Eradicating methicillin-resistant Staphylococcus aureus.
Explore the source record for details and available documents.
Bacitracin↗
Biomedical subjects
M Levi
Publications and source records attributed to M Levi.
Plasminogen activation in vivo upon intravenous infusion of DDAVP. Quantitative assessment of plasmin-alpha 2-antiplasmin complex with a novel monoclonal antibody based radioimmunoassay.
Infusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established. A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor alpha 2-antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated alpha 2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system. Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex. We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.
Adult↗
Deep vein thrombosis in obstetric patients: diagnosis and risk factors.
This study was performed to assess the prevalence of deep vein thrombosis (DVT) in consecutive obstetric patients with clinical symptoms of DVT, using impedance plethysmography (IPG) as the diagnostic method and to establish the safety of withholding anticoagulant therapy in patients with a repeatedly normal IPG. In addition, in patients with DVT the prevalence of coagulation and fibrinolytic disorders, which may explain the occurrence of venous thrombosis was investigated. Of the 77 obstetric patients with symptoms of DVT, 32 (42%) had an abnormal IPG. The remaining 45 patients had a repeatedly normal IPG and showed no venous thromboembolism during a 6 months follow-up period. Twenty percent (six patients) of the patients with an abnormal IPG had a coagulation or fibrinolytic abnormality. These observations suggest that serial IPG can be used effectively in the management of obstetric patients with clinically suspected DVT and that hemostatic abnormalities are frequently found in those patients with DVT.
Adolescent↗
The fortuitous diagnosis of cholera in a two-year-old girl.
We are reporting the fortuitous diagnosis of a case of cholera and the unusual failure of the commercial bacteriologic media that led to the unexpected isolation of Vibrio cholerae. The case demonstrates the need for communication between the medical staff and laboratory personnel when an uncommon disease, such as cholera, is suspected. This case also alerts the clinician to the possibility of multiple enteric pathogens coinfecting a traveller.
Animals↗
Bisacylphosphonates inhibit hydroxyapatite formation and dissolution in vitro and dystrophic calcification in vivo.
Some geminal bisphosphonates are used clinically for a number of important bone/calcium related diseases; however, side effects and lack of selectivity impede their wide use. This work reports the synthesis and evaluation of bisacylphosphonates (e.g., adipoyl- and suberoylbisphosphonate). These compounds were found to inhibit significantly hydroxyapatite formation and dissolution in vitro and the calcification of bioprosthetic tissue implanted subdermally in rats. These are the first instances of nongeminal bisphosphonates [P-(C)n-P, n greater than or equal to 2] that have been reported to be active in calcium-related disorders. The reported bisacylphosphonates possess apparent lower toxicity, and their calcium complexes/salts have improved solubility properties. Therefore, they are of potential importance for clinical applications.
Animals↗
Streptococcal toxic shock syndrome due to noninvasive pharyngitis.
Serious infections due to group A beta-hemolytic streptococcus (GABHS) have been reported with increasing frequency in recent years. We report a case of toxic shock syndrome (TSS) due to GABHS pharyngitis in an otherwise healthy 14-year-old boy. The organism was found to produce toxin A. To our knowledge, this is the second reported case of streptococcal TSS associated with the production of toxin A that is not associated with an invasive disease and the first case associated with a documented rise in the level of antibody to the streptococcal toxin itself. Clinicians must be especially vigilant for this entity in patients who have streptococcal pharyngitis because early recognition and institution of aggressive supportive therapy can be lifesaving.
Adolescent↗
Impaired fibrinolysis in cyclosporine-treated renal transplant patients. Analysis of the defect and beneficial effect of fish-oil.
Cyclosporine treatment has been associated with thrombotic vascular complications. We investigated the activity of the fibrinolytic system and its capacity to respond upon DDAVP stimulation in a group of 20 cyclosporine-treated patients as compared with a group of 9 azathioprine-treated patients. Furthermore, the effect of the administration of fish-oil to these patients on the endogenous fibrinolytic activity was studied in a double-blind randomized, placebo-controlled cross-over study. The cyclosporine-treated patients showed a significantly reduced plasminogen activator activity and plasmin generation response upon the infusion of DDAVP as compared with the azathioprine group. In the cyclosporine group 60% of the patients had an impaired fibrinolytic response, whereas this was found in only 11% of the azathioprine-treated patients (P < 0.05). The impairment of the endogenous fibrinolysis activity could be attributed either to a defective release of plasminogen activator from the vessel wall (67% of patients) or to high plasma levels of plasminogen activator inhibitor 1 (33% of patients). Administration of fish-oil resulted in a significant improvement of the impaired fibrinolysis in the cyclosporine group. Particularly, in patients with a defective release of plasminogen activator from the vessel wall, fish-oil treatment resulted in a normalization of the fibrinolytic activity. These results indicate that cyclosporine treatment induces an impaired fibrinolysis that may contribute to the frequent occurrence of thromboembolic complications and eventually the impairment of renal function in cyclosporine-treated patients. The beneficial effect of the administration of fish-oil on the endogenous fibrinolysis may result in a reduction of the adverse events associated with cyclosporine treatment.
Cyclosporine↗
Inhibition of plasminogen activator inhibitor-1 activity results in promotion of endogenous thrombolysis and inhibition of thrombus extension in models of experimental thrombosis.
BACKGROUND: We investigated the effect of inhibition of plasminogen activator inhibitor-1 (PAI-1) activity by a murine monoclonal anti-human PAI-1 antibody (MAI-12) on in vitro thrombolysis and on in vivo thrombolysis and thrombus extension in an experimental animal model for thrombosis. METHODS AND RESULTS: Thrombolysis, mediated by recombinant tissue-type plasminogen activator (rt-PA), was studied in an in vitro system consisting of fibrinogen, plasminogen, and thrombin. Addition of purified platelets during clot formation inhibited rt-PA-mediated thrombolysis in a dose-dependent manner. Platelet-dependent thrombolysis resistance could be completely neutralized by the monoclonal antibody MAI-12, supporting the notion that the observed resistance is due to PAI-1 released from alpha-granules of platelets. Subsequently, we monitored in vivo thrombolysis and thrombus extension of human whole blood thrombi that were allowed to form in rabbit jugular veins. During thrombus formation, either MAI-12 or an irrelevant antibody was incorporated. Thrombolysis and thrombus extension were simultaneously measured during endogenous thrombolysis or upon administration of different dosages of rt-PA. We observed that endogenous thrombolysis was enhanced in the presence of MAI-12 compared with the control antibody. Significantly, thrombus extension was partially prevented by MAI-12 and not by the control antibody irrespective of whether exogenous rt-PA was systematically administered. CONCLUSIONS: These observations further confirm the essential role of PAI-1 in the regulation of the thrombolytic system and support the exploration of adjunctive therapy based on inhibition of PAI-1 activity in thrombolytic strategies.
Adult↗
Contact system dependent fibrinolytic activity in vivo: observations in healthy subjects and factor XII deficient patients.
The contribution of activation of the contact system to activation of the fibrinolytic system in vivo was investigated in healthy volunteers and in factor XII deficient patients. The plasminogen activating activity in normal plasma was only partially blocked (for 77%) with specific antibodies to tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). The residual activity could be quenched by a monoclonal antibody that inhibits factor XII activity and was not present in patients with a factor XII deficiency. The formation of plasmin upon the DDAVP stimulus as reflected by circulating plasmin-alpha 2-antiplasmin (PAP) complexes was lower in factor XII deficient patients than in healthy volunteers. These results indicate that in vivo the plasminogen activating activity is partially dependent on activation of the contact system. This fibrinolytic activity is impaired in factor XII deficient patients which may explain the occurrence of thromboembolic complications in these patients.
Adult↗
Deep vein thrombosis and fibrinolysis. Defective urokinase type plasminogen activator release.
In the present study 57 consecutive patients with a first episode of venographically proven deep vein thrombosis were investigated to evaluate the release of tissue-type plasminogen activator (t-PA) and of urokinase-type plasminogen activator (u-PA) in response to DDAVP stimulation as well as the resting plasminogen activator inhibitor (PAI) concentration, comparing this to the results obtained in 66 similar patients with a clinical suspicion of thrombosis but with a normal venogram. All assays were performed without knowledge of the patient's status. Four patients in the deep vein thrombosis-group (7%) had an absent u-PA antigen response upon DDAVP infusion, while a normal response was observed in all control subjects. Patients and controls showed similar increases in t-PA antigen level upon DDAVP. High resting PAI antigen levels were encountered in 5 patients in the deep vein thrombosis-group (9%) and in 6 subjects in the control group (9%). The results from this controlled study indicate that a defective release of u-PA may occur in patients with deep vein thrombosis and may have pathogenetic significance. Furthermore it is concluded that elevation of PAI levels cannot be considered as a specific risk factor for venous thrombosis.
Antigens↗
Fibrinolytic response to tumor necrosis factor in healthy subjects.
Tumor necrosis factor (TNF) may be involved in the disturbance of the procoagulant-fibrinolytic balance in septicemia, leading to microvascular thrombosis. To assess the dynamics of the fibrinolytic response to TNF in humans, we performed a crossover saline-controlled study in six healthy men, investigating the effects of a bolus intravenous injection of recombinant human TNF (50 micrograms/m2) on the stimulation and inhibition of plasminogen activation as well as on plasmin activity and inhibition. TNF induced a brief fourfold increase in the overall plasma plasminogen activator (PA) activity peaking after 1 h (p less than 0.0001), which was associated with rises in the antigenic levels of urokinase-type plasminogen activator (p less than 0.0001) and tissue-type plasminogen activator (p less than 0.0001). Plasminogen activator inhibitor type I antigen remained unchanged in the first hour, but showed a rapid eightfold increase thereafter (p less than 0.0001), which coincided with the decrease in PA activity. Generation of plasmin activity in the first hour was signified by an 11-fold rise in D-dimer levels (p less than 0.0001); inhibition of plasmin was reflected by a 36-fold rise in plasmin-alpha 2 antiplasmin complexes (p less than 0.0001), as well as by a transient 16% decrease in alpha 2-antiplasmin activity (p less than 0.01). In conclusion, TNF induced an early activation of the fibrinolytic system becoming maximal in 1 h, with a rapid inhibition thereafter. Earlier observations in the same subjects showed sustained coagulation activation for 6-12 h. The observed disbalance between the procoagulant and fibrinolytic mechanisms after TNF injection confirms the in vivo relevance of the effects of TNF on vascular endothelium in vitro and may explain the tendency towards microvascular thrombosis in septicemia.
Adult↗
Variable effects of radiological contrast media on thrombus growth in a rabbit jugular vein thrombosis model.
We studied the effect of an ionic high osmolar contrast medium (Ioxitalamate), an ionic low osmolar contrast medium (Ioxaglate) and various nonionic low osmolar contrast media (Iopamidol, Iopromide and Iohexol) on thrombus growth in a rabbit jugular vein thrombosis model. Thrombus growth was determined by the accretion of 125I-labeled fibrinogen onto autologous preformed thrombi in rabbit jugular veins at various time-intervals from 15 min up to 10 h after infusion of the study solution. The ionic low osmolar contrast medium markedly inhibited thrombus growth whereas all nonionic low osmolar contrast media promoted thrombus growth. The ionic high osmolar, contrast medium inhibited thrombus growth, but less than the ionic low osmolar contrast medium. Within the group of nonionic contrast media, the Iopamidol associated promotion of thrombus growth was significantly higher than the Iopromide or Iohexol associated effects. The simultaneous administration of the apparently most potent thrombus growth promoting contrast medium (i.e. Iopamidol) and heparin resulted in complete abolishment of the increase in thrombus growth. These results support the claims of prothrombotic properties of nonionic as compared to ionic contrast media and could explain the clinically encountered thromboembolic complications after the use of nonionic low osmolar contrast media.
Animals↗
Technique for drawing blood for cultures: is changing needles truly necessary?
After drawing blood for culture, medical students and house officers are often taught to change needles before inoculating the culture media. Data to support this practice have been scarce. We obtained simultaneous blood cultures on 75 hospital patients using two techniques: changing needles (C) or not changing needles (NC) before inoculating the cultures. Positive cultures judged to be contaminants were obtained in 4/75 patients in the NC group (5.3%) and in 1/75 patients in the C group (1.3%). This difference was not statistically significant. The practice of changing needles after drawing blood for culture may not be necessary, thus reducing the risk of needlestick injury.
Adult↗
Dietary NaCl modulates Na(+)-H+ antiporter activity in renal cortical apical membrane vesicles.
An apical membrane Na(+)-H+ antiporter mediates proximal tubule NaCl and NaHCO3 reabsorption. The present studies examined whether chronic changes in dietary NaCl intake lead to an adaptation of the Na(+)-H+ antiporter. Rats were maintained either on a low-salt (LS, 0% NaCl) or a high-salt (HS, 2% NaCl) diet for 4 days. Na(+)-H+ antiporter was assayed using the acridine orange fluorescence method in apical membrane vesicles prepared by Mg2+ aggregation. Rats on LS diet exhibited a higher maximal activity (Vmax) for antiporter activity (0.109 +/- 0.008 s-1) compared with rats on HS diet (0.090 +/- 0.008 s-1; P less than 0.01), whereas Na activity (KNa) was similar (13.1 +/- 1.5 and 14.2 +/- 0.8 mM in HS and LS groups, respectively). The modulation of Na(+)-H+ antiporter activity was amiloride sensitive. Proton permeability, Na(+)-dependent [3H]glucose uptake, and vesicle enrichments were similar in both groups. In addition, the dietary protocols were not associated with any systemic acid-base disturbances, K+ deficiency, or hyperfiltration, conditions that have previously been demonstrated to alter Na(+)-H+ antiporter activity. Acute differences in extracellular fluid volume, induced by 10% body weight isohydric expansion failed to affect Na(+)-H+ antiporter activity. Thus chronic alterations in dietary NaCl intake alter the maximal activity (Vmax) of the Na(+)-H+ antiporter. This adaptation may contribute to decreased NaCl reabsorption in extracellular fluid volume expansion, enhanced NaCl reabsorption in extracellular fluid volume depletion, and enhanced NaHCO3 reabsorption in chronic metabolic alkalosis associated with volume contraction.
Animals↗
Ontogeny of renal renin release in spontaneously hypertensive rat and Wistar-Kyoto rat.
The role of renin-angiotensin system in generation of genetic hypertension is unclear. Renal renin secretion was examined in renal superficial cortical slices from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 4 wk (prehypertensive), 6 wk (early hypertensive), and 12 wk (established hypertension) of age. Basal renin release in SHR was greater at 4 wk (749 +/- 55 vs. 480 +/- 50 ng/mg, P less than 0.005) and at 6 wk (428 +/- 70 vs. 266 +/- 60 ng/mg, P less than 0.02). Basal renin release declined by 43% between 4 and 6 wk and by 34% between 6- and 12-wk time periods in SHR. In SHR and WKY at all ages, renin responses to stimulation with isoproterenol (ISO, 10(-5) and 10(-6) M, respectively) were similar. Angiotensin II (ANG II) resulted in a significant reduction in renin release in both SHR and WKY at 10(-7) M in all age groups. The ANG II-induced percent change in renin release from control of SHR was less compared with WKY rats at 10(-8) and 10(-9)M at 4 wk of age. When ANG II was tested in presence of beta-adrenergic stimulation, a comparable renin inhibitory response was observed in both SHR and WKY. The number of ANG II-binding sites in proximal tubular brush-border membrane (BBM) was increased in SHR vs. WKY rats (458 +/- 18 vs. 235 +/- 12 fmol ANG II/mg BBM protein, P less than 0.001) at 4 wk of age. These data document increased basal renin release and ANG II-binding sites in proximal tubular BBM in 4 wk SHR compared with age-matched WKY rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Dietary calcium modulates renal BBM angiotensin II binding and Na(+)-H+ antiporter activity in SHR.
Dietary Ca is an important modulator of blood pressure in the spontaneously hypertensive rat (SHR). Since the kidney plays a key role in the pathogenesis of hypertension, the purpose of this study was to determine the potential renal mechanisms of the blood pressure-lowering effect of increasing dietary Ca content. In 21-day-old SHR fed 0.1 vs. 3.6% Ca diet for 14 days, increasing dietary Ca had no significant effects on basal [704 +/- 50 in 0.1% Ca vs. 784 +/- 61 ng angiotensin I (ANG I).mg-1.h-1 in 3.6% Ca, P = not significant (NS)], isoproterenol-stimulated (1,057 +/- 52 in 0.1% Ca vs. 1,104 +/- 59 ng ANG I.mg-1.h-1 in 3.6% Ca, P = NS), or angiotensin II (ANG II)-inhibited (370 +/- 50 in 0.1% Ca vs. 411 +/- 39 ng ANG I.mg-1.h-1 in 3.6% Ca, P = NS) renal superficial cortical slice renin release. In contrast, in apical brush-border membrane (BBM) vesicles isolated from the superficial cortex, increasing dietary Ca caused a significant decrease in ANG II binding, which was mediated by a decrease in the number of binding sites (Bmax, 376 +/- 14 in 0.1% Ca vs. 234 +/- 6 fmol ANG II/mg BBM protein in 3.6% Ca, P less than 0.01), and no change in the affinity [dissociation constant (Kd), 17.8 +/- 1.4 in 0.1% Ca vs. 13.4 +/- 2.8 nM ANG II in 3.6% Ca, P = NS].(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗
Chronic K depletion stimulates rat renal brush-border membrane Na-citrate cotransporter.
Chronic K depletion (KD) causes hypocitraturia. In the present studies, the effect of KD, induced by a low-K diet for 14 days (serum [K] 4.1 +- 0.1, control vs. 2.2 +/- 0.1 meq/l, KD, P less than 0.01), on renal cortical brush-border membrane (BBM) Na-citrate cotransporter activity was examined. KD significantly decreased fractional citrate excretion (3.90 +/- 0.68 vs. 0.53 +/- 0.10%, P less than 0.01). This was paralleled by a significant increase in the initial linear rate of BBM Na-dependent citrate transport (81 +/- 4 vs. 141 +/- 6 pmol citrate.5 s-1.mg protein-1, P less than 0.01). Kinetic studies varying extravesicular citrate concentration demonstrated that KD increased the maximal activity (Vmax) (152 +/- 17 vs. 296 +/- 14 pmol citrate.5 s-1.mg protein-1, P less than 0.01) with no difference in citrate affinity (118 +/- 23, control vs. 135 +/- 22 microM citrate, KD). Similarly, when extravesicular Na concentration was varied, KD increased the Vmax (132 +/- 9 vs. 206 +/- 6 pmol citrate.5 s-1.mg protein-1, P less than 0.01) with no difference in Na affinity (29 +/- 3, control vs. 28 +/- 1 mM Na, KD). The effect of KD on Na-citrate cotransport was specific in that KD did not alter Na-glucose (84 +/- 12, control vs. 89 +/- 5 pmol glucose.5 s-1.mg protein-1, KD) or Na-proline (87 +/- 3, control vs. 84 +/- 5 pmol proline.5 s-1.mg protein-1, KD) cotransport. In conclusion, KD increases the Vmax of the proximal tubule apical membrane Na-citrate cotransporter.(ABSTRACT TRUNCATED AT 250 WORDS)
Alkaline Phosphatase↗
Reduction of contact activation related fibrinolytic activity in factor XII deficient patients. Further evidence for the role of the contact system in fibrinolysis in vivo.
In this study the contribution of activation of the contact system to activation of the fibrinolytic system in vivo was investigated in healthy volunteers and in factor XII deficient patients. The plasminogen activating activity in plasma from healthy volunteers after infusion of desamino D-arginine vasopressin (DDAVP) was only partially blocked (for 77%) with specific antibodies to tissue-type plasminogen activator and urokinase type plasminogen activator. The residual activity could be quenched by a monoclonal antibody that inhibits factor XII activity and was not present in patients with a factor XII deficiency. The formation of plasmin upon the DDAVP stimulus as reflected by circulating plasmin-alpha 2-antiplasmin complexes was lower in factor XII deficient patients than in healthy volunteers. Activation of the contact system occurred after DDAVP infusion in healthy volunteers and was absent in factor XII deficient patients. These results indicate that DDAVP induces a plasminogen activating activity that is partially dependent on activation of the contact system and that contributes to the overall fibrinolytic activity as indicated by the formation of plasmin-alpha 2-antiplasmin complexes. This fibrinolytic activity is impaired in factor XII deficient patients which may explain the occurrence of thromboembolic complications in these patients.
Adult↗