and 149 with combination headache) in accordance with the IHS criteria. In the first three MMPI scales (hypochondria, depression, hysteria) there was a slight increase in T mean values to over 60, but still in the range of two standard deviations of the normal population. There were no statistically significant differences between the four headache groups and between patients with and without analgesic abuse. It was impossible to distinguish headache groups on the basis of their personality profiles by means of reclassification with discriminant analysis. In a cluster analysis, patients with cluster headache showed the highest number (20%) of abnormalities, but also the highest percentage (13%) of completely normal results. Our findings--a cross section analysis of personality profiles--contradict many other MMPI-based studies.

Adolescent↗