Treatment planning for dose escalation in non-small cell lung cancer (NSCLC).

This study was performed to examine potential field arrangements for irradiating non-small cell lung cancer (NSCLC) on a dose escalation study. An example patient was chosen and 7 coplanar treatment plans were created to treat a NSCLC. Two plans included prophylactic nodal irradiation (PNRT) and 5 did not. Four plans used 4 fields, 2 plans used 5 fields, and 1 plan included dynamic conformal 360 degrees rotational therapy. All plans delivered 80 Gy to the isocenter with 10-MV x-rays. Each plan was initially created without dose inhomogeneity corrections and then was recalculated with these corrections, maintaining the same weighting and number of monitor units. Avoiding PNRT spared a considerable volume of normal tissue from radiation. Plans with 5 fields generally spared normal tissues better than 4-field plans. There was no benefit to the dynamic conformal 360 degrees rotational plan. Inhomogeneity corrections revealed that higher doses were delivered to both the tumor and normal structures. Seven beam arrangements for the treatment of NSCLC were compared to develop potential beam arrangements that would be applicable to treating NSCLC on a multi-institutional dose escalation study. We favor the use of at least 5 beams in most situations. It is possible that the use of more fields would further improve plans up to a point of diminishing returns, as exemplified by the lack of benefit seen with the dynamic conformal 360 degrees rotational plan. It is possible that the use of noncoplanar fields or intensity-modulated radiation therapy (IMRT) may further improve the therapeutic ratio.     

Mechanisms of impaired exercise capacity in short duration experimental hyperthyroidism.

To investigate the mechanism of reduced exercise tolerance in hyperthyroidism, we characterized cardiovascular function and determinants of skeletal muscle metabolism in 18 healthy subjects aged 26 +/- 1 yr (mean +/- SE) before and after 2 wk of daily ingestion of 100 micrograms of triiodothyronine (T3). Resting oxygen uptake, heart rate, and cardiac output increased and heart rate and cardiac output at the same submaximal exercise intensity were higher in the hyperthyroid state (P less than 0.05). However, maximal oxygen uptake decreased after T3 administration (3.08 +/- 0.17 vs. 2.94 +/- 0.19 l/min; P less than 0.001) despite increased heart rate and cardiac output at maximal exercise (P less than 0.05). Plasma lactic acid concentration at an equivalent submaximal exercise intensity was elevated 25% (P less than 0.01) and the arteriovenous oxygen difference at maximal effort was reduced (P less than 0.05) in the hyperthyroid state. These effects were associated with a 21-37% decline in activities of oxidative (P less than 0.001) and glycolytic (P less than 0.05) enzymes in skeletal muscle and a 15% decrease in type IIA muscle fiber cross-sectional area (P less than 0.05). Lean body mass was reduced (P less than 0.001) and the rates of whole body leucine oxidation and protein breakdown were enhanced (P less than 0.05). Thus, exercise tolerance is impaired in short duration hyperthyroidism because of decreased skeletal muscle mass and oxidative capacity related to accelerated protein catabolism but cardiac pump function is not reduced.     

Increase in glycocalicin levels in platelet concentrates stored in plasma or synthetic medium for 8 days: comparison with other platelet activation markers

BACKGROUND AND OBJECTIVES: Glycocalicin (GC) is a proteolytic fragment of GpIb and can conveniently be measured in supernatants of platelet concentrates (PCs) by means of a sandwich ELISA. Because of the convenience of the assay and easy sample storage, we tested its suitability as a sensitive platelet activation parameter during PC storage. MATERIAL AND METHODS: Filtered PCs in plasma or additive solution were made from 5 pooled buffy coats and were subsequently stored during 8 days at 22+/-2 degrees C. Correlation coefficients (r) were calculated after comparison of GC levels with platelet parameters. RESULTS: A significant increase in GC concentration was found on all subsequent sampling days. PC stored in plasma showed GC levels that correlated well with the soluble P-selectin levels (r = 0.7506), P-selectin (CD62P) expression on platelet membranes (r = 0. 8843), morphology scores according to Kunicki (r = -0.7102), lactate concentrations (r = 0.9216), glucose concentrations (r = -0.8913) and beta-thromboglobulin (beta-TG) concentrations (r = 0.8913). In PCs stored in additive solution, the correlation coefficients with these markers were 0.9209 with soluble P-selectin, 0.7161 with CD62P expression, -0.7474 with morphology score, -0.8908 with glucose concentrations, 0.8923 with lactate concentrations and 0.8908 with beta-TG concentrations. CONCLUSIONS: The GC concentration correlates well with sensitive platelet (activation) parameters, rendering it a sensitive and convenient parameter for platelet activation.     

Pathogen reduction of buffy coat platelet concentrates using riboflavin and light: comparisons with pathogen-reduction technology-treated apheresis platelet products

BACKGROUND AND OBJECTIVES: A pathogen-reduction technology (PRT) system using riboflavin and light has been developed for the treatment of platelet concentrates (PC) obtained by either buffy coat preparation (BCPC) or apheresis procedures (APPC). The aim of this study was to evaluate the effects of the treatment process on in vitro cell quality and on riboflavin conversion in PC. MATERIALS AND METHODS: BCPC were prepared with the Compomat G4 from whole blood which had been stored overnight after collection. APPC were obtained using the TRIMA apheresis procedure. Both PC products had been stored for 18-24 h prior to PRT treatment. BCPC and APPC were treated with PRT on day 2 and day 1 of shelf-life, respectively. The treated PCs were then maintained for an additional 5 days after the PRT treatment. A panel of cell quality assays and high-performance liquid chromatography (HPLC) analysis were performed. RESULTS: Cell counts and plasma lactate dehydrogenase (LDH) levels during storage indicated that PRT did not induce significant cell lysis. Acceleration of a decrease in glucose and an increase in lactate was observed for treated PCs, but no significant differences were observed between treated BCPC and APPC. The pH of treated samples remained above 7.0, although was lower than that of the control. Platelet morphology of BCPC and APPC was well preserved. P-selectin expression indicated significant platelet activation when compared with control PC (BCPC on day 6: 39% vs. 12%; APPC on day 5: 35% vs. 18%). Both P-selectin expression and microparticle formation were not significantly different between treated BCPC and APPC during storage. The JC-1 assay also displayed no loss of mitochondria integrity during the storage of treated products. Approximately 20% of riboflavin converted into photoproducts, including lumichrome. CONCLUSIONS: PRT treatment had an effect on the development of the normal platelet storage lesion at a level which seems tolerable for clinical usage.     

Differentialdiagnose Synkope

Die Synkope ist ein transienter, selbstlimitierender Bewusstseinsverlust, häufig mit Sturzfolge. Zugrundliegender Mechanismus ist eine transiente globale cerebrale Minderperfusion. Im Gegensatz hierzu werden Anfallsleiden oder metabolische Entgleisungen wie Hypoxie, Hypoglykämie, Hyperventilation als nicht-synkopale Ereignisse klassifiziert, da sie nicht durch eine transiente globale cerebrale Minderperfusion hervorgerufen werden. Am häufigsten ist die neurokardiogene oder vasovagale Synkope, in bis zu 20% der Synkopen lässt sich eine zugrundeliegende strukturelle Herzerkrankung finden. Da die Prognose der Synkope von der zugrundeliegenden Erkrankung abhängt, ist eine genaue Untersuchung des Synkopenpatienten unbedingt notwendig. Hierzu zählt eine genaue Anamneseerhebung, eine ausführliche körperliche Untersuchung mit liegender und stehender Blutdruckmessung und ein 12-Kanal-EKG. Wird eine strukturelle Herzerkrankung vermutet oder ist diese bereits bekannt oder liegt ein abnormales EKG vor, sollte eine mögliche strukturelle Herzerkrankung weiter mit Echokardiographie, Belastungs- EKG und ggfs. Herzkatheteruntersuchung und/oder elektrophysiologischer Untersuchung abgeklärt werden. Die Therapie wird sich in diesen Fällen auf die Behandlung der Grunderkrankung, Behandlung von Bradykardien mit Schrittmachern oder von Tachykardien mit Radiofrequenzablation und/oder implantierbaren Defibrillatoren konzentrieren. Besteht kein Hinweis auf eine strukturelle Herzerkrankung und ist das EKG normal, sollten Reflex vermittelte Synkopen in Betracht gezogen werden, vor allem bei suggestiver Anamnese. Die Provokation einer Synkope auf dem Kipptisch kann die Verdachtsdiagnose erhärten. Die Behandlung wird sich bei den Reflex vermittelten Synkopen meist auf die Aufklärung von Synkopen triggerenden Auslösern und Erkennung von Prodromi beschränken, um rechtzeitig Gegenmaßnahmen vor Eintreten einer Bewusstlosigkeit zu ergreifen.     

Private peer group settings as an environmental determinant of alcohol use in Dutch adolescents: results from a representative survey in the region of Twente

This study supports the hypothesis that the drinking setting can be an environmental risk factor for hazardous alcohol use. In a survey of Dutch adolescents (n = 1516), alcohol consumption and participation in private peer group settings (PPSs), environments where adolescents meet and drink alcohol without direct adult supervision, were measured. After controlling for demographic variables, adolescents visiting PPSs as compared to non-visitors, appeared to have a significantly higher lifetime prevalence of alcohol use, average weekly consumption, and frequency of heavy episodic drinking. Moreover, accounting for school clustering, the frequency of PPS visits was associated with increased alcohol consumption.     

A new ICD morphology criterion for differentiating supraventricular and ventricular tachycardia

The high incidence of inappropriate therapies due to supraventricular tachycardia remains a major unsolved problem of the implantable cardioverter defibrillator. A new morphology discrimination (MD) algorithm has been introduced to improve specificity of ICD therapy without loss of sensitivity. It was the aim of this study to systematically analyze sensitivity and specificity of the MD criterion in combination with the enhanced detection criteria sudden onset and rate stability in the detection of ventricular and supraventricular tachycardia. After ICD implantation in 259 patients, 787 detected episodes in 74 patients with available stored electrograms were documented during a follow-up period of 359 +/- 214 days. With a nominal programming of the MD algorithm at > or = 60%, sensitivity and specificity for all episodes were 82.6%/77.2%. For sinus tachycardia, atrial fibrillation and atrial flutter the specificities were 80.6%, 69.6% and 75%, respectively. In patients with primarily appropriate MD detection, sensitivity and specificity significantly improved to 95.8%/91.7%. Programming the sudden onset criterion with < 100 ms and the stability criterion with < 50 ms, sensitivity and stability of the combined application of the MD algorithm and sudden onset and MD algorithm and stability were 96.2%/52.2% and 94.4%/63.8%, respectively. The MD criterion in combination with other enhanced detection criteria might significantly improve specificity of tachyarrythmia detection of ICD therapy.     

Implantable cardioverter/defibrillator: long-term stability of the defibrillation threshold with a unipolar electrode configuration (active-can")

The majority of cardioverter/defibrillator (ICD) implantations are currently performed with a non-thoracotomy approach. From November 1993 to January 1995, 46 patients underwent implantation of a PCD 7219C with an "active-can" lead configuration at our institution. While the chronic stability of the defibrillation threshold (DFT) for an epicardial lead system is well established, the results are still inconsistent for non-thoracotomy lead systems. Accordingly, the aim of the present study was to compare the acute and chronic defibrillation thresholds of the ICDs implanted with an "active-can" lead system in order to assess the chronic stability of these systems. The defibrillation energy requirements were measured at implant, prior to hospital discharge, three, six and twelve months after implantation of the defibrillator. The patient group consisted of 8 females and 38 males with a mean age of 57.2 years. The mean left ventricular ejection fraction was 43.8%. The most frequent underlying heart disease was coronary artery disease in 31 of 46 patients. Eight patients had idiopathic dilated cardiomyopathy. In 39 of 46 patients, the defibrillation threshold could be successfully determined at all 4 time points after implantation. The mean defibrillation energy requirement at the time of implantation was 9.2 +/- 5.9 Joules (J). The subsequent mean energy requirements were 7.6 +/- 4.8 J at pre-hospital discharge, 8.6 +/- 5.7 J at the 3 month, 8.1 +/- 6.0 J at the 6 month and 8.6 +/- 5.8 J at the 12 month follow-up visits. The mean defibrillation threshold was lowest at the time of prehospital discharge, significantly lower than at the time of initial implantation (p = 0.021). However, at all later time points up to one year, there was no significant difference in the DFT as compared with the time of initial implantation. Comparing the DFT at the time of implantation and the DFT at all other time points, there were no significant differences (9.23 vs. 8.56 J, p = 0.291). Although there was an initial decrease in the DFT at seven to ten days, the long-term stability of the DFT up to one year remained stable in the devices with the "active-can" lead system.