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PubMed1976

A qualitative and quantitative study of the fatty acid composition of selected micro-organisms.

Fatty acid content was found to be an important parameter in the identification and numerical taxonomy of many micro-organisms. Isolates of the same species and genus as well as members of many well defined groups, such as the Enterobacteriaceae, were included in the study. A direct methylation procedure of the bacteria was found to be accurate, efficient and rapid. Fatty acids were found to be reliable indicators of micro-organisms in group, generic, specific and strain identification. Other biochemical tests were especially valuable when used in conjunction with fatty acid profiles in identification and classification of the bacteria studied.

Bacteria↗

PubMed2000

Accuracy of oximetry with thermistor (OxiFlow) for diagnosis of obstructive sleep apnea and hypopnea.

OBJECTIVES: To evaluate the diagnostic accuracy for obstructive sleep apnea and hypopnea (OSAH) of the OxiFlow (OF) device which combines oximetry with recording of thermistor airflow. DESIGN & SETTING: Patients scheduled for overnight diagnostic polysomnography (PSG) were studied with OF either simultaneously during laboratory PSG (L-OF, n=86), at home on a separate night (H-OF, n=66), or both (n=55). PATIENTS: 97 patients with suspected OSAH, of whom 40 had OSAH defined as an apnea-hypopnea index (AHI) of more than 15 events per hour of sleep on PSG. INTERVENTIONS: NA. MEASUREMENTS & RESULTS: The automated respiratory disturbance index (RDI) generated by the OF software considerably underestimated the AHI by PSG for both L-OF and H-OF. Altering the parameters for hypopnea identification by the software did not improve this. Visual inspection of the computerized OF tracings added considerable diagnostic information, but a manual count of RDI during visual review overestimated AHI. For the identification of cases vs. non-cases of OSAH, receiver operating characteristic area-under-the-curve statistics ranged from 0.77-0.90 for L-OF and from 0.71-0.77 for H-OF. Combining automated analysis with subsequent visual inspection of OF tracings yielded an overall sensitivity of 86% and specificity of 74% for the diagnosis of OSAH during H-OF recordings. Analysis of potential technician time saved indicated a benefit from the use of OF. CONCLUSIONS: OF has diagnostic utility for the identification of OSAH. However, because of hardware and software limitations, it is unclear whether this device is superior to oximetry alone.

Adult↗

PubMed2000

Disease control of uterine cervical cancer: relationships to tumor oxygen tension, vascular density, cell density, and frequency of mitosis and apoptosis measured before treatment and during radiotherapy.

Identification of biological parameters of major importance for the control of malignant diseases can be useful for the design of optimal treatment regimes for individual patients. Tumor oxygen tension (pO2), vascular density, cell density, and frequency of mitosis and apoptosis were measured before treatment (40 patients) and after 2 weeks of radiotherapy (22 patients) in patients with uterine cervical cancer. The aim was to investigate whether one of the parameters was more important for disease control than the others. Three sets of data were considered; the pretreatment parameters, the parameters measured after 2 weeks of radiation, and the changes in the parameters during this time. The pO2 was measured polarographically; the other parameters were determined by histological analyses of tumor biopsies. Hypoxic subvolume (HSV5), ie., the fraction of pO2 readings <5 mm Hg multiplied with tumor volume, showed the strongest correlation to control. Patients with a small HSVs before treatment had a higher control probability after a median follow-up time of 50 months than patients with a large HSV5 (P < 0.001). All other parameters or changes in parameters showed impaired correlation to control compared with pretreatment HSV5. The present results suggest that pretreatment oxygenation is more important for disease control of cervical cancer than the oxygenation after 2 weeks of radiotherapy or the changes in oxygenation during this time. Moreover, vascular density, cell density, and frequency of mitosis and apoptosis before treatment or after 2 weeks of therapy are probably not as important as pretreatment oxygenation as well. Although significant correlations between disease control and some of the parameters other than pretreatment oxygenation can occur in studies based on a large number of patients, the specificity of these parameters in the prediction of control is probably not as high as for oxygenation.

Adult↗

PubMed2000

Multiparameter analysis of human epithelial tumor cell lines by laser scanning cytometry.

Laser scanning cytometry (LSC) is a relatively new slide-based technology developed for commercial use by CompuCyte (Cambridge, MA) for performing multiple fluorescence measurements on individual cells. Because techniques developed for performing four or more measurements on individual lymphoid cells based on light scatter as a triggering parameter for cell identification are not suitable for the identification of fixed epithelial tumor cells, an alternative approach is required for the analysis of such cells by LSC. Methods for sample preparation, event triggering, and the performance of multiple LSC measurements on disaggregated fixed human cells were developed using normal lymphocytes and two human breast cancer cell lines, JC-1939 and MCF-7, as test populations. Optimal conditions for individual cell identification by LSC were found to depend on several factors, including deposited cell density (cells per unit area), the dynamic range of probe fluorescence intensities, and intracellular distribution of the fluorescent probe. Sparsely deposited cells exhibited the least cell overlap and the brightest immunofluorescent staining. Major advantages of using DNA probes over a cytoplasmic immunofluorescent protein marker such as tubulin for event triggering are that the former exhibit greater fluorescence intensity within a relatively sharply demarcated nuclear region. The DNA-binding dye LDS-751 was found to be suboptimal for quantitative DNA measurements but useful as a triggering measurement that permits the performance of simultaneous fluorescein isothiocyanate-, phycoerythrin-, and indodicarbocyanine-based measurements on each cell. A major potential advantage of LSC over flow cytometry is the high yields of analyzable cells by LSC, permitting the performance of multiple panels of multicolor measurements on each tumor. In conclusion, we have developed and optimized a technique for performing multiple fluorescence measurements on fixed epithelial cells by LSC based on event triggering using the DNA-binding dye LDS 751. Although not ideal for quantitative measurements of cell DNA content, the large Stokes shift of this dye permits the performance of three or more additional fluorescence measurements on each cell.

Breast Neoplasms↗

PubMed2001

[Medico-legal features of early discharge in acute myocardial infarction and chest pain].

The authors' aim is to outline some of the main medico-legal problems in cardiology, especially those regarding the premature hospital discharge of patients with undefined chest pain and/or with acute myocardial infarction. After a brief overview on the etiology and clinical definition of chest pain and myocardial infarction, premature hospital discharge is defined and the incidental medico-legal risks that physicians operating in such situations are exposed to are pointed out. Next, the profiles regarding both the positive and negative views of professional medical responsibility are described. In the negative frame, the authors outline the most frequent civil and penal aspects of the unpremeditated responsibility. Then the physician's error, in both qualitative (generic or specific guilt) and quantitative (degree) terms, is considered; particularly, negligence, imprudence and inexperience, as qualitatively accepted meanings of generic guilt, are dealt with by adopting illustrative cases settled in the light of the right legal interpretation. The phases of the diagnostic or prognostic error are evaluated, and clinical protocols, as a reference parameter for the identification of error, are considered. Lastly, the problem of causality, essential condition for the judgment about the professional responsibility, and the problem of the patient's consent, including an evaluation of the legal capability or incapability about the declaration of consent, are examined closely.

Chest Pain↗

PubMed1979

Clinical pharmacokinetics of nitroxoline.

14C-Nitroxoline was given orally to the rats, and its distribution as well as plasma and bile levels were determined autoradiographically and by the aid of radioactivity measurements, respectively. Nitroxoline was also given to the human volunteers orally and intravenously in three various doses and the corresponding urine concentrations of unconjugated and conjugated nitroxoline were determined spectrophotometrically. A pharmacokinetical model was generated on the basis of the results. The curve fitting procedure between total nitroxoline cumulative quantities in urine and the model response simulated on analog-hybrid computer enabled the evaluation of the validity of the chosen model as well as of the identification of its parameters.

Adult↗

PubMed2003

Individualization of drug dosage--past, present and future.

The development of drug immunoassays led to the introduction of therapeutic drug monitoring and the use of population pharmacokinetic (PK) methodology to develop guidelines for individualizing drug dosage. Recognition of pharmacodynamic (PD) variability and identification of PK parameters that best correlate with clinical response has occurred in several areas including oncology, infection and immunosuppression. In the future, drugs will be selected to suit the genetic characteristics that determine the likelihood of a response, while individualization of dosage will consider genetic information on drug metabolism.

Drug Monitoring↗

PubMed2003

[Brugada's syndrome].

Brugada syndrome is an inherited arrhythmogenic disease, that may cause syncope and sudden cardiac death in young individuals with a normal heart. It is characterized by a typical electrocardiographic pattern: complete or incomplete right bundle branch block and ST segment elevation in leads V1-V3. Thus far, the only gene linked to this syndrome is the gene SCN5A, the gene encoding for the cardiac sodium channel, that is also responsible of the LQT3 form of the Long QT syndrome. Mutations in SCN5A, responsible for Brugada syndrome, cause a functional reduction in the availability of cardiac sodium current. However, only 20-25% of patients affected by this syndrome have mutations on this gene. Therefore, the diagnosis of the syndrome is difficult, because it could manifest at first time as cardiac arrest without any previous symptom and the electrocardiographic pattern could be intermittent, thus a pharmacological challenge with antiarrhythmic class I drugs is required to unmask ST elevation. The clinical management is still empiricial because pharmacological therapies lack to show effectiveness and the only life-saving option is an implantable cardioverter defibrillator (ICD). So the identification of clinical parameters as predictors of adverse outcome for risk stratification has became of outmost importance for the clinical management of these patients, to discover which patients really need an ICD. This review presents clinical and genetic features of Brugada syndrome and the most recent diagnostic criteria. It will be discussed, therefore, the prognostic value of clinical tests, and especially of the programmed electrical stimulation, as prognostic predictors of sudden cardiac death to identify higher risk patients.

Bundle-Branch Block↗

PubMedDate not supplied

DNA ploidy and nuclear morphometry in adult intracranial ependymomas.

The identification of prognostic parameters in ependymomas remains an important but controversial issue in particular to the significance of histopathological features. Intracranial location is a rare presentation for adult ependymomas. DNA ploidy status and nuclear morphometric features of ependymomas are not well-established. We retrospectively studied the clinicopathologic features of 12 adult intracranial ependymomas and performed image cytometric DNA analysis with nuclear morphometry. The overall survival rate was 75%. Two cases were anaplastic ependymomas. Statistically, histology failed to demonstrate a correlation with clinical outcome or overall survival. DNA ploidy (p = 0.033), DNA index (p = 0.016) and 5c exceeding rate (p = 0.017) were statistically correlated with clinical outcome, but not correlated with overall survival. Nuclear morphometric features measured using 3 different data selection methods were not correlated with clinical outcome or overall survival. It is difficult to identify prognostic factors in a series of cases with limited number. The problem is complicated by the fact that the common criteria used for recognizing malignancy in gliomas are not completely reliable in ependymomas. Nuclear morphometric findings support the general impression that ependymomas are morphologically highly variable tumors. In spite of the small sample size of our series and other factors influencing survival such as the extent of resection and malignant histology, aneuploidy can be suggested as a promising factor, which may reflect potential aggressiveness of the tumor in adult intracranial ependymomas.

Adolescent↗

PubMed2003

[Red cell zinc protoporphyrin and its ratio to serum ferritin (ZPP/logSF index) in the detection of iron deficiency in patients with end-stage renal failure on hemodialysis].

Monitoring of iron metabolism has become a major clinical issue in end-stage renal patients undergoing hemodialysis. It can be done at three levels: storage, transport and marrow availability. The objective of that study was to evaluate if a combination of an iron storage marker, serum ferritin (SF) with red cell zinc protoporphyrin (ZPP), a marker of iron availability for erythron, will improve diagnostic value of both tests. In a baseline survey in the population of 186 haemodialysis patients (75% treated with rHuEpo), the following parameters were determined: complete blood count, serum transferrin saturation (TSAT), transferrin, SF, hypochromic red cells % (HRC) and ZPP; the ZPP/logSF ratio was calculated. Iron deficiency was defined as a fernitin saturation--TSAT < 20%. In the second part of the study, 24 pts with SF < 50 ng/ml were given 50 mg of i.v. iron weekly for three months, then the same tests were repeated. During that time the doses of rhuEpo were stable. An increase in hemoglobin of > 1.0 g/dl was considered as a positive response. In 186 studied patients mean SF was 274 +/- 335 ng/ml, and mean ZPP was 68 +/- 44 mumol/mol heme. A ZPP/logSF ratio > or = 40 had the best combination of diagnostic sensitivity and specificity in detecting iron deficiency (76% and 83% vs: 56% and 89% for ZPP > 90 mumol/mol heme, 84% and 34% for HRC > 5%, 68% and 58% for HRC > 10%) and the strong correlations with all other examined parameters were found. The index showed also the highest correlation with the response to the i.v. iron (r = 59; p < 0.01) of the tests evaluated. After three months the values of ZPP/logSF ratio decreased from 80 +/- 105 to 39 +/- 19 (p < 0.01). A significant difference between responders and nonresponders was found for basal ZPP/logSF (p < 0.05) but not for ZPP. Our data suggest that the ZPP/logSF index provides a new valuable parameter for the identification of hemodialysis patients with iron deficiency and the prediction an erythropoietic response to iron supplementation.

Adolescent↗

PubMed2004

Prognostic impact of early response to induction therapy as assessed by multiparameter flow cytometry in acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: Early response after induction therapy is an independent prognostic factor in acute myeloid leukemia (AML). We improved the identification of this parameter by implementing multiparameter flow cytometry to quantify bone marrow cells carrying leukemia-associated immunophenotypes (LAIP). DESIGN AND METHODS: In 106 uniformly treated patients flow cytometric analyses were performed at diagnosis and one week after induction therapy (day 16). The log-difference between LAIP-positive cells on day 1and day 16 (LD16) was determined for each patient. RESULTS: The LD16 (median, 2.11; range, -0.37 to 4.20) was significantly correlated to CR rate, event-free survival (EFS), overall survival (OS), and relapse-free survival (RFS). Separation of patients by the median LD16 resulted in significant differences in CR rate (81% vs. 51%, p=0.002), EFS (53% at 2 years vs. median 2.8 months, p<0.0001), 2-year OS (58% vs. 43%, p=0.0133), and 2-year RFS (65% vs. 30%, p=0.0037). Multivariate analysis revealed that LD16 was an independent prognostic parameter for CR rate, EFS, and RFS. INTERPRETATION AND CONCLUSIONS: Flow cytometric evaluation of early response may serve as a new response parameter in AML. It may be used for development of risk-adapted therapies. High-risk patients can be identified early after the first induction therapy and assigned alternative and salvage treatment strategies.

Adolescent↗

PubMed2005

Decision analysis for the assessment of a record linkage procedure: application to a perinatal network.

OBJECTIVES: According to European legislation, we must develop computer software allowing the linkage of medical records previously rendered anonymous. Some of them, like AUTOMATCH, are used in daily practice either to gather medical files in epidemiologic studies or for clinical purpose. In the first situation, the aim is to avoid homonymous errors, and in the second one, synonymous errors. The objective of this work is to study the effect of different parameters (number of identification variables, phonetic treatments of names, direct or probabilistic linkage procedure) on the reliability of the linkage in order to determine which strategy is the best according to the purpose of the linkage. METHODS: The assessment of the Burgundy Perinatal Network requires the linking of discharge abstracts of mothers and neonates, collected in all the hospitals of the region. Those data are used to compare direct and probabilistic linkage, using different parameterization strategies. RESULTS: If the linkage has to be performed in real time, so that no validation of indecisions generated by probabilistic linkage is possible, probabilistic linkage using three variables without any phonetic treatment seems to be the most appropriate approach, combined with a direct linkage using four variables applied to non-conclusive links. If a validation of indecisions is possible in an epidemiological study, probabilistic linkage using five variables, with a phonetic treatment adapted to the local language has to be preferred. For medical purpose, it should be combined with a direct linkage with four or five variables. CONCLUSION: This paper reveals that the time and money available to manage indecision as well as the purpose of the linkage are of paramount importance for choosing a linkage strategy.

France↗

PubMed2004

[Patent foramen ovale and stroke].

About a quarter of the adult population is known to have a patent foramen ovale, rarely accompanied by the presence of an interatrial septal aneurysm. A patent foramen ovale is found in more than 40% of patients younger than 60 years who had a cryptogenic ischemic stroke. Clinical and echocardiographic parameters allow the identification of patients at high risk of recurrence after a first cryptogenic stroke even if treated with Aspirin. A multidisciplinary approach allow the selected patients to benefit of a correction of their cardiac anomaly with promising long term results.

Adult↗

PubMedDate not supplied

[The study of arteriogenic erectile impotence by noninvasive methods].

With the development of noninvasive haemodynamic methods, recognition of arterial insufficiency signs is possible also in cases in which, in old times, we just could suspect a psychogenic cause. Although this advance, discrimination permitted by this method can be improved. Eighty-eight supposed healty patients and eighty-four patients with arteriogenic erectile impotency (tested by arteriography) were included into an study, which results are presented in here. Analysis made, avoided the effect of envelleiment on haemodynamic parameters interpretation. For identification of patients which obstructive arterial defect can be cause of sexual disfunction, combination of systolic pressure determination and arterial flow velocity curves (by Doppler ultrasonography) is proposed. We recommend this method as a part of the multifactorial examen required by such type of patients.

Adult↗

PubMed1991

The 'Sicilian Gambit'. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. The Task Force of the Working Group on Arrhythmias of the European Society of Cardiology.

The Queen's Gambit is an opening move in chess that provides a variety of aggressive options to the player electing it. This report represents a similar gambit (the 'Sicilian Gambit') on the part of a group of basic and clinical investigators who met in Taormina, Sicily, to consider the classification of antiarrhythmic drugs. Paramount to their considerations were (1) dissatisfaction with the options offered by existing classification systems for inspiring and directing research, development and therapy, (2) the disarray in the field of antiarrhythmic drug development and testing in this post-CAST era, and (3) the desire to provide an operational framework for consideration of antiarrhythmic drugs that will both encourage advancement and have the plasticity to grow as a result of the advances that occur. The multifaceted approach suggested is, like the title of the manuscript, a gambit. It is an opening rather than a compendium, and is intended to challenge thought and investigation rather than to resolve issues. The manuscript incorporates first, a discussion of the shortcomings of the present system for drug classification; second, a review of the molecular targets on which drugs act (including channels and receptors); third, a consideration of the mechanisms responsible for arrhythmias, including the identification of 'vulnerable parameters' that might be most accessible to drug effect; and finally, clinical considerations with respect to antiarrhythmic drugs. Information relating to the various levels of information is correlated across categories (i.e., clinical arrhythmias, cellular mechanisms and molecular targets), and a 'spread sheet' approach to antiarrhythmic action is presented that considers each drug as a unit, with similarities to and dissimilarities from other drugs being highlighted. A complete reference list for this work would require as many pages as the text itself. For this reason, referencing is selective and incomplete. It is designed, in fact, to provide sufficient background information to give the interested reader a starting frame of reference, rather than to recognize the complete body of literature that is the basis for this paper.

Animals↗

PubMed1991

Testing for association between disease and linked marker loci: a log-linear-model analysis.

One approach frequently used for identifying genetic factors involved in the process of a complex disease is the comparison of patients and controls for a number of genetic markers near a candidate gene. The analysis of such association studies raises some specific problems because of the fact that genotypic and not gametic data are generally available. We present a log-linear-model analysis providing a valid method for analyzing such studies. When studying the association of disease with one marker locus, the log-linear model allows one to test for the difference between allelic frequencies among affected and unaffected individuals, Hardy-Weinberg (H-W) equilibrium in both groups, and interaction between the association of alleles at the marker locus and disease. This interaction provides information about the dominance of the disease susceptibility locus, with dominance defined using the epidemiological notion of odds ratio. The degree of dominance measured at the marker locus depends on the strength of linkage disequilibrium between the marker locus and the disease locus. When studying the association of disease with several linked markers, the model becomes rapidly complex and uninterpretable unless it is assumed that affected and unaffected populations are in H-W equilibrium at each locus. This hypothesis must be tested before going ahead in the analysis. If it is not rejected, the log-linear model offers a stepwise method of identification of the parameters causing the difference between populations. This model can be extended to any number of loci, alleles, or populations.

Alleles↗

PubMedDate not supplied

[Modeling of the activity kinetics of oligomer enzymes using phosphofructokinase as an example. III. A polyligand model].

A general statistical-thermodynamical theory of the oligomeric enzymes was applied for description of the complex regulatory properties of human erythrocyte phosphofructokinase (PFC, EC 2.7.1.11), experimental data were obtained by Wenzel et al. (Eur. J. Biochem. 1976. V. 61. P. 181). Simple two-ligand and hierarchical three-ligand models for polymeric enzymes were analysed. In hierarchical model structural PFK unit (protomer) was treated as tetramer so both interactions between subunits inside the protomer and between protomers themselves were considered. It was shown that except active center of fructoso-6-phosphate (F6P) binding and two or more inhibiting centers of ATP binding. F6P binding by active centers of different subunits inside the protomer caused negative cooperative interactions but F6P binding by activating centers of the same subunits causes positive interactions. The F6P dissociation constant for activating centers is essentially higher than for active centers. ATP binding by inhibiting centers of the protomer causes very high positive cooperative interactions between neighbouring protomers leading to distinguish additional "quaternary" level of the enzyme structure. Numerical non-linear identification for the parameters of these two models was given and five experimental curves were quantitatively described in the wide range of ligand concentrations (0.01-15 mM F6P and 1-5 mM ATP) for high enzyme concentration (greater than 0.5 mkg/ml).

Erythrocytes↗

PubMedDate not supplied

Bone marrow micrometastases detected by a monoclonal antibody in patients with breast cancer.

One major problem in primary breast cancer is the identification of new parameters able to select patients at high risk of recurrence. Our study was aimed at detecting mammary tumor cells in the bone marrow of breast cancer patients using a single bone marrow sampling and the monoclonal antibody AB/3. This antibody recognizes a membrane carbohydrate epitope present in human breast cancer cells but not in normal tissues. Only 2 out of 45 breast cancer patients were found to have a bone marrow positive AB/3 staining reaction. Our data confirm and extend previous reports that single bone marrow sampling coupled with immunocytochemistry is not sensitive enough to be used as a routine procedure to acquire prognostic information in breast cancer.

Antibodies, Monoclonal↗