The effect of endogenous glucocorticoids on the expression of the cyclooxygenase enzyme was studied by contrasting cyclooxygenase expression and prostanoid synthesis in adrenalectomized and ...sham-adrenalectomized mice with or without the concurrent administration of endotoxin. Peritoneal macrophages obtained from adrenalectomized mice showed a 2- to 3-fold induction in cyclooxygenase synthesis and activity when compared to sham controls. Intravenous injection of a sublethal dose of endotoxin (5 μg/kg) further stimulated cyclooxygenase synthesis, resulting in a 4-fold increase in prostaglandin production. Similar cyclooxygenase induction can be achieved in macrophages obtained from normal mice but only after high doses of endotoxin (2.5 mg/kg) that are 100% lethal to adrenalectomized mice. Restoration of glucocorticoids in adrenalectomized animals with dexamethasone completely inhibited the elevated cyclooxygenase and protected these animals from endotoxin-induced death. In contrast, no signs of cyclooxygenase induction were observed in the kidneys of the adrenalectomized mice, even when treated with endotoxin. Dexamethasone did not affect the constitutive cyclooxygenase activity and prostaglandin production present in normal and adrenalectomized kidneys. These data indicate the existence of a constitutive cyclooxygenase that is normally present in most cells and tissues and is unaffected by steroids and of an inducible cyclooxygenase that is expressed only in the context of inflammation by proinflammatory cells, like macrophages, and that is under glucocorticoid regulation. Under normal physiological conditions glucocorticoids maintain tonic inhibition of inducible cyclooxygenase expression. Depletion of glucocorticoids or the presence of an inflammatory stimulus such as endotoxin causes rapid induction of this enzyme, resulting in an exacerbated inflammatory response that is often lethal.
This study evaluates the effect of resident physician work hour limits on surgical patient safety.
Resident work hour limits have been enforced in New York State since 1998 and nationwide from 2003. ...A primary assumption of these limits is that these changes will improve patient safety. We examined effects of this policy in New York on standardized surgical Patient Safety Indicators (PSIs).
An interrupted time series analysis was performed using 1995 to 2001 Nationwide Inpatient Sample data. The intervention studied was resident work hour limit enforcement in New York teaching hospitals. PSIs included rates of accidental puncture or laceration (APL), postoperative pulmonary embolus or deep venous thrombosis (PEDVT), foreign body left during procedure (FB), iatrogenic pneumothorax (PTX), and postoperative wound dehiscence (WD). PSI trends were compared pre- versus postintervention in New York teaching hospitals and in 2 control groups: New York nonteaching hospitals and California teaching hospitals.
A mean of 2.6 million New York discharges per year were analyzed with cumulative events of 33,756 (APL), 36,970 (PEDVT), 1,447 (FB), 10,727 (PTX), and 2,520 (WD). Increased rates over time (expressed per 1000 discharges each quarter) were observed in both APL (0.15, 95% confidence interval, 0.09-0.20, P<0.05) and PEDVT (0.43, 95% confidence interval, 0.03-0.83, P<0.05) after policy enforcement in New York teaching hospitals. No changes were observed in either control group for these events or New York teaching hospital rates of FB, PTX, or WD.
Resident work hour limits in New York teaching hospitals were not associated with improvements in surgical patient safety measures, with worsening trends observed in APL and PEDVT corresponding with enforcement.
Noninvasive pressure estimation in heart cavities and in major vessels would provide clinicians with a valuable tool for assessing patients with heart and vascular diseases. Some microbubble-based ...ultrasound contrast agents are particularly well suited for pressure measurements because their substantial compressibility enables microbubbles to vary significantly in size in response to changes in pressure. Pressure changes should then affect reflectivity of microbubbles after intravenous injection of a contrast agent. This has been demonstrated with a galactose-based contrast agent using 2.0-MHz ultrasound tone bursts. Preliminary results indicate that, over the pressure range of 0–186 mmHg, the subharmonic amplitude of scattered signals decreases by as much as 10 dB under optimal acoustic settings and the first and second harmonic amplitudes decrease by less than 3 dB. An excellent correlation between the subharmonic amplitude and the hydrostatic pressure suggests that the subharmonic signal may be utilized for noninvasive detection of pressure changes.
Macrophage-dependent arachidonate metabolism in hydronephrosis. Unilateral ureteral obstruction in rabbits leads to an influx of macrophages into the kidney, a proliferation of interstitial cells, ...and an increase in arachidonic acid metabolism. The role of the macrophage in the metabolic changes of hydronephrosis was investigated by using endotoxin and nitrogen mustard. The in vivo administration of endotoxin, a macrophage agonist, 1 hour before perfusion of the hydronephrotic kidney markedly enhanced (fourfold to tenfold) the peptide-stimulated arachidonic acid metabolism of the perfused kidney. Nitrogen mustard made animals leukopenic and prevented the influx of macrophages into the hydronephrotic kidney. The peptide-stimulated arachidonic acid metabolism of these kidneys was suppressed, and no enhancement was seen with in vivo endotoxin administration. The macrophage thus appears to be an essential determinant of the enhanced arachidonic acid metabolism seen in experimental hydronephrosis. An inhibitory effect of prostaglandin E2 on macrophage function in this model of renal inflammation was also demonstrated. Hydronephrotic animals were given aspirin during the period of unilateral ureteral obstruction to prevent in vivo prostaglandin E2 production. In the perfused hydronephrotic kidney, the peptide-stimulated arachidonic acid metabolism, which appears to be a marker of macrophage function in this model, was enhanced by aspirin treatment.
Métabolisme dépendant des macrophages de l'arachidonate lors de l'hydronéphrose. L'obstruction urétérale unilatérale chez des lapins conduit à un afflux de macrophages dans le rein, à une prolifération des cellules interstitielles et à une élévation du métabolisme de l'acide arachidonique. Le rôle du macrophage dans les modifications métaboliques de l'hydronéphrose a été étudié en utilisant une endotoxine et une moutarde azotée. L'administration in vivo d'endotoxine, un agoniste des macrophages, 1 heure avant la perfusion du rein hydronéphrotique a stimulé de façon marquée (4 à 10 fois) le métabolisme de l'acide arachidonique stimulé par les peptides dans le rein perfusé. La moutarde azotée a rendu les animaux leucopéniques et a empêché l'afflux de macrophages dans le rein hydronéphrotique. Le métabolisme stimulé par les peptides de l'acide arachidonique dans ces reins était supprimé, et aucune stimulation n'était vue lors de l'administration in vivo d'endotoxine. Le macrophage apparaît ainsi un déterminant essentiel de la stimulation du métabolisme arachidonique observeé lors de l'hydronéphrose expérimentale. Un effet inhibiteur des prostaglandines E2 sur la fonction macrophagique a également été démontré dans ce modèle d'inflammation rénale. Les animaux hydronéphrotiques ont reçu de l'aspirine pendant la période d'obstruction urétérale unilatérale pour empêcher la production in vivo de prostaglandines E2. Le métabolisme de l'acide arachidonique stimulé par les peptides dans le rein hydronéphrotique perfusé, quiapparaît comme un marqueur de la fonction macrophagique dans ce modèle, était stimulé lors du traitement par l'aspirine.
Liver-directed therapy for hepatic metastases includes: intra-arterial techniques such as transarterial chemoembolization (TACE) and yttrium-90 resin ((90)Y) microsphere radioembolization and ...ablative technologies: cryoablation, radiofrequency ablation, and microwave ablation. Combining embolization techniques with liver ablation may enhance the therapeutic benefit of each and result in improved patient survival. We retrospectively reviewed our experience with combined intra-arterial therapies and ablation for unresectable hepatic colorectal metastases from 1996 to 2011. Patient demographics, tumor characteristics, specific liver-directed treatments, procedure-related morbidity and mortality, and overall survival were recorded. There were 17 (53%) males and 15 (47%) females. Average age for the group was 74.1 years (median, 75.5 years). Fifteen patients (46.9%) had a single hepatic metastasis. Eleven (34%) patients had bilobar tumor distribution and seven (22%) patients had vascular invasion of the portal vein or hepatic/caval venous structures. Seven (21%) tumors were greater than 5 cm in diameter. Twenty-seven (84.4%) patients received TACE and five (15.6%) received (90)Y. Fourteen (43%) were embolized before any ablation. Fifty-three per cent of patients required multiple hepatic ablation sessions. Median length of hospital stay was 1 day. There were no procedure-related mortalities and complications occurred in six (18.8%) patients. Mean follow-up for the group was 33 months. Kaplan-Meier 1-, 3-, and 5-year estimated survival was 93.8, 50.0, and 10.1 per cent, respectively. Median survival for the group was 46 months. Hepatic ablation and embolization techniques can be combined safely with minimal morbidity. In our series, we observed 5-year survival in 10 per cent of patients.
Color Doppler imaging has been used to evaluate a variety of abnormalities in the iliofemoral region. This pictorial essay demonstrates how use of color Doppler techniques aids in the diagnoses of ...iliofemoral pseudoaneurysms, fluid collections, aneurysms, arteriovenous fistulas and malformations, venous thrombosis, vascular grafts, and soft-tissue masses including tumors and benign lymphadenopathy.
We have recently put forward the hypothesis that the dual inhibition of proinflammatory nitric oxide (NO) and prostaglandins (PG) may contribute to the antiinflammatory properties of nitric oxide ...synthase (NOS) inhibitors. This hypothesis was tested in the present study. A rapid inflammatory response characterized by edema, high levels of nitrites (NO2-, a breakdown product of NO), PG, and cellular infiltration into a fluid exudate was induced by the administration of carrageenan into the subcutaneous rat air pouch. The time course of the induction of inducible nitric oxide synthase (iNOS) protein in the pouch tissue was found to coincide with the production of NO2-. Dexamethasone inhibited both iNOS protein expression and NO2- synthesis in the fluid exudate (IC50 = 0.16 mg/kg). Oral administration of N-iminoethyl-L-lysine (L-NIL) or NG-nitro-L-arginine methyl ester (NO2Arg) not only blocked nitrite accumulation in the pouch fluid in a dose-dependent fashion but also attenuated the elevated release of PG. Finally, carrageenan administration produced a time-dependent increase in cellular infiltration into the pouch exudate that was inhibited by dexamethasone and NOS inhibitors. At early times, i.e., 6 h, the cellular infiltrate is composed primarily of neutrophils (98%). Pretreatment with colchicine reduced both neutrophil infiltration and leukotriene B4 accumulation in the air pouch by 98% but did not affect either NO2- or PG levels. In conclusion, the major findings of this paper are that (a) selective inhibitors of iNOS are clearly antiinflammatory agents by inhibiting not only NO but also PG and cellular infiltration and (b) that neutrophils are not responsible for high levels of NO and PG produced.
This paper includes an update of a Cochrane systematic review on tobacco use cessation (TUC) in dental settings as well as narrative reviews of possible approaches to TUC and a more detailed ...discussion of referral for specialist TUC services. On the basis of these reviews we conclude that interventions for tobacco users in the dental setting increase the odds of quitting tobacco. However, the evidence is derived largely from patients using smokeless tobacco. Pharmacotherapy (such as nicotine replacements, bupropion and varenicline) is recommended for TUC in medical settings but has received little assessment in dental applications, although such evidence to date is promising. Whether the dental setting or referral to specialist TUC services is the most effective strategy to help people to quit tobacco use is unclear. An effective specialist service providing best available TUC care alone may not be the answer. Clearly, such services should be both accessible and convenient for tobacco users. Closer integration of specialist services with referrers would also be advantageous in order to guide and support oral health professionals make their referral and to maximise follow‐up of referred tobacco users. Future research direction may consider investigating the most effective components of TUC in the dental settings and community‐based trials should be a priority. Pharmacotherapy, particularly nicotine replacement therapy, should be more widely examined in dental settings. We also recommend that various models of referral to external and competent inhouse TUC specialist services should be examined with both experimental and qualitative approaches. In addition to overall success of TUC, important research questions include facilitators and barriers to TUC in dental settings, preferences for specialist referral, and experiences of tobacco users attempting to quit, with dental professionals or specialist services, respectively.
The rabbit hydronephrotic kidney (HNK) is a model of renal inflammation characterized by a marked increase in arachidonic acid metabolism which is temporally associated with an inflammatory cell ...influx into the injured tissue. The HNK exhibits an exaggerated elaboration of eicosanoids ex vivo in response to inflammatory agonists (bradykinin and the chemotactic peptide, n-formyl-methionyl-leucyl-phenylalanine). Essential fatty acid (EFA) deficiency i.e., deprivation of (n-6) fatty acids attenuated markedly the ex vivo elaboration of eicosanoids and prevented the enhancement of the microsomal cyclooxygenase and thromboxane synthase activity associated with 3 days of ureter occlusion. In contrast, postobstructive release prevented the ex vivo elaboration of eicosanoids by the HNK. When the HNK was assessed morphologically by electron microscopy, both EFA deficiency and postobstructive release markedly reduced the population of interstitial macrophages normally seen in the HNK. Apparently, EFA deficiency blocked the influx of macrophages whereas postobstructive release resulted in the efflux of macrophages from the HNK. Because EFA deficiency has been shown to inhibit the synthesis of leukotriene B4, a potential chemotaxin, it was hypothesized that EFA deficiency might prevent the influx of macrophages due to an inhibition of leukotriene B4 synthesis. Indeed, EFA deficiency suppressed the synthesis of this eicosanoid in blood whereas prostaglandin E2 and thromboxane A2 production were unaffected. In summary, this study demonstrates that EFA deficiency prevents the influx of macrophages into the HNK and prevents the enhanced arachidonate metabolism which normally occurs after ureter obstruction. A potential role for leukotriene B4 as a chemotactic agent in this model of renal inflammation also is suggested.
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