Inhibition of IL-1 induced tissue factor (TF) synthesis and procoagulant activity (PCA) in purified human monocytes by IL-4, IL-10 and IL-13

Exposure of monocytes to pro-inflammatory cytokines or lipopolysaccharide (LPS) may induce synthesis and expression of tissue factor (TF). In this paper we have focused on the induction of TF-activity in human monocytes by the pro-inflammatory cytokines recombinant human interleukin 1 (rhIL-1 alpha) (rhIL-1 beta) (rhIL-6) and human tumour necrosis factor alpha (rhTNF-alpha), measured as procoagulant activity (PCA) in a microtitre plate-based clot assay. In addition we have studied the modulation of IL-1 alpha/beta induced TF-mRNA and PCA by rhIL-4, rhIL-10 and rhIL13. IL-1 alpha and IL-1 beta induced a concentration dependent increase in TF-activity. Neither IL-6 nor TNF-alpha gave rise to procoagulant activity at the concentrations tested (0.2-20 ng/ml). IL-4, IL-10 and IL-13, all effectively diminished IL-1 alpha/beta induced PCA, shown at the protein- and at the mRNA-level, while cell viability was unaffected. These results add to the previously demonstrated role of IL-4 and IL-10 as inhibitors of LPS-induced TF-activity, showing that these anti-inflammatory cytokines are not specific for LPS-activation but interfere with other stimulating substances such as IL-1, which may be involved in diseases where LPS is not present.     

Blocking filter vents increases carbon monoxide levels from ultralight, but not light cigarettes

Effect of vent blocking on carbon monoxide (CO) exposure from a best-selling light cigarette was examined in 12 daily cigarette smokers. Mean CO boosts were not different from each other with (a) 0% filter vents blocked (5.0 ppm), (b) vents covered with lips (4.9 ppm), (c) 50% of vents covered with tape (4.8 ppm), and (d) vents covered with a pinch of the fingertips (4.9 ppm). A second study in another 12 smokers was conducted to replicate these findings as well as earlier findings that blocking vents doubles CO intake from 1-mg tar cigarettes. While blocking half the vents with fingers significantly increased CO boost from ultralight cigarettes (2.8 vs. 5.4 ppm, p < 0.001), it did not influence boosts from light cigarettes (6.3 vs. 6.5 ppm, p = 0.8). The lowest yield cigarettes (1 mg tar) may be special. Smoking machine simulations provide poor models of human smoke intake. It is unclear whether tar and nicotine intake from light cigarettes was influenced by vent blocking.     

Doppler grid surface scanning applications for pulmonary subsurface parenchymal perfusion assessment

Subsurface perfusion to lung parenchyma underlying the pleura is difficult to assess in live ventilated animals. The purpose of this study was to assess applicability of a newly developed laser Doppler grid scanning imaging technology that measures perfusion of pleural subsurface lung regions in intact normal and abnormal animal lungs. Eighty-six Doppler grid perfusion measurements were performed in five New Zealand White Rabbits (3-5 kg); four with unilateral bullous lung disease, one normal control. Left upper lobe lung surface was exposed to 10 1-sec spot Nd:YAG exposures (70 W/cm2). One week following laser exposure, all rabbits underwent sequential bilateral open thoracotomy. Unaffected left lower lobes in these animals and all four lobes of a previously untreated rabbit were used as controls. Pleural subsurface perfusion measurements were recorded over a contiguous 900-pixel square surface grid using quantitative noncontact laser Doppler imaging during open thoracotomy procedures. Scans were obtained in a normal volume ventilation mode, at 30 cm of inspiratory hold airway pressure, and postinflation. A perfusion-pressure response curve was obtained in normal lung at 10-, 20-, and 30-cm static airway pressure. Post mortem measurements were used as 0 flow controls. Normal lung tissue was found to have relatively high pleural subsurface perfusion (1362 +/- 328 corrected units on a scale of 0-4095). Areas of atelectasis had decreased perfusion (659 +/- 512 U., 48.4 +/- 12.5% compared to normal lung, p < 0.02), but returned to normal levels after inflation of the lung (1253 +/- 363 U., p = 0.21 compared to normal). Pleural subsurface perfusion decreased uniformly and progressively as lung inflation pressure increased (p < 0.0001). Perfusion increased immediately to supranormal values following release of high inspiratory inflation pressure holds (1603 +/- 626 U., 117 +/- 18% compared to normal lung, p = 0.03). Bullae had markedly decreased perfusion (541 +/- 68 U.) that was not further reduced by increased inflation pressures. Noncontact laser Doppler grid perfusion imaging appears to provide a new tool for measuring pleural subsurface perfusion over a large area of lung surface in clinical experimental settings. Results are rapid, reproducible, and consistent. Sampling errors inherent in current point sampling Doppler flow techniques are reduced by the multiple contiguous measurements. We have used this technique to demonstrate inspiratory pressure-related reduction in pleural subsurface perfusion in normal lung, reversible decreased perfusion in atelectatic regions, and reduced perfusion in bullous and laser-treated lung regions.     

Clinical response of localized recurrent periodontitis treated with scaling, root planing, and tetracycline fiber

The purpose of this study was to compare the clinical efficacy of scaling and root planing alone versus tetracycline fiber therapy used adjunctively with scaling and root planing in the treatment of nonresponsive active periodontitis in patients under supportive periodontal therapy. Thirty patients who were receiving supportive treatment and had at least two nonadjacent periodontitis sites with a probing depth of between 4 and 8 mm and bleeding on probing, or had aspartate aminotransferase (AST) levels above 800 microIU in the gingival crevicular fluid in separate quadrants participated in this study. For each patient, the test sites were treated with scaling and root planing plus tetracycline fibers while the control site was treated with scaling and root planing only. Probing depths, clinical attachment levels, gingival recession, AST levels, and bleeding on probing were recorded and subgingival plaque samples were collected at baseline and 1, 3, and 6 months following treatment. At 3 months after treatment, there was a reduction of bleeding on probing and probing depth, and a gain of clinical attachment in both test and control sites. The mean reduction in probing depth of the test sites was 1.38 mm and the attachment gain was 0.8 mm after 6 months. The clinical response obtained at 3 months following therapy was maintained throughout the 6-month follow-up period. However, there were no statistically significant differences between sites treated with scaling and root planing alone and those treated with combined tetracycline therapy. Most of the reductions of probing depths in the fiber group were attributed to gingival recession. The present study did not confirm the efficacy of adjunctive tetracycline fibers in treating nonresponsive sites in maintenance subjects with regard to probing depth reduction or clinical attachment gain. Reinfection of the pockets from untreated sites and extra-crevicular regions may explain the insignificant response to local tetracycline therapy.     

Kinetic analysis of dynamic 13C NMR spectra: metabolic flux, regulation, and compartmentation in hearts

Control of oxidative metabolism was studied using 13C NMR spectroscopy to detect rate-limiting steps in 13C labeling of glutamate. 13C NMR spectra were acquired every 1 or 2 min from isolated rabbit hearts perfused with either 2.5 mM [2-13C]acetate or 2.5 mM [2-13C]butyrate with or without KCl arrest. Tricarboxylic acid cycle flux (VTCA) and the exchange rate between alpha-ketoglutarate and glutamate (F1) were determined by least-square fitting of a kinetic model to NMR data. Rates were compared to measured kinetics of the cardiac glutamate-oxaloacetate transaminase (GOT). Despite similar oxygen use, hearts oxidizing butyrate instead of acetate showed delayed incorporation of 13C label into glutamate and lower VTCA, because of the influence of beta-oxidation: butyrate = 7.1 +/- 0.2 mumol/min/g dry wt; acetate = 10.1 +/- 0.2; butyrate + KCl = 1.8 +/- 0.1; acetate + KCl = 3.1 +/- 0.1 (mean +/- SD). F1 ranged from a low of 4.4 +/- 1.0 mumol/min/g (butyrate + KCl) to 9.3 +/- 0.6 (acetate), at least 20-fold slower than GOT flux, and proved to be rate limiting for isotope turnover in the glutamate pool. Therefore, dynamic 13C NMR observations were sensitive not only to TCA cycle flux but also to the interconversion between TCA cycle intermediates and glutamate.     

Induced hypothermia in critical respiratory failure after lung transplantation

A practical approach to detect and identify ceftazidime-hydrolyzing extended-spectrum mutants of OXA-10 beta-lactamase is presented. Large numbers of bacteria were screened by colony hybridization, a 720-bp part of blaOXA was amplified by PCR from the hybridization-positive isolates, and the products were digested by PvuII and HaeIII.     

Comparative effects of enteric-coated pancreatin microsphere therapy after conventional and pylorus-preserving pancreatoduodenectomy

BACKGROUND: A comparative study was performed between patients with exocrine pancreatic insufficiency after conventional pancreatoduodenectomy (Whipple's procedure) and pylorus-preserving pancreatoduodenectomy (PPPD). In these patients the pharmacodynamics of 2-mm enteric-coated pancreatin microspheres (ECPMs) and their gastric transit time in relation to that of a solid meal were investigated. The efficacy of ECPM preparations may differ after Whipple's procedure compared with PPPD, because the latter procedure does not include gastrectomy. METHODS: Gastric transit was assessed by double-isotope scintigraphy. A pancake meal was labelled with 99mTc. ECPMs were cold-labelled with 170Er and neutron activated shortly before ingestion to enable imaging with a gamma camera. Intraluminal pancreatic enzyme activity was assessed during a 6-h period with two indirect tests: the cholesteryl [14C]octanoate breath test and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid-p-aminosalicylic acid (NBT-PABA-PAS) test. RESULTS: In patients who had Whipple's procedure, the gastric transit time of ECPMs and of the pancake meal was not significantly different. The outcome of the indirect pancreatic function tests during enzyme supplementation was comparable, and not significantly different, from that in healthy volunteers. In patients who had PPPD, however, the gastric transit time of microspheres was greatly delayed compared with that of the pancake meal (P < 0.05). Improvement in the outcome of the indirect pancreatic function tests during enzyme supplementation was much less and remained well below that of healthy volunteers (P < 0.05). CONCLUSION: In cases of exocrine pancreatic insufficiency after Whipple's procedure, 2-mm ECPM treatment adequately restores pancreatic enzyme activity. Following PPPD, however, ECPM treatment is often ineffective because the microspheres are retained in the stomach. In these patients, use of conventional powdered pancreatin enzyme preparations may improve the efficacy of treatment.     

Petit mal status in a patient with chronic renal failure

A 39-year-old woman with traumatic spinal paraplegia and chronic renal failure had peritoneal dialysis for acute renal failure precipitated by a bout of urinary tract infection. Two weeks after the dialysis she lapsed into coma for a few days. An electroencephalogram indicated petit mal stupor as it showed generalized epileptic discharges during the initial period of her coma.