Continuous venovenous hemofiltration improves arterial oxygenation in endotoxin-induced lung injury in pigs.

BACKGROUND: Hypoxemia is common in septic acute lung failure. Therapy is mainly supportive, and most trials using specific inhibitors of key inflammatory mediators (ie., tumor necrosis factor alpha, interleukin 1) have failed to prove beneficial. The authors investigated if a nonspecific blood purification technique, using zero-balanced high-volume continuous venovenous hemofiltration (CWH), might improve arterial oxygenation in a fluid-resuscitated porcine model of endotoxin-induced acute lung injury. METHODS: Piglets of both sexes weighing 25-30 kg were anesthetized and mechanically ventilated. After baseline measurements, animals received an intravenous infusion of 0.5 mg/kg endotoxin (Escherichia coli lipopolysaccharide). One hour after endotoxin, animals were randomly assigned to either treatment with CWH (endotoxin + hemofiltration, n = 6) or spontaneous course (endotoxin, n = 6). At 4 h after randomization, animals were killed. Hemofiltration was performed from femoral vein to femoral vein using a standard circuit with an EF60 polysulphone hemofilter. RESULTS: Endotoxin challenge induced arterial hypoxemia, an increase in peak inspiratory pressure, pulmonary hypertension, and systemic hypotension. Treatment with CWH did not improve systemic or pulmonary hemodynamics. However, arterial oxygenation was increased in endotoxin-challenged animals at 5 h after completion of endotoxin infusion, as compared with animals not receiving CVVH (arterialoxygen tension, 268+/-33 vs. 176+/-67 mm/Hg, respectively, P < 0.01). In addition, treatment with CWH attenuated the endotoxin-induced increase in peak inspiratory pressure and increased lung compliance. CONCLUSION: These results suggest that nonspecific blood purification with high-volume CWH improves arterial oxygenation and lung function in endotoxin-induced acute lung injury in pigs, independent of improved hemodynamics, fluid removal, or body temperature.

Red cell antibodies in frequently transfused patients with myelodysplastic syndrome.

Therapy for myelodysplastic syndrome (MDS) is often restricted to lifelong support with red blood cell units (RBCU). A variety of immune phenomena associated with antibody production have been reported in MDS patients. Therefore, we hypothesized that red cell antibodies are more frequent in patients with MDS compared to other regularly transfused patients. Red cell antibodies were determined in 42 MDS patients, in 28 patients with other hematological disorders, and in a historical group of 129 patients with end-stage renal failure. All of these patients received frequent red cell substitution therapy, at least two RBCU in biweekly intervals. Red cell antibodies were detected in 9 of 42 patients with MDS, in 3 of 28 patients with other hematological disorders, and in 4 of 129 patients with end-stage renal failure. Evidence of red cell antibodies was displayed by 6 of 27 MDS patients treated with prestorage leukocyte-depleted RBCU and 3 of 15 MDS patients transfused with bedside leukocyte-filtered RBCU. Red cell antibodies are frequent in patients with hematological disorders who require repetitive red cell transfusions. The formation of alloantibodies to red cell antigens is as frequent in MDS patients as in other patients with hematological disorders.

Synthesis and reactivity studies of model complexes for molybdopterin-dependent enzymes.

The molybdenum cofactor (Moco)-containing enzymes are divided into three classes that are named after prototypical members of each family, viz. sulfite oxidase, DMSO reductase and xanthine oxidase. Functional or structural models have been prepared for these three prototypical enzymes: (i) The complex [MoO2(mnt)2]2- (mnt2- = 1,2-dicyanoethylenedithiolate) has been found to be able to oxidize hydrogen sulfite to HSO4- and is thus a functional model of sulfite oxidase. Kinetic and computational studies indicate that the reaction proceeds via attack of the substrate at one of the oxo ligands of the complex, rather than at the metal. (ii) The coordination geometries of the mono-oxo [Mo(VI)(O-Ser)(S2)2] entity (S2 = dithiolene moiety of molybdopterin) found in the crystal structure of R. sphaeroides DMSO reductase and the corresponding des-oxo Mo(IV) unit have been reproduced in the complexes [M(VI)O(OSiR3)(bdt)2] and [M(VI)O(OSiR3)(bdt)2] (M = Mo,W; bdt = benzene dithiolate). (iii) A facile route has been developed for the preparation of complexes containing a cis-Mo(VI)OS molybdenum oxo, sulfido moiety similar to that detected in the oxidized form of xanthine oxidase.

[Cp2V] migration along an octatetrayne chain: from the monometallic complex (Cp2V(2-4eta-tBuC triple bond C2-C triple bond CC triple bond CtBu)] to the dimetallic complex.

The oxidative addition of one equivalent of [Cp2V] (4) to the tetrayne ligand tBuC triple bond CC triple bond CC triple bond CC triple bond CtBu (5) gives the monometallic complex [Cp2V(3-4eta-tBuC triple bond C-C2-C triple bond CC triple bond CtBu)] (7). Compound 7 reacts further with a second equivalent of [Cp2V] to give the dimetallic complex [(Cp2V)2(1-2eta:7-8eta-tBuC2-C triple bond CC triple bond C-C2tBu)] (8), which involves a shift of the first coordinated [Cp2V] unit from the internal C3-C4 to the external C1-C2 positions on the alkynyl ligand. Compound 8 is also directly obtained by the addition of two equivalents of [Cp2V] to 5. Reversibly, reaction of 8 with 5 leads to 7. This exchange reaction between 7 and 8 by adding successively 5 and 4 has been monitored by EPR spectroscopy. By contrast, the oxidative addition of one or two equivalents of [Cp2V] to the tetrayne ligand PhC triple bond CC triple bond CC triple bond CC triple bond CPh (6) gives the homodimetallic complex [(Cp2V)2(1-2eta:7-8eta-PhC2-CC triple bond CC triple bond C-C2-Ph)] (9). Both monometallic and dimetallic complexes 7, 8, and 9 have been characterized by X-ray diffraction. Magnetic moment measurements for 8 and 9 from 300 to 4 K indicated a weak antiferromagnetic J exchange coupling of -12.5 and -4.1 cm(-1), respectively.

Controlled airway pressure therapy, nitric oxide inhalation, prone position, and extracorporeal membrane oxygenation (ECMO) as components of an integrated approach to ARDS.

BACKGROUND: Recent years have seen the introduction of innovative additive therapies for acute respiratory distress syndrome. However, because there are no reliable predictors of response to a particular therapy, potential responders to a specific therapeutic intervention may be lost. Therefore, the authors evaluated the effect of a combined therapeutic approach on the survival of patients with acute respiratory distress syndrome, when treated according to a strict algorithm. METHODS: During a 2.5-yr period, 84 patients with acute respiratory distress syndrome were assigned to a standardized treatment protocol. Data analysis was performed by retrospective review of patient charts. Patients were treated using a stepwise treatment algorithm of pressure-controlled ventilation (peak airway pressure < 35 cm H2O), positive end-expiratory pressure (PEEP; 12-15 cm H2O), permissive hypercapnia, inhaled nitric oxide (5-20 ppm), and prone positioning. These interventions were termed "conventional therapy." Response to treatment was defined as a more than 20% increase in arterial oxygen tension (PaO2). Nonresponders were triaged to extracorporeal membrane oxygenation. RESULTS: The overall survival rate was 80%. All patients received conventional therapy up to 96 h; 71 responded to conventional therapy and 59 survived (83%). Thirteen patients (15%) did not respond to conventional therapy and underwent extracorporeal membrane oxygenation; 8 of these patients (62%) survived. For the group, the mean admission lung injury score was 3.3+/-0.5, the PaO2/fractional inspired oxygen tension (F(I)O2) ratio was 96+/-45, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score was 18+/-6. CONCLUSIONS: The 80% overall survival rate achieved in this group of patients with severe acute respiratory distress syndrome may in part reflect the additive beneficial effects of combined treatment methods, such as airway pressure control, nitric oxide inhalation, prone position, and early triage of nonresponders to extracorporeal membrane oxygenation.

Analgesic and hemodynamic effects of intrathecal clonidine as the sole analgesic agent during first stage of labor: a dose-response study.

BACKGROUND: Intrathecal clonidine produces dose-dependent postoperative analgesia and enhances labor analgesia from intrathecal sufentanil. The authors evaluated the dose-response potency of intrathecally administered clonidine by itself during first stage of labor with respect to analgesia and maternal and fetal side effects. METHODS: Thirty-six parturients requesting labor analgesia were included in this prospective, randomized, double-blind study. Parturients with < 6 cm cervical dilatation received either 50, 100, or 200 microg intrathecal clonidine. The authors recorded visual analog pain score (VAPS), maternal blood pressure and heart rate, ephedrine requirements, and sedation at regular intervals and fetal heart rate tracings continuously. Duration of analgesia was defined as time from intrathecal clonidine administration until request for additional analgesia. RESULTS: Clonidine produced a reduction in VAPS with all three doses. The duration of analgesia was significantly longer in patients receiving 200 microg (median, 143; range, 75-210 min) and 100 microg (median, 118; range, 60-180 min) than 50 microg (median, 45; range, 25-150 min), and VAPS was lower in the 200-microg than in the 50-microg group. In the 200-microg group, hypotension required significantly more often treatment with ephedrine than in the other groups. No adverse events or fetal heart rate abnormalities occurred. CONCLUSIONS: Fifty to 200 microg intrathecal clonidine produces dose-dependent analgesia during first stage of labor. Although duration and quality of analgesia were more pronounced with 100 and 200 microg than with 50 microg, the high incidence of hypotension requires caution with the use of 200 microg for labor analgesia.

The efficacy and safety of a clonidine/bupivacaine combination in caudal blockade for pediatric hernia repair.

UNLABELLED: We evaluated the analgesic efficacy and hemodynamic and respiratory safety of clonidine when added to bupivacaine for caudal blocks in 58 children aged 38 +/- 2 mo (mean +/- SEM). Patients scheduled for ambulatory hernia repair were randomly given a caudal injection (0.75 mL/kg) of either saline placebo (P group), bupivacaine, 0.25% (B group), bupivacaine plus epinephrine 1:200,000 (BE group), bupivacaine plus clonidine 1 microgram/kg (BC1 group), or bupivacaine plus clonidine 2 micrograms/kg (BC2 group). Postoperative measurements included duration of analgesia, hemodynamics, and respiratory monitoring for 6 h. Thereafter, parents assessed their child's analgesic requirements at home every 3 h for 18 h. The duration of analgesia (median [range]) was significantly longer (P < 0.05) in the BC1 and BC2 groups (360 [270-360] min and 360 [355-360] min, respectively) compared with the P (77[45-190]), B (346[105-360]), or BE group (300[75-360]). Similarly, the BC1 and BC2 groups required less additional analgesic within the first 24 h. All groups showed a significant decrease in mean arterial pressure compared with baseline values, but the differences among the groups were not significant. Bradycardia and respiratory depression were not observed. Clonidine 1 and 2 micrograms/kg can be safely added to bupivacaine caudal blockade in small children for ambulatory hernia repair to achieve an increased duration of analgesia compared with bupivacaine alone or bupivacaine plus epinephrine. IMPLICATIONS: The addition of clonidine, an antihypertensive drug with analgesic properties, to local anesthetics in caudal blocks prolongs postoperative pain relief and reduces the need for additional pain treatment in children after hernia operation.

[Historical development of surgical wisdom tooth extraction]. / Die Entwicklung der operativen Weisheitszahnentfernung.

Surgical removal of the wisdom teeth is a routine procedure nowadays. Only at the end of the nineteenth century the use of local anesthesia together with the development of radiology led to the establishment of surgical dentistry. Especially the technique of removal of the lower third molar was totally changed and modified many times, depending on the position of the wisdom teeth. First hand instruments were used; later, mechanical devices for bone resection and tooth splitting were employed. Since the 1950s, highly dangerous infections have become rare, thanks to the use of antibiotics. Many publications concerning incision procedure, bone resection and tooth splitting marked the following years.

Granulocyte colony-stimulating factor (rh G-CSF) as an adjunct to interferon alpha therapy of neutropenic patients with hairy cell leukemia.

Six patients with hairy cell leukemia (HCL) and neutropenia (median neutrophil count 563/microliters, range 30-1200) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 5 micrograms/kg by daily subcutaneous injection as an adjunct to interferon-alpha (IFN-a) therapy, in order to ameliorate neutropenia. Five of six patients responded to G-CSF with normalization of neutrophil counts (> 1800/microliters) within 2-11 days and a median neutrophil count of 5211/microliters (range 4312-10160) at the end of G-CSF therapy. In three of these patients, infections resolved when neutropoiesis recovered. In one patient with very severe neutropenia (30/microliters), in whom myeloid progenitors were not detectable, G-CSF therapy failed to restore granulopoiesis. Cessation or interruption of G-CSF after 2-5 weeks of therapy resulted in a rapid decline of neutrophil counts to lower or subnormal levels (median value 1478/microliters, range 770-2739) within 1 week, suggesting that the improvement of granulopoiesis was dependent on G-CSF and not due to IFN-a therapy. G-CSF may be a useful adjunct to IFN-a therapy in patients with HCL in order to manage or prevent neutropenic complications in the early phase of treatment.

Treatment of drug-induced agranulocytosis with recombinant granulocyte colony-stimulating factor (rh G-CSF).

Five patients with drug-induced agranulocytosis received 300 micrograms recombinant human granulocyte colony-stimulating factor (rh G-CSF) subcutaneously twice daily for 2-5 days. G-CSF therapy resulted in a steep increase of the neutrophil count, which was faster than that in patients with spontaneous recovery reported in the literature. In all four patients with infectious complications fever rapidly declined with the increase of granulocytes. G-CSF may be useful in the management of drug-induced agranulocytosis.