Biomedical subjects

D Girard

Publications and source records attributed to D Girard.

At least 37 records · Page 2Linked to original sources

PubMed1998

Functional responses of human neutrophils to sodium sulfite (Na2SO3) in vitro.

An influx of neutrophils into the airways is a common feature observed during pulmonary inflammation induced by air pollutants, including sulfur dioxide and sulfates. In the present study focusing on the in vitro interactions of sodium sulfite (Na2SO3) with human neutrophils, we confirm results indicating that this sulfite induces superoxide production (O2-) by itself. We demonstrated that this response can occur more rapidly than previously reported (within 5 min), and that Na2SO3 can act as a priming agent, in a concentration-dependent fashion, to the bacterial tripeptide N-formyl-methionine-leucine-phenylalanine (fMLP) by increasing O2-production. In addition, our results show that Na2SO3 induces gene expression in human neutrophils in a concentration-dependent manner as assessed by incorporation of 5-[3H] uridine into total RNA. However, it does not induce cell shape changes. We also demonstrated that Na2SO3 does not modulate neutrophil apoptosis nor reverse the well-known delaying effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on apoptosis. We conclude that Na2SO3 acts rapidly on neutrophil physiology, within a few minutes with respect to superoxide production, and a few hours (4 h) with respect to gene expression without altering a biological process such as the rate of apoptosis evaluated after a long period of incubation (20 h). We further conclude that Na2SO3-induced production of O2does not drive neutrophils to undergo apoptosis, a mechanism known to occur in other conditions. Therefore, the potential toxicity of Na2SO3 during pulmonary inflammation or lung-associated diseases may be related to its ability to induce superoxide production without altering neutrophil apoptosis rate.

Apoptosis↗

PubMed1998

Ecarin Clotting Time: a predictive coagulation assay for the antithrombotic activity of argatroban in the rat.

We studied the use of the Ecarin Clotting Time (ECT) as a predictive assay of the antithrombotic effects of argatroban in a new tissue factor-dependent model of venous thrombosis and a model of arterial thrombosis in the rat. Heparin was used as a reference anticoagulant. Infusions of argatroban dose-dependently increased the ECT across the range of doses required for antithrombotic activity in models of venous and arterial thrombosis (1.25-40 microg/kg/min). The TT was only useful as a marker in the case of venous thrombosis, since, in the arterial thrombosis model, the clotting times were >200 s in the majority of animals receiving antithrombotic doses. The aPTT is not sufficiently sensitive to be predictive of an antithrombotic effect in the venous model, and shows only modest increases in the arterial thrombosis model. Heparin did not significantly increase the ECT at antithrombotic doses in the venous thrombosis model, and only increased the ECT by 53% at 40 microg/kg/min in the arterial model, despite a marked antithrombotic effect. Both the TT and aPTT were dose-dependently increased by heparin at doses active in the venous model, whereas both parameters were >200 s at doses active in the arterial thrombosis model. Thus, the ECT provides a predictive marker for the antithrombotic activity of argatroban in both venous and arterial thrombosis, at least in the rat.

Animals↗

PubMed1997

Responsiveness of human neutrophils to interleukin-4: induction of cytoskeletal rearrangements, de novo protein synthesis and delay of apoptosis.

Interleukin-4 (IL-4) and IL-13 are cytokines that share many biological activities. We have previously demonstrated that IL-13 affects a number of neutrophil responses, and here we extend our observations to IL-4. We present, for the first time, direct evidence for the presence of functional IL-4 receptors on human neutrophils. We report that IL-4 induces RNA synthesis in a concentration-dependent manner and, based on observations of the induction of morphological cell shape changes and spreading onto glass, we demonstrate that IL-4 activates neutrophil cytoskeletal rearrangements. We further show that IL-4 is a potent activator of de novo protein synthesis in neutrophils, and we identify by microsequencing one of these proteins as the cytoskeletal protein actin. We were also able to demonstrate for the first time that actin is cleaved into at least two fragments of approximately 30 kDa (pI 5.4) and approximately 25 kDa (pI 5.0) in neutrophils. Finally, we report that IL-4 delays neutrophil apoptosis, as assessed by morphological observations from cytocentrifuge preparations, as well as by measurement of differences in staining by flow cytometry with both propidium iodide and Hoechst reagent. Taken together, we conclude that IL-4 is a more potent neutrophil agonist than previously believed. We discuss the possibility that the induction of the de novo synthesis of actin by IL-4 is related to the mechanism by which this cytokine delays apoptosis; in addition, the cleavage of this protein is likely to contribute to the apoptotic process.

Actins↗

PubMed1997

Absence of the IL-7 receptor component CDw127 indicates that gamma(c) expression alone is insufficient for IL-7 to modulate human neutrophil responses.

It has been proposed that neutrophils are targets for interleukin-7 (IL-7) because this cytokine was found to increase the number of murine immature neutrophils in vivo. In addition, some nonhuman myeloid cell lines were shown to express the IL-7 receptor (IL-7R). Moreover, it was recently discovered that human neutrophils constitutively express the common gamma chain (gamma(c)), known to be a component of not only IL-7R, but also IL-2R, IL-4R, IL-9R, and IL-15R. Among these, we have recently observed that IL-4 and IL-15 are neutrophil agonists. All of the above observations prompted us to study IL-7-human neutrophil interactions. In this study, we investigated potential effects of IL-7 on a range of neutrophil responses. Although we were able to confirm the presence of the gamma(c) component on human neutrophils, we report, for the first time, that these cells lack the CDw127 component of IL-7R. When studying potential modulatory effects of IL-7 on human neutrophils, we found that IL-7 does not induce respiratory burst, phagocytosis, or cytoskeletal functions and does not alter gene expression. Positive controls were included in each assay and the expected results were obtained. In addition, in contrast to IL-4 and IL-15, we found that neutrophil apoptosis is not modulated by IL-7, while granulocyte-macrophage colony-stimulating factor, used here as control, strongly delayed this process as expected. We conclude that the sole expression of gamma(c) on human neutrophils is insufficient to modulate neutrophil responses with respect to the studied functions. Therefore, it cannot be proposed, based on studies performed with nonhuman cells or cell lines, that human neutrophils are targets for IL-7.

Animals↗

PubMed1997

Haemodynamic effects of mechanical peritoneal retraction during laparoscopic cholecystectomy.

PURPOSE: Abdominal wall retraction (AWR) was recently proposed as an alternative for CO2 pneumoperitoneum. In this study we evaluated the cardiorespiratory effects of AWR during laparoscopic cholecystectomy. METHODS: Fifteen patients were studied during laparoscopic cholecystectomy using AWR. Monitoring included heart rate (HR), mean arterial pressure (MAP), pulse oxymetry (SpO2), end-tidal CO2 (PETCO2) minute ventilation, and peak inspiratory pressure (PIP). Using transoesophageal echocardiography, the transgastric short axis view was obtained to derive the end-diastolic area (EDA), the end-systolic area (ESA), and the ejection fraction (EF). These parameters were measured at predetermined periods: 1) five minutes after anaesthetic induction, 2) five minutes after AWR insertion, 3) 15 min after AWR insertion, and 4) after the end of surgery. RESULTS: No change in any measured parameter was observed over time in the AWR group except for an increase in MAP (P < 0.05) after AWR insertion. There were no changes in EDA, ESA and EF during the study, reflecting stable global cardiac function. In addition, no embolic episodes were observed during surgery. CONCLUSION: Our results demonstrate that the use of gasless abdominal distention for laparoscopic cholecystectomy results in a stable haemodynamic profile in healthy patients without cardiac disease, except for a brief increase in MAP after the AWR insertion. The advantages of AWR over conventional pneumoperitoneum should be confirmed in higher risk patients in a prospective, randomized study.

Adult↗

PubMed1997

Epidural analgesia and intravenous patient-controlled analgesia result in similar rates of postoperative myocardial ischemia after aortic surgery.

UNLABELLED: To assess the role of postoperative analgesia on myocardial ischemia after aortic surgery, we compared intravenous patient-controlled analgesia (PCA) with thoracic epidural analgesia (TEA). One hundred twenty-four patients were prospectively randomized to the PCA or TEA group. In the TEA group, a T6-7 or T7-8 epidural catheter was inserted before the induction of general anesthesia. Within 1 h of the end of surgery, analgesia and 24-h two-channel Holter monitoring were begun. Myocardial ischemia was defined as ST segment depression > or = 1 mm, 0.06 s after the J point, and lasting for more than 1 min. In the PCA group, a bolus of morphine, 0.05 mg/kg, was given, followed by 0.02 mg/kg of morphine on demand every 10 min. Bupivacaine 0.125% and fentanyl 10 microg/mL was used in the TEA group. Analgesics were titrated to maintain a visual analog scale score < or = 3. The overall incidence of myocardial ischemia was 18.4%-18.2% for TEA and 18.6% for PCA (P = not significant). There were no differences between the groups in the total duration of ischemia per patient (22.2 +/- 119.8 min for TEA and 20.5 +/- 99 min for PCA) and the number of episodes per patient (0.69 +/- 2.1 for TEA and 1.2 +/- 4.9 for PCA). Twenty-three patients had an adverse cardiac outcome, although there were no differences between the groups. The postoperative pain control was superior with TEA. In these patients undergoing elective aortic surgery, the use of postoperative TEA did not result in a lower incidence of early myocardial ischemia compared with intravenous PCA with morphine, despite better analgesia with TEA. IMPLICATIONS: Postoperative myocardial ischemia is associated with adverse cardiac outcome. Using Holter monitoring after aortic surgery, this study shows that the use of thoracic epidural analgesia with bupivacaine and fentanyl did not result in a lower incidence of myocardial ischemia compared with intravenous patient-controlled analgesia with morphine.

Aged↗

PubMed1996

Differential effects of interleukin-15 (IL-15) and IL-2 on human neutrophils: modulation of phagocytosis, cytoskeleton rearrangement, gene expression, and apoptosis by IL-15.

Human neutrophils have been shown recently to express both the beta and the gamma chains of the interleukin-2 receptor (IL-2R). IL-15, a cytokine that has recently been cloned and characterized, was found to share many of the biological functions of IL-2 and is known to mediate signals through IL-2R beta and IL-2R gamma. In recent studies, we observed that IL-2 exerts few effects on various neutrophil functions, but information on IL-15-neutrophil interactions is lacking. In this study, we observed that IL-15, in contrast to IL-2, induces important morphological cell shape changes that are typical of activated neutrophils. Furthermore, phagocytosis of opsonized sheep red blood cells was significantly increased by IL-15 but not by IL-2. However, similar to IL-2, IL-15 did not modulate the oxidative burst response. Furthermore, we observed that de novo RNA synthesis is increased in neutrophils by IL-15 along with de novo protein synthesis, whereas no significant effect of IL-2 was noted. Among the different proteins that were found to be upregulated by IL-15, one was identified by microsequencing as the cytoskeletal protein actin. Finally, we found that IL-15 delays apoptosis of neutrophils more efficiently than IL-2 when evaluated by both microscopic observations and flow cytometry procedures. Furthermore, this phenomenon was dose-dependent (10 to 500 ng/mL), and, at 500 ng/mL, IL-15 delayed apoptosis as strongly as granulocyte-macrophage colony-stimulating factor. This study is the first to show that IL-15 is a significant neutrophil agonist. Moreover, in view of the differential effects of IL-15 and IL-2 on this cell type, our results support the existence of a specific IL-15R component(s) on human neutrophils.

Actins↗

PubMed1996

Effects of interleukin-13 on human neutrophil functions.

It was recently shown that interleukin-13 (IL-13) induces the expression and release of the IL-1 decoy receptor (type II) in human neutrophils along with the production of the IL-1 receptor antagonist. In the present study we focused on further studying the modulatory effects of IL-13 on these cells. We found that recombinant human IL-13 (rhIL-13) induces cellular morphological changes in neutrophils that are typical of activated cells. Furthermore, rhIL-13 was shown to increase tyrosine phosphorylation of several neutrophil proteins. We also demonstrate that this cytokine stimulates de novo RNA synthesis in a concentration-dependent fashion as measured by [5-3H]uridine incorporation and that rhIL-13 induces the synthesis of several neutrophil proteins according to high-resolution two-dimensional gel electrophoresis of metabolically [35S]-labeled cells. We observed that the IL-8 levels in the external milieu of IL-13-stimulated cells was almost fivefold increased when compared with control cells. Finally, we observed that rhIL-13 has no significant effect on phagocytosis and apoptosis. Taken together, our results demonstrate that IL-13 is a modulator of several human neutrophil functions. This leads us to conclude that the modulatory role of IL-13 on human neutrophils, a potentially important anti-inflammatory cytokine, is more complex than previously believed. Furthermore, because we show that the synthesis of several as yet unidentified proteins was up-regulated by IL-13, our findings open new avenues of research on the effects of this cytokine on human neutrophils.

Apoptosis↗

PubMed1996

Antithrombotic activity of argatroban in experimental thrombosis in the rabbit.

Argatroban was evaluated in three models of thrombosis in the rabbit: the Wessler model (thromboplastin plus stasis of the left jugular vein), an arteriovenous shunt model, and a model of arterial thrombosis induced by endothelial and intimal damage of the left femoral artery. Calcium heparin was used as a comparator. Both substances inhibited thrombus formation in the Wessler model with ID50 values of 0.32 and 0.16 mg/kg intravenous bolus for argatroban and heparin respectively, with similar changes in thrombin time (4 to 5 times control) and activated partial thromboplastin time (APTT) (1.6 to 2.1 times control) for both substances at antithrombotic doses. The ID50 values of both substances were 2.4 micrograms/kg/min (argatroban) and 0.5 microgram/kg/min (heparin). When they were administered by continuous infusion, no significant effects on the APTT were noted. In the arteriovenous shunt, the ID50 values for argatroban and heparin (respectively) were 0.16 and 0.07 mg/kg intravenous bolus, and 4.5 and 2.8 micrograms/kg/min intravenous infusion. Vessel clamping followed immediately by electrical stimulation (5 mA direct current, 5 minutes) of the left femoral artery leads to the formation of an occlusive thrombus approximately 30 minutes after clamping. Argatroban infused for 60 minutes before the vascular lesion and throughout the 90 minute observation period led to a dose-dependent delay in arterial occlusion with significant effects seen at 5 micrograms/kg/min with five of eight animals showing normal femoral blood flow at 90 minutes postlesion at 20 micrograms/kg/min; no significant increases (Dunnett's test) in APTT were noted with argatroban. Heparin was without effect even at 40 micrograms/kg/min, despite an eight-fold increase in APTT at 20 micrograms/kg/min and values of more than 300 seconds at 40 micrograms/kg/min. Thus, in models of arterial but not venous thrombosis, argatroban is a more potent antithrombotic agent than heparin on a weight basis, with antithrombotic effects at a much lower degree of systemic anticoagulation.

Animals↗

PubMed1996

The relationship of neuropsychological status and productive outcomes following traumatic brain injury.

Neuropsychological assessment is a standard component of traumatic brain injury rehabilitation programmes; however, the relationship between neuropsychological test scores and functional abilities is not clear. The current study compared serial neuropsychological test data with functional outcomes for 152 subjects. Outcome was operationally defined for three activity settings (home, school, work) with six levels of productivity for each. Productivity was defined as one's ability to function at increasing levels of independence. Demographic and caseload variables were analysed utilizing correlation and stepwise multiple regression analyses. Significant relationships to outcome were found between certain neuropsychological test scores, and certain demographic variables. Positive outcomes were related in part to patient's speed of information processing, memory skills, and simultaneous processing abilities. Also related to positive outcomes were mechanism of injury, level of insurance funding, premorbid educational level, and negative history of substance abuse. The activity setting influenced outcome such that it appeared to be most difficult to return to work, suggesting the necessity of adequate vocational assistance. However, cognitive and demographic variables accounted for less than 30% of the total variance in outcome. Therefore, brain injury rehabilitation must be multifaceted.

Activities of Daily Living↗

PubMed1996

Influence of immunosuppression on the pharmacokinetics and pharmacodynamics of azithromycin in infected mouse tissues.

Azithromycin has been shown to preferentially distribute to infection loci. Due to the potential contribution of phagocytes as transporters of drug to these sites, there has been some concern that immunosuppression of the cellular arm of the host defence system would greatly reduce the delivery of azithromycin to sites of infection and hence impair efficacy. Therefore, we evaluated the pharmacokinetics and pharmacodynamics of azithromycin in a Staphylococcus aureus intramuscular infection model in normal and immunosuppressed mice, employing therapeutic and prophylactic regimens. Immunosuppression was induced by daily doses of cyclophosphamide that culminated in leucopenia with an underlying granulocytopenic condition, with circulating peripheral granulocytes numbering from < or = 0.1-0.3 x 10(9)/L. Azithromycin tissue levels were not reduced in infection loci in granulocytopenic mice but moderate increases in Cmax and AUC values were observed, relative to similar tissues from normal mice. The tissue half-life of azithromycin in infected tissues in a therapeutic mode (75 h) was three-fold longer than in a prophylactic mode (25 h); this correlated with the degree of inflammation (therapy was withheld until inflammation was evident; i.e., prophylaxis reduced inflammation). Histological examination of infected tissues from normal and leucopenic mice was indistinguishable despite a 70%-85% reduction in circulating granulocytes. Compared with untreated infected controls, bactericidal activity was noted following prophylaxis with azithromycin and bacteraemia was suppressed in mice receiving azithromycin therapeutically. In summary, these data indicate that azithromycin delivery and efficacy in a moderately immunosuppressed animal model are unimpaired.

Agranulocytosis↗

PubMed1996

Detection of gas embolism by transesophageal echocardiography during laparoscopic cholecystectomy.

Using transesophageal echocardiography (TEE), 16 patients (ASA physical status I-III), undergoing laparoscopic cholecystectomy, were assessed for the occurrence of episodes of gas embolism and cardiovascular changes related to those emboli. The long-axis four-chamber view was monitored continuously, except for predetermined intervals where the transgastric short-axis view was obtained to derive the end-diastolic area (EDA), the end-systolic area (ESA), and the ejection fraction (EF). In one patient, we monitored the longitudinal view of the superior and the inferior vena cava. The monitoring of the patients also included: heart rate (HR), mean arterial pressure (MAP), arterial saturation by pulse oximetry (Spo2), end-tidal CO2 (ETCO2), minute ventilation (VE), and peak inspiratory pressure (PIP). Embolic events were defined as the appearance of gas bubbles in the right cardiac chambers. We observed gas embolism in 11/16 patients (five during peritoneal insufflation and six during gallbladder dissection). Using the longitudinal view of the superior and inferior vena cava (IVC), we found that these emboli were transmitted through the IVC. No episode of cardiorespiratory instability (decrease in MAP > or = 10 mm Hg, Spo2 < 90%) was observed. There was no significant difference in cardiorespiratory variables between patients who presented gas embolism (n = 11) and patients who did not (n = 5) during the studied period. In this small group of patients, we conclude that gas embolism occurs commonly during laparoscopic cholecystectomy but that these gas emboli cause minimal cardiorespiratory instability.

Adult↗

PubMed1996

Haemodynamic interaction of high-dose fentanyl and increasing doses of vecuronium in patients undergoing myocardial revascularization.

BACKGROUND: Bradyarrhythmia has been reported with vecuronium when given with high dose narcotics. We hypothesized that if the bradycardic response is dependent on a vagal reaction mediated by narcotics, it should be independent of the vecuronium dose. A dose-related response of vecuronium on heart rate (HR) would be in favour of a chronotropic action of this agent. METHODS: We examined three induction techniques using high doses of fentanyl in which vecuronium was given in increasing doses. In addition, a reference group received a low dose of atracurium. Forty patients scheduled for elective CABG surgery were anaesthetized with fentanyl (50 mu g/kg) given over 5 min, and were randomly assigned to receive either 0.056, 0.14, 0.28 mg/kg of vecuronium or 0.28 mg/kg of atracurium. Haemodynamic measurements were obtained at the following intervals: before induction (time 0), after the administration of fentanyl (at 5 min), and 1, 2 and 5 min after tracheal intubation (at 10, 11 and 15 min). RESULTS: In vecuronium-treated groups, there were significant decreases in HR, mean arterial pressure, and cardiac output (P<0.05). There were no differences between the three vecuronium groups. Although the atracurium-treated group displayed no significant haemodynamic changes, 2 patients of this group developed HR < 40 bpm. CONCLUSIONS: Over the range of vecuronium doses studied, we observed a reduction in HR during induction for CABG surgery with high doses of fentanyl and vecuronium. This effect was not dose dependent and is likely related to a direct effect of a high-dose narcotic technique and/or due to a vagal stimulation regarding the airway procedure.

Adult↗

PubMed1996

Phototoxicity of some bromine-substituted rhodamine dyes: synthesis, photophysical properties and application as photosensitizers.

The synthesis of some bromine-substituted rhodamine derivatives viz., 4,5-dibromorhodamine methyl ester (dye 2) and 4,5-dibromorhodamine n-butyl ester (dye 3) are reported. These dyes were synthesized to promote a more efficient cancer cell photosensitizer for potential use in in vitro bone marrow purging in preparation for autologous bone marrow transplantation. Spectroscopic and photophysical characterization of these dyes together with rhodamine 123 (dye 1) are reported in water, methanol, ethanol and also in a microheterogeneous system, sodium dodecyl sulfate. The possible mechanism of photosensitization is characterized in terms of singlet oxygen efficiency of these dyes. Singlet oxygen quantum yields for bromine-substituted dyes are in the range of 0.3-0.5 depending on the solvent. For dye 1 no singlet oxygen production is found. The photodynamic actions of these dyes in different cell lines are tested. It was found that dye 2 and dye 3 are efficient photosensitizers and mediate eradication of K562, EM2, myeloid cell lines (CML) and the SMF-AI rhabdomyosarcoma line.

Animals↗

PubMed1996

Activity of the new fluoroquinolone trovafloxacin (CP-99,219) against DNA gyrase and topoisomerase IV mutants of Streptococcus pneumoniae selected in vitro.

The MICs of trovafloxacin, ciprofloxacin, ofloxacin, and sparfloxacin at which 90% of isolates are inhibited for 55 isolates of pneumococci were 0.125, 1, 4, and 0.5 microgram/ml, respectively. Resistant mutants of two susceptible isolates were selected in a stepwise fashion on agar containing ciprofloxacin at 2 to 10 times the MIC. While no mutants were obtained at the highest concentration tested, mutants were obtained at four times the MIC of ciprofloxacin (4 micrograms/ml) at a frequency of 1.0 x 10(-9). Ciprofloxacin MICs for these first-step mutants ranged from 4 to 8 micrograms/ml, whereas trovafloxacin MICs were 0.25 to 0.5 microgram/ml. Amplification of the quinolone resistance-determining region of the grlA (parC; topoisomerase IV) and gyrA (DNA gyrase) genes of the parents and mutants revealed that changes of the serine at position 80 (Ser80) to Phe or Tyr (Staphylococcus aureus coordinates) in GrlA were associated with resistance to ciprofloxacin. Second-step mutants of these isolates were selected by plating the isolates on medium containing ciprofloxacin at 32 micrograms/ml. Mutants for which ciprofloxacin MICs were 32 to 256 micrograms/ml and trovafloxacin MICs were 4 to 16 micrograms/ml were obtained at a frequency of 1.0 x 10(-9). Second-step mutants also had a change in GyrA corresponding to a substitution in Ser84 to Tyr or Phe or in Glu88 to Lys. Trovafloxacin protected from infection mice whose lungs were inoculated with lethal doses of either the parent strain or the first-step mutant. These results indicate that resistance to fluoroquinolones in S. pneumoniae occurs in vitro at a low frequency, involving sequential mutations in topoisomerase IV and DNA gyrase. Trovafloxacin MICs for wild-type and first-step mutants are within clinically achievable levels in the blood and lungs of humans.

Animals↗

PubMed1996

Pharmacokinetics of trovafloxacin (CP-99,219), a new quinolone, in rats, dogs, and monkeys.

The pharmacokinetics of trovafloxacin [CP-99,219; 7-(3-azabicyclo[3.1.0]hexyl)-naphthyridone] were studied in rats, dogs, and monkeys following oral and intravenous administration. After intravenous dosing, the systemic clearances of trovafloxacin in rats, dogs, and monkeys were 12.5, 11.1, and 7.2 ml/min/kg of body weight, respectively, and the respective volumes of distribution were 0.9, 1.7, and 4.3 liters/kg, with corresponding elimination half-lives of 0.7, 1.8, and 7.0 h. After the administration of oral doses of 50, 20, and 20 mg/kg to rats, dogs, and monkeys serum trovafloxacin concentrations reached a maximum at 0.6, 2.3, and 2.3 h, respectively, with respective maximum concentrations of trovafloxacin in serum of 11.5, 3.5, and 5.2 micrograms/ml; the corresponding elimination half-lives were 2.2, 2.5, and 7.5 h. The oral bioavailability of trovafloxacin was 68, 58, and 85% in rats, dogs, and monkeys, respectively. The binding of trovafloxacin to serum proteins was concentration independent, averaging 92, 75, and 66% for rats, dogs, and monkeys, respectively. Trovafloxacin penetrated well into tissues in dogs. The urinary recoveries of unchanged drug were less than 5% in dogs and monkeys, with or without incubation with alkali or Glusulase (beta-glucuronidase and sulfatase). In rats, 99.8% of the orally administered radioactivity was recovered in feces, while 20.6, 3.4, and 67.1% of the radioactive dose in bile duct-cannulated rats were recovered in feces, urine, and bile, respectively. These results suggest that the elimination of trovafloxacin from rats, and possibly from dogs and monkeys, is primarily through biliary excretion.

4-Quinolones↗

PubMed1996

A novel anti-microfilament antibody, anti-135 kD, is associated with Raynaud's disease, undifferentiated connective tissue disease and systemic autoimmune diseases.

We report herein the characterization of a human IgG antibody reactive with a nonmuscle 135 kD microfilament-associated protein, anti-135 kD. Using nonmuscle epithelial PtK2 cells as substrate in indirect immunofluorescence, we identified a distinctive pattern of reactivity with microfilaments in sera from 12 of 165 (7.3%) patients investigated for systemic autoimmune diseases and in only 2 of 171 (1.2%) normal and rheumatic disease controls (P < 0.006, 95% Cl 1.46 to 30.1). An association between anti-135 kD and Raynaud's phenomenon (n = 12/14, 85.7%) with or without an associated systemic autoimmune disease was noted. The anti-135 kD specificity was established by several criteria. (1) The fluorescence was periodically distributed along microfilaments and concentrated at focal adhesions for all sera (n = 14). (2) On immunoblots, the 14 sera reacted with a PtK2 polypeptide of 135 kD. (3) IgG purified by blot-affinity from the 135 kD band (alpha-135) reproduced the fluorescent pattern of the original sera while IgG purified from other bands did not. (4) Double immunofluorescence with alpha-135 and anti-alpha-actinin mAb indicated absence of antibody fluorescence at ruffling membranes where a-actinin was distributed. (5) IgG subclass analysis of anti-135 kD revealed that 12 (85.7%) sera are of IgG3 isotype and 2 (14.3%) are of IgG1 isotype while the light chain expression was kappa restricted. This is the first report of an antibody to a 135 kD microfilament protein. Anti-135 kD expand the repertoire of anti-microfilament and anticytoskeletal antibodies in human sera.

Adult↗

PubMed1996

[Comparison of hemodynamic and ventilatory effects of pneumoperitoneum using carbon dioxide or abdominal suspension during laparoscopic cholecystectomy].

This study compares the cardio-respiratory effects of CO2 pneumoperitoneum to those of abdominal suspension (or laparolift) in laparoscopic cholecystectomy. Between september 1993 et may 1995, 31 patients participated in this non-randomized prospective trial. They consisted of 9 males et 22 females, with a mean age of 47.0 +/- 14 years. Sixteen patients were included in the CO2 group and 15 in the laparolift group. Both groups were comparable for age and gender. All patients were submitted to the same anaesthetic protocol. Repeated measurements of the respiratory and cardiovascular function were made during the intervention. End tidal CO2, minute ventilation, peak inspiratory pressure showed superior elevations in the CO2 group. And for the hemodynamic parameters, only the mean arterial pressure and cardiac frequency differed between the two groups, other hemodynamic parameters including left ventricular ejection fraction were comparable. Also, postoperatory hospital stay, OR time, per and postoperatory complications were comparable. With its stable hemodynamic and ventilatory pattern, abdominal suspension can constitute a safe and secure alternative to CO2 pneumoperitoneum in patients with respiratory dysfunction.

Adult↗