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PubMed2006

Clinical evaluation of a new functional test for detection of activated protein C resistance (Pefakit APC-R Factor V Leiden) at two centers in Europe and the USA.

A new clotting assay, Pefakit APC-R Factor V Leiden (Pentapharm Ltd., Switzerland), for the detection of an increased resistance of coagulation factor V against degradation by activated protein C, caused mainly by the factor V Leiden mutation, was evaluated in clinical studies at two University Centers in Europe and the US. The performance was compared with the performance of the routinely used predicate device COATEST APC Resistance V (Chromogenix IL, USA). Both tests were run in parallel on a STA-R analyzer (Diagnostica Stago, France). Samples from subjects undergoing routine laboratory thrombophilia screening were examined, 187 at the Institute of Medical and Chemical Laboratory Diagnostics (IMCLD), University of Vienna, Austria, and 236 at the Duke University Medical Center (DUMC), Durham/Raleigh NC, USA. All samples were analyzed for factor V Leiden mutation and prothrombin 20210 G/A mutation using standard PCR methods. The data show that the Pefakit APC-R Factor V Leiden assay discriminates very well between healthy controls and carriers of the factor V Leiden mutation, even in patients with lupus anticoagulant or with deficiency in Protein C or Protein S. Furthermore, this new test is able to discriminate well between heterozygous and homozygous carriers of the factor V Leiden mutation. In both studies the Pefakit assay showed 100% sensitivity and 100% specificity for detection of the factor V Leiden mutation, compared to 93.1% sensitivity and 93.0% specificity for the COATEST APC Resistance V in the IMCLD study and 93.9% sensitivity and 95.6% specificity in the DUMC study. The new test has PCR-like discrimination power which will help to decrease costs by reducing the need for PCR verification of borderline cases.

Activated Protein C Resistance↗
PubMed2003

Sarin (nerve agent GB)-induced differential expression of mRNA coding for the acetylcholinesterase gene in the rat central nervous system.

We carried out a time-course study on the effects of a single intramuscular (i.m.) dose (0.5x LD(50)) of sarin (O-isopropyl methylphosphonofluoridate), also known as nerve agent GB, on the mRNA expression of acetylcholinesterase (AChE) in the brain of male Sprague-Dawley rats. Sarin inactivates the enzyme AChE which is responsible for the breakdown of the neurotransmitter acetylcholine (ACh), leading to its accumulation at ACh receptors and overstimulation of the cholinergic system. Rats were treated with 50 microg/kg of sarin (0.5x LD(50)) in 1 mL saline/kg and terminated at the following time points: 1 and 2 hr and 1, 3, and 7 days post-treatment. Control rats were treated with normal saline. Total RNA was extracted, and northern blots were hybridized with cDNA probes for AChE and 28S RNA (control). Poly-A RNA from both treated and control cortex was used for reverse transcription-polymerase chain reaction (RT-PCR)-based verification of the data from the northern blots. The results obtained indicate that a single (i.m.) dose of sarin (0.5x LD(50)) produced differential induction and persistence of AChE mRNA levels in different regions of the brain. Immediate induction of AChE transcripts was noted in the brainstem (126+/-6%), cortex (149+/-4%), midbrain (153+/-5%), and cerebellum (234+/-2%) at 1 hr. The AChE expression level, however, increased over time and remained elevated after a decline at 1 day in the previously shown more susceptible brainstem. The transcript levels remained elevated at a later time point (3 days) in the midbrain, after a dramatic decline at day 1 (110+/-2%). In the cortex, transcript levels came down to control values by day 1. The cerebellum also showed a decline of the elevated levels observed at 2 hr (275+/-2%) to control values by day 1. RT-PCR analysis of the AChE transcript at 30 min in the cortex showed an induction to 213+/-3% of the control level, confirming the expression pattern obtained by the northern blot data. The immediate induction followed by the complex pattern of the AChE mRNA time-course in the CNS may indicate that the activation of both cholinergic-related and unrelated functions of the gene plays an important role in the pathological manifestations of sarin-induced neurotoxicity.

Acetylcholinesterase↗
PubMed2006

Constrained segment shapes in direct-aperture optimization for step-and-shoot IMRT.

Previous studies have shown that, by optimizing segment shapes and weights directly, without explicitly optimizing fluence profiles, effective IMRT plans can be generated with fewer segments. This study proposes a method of direct-aperture optimization with aperture shape constraints, which is designed to provide segmental IMRT plans using a minimum of simple, regular segments. The method uses a cubic function to create smoothly curving multileaf collimator shapes. Constraints on segment dimension and equivalent square are applied, and each segment can be constrained to lie within the previous one, for easy generation of fluence profiles with a single maximum. To simply optimize the segment shapes and reject any shapes which violate the constraints is too inefficient, so an innovative method of feedback optimization is used to ensure in advance that viable aperture shapes are generated. The algorithm is demonstrated using a simple cylindrical phantom consisting of a hemi-annular planning target volume and a central cylindrical organ-at-risk. A simple IMRT rectum case is presented, where segments are used to replace a wedge. More complex cases of prostate and seminal vesicles and prostate and pelvic nodes are also shown. The algorithm produces effective plans in each case with three to five segments per beam. For the simple plans, the constraint that each segment should be contained within the previous one adds additional simplicity to the plan, for a small reduction in plan quality. This study confirms that direct-aperture optimization gives efficient solutions to the segmental IMRT inverse problem and provides a method for generating simple apertures. By using such a method, the workload of IMRT verification may be reduced and simplified, as verification of fluence profiles from individual beams may be eliminated.

Algorithms↗
PubMed2003

GABAC receptors in the rat superior colliculus and pretectum participate in synaptic neurotransmission.

In mammals, GABA(C) receptors seem to be specifically expressed in the retina and the subcortical visual system, with highest extraretinal expression levels in the superior colliculus (SC). Although its presence in the superficial SC has been demonstrated physiologically, a direct involvement of this receptor type in fast synaptic neurotransmission still awaits verification. We addressed the question of a possible synaptic localization of GABA(C) receptors by performing in vitro whole-cell patch-clamp recordings of inhibitory postsynaptic currents (IPSCs) in single neurons of the rat SC and the neighboring pretectal nuclear complex, where GABA(C) receptors are also expressed at significant levels. To increase the likelihood to record IPSCs we induced spontaneous activity by application of the potassium channel blocker 4-aminopyridine (4-AP) and blocked glutamate-mediated excitatory neurotransmission with kynurenic acid. All 4-AP-induced postsynaptic currents were of synaptic origin because they were completely suppressed by lidocaine or by substitution of extracellular calcium with cobalt. In 40% of the SC cells and in 60% of the pretectal neurons, IPSCs in the presence of 4-AP and kynurenic acid were only partly blocked by the selective GABA(A) receptor antagonist bicuculline. Inhibitory currents that were insensitive to bicuculline, however, could be blocked by coapplication of either the specific GABA(C) receptor antagonist 1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid or picrotoxin, an unselective GABA(A) and GABA(C) receptor antagonist. We conclude that GABA(C) receptors are, at least partially, located synaptically in SC and pretectal neurons in the rat, which indicates a direct function of this receptor type for synaptic processing in both structures.

4-Aminopyridine↗
PubMed1999

Synchronized neuronal networks: the GnRH system.

The anatomical substrate for coordinated release from the dispersed gonadotropin-releasing hormone (GnRH) neuronal population remains obscure. There is physiological evidence that the GnRH hormone itself has a role in tonic inhibition or modulation of GnRH function. This has led to the hypothesis that there is an ultrashort negative feedback mechanism subserved by axon collaterals acting back on the GnRH neurons. Recent ultrastructural studies have revealed GnRH synapses on GnRH neurons and their processes. Furthermore, there are alterations in the frequency of these synapses with the age and hormonal condition of the animal. Another candidate for coordination of neuronal activity for which there is some evidence in the magnocellular system, is the gap junction. Recently, physiological and anatomical evidence for gap junctional modifications among an immortalized GnRH-secreting cell line (GT1) has been reported. However, at present there is no immunocytochemical or ultrastructural evidence for gap junctions between GnRH neurons. A third and highly unorthodox anatomical relationship between (among) these cells has been suggested by serial ultrastructural reconstructions of pairs of GnRH neurons in close association. In some regions, GnRH neuronal processes can be seen to extend from each member of a pair of GnRH neurons. These meet and merge, forming an intercellular bridge. This phenomenon has been observed in several pairs of GnRH neurons in rat and monkey. The important caveat in making these observations is that techniques employed to demonstrate sites of antigenicity can severely compromise the ultrastructural integrity of membrane components. For this reason, further verification of the existence of intercellular bridges is being pursued. Should their existence be confirmed, they would be prime candidates for the coordination of secretory events among the scattered GnRH neuronal population.

Animals↗
PubMed2003

Chronic stress effects on memory: sex differences in performance and monoaminergic activity.

Increasing evidence suggests that the time course of advantageous versus deleterious effects of stress on physiologic function is also apparent in some brain functions, including learning and memory. This article reviews the effects of chronic stress on behavioral performance and, more importantly, shows that sex of the subject, as well as duration and intensity of stress, is an important determinant of the functional/behavioral, neurochemical, and anatomical consequences of the stress. Following chronic stress (7-28 days of restraint, 6 h/day), male and female rats were tested on a visual memory task (object recognition) and two spatial memory tasks (object placement and radial arm maze). At 21 days, stress impaired males on all tasks while females were either enhanced (spatial memory tasks) or not impaired (nonspatial memory tasks). Additionally, the influence of the hypothalamic-pituitary-adrenocortical axis in mediating the sex-specific responses to stress is considered. Behavioral and neurochemical assessments following chronic stress in ovariectomized females, with and without estradiol, suggest that estrogen exerts both organizational and activational influences on the observed sex differences in response to stress. Furthermore, stress differentially affected central transmitter levels in the frontal cortex, hippocampus, and amygdala depending on sex. The possible role of these sex-specific changes in neurotransmitter levels in mediating behavioral differences in response to stress is discussed. While these results are thus far limited to a few studies and require both further investigation and verification, chronic stress appears to be associated with distinct, sex-differentiated behavioral/cognitive and neurochemical responses. We conclude that sex differences must be taken into account when investigating or describing stress and associated sequalae.

Animals↗
PubMed2005

Fusiform activation to animals is driven by the process, not the stimulus.

Previous studies have found that the lateral posterior fusiform gyri respond more robustly to pictures of animals than pictures of manmade objects and suggested that these regions encode the visual properties characteristic of animals. We suggest that such effects actually reflect processing demands arising when items with similar representations must be finely discriminated. In a positron emission tomography (PET) study of category verification with colored photographs of animals and vehicles, there was robust animal-specific activation in the lateral posterior fusiform gyri when stimuli were categorized at an intermediate level of specificity (e.g., dog or car). However, when the same photographs were categorized at a more specific level (e.g., Labrador or BMW), these regions responded equally strongly to animals and vehicles. We conclude that the lateral posterior fusiform does not encode domain-specific representations of animals or visual properties characteristic of animals. Instead, these regions are strongly activated whenever an item must be discriminated from many close visual or semantic competitors. Apparent category effects arise because, at an intermediate level of specificity, animals have more visual and semantic competitors than do artifacts.

Adult↗
PubMed1995

"Auctoritas" psychiatric expert system shell.

We present a short description of a complex psychiatric computer expert system, including functions that help the physicians and the hospital staff in the administrative, diagnostic, therapeutic, statistical, and scientific work. There are separate data-storing, health insurance-supporting, or simple advisory programs, but we can not avail a system--in our country--that provides us with all these functions together. Hence the aim of our program is to produce a universal computer system that makes the patients' long distance follow-up possible. Our diagnostic expert system shell, which is appropriate for using the symptoms and criteria scheme of the internationally accepted diagnostic systems such as DSM and ICD, helps to archive homogeneous, up-to-date psychiatric nosology; this is essential for the correct diagnostic, statistical, and scientific work. Let us introduce our expert system. It consists of four parts: administration, diagnostic decision support system, activities concerning treatment, and statistics. The part called "Administration" contains all data about actual and emitted in-patients and out-patients, including their particulars and data necessary for health insurance (duration of treatment, diagnosis); here we find and edit medical documents. The most important part of the "Auctoritas" system is the "Diagnostic decision support system." In practice, expert systems use decision trees with yes-no logic, fuzzy logic, and pattern matching on the basis of the method of deduction; and backward chaining or forward chaining on the basis of the direction of deduction. Our system uses the methods of fuzzy logic and backward chaining. In other medical disciplines, good results are achieved by applying the pattern matching method; to make validity and verification researches, however, these systems are inappropriate. The diagnoses relying on the up-to-date psychiatric diagnostic systems--DSM-IV and ICD-X--are based on classical logic and can be correctly validated and verified. Hence we have chosen the fuzzy logic, which is the up-to-date extension of classical logic and influences the validity and verification researches, for the construction of our system. The diagnostic part is a shell that can be filled up optionally with knowledge bases of the DSM-IV, ICD-X, or other diagnostic systems and has the following structure. The diagnostic course is biphased as we can differ symptoms and criteria (duration of the illness, aethyological factors). We managed to extend the traditional applications using yes-no logic with three factors that make the system more sensitive and flexible. These are the scaling, sorting by importance of symptoms, and reliability-validity results. The "scaling" means that the physician scales the input symptoms by severity; this influences the statistical probability of the possible diagnoses. "Sorting by importance" is gauging certain symptoms by importance in a syndrome. Finally the third point, "reliability-validity results," means taking account of the latest validity values of a certain disorder of the used diagnostic system--according to the latest validity researches--and the diagnostical reliability of our expert system. The "Activity concerning treatment" is a practical part of our program that contents the examination and therapy scheduling and monitoring results. Under the point of "Statistics," we can prepare all data of the patients in various ways. In summary, the "Auctoritas" computer system is a global database managing the newly-developed advisory system; it is appropriate for managing a complete hospital network system for the continuing individual long-distance observation of patients. It collects all the necessary information of one patient in one file. The long-term benefit is that it can compile and process large amounts of information about the patients and help physicians come to scientific conclusions for research and publications.

Decision Making, Computer-Assisted↗
PubMed2001

Commissioning of a commercially available system for intensity-modulated radiotherapy dose delivery with dynamic multileaf collimation.

PURPOSE: To commission commercially available equipment for intensity-modulated radiotherapy (IMRT) using dynamic multileaf collimation (DMLC). MATERIALS AND METHODS: First, the stability in leaf positioning and in realized IMRT profiles on a Varian 2300 C/D machine were determined as a function of time and gantry angle, and as a result of treatment interrupts. Second, dose distributions calculated with the CadPlan (Varian) treatment planning system, using leaf trajectories calculated with the leaf motion calculator (LMC) algorithm, were compared with distributions realized at the 2300 C/D unit. RESULTS: Day-to-day and gantry angle variations in leaf positioning and dose delivery were very small (less than 0.1-0.2 mm and 2%). The effect of treatment interrupts on measured dose distributions was less than 2%. The agreement between the final dose distribution calculated by CadPlan and the measured dose was generally within 2%, or 2 mm at steep dose gradients, using a leaf transmission value of 1.8% and a leaf separation value of 2 mm in LMC. For narrow peaks, deviations of up to 6% were observed. LMC does not synchronize adjacent leaf trajectories resulting in tongue-and-groove underdosages of up to 29% for extreme cases. CONCLUSIONS: The 2300 C/D machine is suitable for accurate and reproducible DMLC treatments. The agreement between dose predictions with LMC and CadPlan, and realized doses at this unit is clinically acceptable for most cases. However, differences between calculated and actual dose values may exist in peaked fluences or due to tongue-and-groove effects. Therefore, pretreatment dosimetric verification for each patient is recommended.

Computer Simulation↗
PubMed1995

The use of digitally reconstructed radiographs for three-dimensional treatment planning and CT-simulation.

PURPOSE: Recent interest in computed tomography-simulation (CT-simulation) suggests the possibility of a shift to digital images for field verification. This article examines the quality of Digitally Reconstructed Radiographs (DRRs) to determine if they can reasonably be substituted for conventional simulator films, and suggests techniques to improve these images. METHODS AND MATERIALS: Special developmental software and computer hardware allowed extremely rapid reformatting of CT data to produce images geometrically equivalent to treatment unit portal films. The technique uses a trilinear interpolation algorithm and gives a 512 x 512 DRR for any arbitrary beam direction. Resolution in line pairs/cm (lp/cm) for both simulator radiographs and DRRs was measured with a special test phantom. Patient data was reformatted to illustrate methods for improving the quality of the DRR. RESULTS: The equipment used for this study reformats 50 512 x 512 CT scans in 8 s. The resolution for a DRR is limited by the voxel size of the CT scans. For typical voxel dimensions, the resolution was found to be 7 lp/cm transverse and 1.0 lp/cm longitudinal compared to 21.0 lp/cm for a simulator radiograph. Patient movement during the scan procedure further degrades the DRR. The reduced quality of this image makes it more difficult to discern structures, and it may not always be possible to perform essential tasks such as counting vertebral bodies. However, viewing the treatment field superimposed on a DRR displayed with a step function to include only bone aided in the identification of relevant landmarks. Switching between soft tissue, bone, or air windows takes less than 10 s on the equipment used for this study, and the use of different display techniques improved the viewer's ability to evaluate field positioning. CONCLUSIONS: A DRR cannot match the spatial resolution of a radiograph taken with a short exposure and small focal spot, but the ability to change the display mode for the DRR increases the usefulness of these images. Fast reformatting is particularly important when evaluation of field position requires the comparison of each portal image to a series of DRRs.

Humans↗
PubMed2005

Effects of various inducers on the expression of P2X7 receptor in human peripheral blood mononuclear cells.

Regulation of P2X7 receptor expression is of interest because activation of this receptor by extracellular ATP triggers a wide variety of cell functions in leukocytes. However, its expression and modulation in human peripheral blood mononuclear cells (PBMC) and monocytes remain unclear. RT-PCR was used to detect the constitutive level of P2X7 receptor and the levels upon stimulation with bacteria, bacterial product, mitogen and various cytokines in human PBMC and monocytes. P2X7 receptor mRNA was detected in PBMC and monocytes. P2X7 receptor expression in PBMC was up-regulated by interleukin-2, -4, -6 (IL-2, IL-4, IL-6) tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS) and heat-inactivated Staphylococcus aureus Cowan strain I (SAC). However, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and phytohemagglutinin-M (PHA-M) had little effect on the expression of P2X7 receptor. Furthermore, LPS and M-CSF could up-regulate P2X7 receptor expression in monocytes, while IFN-gamma, TNF-alpha and GM-CSF had weak effects, but pretreatment with these inducers could not further enhance LPS-stimulated P2X7 receptor expression in monocytes. The results obtained demonstrate that inflammatory stimuli drive P2X7 expression, thus supporting the hypothesis that P2X7 receptor may play a role in the inflammatory responses against bacteria infection, which need further verification.

Humans↗
PubMed1987

Effects of nucleus accumbens lesions in rats on spatial preference in an open field.

Selective lesions placed in three different regions of the nucleus accumbens were performed to assess their effects on spatial preference in the rat. Histological verification allowed to establish three groups of lesioned animals: medial, intermediate and lateral. Sham operations involved all procedures except the passing of a current. All animals were tested once prior to operation and twice postoperatively. Sherman's directionality score (DS) was adopted. Positive values indicate right side preference and negative ones leftward bias. Statistical analysis revealed that rats used in this study showed a nonsignificant spontaneous right side preference in the open field (DS = +0.08). Medial and intermediate lesions increased the right side bias (DS = +0.37), whereas lateral lesioned animals reversed their preoperative rightward bias and showed a significant left side preference (DS = -0.48). These results suggest a participation of the nucleus accumbens in spatial preference and are considered to be due to the well known uneven distribution of the afferent and efferent fiber systems within the nucleus.

Animals↗
PubMed1984

Subtraction gated computed tomography with the dynamic spatial reconstructor: simultaneous evaluation of left and right heart from single right-sided bolus contrast medium injection.

Three-dimensional (3-D) dynamic computed tomography of the heart with the dynamic spatial reconstructor (DSR) is being used for studies of cardiovascular function. Formerly, continuous infusion of bilateral bolus injections of contrast medium were required to visualize both sides of the heart simultaneously. The DSR was used to circumvent many of the drawbacks of these methods. In anesthetized dogs a bolus of 1 ml/kg body weight contrast medium was injected into the superior vena cava and 60/s scans were performed during the dextro- and levophases of the resulting angiogram. The recorded scan data were used to generate successive volume (3-D) images with a scan aperture time of 0.06 s each. Each scanned cardiac cycle was thus represented by sequential volume images with either the right or left chambers opacified. Matching equal time intervals from the R wave of the electrocardiogram, the volume images of the left heart phase were digitally subtracted (voxel for voxel) from the images of the right heart phase, with all resulting negative voxel values set to zero. Only the contrast enhanced right ventricle (RV) chamber remained in the subtraction images, whose brightness was then scaled to match the brightness of the opacified left ventricle (LV). The modified RV phase images were then added to the LV phase images. The resulting volume images contain equally enhanced LV and RV chambers and can be used for retrospective analysis, including display of static and dynamic oblique planar images. Verification of the accuracy of this technique was made by estimation of LV muscle mass in five dogs. Dynamic spatial reconstructor estimates from subtracted gated images were compared with postmortem measurements. The correlation was 0.999 with a mean discrepancy of 2.3 +/- 0.4% SEM.

Animals↗
PubMed1975

[Radioimmunologic determination of plasmatic triiodothyronine. Verification of operative parameters; 1st clinical results].

The experimental determination of the operative parameters of two radioimmunoassay (RIA) systems for the determination of triiodothyronine (T3) level directly in serum is described. The two systems differ both for the agents blocking the aspecific T3-serum protein bindings (sulphonic acid, 8-aniline, 1-Naphtalene in borate buffer: bor-ANS-RIA and Merthiolate in phosphate buffer: PO4-Merth-RIA) and for the methods adopted for compensating the aspecific serum interferences (T3,4 free serum for bor-ANS-RIA and Human Serum Albumine HSA 8% for PO4-Merth-RIA. The tracers are T3-I125 (spec. act. 500 Ci/g for bor-ANS-RIA and 1000 Ci/g for PO4-Merth-RIA). The antisera have been raised in rabbit (T3-bovine SA conjugate for bor-ANS-RIA and T3-HSA conjugate for PO4-Merth-RIA). The incubation conditions are 2degreesC X 24 h for bor-ANS-RIA and room temp. X 2 h for PO4-Merth-RIA. For both systems, the Bound-Free (B-F) separations are carried out by charcoal-dextrane adsorption, 4 mg/tube, 10 min contact. Indicatively, the lowest detection limits of the two systems are about 8 pg T3 for ANS and about 6 pg T3 for Merth. Evidence of parallelism and even superimposition is provided for both assays between the dose-response curve and the serum dilution curve. The calibration curves of the employed antisera are reported (final titres: 1/1000 for ANS and 1/2500 for Merth). 4 different incubation conditions for ANS and 2 for Merth are described and the reasons of choice of the mentioned conditions statistically elucidated. Acceptable statistical comparison between "sample-blank" and the "blank" of the diluents of the employed standard preparations are presented and discussed. F-countings vs. B-countings functions are reported (regression line -- equations: F = 0.93 B + 0.07, n = 15, r = 0.993 for ANS and F = 0.95 B -- 0.02, n = 14, r = 0.992 for Merth) demonstrating the possibility of alternative countings. The recovery regression lines (found f vs. expected e) have equations: f = 1.01 e + 0.08, n = 10, r = 0.999 for ANS and f = 1.08 e -- 1.64, n = 9, r = 0.995 for Merth, implying a practically quantitative recovery in both cases. Thyroxine (T4) cross reaction study has been undertaken under a quite new optics re-calculating the regression lines -- equations of the T3 recovery in the presence of added T4; in that case, the following equations are valid: f = 1.05 e + 0,13, n = 10, r = 0.992 for ANS and f = 1.07 e + 2.26, n = 18, r = 0,985 for Merth. Reducing the maximum added T4 to 1 ng/tube, the cross reaction can be considered as negligible. T3 levels for normal subjects are finally reported: 1.50 +/- 0.80, n= 37 for ANS and 1.40 +/- 0.68, n = 40 for Merth (ng T3/ml, means +/- 2SD).

Antibody Formation↗
PubMedDate not supplied

Successful repair of a ventricular assist system percutaneous lead.

A patient with an implanted, electrically powered, ventricular assist device (Thermo Cardiosystems VE HeartMate) experienced a partial break of the percutaneous lead 5 months after implantation. The break (limited to the Silicone rubber tube) occurred at the junction of the lead with the Y-connector to the controller and vent, leaving approximately 5 cm of exposed lead from the skin exit site to the connector. Electronic and pumping functions of the pump continued, but the opening in the lead (which went more that half way around the circumference) prevented the use of pneumatic actuation as a back-up mode for pump operation, and placed the pump at risk for contamination. Repair of the lead without surgical intervention was desirable, with ease of repair and minimal risk to the patient being the top priorities. The use of multiple layers of heat-shrink tubing or external metal stents was ruled out in favor of a three stage repair procedure. The first stage involved the removal of the Dacron velour in-growth material from the lead to expose the underlying Silicone rubber tube. While the opening in the tube was held shut, a coating of medical grade Silicone rubber adhesive was applied to the tube, then wrapped with a woven Dacron mesh, followed by two layers of plastic wrapping material to protect the adhesive. This initial layer was secured by an external stent of tubing with cable ties. After several days to allow for complete curing of the adhesive, the adhesive coating with mesh was repeated. The final step involved a double layer wrap of a 1 mm thick Silicone rubber sheeting with mesh incorporation and adhesive secured in place with cable ties. After completion of the repair and verification of the ability to operate the device with pneumatic actuation, the patient was discharged with no recurrence of the problem after 8 months of weekly follow-up. This experience demonstrates the need to clinically anticipate component repair or replacement without total device replacement in future implantable blood pump systems.

Adhesives↗
PubMed2003

Effects of different sex hormones on male rabbit urodynamics: an experimental study.

BACKGROUND: The effects of different sex hormones on urodynamics in female rabbits have been investigated previously. Estrogen induces an increase in bladder capacity and compliance, whereas testosterone and progesterone reduced bladder capacity and compliance. OBJECTIVE: The aim of this study was to investigate the effects of sex hormones on bladder urodynamics in male rabbits. METHODS: 5 groups were set up for the study: group I, low midline laparotomy (LML) + 0.9% NaCl; group II, LML + testosterone; group III, LML + bilateral orchiectomy (BO) + testosterone; group IV, LML + BO + progesterone, and group V, LML + BO + estrogen. Baseline urodynamic records and blood sex hormone levels were measured. In the follow-up all rabbits from each group underwent urodynamics 5, 10 and 30 days after injection. Estrogen, progesterone and testosterone levels were also measured during the follow-up period. For statistical verification Mann-Whitney U and Kruskal-Wallis chi(2) tests were used. RESULTS: Hormone levels: Testosterone levels were found to be increased in groups II and III 5 and 10 days after the injection. Testosterone declined thereafter and returned to baseline levels on day 30. In groups IV and V progesterone and estrogen levels increased after the injection and returned to baseline levels on day 30. Urodynamics: In groups II and III testosterone increased the bladder capacity and compliance on days 5 and 10. In these groups, capacity and compliance decreased thereafter and returned to the baseline levels on day 30. These urodynamic findings correlated with the alterations in blood testosterone levels. In groups I and IV no changes were observed in bladder capacity and compliance. In group V capacity and compliance were found to be increased on day 5 after the injection and returned to baseline levels on day 30. The changes in bladder capacity were found to be statistically significant in groups II, III and V. CONCLUSION: In this study, after the injection of testosterone, bladder capacity and compliance increased with high blood testosterone levels in male rabbits. The most interesting finding was observed in the estrogen group, questioning the role of estrogens in males. These findings allow us to reconsider the role of sex hormones in bladder functions.

Abdomen↗
PubMed1992

Estimation of the mean effective organ doses for total body irradiation from Rando phantom measurements.

For the total body irradiation (TBI) procedure, it is necessary to compare the mean dose obtained from the tissue or organs and the estimated dose equivalent value from the computer program. Due to the easy-access of the Rando phantom and repeatability of TLDs and its output, the results from the experiment are quite encouraging for the verification of the dose distributions from total body irradiation at the given prescribed monitor units. The estimation of effective dose equivalent particularly across the lung sections was studied by combinations of using arms as the scatter volume to compensate for the inhomogeneity across the breast portion, as well as using the spoiler for skin-sparing purposes. The results were based upon various beam quality such as 4 MV, 6 MV, and 10 MV X rays. One series of experiments performed for this survey to ascertain the dose equivalent of the tissues was conducted. This paper describes the method and procedure for comparison between the measured data and computed data as a reference in the dosimetry of total body irradiation. Comparison of the measured and computed data for the largest collimated field shows that the calculated dose rates do not differ by more than 2% from the measured data. Because uncertainty is inherent in non-patient-like phantoms, the calculated data may be served as a reference for the dosimetry. For the total body irradiation setup, considering the radiation field size and treatment distances commonly employed, we conclude that the best combination of the patient setup will be (1) laying both arms down as compensation for lung inhomogeneity, and (2) the spoiler, which is made of acrylic about 8 mm thick and functions like a bolus, is needed to reduce the skin sparing effects and contribute the uniform dose distribution. The beam spoiler with the frame stands near the patient during the treatment.

Humans↗
PubMed2005

Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: COPD is a common condition, mainly related to smoking. The burden of the disease is increasing and it is projected to rank fifth in 2020 for the world-wide burden of disease. Acute exacerbations of COPD, usually related to superimposed infection occur commonly and systemic corticosteroids are widely used in their management in combination with other treatments including antibiotics, oxygen supplementation and bronchodilators. OBJECTIVES: To determine the efficacy of corticosteroids, administered either parenterally or orally, on the outcome in patients with acute exacerbations of COPD. SEARCH STRATEGY: Searches were carried out using the Cochrane Airways Group COPD RCT register with additional studies sought in the bibliographies of randomised controlled trials and review articles. Authors of identified randomised controlled trials were contacted for other published and unpublished studies. The last search was carried out in August 2004. SELECTION CRITERIA: Randomised controlled trials comparing corticosteroids, administered either parenterally or orally, with appropriate placebo. Other interventions e.g. bronchodilators and antibiotics were standardised. Clinical studies of acute asthma were excluded. DATA COLLECTION AND ANALYSIS: Data was extracted independently by two reviewers. Outcome data was sent to authors for verification. All trials were combined using Review Manager (version 4.2.4) for analyses. MAIN RESULTS: Ten studies were identified that fulfilled the inclusion criteria. There were significantly fewer treatment failures within thirty days in patients given corticosteroid treatment, odds ratio 0.48; 95% confidence interval 0.34 to 0.68 and Hazard Ratio 0.78; 95% confidence interval 0.63 to 0.97. It would have been necessary to treat 9 patients (95%CI 6 to 14) with systemic corticosteroids to avoid one treatment failure in this time period. There was no significant difference in mortality. The early FEV1, up to 72 hours, showed a significant treatment benefit, weighted mean difference 140 mls (95% confidence interval 80-200 mls), although this benefit was not found for later time points. There was a significant improvement in breathlessness and blood gases between 6 - 72 hours after treatment. There was an increased likelihood of an adverse drug reaction with corticosteroid treatment, odds ratio 2.29; 95% confidence interval 1.55 to 3.38. Overall one extra adverse effect occurred for every 6 people treated (95% CI 4 to 10). The risk of hyperglycaemia was significantly increased, odds ratio 5.48; 95% confidence interval 1.58 to 18.96. AUTHORS' CONCLUSIONS: Treatment of an exacerbation of COPD with oral or parenteral corticosteroids significantly reduces treatment failure and the need for additional medical treatment . It increases the rate of improvement in lung function and dyspnoea over the first 72 hours, but at a significantly increased risk of an adverse drug reaction.

Acute Disease↗