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PubMed1997

Quick Reference Guide for Clinicians. Early identification of Alzheimer's disease and related dementias. U.S. Department of Health and Human Services.

This Quick Reference Guide for Clinicians contains highlights from Recognition and Initial Assessment of Alzheimer's Disease and Related Dementias, Clinical Practice Guideline No. 19, which was developed by a multidisciplinary panel composed of health care professionals and consumer representatives. The Quick Reference Guide focuses on (a) symptoms that suggest the presence of a dementing disorder and (b) steps to follow in conducting an initial assessment for Alzheimer's disease or a related dementia, including use of specific mental and functional status tests on the basis of their efficacy and clinical utility in discriminating early-stage dementia. It also addresses how to interpret test results, the role of neuropsychological testing, and resources for patients and families facing a diagnosis of probable dementia.

Adult↗

PubMed1997

Early identification of Alzheimer's disease and related dementias.

This Quick Reference Guide for Clinicians contains highlights from Recognition and Initial Assessment of Alzheimer's Disease and Related Dementias, Clinical Practice Guideline No. 19, which was developed by a multidisciplinary panel composed of health care professionals and consumer representatives. The Quick Reference Guide focuses on (a) symptoms that suggest the presence of a dementing disorder, and (b) steps to follow in conducting an initial assessment for Alzheimer's disease or a related dementia, including use of specific mental and functional status tests on the basis of their efficacy and clinical utility in discriminating early-stage dementia. It also addresses how to interpret test results, the role of neuropsychological testing, and resources for patients and families facing a diagnosis of probable dementia.

Aged↗

PubMed1993

Significance of a hot spot on the bone scan after carpal injury--evaluation by computed tomography.

The use of bone scintigraphy in patients with negative radiographs after carpal injury is widely advocated. However, focally increased activity on the bone scan in the scaphoid or other carpal bones cannot always be radiologically confirmed as a fracture. To confirm scintigraphically suspected carpal fractures, computed tomography (CT) of the wrist was performed in patients with clinically suspected scaphoid fracture and initially negative radiographs. All patients underwent plain radiography, bone scintigraphy and CT. The combination of plain radiographs and CT, as judged by a panel of experienced observers, was used as the reference standard. In 18 patients, 21 out of 22 carpal hot spots on bone scintigraphy could be radiologically confirmed as a fracture. The diagnosis was missed by CT scan in three patients with proven fractures on plain radiographs. We conclude that, in patients with negative initial radiographs following carpal injury, a positive bone scan must be interpreted as a fracture.

Adult↗

PubMed1984

Off-line montage reformatting.

A method is described for off-line reformatting of recorded EEG data to any desired montage, gains, filter settings and paper speed. Thirty-two channels, including every scalp electrode, are recorded in a common referential montage and multiplexed onto videocassettes . Playback onto an EEG machine faithfully reproduces the original signals, so that any final montage may be specified at the EEG selector panel, with common mode rejection of the recording reference. The technique has proven especially useful in prolonged seizure monitoring and in the clarification of events which occur only rarely in the course of routine EEGs.

Child, Preschool↗

PubMed2006

Monomorphism of human cytochrome c.

Cytochrome c (Cyt c) has key roles in both mitochondrial electron transfer and apoptosis onset and is therefore likely undergoing a strong selective pressure against amino acid variation. Nevertheless, a phylogenetically fast amino acid replacement rate in the Cyt c of species of the anthropoid primate lineage was recently reported. We therefore looked for the presence of nonsynonymous single nucleotide polymorphisms (nsSNPs) in the human Cyt c (HGNC approved gene symbol: CYCS), which, given its cellular constraints, could have important functional consequences, and found a large number of putative nsSNPs reported in the dbSNP database. We then subjected these putative SNPs to experimental validation by sequencing the Cyt c gene in a panel of 95 individuals assumed as a standard reference of the human population diversity. Surprisingly, none of the putative SNPs survived experimental validation. We conclude that non-rare allelic variants of the Cyt c protein are absent in the human populations analyzed in this study.

Alleles↗

PubMed2002

2,6-Di(omega-aminoalkyl)-2,5,6,7-tetrahydropyrazolo[3,4,5-mn]pyrimido[5,6,1-de]acridine-5,7-diones: novel, potent, cytotoxic, and DNA-binding agents.

DNA-binding agents with potential antitumor activities bearing two cationic side chains, the 2,6-di(omega-aminoalkyl)-2,5,6,7-tetrahydropyrazolo[3,4,5-mn]pyrimido[5,6,1-de]acridine-5,7-diones (4a-r), have been prepared either by reaction of the appropriate 2-(omega-aminoalkyl)-6-chloro-2,3-dihydro-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7-trione with the appropriate (omega-aminoalkyl)hydrazine or by cyclization of the requisite N-6,2-di(omega-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-6-carboxamide with phosgene. In vitro cytotoxic properties of these derivatives against three human colon adenocarcinoma cell lines (HT29, LoVo, and LoVo/Dx) and against some cell lines of the NCI panel are described and compared to that of reference drugs. Some of the new compounds showed outstanding potency while lacking cross-resistance with anthracyclines. Structure-activity relationships are discussed, and a mechanistic analysis is performed using the COMPARE procedure. The mechanism and efficiency of noncovalent DNA binding of these compounds are examined using gel electrophoresis and fluorometric techniques. The 2,6-di(omega-aminoalkyl)-2,5,6,7-tetrahydropyrazolo[3,4,5-mn]pyrimido[5,6,1-de]acridine-5,7-diones (4) constitute a new class of potent, cytotoxic DNA-binding agents not cross-resistant with doxorubicin.

Acridines↗

PubMed1998

Stable binding to E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumor cell growth.

The retinoblastoma tumor suppressor protein (pRB) can inhibit cell cycle progression and promote differentiation. pRB interacts with a variety of transcription factors, including members of the E2F and C-EBP protein families and MyoD, and can either repress or activate transcription depending on the promoter under study. These biological and biochemical activities of pRB have been mapped previously to a core domain, referred to as the pRB pocket. Using a panel of synthetic pRB pocket mutants, we found that the acute induction of a G1/S block by pRB is linked to its ability to both bind to E2F and to repress transcription. In contrast, these functions were not required for pRB to promote differentiation, which correlated with its ability to activate transcription in concert with fate-determining proteins such as MyoD. All tumor-derived pRB mutants tested to date failed to bind to E2F and did not repress transcription. Despite an inability to bind to E2F, pRB mutants associated with a low risk of retinoblastoma, unlike high-risk mutants, retained the ability to activate transcription and promote differentiation. Thus, the pRB pocket participates in dual tumor suppressor functions, one linked to cell cycle progression and the other to differentiation control, and these functions can be genetically and mechanistically dissociated.

Carrier Proteins↗

PubMed2005

A comparison of clinically important differences in health-related quality of life for patients with chronic lung disease, asthma, or heart disease.

OBJECTIVE: On the eight scales of the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36), Version 2, we compared the clinically important difference (CID) thresholds for change over time developed by three separate expert panels of physicians with experience in quality of life assessment among patients with chronic obstructive pulmonary disease (COPD), asthma, and heart disease. STUDY DESIGN: We used a modified Delphi technique combined with a face-to-face panel meeting within each disease to organize and conduct the consensus process among the expert panelists, who were familiar with the assessment and evaluations of health-related quality of life (HRQL) measures among patients with the panel-specific disease. PRINCIPAL FINDINGS: Each of the expert panels first determined the magnitude of the smallest numerically possible change on each SF-36 scale, referred to as a state change, and then built their CIDs from this metric. All three panels attained consensus on the scale changes that constituted small, moderate, and large clinically important SF-36 change scores. The CIDs established by the heart disease panel were generally greater than the CIDs agreed on by the asthma and COPD panels. CONCLUSIONS: These panel-derived thresholds reflect possible differences in disease management among the represented panel-specific diseases, and are all greater than the minimal CID thresholds previously developed for the SF-36 scales among patients with arthritis. If confirmed among patients with the relevant diseases and those patients' physicians, these disease-specific CIDs could assist both researchers and practicing clinicians in the use and interpretation of HRQL changes over time.

Asthma↗

PubMed1996

Characterization of the genetic locus encoding Haemophilus influenzae type b surface fibrils.

Haemophilus influenzae is a common gram-negative pathogen that initiates infection by colonizing the upper respiratory tract epithelium. In previous work, we reported the isolation of a locus involved in expression of short, thin surface fibrils by H. influenzae type b and presented evidence that surface fibrils promote attachment to human epithelial cells. In the present study, we determined that the fibril locus is composed of one long open reading frame, designated hsf, which encodes a protein (Hsf) with a molecular mass of approximately 240 kDa. The derived amino acid sequence of the hsf product demonstrated 81% similarity and 72% identity to a recently identified nontypeable H. influenzae adhesin referred to as Hia. In experiments with a panel of eight cultured cell lines, the Hsf and Hia proteins were found to confer the same binding specificities, suggesting that hsf and hia are alleles of the same locus. Southern analysis and mutagenesis studies reinforced this conclusion. Further investigation revealed that an hsf homolog is ubiquitous among encapsulated H. influenzae strains and is present in a subset of nontypeable Haemophilus strains as well. We speculate that the hsf gene product plays an important role in the process of respiratory tract colonization by H. influenzae.

Adhesins, Bacterial↗

PubMed2002

Use of the sensititre colorimetric microdilution panel for antifungal susceptibility testing of dermatophytes.

The Sensititre YeastOne antifungal panel was used to test 49 dermatophytes belonging to the species Epidermophyton floccosum, Microsporum gypseum, Microsporum canis, Trichophyton tonsurans, Trichophyton rubrum, and Trichophyton mentagrophytes. The MICs of four antifungals obtained with the Sensititre YeastOne antifungal panel were compared with those obtained by the reference NCCLS microdilution method. The levels of agreement between the two methods (<or=2 dilutions) were 81.6% with amphotericin B, 87.7% with itraconazole, 67.3% with fluconazole, and 69.4% with ketoconazole.

Amphotericin B↗

PubMed2003

Use of amplified ribosomal DNA restriction analysis for identification of Ralstonia and Pandoraea species: interest in determination of the respiratory bacterial flora in patients with cystic fibrosis.

The recovery of Ralstonia and Pandoraea species from respiratory tract cultures of patients with cystic fibrosis has recently been reported. These species are difficult to identify, and especially to differentiate from Burkholderia cepacia complex organisms, with classical methods. The discriminatory power of amplified ribosomal DNA restriction analysis (ARDRA) within the two genera was assessed by comparing the restriction profiles of reference strains of each species by using a panel of six enzymes already proven suitable for the identification of Burkholderia species. ARDRA provided differentiation of all the Ralstonia species tested and of Pandoraea norimbergensis. Pandoraea species P. pnomenusa, P. sputorum, P. pulmonicola, and P. apista were not discriminated to the species level. This method allowed the identification of five clinical isolates recovered from French cystic fibrosis patients as Ralstonia mannitolilytica.

Bacterial Typing Techniques↗

PubMed2005

External quality assessment for molecular detection of Bordetella pertussis in European laboratories.

Although the PCR for the detection of Bordetella pertussis is routinely performed in diagnostic laboratories, no quality assessment program has so far been described. We report on the results obtained with two external quality assessment proficiency panels sent to European laboratories. The first proficiency panel contained a series of dilutions of three previously characterized B. pertussis clinical isolates and two negative controls. No false-positive results were reported by six laboratories providing seven data sets. The reported limits of detection of the three B. pertussis strains varied between 4 and 4,000, 9 and 9,000, and 3 and 30,000 CFU/ml, respectively. The second proficiency panel, composed of a series of dilutions of reference strains of B. pertussis, B. holmesii, B. hinzii, and B. bronchiseptica, as well as negative controls, was sent to nine laboratories. One laboratory reported a negative result for a sample and reported a B. parapertussis-positive sample to be positive for B. pertussis. By using the B. pertussis-specific target gene pertactin, one laboratory detected B. pertussis with 100% specificity. All other laboratories, which used IS481-based assays, reported positive results for the samples containing B. holmesii and B. bronchiseptica, species that have occasionally been recovered from human respiratory samples. These data show that the choice of the target gene is particularly critical for the species specificity of B. pertussis PCR assays.

Bordetella pertussis↗

PubMed1989

Production and characterization of neutralizing monoclonal antibodies against poliovirus type 1, 2, and 3.

Neutralizing monoclonal antibodies were produced against a reference vaccine or a reference wild strain of poliovirus type 1, 2, and 3. After 26 fusions, 55 monoclonal antibodies were obtained with serotype 1 as the immunizing antigen, 180 with serotype 2, and 115 with serotype 3. The neutralizing activity of these monoclonal antibodies was tested first with the two reference strains and then if reactive, against a panel of 10 well-characterized strains of each serotype, 5 vaccinelike (VL) and 5 nonvaccinelike (NVL). All monoclonal antibodies were type specific without reactivity with any of the heterologous strains. There was a wide range of reactivity within the strains of each serotype. Several monoclonal antibodies to serotype 1 reacted with all type 1 strains, while several neutralized strongly all VL strains and weakly one or more of the NVL strains. Most of the 180 monoclonal antibodies to serotype 2 neutralized to various degrees all strains of this serotype and about half reacted very strongly with all homologous strains whether VL or NVL. None could differentiate all VL and NVL homologous strains. Of the 115 monoclonal antibodies to serotype 3, several monoclonal antibodies neutralize to various levels all homologous strains and some can differentiate VL and NVL strains.

Animals↗

PubMed1989

Quality of death certificates in Valencia, Spain.

Certificates of 1,454 deaths occurring over 11 months were retrieved from the Civil Register in Valencia, Spain. Relevant medical information was systematically gathered from hospital records, questionnaires, and Coroner reports. We compared the underlying cause of death (UCD) from the original death certificate, and a reference cause of death (RCD) determined by a panel of experts based on all available information. Overall, 80.2 percent of the certificates were concordant for disease category, but there was a great disparity among some specific disease categories.

Cause of Death↗

PubMedDate not supplied

The peripheral blood lymphocyte pattern in psoriasis preceded by an infection.

BACKGROUND: There is a great deal of information to suggest that activated T cells play a major role in the pathogenesis of psoriasis. Less is known about the possible influence of a trigger bacterial antigen on circulating blood cells. The purpose of our study was to analyze the quantity and subpopulations of activated lymphocytes in peripheral blood in patients with psoriasis preceded by an infection and in a control group. MATERIAL AND METHODS: Thirty-two patients with psoriasis induced by an infection and twenty-two healthy controls were examined. The T lymphocytes in peripheral blood were examined by means of flow cytometry, using panels of monoclonal antibodies. Expression was estimated by reference to the fluorescence intensity of the surface antigens studied. RESULTS: A decreased percentage of CD3+, CD4+, and CD4+-bearing IL-6 receptor cells, a decreased expression of CD3, CD19, and CD4 antigens, and a significantly increased percentage of CD45RO+CD4+ were found in the studied subpopulation of lymphocytes. CONCLUSIONS: Our research demonstrated changes in the percentage and expression of certain subpopulations of T lymphocytes in peripheral blood in the course of psoriasis preceded by a bacterial infection, which suggests not only local, but also systemic activation of the immune system.

Adolescent↗

PubMed1978

An "oncometer" of clinical measurement of colloid osmotic pressure of plasma.

Measurement of colloid osmotic pressure complements measurements of pulmonary artery wedge pressure for assessing the risks of pulmonary edema and constitutes an increasingly important reference for purposes of guiding selection of colloid or crystalloid fluids in patients with acute cardiac disease. We describe a simple device for its routine clinical measurement. A membrane, selectively impermeable to molecules of relative molecular mass (Mr) greater than 30000, is rigidly mounted between a sample chamber and a reference chamber filled with isotonic saline. A pressure transducer measures the negative pressure developed in the reference chamber and displays it on a digital panel meter. The sensor chamber accommodates samples of 50 to 300 microliter. Equilibration is completed within 2 min. A control solution of human serum albumin (50 g/liter) is measured to confirm the accuracy of calibration of the system, with reproducible readings of 25.9 g/cm2 within one SD (equivalent to 0.4 g/cm2). Technical simplicity of operation and modest costs of disposables have made feasible the routine measurement of colloid osmotic pressure.

Colloids↗

PubMed1999

Appropriateness of referral of coronary angiography patients in Sweden. SECOR/SBU Project Group.

OBJECTIVE: To evaluate the appropriateness of referral following coronary angiography in Sweden. DESIGN: Prospective survey and review of medical records. PATIENTS: Consecutive series of 2767 patients who underwent coronary angiography in Sweden between May 1994 and January 1995 and were considered for coronary revascularisation. MAIN OUTCOME MEASURES: Percentage of patients referred for coronary artery bypass graft surgery (CABG) and percutaneous transluminal coronary angioplasty (PTCA) for indications that were judged necessary, appropriate, uncertain, and inappropriate by a multispecialty Swedish national expert panel using the RAND/University of California Los Angeles (UCLA) appropriateness method, and the percentage of patients referred for continued medical management who met necessity criteria for revascularisation. RESULTS: Half the patients were referred for CABG, 25% for PTCA, and 25% for continued medical therapy. CABG was judged appropriate or necessary for 78% of patients, uncertain for 12% and inappropriate for 10%. For PTCA the figures were 32%, 30% and 38%, respectively. Two factors contributed to the high inappropriate rate. Many of these patients did not have "significant" coronary artery disease (although all had at least one stenosis > 50%) or they were treated with less than "optimal" medical therapy. While 96% of patients who met necessity criteria for revascularisation were appropriately referred for revascularisation, 4% were referred for continued medical therapy. CONCLUSIONS: Using the RAND/UCLA appropriateness method and the definitions agreed to by the expert panel, which may be considered conservative today, it was found that 19% of Swedish patients were referred for coronary revascularisation judged inappropriate. Since some cardiovascular procedures evolve rapidly, the proportion of patients referred for inappropriate indications today remains unknown. Nevertheless, physicians should actively identify those patients who will and will not benefit from coronary revascularisation and ensure that they are appropriately treated.

Adult↗

PubMed1999

Laboratory testing, diagnosis, and management of von Willebrand disease. Current practice in Australasia. RCPA Quality Assurance Program in Haematology Scientific Haemostasis Advisory Panel.

We report an evaluation of current laboratory and clinical practice for the diagnosis and management of von Willebrand disease (VWD) for a wide geographic area including Australia, New Zealand, and parts of Southeast Asia. This assessment has been undertaken in conjunction with the RCPA Quality Assurance Program (QAP) in Haematology. This external QAP currently comprises around 550 participating laboratories, of which some 450 perform coagulation testing, and from which 32 laboratories were identified to be actively involved in testing for VWD. These laboratories were targeted and their current laboratory and clinical practice evaluated by using various questionnaires. Our overall findings indicate a wide variation in laboratory test practice for VWD-based investigations. There was considerable variation among laboratories in the tests and test methods used, the control and calibration material used, the reported test reference intervals and units used, and the composite test panels used to diagnose VWD. However, substantial consensus in the clinical evaluation process, as undertaken by hematologists, also was identified. Despite the observed variations, most laboratory professionals seemed to understand the complexities involved in the diagnosis and subclassification of VWD, and the laboratories can provide an effective diagnostic service.

Asia, Southeastern↗