Functional mri of human brain activation combining high spatial and temporal resolution by a cine flash technique

Functional mapping of human brain activation has been accomplished at high spatial and temporal resolution (voxel size 4.9 μl, temporal increment 100 ms). The approach was based on oxygenation-sensitive long-echo time FLASH MRI sequences synchronized to multiply repeated cycles of visual stimulation in a CINE acquisition mode. This high temporal resolution revealed that stimulus-related signal intensity changes in human visual cortex display an initial latency followed by increases extending over several seconds. Furthermore, the temporal characteristics of the complete CINE MRI signal time course depended on the absolute and relative durations of activation and control periods and, for example, caused an apparent absence of a poststimulation “undershoot” phenomenon. Complementing hyperoxygenation due to rapid hemodynamic adjustments, these results suggest signal intensity modulation by enhanced oxygen consumption and concomitant deoxygenation during prolonged and/or repetitive stimulation.     

Wirkung des Äthylazetatextraktes von Chrysanthemum morifolium auf Plasmodium falciparumIn Vitro

Zusammenfassung Die Wirkung des ?thylazetatextraktes von Chrysanthemum morifolium auf P. falciparum wurde in vitro untersucht. W?hrend sich die Parasit?mie bei der Kontrollgruppe bis zu 10. 90 % entwickelte, wurde bei dem mit ?thylazetatextrakt in einer Konzentration von 100 μg/ml Medium am 5. Tag der Kultur eine signifikante Hemmwirkung auf die Parasiten beobachtet. Die Parasit?mie blieb bei 1. 00 %.

Diese Arbeit wurde durch die Stiftung von “National Nature Science Foundation of China” finanziert (No. 39260066)     

Necrosectomy and postoperative local lavage in patients with necrotizing pancreatitis: Results of a prospective clinical trial

Seventy-four patients with necrotizing pancreatitis were included in a prospective clinical trial of a surgical management protocol comprising necrosectomy and postoperative local lavage of the lesser sac and of the necrosis cavity. Fifty-eight patients showed preoperative organ failures such as pulmonary dysfunctions (57%), renal dysfunctions (37%), shock (12%), and sepsis (26%) in spite of intensive care treatment. The median value of the early prognostic signs was 4.5 points. Intraoperatively, 62% of the patients revealed extensive intrapancreatic parenchymal necrosis, 69% had extrapancreatic necrosis, and 39% showed bacterial contamination of the necrotic material. Following the necrosectomy, postoperative local lavage was performed for an average period of 25 days with 7 liters (median) of lavage fluid per 24 hours. In each of 18 studied patients, a considerable release of immunoreactive trypsin was demonstrated and, in each of 20 studied patients, a high concentration of immunoreactive phospholipase A₂ was demonstrated in the lavage fluid up to the 12th/14th postoperative day. The intensive care period averaged 6 1/2 days, the hospital stay averaged 54 days. The hospital mortality rate was 8.1%. It is concluded that restricted necrosectomy and postoperative local lavage treatment correspond in particular to the pathomorphologic conditions and to the local release of biologically active compounds such as bacteria, endotoxin, trypsin, and phospholipase A₂ in patients with necrotizing pancreatitis.

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Resumen Setenta y cuatro pacientes con pancreatitis necrotizante fueron incluídos en un ensayo clínico prospectivo aplicando un protocolo de manejo quirÚrgico que comprende necrosectomía y lavado peritoneal postoperatorio de la transcavidad de los epiplones y de la cavidad necrótica. Cincuenta y ocho pacientes exhibierion fallas orgánicas postoperatorias tales como disfunción pulmonar (57%), disfunción renal (37%), shock (12%), y sepsis (26%) a pesar de cuidado intensivo. El valor promedio de los signos précoces pronóstico (Ranson), con exclusión de la retención de líquido fue de 4.5 puntos. Los hallazgos intraoperatorios revelaron necrosis pancreática extensa en 62% de los pacientes, necrosis extrapancreática en 69%, y contaminación bacteriana del material necrótico en 39%. Realizada la necrosectomía se instauró lavado peritoneal postoperatorio por un período promedio de 25 días con 7 litros (promedio) de líquido por cada 24 horas. En cada uno de los 18 pacientes estudiados se demostró liberación considerable de tripsina inmunorreactiva, así como una elevada concentración de fosfolipasa A₂ inmunorreactiva, en el líquido de lavado hasta el 12/14 días postoperatorios. El período de cuidado intensivo fue de 6 1/2 días, y la hospitalización de 54 días en promedio. La mortalidad hospitalaria fue de 8.1%. En conclusión, se plantea que el tratamiento mediante la necrosectomía restringida y el lavado peritoneal local postoperatorio está indicado en pacientes con las condiciones patomorfológicas de pancreatitis necrotizante que resultan en la liberación local de compuestos biológicamente activos tales como bacterias, endotoxina, tripsina, y fosfolipasa A₂. Serán necesarios ulteriores estudios clínicos controlados para confirmar los resultados favorables que hemos obtenido con la necrosectomía y el lavado peritoneal postoperatorio en pacientes con pancreatitis necrotizante y extensa e infectada necrosis pancreática.

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Résumé Un essai prospectif d'une méthode de traitement chirurgical consistant en nécrosectomie associée au lavage de l'arrière cavité des épiploons et de la cavité nécrotique a concerné 74 malades présentant une pancréatite nécrotique. Malgrè le traitement intensif 58 d'entre eux ont accusé des complications telles que troubles pulmonaires (57%), rénaux (37%), choc (12%), et infection (26%). La valeur moyenne des signes de pronostic précoce fut de 4.5 points. A l'intervention 62% des opérés présentaient une nécrose pancréatique étendue, 69% des opérés une nécrose extra-pancréatique, 39% une surinfection du tissu pancréatique. Après l'exèrése de la nécrose le lavage fut pratiqué quotidiennement avec en moyenne 7 litres de liquide pendant une période de 25 jours. Chez 18 malades fut constaté une libération importante de trypsine immunoactive et chez 20 malades un taux élevé de phospholipase cA dans le liquide de lavage pendant 12/14 jours après l'intervention. La durée des soins intensifs fut en moyenne de 6.5 jours et celle de l'hospitalisation de 54 jours. Le taux de mortalité opératoire fut de 8.1%. On peut conclure de ces faits que la nécrosectomie limitée, associée au lavage local constitue un traitement adapté aux lésions et à la libération locale d'éléments biologiques pathologiques: bactérie, endotoxine, trypsine, et phospholipase A au cours de la pancréatite nécrotique.

     

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Summary Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activiy in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m² and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m². At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m² consisted of ocular symptoms (light flashes) accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m²/1 hour was considered the MTD. There were four deaths on study, all considered diseaserelated. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center.The recommended dose for phase II trials derived from our results is 12,550 mg/m²/2 hours. However, with regard to experiences in other phase I studies, the subsequent phase II studies will be performed with a dose of 6,500 mg/m².     

A Biotin–Avidin-Based Enzyme Immunoassay for βh-Endorphin

An avidin–biotin enzyme-linked immunosorbent assay (ELISA) is described for _h-endorphin (_h-EP). Microtiter plates coated with commercially available antibodies were used together with _h-EP tracer derivatives that were biotinylated in positions 24, 28, and 29 via a C₆ spacer arm. Nonspecific binding of biotinylated derivatives to the microtiter plates was blocked with a mixture of 1% casein and 10% ethanolamine in 0.1 M NaHCO₃. A sequential saturation procedure using a high-affinity antiserum in combination with an avidin–alkaline phosphatase complex matched the sensitivity of reported radioimmunoassays (RIAs), with a detection limit of 0.5 fmol/assay. The intra- and interassay coefficients of variation were 5 and 12%, respectively. Results obtained by ELISA and RIA showed good correlations (r = 0.95). The -EP concentration in extracted rat plasma after high-performance liquid chromatographic (HPLC) fractionation was determined by this method to be 1600 fmol/ml.     

Can a clinician predict the technical equipment a patient will need during intensive care unit treatment? An approach to standardize and redesign the intensive care unit workstation

The technical equipment of today's intensive care unit (ICU) workstation has been characterized by a gradual, incremental accumulation of individual devices, whose presence is dictated by patient needs. These devices usually present differently designed controls, operate under different alarm philosophies, and cannot communicate with each other. By contrast, ICU workstations could be equipped permanently and in a standardized manner with electronically linked modules if the attending physicians could reliably predict, at the time of admission, the patient's equipment needs. Over a period of 3 1/2 months, the doctors working in our 20-bed surgical ICU made 1,000 predictions concerning outcome, equipment need, duration of artificial ventilation, and duration of hospitalization for 300 recently admitted patients. The interviews were made within the first 24 hours after admission. The doctors being interviewed were usually (i.e., in over 90% of cases) unfamiliar with the patient. Information concerning the patient's general state of health, special pre-ICU events, and complications was offered to the interviewed clinician because this information represents standard admission data. It was found that the equipment need (represented by two different setups, high tech and low tech) could be predicted most reliably (96.4% correct predictions) compared with a prediction on outcome of ICU treatment (94.5%), on duration of artificial ventilation (75.4%), and on duration of stay (43.4%). There was no significant (p>0.05) difference in the reliability of predictions between residents and consultants. Factors influencing the postoperative equipment need varied with surgical specialty. The general state of health, as indicated by the ASA classification (p<0.001), and the specific intervention (all multiple-valve replacements needed the high-level equipment standard) appeared to be most important in cardiac surgery, while a state of septicemia was important in general surgery (p<0.001). Our findings suggest that ICU workstations may be standardized into at least two types.     

Effect of Ethanol and Stress on Plasma Catecholamines and Their Relation to Changes in Emotional State and Performance

The "tension reduction hypothesis" of ethanol was investigated with respect to stress- and ethanol-induced changes of plasma catecholamines and their relations to changes in emotional state and performance. Twenty-two healthy male volunteers were tested under the influence of 0.8 g/kg ethanol and compared to 22 matched controls receiving a placebo drink. Stress was induced by mental arithmetic applied prior to and 45 min after fluid consumption. Plasma epinephrine (E) and norepinephrine (NE) obtained from an indwelling cannula inserted 50 min prior to stress application were determined prior to and after each stress session. Percentage changes were compared within and between groups and correlated with respective changes of emotional states and performance in mental arithmetic. While ethanol decreased performance and stress-related emotional arousal, it did not affect stress-induced changes in plasma catecholamines. Rather, the fluid (ethanol as well as placebo) increased NE levels. Emotional tension reduction was associated with low resting or average levels of E in the placebo group but this relationship was disrupted by ethanol. High NE resting levels and drink induced increases predicted emotional tension reduction with placebo but an increase in stress induced depression with alcohol. "Biochemical tension reduction" (represented by both reduced E and NE stress response) may be predicted from generally lower levels of activation and elation by alcohol but not with the placebo condition. Although performance was positively related to low NE resting levels and stress responses, no influence of alcohol on this relationship was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measured attenuation correction methods

Accurate attenuation correction is a prerequisite for the determination of exact local radioactivity concentrations in positron emission tomography. Attenuation correction factors range from 4–5 in brain studies to 50–100 in whole body measurements. This report gives an overview of the different methods of determining the attenuation correction factors by transmission measurements using an external positron emitting source. The long-lived generator nuclide⁶⁸Ge/⁶⁸Ga is commonly used for this purpose. The additional patient dose from the transmission source is usually a small fraction of the dose due to the subsequent emission measurement. Ring-shaped transmission sources as well as rotating point or line sources are employed in modern positron tomographs. By masking a rotating line or point source, random and scattered events in the transmission scans can be effectively suppressed. The problems of measured attenuation correction are discussed: transmission/emission mismatch, random and scattered event contamination, counting statistics, transmission/emission scatter compensation, transmission scan after administration of activity to the patient. By using a double masking technique simultaneous emission and transmission scans become feasible.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)