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[New aspects on the identification of genetic alterations and prognostically important biological parameters in renal cell cancer].

The observation of extremely variable clinical courses for patients with renal cell carcinomas of an identical pathological stage as well as a comparable histological differentiation resp. growth pattern strongly indicates the existence of tumors harboring different biological aggressiveness. Currently available histopathological classification systems do not predict the biological behaviour of renal cell cancer as sufficiently as the establishment of a therapeutical strategy adjusted to the individual patient would require. The need for a more refined characterization of the biological potential of the individual tumor results from the introduction of modified operative strategies as organ-preserving surgery, for example, as well as from the recently suggested application of an adjuvant systemic therapy adapted to the individual risk for tumor recurrence resp. the development of progressive disease. Therefore, the clinically orientated basic scientist and the basic scientifically orientated clinician intensively try to determine prognostically important biological variables which would allow to better predict the biological aggressiveness of a single tumor in addition to "classical" prognostic parameters (T-stage, histological grading, growth patterns). In this context, several biological parameters including the identification of alterations on the DNA-, RNA- and protein level have been discussed as possible biological prognostic markers for renal cell cancer. The present review tries to reflect currently available biological characteristics of RCC which might gain clinical importance with regard to an individualized therapy in the near future.

Biomarkers, Tumor↗

[Effect of laparoscopic trocar model on the quality of the movement: experimental study of friction].

OBJECTIVE: To keep the pneumoperitoneum and the tightness of the abdominal and pelvic cavity during a laparoscopy, the sheaths of trocar are provided with a device (valvule, membranes etc.) inducing a friction during the handling of the instrument. The objective of this article is to analyse friction from different types of trocar's port. MATERIALS AND METHODS: We present here the experimental results obtained during a testing bench of three different trocar sheaths. The mechanism of tightness of the first trocar sheath is made of a fine membrane associated to a valve, of a thick membrane for the second trocar sheath, whereas the third trocar sheath is made of two membranes, a fine and a thick, associated to a valve. After reporting the experimental device and the analytic model adopted to describe the relationship between the measured physical parameters, we lay out our results. The identification of parameters of this model makes it possible to objectively compare the three trocars. RESULTS: Our results revealed that, under experimental conditions, the amplitude of friction was significantly lower with trocar's port provided with a valve and a fine membrane than with both other ports (fivefold weaker). DISCUSSION AND CONCLUSION: We evoke the importance of the possible disruption brought by these frictions while referring these values to those of other measurements concerning interactions between instrument and organs. These different behaviours of the material could have some consequences in choosing the tools for the performance of precise gestures.

Laparoscopy↗

Carcinoma of the esophagus: pretreatment assessment, correlation of radiation treatment parameters with survival, and identification and management of radiation treatment failure.

Between January 1969 and February 1975, 344 patients with carcinoma of the esophagus were managed primarily at the Princess Margaret Hospital, Toronto. One hundred sixty-eight (168) of the patients were treated palliatively and 176 of the patients were treated by radical doses of radiation, surgical resection or both. Survival of the radical treatment group was biphasic, the steeper component being identical to the survival of the palliative treatment group, thereby representing a group of patients that did not respond to radical treatment. Analysis of pretreatment assessment parameters indicated that all patients with T1 lesions (length less than or equal to 5 cm, circumference incomplete) and all patients with Stage I disease responded to treatment. Patients who were female, age greater than or equal to 70 years, N0 or had well differentiated squamous cell histology, responded to treatment in at least 80% of cases. No patient with extralymphatic distant metastases responded to treatment. The presence of other major disease did not affect response to treatment. Thirty patients had surgical resections and their survival was not significantly greater than the 146 patients who had radical radiation alone. Survival analysis revealed an optimum range of nominal standard dose (NSD) of 1602--1714 rets (median 1679 rets) for patients treated by radiation alone. An optimum port size (area) of 100--140 cm2 was observed for patients receiving 5000 rads and supervoltage irradiation gave a significantly improved survival in comparison with megavoltage irradiation. Sixty-seven percent (67%) of patients treated by radical doses or radiation developed esophageal strictures postradiation and on the basis of radiological, endoscopic or histological evidence 75% of these strictures were considered to be associated with the persistence of malignancy. On the basis of postmortem examinations (32) and death certificates there was overall an 80% failure to control the disease locally and 95% of strictures were associated with persistence of malignancy in the esophagus. Thirty-one of the 146 patients receiving radical radiation alone had palliation for esophageal obstruction following radiotherapy. The construction of a physiological bypass (e.g., colon) resulted in a mean survival of 215 days which was much longer than the survival observed with rigid esophageal tubes (35 days) or gastrostomy tubes (58 days).

Aged↗

Individual prior information in a physiological model of 2H8-toluene kinetics: an empirical Bayes estimation strategy.

Physiologically-based toxicokinetic (PBTK) models are widely used to quantify whole-body kinetics of various substances. However, since they attempt to reproduce anatomical structures and physiological events, they have a high number of parameters. Their identification from kinetic data alone is often impossible, and other information about the parameters is needed to render the model identifiable. The most commonly used approach consists of independently measuring, or taking fom literature sources, some of the parameters, fixing them in the kinetic model, and then performing model identification on a reduced number of less certain parameters. This results in a substantial reduction of the degrees of freedom of the model. In this study, we show that this method results in final estimates of the free parameters whose precision is overestimated. We then compared this approach with an empirical Bayes approach, which takes into account not only the mean value, but also the error associated with the independently determined parameters. Blood and breath 2H8-toluene washout curves, obtained in 17 subjects, were analyzed with a previously presented PBTK model suitable for person-specific dosimetry. Model parameters with the greatest effect on predicted levels were alveolar ventilation rate QPC, fat tissue fraction VFC, blood-air partition coefficient Kb, fraction of cardiac output to fat Qa/co and rate of extrahepatic metabolism Vmax-p. Differences in the measured and Bayesian-fitted values of QPC, VFC and Kb were significant (p < 0.05), and the precision of the fitted values Vmax-p and Qa/co went from 11 +/- 5% to 75 +/- 170% (NS) and from 8 +/- 2% to 9 +/- 2% (p < 0.05) respectively. The empirical Bayes approach did not result in less reliable parameter estimates: rather, it pointed out that the precision of parameter estimates can be overly optimistic when other parameters in the model, either directly measured or taken from literature sources, are treated as known without error. In conclusion, an empirical Bayes approach to parameter estimation resulted in a better model fit, different final parameter estimates, and more realistic parameter precisions.

Adult↗

Computer-aided automatic identification of rice chromosomes by image parameters.

An automatic, computer-aided method for identification of rice chromosomes was developed based on image parameters obtained by image analysis. Numerical data of the 360 condensation patterns (CPs) or the density profiles of rice chromosomes obtained from 30 chromosomal spreads of haploid rice were subjected to three different discrimination methods for identifying the chromosome: (1) discrimination flow chart, (2) linear discrimination functions, and (3) minimum distance classifier based on standardized Euclidean distance. Discrimination based on the minimum distance classifier resulted in the correct identification of more than 92% of the rice chromosomes. The first and second methods gave a correct identification of 91% and 84%, respectively. It is concluded that the 12 rice chromosomes in most spreads could be identified by a computer.

Chromosomes↗

Identification of the cable parameters in the somatic shunt model.

We show that the first five moments of the soma potential and soma current uniquely and stably determine the soma conductance and capacitance and the dendritic electrotonic length, conductance, and capacitance in the so-called somatic shunt model of the passive behavior of a neuron. We test our resulting input admittance algorithm on synthetic data and demonstrate the regularizing effect of knowledge of the ratio of soma to dendrite surface areas.

Computer Simulation↗

[Identification of possible cognizance parameters of "mimic disintegration" in schizophrenia using facial electromyography].

UNLABELLED: The aim of this study was to identify signs of "mimic disintegration" in schizophrenics using a facial electromyographic (EMG) method. We compared a group of 20 unmedicated schizophrenics with a group of 20 healthy subjects, measuring the activity of three joy-relevant facial muscles (zygomaticus major, orbicularis oculi, levator labii superioris) and two nonjoy-relevant facial muscles (frontalis, corrugator supercilii) as control muscles during two consecutive presentations of an erotic slide from the International Affective Picture System. RESULT: Schizophrenics show significantly less activity of joy-relevant facial muscles and a lower smile frequency than healthy subjects. Two signs of mimic disintegration" could be identified: 1. undefined mimic reactions and 2. lack of mimic consistency. CONCLUSION: Facial EMG is a state-of-the-art method for analyzing possible signs of mimic disintegration as described by Heimann and Spoerri. We suggest further examination of the two mimic disintegration signs regarding other emotions, necessarily including more facial muscles in the testing.

Adult↗

Identification of the testing parameters in high frequency dynamic shear measurement on agarose gels.

Dynamic mechanical analysis (DMA) on agarose gels can be used to validate magnetic resonance elastography (MRE) measurements as well as to provide better understanding for the biological responses of cells to the dynamic loadings in cell culture studies. Various parameters potentially affecting the repeatability and accuracy of the DMA shear modulus measurements were investigated systematically in the present study, including sample thickness, shear strain, testing frequency, and compressive clamping strain. The study showed that the thickness of the agarose gel sample must be sufficiently small (1 mm) to prevent the erroneous fluctuation in the measured modulus. The appropriate levels of shear strain (< or = 0.5%) and compressive clamping strain (5-10%) must be applied to overcome the slippage at the gel-clamp interface without causing significant boundary and stress non-uniformity or micro-cracks in the agarose gel sample.

Cell Culture Techniques↗

Identification of in vitro parameters predictive of graft function: a study in an animal model of islet transplantation.

The quality of human islets is one of the factors decisive for the success of human islet transplantation. Several parameters have been proposed to characterize islet quality, but none of them has been able to predict the fate of a transplant. The aim of our study was to correlate a panel of in vitro parameters for islet viability with their in vivo function after transplantation in nude mice. Islets were obtained after enzymatic digestion of a human pancreas; they were purified from exocrine tissue using a continuous-density gradient. Two aliquots of islets (1000 and 2000 islets) were transplanted under the kidney capsule of diabetic nude mice. The animals were followed for 1 month with repeated measurements of blood glucose and body weight. One month after transplantation, mice were killed and their graft harvested for histologic analysis. In parallel we studied in vitro islet viability with propidium iodide and fura-2, their insulin content, their purity, and their insulin response to glucose upon static incubation. Ten islet preparations were transplanted: 3 out of 10 preparations did not restore normoglycemia; 4 out of 10 normalized glycemia only in mice receiving 2000 islets, and 3 out of 10 fully restore normoglycemia in all mice. The purity of preparations (R(2) = 0.63 and 0.85, respectively, with 1000 and 2000 islets) and the insulin content (R(2) = 0.75 with 2000 IE) correlated with transplant success. These data show that purity of islet preparations and their insulin content should be useful parameters for the selection of islet preparations for transplant purposes.

Animals↗

Identification of the optimal parameters for recording cortical evoked potentials to human oesophageal electrical stimulation.

Cortical evoked potentials in response to stimulation of the oesophagus may prove to be a powerful technique for assessing the oesophageal afferent pathway in health and disease. However, in order to maximize the potential of this technique it is essential that the optimal parameters for recording oesophageal CEP are established. The aim was to determine the optimal parameters required to record reproducible CEP. CEP were recorded from the vertex in eight subjects (age range 23-44 years). Electrical stimulation was performed 5 cm above the lower oesophageal sphincter using a bipolar ring electrode at 0.2 Hz. Protocol 1: to determine the stimulation intensity which generates the largest amplitude and shortest latency, two runs of 50 stimuli were applied at increasing intensities. Protocol 2: to determine the number of stimuli for optimal signal to noise ratio, 10 runs of 50 stimuli were recorded. Individual runs were averaged. Protocol 3: to determine the optimal inter-run interval, CEP evoked by 200 stimuli were averaged using randomly chosen inter-run intervals. Protocol 4: CEP reproducibility using parameters determined from Protocols 1-3 was assessed in three subjects on three separate occasions. The results were as follows: Protocol 1; P1 latency was shortest and P1-N1 amplitude largest at an intensity of 75% above threshold. Protocol 2; optimal signal-to-noise was achieved by averaging four runs of 50 stimuli. Protocol 3; the optimal interstudy interval was 10 min. Protocol 4; highly reproducible CEP were obtained in all individuals. Using these optimal parameters, it is possible to obtain highly reproducible oesophageal CEP to ES which can now be used for clinical study.

Adult↗

Identification of the optimal parameters for recording cortical potentials evoked by mechanical stimulation of the human oesophagus.

Cortical evoked potentials (CEP) have been recorded in response to both electrical stimulation (ES) and mechanical stimulation (MS) of the oesophagus. While the optimal parameters for recording reproducible oesophageal CEP to ES have recently been established, they have not yet been determined for MS, and reported CEP to MS show considerable variability. This study aimed to identify the optimal parameters required to record reproducible MS induced CEP. CEP were recorded from the vertex (Cz) in six subjects (one female; age range 23-47 years). MS was performed 5 cm above the lower oesophageal sphincter by rapidly inflating a 2-cm long silicone balloon at a frequency of 0.2 Hz. The rise time to maximum inflation was 165 ms. In order to determine the minimum number of stimuli required to produce optimal signal-to-noise quality, we acquired data in runs of 25, 50, 100 and 300 stimuli and to determine the stimulation intensity that produced the shortest latency and the largest amplitude CEP, we averaged four runs of 50 stimuli at five different intensities ranging from sensory threshold to pain. CEP reproducibility was then assessed in three subjects on three separate occasions using parameters determined from these measurements. We found that optimal signal-to-noise quality was achieved by averaging four runs of 50 stimuli; that P1 latency was shortest and P1-N1 amplitude largest at intensities of 75% and pain threshold and that highly reproducible CEP were obtained in all individuals. We conclude that it is possible to obtain highly reproducible oesophageal CEP to MS which can now be compared to those obtained by ES in order to identify which is most suitable for clinical studies.

Adult↗

Identification of metabolic system parameters using global optimization methods.

BACKGROUND: The problem of estimating the parameters of dynamic models of complex biological systems from time series data is becoming increasingly important. METHODS AND RESULTS: Particular consideration is given to metabolic systems that are formulated as Generalized Mass Action (GMA) models. The estimation problem is posed as a global optimization task, for which novel techniques can be applied to determine the best set of parameter values given the measured responses of the biological system. The challenge is that this task is nonconvex. Nonetheless, deterministic optimization techniques can be used to find a global solution that best reconciles the model parameters and measurements. Specifically, the paper employs branch-and-bound principles to identify the best set of model parameters from observed time course data and illustrates this method with an existing model of the fermentation pathway in Saccharomyces cerevisiae. This is a relatively simple yet representative system with five dependent states and a total of 19 unknown parameters of which the values are to be determined. CONCLUSION: The efficacy of the branch-and-reduce algorithm is illustrated by the S. cerevisiae example. The method described in this paper is likely to be widely applicable in the dynamic modeling of metabolic networks.

Algorithms↗

Identification of a morphometrical parameter that predicts the response to splenectomy in patients with idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is an isolated thrombocyte disease that has no correlation with other causes of clinical thrombocytopenia in adults. About 70% of patients with ITP were successfully treated by medical care and splenectomy, but nearly 30% of ITP patients do not respond to these treatments. The aim of this study is to evaluate the predictive factors that affect the success of treatment in 26 patients with ITP. Thirteen patients with ITP responded to splenectomy (responsive group), whereas 13 other patients were resistant to medical treatment and splenectomy (resistant group). The control group consisted of 13 patients who had undergone posttraumatic splenectomy. Age, sex, spleen weight, the number of follicles per mm(2), and the length of time between diagnosis and splenectomy were retrospectively analyzed. No significant difference was found between the groups with respect to these variables. Mean maximum follicle diameter (MMaFD), mean minimum follicle diameter (MMiFD), and the number and distribution of CD56 (+) cells were evaluated for each spleen specimen. There was no statistical difference in the distribution of CD56 (+) cells between the ITP patients and the control group, but the number of CD56 (+) cells was significantly higher in the control group than in patients with ITP. While MMiFD showed no statistical difference between the groups of ITP patients, a MMaFD of 350 microm and above was significantly more likely in the resistant group than in the other groups. In conclusion, this study has shown that the MMaFD is a significant predictor of the response to splenectomy.

Adolescent↗

[Identification of individual genotype parameters, informative for medical care in piloted space missions: modern and future capabilities].

The factors of space flight provoke some negative shifts in crew health. Improvement of the methods of diagnostics, evaluation of predisposition to diseases and correction of functional deviations is within the scope of the crew medical operations personnel. It is also a new focus of biomedical research referred to as "personalized medicine" the corner stone of which is genetic analysis. Investigations in this area are prediscovery by character; population genetics seems to be the most adequate approach. The authors give examples of candidate genes the genotypes of which could be of significance to medical operations and discuss the genetic safety of space flight. Aside from the applied aspects, the genetic investigations of space crews are of their own concernment in understanding the genetic basis of differences in biological resistance to unhealthy environment.

Adaptation, Physiological↗

Prescreening of cervical smears using two-parameter flow cytometry. Cytologic identification of artifacts.

Individual properties of gynecologic specimens can produce artifacts in flow cytometric (FMC) measurements, possibly leading to false interpretations. An identification of such artifacts was undertaken by parallel FCM and microscopic investigations. One hundred fifty unselected cervical smears were measured by FCM using the fluorochromes 4'-6-diamidino-2-phenylindole (DAPI) for DNA and sulforhodamine (SR 101) for protein. Microscopic specimens were stained by the Papanicolaou technique, and a detailed cytogram was prepared from each smear. FCM discrimination of fluorochrome-stained superficial and intermediate cells was very difficult. On the other hand, a correlation could be established between the fraction of cells from the deeper epithelial layers in the microscopic cytogram and the mean protein content in the FCM histogram. Furthermore, the role of microorganism could be elucidated. Some microorganisms may produce a reduction of the protein content by cytolytic changes. Other microorganisms adhere to the cell surface, resulting in a misleading increase of the DNA fluorescence. Implications for the problem of false alarms are discussed.

Bacteria↗