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Biomedical subjects

A A Weinbroum

Publications and source records attributed to A A Weinbroum.

At least 19 recordsLinked to original sources
PubMed2006

Acute lung injury following pancreas ischaemia-reperfusion: role of xanthine oxidase.

BACKGROUND: Acute pancreatitis can lead to increased pulmonary vascular permeability and respiratory failure. Oxidants (and their generator, xanthine oxidase (XO)) play an important role in injuring the structural integrity of the pulmonary epithelium and endothelium, but their importance in the induction of acute lung injury following pancreas ischaemia-reperfusion (IR) has not been defined. MATERIALS AND METHODS: Rats (n = 48) received a regular or a tungsten (oxidoreductase inhibitor)-enriched diet for 14 days. Their isolated pancreases were then either perfused (controls) or made ischaemic (IR) for 40 min (12 replicates/group). This was followed by in-series pancreas plus normal isolated lung reperfusion for 15 min. Lungs only were subsequently perfused with the 15-min accumulated pancreas effluents for 45 min. RESULTS: Injury was induced in all IR pancreases as expressed by reperfusion pressure, wet-to-dry ratio and amylase and lipase concentrations. Tissue XO activity was high and reduced glutathione pool was low in the tungsten-free IR pancreases. Pulmonary plateau pressure increased by 46% and final PO(2)/FiO(2) decreased by 24%. Capillary pressure and weight rose two- to fourfold in lungs paired with IR non-treated pancreases. Twofold increases in bronchoalveolar lavage volume and contents, including XO, were also recorded in this group of lungs. Lungs exposed to tungsten-treated ischaemic pancreas effluents were minimally damaged and tissue XO content was low compared to controls. CONCLUSIONS: Ex-vivo acute pancreatitis induces acute lung injury via oxidants/antioxidants misbalance, which may be prevented by attenuating pancreas oxidative stress.

Acute Disease↗
PubMed2004

Faecal sterol output is increased by arachidyl amido cholanoic acid (Aramchol) in rats.

Fatty acid-bile acid conjugates (FABACs) were shown recently to have important and multiple effects on cholesterol metabolism. In human fibroblasts, they were found to markedly enhance cholesterol efflux by an ATP-binding cassette transporter A1-dependent pathway. In C57L/J mice, they increased CYP7A1 activity and RNA expression, while decreasing moderately 3-hydroxy-3-methylglutaryl-CoA reductase activity. In C57L/J mice and in hamsters, they also decreased serum cholesterol levels, whereas in other animals, this effect was not seen in short-term experiments. In the present study, we investigated potential mechanisms of action of arachidyl amido cholanoic acid (Aramchol), with particular reference to biliary and faecal sterol outputs in rats. Supplementation with Aramchol at a dose of 150 mg x kg(-1) x day(-1) increased neutral sterol output by approx. 50%, while the faecal outputs of bile salts and total sterols increased by almost 2-fold. Biliary lipid outputs were not significantly different between the control and FABAC-supplemented animals. These findings indicate an overall catabolic effect of FABACs on body cholesterol.

Animal Feed↗
PubMed2004

Methylene blue attenuates lung injury after mesenteric artery clamping/unclamping.

BACKGROUND: This controlled, experimental study was designed to assess the effects of intratracheal and intravenous methylene blue on reperfusion lung injury following superior mesenteric artery clamping/unclamping. MATERIALS AND METHODS: Superior mesenteric arteries of 144 anaesthetized adult male Wistar rats (n = 12/group) were clamped for 1 h. Ten minutes before unclamping, methylene blue or its vehicle was administered intratracheally or intravenously, followed by a 3 h-respiratory assessment and postexperimental assessment of survival. RESULTS: Intravenous 3 and 9 mg kg(-1) but not higher methylene blue doses, and intratracheal 6-mg kg(-1) but not lower doses, significantly (P < 0.05) reduced the 100% increase in plateau pressure, 30% reduction in PO(2)/FiO(2), fourfold augmented bronchoalveolar lavage-retrieved volume and the increased polymorphonuclear leukocytes/bronchoalveolar cells' ratio associated with unclamping of the superior mesenteric artery. Lung tissue polymorphonuclear leukocytes count, total xanthine oxidase activity and wet-to-dry-weight ratio were also normal in these dose-treated groups. These effective regimens were also associated with longer animal survival. CONCLUSIONS: Intratracheal methylene blue mitigates lung reperfusion injury following superior mesenteric artery clamping/unclamping at a similar magnitude as an intravenous regimen. This finding is a novel potential use of methylene blue in vivo.

Administration, Oral↗
PubMed2002

Mannitol dose-dependently attenuates lung reperfusion injury following liver ischemia reperfusion: a dose-response study in an isolated perfused double-organ model.

We had previously studied different modes of prevention of liver ischemia-reperfusion (IR)-induced remote organ reperfusion injury, a challenge that remains partly unmet. We have now studied the capability of mannitol at different doses in abrogating liver IR-induced lung reperfusion injury in an isolated double-organ model. Rat livers ( n = 8/group) were perfused with Krebs-Henseleit solution (control) or made globally ischemic (IR) for 2 h, after which they were paired with normal lungs and "reperfused" together for 15 min. The lungs were then perfused alone with the accumulated Krebs for an additional 45 min. Another 4 control and 4 IR pairs were reperfused with Krebs containing mannitol at.22 mmol,.55 mmol,.77 mmol, or 1.1 mmol. Mannitol.22 mmol and 1.1 mmol failed to attenuate IR-lung injury as indicated by 50-95% increases in inspiratory and perfusion pressures and compliance reduction, a 70% increase in weight gain, and a 2-50-fold increase in bronchoalveolar lavage volume and content. Mannitol.55 mmol prevented all these abnormalities, and.77 mmol attenuated only changes in ventilatory parameters. The latter two treatments were also associated with a 50% reduction in xanthine oxidase activity and a 35-45% increase in the reduced glutathione tissue content compared with the nontreated IR-paired lungs. It is concluded that mannitol in a narrow therapeutic dose range can reduce oxidalive stress-induced lung damage that is related to liver IR.

Animals↗
PubMed2001

Selective attenuation of acute lung ventilatory injury by methylene blue after liver ischemia-reperfusion: a drug response study in an isolated perfused double organ model.

BACKGROUND: Liver transplantation-related ischemia-reperfusion (IR) is associated with the generation of stress oxidants that can spread damage remotely. Methylene blue (MB) had been shown to reduce lung neutrophils sequestration after in vivo intestinal IR and to have a dose-dependent potential for abrogating oxidant-induced ex vivo aortal ring reperfusion injury after liver IR. We now investigated MB's dose-dependent capabilities in preventing acute lung injury after the same liver IR. METHODS: Wistar rat livers (eight replicates/group) were perfused (control) with modified Krebs-Henseleit solution or put globally in no flow (IR) conditions for 2 hr. Separately prepared lungs were then paired with livers and "reperfused" (15 min) together. The livers were then removed, and the lungs were left to recirculate alone with the accumulated Krebs for 45 min. Three additional control and three IR groups were reperfused with Krebs containing 20, 40, or 60 mg/kg MB at concentrations of 42, 86, or 128 microM. RESULTS: All IR livers had hepatocellular and biochemical abnormalities compared with normal functions in the controls. Liver IR was associated with a 50%-75% increase in lung ventilation and perfusion pressures, vascular resistance and decreased compliance, and abnormal bronchoalveolar lavage (BAL) volume and content. Adding 42 and 86 microM MB selectively maintained normal the vascular parameters, intra-experimental lung weight gain, BAL indices, and wet-to-dry ratios. MB128 microM but not 42 or 86 microM best prevented IR-induced deterioration in lung ventilatory pressure and compliance. CONCLUSIONS: MB selectively affords maintenance of normal lung ventilatory versus vascular measures after liver ischemia-reperfusion. Its proposed differential mechanism of action is discussed.

Acute Disease↗
PubMed2001

Lung preconditioning with N-acetyl-L-cysteine prevents reperfusion injury after liver no flow-reflow: a dose-response study.

BACKGROUND: Circulating xanthine oxidase activity and the generated oxidants have been linked to lung reperfusion injury from no flow-reflow conditions in other organs after organ transplantation or surgery. N-acetyl-1-cysteine (NAC), an oxidant scavenger, promotes glutathione in its reduced form (GSH) that is depleted during ischemia. We have recently demonstrated its efficacy in protecting lungs from reperfusion injury if administered during reperfusion of postischemic liver. We now investigated whether preconditioning of lungs with NAC could attenuate lung respiratory or vascular derangement after no flow-reflow (ischemia-reperfusion, IR) and if this depends on lung GSH levels. METHODS: Rat isolated livers were stabilized and perfused with modified Krebs-Henseleit solution (KH) (control, n=12) or made ischemic (no flow, IR-0, n=12) for 2 hr. Meanwhile, lungs were isolated, ventilated, and stabilized (KH+bovine albumin 5%). Serial perfusion (15 min) of liver+lung pairs took place followed by lung only recirculation (45 min) with the accumulated solution. Another three controls and three ischemic groups included lungs treated during stabilization with NAC at 100 mg x kg(-1), 150 or 225 mg x kg(-1) (in 2.5, 3.7 or 5.5 mmol solutions, respectively). Results. Ischemic liver damage, expressed by circulating hepatocellular constituents, was associated with pulmonary artery and ventilatory pressure increases by 70-100% of baseline, abnormal wet-to-dry weight ratio, and abnormal bronchoalveolar lavage volume and content in the IR-0 (nontreated) and the IR-100 and IR-225 pretreated lungs. NAC-150 pretreatment afforded preservation for most parameters. GSH content in the IR-150 lung tissue was only 11% higher than that of IR-225, but 2-fold that in IR-0 and IR-100 GSH lungs. CONCLUSION: Lung preconditioning with NAC prevents reperfusion injury but not in a dose-related manner. Although enhanced GSH tissue content explains lung protection, GSH-independent NAC activity is another possibility.

Acetylcysteine↗
PubMed2001

Flumazenil improves cognitive and neuromotor emergence and attenuates shivering after halothane-, enflurane- and isoflurane-based anesthesia.

PURPOSE: To conduct a randomized, placebo-controlled, double-blinded, clinical experiment testing the hypothesis that flumazenil, a benzodiazepine antagonist, may affect recovery from halothane-, enflurane- and isoflurane-based anesthesia. METHOD: Patients who underwent surgery under N(2)O/O(2) plus halothane (n=100), enflurane (n=100) or isoflurane (n=70) anesthesia were administered flumazenil 1 mg or placebo upon emergence from anesthesia, and their postanesthesia vital signs, vigilance, neurological recovery, shivering, amnesia reversal, and general subjective feeling were assessed. RESULTS: A ten-point vigilance score showed better recovery of flumazenil-treated patients compared to those who received placebo (60-min after halothane anesthesia: 9.9 +/- 0.1 vs 9.5 +/- 0.2, P <0.01; after enflurane: 10 +/- 0 vs 9.4 +/- 0.2, P <0.01; after isoflurane: 10.0 +/- 0 vs 9.3 +/- 0.1, P <0.01). Halothane- and enflurane-flumazenil-treated patients (but not isoflurane) reached a better neurological score (2.97 +/- 0.05 or 3 +/- 0) compared to placebo (2.8 +/- 0.4 or 2.6 +/- 0.4, P <0.01), respectively. Reversal of amnesia was superior in the flumazenil group at 60 min and at 24 hr postsurgery, and more flumazenil patients rated recovery as "pleasant". Flumazenil patients shivered less than placebo patients despite their lower core temperature (at 30 min: halothane: 11% vs 28%, P <0.05; enflurane: 11% vs 30%, P <0.05; isoflurane: 17% for both groups). CONCLUSION: Flumazenil improves recovery of high cortical and neuromotor functions following halothane, enflurane and isoflurane anesthesia, reduces shivering and improves the overall quality of emergence, including patients' subjective feeling.

Adult↗
PubMed2001

Dextromethorphan attenuation of postoperative pain and primary and secondary thermal hyperalgesia.

PURPOSE: To determine the effect of 90 mg dextromethorphan (DM) p.o. vs placebo 90 min preoperatively, on the immediate and delayed postoperative course. METHODS: Thirty patients undergoing laparoscopic cholecystectomy or inguinal hernioplasty under general anesthesia were studied. Half (DM) received 90 mg dextromethorphan and half received placebo 90 min before anesthesia. Intravenous Patient Controlled Aanalgesia with morphine was available for two hours within a six-hour observation period; 75 mg diclofenac i.m. prn was given later in PACU and on-ward (24 hr). Pain was assessed using the visual analogue scales. Thermal thresholds for cold and hot sensation and for pain (by limit method) were evaluated at the site of skin incision (primary-) and distantly (secondary hyperalgesia). Von Frey filaments were applied testing touch sensation. Sedation level and morphine consumption were also assessed in PACU. RESULTS: Demographic, surgical and perioperative parameters were similar; no untoward effects were encountered. Pain intensity and sedation were lower, and the feeling of well-being was greater, in the DM patients: one vs five (median), two vs five, five vs two, respectively, P <0.01 (90 min time-point). Thermal application revealed absence of primary and secondary hyperalgesia only in the DM patients; von Frey filaments induced similar pain sensation in both groups. Mean morphine/group, morphine/weight and diclofenac injection rates were approximately 55% lower in the DM group: 2.1 +/- 1.2 (SD) vs 4.7 +/- 2.3, 0.03 +/- 0.02 vs 0.07 +/- 0.03, 1.0 +/- 0.3 vs 2.4 +/- 0.2, respectively, P <0.01. CONCLUSIONS: Compared with placebo, DM enabled reduction of postoperative analgesics consumption, improved well-being, and reduced sedation, pain intensity and primary and secondary thermal hyperalgesia.

Adult↗
PubMed2001

Antagonization of TNF attenuates systemic hemodynamic manifestations of envenomation in a rat model of Vipera aspis snakebite.

OBJECTIVES: Tumor necrosis factor (TNF) has been reported as a mediator of local tissue injury following snake envenomation in an intact rat model. We investigated whether systemic release of TNF occurs following Vipera aspis envenomation. We further analyzed the possible connection between envenomation-related hemodynamic depression and TNF antagonization (TNF antibodies or soluble TNF receptor). DESIGN: A prospective, randomized, controlled experimental study using a rat model for snake envenomation. SETTINGS: A medical university hospital research laboratory. INTERVENTION: Eighty rats (300-400 g) were divided into four groups (n = 20): control and three experimental groups. Intramuscular injection of V. asis 500 microg/kg was administered to the three experimental groups: venom only (group 1), venom and 40 microg anti-TNF antibodies (group 2), venom and 250 microg soluble TNF receptor (p55-R; group 3). Hemodynamic parameters were monitored up to 4 h following venom injection. MEASUREMENTS AND RESULTS: A significant hemodynamic deterioration (reduction in heart rate and blood pressure) occurred 30 min following venom injection in group 1 compared to groups 2 and 3, where hemodynamic parameters remained stable throughout the 4 h observation period. Serum levels of TNF were detected 15 min after venom injection and peaked after 2 h at 485+/-12 pg/ml. CONCLUSIONS: The hemodynamic consequences of intramuscular injection of V. aspis venom can be blunted in a rat by systemic antagonization of TNF activity prior to venom injection. The poisonous hemodynamic effects of the V. aspis venom might be caused by systemic release of TNF.

Animals↗
PubMed2001

Beta-chemokine secretion patterns in relation to clinical course and outcome in children after cardiopulmonary bypass: continuing the search to abrogate systemic inflammatory response.

BACKGROUND: Surgery involving cardiopulmonary bypass (CPB) is frequently accompanied by a systemic inflammatory response partly triggered by neutrophils and monocyte-macrophages. Certain cytokines that are powerful leukocyte-chemotactic factors have recently been characterized and shown to be important in evoking inflammatory responses: monocyte chemoattractant protein-1 (MCP-1) has monocyte-macrophage chemotactic activity, and regulated-upon-activation normal T-cell expressed and secreted (RANTES) has a potent chemoattractant activity for mononuclear phagocytes. This prospective cohort study investigated possible roles of these chemokines in the inflammatory response to CPB and relationships between the changes in chemokine levels and the clinical course and outcome. METHODS: Systemic blood of 16 children undergoing CPB was collected after induction of anesthesia (base line); at 15 minutes after bypass onset; at CPB cessation; and at 1, 2, 4, 8, 12, and 24 hours afterward to measure MCP-1 and RANTES. RESULTS: The significant changes of plasma beta chemokine levels following CPB were associated with patient characteristics, operative variables, and postoperative course. Cardiopulmonary bypass of more than 2 hours, longer surgical times, inotropic support, and reoperation were associated with higher MCP-1 levels and lower RANTES levels. CONCLUSIONS: Our results suggest a relation between CPB-induced mediators and clinical effects, implying pathogenic roles for chemokines following CPB. These molecules should be considered as possible targets for therapeutic intervention.

Adolescent↗
PubMed2001

Hemodynamic effects of tracheal administration of vasopressin in dogs.

BACKGROUND: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) has been shown to be more effective than optimal doses of epinephrine. Earlier studies had been performed on a porcine model, but pigs produce lysine vasopressin hormone, while humans and dogs do not. This study was designed to compare the effects of tracheal vasopressin with those of NaCl 0.9% (placebo) on haemodynamic variables in a dog model. METHODS: Five dogs were allocated to receive either vasopressin 1.2 U/kg or placebo (10 ml of NaCl 0.9%) via the tracheal route after being anesthetized and ventilated. Haemodynamic variables were determined and arterial blood gases were measured. RESULTS: All animals of the vasopressin group demonstrated a significant increase of the systolic (from 135+/-7 to 165+/-6 mmHg, P<0.05), diastolic (from 85+/-10 to 110+/-10 mmHg, P<0.05) and mean blood pressure (from 98.5+/-3 to 142.2+/-5, P<0.05). Blood pressure rose rapidly and lasted for more than an hour (plateau effect). Heart rate decreased significantly following vasopressin (from 54+/-9 to 40+/-5 beats per min, P<0.05) but not in the placebo group. These changes were not demonstrated with placebo injection. CONCLUSION: Tracheal administration of vasopressin was followed by significantly higher diastolic, systolic and mean blood pressures in the vasopressin group compared with the placebo group. Blood gases remained unchanged in both groups. Vasopressin administered via the trachea may be an acceptable alternative for vasopressor administration during CPR, when intravenous access is delayed or not available, however, further investigation is necessary.

Animals↗
PubMed2001

Wrist actigraphy in anesthesia.

STUDY OBJECTIVES: To examine the use of wrist actigraphy during and following anesthesia or monitored sedation and its ability to objectively assess sleep-related events. DESIGN: Uncontrolled study. SETTING: 1100-bed tertiary care municipal, university-affiliated medical center. PATIENTS AND INTERVENTIONS: 18 patients who underwent minor to medium lower-body surgical procedures with spinal or epidural anesthesia with sedation by propofol, midazolam, or isoflurane-based general anesthesia. MEASUREMENTS AND MAIN RESULTS: Wrist actigraphy was measured and evaluated. The actigraphic recordings accurately indicated the presence and time of occurrence of all relevant perioperative events including those related to anesthesia. Actigraphic data were more precise than equivalent attending anesthesiologist's subjective observations. The anesthesiologist detected changes in the patient's activity with a delay of minutes after they had been picked up by the actigraph. The integrated areas of recorded phases of midazolam-induced sedation and the occurrence and reversal of paradoxical reactions were distinctly discernible as such, unlike the less specifically defined description of the anesthesiologist. CONCLUSIONS: Real time actigraphic monitoring can provide clear-cut and objective indications of changes in the depth of anesthesia or sedation and its associated events during surgery and recovery.

Adult↗
PubMed2001

Combined pre-incisional oral dextromethorphan and epidural lidocaine for postoperative pain reduction and morphine sparing: a randomised double-blind study on day-surgery patients.

The reduction in acute pain perception following dextromethorphan has previously been investigated in patients undergoing general anaesthesia. This random and double-blind study examined the effects of pre-incisional oral dextromethorphan on postoperative pain and intravenous patient-controlled morphine demand in 60 day-surgery patients undergoing lower body surgery under lidocaine (1.6%-16 ml) epidural anaesthesia after receiving placebo, 60 or 90 mg dextromethorphan, 90 min pre-operatively. Postoperative pain was scored on a visual analogue scale from 1 to 10. In-hospital observation continued for 6 h and for 3 days at home; diclofenac was available throughout. Dextromethorphan-treated patients reported significantly (p < 0.05) less pain and sedation, and felt better. Patients who received dextromethorphan 90 mg had significantly (p < 0.05) lower heart and respiratory rates than those who received 60 mg. Medicated patients required half the morphine and diclofenac of placebo patients: 38% of patients who received 90 mg and 21% who received dextromethorphan 60 mg used no morphine or diclofenac whatsoever, a previously unreported finding.

Aged↗
PubMed2001

The midazolam-induced paradox phenomenon is reversible by flumazenil. Epidemiology, patient characteristics and review of the literature.

BACKGROUND AND OBJECTIVE: Midazolam may occasionally precipitate hostility and violence instead of tranquility. We characterized these episodes, their rate of occurrence, the potential paradoxical responders and possible predisposing circumstances among patients undergoing lower body surgery under spinal or epidural anaesthesia and midazolam sedation. PATIENTS AND METHODS: Fifty-eight patients who fulfilled the study entry criteria and who underwent surgery within a 3-month period in a large metropolitan, university-affiliated hospital were enrolled. Sedation and restlessness in all patients were controlled by midazolam administered intravenously by the attending anaesthesiologist; these parameters were later objectively confirmed by recorded actigrams. If "paradoxical" events occurred, flumazenil 0.1 mg 10 s-1 was injected until the aberrant behaviour ceased. Patients with paradoxical reactions were later compared with matched control patients selected from the study group to identify epidemiological characteristics. RESULTS: The incidence of paradoxical events was 10.2% (six out of 58 patients, confidence limits 2.3-18.3%) and they occurred 45-210 min after sedation started; the only independent predictor was an age older than that of the entire study group. The mean cumulative and per weight doses of midazolam were similar for both the experimental and the study groups of patients: 7.3 +/- 2.8 to 10.1 +/- 3.6 mg, and 0.1 +/- 0.04 to 0.12 +/- 0.05 mg kg-1. Flumazenil 0.2-0.3 mg (range 0.1-0.5 mg) effectively stopped the midazolam-induced paradoxical activity within 30 s and surgery continued uneventfully. CONCLUSIONS: Flumazenil completely reverses midazolam-induced paradoxical reactions and they are more frequent in older patients.

Aged↗
PubMed2001

Perioperative care of children with nerve agent intoxication.

Nerve agents (NA) present a major threat to civilian populations. When a ballistic system is used for spreading poison, multiple trauma, as well as toxic trauma could be caused. Children are more susceptible, due to their smaller physiological reserve. Urgent surgical intervention for combined intoxication in the multiple-traumatized child could be a tremendous task in view of the background of physiological instability. Nerve agents affect the autonomic, as well as the central nervous system, leading occasionally to unexpected interactions with agents normally used for resuscitation. This can cause additional instability, and possibly systemic collapse. This review presents and emphasizes points concerning treatment of a child who suffers from combined multiple and toxic traumas. The review is based on scant knowledge of a database of similar cases of pesticide organophosphate poisoning in children since these compounds are alike. We also extrapolated data from reports concerning episodic civilian exposure to NA.

Antidotes↗
PubMed2001

Acute respiratory distress syndrome in children with malignancy--can we predict outcome?

PURPOSE: The purpose of this study was to delineate early respiratory predictors of mortality in children with hemato-oncology malignancy who developed acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: We conducted a retrospective chart review of children with malignant and ARDS who needed mechanical ventilation and were admitted to a pediatric intensive care unit from January 1987 to January 1997. RESULTS: Seventeen children with ARDS and malignancy aged 10.5 +/- 5.1 years were identified. Six of the 17 children (35.3%) survived. Sepsis syndrome was present in 70.6% of all the children. Peak inspiratory pressure, positive end-expiratory pressure (PEEP), and ventilation index values could distinguish outcome by day 3. A significant relationship between respiratory data and outcome related to efficiency of oxygenation, as determined by PaO(2)/FIO(2) and P(A-a)O(2), was present from day 8 after onset of mechanical ventilation. CONCLUSIONS: Peak inspiratory pressure, PEEP, and ventilation index values could distinguish survivors from nonsurvivors by day 3. This may assist in early application of supportive nonconventional therapies in children with malignancy and ARDS.

Adult↗