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Standardization of pulsed-field gel electrophoresis protocols for the subtyping of Escherichia coli O157:H7, Salmonella, and Shigella for PulseNet.

Standardized rapid pulsed-field gel electrophoresis (PFGE) protocols for the subtyping of Escherichia coli O157:H7, Salmonella serotypes, and Shigella species are described. These protocols are used by laboratories in PulseNet, a network of state and local health departments, and other public health laboratories that perform real-time PFGE subtyping of these bacterial foodborne pathogens for surveillance and outbreak investigations. Development and standardization of these protocols consisted of a thorough optimization of reagents and reaction conditions to ensure that the protocols yielded consistent results and high-quality PFGE pattern data in all the PulseNet participating laboratories. These rapid PFGE protocols are based on the original 3-4-day standardized procedure developed at Centers for Disease Control and Prevention that was validated in 1996 and 1997 by eight independent laboratories. By using these rapid standardized PFGE protocols, PulseNet laboratories are able to subtype foodborne pathogens in approximately 24 h, allowing for the early detection of foodborne disease case clusters and often aiding in the identification of the source responsible for the infections.

Cluster Analysis↗

Analysis and interpretation of the HLA DQ alpha "1.1 weak-signal" observed during the PCR-based typing method.

The Perkin-Elmer (PE) AmpliType DQ alpha Forensic Kit is currently available for amplification and typing of a polymorphic region in the Human Leukocyte Antigen (HLA) DQ alpha DNA sequence. Following amplification of the DQ alpha region with the PE kit, typing strips are processed. These strips contain immobilized DNA probes designed to distinguish six possible HLA DQ alpha alleles. It has been observed in this laboratory and others that in a single source DNA sample, it is possible to detect a weak signal on the 1.1 specific allele dot when the samples' genotype clearly does not contain the 1.1 allele. It has been suggested that a potential source of this weak-signal is the non-specific amplification of a HLA DX alpha gene sequence. To demonstrate the relationship of the DX alpha gene to the 1.1 nonspecific signal, we designed biotinylated DX alpha PCR primers specific for a 178 bp region in which the amplified product spans the homologous DQ alpha region encompassing the DNA probes present on the typing strips. DX alpha DNA sequences from various DQ alpha genotypes were amplified and hybridized to DQ alpha typing strips. We have demonstrated that DX alpha PCR products do not always hybridize to the 1.1 probe on the typing strips. Sequence analysis of DX alpha PCR products show that this region is polymorphic which may explain why the occurrence of the "1.1 weak-signal" is unpredictable. We have further analyzed the effect of DNA template concentration for the DQ alpha amplification protocol and have shown that regulation of PCR input DNA optimizes the amplification and typing protocols for HLA DQ alpha alleles and minimizes the potential observation of the "1.1 weak-signal."

Base Sequence↗

A sensitivity-guided algorithm for automated determination of IMRT objective function parameters.

Optimizing intensity-modulated radiotherapy (IMRT) plans involves tradeoffs that balance normal-tissue objectives against each other and against tumor objectives. Adjusting the parameters that determine the appropriate contributions of individual anatomic structures to the objective functions through trial and error is time consuming and may not produce the best achievable plans. We have developed a sensitivity-guided parameter optimization (SGPO) method to assist in the automatic determination of parameters to drive the IMRT optimization to better achieve, or even exceed, specified planning goals. The method is based on the trade-off relationships among multiple objectives: In a globally optimal plan (or within a convex subspace of the plan objectives), any attempt to improve the achievement of goals for a structure will result in sacrificing the goals for at least one other structure. However, different objectives may have different sensitivities to the overall goal of an IMRT plan. For instance, changes in dose distribution, hence the subscore corresponding to an objective for a given normal structure, may minimally impact the target dose distribution. Stated differently, the target coverage is insensitive to the changes in dose distribution of the specific normal structure. A lung cancer treatment plan designed with the SGPO method was used to demonstrate that IMRT plans could be designed to favor a structure with the highest target sensitivity and spare the structures with the least target sensitivity without compromising the target coverage. Using one case each of prostate and paranasal sinus cancers, we also demonstrated that several alternative optimal solutions could be designed with the SGPO algorithm favoring different structures. Finally, we applied the method to eight oropharyngeal cancer cases to obtain objective function parameters that satisfied the Radiation Therapy Oncology Group RTOG-H-0022 protocol. The eight plans optimized using the computer-generated objective function parameters met the protocol's scoring criteria with no or only minor protocol violations. Our preliminary study indicates that the SGPO method may be an effective and practical way to improve IMRT planning.

Artificial Intelligence↗

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↗

A review of the methodological aspects of aspartic acid racemization analysis for use in forensic science.

Accurate age determination of adult cadavers and human remains is a key requirement in forensic practice. The current morphological methods lack accuracy and precision, require specialist training and are costly. The use of aspartic acid racemization (AAR) in human dentine provides a simple, cost-effective solution and the method can achieve accuracies of +/- 3 years at best. Currently, there are differences in AAR methodology between laboratories which produce different results on the rate of racemization in teeth. These inconsistencies must be resolved if the technique is to be successfully applied to age determinations in forensic cases. This paper reviews the differences in protocol which have been used, discusses how each method will affect the results obtained from AAR analysis and gives recommendations for optimization of the methological protocol as a first step towards international standardization.

Adult↗

An intelligent case-adjustment algorithm for the automated design of population-based quality auditing protocols.

We develop a method and algorithm for deciding the optimal approach to creating quality-auditing protocols for guideline-based clinical performance measures. An important element of the audit protocol design problem is deciding which guide-line elements to audit. Specifically, the problem is how and when to aggregate individual patient case-specific guideline elements into population-based quality measures. The key statistical issue involved is the trade-off between increased reliability with more general population-based quality measures versus increased validity from individually case-adjusted but more restricted measures done at a greater audit cost. Our intelligent algorithm for auditing protocol design is based on hierarchically modeling incrementally case-adjusted quality constraints. We select quality constraints to measure using an optimization criterion based on statistical generalizability coefficients. We present results of the approach from a deployed decision support system for a hypertension guideline.

Algorithms↗

A custom library construction method for super-resolution ribosome profiling in Arabidopsis.

BACKGROUND: Ribosome profiling, also known as Ribo-seq, is a powerful technique to study genome-wide mRNA translation. It reveals the precise positions and quantification of ribosomes on mRNAs through deep sequencing of ribosome footprints. We previously optimized the resolution of this technique in plants. However, several key reagents in our original method have been discontinued, and thus, there is an urgent need to establish an alternative protocol. RESULTS: Here we describe a step-by-step protocol that combines our optimized ribosome footprinting in plants with available custom library construction methods established in yeast and bacteria. We tested this protocol in 7-day-old Arabidopsis seedlings and evaluated the quality of the sequencing data regarding ribosome footprint length, mapped genomic features, and the periodic properties corresponding to actively translating ribosomes through open resource bioinformatic tools. We successfully generated high-quality Ribo-seq data comparable with our original method. CONCLUSIONS: We established a custom library construction method for super-resolution Ribo-seq in Arabidopsis. The experimental protocol and bioinformatic pipeline should be readily applicable to other plant tissues and species.

3-nt periodicity↗

Optimization and clinical use of multisegment intensity-modulated radiation therapy for high-dose conformal therapy.

Intensity-modulated radiation therapy (IMRT) may be performed with many different treatment delivery techniques. This article summarizes the clinical use and optimization of multisegment IMRT plans that have been used to treat more than 350 patients with IMRT over the last 4.5 years. More than 475 separate clinical IMRT plans are reviewed, including treatments of brain, head and neck, thorax, breast and chest wall, abdomen, pelvis, prostate, and other sites. Clinical planning, plan optimization, and treatment delivery are summarized, including efforts to minimize the number of additional intensity-modulated segments needed for particular planning protocols. Interactive and automated optimization of segmental and full IMRT approaches are illustrated, and automation of the segmental IMRT planning process is discussed.

Abdominal Neoplasms↗

[Progress in optimizing dosimetry plans in stereotactic radiotherapy in the Salt Group (Saint-Anne-Lariboisière-Tenon].

We began intracranial stereotactic irradiation under the direction of O Betti 11 years ago. At the present time, we believe it is interesting to present the methodologies of the SALT (Saint-Anne-Lariboisière-Tenon) group. Up to the present time we have irradiated 693 patients using a single fraction. Arteriovenous malformations (AVMs) represented the majority (90%) of treated lesions. Irradiation protocol has little changed since 1986, and the localization of the target volume was performed in the neurosurgery department of St Anne Hospital, France. The stereotactic images (computerized tomography [CT], angiography) were sent to the radiotherapy department of Tenon Hospital through the French public digital network NUMERIS. Protocol was realized using the stereotactic ARTEMIS-3D/Dosigray TPS. The lesion volume was filled by one or more spherical or elliptical subvolumes using the "Associated Target Methodology". The interactive adjustment of subvolumes was based on the 3D graphical representations of the lesion. The direct optimization of the irradiation space was performed by managing parameters provided by the DDB (Dosimetric Data Base) such as the number of arcs, their angular position, as well as the starting and the ending point of each arc. The evaluation of the calculated dose distribution was made using quantitative parameters. The second method of optimization was based on the minibeam intensity modulation using a mathematical theory of inverse problems and singular value decomposition (SVD) analysis. At the present time, due to technical reasons, linear accelerators do not permit the modulation of intensity of arctherapy. Thus we transformed the profiles of irregular forms into rectangular profiles of modulated ponderation, with each optimized plan being evaluated before its implementation. The criteria of evaluation were derived from the differential and cumulative dose volume histograms (DVH). The DVHs permitted the evaluation of the volumes of underdosage and overdosage inside the lesion and in the healthy tissue, respectively. Using DVHs, we have defined parameters such as the conform factor and the homogeneity index. We stress that the methodology of protocol optimization is valid for single or multiple fractions as well as for intra- and extra-cranial irradiation.

Humans↗

Performance of a rate responsive accelerometer-based pacemaker with autocalibration during standardized exercise and recovery.

The rate responsiveness of a single chamber, accelerometer-based pacemaker with an autocalibration function (Opus G VVIR pacemaker, ELA Medical) was studied with a daily life protocol developed to automatically optimize the programming of accelerometer-based sensors. This new sensor was compared with two other body activity sensors that were manually optimized patient by patient. Forty-three pacemaker recipients (mean age 71 +/- 11 years), paced > 95% of the time, underwent a daily life protocol consisting of rapid walking for 6 minutes (W), climbing upstairs for 1.5 minutes (U), and downstairs for 1.5 minutes (D), alternated by recovery phases. The results were compared with performances measured in a control population of healthy subjects and in two paced patient populations (one equipped with a Dash Intermedics VVIR pacemaker and the other equipped with a Sensolog III Pacesetter/St. Jude VVIR pacemaker). Sex distribution and mean age between paced patients and control subjects were statistically comparable. The mean heartrate achieved by all paced patients at each time sample was compared with the normograms, assigning acceleration (slope) and rate (rate) scores for exercise and recovery phases. Scores ranged from -10 (hypochronotropic) to +10 (hyperchronotropic). Zero represents exact concordance with the responses of healthy individuals, and values between -2.5 and +2.5 were considered statistically similar to normal. During W, although the overall performances of the Dash, Sensolog, and Opus G did not statistically differ from healthy controls, the scores obtained by the Opus G were significantly closer to controls than those of the two other pacemakers (P = 0.02). For U, the three sensors were hypochronotropic (P = 0.03), though the Opus G was associated with a heart rate response closer to that of healthy controls (P = 0.04). D provided similar mean heart rate scores for the Opus G and the Dash compared with healthy controls, in contrast with the hyperchronotropic behavior of the Sensolog (P = 0.02). Opus G revealed a physiological modulation of the heart rate for W and D tests with a slightly hypochronotropic behavior during U. The Opus G autocalibration function provided daily life performances closer to those of healthy controls than two other pacemakers equipped with a body activity sensor that were manually optimized.

Aged↗

Optimization of RNA isolation from the archaebacterium Methanosarcina barkeri and validation for oligonucleotide microarray analysis.

The recent completion of a draft genome sequence for Methanosarcina barkeri has allowed the application of various high throughput post-genomics technologies, such as nucleic acid microarrays and mass spectrometry of proteins to detect global changes in transcription and translation that occur in response to experimental treatments. However, due to the production of a thick heteropolysaccharide outer layer, M. barkeri usually grows in large aggregates of cells rather than as individual, planktonic cells. Complete disruption of these aggregates and lysis of the released cells presents technical difficulties in ensuring the isolation of intact RNA from the entire population of cells. Initial attempts at isolating RNA from M. barkeri using several standard extraction protocols gave incomplete lysis of cells and resulted in low yields of poor quality RNA. In this study, we tested several chemical and mechanical disruption modifications of standard RNA extraction methods to optimize the extraction efficiency and minimize the number of unlysed cells remaining after extraction. As a further test of the quality of the resulting RNAs, their performance in replicate microarray analyses were determined. The results showed that inclusion of a liquid nitrogen grinding step prior to Trizol extraction, combined with moderate bead beating, yielded the most complete cell lysis, the highest yield of RNA and the most reproducible microarray results for M. barkeri. From these results it is clear that the methods used to isolate RNA can have a significant impact on the variability, trend and, presumably, the accuracy of microarray data. In addition, functional analysis of the microarray results obtained with RNA from the optimized protocol showed that, as expected, the genes involved in methanogenesis were among the most highly expressed genes in M. barkeri.

Gene Expression↗

Multicenter controlled clinical trial of high-frequency jet ventilation in preterm infants with uncomplicated respiratory distress syndrome.

OBJECTIVE: To test the hypothesis that high-frequency jet ventilation (HFJV) will reduce the incidence and/or severity of bronchopulmonary dysplasia (BPD) and acute airleak in premature infants who, despite surfactant administration, require mechanical ventilation for respiratory distress syndrome. DESIGN: Multicenter, randomized, controlled clinical trial of HFJV and conventional ventilation (CV). Patients were to remain on assigned therapy for 14 days or until extubation, whichever came first. Crossover from CV to HFJV was allowed if bilateral pulmonary interstitial emphysema or bronchopleural fistula developed. Patients could cross over to the other ventilatory mode if failure criteria were met. The optimal lung volume strategy was mandated for HFJV by protocol to provide alveolar recruitment and optimize lung volume and ventilation/perfusion matching, while minimizing pressure amplitude and O2 requirements. CV management was not controlled by protocol. SETTING: Eight tertiary neonatal intensive care units. PATIENTS: Preterm infants with birth weights between 700 and 1500 g and gestational age <36 weeks who required mechanical ventilation with FIO2 >0.30 at 2 to 12 hours after surfactant administration, received surfactant by 8 hours of age, were <20 hours old, and had been ventilated for <12 hours. Outcome Measures. Primary outcome variables were BPD at 28 days and 36 weeks of postconceptional age. Secondary outcome variables were survival, gas exchange, airway pressures, airleak, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and other nonpulmonary complications. RESULTS: A total of 130 patients were included in the final analysis; 65 were randomized to HFJV and 65 to CV. The groups were of comparable birth weight, gestational age, severity of illness, postnatal age, and other demographics. The incidence of BPD at 36 weeks of postconceptional age was significantly lower in babies randomized to HFJV compared with CV (20.0% vs 40.4%). The need for home oxygen was also significantly lower in infants receiving HFJV compared with CV (5.5% vs 23.1%). Survival, incidence of BPD at 28 days, retinopathy of prematurity, airleak, pulmonary hemorrhage, grade I-II IVH, and other complications were similar. In retrospect, it was noted that the traditional HFJV strategy emphasizing low airway pressures (HF-LO) rather than the prescribed optimal volume strategy (HF-OPT) was used in 29/65 HFJV infants. This presented a unique opportunity to examine the effects of different HFJV strategies on gas exchange, airway pressures, and outcomes. HF-OPT was defined as increase in positive end-expiratory pressure (PEEP) by >/=1 cm H2O from pre-HFJV baseline and/or use of PEEP of >/=7 cm H2O. Severe neuroimaging abnormalities (PVL and/or grade III-IV IVH) were not different between the CV and HFJV infants. However, there was a significantly lower incidence of severe IVH/PVL in HFJV infants treated with HF-OPT compared with CV and HF-LO. Oxygenation was similar between CV and HFJV groups as a whole, but HF-OPT infants had better oxygenation compared with the other two groups. There were no differences in PaCO2 between CV and HFJV, but the PaCO2 was lower for HF-LO compared with the other two groups. The peak inspiratory pressure and DeltaP (peak inspiratory pressure-PEEP) were lower for HFJV infants compared with CV infants. CONCLUSIONS: HFJV reduces the incidence of BPD at 36 weeks and the need for home oxygen in premature infants with uncomplicated RDS, but does not reduce the risk of acute airleak. There is no increase in adverse outcomes compared with CV. HF-OPT improves oxygenation, decreases exposure to hypocarbia, and reduces the risk of grade III-IV IVH and/or PVL.

Bronchopulmonary Dysplasia↗

The importance of being exhaustive. Optimization of bridging structural water molecules and water networks in models of biological systems.

Algorithms and protocols are described for the optimization for H-bonding of isolated singular H2O molecules and entire networks of H2O molecules. Unlike other approaches that are prone to being trapped in local energy minima, these methods rely on exhaustive searches of orientation space for the H2O molecules. The results are scored with the HINT hydropathic interaction model, but the algorithms should be general for any energy-scoring computation. Two examples are provided: 1) the tightly-bound H2O molecule 301 of HIV-1 protease is shown to be more reasonably oriented in terms of forming H-bonds with this method than with a molecular mechanics energy minimization method; and 2) the H2O network surrounding carbonmonoxymyoglobin is constructed and analyzed for a 1.80-A neutron-diffraction structure. The H-atom positions calculated with this method show a somewhat better agreement with the experimental results than do the H-atom positions calculated with molecular mechanics, and both are considerably better than random.

Hydrogen↗

The wash-in/washout protocol in stable xenon CT cerebral blood flow studies.

PURPOSE: We conducted a comparative study to optimize the scanning and inhalation protocols for xenon CT cerebral blood flow (CBF) examination (Xe CT), with the aim of improving the practical performance of Xe CT as a routine clinical examination. MATERIALS AND METHODS: Four different inhalation protocols, including 3-min, 6-min, and 8-min wash-in protocols, and a 3-min wash-in/5-min washout protocol, were compared in five healthy volunteers. Each subject underwent two serial Xe CT examinations with an interval of 30 min between the first one (wash-in) and the second one (wash-in/washout). A computer simulation was also performed to support the results of the clinical study. The rate of success was calculated from our experience of 110 clinical cases examined with the wash-in/washout protocol over the last 9 months. RESULTS: The mean CBF values with 6-min and 8-min wash-in protocols were 59.0 and 59.5 mL/100-g brain per min in the thalamus, and 19.5 and 19.0 mL/100-g brain per min in the frontal white matter, respectively. The mean CBF values with 3-min wash-in/5-min washout protocol were 60.0 mL/100-g brain per min in the thalamus and 18.5 mL/100-g brain per min in the frontal white matter, respectively. Computer simulation showed improved signal-to-noise ratio by employing the 3-min wash-in/5-min washout protocol instead of 8-min wash-in protocol for the same number of data points. The rate of success improved to 99.1% due to the significant decrease in head motion with the shorter period of inhalation. CONCLUSION: A wash-in/washout protocol is a useful alternative in Xe CT CBF measurement and more useful than the wash-in method for clinical purposes.

Administration, Inhalation↗

Optimization of radioimmunotherapy interactions with hyperthermia.

The efficacy of radioimmunotherapy (RIT) employing radiolabelled monoclonal antibodies (MAb) is currently limited in most solid tumours. The combination of local hyperthermia (HT) with RIT has the potential to enhance tumour targeting of MAb; moreover, this approach may add an antitumour effect to radioresistant hypoxic and S-phase cells and may inhibit the cells from repairing sublethal damage or potentially lethal damage caused by ionizing radiation. There are distinct types of protocols in this combination. Hyperthermic temperature and timing relative to RIT administration appear to affect the efficacy of the combination therapy. Responses to heating at any particular condition are not always the same among different tumour types. There are many papers describing influence of HT on the biodistribution of radiolabelled MAb, but only limited information is currently available on 'therapeutic' outcomes regarding the dependency of combination protocols. A previous study suggested that the best therapeutic improvement would be achieved when HT was combined immediately after the administration of MAb, which significantly increases the radiation absorbed dose to tumours and produces a uniform intratumoural dose distribution. Further therapeutic investigation should be required to reach the optimal protocol of combining these two modalities.

Animals↗

Total parathyroidectomy without autotransplantation for renal hyperparathyroidism: experience with a qPTH-controlled protocol.

BACKGROUND: Controversy regarding the optimal surgical treatment for secondary hyperparathyroidism (sHPT) continues. Subtotal parathyroidectomy (PTX) with a small remnant and total parathyroidectomy with autotransplantation prevail, although impaired by considerable recurrence rates. Concerns about postoperative management and long-term supplementation prevent broader acceptance of total parathyroidectomy without autotransplantation. MATERIALS AND METHODS: The standardized surgical procedure with intraoperative PTH assessment (qPTH) included cervical thymectomy, histological proof of four parathyroid specimens and obligatory cryopreservation of parathyroid tissue in all 23 patients undergoing total PTX without autotransplantation. Whenever qPTH did not normalize, complete cervical exploration of ectopic sites was performed. Another 64 patients with subtotal PTX for sHPT served as comparison for the postoperative course. RESULTS: There were 13 primary and 10 completion (5 persistent, 5 recurrent sHPT) total PTX with 14 concurrent thyroid resections performed. Mean preoperative PTH was 1.351 pg/ml (12-72 pg/ml) and serum calcium was 2.5 mmol/l (2.25-2.5 mmol/l). PTH showed intraoperative normalization in 15 patients and a 50% PTH reduction from preoperative values in all. Postoperative course was not significantly different from the subtotal PTX group and showed PTH within the normal range for 5 patients (4 < 35 pg/ml), 7 with PTH < 12 pg/ml, and 4 without measurable PTH. In 4 patients PTH did not normalize postoperatively. Serum calcium levels were below normal in all patients: < 2.25 mmol/l in 9, < 2.00 mmol/l in 7, and <1.8 mmol/l in 6 patients. Only 1 patient required intermittent early postoperative i.v. calcium supplementation, 6 patients received oral calcium and vitamin D supplement for low calcium levels, but no severe hypocalcemic symptoms were encountered. Mean postoperative hospital stay was 5 days. No recurrent laryngeal nerve palsies were encountered. Complications were two cervical bleedings following postoperative hemodialysis requiring evacuation. CONCLUSIONS: Total PTX without autotransplantation proves to be an equally safe and successful procedure for sHPT as subtotal PTX or total PTX with autotransplantation. Measurable PTH after total PTX as demonstrated in this study, supports the idea of uncontrollable isolated cell nests that are inevitably prone to stimulated growth with time. Therefore, total PTX is superior with regard to prevention of recurrence. Adequate supplementation with calcium and vitamin D, often necessary after subtotal PTX to suppress inadequate PTH and protect from recurrence, will prevent severe hypocalcemia and with the modern aluminium-diminishing dialysis regimen, development of adynamic bone disease appears less likely than feared. If necessary, cryopreserved parathyroid tissue can be autotransplanted on demand.

Adult↗

Tetrahedral irradiation protocol for microbeam radiation therapy.

Optimizing microbeam radiation therapy requires that the patient be repositioned between exposures. Optional movements of a patient-gantry are described that would enable a lesion to be cross-fired pseudo-orthogonally in two, three or four exposures to a fixed, horizontally propagated array of vertical, parallel microplanar beams, with minimal tilting of the patient-gantry.

Humans↗

Recovery of systolic and diastolic left ventricular function early after cardiopulmonary bypass.

BACKGROUND: Impairment of left ventricular function after cardiopulmonary bypass (CPB) is well recognized, but little is known about the time course of recovery of cardiac function early after separation from CPB. Therefore, recovery of left ventricular function was evaluated early after separation from CPB in patients undergoing coronary artery surgery. The authors tried to determine whether this recovery might be attributed to autoregulation of function by preload. METHODS: Left ventricular pressure was measured with fluid-filled catheters. Data were digitally recorded during increased pressure induced by elevating the legs. Transgastric short-axis echocardiographic views of the left ventricle were simultaneously recorded on videotape. Systolic function was evaluated with the slope (Ees, mmHg/ml) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, ml-1) of the diastolic pressure-volume relation. Cardiac function was assessed before CPB, after termination of CPB, and 5, 10, and 15 min later. Two different separation procedures from CPB were compared: in protocol 1, left ventricular function was documented during the standard procedure (n = 24); in protocol 2, the heart was optimally filled 10 min before separation from CPB (n = 12). RESULTS: In protocol 1, Ees was 2.88 +/- 0.21 mmHg/ml (mean +/- SEM) and Kc was 0.012 +/- 0.001 ml-1 before CPB. Within 10 min after separation from CPB, Ees increased from 1.10 +/- 0.32 to 2.92 +/- 0.34 (P = 0.001) and Kc decreased from 0.022 +/- 0.002 to 0.011 +/- 0.001 (P = 0.001). The parameters remained stable thereafter. In protocol 2, Ees was 2.92 +/- 0.51 mmHg/ ml and Kc was 0.011 +/- 0.002 ml-1 before CPB. Depression of systolic and diastolic function was not observed in these patients. At time 0, Ees was 2.46 +/- 0.16 and Kc was 0.012 +/- 0.002. These values remained stable throughout the entire observation period. CONCLUSIONS: Significant functional recovery was observed early after separation from CPB, which was suggestive of time-dependent changes in both systolic and diastolic left ventricular function induced by preload restoration.

Anesthesia↗