Effects of chronic doxepin and amitriptyline administration in naïve mice and in neuropathic pain mice model.

Neuropathic pain is a severe clinical problem, often appearing as a co-symptom of many diseases or manifesting as a result of damage to the nervous system. Many drugs and agents are currently used for the treatment of neuropathic pain, such as tricyclic antidepressants (TCAs). The aims of this paper were to test the effects of two classic TCAs, doxepin and amitriptyline, in naïve animals and in a model of neuropathic pain and to determine the role of cytokine activation in the effects of these drugs. All experiments were carried out with Albino-Swiss mice using behavioral tests (von Frey test and the cold plate test) and biochemical analyses (qRT-PCR and Western blot). In the mice subjected to chronic constriction injury (CCI), doxepin and amitriptyline attenuated the symptoms of neuropathic pain and diminished the CCI-induced increase in the levels of spinal interleukin (IL)-6 and -1ß mRNA, but not the protein levels of these cytokines, measured on day 12. Unexpectedly, chronic administration of doxepin or amitriptyline for 12 days produced allodynia and hyperalgesia in naïve mice. The treatment with these drugs did not influence the spinal levels of IL-1ß and IL-6 mRNA, however, the protein levels of these pronociceptive factors were increased. The administration of ondansetron (5-HT3 receptor antagonist) significantly weakened the allodynia and hyperalgesia induced by both antidepressants in naïve mice; in contrast, yohimbine (α2-adrenergic receptors antagonist) did not influence these effects. Allodynia and hyperalgesia induced in naïve animals by amitriptyline and doxepin may be associated with an increase in the levels of pronociceptive cytokines resulting from 5-HT3-induced hypersensitivity. Our results provide new and important information about the possible side effects of antidepressants. Further investigation of these mechanisms may help to guide decisions about the use of classic TCAs for therapy.

Qualitative comparison of bremsstrahlung X-rays and 800 MeV protons for tomography of urania fuel pellets.

We present an assessment of x-rays and proton tomography as tools for studying the time dependence of the development of damage in fuel rods. We also show data taken with existing facilities at Los Alamos National Laboratory that support this assessment. Data on surrogate fuel rods have been taken using the 800 MeV proton radiography (pRad) facility at the Los Alamos Neutron Science Center (LANSCE), and with a 450 keV bremsstrahlung X-ray tomography facility. The proton radiography pRad facility at LANSCE can provide good position resolution (<70 µm has been demonstrate, 20 µm seems feasible with minor changes) for tomography on activated fuel rods. Bremsstrahlung x-rays may be able to provide better than 100 µm resolution but further development of sources, collimation, and detectors is necessary for x-rays to deal with the background radiation for tomography of activated fuel rods.

Charged particle radiography.

New applications of charged particle radiography have been developed over the past two decades that extend the range of radiographic techniques providing high-speed sequences of radiographs of thicker objects with higher effective dose than can be obtained with conventional radiographic techniques. In this paper, we review the motivation and the development of flash radiography and in particular, charged particle radiography.

Towards hard x-ray imaging at GHz frame rate.

Gigahertz (GHz) imaging using hard x-rays (> or approximately equal to 10 keV) can be useful to high-temperature plasma experiments, as well as research and applications using coherent photons from synchrotron radiation and x-ray free electron lasers. GHz framing rate can be achieved by using multiple cameras through multiplexing. The advantages and trade-offs of single-photon detection mode, when no more than one x-ray photon is detected per pixel, are given. Two possible paths towards x-ray imaging at GHz frame rates using a single camera are: (a) avalanche photodiode arrays of high-Z materials and (b) microchannel plate photomultipliers in conjunction with materials with large indices of refraction.

Gas gun shock experiments with single-pulse x-ray phase contrast imaging and diffraction at the Advanced Photon Source.

The highly transient nature of shock loading and pronounced microstructure effects on dynamic materials response call for in situ, temporally and spatially resolved, x-ray-based diagnostics. Third-generation synchrotron x-ray sources are advantageous for x-ray phase contrast imaging (PCI) and diffraction under dynamic loading, due to their high photon fluxes, high coherency, and high pulse repetition rates. The feasibility of bulk-scale gas gun shock experiments with dynamic x-ray PCI and diffraction measurements was investigated at the beamline 32ID-B of the Advanced Photon Source. The x-ray beam characteristics, experimental setup, x-ray diagnostics, and static and dynamic test results are described. We demonstrate ultrafast, multiframe, single-pulse PCI measurements with unprecedented temporal (<100 ps) and spatial (∼2 µm) resolutions for bulk-scale shock experiments, as well as single-pulse dynamic Laue diffraction. The results not only substantiate the potential of synchrotron-based experiments for addressing a variety of shock physics problems, but also allow us to identify the technical challenges related to image detection, x-ray source, and dynamic loading.

Morphology of sighs and their role in the control of breathing in preterm infants, term infants and adults.

BACKGROUND: Although there is evidence that sighs are important to restore lung volume, the factors responsible for inducing a sigh and the effects of sighs on the stability of the respiratory system remain unclear. OBJECTIVE: To compare newborn with adult sigh morphology in order to better understand the physiological mechanisms that induce sighs and the role sighs play on the control of breathing in infants. DESIGN/METHODS: We measured respiratory variables during control, the pre-sigh, the sigh, and the post-sigh period during quiet and REM sleep in 10 preterm infants, 10 term infants and 10 adults using a flow-through system. RESULTS: No significant differences were observed in any of the respiratory variables between the pre-sigh and the control breaths in any of the subjects in any of the two sleep states, suggesting that indices of respiratory drive are not predictive of an impending sigh. Sighs were relatively larger in infants than in adults and had a characteristic biphasic inspiratory flow observed almost exclusively in infants. While post-sigh ventilation was usually increased in adults, it was usually decreased in infants due to the presence of apneas. CONCLUSIONS: The established indexes of respiratory drive are not predictive of an impeding sigh. When compared with control breaths, sighs are much larger in preterm and term infants than in adults. These big augmented breaths in infants are often followed by apnea and hypoventilation likely secondary to the increased activity of the peripheral chemoreceptors present in neonates.

The effects of airway closure in central apneas and obstructed respiratory efforts in mixed apneas in preterm infants.

BACKGROUND: Airway closure during central apnea could allow for better gas exchange. However, the return of inspiratory efforts against a closed airway may cause greater desaturation and prolongation of apnea. OBJECTIVE: To investigate the effect of patency of the airway and obstructed respiratory efforts on the length of apneas and the degree and slope of O(2) desaturation and bradycardia. METHODS: All mixed apneas observed in 15 preterms were matched 1:2 with the longest central apneas in each infant. Central apneas were further classified using the amplified cardiac airflow oscillation in those with airway open and in those with airway closed. RESULTS: No differences were found in the length of apnea, slope of O(2) desaturation, delay between the onset of apnea and onset of desaturation, lowest post-apneic SpO(2), and time of recovery of SpO(2) between central apneas with and without airway closure. Although mixed apneas were significantly longer than central apneas, their initial central component was significantly shorter than the length of central apneas. In mixed apneas, the onset of O(2) desaturation occurred faster, SpO(2) decreased lower, and recovered slower compared with central apneas. The slope of O(2) desaturation after the obstructed respiratory efforts was significantly greater than before the obstructed respiratory efforts. CONCLUSIONS: In preterm infants: (1) airway closure during central apneas does not limit oxygen desaturation; (2) respiratory efforts against a closed airway prolong apnea and worsen the degree of desaturation and bradycardia. Although respiratory efforts are not necessary to induce airway closure, inspiratory efforts against a closed airway could trigger inhibitory cardio-respiratory responses causing significant desaturation, bradycardia, and prolongation of apnea.

Direct observation of the phenomenology of a solid thermal explosion using time-resolved proton radiography.

We present a new phenomenology for burn propagation inside a thermal explosion based on dynamic radiography. Radiographic images were obtained of an aluminum cased solid cylindrical sample of a plastic bonded formulation of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine. The phenomenology observed is ignition followed by cracking in the solid accompanied by the propagation of a radially symmetric front of increasing proton transmission. This is followed by a further increase in transmission through the sample, ending after approximately 100 micros. We show that these processes are consistent with the propagation of a convective burn front followed by consumption of the remaining solid by conductive particle burning.

Testing the stability of the polyethylene acetabulum cemented on a frozen bone graft substrate on a model of an artificial hip joint.

The stability of the polyethylene acetabulum cemented on a substrate made of frozen bone grafts was investigated. The force was applied to the edge of the acetabulum and the magnitude of the force and resulting displacement were recorded. These tests were preceded by stress testing, during which the acetabulum was subjected to loading forces of 1 or 3 kN through 100,000 cycles. Additionally the influence of the thickness of grafts layer on the overall stability of an implant was also determined. The experiments proved that such factors as initial compacting of bone grafts, magnitude of the loading force and thickness of grafts layer greatly affect the stability of the artificial acetabulum.

Breakup densities of hot nuclei.

Breakup densities of hot 197Au-like residues have been deduced from the systematic trends of Coulomb parameters required to fit intermediate-mass-fragment kinetic-energy spectra. The results indicate emission from nuclei near normal nuclear density below an excitation energy E(*)/A less, similar 2 MeV, followed by a gradual decrease to a near-constant value of rho/rho(0) approximately 0.3 for E(*)/A greater, similar 5 MeV. Temperatures derived from these data with a density-dependent Fermi-gas model yield a nuclear caloric curve that is generally consistent with those derived from isotope ratios.

Measurement of analyzing power for proton-carbon elastic scattering in the coulomb-nuclear interference region with a 22-GeV/c polarized proton beam.

The analyzing power for proton-carbon elastic scattering in the Coulomb-nuclear interference region of momentum transfer, 9.0x10(-3)<-t<4.1x10(-2) (GeV/c)(2), was measured with a 21.7 GeV/c polarized proton beam at the Alternating Gradient Synchrotron of Brookhaven National Laboratory. The ratio of hadronic spin-flip to nonflip amplitude, r(5), was obtained from the analyzing power to be Rer(5)=0.088+/-0.058 and Imr(5)=-0.161+/-0.226.

Event-by-event analysis of proton-induced nuclear multifragmentation: determination of the phase transition universality class in a system with extreme finite-size constraints.

A percolation model of nuclear fragmentation is used to interpret 10.2 GeV/c p+197Au multifragmentation data. Emphasis is put on finding signatures of a continuous nuclear matter phase transition in finite nuclear systems. Based on model calculations, corrections accounting for physical constraints of the fragment detection and sequential decay processes are derived. Strong circumstantial evidence for a continuous phase transition is found, and the values of two critical exponents, sigma = 0.5+/-0.1 and tau = 2.35+/-0.05, are extracted from the data. A critical temperature of T(c) = 8.3+/-0.2 MeV is found.

Liquid to vapor phase transition in excited nuclei.

The thermal component of the 8 GeV/c pi+ Au data of the ISiS Collaboration is shown to follow the scaling predicted by Fisher's model when Coulomb energy is taken into account. Critical exponents tau and sigma, the critical point (p(c),rho(c),T(c)), surface energy coefficient c(0), enthalpy of evaporation DeltaH, and critical compressibility factor C(F)(c) are determined. For the first time, the experimental phase diagrams, (p,T) and (T,rho), describing the liquid vapor coexistence of finite neutral nuclear matter have been constructed.

Information technology for children's health and health care: report on the Information Technology in Children's Health Care Expert Meeting, September 21-22, 2000.

In September 2000, the Agency for Healthcare Quality and Research and the American Academy of Pediatrics Center for Child Health Research sponsored a meeting of experts and knowledgeable stakeholders to identify 1) the special information needs of pediatric care and 2) health service research questions related to the use of information technology in children's health care. Technologies that support the care of children must address issues related to growth and development, children's changing physiology, and the unique diseases of children and interventions of pediatric care. Connectivity and data integration are particular concerns for child health care workers. Consumer health information needs for this population extend beyond the needs of one individual to the needs of the family. Recommendations of the attendees include rapid implementation of features in electronic health information systems that support pediatric care and involvement of child health experts in policy making, standards setting, education, and advocacy. A proposed research agenda should address both effectiveness and costs of information technology, with special consideration for the needs of children, the development and evaluation of clinical decision support in pediatric settings, understanding of the epidemiology of iatrogenic injury in childhood, supplementation of vocabulary standards with pediatrics-specific terminology, and improvement in health care access for children, using telemedicine.

Linking personal and public health information: a vision for community-centered health information systems.

As health care in the U.S. and worldwide has shifted from a centralized, institution-based model to a distributed process occurring largely in the communities, Integrated Advanced Information Management Systems (IAIMS) initiatives must also move toward addressing the challenges of integrating health information at the community level. The Wisconsin IAIMS initiative strives to create such a solution, anchoring its efforts in a regional health information technology architecture by partnering with Wisconsin-area communities as the foundation that will ensure the establishment of the appropriate collaborations to gain adequate investment and generate sustainable solutions for health information integration.

The morphology of periodic breathing in infants and adults.

To test the hypothesis that the crescendo-decrescendo type of pattern of periodic breathing is more common in infants than in adulthood, we examined the morphologies of periodic breathing in four groups of subjects: group 1 (n=10, gestational age 30+/-1 week), group 2 (n=10, GA 31+/-1 week), group 3 (n=10, GA 38+/-1 week), and group 4 (n=10, age 50+/-4 years). Respiratory pattern and ventilation were measured using a flow-through system. The breathing morphologies were defined according to the respiratory flow. We found (1) a predominant crescendo-decrescendo pattern in preterm infants (groups 1 and 2, >50%) and this changed to a predominant decrescendo breathing in adults (group 4, 50%); (2) total breathing cycle and its phases did not change significantly among the neonatal groups, but they almost doubled in adult subjects; however, the number of breaths per breathing interval remained the same (crescendo-decrescendo) or less (flat and decrescendo) in adults as compared to preterm infants; (3) the duty cycle (breathing interval/cycle duration) remained consistent with age; and (4) at the beginning of each breathing interval, alveolar P(CO2) was highest and alveolar P(O2) and O2 saturation lowest. The findings suggest a change in the strategy of the respiratory control system during periodic breathing between the infant and the adult, perhaps dictated by mechanical and chemoreceptor limitations early in age, with a switch from a crescendo-decrescendo to a predominantly decrescendo pattern.

Inhalation of low (0.5%-1.5%) CO2 as a potential treatment for apnea of prematurity.

Apnea of prematurity is common and none of the treatments being used are fully effective and free of significant adverse side effects. We hypothesized that low concentrations of CO2 (< or = 1.5%) may reduce apnea without causing discomfort from an increase in ventilation. We studied 10 preterm infants at a gestational age of 32+/-1 wk (mean +/- SEM) and birthweight 1.8+/-0.2 kg. After a control period of 1 hour, concentrations of CO2 were given (0.5%, 1%, and 1.5%) for 1 hour each, followed by a recovery period of 1 hour. Apnea number significantly decreased from 2.0+/-0.3 apneas/min during control to 1.0+/-0.1 apneas/min (0.5% CO2; P < .05), 1.1+/-0.2 (1% CO2; P < .05), and to 0.7+/-0.2 (1.5% CO2; P < .01). The apnea time significantly decreased from 14.2+/-2.5 s/min during control to 5.2+/-0.8 (0.5% CO2; P < .01), 5.8+/-0.7 (1% CO2; P < .01), and to 3.7+/-0.9 (1.5% CO2; P < .01). Minute ventilation significantly increased with CO2 without evidence of respiratory discomfort. TcPCO2 did not change and TcPO2 increased slightly. These findings suggest that inhalation of low concentrations of CO2 in preterm infants with apnea 1) decreases the number and time of apneas, 2) improves oxygenation, 3) increases ventilation, and 4) is effective even in such low concentrations as 0.5%. We speculate that inhalation of CO2 (< 1%) is more effective and safer than methylxanthines for the treatment of apnea of prematurity.

[Allogeneic transplantation in reconstruction of cruciate ligaments in the knee joint]. / Przeszczepy allogenne w rekonstrukcji wiezadel krzyzowych stawu kolanowego.

Allografts have been used successfully by orthopaedic surgeon for reconstructing ligaments, including intraarticular reconstructions of cruciate ligaments. This type of grafts are particularly attractive alternative for reconstruction surgery because donor site morbidity is eliminated, operative time is shorter, incision can be smaller and the availability of different transplant sizes is almost unlimited. This article offers some summaries of scientific background on ACL reconstruction with allografts in animals, clinical follow-up in the humans and discussions on the risk of disease transmission, secondary sterilization, incorporation and remodeling of the allografts after transplantation.

Results of treatment of aseptic loosening of hip prostheses using frozen spongy bone allografts.

BACKGROUND: [corrected] The authors present the results of treatment of aseptic loosening of hip prostheses using frozen allogenic spongy bone grafts. MATERIAL AND METHODS: 34 patients (8 men and 26 women) between 34 and 79 years of age were evaluated. These patients all underwent revision hip arthroplasty during the period from 1995 to 1998. Surgical treatment using frozen spongy bone grafts was performed on patients with defects of the acetabulum and femur after loosening of hip prostheses. In each case bone grafts were used for acetabular and femoral reconstruction. To evaluate the progress of graft incorporation, radiological examinations were made at 6 weeks, 3 months, 6 months, 1 year and 2 years after the date of surgery. We observed the process of calcification abilities of the reconstructed structures were evaluated according to the Merle d'Aubigne-Postel scale. RESULTS: In all cases the spongy bone grafts were reconstructed and rebuilt successfully. 24 patients had good results in further clinical examinations. We argue that frozen allogenic grafts of spongy bone are very useful in filling acetabular and femoral defects in aseptic loosening of hip prostheses. CONCLUSIONS: This method of treatment provides good results and should recommended.

Rehabilitation following revision hip arthroplasty using morselized bone grafts.

For over 25 years, arthroplasty has been in general use as a means of treating degenerative changes in the coxofemoral joint. Loosening of the hip prosthesis is often observed, accompanied by bone defects in the area enveloping the prosthesis. This constitutes an indication for revision surgery.
The authors present their own technique for rehabilitation following revision hip arthroplasty using frozen morselized bone grafts. The procedures used in such cases should be highly individualized. It is necessary to apply a controlled early load on the operated limb at bedside. The authors emphasize the necessity to reduce flexion contracture of the joint. Full load on the limb is proposed between the 4th and 6th month after surgery, depending on the extent of the reconstructed bone defects.