Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET.

The aim of this study was to assess synovitis by (18)F-FDG PET in an individual joint analysis and in a global analysis of rheumatoid arthritis (RA) disease activity and to compare (18)F-FDG PET parameters with clinical, biologic, and sonographic (US) rheumatoid parameters. METHODS: Three hundred fifty-six joints were assessed in 21 patients with active RA: the knees in all subjects and either wrists as well as metacarpophalangeal and proximal interphalangeal joints in 13 patients, or ankles and the first metatarsophalangeal joints in the remaining 8 patients. PET analysis consisted of a visual identification of (18)F-FDG uptake in the synovium and measurements of standardized uptake values (SUVs). Independent assessors performed the clinical and US examinations. RESULTS: PET positivity was found in 63% of joints, whereas 75%, 79%, and 56% were positive for swelling, tenderness, and US analysis, respectively. Both the rate of PET-positive joints and the SUV increased with the number of positive parameters present (swelling, tenderness, US positivity) and with the synovial thickness. The mean SUV was significantly higher in joints where a power Doppler signal was found. In a global PET analysis, the number of PET-positive joints and the cumulative SUV were significantly correlated with the swollen and tender joint counts, the patient and physician global assessments, the erythrocyte sedimentation rate and C-reactive protein serum levels, the disease activity score and the simplified disease activity index, the number of US-positive joints, and the cumulative synovial thickness. CONCLUSION: (18)F-FDG PET is a unique imaging technique that can assess the metabolic activity of synovitis and measure the disease activity in RA.     

Efficacy and safety of topical application of human fibrinogen/thrombin-coated collagen patch (TachoComb) for treatment of air leakage after standard lobectomy.

OBJECTIVES: Persisting air leakage after pulmonary resection remains a significant problem. The aim of the study was to evaluate the incidence of air leakage after standard lobectomy and test the efficacy and safety of TachoComb (TC). METHODS: A total of 189 patients undergoing lobectomy were enrolled in a multi-centre, open, randomised, and prospective study to test the efficacy and safety of TachoComb (TC) for air leakage treatment. Air leakage was assessed by water submersion test, and scored as grades 0 if no, 1 if countable, 2 if a stream of and 3 if coalescent bubbles have been observed. Any sites with grade 3 air leakage received further stapling or limited suturing until grade 0, 1 or 2 was obtained. Treatment of air leakage was done with TC or suturing according to randomisation. Air leakage was assessed by further submersion tests. Postoperative air leakage was assessed using the Pleur-Evac system. RESULTS: Overall incidence of air leakage 48+/-6 h after surgery was 34% for TC and 37% for standard treatment (P=0.76). The reduction of intra-operative air leak intensity in the subgroup with grades 1-2 was significantly higher for the TC group (P=0.015). Postoperative air leakage intensity in the subgroup with air leakage grades 1-2 was lower for TC than standard treatment (P=0.047). The mean duration of postoperative air leakage in the subgroup with grades 1-2 was shorter for the TC group than for standard treatment, i.e. 1.9+/-1.4 vs. 2.7+/-2.2 days (P=0.015). CONCLUSIONS: TC could be proven as well-tolerated and safe. In the subgroup of patients with established air leakage, TC showed superior potential in reduction of intra-operative air leakage as well as in reduction of intensity and duration of postoperative air leakage.     

Morphine Enhances Pharmacological Preconditioning by Isoflurane: Role of Mitochondrial KATP Channels and Opioid Receptors

Background: Adenosine triphosphate-regulated potassium channels mediate protection against myocardial infarction produced by volatile anesthetics and opioids. We tested the hypothesis that morphine enhances the protective effect of isoflurane by activating mitochondrial adenosine triphosphate-regulated potassium channels and opioid receptors.

Methods: Barbiturate-anesthetized rats (n = 131) were instrumented for measurement of hemodynamics and subjected to a 30 min coronary artery occlusion followed by 2 h of reperfusion. Myocardial infarct size was determined using triphenyltetrazolium staining. Rats were randomly assigned to receive 0.9% saline, isoflurane (0.5 and 1.0 minimum alveolar concentration [MAC]), morphine (0.1 and 0.3 mg/kg), or morphine (0.3 mg/kg) plus isoflurane (1.0 MAC). Isoflurane was administered for 30 min and discontinued 15 min before coronary occlusion. In eight additional groups of experiments, rats received 5-hydroxydecanoic acid (5-HD; 10 mg/kg) or naloxone (6 mg/kg) in the presence or absence of isoflurane, morphine, and morphine plus isoflurane.

Results: Isoflurane (1.0 MAC) and morphine (0.3 mg/kg) reduced infarct size (41 +/- 3%; n = 13 and 38 +/- 2% of the area at risk; n = 10, respectively) as compared to control experiments (59 +/- 2%; n = 10). Morphine plus isoflurane further decreased infarct size to 26 +/- 3% (n = 11). 5-HD and naloxone alone did not affect infarct size, but abolished cardioprotection produced by isoflurane, morphine, and morphine plus isoflurane.     

Detection of microemboli in the subclavian vein of patients undergoing haemodialysis and haemodiafiltration using pulsed Doppler ultrasound.

BACKGROUND: The pathophysiology leading to pulmonary side effects during haemodialysis and haemodiafiltration is not yet fully understood. Chronic microembolization, which can be demonstrated by pulsed Doppler ultrasound, may be one cause. METHODS: The study cohort consisted of 24 long-term dialysis patients undergoing haemodialysis (n=21) and online-haemodiafiltration (n=3), respectively. The subclavian vein downstream to the venous access was investigated during different phases of the procedure using a 2-MHz pulsed ultrasound device. RESULTS: In all periods investigated (connection, dialysis, disconnection), numerous microembolic signals (MES) were found in the subclavian vein. The numbers of MES detected during haemodiafiltration (314-709 MES per 10 min) were higher than during haemodialysis (0-81 MES per 10 min). CONCLUSIONS: The composition (gaseous or solid) and origin (pump, tubing system or shunt) of the microemboli detected remains unclear. Chronic microembolization may be one cause of pulmonary complications of haemodialysis and haemodiafiltration. The detection method described in this article will help us to better understand this process and to determine what role microemboli might play in pulmonary and central nervous system disorders. It may also help to optimize the devices and techniques used.     

Zur copolymerisation von ethylen und α-olefinen mit ziegler-katalysatoren

Starting with four reaction equations which are at least necessary to describe the copolymerization of two monomers, equations for the kinetics and the molecular weight regulation with and without hydrogen are derived. The equations are used to evaluate the results of the copolymerization of ethylene and 1-butene. The numerical values of the reactivity ratios r differ by approximately 3 orders of magnitude, but do not depend on whether the molecular weight is regulated by hydrogen or not. The rate of polymerization is scarcely influenced even by great amounts of 1-butene. It depends nearly completely on the concentration of ethylene. On the other hand the comonomer enormously influences the average molecular weight of the copolymer. This influence increases with hydrogen content.     

Die doppler-sonographische beurteilung der funktionsfähigkeit extra-intracranieller anastomosen

Zusammenfassung Wir berichten fiber die Doppler-sonographischen Ergebnisse bei 33 Patienten mit einer Anastomose zwischen der A. temporalis superficialis and der A. cerebri media. Die Indikation zur Bypass-Operation beinhaltete rezidivierende TIA oder ein kurz zuvor erworbenes leichtes neurologisches Defizit bei angiographischem Nachweis einseitiger oder beidseitiger tiefer Obliterationen der A. carotis interna und hochgradiger Stenosen oder Verschlüsse im distalen Abschnitt der A. carotis interna bzw. im proximalen Abschnitt der A. cerebri media. Die Funktionsfahigkeit der Anastomose wurde überpriift durch die Berechnung der modifizier ten Pourcelot-Indices (relative enddiastolische Strömungsgeschwindigkeit) der A. temporalis superficialis praeauriculär und am Bohrlochrand Bowie durch den EinfluB der intermittierenden Kompression des den Bypass-versorgenden Gefäßes auf den modifizierten Pourcelot-Index der ipsilateralen A. carotis communis. Bei allen Patienten mit funktionsfahigen Anastomosen, definiert durch einen modifizierten Pourcelot-Index von zumindest 0,20 am Bohrlochrand, kam es zu einer Reduktion dieses Parameters um durchschnittlich 0,08 an der A. carotis communis bei kurzfristiger Kompression des den Bypass-versorgenden Astes. Bei den 18 Patienten mit unilateraler Obliteration der A. carotis interna war der Bypass über-wiegend dann funktionsfähig, wenn die summierten modifizierten Pourcelot-Indices der verbliebenen hirnversorgenden Gefäße um zumindest 10% gegenüber einem vergleichbaren Normalkollektiv reduziert waren. Das Vorhandensein bzw. das Fehlen von Ophthalmica-Kollateralen hatte dabei keinen Einfluß auf den Prozentsatz der funktionsfahigen Anastomosen in diesen Untergruppen. Bei den vier Patienten mit bilateraler Obliteration der A. carotis interna war die angelegte Anastomose in jedem Fall funktionsfähig, während die Hälfte der Patienten mit Stenosen and Verschlüssen im distalen Abschnitt der Carotisstrombahn nur eine ungeniigende Bypass-Funktion zeigten. Die zwei Patienten mit einer Mediahauptstammstenose bzw. -obliteration hatten Indices von 0,45 bzw. 0,46 am Bohrlochrand als Hinweis auf die Funktionstüchtigkeit. Wir Bind der Auffassung, daß man mittels Doppler-sonographischer Kriterien die Funktionsfahigkeit einer Temporalis superficialis-Cerebri media-Anastomose überprüfen kann. Der praeoperativ berechnete summierte modifizierte Pourcelot-Index der verbliebenen hirnversorgenden Arterien kann zumindest bei uni- and bilateraler Internaobliteration als zusatzlicher Parameter herangezogen werden, um die Indikation zur Bypass-Operation zu klären.     

Haemodynamics as a determinant of the pharmacokinetics of and the plasma catecholamine responses to isoprenaline

Summary The total body clearance and fractional extraction of isoprenaline (ISO) have been determined, and the relation between these parameters and cardiac output established. Whether desipramine, an inhibitor of neuronal uptake, altered the plasma catecholamine response to ISO was also investigated.Seven healthy subjects were given i.v., infusions of ISO in two, consecutive 25-min periods, at constant dose rates of 31–43 and 80–124 pmol·kg^–1·min^–1, respectively. The total-body (ER), pulmonary (ER_p) and forearm (ER_f) fractional extractions and the total body clearance (CL) of ISO were obtained from measurements of cardiac output and the steady-state ISO concentration in mixed central venous, arterial and forearm venous plasma.ISO-induced increases in cardiac output resulted in increases in CL, decreases in ER and no consistent change in ER_f. ER_p did not differ from zero. ISO also produced a dose-dependent increase in the mixed venous plasma concentrations of noradrenaline and 3,4-dihydroxyphenylglycol (DOPEG), and a decrease in that of adrenaline. Pretreatment with desipramine did not alter any of the pharmacokinetic parameters of ISO. Desipramine, however, reduced the mixed venous baseline plasma levels of noradrenaline (47%) and DOPEG (40%), and tended to reduce that of adrenaline (34%). It enhanced the plasma noradrenaline response 2.4-fold, abolished the plasma DOPEG response and did not alter the plasma adrenaline response to ISO.Hence, owing to its haemodynamic effects, ISO modifies its own pharmacokinetics which involve non-neuronal removal processes only. The increased DOPEG in plasma resulting from the ISO-induced increase in noradrenaline release was presynaptic in origin. Desipramine appears to reduce sympathetic activity. The enhancement by desipramine of the ISO-induced increase in plasma noradrenaline points towards recapture by neuronal uptake of at least 58% of the noradrenaline released in response to ISO.