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PubMed1992

Incorporating new technologies in periodontal diagnosis into training programs and patient care: a critical assessment and a plan for the future.

New diagnostic technologies may be capable of providing the dental practitioner with powerful tools that can assist in the early identification of periodontal disease that can result in expediated treatment. In this paper, clinical, host, and microbiological parameters will be evaluated for their ability to assess disease activity and to assist in the treatment decision-making process. The discussion will focus on: 1) the perceived need for markers of disease activity; 2) the most commonly proposed markers of disease activity currently under consideration for clinical application; and 3) a plan for future use of disease activity markers. The review concludes that: 1) tooth loss and most forms of rapid disease progression is limited to a small subset of patients within the periodontally diseased population; 2) no single parameter will stand alone as a measure of disease activity; 3) different aspects of treatment may require different combinations of tests to successfully intercept disease in this vulnerable patient group; and 4) early diagnosis can affect long-term periodontal status. Best estimates are presented for: 1) pre-disease identification of high-risk population groups; 2) early diagnosis of disease activity on a site and patient basis; and 3) assistance in the therapeutic decision-making process. It is further concluded that the complexity of the problem may require a re-examination of priorities such that more time and money is allocated to early diagnosis as opposed to treatment in this highly vulnerable patient population.

Disease Susceptibility↗

PubMed1968

New diagnostic system for the identification of lactose-fermenting gram-negative rods.

The identification of prompt lactose-fermenting gram-negative rods has generally relied heavily upon colonial morphology coupled with one or more indole, methyl red, Voges-Proskauer, citrate (IMViC) parameters, hydrogen sulfide, and motility. Studies were undertaken to compare diagnoses dependent solely upon the more orthodox criteria to a system for identification based upon hydrogen sulfide, ornithine decarboxylase, and citrate utilization (HOC). The results suggest that the IMViC scheme of identification is neither consistent nor applicable when applied to the current nomenclature of the above group of organisms and should be discarded, whereas the HOC system may prove to be of significant value to clinical microbiologists.

Bacteriological Techniques↗

PubMed1998

[Early detection of atherosclerosis with high resolution ultrasound exemplified by type II diabetic patients].

AIM: Endothelial Dysfunction (ED) is an early functional marker and Intima-Media-Thickness (IMT) an early morphological parameter of atherogenesis. Is there a simple, non-invasive routine method for the identification of atherosclerosis including the detection of the early functional endothelial impairment seen for example in Type 2 diabetic patients? METHODS: Using high resolution ultrasound we studied peripheral endothelial function expressed as flow-associated dilation (FAD %) and endothelial independent vasodilation after administration of 400 micrograms glycerol trinitrate (postnitro %) of the brachial artery as well as IMT of the common carotid artery in 25 Type 2 diabetic patients and their matched controls. RESULTS: (mean +/- SD): The diabetic patients showed a remarkable ED (FAD%: 3.8 +/- 3.3 vs. 6.9 +/- 4.4%, p = 0.01) and an already increased IMT (0.72 +/- 0.14 vs. 0.62 +/- 0.10 mm, p < 0.01). The similar postnitro % in diabetic patients and controls suggests normal dilating capacity of the studied vessels in the diabetic patients (postnitro %: 14.3 +/- 9.4 vs. 14.9 +/- 8.5%, p = ns). CONCLUSION: With a combination of these three sonomorphological parameters it is possible to document the stage of atherosclerosis including endothelial dysfunction in Type 2 diabetic patients.

Adult↗

PubMed1999

Low back pain. Evaluation and management in the primary care setting.

The primary care physician plays a major role in the identification of low back pain and the entry of the patient into the health care system. Acute low back pain remits within a short period of time in most patients, and major diagnostic studies are not required. If the pain persists beyond the treatment parameters of the primary care physician, consultation is necessary. A basic component of the initial evaluation is the identification of myofascial syndromes that mimic so-called root syndromes. Further, low back pain in the population at large is not usually a surgical problem, and the chances of there being significant pathology requiring surgical or other forms of intervention may be less than 1% of those affected. When the initial attempts at treatment fail, the patient should be referred to a multidisciplinary comprehensive pain center so as to avoid or limit chronicity, the earlier, the better. Practitioners should feel comfortable in asking the centers to which they make a referral for outcome data. If these are not available, the choice should be made elsewhere. Low back pain per se is in the majority not a neurologic problem, an orthopedic problem, or a neurosurgical problem, so that consultation with these groups, unless there are strong suspicions otherwise, has limited value. The criteria for selection and referral of patients to multidisciplinary pain centers have been presented, including specific considerations for the geriatric age group. The overwhelming cost of low back pain to the economy can be decreased along with suffering and the adverse impact that pain has on all social strata.

Chronic Disease↗

PubMed2004

Quantitative structure toxicity relationships for catechols in isolated rat hepatocytes.

One- and two-parameter quantitative structure toxicity relationship (QSTR) equations were obtained to describe the cytotoxicity of isolated rat hepatocytes induced by 23 catechols in which LD(50) represents the catechol concentration required to induce 50% cytotoxicity in 2 h. A QSTR equation logLD(50) (microM = - 0.464(+/-0.065) log P + 3.724(+/-0.114) (n = 20, r(2) = 0.740, s(y,x) = 0.372, P < 1 x 10(-6), outliers: 4-methoxycatechol, 3-methoxycatechol, L-dopa) was derived where logP represents octanol/water partitioning. Outliers were determined by adopting a statistical method to standardize the identification of outliers. When pK(a1), the first ionization constant, was considered as a contributing parameter a two-parameter QSTR equation was derived: logLD(50) (microM = - 0.343(+/-0.058) log P - 0.116(+/-0.041) pK(a1)+4.389 (+/-0.315) (n = 22, r(2) = 0.738, s(y,x) = 0.375, P < 0.01, outlier: 4-methoxycatechol). Replacing logP with logD(7.4), the partition coefficient at pH 7.4, improved the first correlation by limiting the outlier to 4-methoxycatechol: logLD(50) (microM)=-0.252(+/-0.039) logD(7.4)+3.168(+/-0.090) (n = 22, r(2) = 0.671, s(y,x) = 0.420, P < 1 x 10(-5). In this study, 4-methoxycatechol (readily autooxidizable) was found to be an outlier for all QSTR equations derived. These findings point to lipophilicity and pK(a1) as two important characteristics of catechols that can be used to predict their cytotoxicity towards isolated rat hepatocytes. The catechols with the higher lipophilicity/distribution coefficient, the lower degree of ionization and the higher pK(a(catechol)) were more toxic towards hepatocytes than the other catechols.

Animals↗

PubMed2001

Use of intraoperative transesophageal echocardiography to predict atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Postoperative atrial fibrillation in coronary artery bypass graft surgery occurs in 10-40% of patients. It is associated with a significant degree of morbidity and results in prolonged lengths of stay in both the intensive care unit and hospital. METHODS: The authors prospectively evaluated patients undergoing coronary artery bypass with detailed transesophageal echocardiography examinations conducted before and after cardiopulmonary bypass to study whether risk factors for atrial fibrillation could be identified. Demographic and surgical parameters were also included in the analysis. Selected variables were subjected to univariate and subsequent multivariate analyses to test for their independent or joint influence on atrial fibrillation. RESULTS: Seventy-nine patients had assessable transesophageal echocardiography examinations. Significant univariate predictors of atrial fibrillation included advanced age (P = 0.002), pre-cardiopulmonary bypass left atrial appendage area (P = 0.04), and post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio (P = 0.03). When these three factors were considered together in a multiple logistic regression analysis, left upper pulmonary vein systole/diastole velocity ratio was a significant predictor (P < 0.05), as was the joint effect of age plus pre-cardiopulmonary bypass left atrial appendage area (P = 0.005). The probability of developing atrial fibrillation for the combination of age = 75 yr, post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio = 0.5, and left atrial appendage area = 4.0 cm was 0.83 (95% confidence interval, 0.51-0.96). CONCLUSIONS: Early identification of patients at risk for postoperative atrial fibrillation may be feasible using the parameters identified in this study.

Age Factors↗

PubMed1983

Morphology of cyclosporine nephrotoxicity and acute rejection in patients immunosuppressed with cyclosporine and prednisone.

Cyclosporine nephrotoxicity is a common and usually reversible cause of renal insufficiency in the renal allograft recipient. We examined 132 renal biopsy specimens of 54 patients with elevated serum creatinine concentrations in the posttransplant period in an attempt to characterize histologic features that would identify patients with cyclosporine nephrotoxicity as opposed to those with acute rejection. Nine histologic parameters were examined--vasculitis, interstitial edema, distribution and intensity of mononuclear cell interstitial infiltrate, mononuclear cell exudation within glomerular capillaries ("glomerulitis"), tubular ectasia, tubular necrosis, exudation of mononuclear cells within tubular epithelial cells ("tubulitis"), and the ratio of mononuclear cells in interstitial tissues and in the peritubular capillaries (I/C ratio). A clinical response to an increased dose of steroids or a reduced dose of cyclosporine was correlated with the histologic picture. Tubulo-interstitial nephritis was identified in all but one patient with cyclosporine nephrotoxicity and only the finding of vasculitis allowed the identification of rejection with any certainly. However, the linear logistic regression method identified four histologic parameters--vasculitis, edema, glomerulitis, and I/C ratio, which were useful in differentiating the nephritis of cyclosporine nephrotoxicity from that of acute rejection in 94% of the biopsies. Although it is possible to precisely predict clinical response to antirejection therapy or reduction in cyclosporine dose based on histologic criteria, it is possible that cyclosporine toxicity, alone or in combination with rejection, may lead to chronic interstitial fibrosis responsible for late graft loss.

Animals↗

PubMed2003

Characterisation of quaternary mixtures by the apparent content curves method: identification of tocopherols in vegetable oils.

A procedure for identification of the compounds in quaternary mixtures has been developed. The proposed procedure is based on the apparent content curves method. From these curves and using the Q parameter, work conditions are selected and quaternary mixtures treated as "pseudoternary" mixtures.A simple strategy to test matrix effects at working wavelengths has been developed, identification limits established and following the identification table quaternary mixtures were easily characterised. The procedure has been applied to the identification of phenols in mixtures by UV-visible spectrophotometry and tocopherols in edible oils by fluorimetry. Results obtained for edible oils are in agreement with the composition obtained by use of the reference method.

Plant Oils↗

PubMed1999

Antibacterial-induced nephrotoxicity in the newborn.

Antibacterials are the primary cause of drug-induced kidney disease in all age groups and these agents bring about renal damage by 2 main mechanisms, namely, direct and immunologically mediated. For some antibacterials (aminoglycosides and vancomycin) nephrotoxicity is very frequent but generally reversible upon discontinuation of the drug. However, the development of acute renal failure with these agents is possible and its incidence in the newborn seems to be increasing. Antibacterials are very often used in the neonatal period especially in very low birthweight neonates. The role of neonatal age in developing nephrotoxicity has still to be defined. Since the traditional laboratory parameters of nephrotoxicity are abnormal only in the presence of substantial renal damage, the identification of early non-invasive markers of the renal damage (urinary microglobulins, enzymes and growth factors) is of importance. Aminoglycosides and glycopeptides are still frequently used, either alone or in combination, despite their low therapeutic index. Numerous factors intervene in bringing about the kidney damage induced by these 2 classes of antibacterials, such as factors related to the antibacterial itself and others related to the associated pathology as well as pharmacological factors. Nephrotoxicity can be caused by the beta-lactams and related compounds. Their potential to cause nephrotoxicity decreases in the order: carbapenems > cephalosporins > penicillins > monobactams. Third generation cephalosporins are frequently used in neonates. However, they are well tolerated compounds at the renal level. The nephrotoxicity of other classes of antibacterials is not discussed either because they are only used in neonates in exceptional circumstances, for example, chloramphenicol and cotrimoxazole (trimethoprim-sulfamethoxazole) or are not associated with significant nephrotoxicity, for example macrolides, clindamicin, quinolones, rifampicin (rifampin) and metronidazole. Antibacterial-induced nephrotoxicity is an important parameter to be considered when treating the newborn and this is particularly true when use of a combination of different antibacterials and/or drugs with a nephrotoxic potential is being considered. However, other parameters, such as antibacterial spectrum, pharmacokinetics, post-antibacterial effect, clinical efficacy, general adverse effect profile and cost, must also be considered in the choice of antibacterial therapy in the neonate. Knowledge of the renal safety of antibacterials and the correct approach to therapeutic drug monitoring may be useful elements for preventing iatrogenic renal disorders.

Aminoglycosides↗

PubMed2000

Comparative genome sequence analysis of the Bpa/Str region in mouse and Man.

The progress of human and mouse genome sequencing programs presages the possibility of systematic cross-species comparison of the two genomes as a powerful tool for gene and regulatory element identification. As the opportunities to perform comparative sequence analysis emerge, it is important to develop parameters for such analyses and to examine the outcomes of cross-species comparison. Our analysis used gene prediction and a database search of 430 kb of genomic sequence covering the Bpa/Str region of the mouse X chromosome, and 745 kb of genomic sequence from the homologous human X chromosome region. We identified 11 genes in mouse and 13 genes and two pseudogenes in human. In addition, we compared the mouse and human sequences using pairwise alignment and searches for evolutionary conserved regions (ECRs) exceeding a defined threshold of sequence identity. This approach aided the identification of at least four further putative conserved genes in the region. Comparative sequencing revealed that this region is a mosaic in evolutionary terms, with considerably more rearrangement between the two species than realized previously from comparative mapping studies. Surprisingly, this region showed an extremely high LINE and low SINE content, low G+C content, and yet a relatively high gene density, in contrast to the low gene density usually associated with such regions.

3-Hydroxysteroid Dehydrogenases↗

PubMed2005

Method for detection and quantitation of fathead minnow vitellogenin (Vtg) by liquid chromatography and matrix-assisted laser desorption/ionization mass spectrometry.

Vitellogenin (Vtg) is a well-recognized biomarker of estrogen exposure in many species, particularly fish. This large protein shares a high degree of sequence homology across a large number of species. Quantitative measurement is currently done using antibody-based assays. These assays frequently require purification of Vtg and antibody production from each species because there is poor cross reactivity between antibodies for different fish. Therefore, complementary methods of measuring Vtg are desirable. Mass spectrometric (MS) analysis coupled to database searching offers the promise of a general method for protein identification. In this study, we used the well-characterized Vtg from rainbow trout (Oncorhynchus mykiss) to evaluate the analytical parameters for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis of the intact protein. The low sensitivity observed for the intact protein demonstrated that a proteolytic digestion would be necessary for MALDI-MS identification of Vtg. An analytical scale high performance liquid chromatography (HPLC) separation combined with MALDI-MS was used to measure and confirm the identity of Vtg from the plasma of an important species for regulatory agencies, fathead minnow (Pimephales promelas). The small volume requirement of this method (<10 microL) was found to be compatible with the plasma volume obtained from a few minnows. Importantly, the HPLC-MALDI-MS measurement of fathead minnow Vtg abundance after exposure to estradiol was similar to previously obtained enzyme linked immunosorbant assays (ELISA) data.

Amino Acid Sequence↗

PubMed2005

Visual processing in schizophrenia: Structural equation modeling of visual masking performance.

Schizophrenic patients consistently demonstrate performance deficits on visual masking procedures. In visual masking, the subject's ability to process a target stimulus is reduced by another stimulus (mask) presented either before (forward masking) or after (backward masking) the target. Masking procedures employed in schizophrenia research have used several experimental paradigms. Most early studies have used high-energy masks (i.e., the mask is stronger than the target) and spatially overlapping target and mask. More recently, studies have begun to employ relatively weak (i.e., low-energy) masks, as well as masks that surround, but do not spatially overlap, the target. Data for forward and backward masking components of four masking conditions (target location and identification with a high-energy mask, target identification with a low-energy mask, and target identification with equal energy paracontrast/metacontrast) were collected from 75 patients with schizophrenia. Based on theoretical distinctions among masking procedures, we compared four models of visual masking using structural equation modeling. Although high zero-order correlations were found among the masking parameters, a four-factor model, in which factors were separated on the type of response (target location and identification), the shape of the function (monotonic and non-monotonic), and the overlap of the stimuli (overlapping and non-overlapping), provided the best fit for the data. These findings suggest that the four masking procedures used in this study may tap unique aspects of visual processing and are not redundant. The results also support theories of the different mechanisms underlying performance on these measures.

Adult↗

PubMed2007

Protein identification by tandem mass spectrometry and sequence database searching.

The shotgun proteomics strategy, based on digesting proteins into peptides and sequencing them using tandem mass spectrometry (MS/MS), has become widely adopted. The identification of peptides from acquired MS/MS spectra is most often performed using the database search approach. We provide a detailed description of the peptide identification process and review the most commonly used database search programs. The appropriate choice of the search parameters and the sequence database are important for successful application of this method, and we provide general guidelines for carrying out efficient analysis of MS/MS data. We also discuss various reasons why database search tools fail to assign the correct sequence to many MS/MS spectra, and draw attention to the problem of false-positive identifications that can significantly diminish the value of published data. To assist in the evaluation of peptide assignments to MS/MS spectra, we review the scoring schemes implemented in most frequently used database search tools. We also describe statistical approaches and computational tools for validating peptide assignments to MS/MS spectra, including the concept of expectation values, reversed database searching, and the empirical Bayesian analysis of PeptideProphet. Finally, the process of inferring the identities of the sample proteins given the list of peptide identifications is outlined, and the limitations of shotgun proteomics with regard to discrimination between protein isoforms are discussed.

Amino Acid Sequence↗

PubMed1996

Application of neural networks to flow cytometry data analysis and real-time cell classification.

Conventional analysis of flow cytometric data requires that population identification be performed graphically after a sample has been run using two-parameter scatter plots. As more parameters are measured, the number of possible two-parameter plots increases geometrically, making data analysis increasingly cumbersome. Artificial Neural Systems (ANS), also known as neural networks, are a powerful and convenient method for overcoming this data bottleneck. ANS "learn" to make classifications using all of the measured parameters simultaneously. Mathematical models and programming expertise are not required. ANS are inherently parallel so that high processing speed can be achieved. Because ANS are nonlinear, curved class boundaries and other nonlinearities can emerge naturally. Here, we present biomedical and oceanographic data to demonstrate the useful properties of neural networks for processing and analyzing flow cytometry data. We show that ANS are equally useful for human leukocytes and marine plankton data. They can easily accommodate nonlinear variations in data, detect subtle changes in measurements, interpolate and classify cells they were not trained on, and analyze multiparameter cell data in real time. Real-time classification of a mixture of six cyanobacteria strains was achieved with an average accuracy of 98%.

Animals↗

PubMed2001

In vitro effects of low-intensity ultrasound stimulation on the bone cells.

Mechanical perturbations serve as extracellular signals to a variety of cells, including bone cells. Low-intensity pulsed ultrasound produces significant multifunctional effects that are directly relevant to bone formation and resorption. Ultrasound stimulation has been shown to accelerate bone-defect healing and trabecular bone regeneration. In this study, we use an in vitro bone cell culture model to investigate the effect of low-intensity pulsed ultrasound. The rat alveolar mononuclear cell-calvaria osteoblast coculture system was used in this study. Before treatment, the bone cells were cultured for 3 days to facilitate their attachment and differentiation. Then, ultrasound exposure (frequency = 1 MHz, intensity = 0.068 W/cm(2)) or sham exposure for 20 min per day was applied until the end of the experiment. Half of the culture media were obtained on the 4th, 5th, 6th, 7th, 8th, 9th, and 10th days for the analysis of cytokines and biochemical parameters. At the end of the experiment, cells were fixed and stained for identification and quantification of the osteoblast and osteoclast cells. After low-intensity pulse ultrasound stimulation, the osteoblast cell counts were significantly increased, whereas the osteoclast cell counts were significantly decreased. The total alkaline phosphatase amount in the culture medium was increased after 7 days of ultrasound stimulation, and tumor necrosis factor-alpha in ultrasound-stimulated bone cells was significantly increased after the 7th day of culture and reached 474.77% of the control medium on the 10th day of culture. The results of this study suggest that low-intensity ultrasound treatment may have a stimulatory effect on bone-healing processes.

Acid Phosphatase↗

PubMed2005

Kinetic characterization of sequencing grade modified trypsin.

Prior to analysis by mass spectrometry, protein samples are often digested. Maximizing the peptide yield from digestion can increase the number of peptides detected and the confidence in protein identification. To determine the optimal conditions for digestion, the Michaelis-Menten kinetic parameters for Promega sequencing grade modified trypsin were measured over a range of temperatures and pHs. The results indicate that an increase in digestion temperature above 37 degrees C, the temperature traditionally used in digestion methods, could offer an increase in peptides detected.

Caseins↗

PubMed2006

Predicting operative delivery.

OBJECTIVE: Unplanned operative delivery (vaginal or abdominal) is associated with maternal anxiety, maternal and neonatal morbidity and increased resource use. We aimed to identify potential predictors for emergency operative delivery. METHODS: This was a prospective observational study of 202 nulliparous women in a tertiary antenatal unit between 36 and 40 weeks' gestation. The assessment included an interview, a vaginal examination for Bishop score (optional), and a translabial ultrasound examination performed with the woman in a supine position and after voiding to determine cervical length, bladder position on Valsalva, and fetal head engagement. Clinical data were obtained from the institutional obstetric database and patient records. RESULTS: In the late third trimester, body mass index (P = 0.016), maternal age at due date (P < 0.0001), history of Cesarean section in first-degree relatives (P = 0.009), Bishop score (P = 0.0004), cervical length (P = 0.001), bladder position on Valsalva (P = 0.003) and head engagement (P < 0.0001) were significantly associated with delivery mode. On multivariate logistic regression analysis, the best model for predicting normal vaginal delivery contained maternal age, history of Cesarean section, Bishop score and bladder position on Valsalva and had excellent ability to discriminate between normal vaginal delivery and operative delivery (c = 0.85). The model with the best ability to discriminate between vaginal delivery and Cesarean section contained the same parameters plus body mass index; this model performed even better (c = 0.87). CONCLUSIONS: Identification of women at increased risk of operative delivery appears feasible. A combination of clinical and ultrasound variables yielded a model that is likely to predict delivery mode accurately in up to 87% of cases. Such a model may become useful as an entry criterion for intervention trials in women at low or very high risk of operative delivery.

Adult↗

PubMed2000

Assay of glycoamidases and endo-beta-N-acetylglucosaminidases by lectin capture and dissociation-enhanced lanthanide fluorescence immunoassay.

We have developed an assay system for endo-beta-N-acetylglucosaminidase and glycoamidase (PNGase), using Eu(3+)-labeled Man(9)GlcNAc(2) glycopeptides as substrates in combination with lectin capture. Two glycopeptides of different peptide lengths, derived from soybean agglutinin, were labeled with Eu(3+) via a diethylenetriaminepentaacetate (DTPA) chelating linker and served as substrates for two types of enzymes: one with (Man(9)GlcNAc(2))Asn for endo-beta-N-acetylglucosaminidase and the other with Ala-Ser-Phe-(Man(9)GlcNAc(2))Asn-Phe-Thr for glycoamidase activities. Following enzymatic hydrolysis, concanavalin A, immobilized or soluble, was added to the mixture to bind unreacted substrate and unlabeled hydrolysis product. The labeled peptide product could then be separated from the lectin-bound complexes by filtration for quantification by dissociation-enhanced lanthanide fluorescence immunoassay. Activities as low as 2 fmol min(-1) could be rapidly quantified for both types of enzymes, and enzymological parameters could be determined within minutes. Applicability of the assay was tested for identification of a glycoamidase activity peak in the fractionation of sweet almond emulsin, a classic example. This assay offers sensitivity, ease of use, and high throughput. In addition, it is versatile and should be applicable to other glycobiology enzyme systems.

Fluorescence↗