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Multiple linear regression modeling of furosemide renal clearance and urinary excretion rate.

Multiple linear regression techniques were utilized to determine models for the renal clearance and urinary excretion rate of furosemide. Models for the renal clearance were formulated based on data collected from the literature. The best model predicted that the weight-normalized renal clearance was a function of the weight-normalized creatinine clearance, with coefficient values dependent on the presence or absence of heart, liver, and/or kidney failure. The predictive performance of this model was evaluated using a separate verification data set, and, prospectively, for a group of cardiac patients. The urinary excretion rate of furosemide is the primary determinate of response. Models for the furosemide excretion rate were formulated from data collected prospectively from a group of patients with cardiac disease. The best model predicted that the dose-normalized morning urinary excretion rate was a function of the blood urea nitrogen concentration (BUN), with modifications for the presence of liver failure and/or decompensated heart failure. The oral dosage required to produce a clinically optimal furosemide excretion rate in cardiac patients without liver disease was dose (mg) = 42.1/(0.925-0.0151 BUN).

Aged↗

Mass spectrometrical verification of stomatin-like protein 2 (SLP-2) primary structure.

Stomatin-like protein 2 (SLP-2) (syn.: EPB72-like 2 [NP_038470], HSPC108 [AAF29073]), a protein of unknown function, has been described in several tissues and cells but its primary structure is still not completely elucidated. Moreover, sequence conflicts appear in several databases. It was the aim of the study to further describe SLP-2 primary sequence and to solve existing sequence conflicts. For this purpose a protein extract was run on two-dimensional gel electrophoresis and SLP-2 was identified by MALDI-TOF/TOF. SLP-2 was digested with trypsin, chymotrypsin, Lys-C, and de novo sequencing studies as well as Nano-HPLC-ESI-MS/MS analysis were carried out. By the use of several proteases sequence coverage of 90% was obtained but the N-terminal 34 amino acids harbouring database conflict 1 were not covered. The presence of Leucine 129 (sequence conflict 2) and Alanine 202 (sequence conflict 3) was verified by three independent approaches. High sequence coverage resulting from multiple proteolytic cleavage, MALDI-TOF/TOF, Nano-HPLC-ESI-MS/MS and de novo sequencing completed unambiguous analysis of SLP-2 primary structure of approximately = 90% of sequence coverage. In addition, methodology used was able to solve so far pending sequence conflicts in databases and literature. SLP-2 is a high abundance protein in several tissues and cells and may play an important biological role and therefore characterization of its primary structure is of importance.

Amino Acid Sequence↗

Statistical limitations in functional neuroimaging. I. Non-inferential methods and statistical models.

Functional neuroimaging (FNI) provides experimental access to the intact living brain making it possible to study higher cognitive functions in humans. In this review and in a companion paper in this issue, we discuss some common methods used to analyse FNI data. The emphasis in both papers is on assumptions and limitations of the methods reviewed. There are several methods available to analyse FNI data indicating that none is optimal for all purposes. In order to make optimal use of the methods available it is important to know the limits of applicability. For the interpretation of FNI results it is also important to take into account the assumptions, approximations and inherent limitations of the methods used. This paper gives a brief overview over some non-inferential descriptive methods and common statistical models used in FNI. Issues relating to the complex problem of model selection are discussed. In general, proper model selection is a necessary prerequisite for the validity of the subsequent statistical inference. The non-inferential section describes methods that, combined with inspection of parameter estimates and other simple measures, can aid in the process of model selection and verification of assumptions. The section on statistical models covers approaches to global normalization and some aspects of univariate, multivariate, and Bayesian models. Finally, approaches to functional connectivity and effective connectivity are discussed. In the companion paper we review issues related to signal detection and statistical inference.

Bayes Theorem↗

Evaluation of Tc99m-glucoheptonate for SPECT functional imaging of medulloblastoma.

OBJECTIVES: Functional imaging of medulloblastoma using SPECT has been a difficult problem as this tumour does not concentrate conventional brain tumour imaging radiopharmaceuticals. This study aimed to evaluate Tc99m-glucoheptonate as a "brain tumour-seeking" radiopharmaceutical for functional imaging of medulloblastoma. METHODS: Tc99m-glucoheptonate brain SPECT was performed in 27 patients with medulloblastoma after radiation therapy and with clinical suspicion of tumour recurrence. Histological verification was obtained within 7 days in patients with a SPECT diagnosis of tumour recurrence. Patients with a SPECT diagnosis of post-radiation gliosis were clinically observed for a minimum period of one year after the SPECT study. RESULTS: Fourteen patients had increased radiotracer uptake in the primary tumour bed, suggesting tumour recurrence. Histopathology confirmed viable medulloblastoma in all cases. Thirteen patients had no increased tracer uptake in the primary tumour bed, suggesting post-radiation gliosis. They all had a clinical course consistent with post-radiation gliosis. CONCLUSION: Tc99m-glucoheptonate is an ideal SPECT tracer for functional evaluation of medulloblastoma. SPECT utilising Tc99m-glucoheptonate is a reliable diagnostic modality to differentiate tumour recurrence from post-radiation gliosis in patients with medulloblastoma.

Adolescent↗

Numerical estimation of heat distribution from the implantable battery system of an undulation pump LVAD.

We have been developing an implantable battery system using three series-connected lithium ion batteries having an energy capacity of 1,800 mAh to drive an undulation pump left ventricular assist device. However, the lithium ion battery undergoes an exothermic reaction during the discharge phase, and the temperature rise of the lithium ion battery is a critical issue for implantation usage. Heat generation in the lithium ion battery depends on the intensity of the discharge current, and we obtained a relationship between the heat flow from the lithium ion battery q(c)(I) and the intensity of the discharge current I as q(c)(I) = 0.63 x I (W) in in vitro experiments. The temperature distribution of the implantable battery system was estimated by means of three-dimentional finite-element method (FEM) heat transfer analysis using the heat flow function q(c)(I), and we also measured the temperature rise of the implantable battery system in in vitro experiments to conduct verification of the estimation. The maximum temperatures of the lithium ion battery and the implantable battery case were measured as 52.2 degrees C and 41.1 degrees C, respectively. The estimated result of temperature distribution of the implantable battery system agreed well with the measured results using thermography. In conclusion, FEM heat transfer analysis is promising as a tool to estimate the temperature of the implantable lithium ion battery system under any pump current without the need for animal experiments, and it is a convenient tool for optimization of heat transfer characteristics of the implantable battery system.

Electric Power Supplies↗

Mimics of yeast tRNAAsp and their recognition by aspartyl-tRNA synthetase.

Assuming that the L-shaped three-dimensional structure of tRNA is an architectural framework allowing the proper presentation of identity nucleotides to aminoacyl-tRNA synthetases implies that altered and/or simplified RNA architectures can fulfill this role and be functional substrates of these enzymes, provided they contain correctly located identity elements. In this work, this paradigm was submitted to new experimental verification. Yeast aspartyl-tRNA synthetase was the model synthetase, and the extent to which the canonical structural framework of cognate tRNAAsp can be altered without losing its ability to be aminoacylated was investigated. Three novel architectures recognized by the synthetase were found. The first resembles that of metazoan mitochondrial tRNASer lacking the D-arm. The second lacks both the D- and T-arms, and the 5'-strand of the amino acid acceptor arm. The third structure is a construct in which the acceptor and anticodon helices are joined by two connectors. Aspartylation specificity of these RNAs is verified by the loss of aminoacylation activity upon mutation of the putative identity residues. Kinetic data indicate that the first two architectures are mimics of the whole tRNAAsp molecule, while the third one behaves as an aspartate minihelix mimic. Results confirm the primordial role of the discriminator nucleotide G73 in aspartylation and demonstrate that neither a helical structure in the acceptor domain nor the presence of a D- or T-arm is mandatory for specific aspartylation, but that activity relies on the presence of the cognate aspartate GUC sequence in the anticodon loop.

Acylation↗

Levels of mRNA coding for motoneuron growth-promoting factors are increased in denervated muscle.

Partial denervation of skeletal muscle induces sprouting of axons remaining within the muscle, possibly as a result of increased synthesis by denervated muscle fibers of motoneuron growth-promoting factors. Direct verification of this hypothesis has not been possible because the molecules responsible are not unambiguously characterized. We used Xenopus oocytes as a functional assay for mRNAs coding for secreted growth factors: preparations of mRNA from innervated and denervated neonatal muscle were injected into oocytes. Three days later, oocytes injected with denervated muscle mRNA expressed increased levels of nicotinic acetylcholine receptor and voltage-dependent sodium channels at their membrane. Proteins secreted by the same oocytes were tested for their effects on (i) neurite outgrowth from embryonic chicken ventral spinal cord neurons; (ii) survival in mixed culture of embryonic chicken motoneurons identified using the SC1 antibody; and (iii) survival of embryonic motoneurons purified by panning on SC1 antibody. In all three assays, media conditioned by oocytes injected with mRNA from denervated muscle contained significantly higher levels of biological activity than did those from oocytes injected with innervated muscle mRNA or water. mRNA was prepared from muscle at different times after denervation: a maximal increase was obtained already after 1 day, consistent with an involvement in sprouting. Synthesis of motoneuron growth-promoting factors is thus regulated by denervation in a parallel fashion to that of other key components of the neuromuscular junction.

Animals↗

Desmopressin and antifibrinolytics.

Desmopressin appears to be a safe and effective hemostatic agent for use during surgery in patients with mild to moderate hemophilia or von Willebrand disease. Uremic patients also benefit from substitution of desmopressin for cryoprecipitate to control bleeding. The highly variable response to desmopressin by individual patients with hemophilia or von Willebrand disease dictates that each patient receive a trial administration prior to surgery; surgery should proceed only following verification of a therapeutically effective increase in Factor VIII and vWF after desmopressin. Use of desmopressin in patients with normal baseline hemostatic function is not clearly advantageous, although certain patient subgroups might benefit, and prospective studies have documented the drug's safety in these cases. Data are lacking to clarify a role for desmopressin during surgery in patients taking aspirin. Antifibrinolytic therapy appears to decrease bleeding without increased risk after cardiac surgery. In addition, specific use after urological surgery may be beneficial in the absence of upper urinary tract bleeding. In the last ten years, other applications for antifibrinolytic therapy have been found--both surgical (intracranial aneurysms, oral and lacrimal surgery) and nonsurgical (in cancer patients and for gastrointestinal bleeding). Although anecdotal reports have fueled fears of increased thrombosis with antifibrinolytics, controlled studies indicate no increased risk.

Antifibrinolytic Agents↗

Diffractive properties of volume phase gratings in photorefractive sillenite crystals of arbitrary cut under the influence of an external electric field.

We study the influence of bias dc electric field on the optical properties of volume phase gratings formed in optically active photorefractive sillenite crystals. By considering a general case where the external electric bias direction, the grating vector orientation, the light propagation direction (crystal cut), and state of polarization are arbitrary, we deduce analytical expressions for the diffraction efficiency and the polarization state of the diffracted beam. The influence of the inverse piezoelectric effect is taken into account both in the uniform and the spatially varying part of the impermeability tensor, as well as into the calculation of the effective static permittivity. A theoretical comparative study of the dynamic behavior of the diffraction efficiency as a function of the physical parameters that affect the diffraction process (crystal cut, electric bias, input polarization, and grating orientation) along with experimental verification is provided. The general analytical solution provides means of exploitation of the capabilities of sillenite crystals in several applications.

Journal Article↗

Dynamics of a tracer granular particle as a nonequilibrium Markov process.

The dynamics of a tracer particle in a stationary driven granular gas is investigated. We show how to transform the linear Boltzmann equation, describing the dynamics of the tracer into a master equation for a continuous Markov process. The transition rates depend on the stationary velocity distribution of the gas. When the gas has a Gaussian velocity probability distribution function (PDF), the stationary velocity PDF of the tracer is Gaussian with a lower temperature and satisfies detailed balance for any value of the restitution coefficient alpha. As soon as the velocity PDF of the gas departs from the Gaussian form, detailed balance is violated. This nonequilibrium state can be characterized in terms of a Lebowitz-Spohn action functional W(tau) defined over trajectories of time duration tau. We discuss the properties of this functional and of a similar functional W(tau), which differs from the first for a term that is nonextensive in time. On the one hand, we show that in numerical experiments (i.e., at finite times tau), the two functionals have different fluctuations and W always satisfies an Evans-Searles-like symmetry. On the other hand, we cannot observe the verification of the Lebowitz-Spohn-Gallavotti-Cohen (LS-GC) relation, which is expected for W(tau) at very large times tau. We give an argument for the possible failure of the LS-GC relation in this situation. We also suggest practical recipes for measuring W(tau) and W(tau) in experiments.

Journal Article↗

[Crisis interventions: a psychotherapeutical challenge for psychiatric emergencies?].

Taking care of patients consulting the emergency psychiatric unit, raises nosological, legal, ethical and even logistic questions for the emergency departments. The need for emergency psychiatric interventions has grown constantly during the last twenty years and clinicians were challenged to find a new psychotherapeutic approach, more focused on the actual symptoms presented by the patients than the 'classic' psychiatric interventions. The goal of this article is to discuss the possibility of a psychotherapeutic approach in an emergency department, departing from a treatment model that has been developed at the psychiatric emergency of the University of Milan. In this approach, the psychotherapeutic treatment is divided in four different stages: preparation, incubation, transformation and verification. The "psychiatric crisis" becomes an opportunity to change for the patient, being a passage rite towards a new and better psychological functioning.

Crisis Intervention↗

[Disorganized eye movements and visuospatial dysfunctions in an early stage of the patients with Alzheimer's disease--the effects of language and visual information processing on constructional performances].

In Alzheimer's disease higher brain function disorders such as geographical disorientation, visual agnosia and constructional disability are frequently observed in addition to the progressive memory loss. Visual information processing was studied through newly developed technology, vision analyzer, since visuospatial functions play an important role in the pathophysiology underlying these neuropsychiatric symptoms and dementia itself. We found characteristic findings as to eye movements of focus indicating visual cognitive disorders. Language or language functions, however, are considered to be essentially involved in visuospatial functions. We examined eye movements of patients suffering from Alzheimer's disease (15 cases), MID (5 cases), Parkinson's disease (5 cases) and 10 control subjects during constructional behavior under various conditions in terms of visual information processing. 1. Alzheimer's disease (n = 15): All patients showed constructional disabilities when copying geometrical figures. 1) Three dimensional drawing was possible following verbal instructions in 7 out of 15 patients. 2) Three dimensional drawing was successful when the model figure to be copied was covered in 4 out of these 7 patients. 3) Three dimensional drawing was possible following verbal instruction in a dark room, although they were not so accurate but better than those when copied in 4 out of 7 patients. 4) The analysis of eye movements revealed that typical eye movements were confirmed during copying geometric figures. The distribution of the gazing points of focus, and the average eye movement velocity distribution were also distinctive. But these disorganized eye movements in description of graphic figures following verbal instruction became more similar to those of healthy controls when compared to those in the copying graphic figures. 2. MID (n = 5), Parkinson disease (n = 5), healthy controls (n = 10): 1) No subject showed constructional disability when copying a graphic figure. They were also capable to describe a graphic figure both in the dark and following verbal instruction. 2) No remarkable change was observed in the distribution of the eye movement, or in the average eye movement velocity on these subjects. 3. These results indicate that in an early stage of the patients with Alzheimer's disease, primary or fundamental disorders seem to lay in the verification process of visual information, which results in the difficulties in categorization process of the visual objects. The categorization process is involved with language function, which was preserved in a certain period at an early stage of the disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Alzheimer Disease↗

Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti-myelin-associated glycoprotein antibody.

Axonal injury is a hallmark of traumatic brain injury (TBI) and is associated with a poor clinical outcome. Following central nervous system injury, axons regenerate poorly, in part due to the presence of molecules associated with myelin that inhibit axonal outgrowth, including myelin-associated glycoprotein (MAG). The involvement of MAG in neurobehavioral deficits and tissue loss following experimental TBI remains unexplored and was evaluated in the current study using an MAG-specific monoclonal antibody (mAb). Anesthetized rats (n=102) were subjected to either lateral fluid percussion brain injury (n=59) or sham injury (n=43). In surviving animals, beginning at 1 h post-injury, 8.64 microg anti-MAG mAb (n=33 injured, n=21 sham) or control IgG (n=26 injured, n=22 sham) was infused intracerebroventricularly for 72 h. One group of these rats (n=14 sham, n=11 injured) was killed at 72 h post-injury for verification of drug diffusion and MAG immunohistochemistry. All other animals were evaluated up to 8 weeks post-injury using tests for neurologic motor, sensory and cognitive function. Hemispheric tissue loss was also evaluated at 8 weeks post-injury. At 72 h post-injury, increased immunoreactivity for MAG was seen in the ipsilateral cortex, thalamus and hippocampus of brain-injured animals, and anti-MAG mAb was detectable in the hippocampus, fimbria and ventricles. Brain-injured animals receiving anti-MAG mAb showed significantly improved recovery of sensorimotor function at 6 and 8 weeks (P<0.01) post-injury when compared with brain-injured IgG-treated animals. Additionally, at 8 weeks post-injury, the anti-MAG mAb-treated brain-injured animals demonstrated significantly improved cognitive function and reduced hemispheric tissue loss (P<0.05) when compared with their brain-injured controls. These results indicate that MAG may contribute to the pathophysiology of experimental TBI and treatment strategies that target MAG may be suitable for further evaluation.

Animals↗

Perspectives of leprosy patients on MDT services after integration of NLEP functions into primary health care.

Sixty-five leprosy patients residing in rural Digapahandi block of Ganjam district were studied during July-August 2001 in order to ascertain their perspectives regarding different MDT services after NLEP functions were integrated into primary health care (PHC) in Orissa after September 1999. They included 43.08% multibacillary (MB) cases and 61.92% paucibacillary (PB) cases. Assessment was done by personal interviews of adult patients and the parents of child cases after verification of their treatment cards at the sub-centre. Patient's knowledge regarding the availability of MDT services under PHC services and utilization of these services were highlighted. Influence of different socio-demographic factors was also studied. Basing on the study results, recommendations were made for sustained NLEP functions through PHC in order to improve the utilization of MDT services, which will help in the elimination of leprosy.

Adult↗

[Toxicological significance of metallothionein on environmental harmful factors: verification and suggestions from a metallothionein-I/II null mouse model study].

In many research groups including our laboratory, metallothionein (MT)-I/II null mice have been used to clarify the biological function and physiological role of MT. Recent studies with MT-I/II null mice concerning the role of MT in the toxicity and distribution of metal, oxidative stress and chemical carcinogenesis were reviewed. Some reports, including our findings, showed that MT-I/II null mice have an increased sensitivity to harmful metals such as cadmium, mercury, zinc and arsenic. Moreover, it was clarified using MT-I/II null mice that MT plays a major role in the retention of cadmium, mercury and zinc in target tissues. MT-I/II null mice were found to be much more sensitive than wild-type mice to the toxicity caused by free radical-inducing factors, which include paraquat, acetaminophen, ethanol, X-ray, ultraviolet B, carbon tetrachloride, cisplatin, doxorubicin, cerulein and streptozotocin. In addition, MT-I/II null mice were highly susceptible to skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene and bladder carcinogenesis caused by N-butyl-N-(4-hydroxybutyl)nitrosamine. These results suggest that MT is an important protective factor against metal toxicity, oxidative stress and chemical carcinogenesis.

Animals↗

[Chronic inflammatory intestinal disease and nephritis].

An 11 year old CD-patient developed an interstitial nephritis and acute kidney failure following treatment with Mesalazine (5-ASA) and Salazosulfapyridine (SASP). After removal of the medication and treatment with hemofiltration and prednisone there was only an incomplete recovery of the renal function (creatinine-clearance 34 ml/1,73 m2/min). It is thought that an hyperergic-allergic reaction due to SASP and 5-ASA causes interstitial nephritis in inflammatory bowel disease (IBD). This reaction can be induced by re-exposition too. On the other hand IBD can be associated with glomerulonephritis. This could be a not very well known extraintestinal manifestation in IBD caused by immune-complexes in serum and glomerula. A rapid histological verification of the renal disease is necessary for successful treatment. In both renal manifestations chronic courses are possible. These observations should not lead to avoid SASP/5-ASA in treatment of IBD, but renal function should be routinely investigated.

Acute Kidney Injury↗

Concentration and velocity field measurements by magnetic resonance imaging in aperiodic heterogeneous porous media.

Magnetic resonance imaging (MRI) techniques were investigated as a means to obtain concentration and velocity field measurements for the verification of a stochastic model for conservative chemical transport. MRI techniques were successfully applied to obtain one-dimensional breakthrough images and two-dimensional velocity images along the length of an aperiodic heterogeneous porous medium. Experimental moment data showed the concentration field in the experimental model to be slightly positively skewed. Velocity images showed the velocity field to be relatively uniform with no channeling or preferential flow behavior. Measured covariance functions showed evidence of negative correlation in the velocity field. The detailed spatial information provided by these imaging experiments has demonstrated that MRI is a valuable tool for obtaining experimental data for the verification of existing theoretical models.

Attention↗

Teaching image-guided stereotactic methodology and functional neuroanatomy of the thalamus and pallidum: a simple ex vivo technique.

A simple and cheap model that enables on site, ex vivo, but very practical, learning of frame-based image-guided stereotactic technique and methodology, and the functional anatomy of the pallidum and thalamus is described. Using a cadaver skull, a specially prepared, formalin-fixed cadaver brain, and a modified stereotactic probe application of a stereotactic frame to the cranium, fiducial point acquisition, target point acquisition, computation of both arc and probe depth settings, and verification of target point accuracy can all be practiced. If diencephalic targets are selected for targeting with ball bearings then section of the cadaver brains, and study of a human thalamic stereotactic atlas provides an excellent and clinically relevant method of learning functionally important thalamic and pallidal anatomy. The method and techniques are described for CT imaging using the Brown-Roberts-Wells frame, but they are equally applicable to other frame types.

Brain Mapping↗